Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Properties of time domain parameters of the vibration signal have been extensively studied for the fault diagnosis of rolling element bearings (REB). Parameters like kurtosis and Envelope Harmonic-to-Noise Ratio are most widely applied in this field and some important progress has been made. However, since only one-sided information is contained in these parameters respectively, problems still exist in practice when the signals collected are of complicated structure and/or contaminated by strong background noises. A new parameter, named Shock pulse index (SPI), is proposed in this paper. It integrates the mutual advantage of both parameters above and can help effectively identify fault related impulse components under the interference of strong background noises, unrelated harmonic components and random impulses. The SPI optimizes the parameters of Maximum Correlated Kurtosis Deconvolution (MCKD), which is used to filter the signals under consideration. Finally, the interested transient information contained in the filtered signal can be highlighted through demodulation with Teager Energy Operator (TEO). Fault related impulse components can therefore be extracted accurately. Simulations and experiment analyses verify the effectiveness and correctness of the SPI.

Selenium is essential for the synthesis and function of various selenoenzymes, such as glutathione peroxidases, selenoprotein P, and thioredoxin reductase, which play an important role in both antioxidant defense and limiting oxidative damage. Associations between serum selenium concentration and obstetric complications as well as pregnancy outcomes has been reported in many studies. The aim of this study was to determine whether the dietary intake of selenium, its concentration in serum and the activity of glutathione peroxidase in subsequent trimesters of pregnancy affect the birth condition of newborns assessed on the basis of the Apgar score in the 1st and 5th minute of life, birth weight, body length and head and chest circumference in physiological and complicated pregnancy course. Twenty-seven pregnant women at a mean age 29.6 ± 4.8 years from the Lower Silesia region of Poland were recruited to the study, 55% of studied group had pregnancy complications. The mean reported Se intake and serum selenium content for Polish pregnant women was in the first trimester – 56.53 μg/day and 43.75 μg/l, the second trimester – 61.79 μg/day and 41.77 μg/l and the third trimester – 58.37 μg/day and 42.13 μg/l, respectively. In the subgroup of pregnant women with a physiological pregnancy course, a weak, although statistically significant, positive correlation was found in the first trimester between Se intake and the length (R=0.48, p=0.019) and birth weight of newborns (R=0.472, p=0.022), and in the second trimester with the APGAR score at 1 (R=0.680, p=0.005) and 5 minutes (R=0.55, p=0.033), as well as in the third trimester with th APGAR score at 1 minut (R=0.658, p=0.019). The GPX value had a strong positive correlation with the APGAR score at 1 min. (R=0.650, p=0.008) in the second trimester and with the birth weight of the newborns (R=0.598, p=0.039) in the third trimester. There was no correlation between newborns' birth measurements and serum selenium concentration. In the subgroup of pregnant women with pregnancy complications, a strong, statistically significant, negative correlation was found between Se intake in the second trimester and gestational age (R=-0.618, p=0.032), and in the third trimester, a positive correlation between Se concentration in serum and head circumference (R=0.587, p=0.021). The obtained results indicate that there is a relationship between the maternal selenium status during pregnancy, both in terms of the intake of this element, its serum concentration as well as the glutathione peroxidase activity, and the anthropometric parameters of the newborn, such as birth weight, length and APGAR score, especially in the group with physiological course of pregnancy, but when pregnancy complications occur, these relationships lose their importance.

Background: SARS-CoV-2 Omicron JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used RT-qPCR SGTF as the proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing for diagnosis of JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed Q229K, usually associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: The CDC should consider Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Scedosporium species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. Diagnosis of Scedosporium infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Scedosporium-specific biomarkers. Here we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a Scedosporium-specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens of between ~15 kDa and 250 kDa secreted during hyphal growth of the pathogens. The test is compatible with human serum, and allows the detection of the Scedosporium species most-frequently reported as agents of human disease (Scedosporium apiospermum, Scedosporium aurantiacum, and Scedosporium boydii), with limits of detection (LOD) of the EPS biomarkers in human serum of ~0.81 ng/mL (S. apiospermum), ~0.94 ng/mL (S. aurantiacum), and ~1.95 ng/mL (S. boydii). The Scedosporium-specific LFD (ScedLFD) test therefore provides a potential novel opportunity for the detection of infections caused by different Scedosporium species.

The advent of AI in medicine has transformed various medical specialties, including orthodontics. AI has shown promising results in enhancing the accuracy of diagnoses, treatment planning, and predicting treatment outcomes. With the growing number of AI applications and commercially available tools, there is an increase in their usage in orthodontic practices worldwide. This review aims to explore the principles of artificial intelligence (AI), its applications in the diagnostic process of modern orthodontic practices, and concerns associated with the implementation of AI algorithms in clinical practice. A comprehensive review of the literature was conducted, focusing on five categories where AI has been applied in orthodontics: dental diagnostics, cephalometric evaluation, skeletal age determination, temporomandibular joint (TMJ) evaluation, and extraction decision making. AI has demonstrated high efficacy in all those fields. However, variations in performance and the necessity of manual supervision indicate that AI should be used cautiously in clinical settings. Nevertheless, the high complexity and potential unpredictability of AI algorithms call for cautious implementation and regular manual validation of results. Continuous AI learning, proper governance, and addressing privacy and ethical concerns are crucial for the successful integration of AI into orthodontic practice.

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is the first-line therapy, however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficit. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case, the surgical plan was adjusted and the patient showed no postoperative deficit. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

Surgeries that take place in medicine and dentistry or during any form of childbirth results in a significant amount of blood loss. The prevalent measurement methods that surgeons and anesthesiologists utilize as the “gold - standard” has several drawbacks. There are numerous other methods to measure blood loss, which, however, due to their impracticality and limitations, are not ideal either. This paper focuses on minimally invasive neurosurgery in particular, by taking into account a surgical technique known as Endoscopic Endonasal Transphenoidal surgery (EETS), which is used to treat pituitary tumors and adenomas. Along with the review of the existing literature pertaining to blood loss management, this paper proposes a modified electrode probe method along with the concept of usage, computer interface, and the system of integration. The probe is intended to measure the hematocrit count from the collected blood under all circumstances, such that the medical practitioner is assisted to improve the blood loss management technique for better patient recovery.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

Type 2 Diabetes Mellitus is a chronic metabolic disease that poses a significant long-term health risk due to its debilitating complications. While the diagnosis and monitoring of diabetes are well-established, the monitoring of its numerous complications presents a challenge, which can compromise patients' prognosis and quality of life. We analyzed the proteome of ten saliva samples, five from healthy individuals and five from patients with Type 2 Diabetes Mellitus. The aim was to identify potential biomarkers of Type 2 Diabetes Mellitus and its complications. We used PANTHER and FUNRICH tools to conduct a functional analysis and enrichment approach. Our findings revealed 622 proteins involved in 16 disrupted biological processes, which are linked to Type 2 Diabetes Mellitus. Metabolic processes, response to stimuli, processes of the immune system, and signaling are notable due to their known relation with Type 2 Diabetes Mellitus. Enrichment analysis has revealed that there are eleven biological processes that have been deregulated. These processes involve twenty different salivary proteins that are associated with multiple complications in diabetes. Our findings demonstrate that saliva is a dependable source of possible biomarkers that can be used to monitor diabetes and its complications.

Sports traumatic brain injury (TBI) accounts for up to 20% of all sports injuries, and the number of cases is growing year by year due to an increase in the number of people involved in sports, the growing popularity of extreme and contact sports, as well as a high level of motivation to achieve record results. Mild TBI dominates, which can provoke the development of a very wide range of complications and negative consequences. In the programs for the prevention of complications and the rehabilitation of athletes after TBI, TBI features are not sufficiently considered, which significantly differ from household, road or criminal injuries. There are no instrumental methods for diagnosing the severity of the injury. Sports TBI is characterized by repeated frequent TBI, elevated body and brain temperature, peripheral redistribution of blood flow and hypocapnia, which significantly affect cerebral blood flow. Brain injury is an independent cause of the development of cerebral hyperthermia, which significantly worsens the consequences of TBI. To diagnose sports TBI, the method of microwave radiometry of the brain (MWR) can be used. For the prevention of complications, the technology of craniocerebral hypothermia (CCH), which allows for to reduce of physical general and cerebral hyperthermia, and increases the resistance of cerebral cortex neurons to hypoxia and trauma could be used However, these approaches in sports medicine are used sporadically, which, is due to the lack of awareness of coaches and doctors of sports teams. The purpose of the review is to present MWR and CCH in sports TBI.

