Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

Background: Morphological alterations in intracranial pressure pulse waveform (ICPPW) secondary to intracranial hypertension (ICP >20 mmHg) and reduction in intracranial compliance (ICC) are well known indicators of neurological severity. To date, no studies have documented the ICPPW modifications after intracranial hypertension resolution with decompressive craniectomy (DC). The present study aimed to assess the morphological alterations in ICPPW among neurocritical care patients with and without DC, by comparing the variations of ICPPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of severe traumatic or spontaneous conditions were included. Mean ICP values were compared with ICPPW features (P2/P1 ratio, TTP and pulse amplitude). Elevation in ICP was produced by means of ultrasound-guided manual internal jugular veins compression. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. 21 (36%) presented no skull defects, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±13.59 for intact and ±17.66 mmHg for DC, with ICP induced elevation also similar between groups (p= 0.56). Significant elevation was observed for P2/P1 ratio for groups 1 and 2, whereas reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, whereas reduction of 0.03 for group 3, p=0.01). Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPPW indicated DC to be protective for further influences of ICP elevations over the brain. Analysis of ICPPW seems to be an alternative to real time ICC assessment.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

The focus of this work lies in the construction of monitoring system designed in the form of a patch using a long-lasting potentiometric electrolyte concentration sensor from metal electrodes, in a galvanic cell configuration Mg(s)|NaCl(aq)|Cu(s). Initially, a mathematical analysis was conducted on the expected sensor output through the Nernst equation. The experimental phase involved conducting controlled tests in the laboratory using various molar concentrations of sodium chloride (NaCl) in aqueous solution. Results showed that the electrolyte sensor allows for monitoring electrolyte levels in NaCl in the range of 0.02 to 1 M/L, with electrode lifespan exceeding 10 days. On the other hand, when patch is using human sweat during controlled exercise routines, it showed the sensor's capability for monitoring changes in the subjects' hydration levels in real time. The sensor output potential is greater than 1.7 volts when the sensor electrodes are in contact with human sweat, which is equivalent to measuring molar concentrations at normal hydration and moderately high hydration levels. Sensor results indicate that the system can function in a self-powered manner without external batteries. Additionally, the extended lifespan of its electrodes allows for continuous monitoring of imbalances in the human body, showcasing the system capability for long-term health assessment.

Background: Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurement when the ICP probe was inserted in the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values. Methods: Two Spiegelberg 3PN-sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared. Results: The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0mmHg and 50mmHg (p<0.001); at 60mmHg there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma. Conclusion: Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to falsely addresses falsely elevated ICPs.

Ab initio density functional theory molecular dynamics extensive calculations were used for the first time to evaluate stability conditions for relevant phases of InN. In particular, thermal decomposition of InN with formation of N2 molecules and pressure induced wurtzite – rocksalt solid-solid phase transition were established. The results consistent with available experimental data allowed a critical evaluation of potential and limitations of the proposed simulation method. The ab initio molecular dynamics as an efficient tool for simulations of phase transformations of InN including solid-solid structural transition and thermal decomposition with formation of N2 molecules has been demonstrated. It is of high interest because InN being important component of epitaxial quantum structures has still not been obtained as a bulk single crystal making difficult a determination of its basic physical properties and designing new applications.

The Eastern Kunlun Fault Zone (EKFZ) is located in a seismic blank area. This study investigates the hydrogeochemical characteristics of varied-temperature springs in the EKFZ to understand the relationship between fractures, fluids and earthquakes. It aids in establishing their induction mechanisms and assists in monitoring the earthquake precursors of the EKFZ. In this study, the main elements, trace elements, hydrogen and oxygen isotopes and strontium isotopes of 23 varied-temperature springs in the EKFZ were analyzed. The results reveal the source of groundwater recharge, hydrochemical types, mineral saturation, and for a select few springs indicative of geothermal activity, collected geothermal reservoir temperatures. The study also explores the relationship between earthquakes and springs, identifying sensitive chemical indicators. Based on continuous monitoring at Maqu Station, we found that before the occurrence of the Maerkang Ms 6.0 earthquake, the concentration of Cl− rose by 2.9 times, and 46 days before the Gande earthquake (Ms = 4.7), the concentrations of Na+ and SO42− significantly increased. Finally, a conceptual model of the hydrogeochemistry of springs is presented to describe the groundwater circulation in the study area. This research is of great significance for the analysis of fluid geochemistry in this area and for assessing the seismic hazards of the EKFZ.

Sentinel eggs used to monitor field parasitism of stink bug pests (Hemiptera: Pentatomidae) can only be deployed for a few days to avoid releasing the pest in the monitored area. Using sterile eggs removes the risk of accidental pest introduction and extends deployment time. Freezing the eggs before deployment is one common method for sterilizing sentinel eggs. However, some egg parasitoid species have lower to no parasitism on frozen eggs. In this study, x-ray irradiation was used to sterilize Bagrada hilaris sentinel eggs intended for monitoring parasitism by Gryon aetherium (Hymenoptera: Scelionidae), the most promising biological control candidate. In this case, freezing sentinel eggs is not recommended because G. aetherium has low levels of parasitism on frozen eggs. Doses as low as 10 Gy induced 100% sterility. Irradiated eggs successfully sustained the development of G. aetherium and Ooencyrtus californicus (Hymenoptera: Encyrtidae), another egg parasitoid attacking B. hilaris, and parasitism levels were comparable to fresh eggs up to seven days. In addition, G. aetherium showed no preference for fresh non-irradiated over seven-day-old irradiated eggs. Our results indicate that x-ray irradiation is a suitable alternative to produce safe and reliable sentinel eggs to monitor egg parasitism of B. hilaris and possibly other species.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

Thyroid surgery rates have tripled over the past 3 decades making it one of the most frequently performed procedures within general surgery. They are associated with the possibility of serious postoperative complications having a significant impact on the patient's quality of life. The recurrent laryngeal nerve (RLN) palsy and the external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and bleeding after operation, one of the most common complications. The introduction of neuromonitoring into thyroid surgery, enabling both confirmation of anatomical integrity and assessment of laryngeal nerve function, was a milestone that has begun a new era in thyroid surgery. The International Neural Monitoring Study Group made standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery which increased prevalence of neural monitoring during thyroidectomy. Current status of IONM and benefits of its use have been presented in this publication.