The progression of the recent COVID-19 pandemic surprised political authorities as well as scientists. The possibility to design powerful strategies for health care and preserving economic and social activities strongly relies on the capacity to monitor correctly the virus spreading and the immune response in the symptomatic and asymptomatic population. The available data relative to the first pandemic months indicate that the test reliability was progressively improved but also that the extremely variable methodologies used in the diagnostic studies generated data that are often not comparable. This condition prevents a simple metadata analysis for the identification of reliable diagnostics guidelines. Nevertheless, there are converging evidences that combinations of complementary approaches may enable more precise identification of virus infection. Furthermore, it appears that the similarities between SARS-CoV2 and the related types SARS-CoV1 and MERS that caused outbreaks in the last 20 years can be exploited to infer some information for which no direct evidence is still available

The regulation of cell death is a fundamental issue in cell biology and continues to be intensely investigated worldwide. The significance of research in this field persists because understanding the determinants of cell lifespan directly impacts the maintenance of multicellular organism homeostasis and, consequently, is crucial for addressing biomedical challenges associated with various diseases. It is recognized that the initiation of cell death can be prompted by both specific signals (such as cytokines or hormones) and nonspecific stimuli, including radiation, temperature increase, or oxidants. When these factors affect a cell, numerous signaling pathways are triggered in the cell, leading to neutralization of the effects of their negative effects or, in case of irreparable damage, to cell elimination. This removal of damaged cells occurs through apoptosis or programmed cell death, a highly regulated process. Numerous signaling molecules participate in orchestrating the apoptotic process, many of which also govern other essential functions within the organism. Physiological factors capable of triggering the apoptotic program in cells include nitric oxide (NO), which serves as one of the key signaling molecules regulating the functions of the cardiovascular, nervous, and immune systems of the organism. The unique chemical nature of NO, along with its numerous intracellular targets and physiologically active redox forms, raises questions about the specific mechanisms through which NO exerts its damaging effects on cells. Utilizing pharmacological preparations- such as sources (donors) of exogenous nitric oxide- represents an approach to investigating the initiation and execution of the apoptotic program in sensitive target cells. Furthermore, this approach holds promise as a direction for discovering new selective drugs.

Ovarian cancer is the third most common female genital cancer. Therefore, the timely diagnosis and comprehensive treatment of postmenopausal patients with benign ovarian tumors remains crucial in the field of gynecology. The significance of ovarian tumors depends on their frequency and their effects on the quality of life of a woman, as well as the possible development of ovarian cancer. Most ovarian cancers are diagnosed late and as a result are difficult to treat and often carry a poor prognosis. Currently there is no clear algorithm available for examining and accurately diagnosing patients with postmenopausal ovarian tumors; moreover, reliable criteria allowing dynamic observation and determining surgical access and optimal surgical intervention measures in postmenopausal patients is lacking.

AbstractWhile the technology is relatively new, low cost 3D printing has impacted many aspects of human life. 3D printers are being used as manufacturing tools for a wide variety of devices in a spectrum of applications ranging from diagnosis to implants to external prostheses. The ease of use and availability of 3D design software and low cost has made 3D printing an accessible manufacturing and fabrication tool in many research laboratories. 3D printers can print materials with varying density, optical character, strength and chemical properties providing platforms for a huge number of strategies that can be chosen for user’s needs. In this review, we focus on applications in biomedical diagnostics and how this revolutionary technique is facilitating development of low cost, sensitive and often geometrically complex tools. 3D printing in fabrication of microfluidics, supporting equipment, optical and electronic components of diagnostic devices is presented. Emerging diagnostic 3D bioprinting as a tool to incorporate living cells or biomaterials into 3D printing is also discussed.

Breast cancer prevention is very important for a woman's health worldwide. We have demonstrated a correlation between mammography and ultrasound with diagnoses using passive microwave radiometry (MWR) and a miRNA oncopanel. While mammography screening dynamics could be completed in 3-6 months, MWR will provide us with a prediction in a matter of weeks or even days with the potential for complementary miRNA diagnostics. An early breast cancer diagnosis may be accomplished using either one of these novel techniques alone or in conjunction with more established techniques

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

Optical coherence tomography (OCT) is one of the most promising, innovative and rapidly emerging intraoperative imaging modalities for neurosurgical guidance in brain tissue imaging, "optical biopsy", brain cerebral vascular detection, nerve fibers and white matter tracts detection. In this article, we provide a short survey of cross-polarization OCT and different types of OCT probes that can be used in routine neurosurgical practice. Through different types of probes there are multiple applications where OCT can play a highly complementary role in offering the real-time microscopic assessment and imaging of normal and pathological brain tissues. The biopsy-needle based probe for CP OCT was shown to be an effective instrument for brain tissue mapping and express estimation of tissue status as well as for detecting large blood vessels to prevent causing bleeding during biopsy sampling. The folded CP OCT probe for intraoperative use for brain tissue examination was shown as a potentially efficient sensor head for CP OCT. The probe demonstrated high lateral resolution in diffractive limited probing beam quality. The length of dismountable probe tip allows using the probe under operating microscope. Due to the designed family of specialized probes CP OCT fills in the niche of devices for express brain tissue examination in situ.

Background: The role played by the non-dominant parietal lobe in motor cognition, attention and spatial awareness networks has potentiated the use of awake surgery. When this is not feasible, asleep monitoring and mapping techniques should be used to achieve an onco-functional balance. Objective: This study aims to assess the feasibility of a dual-strip method to obtain direct cortical stimulation for continuous real-time cortical monitoring and subcortical mapping of motor and visual pathways simultaneously in parietal lobe tumour surgery. Methods: Single-centre prospective study between May’19-November’20 of patients with intrinsic non-dominant parietal-lobe tumours. Two subdural strips were used to simultaneously map and monitor motor and visual pathways. Results: Fifteen patients were included. With regards to motor function, a large proportion of patients had abnormal interhemispheric resting motor threshold ratio (iRMTr) (71.4%), abnormal Cortical Excitability Score (CES) (85.7%), close distance to the corticospinal tract – Lesion-To-Tract Distance (LTD) – 4.2mm, Cavity-To-Tract Distance (CTD) – 7mm and intraoperative subcortical distance - 6.4mm. Concerning visual function, the LTD and CTD for optic radiations (OR) were 0.5mm and 3.4mm, respectively; the mean intensity for positive subcortical stimulation of OR was 12mA±2.3mA and 5/6 patients with deterioration of VEPs>50% had persistent hemianopia and transgression of ORs. 12 patients remained stable, one patient had a de-novo transitory hemiparesis, and two showed improvements in motor symptoms. A higher iRMTr for lower limbs was related with a worse motor outcome (p=0.013) and a longer CTD to OR was directly related with a better visual outcome (p=0.041). At 2 weeks after hospital discharge, all patients were ambulatory at home and all proceeded to have oncological treatment. Conclusion: We propose motor and visual function boundaries for asleep surgery of intrinsic non-dominant parietal tumours. Pre-operative abnormal cortical excitability of the motor cortex, deterioration of the VEP recordings and CTD<2mm from the OR were related to poorer outcomes.

The effectiveness of combining strength-specific training with endurance training to enhance the performance of endurance runners remains uncertain. This study aimed to analyze effect of practising maximum-strength (MAX), explosive strength (EXP) or both combined (COMB) on seven runners’ performance-indicators: vertical jump (VJ), one-repetition-maximum-squat (1RM), peak-velocity/peak-running-speed (PV), lactate-threshold (over incremental-test-protocols, LT), middle-distance-time-trial (TT), maximum-oxygen-consumption (VO2max), running-economy (RE). Systematic-review (Scopus, Wed of Science, Sports Discuss, PubMed) with meta-analysis was conducted following PRISMA standards. Inclusion-criteria (PICOS) were: recreational or well-trained athletes aged 18-45 performing concurrent-training ≥five-week. Used search-terms were related to different types of strength/endurance, participants’ age, sport-modality. 20 manuscripts were selected, quality-assessed with PEDro. MAX training is more effective than EXP, COMB in improving VJ, 1RM, PV, while COMB is more effective than MAX, EXP to enhance TT. MAX is more effective than EXP in improving LT. Concurrent-workouts do not provide additional benefits to VO2max. It is unknown which strength-modality (MAX, EXP or COMB) is more effective in improving RE. Concurrent-training is more effective than single-mode-endurance-training for enhancing specific performance-variables in adult-endurance-runners. Middle-, long-distance-runners may consider incorporating MAX-training to target specific goals, e.g., improving VJ, 1RM, LT, PV while utilizing COMB-training to enhance TT. Certain variables may benefit from EXP. New randomized-controlled-trials are required to confirm these findings.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

FPGA-based data acquisition and processing systems play an important role in modern high-speed, multichannel measurement systems, especially in High-Energy and Plasma Physics. Such FPGA-based systems require an extended control and diagnostics part corresponding to the complexity of the controlled system. Managing the complex structure of registers while keeping the tight coupling between hardware and software is a tedious and potentially error-prone process. Various existing solutions aimed at helping that task do not perfectly match all specific requirements of that application area. The paper presents a new solution based on the XML system description, facilitating the automated generation of the control system’s HDL code and software components and enabling easy integration with the control software. The emphasis is put on reusability, ease of maintenance in case of system modification, easy detection of mistakes, and the possibility of use in modern FPGAs. The presented system has been successfully used in data acquisition and preprocessing projects in High-Energy Physics experiments. It enables easy creation and modification of the control system definition and convenient access to the control and diagnostic blocks. The presented system is an open-source solution and may be adopted by the user for particular needs.

The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis to support endometriosis diagnosis and treatment. Material and Methods Blood samples (n=423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, the presence and character of CECs was tested during phases of menstrual cycle (MC) (n= 11). CECs were isolated by size-based separation from 2x 8ml PB. Results CECs were detected in 78.4% of blood samples. In line with the revised American Fertility Society (rAFS) classification CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate and severe. Surprisingly, the highest CEC negativity rate was reported for severe disease (21.1%). The highest CEC numbers were detected in the mid-secretory periods of MC, which corresponds with uterine lining decidualization. The cytomorphology of CECs captured during MC is changing between the epithelial, stromal and stem cell-like. CECs captured in mid-secretory period expressed KRT18, NANOG and VIM in higher amounts when compared to the genes in the proliferative phase of MC when KRT19 and ESR1 were mostly observed. GEA of the super-positive CECs samples (1000 CECs/8mL PB) revealed high expression of KRT18, VIM, NANOG and FLT1. The expression of these genes was elevated in the endometriosis tissue samples and endometrioma, too. Conclusion The panel of the identified CECs - genes could be tested in a prospective manner to confirm the predictive value of CECs in endometriosis diagnostics.

Due to species barriers and poor adaptability to new host environments, few pathogens cause global pandemics. But, SARS-CoV-2 is one exception with its high transmissivity and delayed onset of symptoms. Fortunately, the world was able to tap on the technologies especially the maturing RT-qPCR designed to combat SARS to launch an initial offensive on SARS-CoV-2. These initial efforts may have bought time for scientists to develop more refined diagnostic tests that specifically target SARS-CoV-2. This article describes the effort put forth by the biotech industry and academia in Singapore to develop diagnostic tests that aid the early detection of positive cases, and thereby help contain the virus. Direct tests such as RT-qPCR and antigen rapid test profile the virus nucleic acid and surface proteins, respectively. But, of equal importance in case detection and treatment is serological tests that measure the relative abundance of IgM and IgG which is indicative of infection phase and quality of immune response in positive cases. Other tests such as isothermal amplification, CRISPR-based diagnostics and breath tests are also in development or at initial field deployment, and would undoubtedly provide valuable use experience useful for the development of molecular assays to detect and combat the next pathogen of global concern.

Intraoperative load sensors have been developed with the aim of balancing the soft tissue in the knee during Total Knee Replacements (TKRs). Literature has shown success in soft tissue bal-ancing however, concerns regarding the accuracy of these sensors remain. For this reason, pre-vious research has attempted to create robust sensors for intraoperative use. The design of the sensor in this research has aimed to address the concerns outlined in the literature to create a new and novel smart-sensor for soft-tissue balancing. This new intraoperative load sensor included design features to increase accuracy while artificial intelligence allowed for comprehensive sensing across the entirety of the sensor, providing unparalleled insight during the operation. Notably, the sensor was designed to withstand loads of at least 450 N, ensuring robust perfor-mance of the sensor. To optimize the design process while minimizing cost, Finite Element Analysis was employed. This approach ensured the design features fulfilled their function while maintaining structural integrity to withstand loads. Moreover, the novelty of using training data from simulated data will reduce the iterative process of the labor-intensive collection of training data for the artificial intelligence while reducing human error associated with it. Results from the evaluation demonstrated the ability of this design to successfully bridge the current gap in the market by fulfilling all essential design criteria established within the literature. This innovative smart-sensing tool will in turn enhance patient outcomes and alleviate financial burdens to pa-tients and the healthcare systems by reducing the need for early revision surgeries associated with improper joint tension.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general progress of emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), where the ischemic segments of the intestine were examined. Nine others were operated for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT image of non-ischemic (control group), viable ischemic and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The COVID-19, caused by the SARS-CoV-2 virus is a pandemic that has affected 214 countries affecting more than 30.8 million people causing 0.957 million deaths as of third week of September, 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a check-list of factors to be taken care to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

The diagnostics of natural landscapes geoecological state in the course of the permafrost zone economic development should be based on the assessment of the destructive cryogenic processes formation. It is expedient to consider it in terms of landscapes resistance to cryogenic processes increase. The choice of lithocryogenic stability parameters is substantiated. These are: permafrost distribution over the area, its annual mean temperature and ice content, protective properties of the vegetation and etc. Cryogenic processes activation is estimated with regard to their area, development rate and attenuation, natural landscapes damage, hazard for engineering facilities operation. The assessment procedure, and the way of improving expert numerical scores are shown. At Geography Faculty of Lomonosov Moscow State University, the authors have developed a number of the approved methods of making evaluation maps of different scales applying the methods of landscape indication, modern methods of space images decoding, methods of expert scores, the method statistical calculations and methods of spatial GIS-analysis. The technique of Atlas geo-information mapping on the landscape basis has been introduced in seven atlases at scales from 1:3 000 000 to 1:20 000 000. These maps are widely used in design and survey organizations and in education.

The development of the automotive industry leads to the improvement of the designs of automatic transmissions and drives and to the development of methods for monitoring and diagnosing their condition. The trend of improving transmissions comes down mainly to the endless improvement of existing designs of CVTs and variators, which inevitably leads to the complication of designs and methods for their control and diagnostics.There is a need to create a fundamentally new simplified gearbox based on the scientific achievements of mechanics. However, the created structures remained inoperable due to the lack of theoretical justification.The adaptive gear variator developed by the author, which has CVT functions, is a mechanism with two degrees of freedom and with an additional constraint of a fundamentally new type, called a force - speed constraint. The force - speed constraint imposes a force restriction on the movement of links, while maintaining the number of degrees of freedom in the kinematics. Monitoring the state of the developed gearbox in the form of a non-switchable gear variator is greatly simplified, since the largest number of faults occur in the control system, and there is no control system in the gear variator. It seems possible to apply the digital twin method to diagnose the developed simplified CVT.The proposed article is devoted to a theoretical description of a fundamentally new adaptive gearbox, created on the basis of the latest achievements in mechanics, with the prospect of developing a simplified monitoring and diagnostic system for it

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Despite their relatively low incidence globally, CNS tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes..