The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient’s cerebral compliance. This characterization is particularly informative on the overall state of the cerebrospinal system. We developed a recurrent neural network-based framework for P2/P1 ratio computation that only takes a raw ICP signal as an input. Two tasks are performed, namely pulse classification and subpeak designation. Pulse classification was achieved with an area under the curve of 0.90 on a 4,344-pulse testing dataset, while the peak designation algorithm identified pulses with a P2/P1 ratio > 1 with a 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool for improving bedside monitoring devices.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Using the example of III-V nitrides crystallizing in a wurtzite structure (GaN, AlN, InN), this review presents the special role of hydrostatic pressure in studying semiconductor properties. Starting with a brief description of high pressure techniques for growing bulk crystals of nitride compounds, we focus on the use of hydrostatic pressure techniques in both experimental and theoretical investigations of special properties of nitride compounds, their alloys and quantum structures. The band gap pressure coefficient is one of the most important parameters in semiconductor physics. Trends in its behavior in nitride structures, together with trends in pressure-induced phase transitions, are discussed in the context of the behavior of other typical semiconductors. Using InN as an example, the pressure-dependent effects typical of very narrow bandgap materials, such as conduction band filling or effective mass behavior, are described. Interesting aspects of bandgap bowing in In-containing nitride alloys, including pressure and clustering effects, are discussed.Hydrostatic pressure also plays an important role in the study of native defects and impurities, as illustrated by the example of nitride compounds and their quantum structures. Experiments and theoretical studies on this topic are reviewed. Special attention is given to hydrostatic pressure and strain effects in short periods nitride superlattices. The explanation of the discrepancies between theory and experiment in the optical emission and its pressure dependence from InN/GaN superlattices led to the well-documented conclusion that InN growth on the GaN substrate is not possible. The built-in electric field present in InGaN/GaN and AlGaN/GaN heterostructures crystallizing in wurtzite lattice can reach several MV/cm, leading to drastic changes in the physical properties of these structures and related devices. It is shown how hydrostatic pressure modifies these effects and helps to understand their origin.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

The European Green Deal poses a two-pronged challenge for the automotive industry: migrating to solutions based in light structures, requiring light weight concepts and light materials, while at the same time avoiding dependence towards the importation of these advanced materials. Aluminium alloys are lightweight and cost-effective materials that can successfully cover the requirements of many structural applications, however their production requires from bauxite and other Critical Raw Materials (CRM), such as Si and Mg. Aluminium alloys are fully recyclable, but scrap is usually contaminated and its use is related to an increment of impurities, tramp element and undesired inclusions. Traditionally, the use of secondary alloys has been restricted to low performance applications. The present work analyses the effect that the use of scrap has in the quantity of inclusions present in the alloy and in other properties relevant for the material processing. The study was carried out for common alloys belonging to 3 of the most common aluminium processes used in the car manufacturing industry: High Pressure Die Casting (HPDC) (EN AC-43500), extrusion (6063) and sheet metal forming (5754 and 6181). Reference alloy were mixed with different level of scrap (0, 20, 40, 60, 80 and 100%) trying to keep the chemical composition as unaffected as possible. The inclusions level of the alloy was characterized with the Prefil Foot-printer® test. In addition, the obtained materials, after being cast in an open mould, were subjected to metallographic characterization. Relevant properties to assess the formability quality of the alloys for the corresponding transforming process, were obtained: flowability test for HPDC alloy and high temperature compression for extrusion alloys. The results obtained suggest that the number of inclusions present in the melt highly increase with the amount of scrap used to produce the alloy. These inclusions are also related with an important lost of flowability, but do not have a noticeable impact on microstructure.

While the beneficial effects of using magnetic and electromagnetic treatment (ET) of brackish and saline waters on soil salinity reduction in the root zone were widely reported more studies are needed to answer questions about the soil salt leaching efficiency and the effect of the duration of the exposure to ET. For this aim, pot experiments were conducted using an Aqua-4DR physical water treatment device. The first experiment included two trials. The first considered 5 concentrations: C0:1.0; C1:4.5; C2:9; C3:13.5; and C4:18 dSm-1. The results revealed that the volume and the salt concentrations of the drained waters were significantly higher under irrigation with ET saline waters than those provided by untreated waters. The drained fraction of water varied from 20 to 26% under irrigation with untreated water and increased from 33 to 56% under irrigation with electromagnetized water indicating an improvement of salt leaching. The second trial was carried out with different irrigation doses. The result showed that the higher the dose, the more obvious and significant ET effect. The different treatment durations of water exposure revealed that the volume and salinity of drained water significantly increase as the ET duration increases. An increase in ET duration induces also an increase in soil water content of around 2.5%. Based on the experimental findings, we may conclude that the ET of saline water can reduce the adverse effect of salinity on the top soil, but these leached salts are carried away in depth and there is no concentration limit of water to the effect of the ET.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often over a prolonged duration, the symptoms resemble migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a possible solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible stenosis of the aqueduct. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and considering that the patient had not a total response, bilateral parietal stimulation was added. Three months after the combined PNS she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus associated headache.

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.

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.

Background/Objectives Bowel endometriosis (BE) is defined as the presence of endometrial-like tissue in the muscular layer of the bowel wall. When BE does not cause severe obstruction to fecal transit, not leading to (sub)occlusive symptoms, the decision to operate becomes challenging as intestinal surgery is associated with higher complication rates and long-term bowel dysfunction. The aim of this cross-sectional study is to evaluate the quality of life (QoL) in patients with BE undergoing medical therapy or expectant management, investigating the impact of characteristics of BE nodules on QoL and intestinal function. Methods A retrospective cross-sectional analysis was conducted on 580 patients with BE who did not undergo surgery but were treated conservatively by medical therapy or expectant management between January 2017 and August 2022. The diagnosis of BE was done by transvaginal ultrasound and confirmed at double contrast barium enema. After at least one year of follow-up, QoL and intestinal function of patients were evaluated by the Endometriosis Health Profile-5 (EHP-5) questionnaire and Bowel Endometriosis Symptom score (BENS), whereas pain symptoms were assessed by the Visual Analogic Scale (VAS 0-10). Statistical analysis was performed to investigate possible associations between QoL and characteristics of bowel nodules (dimension, location, and evidence of stenosis) as well as type and length of eventual medical therapy. Results Patients with BE had a satisfying overall QoL with a mean EHP-5 score of 105.42 ± 99.98 points and VAS lower than 3 for all pain domains; additionally, they did not show a significant impartment of bowel function with mean BENS score of 4.89 ± 5.28 points. Notably, patients under medical therapy had a better QoL than patients without therapy (p