During the last two decades several cases of venous thrombosis (VTE) after a prolonged period at a computer has been described, denominated “eThrombosis”. Video gaming on a computer has become very popular and can be a social activity where several players are gathered to play against each other or in a virtual environment for several days (“LAN (i.e., Local Area Network) parties”) where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate a potential coagulation activation during a 42 hour LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 hours, and plasma was analyzed for thrombin generation, and Thrombin-antithrombin-complexes (TAT), prothrombin Fragment 1+2 (F1+2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h gaming with minimal physical activity. Although an increased activity cannot be excluded, it does not directly indicate a risk of VTE in general. It may be specific and particularly susceptible in-dividuals who are prone to thrombosis and, therefore, are at risk of developing e-thrombosis.

The reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an established tool for the diagnosis of RNA pathogens. Its potential for automation has caused it to be used as a presence/absence diagnostic tool even when RNA quantification is not required. This technology has been pushed to the forefront of public awareness by the COVID-19 pandemic, as its global application has enabled rapid and analytically sensitive mass testing, with the first test targeting three viral genes published within days of the publication of the SARS-CoV-2 genomic sequence. One of those, targeting the RNA-dependent RNA polymerase gene, has been heavily criticised for supposed scientific flaws at the molecular and methodological level and this criticism has been extrapolated to doubts about the validity of RT-qPCR for COVID-19 testing in general. We have analysed this assay in detail and our findings reveal some limitations, but also highlight the robustness of the RT-qPCR methodology for SARS-CoV-2 detection. Whilst our data show that some errors can be tolerated, it is always prudent to confirm that primer and probe sequences complement their intended target, since when errors do occur, they may result in a reduction in the analytical sensitivity. However, in this case it is unlikely that a mismatch will result in poor specificity or significant number of false positive SARS-CoV-2 diagnoses, especially as this is routinely checked by diagnostic laboratories as part of their quality assurance.

The paper presents the results of a study of the concept of address fiber Bragg structures in the problem of vibration control. The mathematical model of measuring transformation is presented; the experimental study of a vibration diagnostics system based on Address Fiber Bragg Gratings is carried out; the quantitative and qualitative comparative assessment with electronic accelerometers is made; the gain by an order of magnitude in some parameters is shown.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Introduction: Austere environments include the wilderness and many lower-and-middle-income countries, many of these facing unrest and war. The access to advanced diagnostic equipment is often unaffordable even if available and is often liable to breakdown. This short review paper examines the options available to medical professionals to undertake clinical and point of care diagnostic testing in resource constrained environments and also illustrates the development of mobile advanced diagnostic equipment. The aim is to provide an overview of the spectrum and functionality of these devices beyond clinical acumen.

Abstract Background and Objective: Medical Microwave Radiometry (MWR) is used to capture the thermal properties of internal tissues and has usages in breast cancer detection. Our goal in this paper is to improve classification performance and investigate automated neural architecture search methods. Methods: We investigate optimizing the weights of a weight agnostic neural network using bi-population covariance matrix adaptation evolution strategy (BIPOP-CMA-ES) once the topology is found. We compare it against a weight agnostic and cascade correlation neural network. Results: The experiments are conducted on a breast cancer dataset of 4912 patients. Our proposed weight agnostic BIPOP-CMA-ES model achieved the best performance. It obtained an F1-score of 0.9225, accuracy of 0.9219, precision of 0.9228, recall of 0.9217 and topology of 153 connections. Conclusions: The results are an indication of the potential of MWR utilizing a neural network-based diagnostic tool for cancer detection. By separating the tasks of topology search and weight training, we are able to improve the overall performance.

Background: We aimed to explore microvascular changes evaluated with optical coherence tomography angiography (OCTA) in patients undergoing epiretinal membrane (ERM) pars-plana vitrectomy (PPV) combined with intravitreal Ozurdex implantation, compared with standard PPV. (2) Methods: Prospective interventional analysis on 25 eyes undergoing PPV+Ozurdex (Group A) and 25 eyes undergoing PPV alone. Best corrected visual acuity (BCVA) and OCTA parameters, such as vessel density (VD) of the superficial and deep capillary plexi (SCP and DCP) in the whole 6.4x6.4 mm and fovea area, were evaluated preoperatively and 3 months after surgery. (3) Results: Postoperative BCVA significantly improved in both groups. No cases of post-operative cystoid macular edema (CME) were reported in Group A vs. 2 eyes in Group B. In Group A we found a statistically significant increase of SCP’s VD in either the whole image (from 42.1±4.1 to 45.6±4.3 %, p=0.01) and the fovea image (from 38.5±7.5 to 41.7±4.2%, p=0.03). In Group B, we reported no significant variations in the SCP’s VDs. In the DCP, VD significantly increased only in the whole image in Group A. Stage 4 ERMs showed the greatest improvement in VD, especially in Group A. (4) Conclusions: In conclusion, intraoperative Ozurdex prompted a significant BCVA recover and limited the occurrence of postoperative CME compared to the standard procedure. Moreover, Ozurdex implant is associated with a better restoration of microvascular structure in either SCP and DCP.

Brainstem auditory evoked potentials (BAEPs) testing is very important when microvascular decompression (MVD) is performed with hemifacial spasm (HFS). The reason for this is that the vestibulocochlear nerve is located right next to the facial nerve, so the vestibulocochlear nerve may be affected by manipulation by surgery. The BAEPs test method for detecting vestibulocochlear nerve damage during surgery has been developed a lot and is helping a lot during surgery. In most HFS patients with normal vestibulocochlear nerve, the degree of vestibulocochlear nerve damage caused by surgery is reflected very well in the BAEPs test waveforms. Therefore, a real time test is the best way to minimize the damage to the vestibulocochlear nerve. The purpose of this study was to review the most recently published BAEPs test used in MVD surgery and to find out in detail the relationship between the vestibulocochlear nerve damage and the BAEPs waveforms.

Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Rapidly providing a definitive diagnostic test that can be used broadly by healthcare providers and members of the public in the setting of a disease emergency is critical to limit pathogen spread, develop and deploy medical countermeasures, and mitigate the social and economic harms of a serious epidemic or pandemic. There is extraordinary expertise within and outside of government working on these issues, and major accomplishments have been made to accelerate test development, expand laboratory testing capacity, and establish widespread point-of-care testing. Still, the United States does not have a plan to rapidly respond, to develop, manufacture, or deploy at national scale diagnostic testing in the earliest days of a new infectious disease crisis. Nor does the nation have a plan to sustain testing capacity at high volume over the course ofan enduring epidemic or pandemic. To address this gap, we are proposing a National Diagnostics Action Plan that describes the steps that are urgently needed to prepare for future infectious disease emergencies, as well as the actions we must take at the first signs of such events. These recommendations require substantial collaboration between the US government (USG) and the private sector to solve a series of challenges now, as well as to prepare for the massive and rapid scale-up of laboratory and point-of-care test development and testing capacity in future emergencies. The recommendations include establishing pre-event contracts; ensuring rapid access to clinical samples; creating a permanent public-private testing coordinating body to allow for rapid information sharing and improved cooperation among the USG, test developers, and clinical laboratories; and accelerating testing rollout at the beginning of an event—andthus, the effective public health management of a disease crisis. These recommendations were informed by extensive discussion with people who managed the COVID-19 and monkeypox responses, review of past reports written on diagnostic challenges, and the experiences of the authors.

Micro turbojets are used for propelling radio-controlled aircraft, aerial targets and personal air vehicles. When compared to full-scale engines, they are characterized by relatively low efficiency and durability. In this context, the degraded performance of gas path components could lead to an unacceptable reduction in the overall engine performance. In this work, a data-driven model based on a conventional Artificial Neural Network (ANN) and an extreme learning machine (ELM) was used for estimating the performance degradation of the micro turbojet. The training datasets containing the performance data of the engine with degraded components were generated using the validated GSP model and the Monte Carlo approach. In particular, compressor and turbine performance degradation were simulated for three different flight regimes. It was confirmed that component degradation had a similar impact in flight than at sea level. Finally, the datasets were used in the training and testing process of the ELM algorithm with four different input vectors. Two vectors had an extensive number of virtual sensors, and the other two were reduced to just fuel flow and Exhaust Gas Temperature. Even with the small number of sensors, the high prediction accuracy of ELM was maintained for takeoff and cruise but was slightly worse for variable flight conditions.

Retinopathy is a human eye disease that causes changes in retinal blood vessels that leads to bleed, leak fluid and vision impairment. Symptoms of retinopathy are blurred vision, changes in color perception, red spots, and eye pain. In this paper, a new methodology based on Convolutional Neural Networks (CNN) is developed and proposed to diagnose and give a decision about the presence of retinopathy. The CNN model is trained by different images of eyes that have retinopathy and those which do not have retinopathy. The performance of the proposed model is compared with the related methods of DREAM, KNN, GD-CNN and SVM. Experimental results show that the proposed CNN performs better.

The increased cultivation of Cannabis sativa L. in North America, represented by high Δ9-tetrahydrocannabinol-containing (high-THC) cannabis genotypes and low THC-containing hemp genotypes, has been impacted by an increasing number of plant pathogens. These include fungi which destroy roots, stems and leaves, in some cases causing a build-up of populations and mycotoxins in the inflorescences that can negatively impact quality. Viroids and viruses have also increased in prevalence and severity and can reduce plant growth and product quality. Rapid diagnosis of the occurrence and spread of these pathogens is critical. Techniques in the area of molecular diagnostics have been applied to study these pathogens in both cannabis and hemp. These include polymerase chain reaction (PCR)-based technologies, including RT-PCR, multiplex RT-PCR, RT-qPCR, and ddPCR, as well as whole genome sequencing (NGS) and bioinformatics. In this study, examples of how these technologies have enhanced the rapidity and sensitivity of pathogen diagnosis on cannabis and hemp will be illustrated. These molecular tools have also enabled studies on the diversity and origins of specific pathogens, specifically viruses and viroids, and these will be illustrated. Comparative studies on the genomics and metabolomics of healthy and diseased plants are urgently needed to provide insight into their impact on quality and composition of cannabis and hemp-derived products. Management of these pathogens will require monitoring of their spread and survival using the appropriate technologies to allow accurate detection, followed by appropriate implementation of disease control measures.

Machine learning (ML) is growing in popularity for various particle accelerator applications including anomaly detection such as faulty beam position monitor or RF fault identification, for non-invasive diagnostics, and for creating surrogate models. ML methods such as neural networks (NN) are useful because they can learn input-output relationships in large complex systems based on large data sets. Once they are trained, methods such as NNs give instant predictions of complex phenomenon, which makes their use as surrogate models especially appealing for speeding up large parameter space searches which otherwise require computationally expensive simulations. However, quickly time varying systems are challenging for ML-based approaches because the actual system dynamics quickly drifts away from the description provided by any fixed data set, degrading the predictive power of any ML method, and limits their applicability for real time feedback control of quickly time-varying accelerator components and beams. In contrast to ML methods, adaptive model-independent feedback algorithms are by design robust to un-modeled changes and disturbances in dynamic systems, but are usually local in nature and susceptible to local extrema. In this work, we propose that the combination of adaptive feedback and machine learning, adaptive machine learning (AML), is a way to combine the global feature learning power of ML methods such as deep neural networks with the robustness of model-independent control. We present an overview of several ML and adaptive control methods, their strengths and limitations, and an overview of AML approaches. A simple code for the adaptive control algorithm used here can be downloaded from: https://github.com/alexscheinker/ES_adaptive_optimization

The target of an antibody plays a significant role in the success of antibody-based therapeutics and diagnostics, and to an extent, that of vaccine development. This importance is focussed on the target binding site – epitope, where epitope selection as a part of design thinking beyond traditional antigen selection using whole cell or whole protein immunisation can positively impact success. With purified recombinant protein production and peptide synthesis to display limited/selected epitopes, intrinsic factors that can affect the functioning of resulting antibodies can be more easily selected for. Many of these factors stem from the location of the epitope that can affect accessibility of the antibody to the epitope at a cellular or molecular level, direct inhibition of target antigen activity, conservation of function despite escape mutations, and even non-competitive inhibition sites. Through the incorporation of novel computational methods for predicting antigen changes to model-informed drug discovery and development, superior vaccines and antibody-based therapeutics or diagnostics can now be more easily designed to mitigate failures. With detailed examples, this review highlights the new opportunities, factors and methods of predicting antigenic changes for consideration in sagacious epitope selection.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

Objective: Surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain-tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence-guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we developed an intraoperative rapid fluorescence cytology system, and evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: Twenty-five selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A “weak fluorescence” indicated a reduction in the tumor cell density, whereas “no fluorescence” did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence.Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was a useful to evaluate the presence of tumor cells in the resection cavity walls, and provides surgical implications for the more complete resection of malignant gliomas.

Deep Neutral Networks (DNNs) were initially proposed towards the midst of the 20th century, motivated by the neural structure and mechanism of the human brain. Thanks to major ad-vancements in computational resources, during the past decade DNN-based systems have demonstrated unprecedented performance in terms of accuracy and speed. However, recent work has shown that such models may not be sufficiently robust during the inference process. Furthermore, due to the data-driven learning nature of DNNs, designing interpretable and gen-eralizable networks is a major challenge, especially in critical applications, such as medical Computer Aided Diagnostics (CAD) and other medical imaging tasks, including classification, regression and reconstruction. Within this context, a line of physics-driven approaches for deep learning has recently emerged, aimed at improving the stability and generalization capacity of DNNs for medical imaging applications. In this paper, we review recent work focused on phys-ics-driven or prior-information learning for a variety of imaging modalities and medical applica-tions. We discuss how the inclusion of domain-related knowledge into the learning process and networks’ design supports their stability and generalization capability. In addition, we highlight current and future challenges within this scope.

Sudden unexpected death (SUD) is a fatal event that occurs in an apparently healthy subject so that such an abrupt outcome could have not been predicted. SUD - including sudden intrauterine unexplained death (SIUD), sudden neonatal unexpected death (SNUD), sudden infant death syndrome (SIDS), sudden unexpected death of the young (SUDY), sudden unexpected death in the adult (SUDA) - occurs as the first manifestation of an unknown underlying disease or within a few hours of presentation of a disease. SUD is a major unsolved, shocking form of death that occurs frequently and can happen at any time without warning. For each case of SUD, a review of clinical history data and performance of a complete autopsy, particularly focused on the study of the cardiac conduction system were carried out according to the necropsy protocol devised by the Lino Rossi Research Center, Università degli Studi di Milano, Italy. Research cases are represented by 75 SUD victims, subdivided into 15 SIUD, 15 SNUD, 15 SUDY, and 15 SUDA victims, collected and selected for this study. After the routine autopsy and clinical history analysis, the death remained unexplained and hence a diagnosis of SUD was assigned to the 75. subjects, which included45 females (60%) and 30 (40%) males, ranging in age from 27 gestational weeks to 76 years. Serial sections of the cardiac conduction system disclosed frequent congenital alterations, of the cardiac conduction system in fetuses and infants. An age-related significant difference in distribution among the 5 age-related groups was detected for the following anomalies of the conduction system: central fibrous body (CFB) islands of conduction tissue, fetal dispersion, resorptive degeneration, Mahaim fiber, CFB cartilaginous meta-hyperplasia, His bundle septation, sino-atrial node (SAN) artery fibromuscular thickening, atrio-ventricular junction hypoplasia, intramural right bundle branch, and SAN hypoplasia. The results data are useful to understand the cause of death for all SUD cases that were unexpected and would have otherwise remained unexplained, so to motivate medical examiners and pathologists to perform more in-depth studies.

We have used Mass Multivariate Method on structural, resting state and task related fMRI data from two groups of patients with schizophrenia and depression, respectively, in order to define several regions of significant relevance to the differential diagnosis between those conditions. The regions included the left Planum polare, Left opercular part of the inferior frontal gyrus (OpIFG), Medial orbital gyrus (MOrG), Posterior Insula (PIns), and Parahippocampal gyrus (PHG). This study delivers evidence that multimodal neuroimaging approach can potentially enhance the validity of psychiatric diagnosis. Either structural, or resting state or task related functional MRI modality cannot provide independent biomarkers. Further studies need to consider and implement a model of incremental validity to combine clinical measures with different neuroimaging modalities to discriminate depressive disorders from schizophrenia. Biological signatures of disease on the level of neuroimaging are more likely to underpin broader nosological entities in psychiatry.

COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccine will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow for society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point of care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of appropriate test for specific use case difficult. In this review, we have used the World Health Organization’s (WHO) recently published Target Product Profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several top-performing POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, that meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection), or indirect diagnosis of past infection (host antibodies) are highlighted here.

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

Knowledge of a lasers beam’s profile throughout a laser system and experiment can help immensely in diagnosing laser problems and assisting in beam alignment and focusing at a sample. Obtaining such profiles is a trivial task in the ultraviolet-visible wavelength range but more challenging with near-infrared to infrared beams. Scientific grade bolometer arrays, suitable for such a task, do exist but are extremely costly, relatively large and have a large pixel size, of the order of 80 μm, which is adequate for profiling larger beams but poses an issue when trying to profile sub 100 μm beams for example at a focal point. This communication identifies a micro-bolometer array for near- to mid-infrared laser beam profiling, which is extremely low cost. In addition, the device is very compact, enabling use in confined spaces, and has a small, 12 μm, pixel size permitting the profiling of focused laser beams. The best scientific grade device identified has a pixel size of 17 μm. This device is a powerful tool for infrared laser spectroscopists, reducing the time required to measure the spot size of beams and to achieve spatial overlap of multiple infrared beams as used in two-dimensional infrared spectroscopy, saving many hours of setup time. The use of the bolometer array as a spectrographic detector and probe of long-term beam drifts is also demonstrated.

Background and objectives: As the oblique lateral interbody fusion at L5/S1 (OLIF51) and lateral corridor approach (LCA) have gained popularity, the understanding of precise vascular structure at L5/S1 level is indispensable. The objectives of this study were to investigate the vascular anatomy at L5/S1 level, and to compare the movement of vascular tissue between supine and lateral decubitus position using the intraoperative enhanced CT and MRI. Materials and Methods: A total of 43 patients who underwent either OLIF51 or LCA were investigated with the average age at surgery of 60.4 (37-80) years old. The preoperative MRI was taken to observe axial and sagittal anatomy of vascular position under supine position. The intraoperative vein-enhanced CT was taken just before incision in the right decubitus position, and compared to supine MRI anatomy. The iliolumbar vein appearance and its types were also classified. Results: The average vascular window allowed for OLIF51 was 22.8 mm and 34.1 mm at either L5 caudal endplate or S1 cephalad endplate level, respectively. It allowed for LCA was 14.2 mm and 12.6 mm at either level, respectively. The left common iliac vein moved 3.8 mm and 6.9 mm to right direction at either level from supine to right decubitus position, respectively. The bifurcation moved 6.3 mm to caudal direction from supine to right decubitus. The iliolumbar vein was located at 31 mm lateral from midline, and MRI detection rate was 52%. Conclusions: The precise measurement of vascular anatomy indicated that OLIF51 approach was the standard minimally invasive anterior approach for L5/S1 disc level compared to LCA, however, there were many variations in quantitative anatomy as well as significant vascular movements between supine and right decubitus position. In the clinical setting of OLIF51 and LCA surgeries, the careful preoperative evaluation and intraoperative 3D imaging are recommended for the safe and accurate surgery.

We present a laser-plasma electron accelerator module designed to be driven by high repetition rate lasers for industrial applications of laser-driven electron beams. It consists of a single vacuum chamber containing all the necessary components for producing, optimizing, and monitoring electron beams generated via laser wakefield acceleration in a gas jet. The core methods involve comprehensive metrological assessments, including rigorous temporal laser pulse characterization and contrast measurements, supplemented by detailed spatio-temporal distribution analyses of the laser system. Results demonstrate the good stability and reproducibility of the laser system, confirming its suitability for advanced scientific and industrial applications. We demonstrate the full functionality of the laser-plasma accelerator module and perform target density and laser-plasma characterizations. Our work is a first step towards the wide dissemination of fully integrated laser-plasma accelerator technology.

Helminths are commonly found in grazing equids, with the cyathostomin nematodes and the cestode, Anoplocephala perfoliata, being the most prevalent. Most horses harbour low burdens of these parasites and do not develop signs of infection; however, in a small number of animals, high burdens can accumulate and cause disease. Cyathostomins are associated with a syndrome known as larval cyathostominosis. This occurs when large numbers of larvae emerge from the large intestinal wall. This disease has a case fatality rate of up to 50%. A. perfoliata infection has been associated with various types of colic, with burdens of >20 worms associated with pathogenicity. Anthelmintic resistance is a serious problem in cyathostomins and is emerging in A. perfoliata. Control methods that reduce reliance on anthelmintics now need to be applied, especially as no new dewormer compounds are on the horizon. Sustainable control methods must employ diagnostics to identify horses that require treatment. Coprological tests (faecal egg counts, FEC), have been used for several decades to inform treatment decisions to reduce helminth egg shedding. These tests cannot be used to assess host burdens as FEC do not correlate with cyathostomin or A. perfoliata burdens. In the last decade, new tests have become available that measure parasite-specific antibodies, levels of which have been shown to correlate with parasite burden. These tests measure antigen-specific IgG(T) and are available in serum (cyathostomin, A. perfoliata) or saliva (A. perfoliata) formats. Tests for other helminths have been developed as research tools and need to be translated to support equine clinicians in practice. A key element of sustainable control strategies is that diagnostics must be used in combination with management approaches to reduce environmental transmission of helminths; this will help limit the proportion of horses harbouring parasite burdens that need to be targeted by treatment.

The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) became recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure or exposure to the contrast agent. The novel ultrasound modalities such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS) or high frequency micro-ultrasound (MicroUS) may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.

The work is devoted to the search for effective solutions to the applied problem of early diagnostics of plant stress in the conditions of smart farming and based on modern explicable artificial intelligence (XAI). The study mostly oriented on the theory and practice of XAI, focused on the use of hyperspectral imagery (HSI) and Thermal Infra-Red (TIR) sensor data at the input of a neural network. The first our goal is to build an XAI neural network, explainable due to its structure, the input of which is a datascientist oriented HSI 'explanator', and the output is a biologist oriented TIR 'explanator'. In the middle is SLP-regressor which solves the universal problem of training HSI pixels to temperatures of plants, needed for early plant stress diagnostic. The result can be considered as prototype of a special XAI explanator which is assigned to transform explanator specialized on area 1 onto explanator specialized on area 2. Using this HSI-TIR explanator we ensured the follows: extend HSI data by TIR attribute; providing TIR data for early diagnostic of plant stress; reducing dimensionality HSI needed for TIR training 25 times (from 204 to 8) preserving the same accuracy of temperature prediction (RMSE=0.2-0.3C). This reducing was achieved without using PCA methods. The constructed model is computationally efficient in training: the average training time is significantly less then 1 min (Intel Core i3-8130U, 2.2 GHz, 4 cores, 4 GB). One of the 8 channels, 820 nm, is the leader in correlation with TIR, what allows building local linear temperature prediction functions.

Both SARS-CoV-2 and SARS-CoV initially appeared in China and spread to other parts of the world. SARS-CoV-2 has generated a COVID-19 pandemic causing more than 6 million human deaths worldwide while the SARS outbreak quickly ended in six months with a global total of 774 reported deaths. One of the factors contributing to this stunning difference in the outcome between these two outbreaks is the inaccuracy of the RT-qPCR tests for SARS-CoV-2, which generated a large number of false-negative and false-positive test results that have misled patient management and public health policy-makers. This article presented Sanger sequencing evidence to show that the RT-PCR diagnostic protocol established in 2003 for SARS-CoV can in fact detect SARS-CoV-2 accurately due to the well-known nonspecific PCR amplification of DNAs with similar sequences. Using nested RT-PCR followed by Sanger sequencing to retest 50 patient samples collected in January, 2022 and sold as RT-qPCR positive reference confirmed 21 (42%) were false-positive. Although the other 29 positive isolates were categorized as Omicron variant by partial sequencing of the N gene, and the RBD and the NTD of the S gene, 9 (31%) showed focal to complete sequencing failure in the S gene segments due to multi-allelic SNPs. During the course of the study, an Omicron variant isolate containing a BA.1 NTD and a BA.2 RBD in its S gene was also detected. Routine partial S gene sequencing of all PCR-positive samples can timely discover multi-allelic SNPs and viral recombination in the circulating variants for investigation of their impacts on vaccine efficacies, therapeutics and diagnostics.