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

In this work, studies were carried out on the extraction of silver and gold from cakes of pressure oxidation leaching of sulfide concentrate containing pyrite and arsenopyrite. The addition of gypsum at a consumption of 0.1 g/g of concentrate helps to increase silver extraction from 13.4 to 95–98% at the cyanidation stage, with no conditioning operation. Gold recovery was 99%. An increase in gypsum consumption contributes to the formation of BFAS with an increased content of sulfate sulfur, and a decrease in the As/S(sulfate) molar ratio in the cake from 3.7 down to 0.88 contributes to an increase in silver extraction at the cyanidation stage up to 98%, and its further decrease from 0.88 down to 0.58 leads to a gradual reducing silver transfer into solution from 98 down to 75.1% at the cyanidation stage. Basic ferric sulfate (BFS) is not formed in this case, since according to EDS mapping the distribution of arsenic and sulfur over iron-containing particles is uniform. According to TCLP analysis, the cake obtained after pressure oxidation leaching with the addition of gypsum and cyanidation is stable and suitable for disposal, since the final concentration of arsenic in the solution was 0.45 mg/dm3.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Predetermined physical properties cannot manifest at the same time if they are mutually exclusive. As part of a single system, they become observable at different times, in sequence. In this case, pairwise detections in a narrow window of coincidence allow for maximal Bell violations (S=4 for the CHSH protocol), without room for doubt about the local nature of the process. This shows that a deeper description of physical reality is possible, as suggested by Einstein, Podolsky and Rosen. Though, a more inclusive definition of Realism is required, in order to account for Bohr’s Contextuality.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

This article provides a detailed analysis of non-invasive techniques for prediction and diagnosis of faults in internal combustion engines, focusing on the application of the Proknow-C and Methodi Ordinatio systematic review methods. Initially, the relevance of these techniques in promoting energy sustainability and mitigating greenhouse gas emissions is discussed, aligning with the Sustainable Development Goals (SDGs) of Agenda 2030 and the Paris Agreement. The systematic review conducted in the subsequent sections offers a comprehensive mapping of the state-of-the-art, highlighting the effectiveness of combining these methods in categorizing and systematizing relevant scientific literature. The results reveal significant advancements in the use of artificial intelligence (AI) and digital signal processors (DSP) to enhance fault diagnosis, as well as underscore the crucial role of non-invasive techniques in minimizing interference in monitored systems. Finally, concluding remarks point towards future research directions, emphasizing the need to develop digital twins for internal combustion engines and identify gaps for further improvements in fault diagnosis and prediction techniques.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Mechanically homogenized composite of expanded graphite and cobalt(II) rhenate(VII) has been described. Cobalt(II) rhenate(VII) was obtained in a reaction of perrhenic acid with cobalt(II) nitrate. A simple mortar homogenization method was used to enhance intercalation of cobalt species within carbon matrix. The specific capacity of composite was enhanced by 50% in comparison to bare expanded graphite. The electrochemical characteristic was significantly improved including better cyclability, lower resistance of electrode material, lower iR drop, with respect to expanded graphite without cobalt(II) rhenate(VII) active species. Expanded graphite with its unique specific surface area and pore size diameter was proved as potential and cheap carbon support.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition include bacterial contamination, tissue perfusion, and mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments.In this review, we discuss bioengineering advances in non-invasive detection of biologic and physiologic factors of the healing wound, visualizing and modeling the ECM, and computational tools to efficiently evaluate the complex data acquired from the wounds to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the matrix, linearity of collagen, and live tracking of components within the ECM. Computational modeling of the matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

The Pygmy hog (Porcula Salvania), till recently, classified as a critically endangered suid, is facing the threat of extinction globally due to habitat degradation. Efforts are being made to protect the pygmy hogs from extinction and breed them in captivity under Pygmy Hog Conservation Pro-gramme (PHCP). However, very little information is available on the reproductive physiology of pygmy hogs. Therefore, the present study aimed to standardize enzyme immunoassays (EIAs) for monitoring pregnancy and reproductive status using progesterone and testosterone metabolites. A total of 785 faecal samples were collected from five females and two males over a period of one year from PHCP Research and Breeding Centre, Guwahati, Assam. High-pressure liquid chro-matography (HPLC) analysis revealed the presence of immunoreactive progesterone and testos-terone metabolites in faeces. Mating was observed in all the five females and four of them gave birth successfully. We were able to detect pregnancy using faecal progesterone metabolites. Based on mating and parturition, the mean gestation period was estimated to be 153.25 days from four females. The breeding centre recorded 172 births between 1996 and 2000 and found strong sea-sonality in births and most of the births were between May and June. Faecal testosterone metabo-lites were significantly higher in the breeding season than the non-breeding season. This is the first study and will help in future breeding programs in other captive breeding centres and reproduc-tive monitoring of reintroduced populations.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

Counterfeiting electronic components is a serious problem for the security and reliability of any electronic systems. Unfortunately, the number of counterfeit components has increased considerably after the introduction of horizontal semiconductor supply chain. In this paper, we propose a new method for detecting recycled Flash memory, a major target of the counterfeiters due to its ubiquitous usage. Proposed method is based on measurement of change in Flash array characteristics (such as erase time, program time, fail bit count, etc.) with its usage. We find that erase time is the best metric to distinguish a used Flash chip from a fresh one for the following reasons: (1) erase time shows minimal variation among different fresh memory blocks/chip and (2) erase time increases significantly with usage. We verify our method for a wide range of commercial off the shelf Flash chips from several vendors, technology nodes, storage density and storage type (single-bit per cell and multi-bit per cell). The minimum detectable chip usage varies from 0.05% to 3.0% of its total lifetime depending on the exact details of the chip.

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.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the most ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, South America. Due to their natural characteristics as a hermaphroditic species with high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments to reactively control invasive mollusc populations and proactively prevent their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in open water systems was performed to evaluate molluscicides and identify toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize negative impact to water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners on invasive Asian clam management.