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

COVID-19, the disease caused by the new coronavirus, SARS-CoV-2, has caused significant human and economic burden. Of the three major methods to mitigate the effect of the virus, diagnostics have become the focal point because vaccines and therapeutics, despite the intense effort of scientists worldwide, will take months to develop, test for safety and efficacy, scaleup and distribute to millions. This perspective aims to clarify some of the issues related to COVID-19 diagnostics and highlights some of the challenges key stakeholders including policymakers, businesses, managers, scientists and individuals face during this evolving pandemic.

.Background: Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in patients with colorectal carcinoma at high risk of recurrence but still without clinically and radiologically evident signs of peritoneal spread. This study aims to analyze the feasibility of this proactive, early phase, multimodality approach. Methods: A mono-institutional, prospective, parallel, two-stage phase II trial enrolled 49 patients to standard surgery or surgery plus intraoperative HIPEC. Before the procedure and during surgery, patients received intravenous fluorouracil (and leucovorin to potentiate oxaliplatin activity. Data analysis included length of hospital stay, surgery duration, type of surgery and chemotherapy-related complications risk score. Results: No significant difference was seen in the median time spent in the hospital with a median stay of 7 days in both groups (p=0.5720). The surgical procedure's median duration was longer in the HIPEC group than in the control one. Side-effects and surgical complications did not cross at any time the Pocock-type boundary for side/effect monitoring (p=0.80, N.S.). Conclusions: The present prospective study results demonstrate the feasibility and safety of the colorectal surgery plus HIPEC treatment in patients with colorectal cancer patients at high-risk for peritoneal invasion, although clinically and radiologically undetectable.

Background: This prospective study assesses the use of Rapid Remote Online Cytological Evaluation analysis for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved a total of 314 Rapid Remote Online Cytological Evaluations (17 brush, 143 fine needle aspirations and 154 imprint cytologies) analyses performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was determined and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of Rapid Remote Online Evaluation, 86 cytological benign and 190 malignant and 38 findings of unclear diagnosis were recorded (Ø assessment time 100 sec., range 11 - 370sec.). In 27 of the 38 cases with unclear diagnosis, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another five of these 38 cases remained unclear. Excluding these 38 findings, the Rapid Remote online cytology achieved a sensitivity of 78.6% with a specificity of 99.5% and a correct classification rate of 93.1% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived.

Novel treatment strategies are emerging for rare, genetic diseases, resulting in clinical trials that require adequate biomarkers for the assessment of the treatment effect. For enzyme defects, biomarkers that can be assessed from patient serum, such as enzyme activity, are highly useful, but the activity assays need to be properly validated to ensure a precise, quantitative measurement. Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by the deficiency of the lysosomal hydrolase aspartylglucosaminidase (AGA). We have here established and validated a fluorometric AGA activity assay for human serum samples from healthy volunteers and AGU patients. We show that the validated AGA activity assay is suitable for the assessment of AGA activity in the serum of healthy controls and AGU patients, and it can be used for diagnostics of AGU and, potentially, for following a treatment effect.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is encountered in a subset of children who have undergone an operative procedure of the posterior cranial fossa, mainly involving the vermis, and the most frequent underlying pathology is proved to be medulloblastoma. The most common characteristics of this syndrome include an often transient, although protracted, language impairment, emotional lability, along with cerebellar, and brainstem dysfunction. Nevertheless, a significant number of patients experience persistent neurological deficits and lasting neurocognitive impairment. A lot of research and clinical studies have been performed in order to better delineate this syndrome. The main obstacles in our way to highlight all aspects of this syndrome were related with an inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty surrounding risk factors and etiology. Currently, there is a combination of diagnostic criteria that are regarded as prerequisites in order to establish the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. Several risk factors are recognized as implicated in the pathogenesis of this syndrome, including midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment. A proposed etiology of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Specific treatment for CMS is lacking, and it continues to be directed at symptom management. Our aim is to present a comprehensive narrative review of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Moreover, we attempt to recognize the most widely recognized priorities of the research community in order to expand our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/ml and/or Gleason score ≥8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes / lymph node metastases outside the established node template in high-risk PCa.

Neuromonitoring of the efferent nerve impulses transmission in the spinal cord tracts during surgical scoliosis treatment makes it possible to assess whether the functional status is deteriorating, affecting the procedure's safety. Is there any relationship between pre- and intraoperative motor evoked potentials recordings and does idiopathic scoliosis (IS) surgical correction improve directly the spinal efferent transmission? This study aimed to compare the results of surface recorded electromyography (EMG), electroneurography (ENG, M and F-waves), and especially motor evoked potentials (MEP) from tibialis anterior (TA) muscle bilaterally in 353 girls with the right idiopathic scoliosis (types 1A-4C according to Lenke classification). It has not yet been documented whether the results of MEPs recordings induced by transcranial single magnetic stimulus (TMS, pre – and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1 – after pedicle screws implantation, T2 – after scoliosis curvature distraction and derotation following two rods implantation) can be compared for diagnostic verification of improvement of the spinal neural transmission. The study also attempted to determine whether the constant level of optimal anesthesia during the certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. Values of amplitudes but not latencies in MEPs recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts postoperatively. Results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p=0.04. This asymmetry had been significantly reduced following IS surgery. The surgeries in IS patients brought significant improvement (p=0.04) in parameters of amplitudes of sEMG recordings, however reflecting still the consequences of the neurogenic injury of TA muscle motor units. ENG studies results indicated the symptoms of the axonal type injury in peroneal motor fibers improved only on the concave side at p=0.04 in parallel with the significant improvement of F-waves parameters, which suggests that surgeries might result in the lumbar ventral roots decompression. There were not detected significant differences in amplitudes or latencies of MEPs induced with TMS or TES comparing the parameters recorded preoperatively (one day before surgery) and intraoperatively in T0. The amplitudes of TES evoked MEPs increased gradually at p=0.04 in the subsequent periods (T1 and T2) of observation. The significant reduction of MEPs latency at p=0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEPs amplitude changes measured in T0-T2 revealed lack of relationships. It is not likely that they could be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Considering that MEPs amplitude parameter reflects the number of axons excited from the motor cortex and transmitting the efferent impulses via spinal descending tracts in the white matter, pre- (TMS evoked) and intraoperative (TES evoked) recordings are reliable for evaluating the patient’s neurological status before and during surgical scoliosis correction procedures. The results of this study indicate an agreement between preoperative and early-intraoperative evaluations with these both diagnostic methods. An increase of MEPs amplitude parameters recorded on both sides after scoliosis surgery proves immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings it can be concluded that surgeries might directly result in the additional lumbar ventral roots decompression. Our results of the tests on the possible variability of the anesthesia level on the parameters of intraoperative recorded MEPs show no clear relationships. We can conclude that MEPs parameters changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings. Further studies on a larger population of patients with long-lasting observation postoperatively are required to confirm the presented conclusions on the direct influences of scoliosis surgery on improvement of the motor function in patients with IS.

Condition monitoring is today a crucial and unavoidable practice related to the use of widespread mechanical components as rolling element bearings. Despite the diffusion of new data-driven techniques to analyze vibrational signals and detect the state of health of the system, mathematical tools, deriving more or less directly from the Fourier transform and defined either on the time or the frequency domain or on a combination of them (i.e. signal-based techniques), remain still essential and irreplaceable in the light of the deep and detailed information they provide. In this paper the diagnostic efficacy of an ample spectrum of these methods is investigated, applying them to study faults occurrence in the first bearing dataset released by NASA IMS Center. Thanks to their analytical definition, which is formulated taking into consideration to some extent the mathematical nature of the signal, faults signatures can be clearly identified and their temporal development can be fully traced, confirming their ability as powerful means to constantly monitor the state of a system even in real-time applications.