Background: Glutathione and its related enzymes constitute one of the most important antioxidant defense mechanisms against oxidative stress and cancer formation in the body. Bladder cancer is the second most common urological malignancy after prostate cancer. Oxidative stress plays a significant role in the development and prognosis of bladder cancer. The aim of this study was to examine the effect of glutathione on the prognosis of non-muscle-invasive bladder cancer. Methods: The 98 patients with bladder tumors were those with T1G3 pathology who had undergone intravesical Bacillus Calmette-Guérin therapy, while the 30 controls were healthy individuals with no history of transitional cell carcinoma of the bladder. The 128 participants were divided into four groups: Group 1 comprised 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, Group 3 consisted of 29 patients who progressed to muscle-invasive stages, and Group 4 was composed of 30 healthy volunteers. Blood samples were collected from all participants. Glutathione levels were measured, and statistical analysis were performed. Results: There was a statistically significant difference in reduced glutathione levels among the groups (p < 0.001), attributed to Group 4 exhibiting higher reduced glutathione levels compared to Groups 1, 2, and 3 (p < 0.001). No significant differences were observed in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.999). Total glutathione levels varied significantly among the groups (p < 0.001), with Group 4 having higher levels than Groups 1, 2, and 3 (p < 0.001). However, there were no significant differences between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in terms of total glutathione levels (p = 0.473, p = 0.747, and p > 0.999, respectively). Regarding oxidized glutathione levels, a significant difference was observed (p < 0.001), with Group 4 showing lower levels than the remaining three groups (p < 0.001). No significant differences were found between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in relation to oxidized glutathione levels (p > 0.999, p = 0.171, and p > 0.999, respectively). Conclusions: The current study revealed that glutathione is a factor influencing the development of new bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the effect of glutathione on the prognosis of bladder cancer.

Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.

Background: In response to the COVID-19 pandemic, the European Association of Urology (EAU) Guidelines defined priority groups to guide the prioritization of surgery for urological malignancies. The objective of this study was to evaluate the impact of the COVID-19 prioritization recommendations on tumor pathological characteristics in a real-world setting at our academic referral Institution. Methods: We compared baseline and pathological tumor features of all patients with urological malignancies treated during the pandemic period (2020-2021) versus in the post-pandemic period (2022-2023). Our institution adhered to the International recommendations and prioritized those cases defined as “high-risk”. Results: Data of 9196 patients treated for urological malignancies were reviewed and grouped according to period of surgery (4401 in the pandemic vs 4785 in non-pandemic period). The overall number of surgical procedures was comparable for all diseases except for the number of radical prostatectomy (1117 vs 1405; p=0.03) and partial nephrectomy (609 vs 759; p=0.02) which were significantly lower in the pandemic period. Regarding tumors’ pathological features, none of the recorded variable was found to differ according to period of surgery, including disease stage, tumor grading, presence of necrosis, lymphovascular invasion, histological variants. Conclusion: A correct policy of prioritization of oncological pathologies during emergency periods and a centralization of oncological cases in reference centers reduces the possible risk of worsening cancer disease features related to the reorganization of healthcare resources.

Current commercial, pre-commercial, and experimental in ovo techniques for the sex determination of fertilised eggs employ either minimally invasive biomolecular assays (extracting fluid via a small laser-drilled window in the eggshell, for detection of genetic or hormonal biomarkers), analysis of volatile compounds emitted from the eggshell, visible imaging, and reflectance or transmission spectroscopic analysis exploiting molecular optical fluorescence, polarisation, and scattering phenomena, including various combinations of these modalities. , to date no endeavour employing the NIR and FTIR based spectroscopic techniques has resulted in a commercially sustainable solution to the egg sexing problem. Besides achieving only subpar performance in overall accuracy, specificity, and sensitivity, the least invasive of the current state-of-the-art optical methods still requires, creating a transmission window (fenestration) of 12–15 mm diameter through to the mammillae layer of the shell, proximal to the external shell membrane, which can affect the incubation or post-hatch development viability of up to 10% of incubated eggs. Multimodal solution combining Raman spectroscopy and hyperspectral imaging has strong prospects to overcome the hard barriers existing before the perfection of a non-invasive in-line process for high reliability and rapid throughput for sex determination of eggs within 3 days of incubation. The method for sexing of chicken embryos needs to take a multipronged approach in collecting and analyzing spectral data that points to biomarkers using the machine learning approaches to look for nanomolar to picomolar concentrations of these in the fluid.

The article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 years and was asymptomatic. The disqualification from pacemaker implantation included detailed history of a patient’s symptoms, echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.

An experimental study is carried out in a cavitation tunnel on a propeller operating downstream of a non-uniform wake. The goal of this work is to establish quantitative correlations between the near pressure field and the cavitation pattern that takes place on the propeller blades. The pressure field is measured at the walls of the test section and in the near wake of the propeller, and is combined with quantitative high-speed image recording of the cavitation pattern. Through simple harmonic analysis of the pressure data and image processing techniques that allow to retrieve the cavitation extension and volume, we discuss the potential sources that generate the pressure fluctuations. Time correlations are unambiguously established between pressure peak fluctuations and cavitation collapse events, based upon the Rayleigh collapse time. Finally, we design a model to predict the cavitation-induced pressure fluctuations from the derivation of the cavitation volume acceleration. This simple model demonstrates a remarkable agreement with the actual pressure field.

Ovarian torsion (OT) is a rare gynaecological emergency that requires a prompt diagnosis for optimal patient management. To determine whether there were any biomarkers suitable for the non-invasive detection of OT, two independent reviewers performed systematic searches of five literature databases following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Full-texts of 24 selected articles were assessed for risk of bias and quality assurance using a modified Newcastle-Ottawa Scale (NOS).  15 articles described studies on animals and all described serum biomarkers comparing results between OT versus a sham operation, a control group or readings before and after OT. Ischaemia modified albumin (IMA), serum D-dimer (s-DD), heat shock protein-70 (hsp-70), Pentraxin-3 (PTX-3) and c-reactive protein (CRP) showed the most promise, each with p-values for the difference between groups achieving ≤0.001. In studies of humans, the biomarkers ranged from 16.4-92.3% sensitivity and 77-100% specificity. The most promising biomarkers for the early prediction of OT in patients included s-DD, interleukin-6 (IL-6), IMA and tumour necrosis factor-alpha (TNF-. IL-6 had the highest sensitivity of any biomarker identified in this review and was raised in all 13 patients with proven OT, with values of ≥10.2pg/ml, indicative of a 16 times higher risk of having OT. Signal peptide, CUB domain and EGF like domain containing 1 (SCUBE1) had a high specificity at 93.3%, second only to s-DD and a positive likelihood ratio (LR)&gt;10. IMA was the only other biomarker that also had a positive LR&gt;10, making it a promising diagnostic biomarker. The studies identified by this systematic literature review each analysed small patient groups but IMA, DD and SCUBE1 nevertheless showed promise as serum biomarkers with a pooled LR&gt;10. However, further well-designed studies are needed to identify and evaluate individual markers, or diagnostic panels to help clinicians manage this important, organ-threatening condition.