Juvenile idiopathic arthritis (JIA) is a disease with unknown causes within all forms of arthritis in children under 16 years of age. The diagnosis is made when another joint pathology is excluded. Difficulties in early and differential diagnosis lead to the rapid disability of patients and an unfavourable life prognosis. Therefore, timely diagnosis is necessary to prevent irreversible damage to the joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, which includes X-ray, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring disease activity, prognosis during the course, and outcome in children with JIA. Each method has its own advantages and disadvantages. The introduction of the method of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as sub-Saharan Africa (SSA). The advent of coronavirus has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis (PRISMA). We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full-text via EBSCOhost databases from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to the gold reference standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458-0.541); 0.535 (95% CI: 0.401-0.663); 0.952 (95% CI: 0.60-1.324); 1.381 (95% CI: 0.391-4.879); and 0.944 (95% CI: 0.579-1.538), respectively. Evidence shows that mobile-linked POC diagnostics' diagnostic accuracy is presently moderate in detecting infections in sub-Saharan Africa. Future research is recommended to evaluate mHealth devices' diagnostics with excellent sensitivities and specificities in diagnosing diseases in this setting.

Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.

Novel sensing technologies for liquid biopsies offer a promising prospect for the early detection of metabolic conditions through -omics techniques. Indeed, high-field NMR facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognize unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimized experiments, including glucose (≤ 2.6 mmol./L) and acetone (25 μmol./L), and additionally in readily-accessible biofluids. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics, and offer a perspective on the future of this technique appealing to point-of-care applications.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

Within an Internet of Multimedia Things, the risk of disclosing streamed video content, such as arising from video surveillance, is of heightened concern. This leads to the encryption of that content. To reduce the overhead and lack of flexibility arising from full encryption of the content, a good number of selective-encryption algorithms have been proposed in the last decade. Some of them have limitations, in terms of significant delay due to computational cost, or excess memory utilization, or, despite being energy efficient, do not provide a satisfactory level of confidentiality, due to their simplicity. To address such issues, this paper presents a lightweight selective encryption scheme, in which encoder syntax elements are encrypted with the innovative EXPer (EXtended Permutation with exclusive OR). The selected syntax elements are taken from the final stage of video encoding that is during entropy coding. As a diagnostic tool, the Encryption Space Ratio measures encoding complexity of the video relative to the level of encryption so as to judge the success of the encryption process, according to entropy coder. A detailed comparative analysis of EXPer with state-of-the-art algorithms confirms that the EXPer provides significant confidentiality with a small computational cost and negligible encryption bitrate overhead. Thus, the results demonstrate that the proposed security scheme is a suitable choice for constrained devices in an Internet of Multimedia Things environment.

Heavy Ion Beam Probing (HIBP) diagnostic is a powerful tool for electric field studies in hot dense plasma of modern day toroidal magnetic confinement devices. On the TUMAN-3M to-kamak, the HIBP have been used in regimes with improved plasma confinement to clear up the role of radial electric field in the transition to good confinement regimes. Recently, a moderni-zation of the TUMAN-3M HIBP diagnostics was performed aiming to reconfigure it for a work with a reversed plasma current direction and improvement of overall stability of the diagnostic. The results of first measurements of plasma potential in co-NBI scenario are reported and dis-cussed.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Objectives: Endovascular aneurysm repair (EVAR) in hostile neck has been associated with adverse outcomes. We aimed to determine the association of infrarenal aortic neck angle and length and establish an optimal cutoff value to predict intraoperative neck complications and post-operative outcomes. Methods: This was a retrospective review of intact infrarenal abdominal aortic aneurysm (AAA) with severe neck angulation (> 60 degrees) who underwent EVAR from October 2010 to October 2018. Demographic data, aneurysm morphology, and operative details were collected. The ratio of neck angle and length was calculated the optimal cutoff value of the aortic neck angle-length index. Patients were classified into two groups using latent profile analysis. Intraoperative neck complications, adjunct neck procedures, and early and late outcomes were compared. Results: 115 patients were included. Group 1(G1), aortic neck angle-length index ≤ 4.8, had 95 patients and Group 2 (G2), aortic neck angle-length index > 4.8, had 20 patients. Demographic data and aneurysm morphology were not significantly different between groups except for neck length (P < 0.001). G2 had more intra-operative neck complications than G1 (21.1% vs 55%, P = 0.005). Adjunctive neck procedures were more common in G2 (18.9% vs 60%, P < 0.001). Thirty-day mortality rate was not statistically different. G1 patients had a 5-year proximal neck re-intervention free rate comparable to G2 patients (93.7%G1 vs 87.5%G2, P = 0.785). The 5-year overall survival rate was not statistically different (59.9%G1 vs 69.2%G2, P = 0.891). Conclusions: Patients with aortic neck angle-length index > 4.8 are at greater risk of intraoperative neck complications and adjunctive neck procedures than patients with an aortic neck angle-length index ≤ 4.8. The 5-year proximal neck re-intervention free rate and the 5-year survival rate were not statistically different. The aortic neck angle-length index is a reliable predictor of intra-operative neck complications during EVAR in AAA with severe neck angulation.

Background: due to increase in total hip arthroplasties (THAs), the incidence of periprosthetic hip fractures (PPHFs) is forecast to raise considerably in the next decades, with Vancouver B1 fractures (VB1) accounting for one third of total cases. Femur fixation with cerclages (with or without screws) is considered the current treatment option for intraoperative VB1. Methods: the study retrospectively includes data from patients who developed VB1 PPHFs during THAs from December 3rd 2020 to November 30th 2022. The primary outcome of this study was to identify the reintervention-free survival rate. The secondary aim was to determine clinical and radiographic assessment at follow-up, based on Harris hip score (HHS) and limb length discrepancy (LLD). Results: 37 patients with mean age 60.03 ± 15.49 (22 to 77) years old were included. Overall, the Kaplan-Meier estimated a re-operation free survival rate of 99% (CI 95%) at 6 months. The mean limb length discrepancy (LLD) improved from -3.69±6.07 (range -27.9 to 2.08) mm to 0.10±0.67 (range -1.07 to 1.20) mm. The mean HHS improved from 42.72±14.37 (range 21.00-96.00) to 94.40±10.32 (range 56.00-100.00).

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Background: We assess locoregional drug targeting effectiveness of intraoperative (IO) cryoprobe-assisted injection of blue dye (BD) and cytotoxic-tracer mixture (TTM), in VX2 tumor model, and its translational value to cryo-assisted breast tumor surgery with BD alone. Methods: Under computed tomography (CT) guidance, we injected two ml TTM in five aliquots in the margin of 16 frozen or normothermic VX2 tumors. We evaluated the IO and post-operative drug targeting and therapeutic efficacy in tumor-host interface (T-HI) by CT, gross examination, and histopathology. In twenty-six T1 to T4 primary breast cancer (BRCA) we performed ultrasound-guided (US) cryoprobe-assisted tumor freezing, BD guided lymphatic mapping, and surgery. We evaluated, IO and in freshly resected specimen, BD distribution pattern in T-HI, lymph node(s), breast parenchyma, and resection cavity. Results: Fluids-impervious frozen VX2 or breast tumor transported drug(s) an arc-like pattern at T-HI regardless of freeze dose, number of freeze-thaw cycles, drug dose fractionation, tumor characteristics or dimensions. During melting, TTM spread within fifty percent VX2 tumor mirrored that of T-HI; it was massive in normothermia. In VX2 twenty percent focal margin necrosis at pathology coincided with CT gap; in both studies, BD dose-staining spread in T-HI and tumor was linear. Eighty-four patients had one to twelve stained axillary lymph nodes; sixty-nine percent and all respectively, had another quadrant and resection cavity stained. Conclusion: Intraoperative freezing-assisted drug delivery and targeting techniques during cryoablation of VX2 tumor translate successfully to locoregional BD targeting, lymphatic mapping during cryo-assisted surgery of breast cancer.

Abstract: Background: Non-invasive acquistion of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r=0.64) and PCS (r=0.55) (p<0.01), as well as MAPIBP/DBPIBP for PES (r=0.6/0.55) and PCS (r=0.5/0.45) (p<0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease(0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.