Previous research has indicated that ultra-high pressure (UHP) technology is useful in speeding up the extraction process of cold brew (CB) coffee. However, the impact of different degrees of roasting on UHP CB coffee is still unclear. Therefore, this study aimed to investigate the effects of three different degrees of roasting (light, medium, and dark) on the physicochemical and flavor characteristics of UHP CB coffee. The results of this study showed that most physicochemical characteristics of UHP coffee were similar to those of conventional CB coffee, regardless of the degree of roasting. However, the majority of physicochemical characteristics, non-volatile components, and sensory evaluation significantly increased with an increase in roasting degree. The HS-SPME-GC/MS analysis showed that most volatile components, such as pyrazines, furans (except furfural), esters, pyrrole, pyridine, and most aldehydes, increased from light to dark roasting, and this was significantly evident in CB coffee compared with UHP. The content of volatile components in UHP coffee was significantly (P<0.05) higher than that in CB coffee at the same degree of roasting, especially with dark roasting. The combination of orthogonal partial least squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA) indicated that the distance between coffee samples at different degrees of roasting under CB coffee was greater than that under UHP coffee. However, the distance between these two extraction methods at medium roasting was evidently closer than that at light and dark roasting. Moreover, 15 representative differential compounds, such as were Hazelnut pyrazine, linalool, butane-2,3-dione, 3- methylbutanal found by the calculation of odor-active values (OAVs) indicating the main contributing compounds to odor. Overall, the effect of roasting degrees on UHP coffee was less than that on CB coffee, which was consistent with the results of physicochemical characteristics, volatile components, and sensory evaluation.

A 12 year old boy was diagnosed with temporal lobe epilepsy (TLE) along with mesial temporal sclerosis based on MRI (magnetic resonance imaging) results. The diagnosis was further confirmed by genetic analysis. He also had minor psychiatric symptoms of obsessive-compulsive disorders and mood swings. After 4 years of treatment with Sodium Valproate no change in symptoms was observed. Genetic testing along with deep phenotyping revealed altered glutamate pathway and metabolism. Post genetic testing the patient was put on a combination of Sodium Valproate and Valproic acid along with supplementation of N-acetylcysteine (NAC), Cyanocobalamin, Pyridoxine and Cholecalciferol. Within three months of this combined therapy the patient experienced complete elimination of seizures and drastic improvement in mood and social behaviour. The case report highlights the importance of precision diagnosis in understanding the underlying perturbed pathways in structural epilepsy like TLE and demonstrates the importance of non-invasive targeted therapy in such cases.

Olivine-like NaFePO4 glasses and nanocomposites are promising materials for cathodes in sodium batteries. Our previous study concerned the influence of high pressure on DC electric conductivity of NaFePO4 glasses. This work presents the results of AC measurements of glasses and nanocomposites from pressure treatment. Depending on the temperature range, the electronic conduction mechanism changed from variable range hopping (between Fe2+/Fe3+centers) to phonon-assisted hopping. For DC electric conductivity the portrayal via the classic Mott’s Variable Range Hopping is limited to low temperatures. Spectra of AC conductivity for glasses and pressure-formed nanocomposites fulfill Jonscher’s scaling law with power exponents ranging from 0.3 to 0.9 depending on temperature and the electron hopping mechanism. Due to the decrease in distance between hopping centers, an increase of AC conductivity around 2-3 orders of magnitude was observed after high pressure-high temperature treatment. Up to 200 K temperature dependencies of AC conductivity follow the pattern suggested by Mott's theory. Above that temperature corresponds to phonon-assisted hopping with activation energies EAC≈0.40 eV (for glass: amorphous solid) and EAC≈0.18 eV (for glass + nanocrystallites nanocomposite). Notable that they are considerably lower than values of EDC for DC conductivity. Results obtained show that high-temperature compressing, just below the glass temperature, significantly leads to a stable decrease in distance between hopping centers related to nanocrystallites in a glassy matrix. Consequently, it leads to an essential rise in electric conductivity and volumetric capacity. AC spectra of electronic conductivity are disturbed by the conduction of Na+ mobile ions, which impacts polaron conductivity and can be a limiting factor for conductivity.

Continuous glucose monitoring devices allow diabetes condition management. However, when limited data is available, one option is to increase their size by generating synthetic samples. From a homemade wearable prototype was created a real dataset with 18 instances and 53 attributes that capture characteristics of capillary and venous blood glucose, oxygen concentration, pulse rate, skin temperature, and 24 modules and 24 phases related to bio-impedance. The objective of this article is to generate synthetic datasets, and also it investigates the ideal features subset and optimal model for non-invasive diabetes prediction. Gaussian-Copulas (GC), conditional generative adversarial networks (CG), variational autoencoders, and Copula-GAN techniques' were used to generate five synthetic datasets. Experiments show that GC1 and GC2 datasets follow min/max boundaries and are not copies of the original data. Multilayer perceptron regressor outperformed (train and test) with 2.17, 2.51 in MAE; 9.29, 13.59 in MSE; 3.05, 3.69 in RMSE, and 0.95, 0.92 in R2 in GC1, and 2.64, 3.02 in MAE; 11.43, 15.11 in MSE; 3.38, 3.89 in RMSE, and 0.94, 0.92 in R2 in GC2 with eight features. Future work is necessary to explore autoencoder and generative architectures, datasets with diverse characteristics, and the effect of the number of features.

Keywords: flow mediated skin fluorescence; FMSF technique; NADH fluorescence, microcirculation, flowmotion, reactive hyperemia response, RHR, hypoxia sensitivity, HS, normoxia oscillatory index, NOI

The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

Adenine nucleotide (AN) 2^nd messengers such as 3’,5’-cyclic adenosine monophosphate (cAMP) are central elements of intracellular signaling, but many details of underlying processes remain still elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca²⁺ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Consequently, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.

This paper presents a piezoresistive pressure sensor with a shield layer for improved stability. Compared with the conventional piezoresistive pressure sensors, p-type piezoresistors are covered by an n-type shield layer, which is formed by ion implantation. The proposed pressure sensors have been successfully fabricated by bulk micromachining techniques. The impact of electrical field on piezoresistors is studied by simulation. The temperature drift of the pressure sensor has been investigated by both simulation and experimental measurement. Characteristics of developed pressure sensors are tested from -40 C to 125 C. A sensitivity of 0.022 mV/V/KPa and a maximum non-linearity of 0.085% FS are measured for the fabricated sensor in a pressure range of 1 MPa. The temperature coefficients of resistance of shielded piezoresistors are found to be smaller than those of un-shielded ones. It is demonstrated that the shield layer is able to reduce the drift caused by electrical field and ambient temperature variation.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

Intracranial hemorrhage is a serious medical problem that requires rapid and often intensive medical care. Identifying the location and type of any hemorrhage present is a critical step in the treatment of the patient. Diagnosis requires an urgent procedure, and the detection of hemorrhage is a difficult and time-consuming process for human experts. In this paper, we propose methods based on EfficientDet’s deep-learning technology that can be applied to the diagnosis of hemorrhages and thus become a decision-support system. Our proposal is two-fold. On the one hand, the proposed technique classifies slices of computed tomography scans for the presence hemorrhage or its lack, achieving 92.7% accuracy and 0.978 ROC-AUC. On the other hand, our methodology provides visual explanations of the classification chosen using the Grad-CAM methodology.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

In order to enable patients with severe disabilities who have lost their limbs to accurately control their wheelchair movement and optimize the power loss of smart wearable tongue control devices, a non-invasive intraoral stand-alone tongue control system based on RSIC-V edge computing is proposed in this paper. Patients can detect the pressure signal of the tongue muscles’ touching the palate by placing the flexible carbon nanotube-PDMS pressure sensor array in the mouth, and the erroneous movement signal can be avoided by setting the pressure threshold, thereby improving the reliability of the device and the user's experience. The system converts the pressure data into specific control instructions on the edge of the RSIC-V chip and transmits them to the receiver, thus reducing the transmission of data. In this experiment, the speed response time test, the center click task and the power consumption experiment are carried out, whose results show that the adaptive fuzzy PID control algorithm has good robustness in the system: when the DC motor with a given speed of 750r/min reaches the steady state, its rise time is 0.108s and the adjustment time is 0.59s. The dynamic power consumption of the non-intrusive intraoral stand-alone tongue control system proposed in this paper is tested to be 3.745 MW, which is 11.5% lower than the total power consumption of the sTDs system.

In this paper, we introduce a non-invasive approach for monitoring bridge infrastructure with ground-based interferometric radar. This approach is called the mirror mode, since it utilises the flat surface of the bridge underside as a mirror to reflect the signal to a corner reflector on the ground placed opposite of the radar sensor. For proving the feasibility of this approach, a measurement campaign has been carried out at an exemplary bridge in Karlsruhe (Germany) including a radar sensor in mirror mode, a second radar sensor in the default mode and a laser profile scanner. We investigate the potential of this approach to monitor the bridge displacement in vertical direction and compare the results with the two other sensors. The derived results reveal the potential for monitoring bridge infrastructure. Finally, we propose further research aspects of this approach to analyse its capabilities and limitation in the context of non-invasive infrastructure monitoring.

The chicken embryo is a widely used experimental animal-model in many studies such as developmental biology and to study the physiological responses and adaptation to altered environments as well as for cancer and neurobiology research. Embryonic heart rate is an important physiological variable useful as an index reflecting the embryo's natural activity and is considered one of the most difficult parameters to measure. An acceptable measurement technique of embryonic heart rate should provide a reliable cardiac signal quality while maintaining adequate gas exchange through the eggshell along the incubation and embryonic developmental period. In this paper, we presented a detailed design and methodology for a non-invasive PPG-based prototype (Egg-PPG) for real-time and continuous monitoring of embryonic heart rate during incubation. An automatic embryonic cardiac wave detection algorithm, based on normalised spectral entropy, is described. The developed algorithm successfully estimated the embryonic heart rate with 98.7% accuracy. We believe that the developed overall system presented in this paper is showing a promising solution for non-invasion, real-time monitoring of embryonic cardiac signal, which can be used in both experimental studies (e.g., developmental embryology and cardiovascular research) and in industrial incubation applications.

The Dutch Konik is valued from a genetic conservation perspective and also for its role in preservation of natural landscapes. The primary management objective for the captive breeding of this primitive horse is to maintain its genetic purity, whilst also maintaining the nature reserves on which they graze. Breeding selection has traditionally been based on phenotypic characteristics consistent with the breed description, and the selection of animals for removal from the breeding program is problematic at times due to high uniformity within the breed. With the objective of identifying an additional non-invasive selection criterion with potential uniqueness to the Dutch Konik, this study investigates the anatomic parameters of the distal equine limb, with a specific focus on the relative lengths of the individual splint bones. Post-mortem dissections performed on distal limbs of Dutch Konik (n = 47) and modern domesticated horses (n = 120) revealed significant differences in relation to the length and symmetry of the 2nd and 4th Metacarpals and Metatarsals. Distal limb characteristics with apparent uniqueness to the Dutch Konik are described which could be an important tool in the selection and preservation of the breed.

We propose novel spectrometer designs that aim to enhance the measured spectral range 1 of ions on a finite-sized detector. In contrast to the traditional devices that use uniform magnetic 2 field, in which the deflection of particles increases inversely proportional to their momentum, in a 3 gradient magnetic field, the deflection of particles will be decreased due to the reduction of the 4 magnetic field along their propagation. Low energy ions are particularly impacted, as they are 5 deflected less and are more likely to reach the detector compared to being driven out of it while 6 using a uniform magnetic field. By the means of a gradient magnetic field, the nonlinear dispersion 7 of ions in a homogeneous magnetic field can approach a nearly linear dispersion. Nonetheless, 8 the dispersion of low energy ions in a homogeneous magnetic field remains unnecessarily high. 9 In this article, we explore linear, quadratic, and higher-order field profiles in comparison to the 10 homogeneous field case. We discuss the employed methodology and present simulation results of 11 the spectrometer with an extended ion spectral range, focusing on the minimum detectable energy 12 (energy dynamic range) and energy resolution

Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding. So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort. This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs’ sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3. 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5mm,) AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE (p = 000.1). All grades of AWE were significantly associated with reperfusion. Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion.

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these maladies can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life, and long-term survival of the patient. Still cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also are vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for detection of health conditions has been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins), to provide valuable information on individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network, that has gained growing recognition as a rich source of biomarkers of airway infections, pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors, ranging from considerable subjection to air pollution and occupational contaminants, to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase of these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. We therefore highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic maladies, to predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgency for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and limitations faced when dealing with their complex matrices.

Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Early screening, particularly in blood has been regarded as an effective approach for AD diagnosis and prevention. In addition, metabolic dysfunction has been demonstrated to be closely related to AD, which might be reflected in whole blood transcriptome. Hence, we hypothesized that establishment of diagnostic model based on metabolic signatures of blood is a workable strategy. To the end, we initially constructed metabolic pathway pairwise (MPP) signatures to characterize the interplay among metabolic pathways. Then, a series of bioinformatic methodologies, e.g., differential expression analysis, functional enrichment analysis, and network analysis, etc. were used to investigate the molecular mechanism behind AD. Moreover, an unsupervised clustering analysis based on the MPP signature profile via Non-Negative Matrix Factorization (NMF) algorithm was utilized to stratify AD patients. Finally, aimed at distinguishing AD patients from non-AD group, a metabolic pathway-pairwise scoring system (MPPSS) was established using multi-machine learning methods. As a result, many metabolic pathways correlated to AD were disclosed, including oxidative phosphorylation and fatty acid biosynthesis, etc. NMF clustering analysis divided AD patients into two subgroups (S1 and S2), which exhibit distinct activities of metabolism and immunity. Typically, oxidative phosphorylation in S2 exhibits a lower activity than that in S1 and non-AD group, suggesting the patients in S2 might possess a more compromised brain metabolism. Additionally, Immune infiltration analysis showed that the patients in S2 might have phenomena of immune suppression, compared with S1 and non-AD group. These findings indicated that S2 probably have a more severe progression of AD. Finally, MPPSS could achieve an AUC of 0.73 in training dataset, 0.71 in testing dataset and an AUC of 0.82 on weighted average in five external validation datasets. Overall, our study successfully established a novel metabolism-based scoring system for AD diagnosis using blood transcriptome, and provided new insight into the molecular mechanism of metabolic dysfunction implicated in AD.

Reflected light carries ample information about biochemical composition, tissue architecture, and physiological condition of plants. Recent technical progress brought about affordable imaging hyperspectrometers (IH) providing spatially resolved spectral data on plants. The extraction of sensible information from hyperspectral reflectance images is difficult due to inherent complexity of plant tissue and canopy optics, especially when recorded by IH under ambient sunlight. We aimed at obtaining a deeper insight into plant optics as perceived by IH since there is a high demand for algorithms for fruit harvesting and grading systems equipped with computer vision and robotic systems capable of working in orchard. We report on the characteristic changes in hyperspectral reflectance accompanying the accumulation of anthocyanins in healthy fruit, pigment breakdown during sunscald and phytopathogen attacks. The measurements made outdoors with a snapshot IH were compared with traditional “point” reflectance measured with a conventional spectrophotometer under controlled illumination conditions. Most of the spectral features and patterns of plant reflectance were evident in the IH-derived reflectance images. As a step forward, a novel index for highlighting tissue damages on the background of the anthocyanin absorption, BRI-M = (1/Rorange – 1/Rred + 1/RNIR), is suggested. Difficulties of the interpretation of fruit hyperspectral reflectance images recorded in situ are discussed with possible implications for plant physiology and precision horticulture practices.

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In-silico investigation on porcine skin was carried out using the Monte Carlo modelling strategy to evaluate the feasibility and characterise the sensor. Subsequently, an in-vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

Salmonella, especially invasive non-typhoidal Salmonella (iNTS) are responsible for developing various invasive diseases, and possess higher mortality rate, due to their higher antibiotic resistance profile than the other bacteria. Therefore, the present study was concerned to develop epitope based peptide vaccine against iNTS species as a successive and substitute protective measures. The study considered comprehensive Immunoinformatic approaches, followed by molecular docking and molecular dynamics simulation to predict the efficient vaccine candidate T cell and B cell epitopes, based on the outer membrane proteins. The study identified two best epitopes YGIFAITAL and KVLYGIFAI from total iNTS outer membrane proteins, which showed higher immunity, non-allergenicity, non-toxicity and also showed higher conservancy and population coverage values. Both epitopes showed higher binding affinity and stability towards HLA-C* 03:03. The MM-PBSA binding free energy showed the YGIFAITAL epitope binds more tightly with both MHC-I and MHC-II molecules. The total contact, H-bond analysis and RMSF results also validate the efficiency of these epitopes as vaccine candidate. The projected B cell epitopes AAPVQVGEAAGS, TGGGDGSNT and TGGGDGSNTGTTTT showed higher antigenicity. Overall, the study concluded that these epitopes can be considered as the potential vaccine candidate to make a successive vaccine against iNTS species. However, this result further needs to be validate by wet lab research to make successive vaccine with these projected epitopes.

This paper discusses a cross-disciplinary, international collaboration aimed at researching a series of 15th century choir books at the abbey of San Giorgio Maggiore on the homonymous island in Venice. Produced for the abbey itself, the books have never left the island during their 500-years history, thereby allowing a unique opportunity to analyse historic artefacts, which have undergone little modification over time. Prompted by ongoing cataloguing work on the manuscripts, a week-long analytical campaign using a combination of non-invasive analytical methods used in portable configuration allowed the comprehensive characterisation of ten volumes. The manuscripts’ palette and painting techniques were analysed using near-infrared imaging, reflectance spectroscopy in the UV-vis-NIR range, Raman spectroscopy, X-ray fluorescence mapping and digital microscopy. The paper will discuss the challenges linked to the fragility and the large dimensions of the volumes as well as the most interesting results of the investigation. These include the detection of unusual painting materials such as bismuth ink, as well as the discovery of a less homogeneous palette than originally expected, which prompted a partial revision of the attribution of the decoration in one of the volumes to a single artist.

Three-phase motors are commonly adopted in several industrial contexts and their failures can result in costly downtime causing undesired service outages; this way, motor diagnostics is an issue that assumes great importance. To prevent their failures and timely face the considered service outages, a non-invasive method to identify electrical and mechanical faults in three-phase asynchronous electric motors is proposed in the paper. In particular, a measurement strategy along with a machine learning algorithm based on Artificial Neural Network is exploited to properly classify failures. In particular, digitized current samples of each motor phase are first processed by means of FFT and PSD in order to estimate the associated spectrum. Suitable features (in terms of frequency and amplitude of the spectral components) are then singled out to either train or feed a neural network acting as a classifier. The method is preliminary validated on a set of 28 electric motors, and its performance is compared with common state-of-art machine learning techniques. The obtained results show that the proposed methodology is able to reach accuracy levels greater than 98\% in identifying anomalous conditions of three-phase asynchronous motors.

We compared two approaches to non-invasive proximal sensing of the early changes in fresh-cut lettuce leaf quality: hyperspectral imaging and imaging PAM-fluorometry of chlorophyll contained in the leaves. The assessments made by the imaging techniques were confronted with the quality assessments made by traditional biochemical assays: relative water content and foliar pigment (chlorophyll and carotenoid) composition. The hyperspectral imaging-based approach provided the highest sensitivity to the decline of fresh-cut lettuce leaf quality taking place within 24 h from cutting. Using of the imaging PAM was complicated by (i) weak correlation of the spatial distribution pattern of the Qy parameter with the actual physiological condition of the plant object and (ii) its high degree of heterogeneity. Accordingly, the imaging PAM-based approach was sensitive only to the manifestations of leaf quality degradation only at advanced stages of the process. Sealing the leaves in the polyethylene bags slowed down the leaf quality degradation at the initial stages (&lt; 3 days) but promoted its rate at more advanced stages, likely due to build-up of ethylene in the bags. An approach was developed to the processing of hyperspectral data for non-invasive monitoring of the lettuce leaves with a potential for implementation in greenhouses and packinghouses.

Many studies utilize sensors to measure foot plantar pressure and analyze gait patterns, often focusing on assessing weight-bearing symmetry or asymmetry compared to control groups. However, a critical question arises: does the selection of the control group significantly impact study outcomes? Does chronic low back pain affect foot plantar pressure measurements? This experimental study involved 23 participants, including healthy individuals and those without foot disorders but with chronic low back pain. Dynamic foot pressure measurements were conducted using the Ortopiezometr, and data were analyzed using the "Steps" program. Participants were divided into two groups: Group 1 comprised completely healthy individuals, while Group 2 consisted of individuals without foot problems but with moderate chronic low back pain. The findings highlight a prevalence of energy release in the forefoot sensors compared to the hindfoot for both the right and left legs in most cases. Even among healthy volunteers, achieving perfect symmetry in the maximum values on the sensors for the right and left feet was a challenge. Results showed no statistically significant differences in energy released on specific sensors or duration of gait phases between the groups. Essentially, this suggests that foot pressure patterns are comparable between healthy individuals and those with low back pain. The use of sensor-equipped inserts for pedobarographic examinations indicates that, in cases of degenerative changes in the lumbar and sacral spine without accompanying acute pain, gait patterns resemble those of the healthy population.

Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, which contributes significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

The electronic properties of calcium intercalated graphite (CaC6) as a function of pressure are revisited using density functional theory (DFT). The electronic band structures of CaC6, like many other layered superconducting materials, display cosine-shaped bands at or near the Fermi level (FL). Such bands encompass bonding/antibonding information with a strong connection to superconducting properties. Using an hexagonal cell representation for CaC6, construction of a double supercell in the c-direction effects six-folding in reciprocal space of the full cosine function, explicitly revealing the bonding/antibonding relationship divide at the cosine midpoint. Similarly, folding of the Fermi surface (FS) reveals physical phenomena relevant to electronic topological transitions (ETT) with application of pressure. For CaC6, the peak value for the superconducting transition temperature, Tc, occurs at about 7.5 GPa, near to the observed pressure of the calculated ETT. At this pressure, the radius of the nearly spherical Ca 4s-orbital FS coincides with three times the distance from the G centre point to the Brillouin zone (BZ) boundary of the 2c supercell (which is equal to half the identically defined distance for the primitive rhombohedral BZ). In addition, the ETT coincides with alignment of the non-bonding (inflection) point of the cosine band (the point at which the sign of the cosine amplitude modulation is reversed) with the FL. At other calculated pressure conditions, the Ca 4s-orbital FS undergoes topological changes that correspond and can be correlated to experimentally determined changes in Tc. The ETT is a key mechanism that circumscribes the known significant drop in Tc for CaC6 as a function of increasing pressure.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

Background: Maladaptive neuroplasticity related learned response in substance use disorder (SUD) can be ameliorated using non-invasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on competing neurobehavioral decision systems model. Next objective was to conduct computational simulation of NIBS of cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD) related dysfunctional “cue-reactivity” – a closely related construct of “craving” that is a core symptom. Our third objective was to test the feasibility of our neuroimaging guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG), metrics of sensorimotor gating. Therefore, we conducted computational simulation of NIBS, including transcranial direct current stimulation(tDCS) and transcranial alternating current stimulation(tACS) of the cerebellar cortex and deep cerebellar nuclei(DCN), of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging guided NIBS approach for cerebellar lobule (VII) and prefrontal cortex based on healthy human study. Results: Simulation study of cerebellar tDCS induced gamma oscillations in the cerebral cortex while tTIS induced gamma-to-beta frequency shift. Experimental fNIRS study found that 2mA cerebellar tDCS evoked similar oxyhemoglobin(HbO) response in-the-range of 5x10-6M across cerebellum and PFC brain regions (=0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO driven(phase-amplitude-coupling, PAC) 4Hz, ±2mA (max.) cerebellar tACS evoked HbO in-the-range of 10-7M that was statistically different (=0.01) across those brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC as well as fNIRS-driven ctACS at 4Hz that may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

BackgroundIntracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasound (US) and MRI. Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of two cases of prenatal ICH.Cases presentationThe first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530g.ConclusionFetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

Intraprocedural rupture (IPR) is a severe complication of coil embolization (CE) for intracranial aneurysms, yet the clinical and hemodynamic features of rupture risk areas remain unclear. From January 2013 to December 2023, 435 saccular cerebral aneurysms (316 unruptured, 119 ruptured) underwent CE at our institution. Included were cases where extravasation or coil protrusion occurred during CE. The rupture point was determined from postoperative data, and computational fluid dynamics (CFD) analysis was conducted to assess hemodynamic features. IPR occurred in six aneurysms (1.3%; three ruptured, three unruptured; dome size: 4.7±1.8 mm, D/N: 1.5±0.5, locations: four internal carotid artery [ICA], one anterior cerebral artery, one middle cerebral artery). ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with maximum pressure (Pmax) in five aneurysms (83.3%). Time-averaged wall shear stress (WSS) was locally reduced around this area (1.3±0.7 [Pa]). Hemodynamically unstable areas indicated fragile, thin walls with rupture risk. Microcatheter insertion along the inflow zone, directed towards the caution area, was practiced. The presence of a flow impingement zone with Pmax and low WSS suggests potential aneurysm rupture in CE, particularly with adjunctive techniques. Small aneurysms, especially those with axial misalignment, warrant careful consideration due to the risk of excessive flow impact stress on the aneurysm wall.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

1. Background and Objective: Spontaneous Intracranial Hemorrhage (ICH) is a catastrophic medical condition associated with significant morbidity and mortality. As the accumulation of unbound iron following ICH contributes to secondary brain injury, deferoxamine, an approved chelation drug, has become the center of attention. At the same time, its therapeutic remains a matter of dispute. This double-blinded Randomized Controlled Trial (RCT) aims to investigate the therapeutic potential of deferoxamine in neurological and radiological aspects. 2. Methods and Materials: The study enrolled 42 participants diagnosed with spontaneous ICH and confirmed by CT scan, randomly assigning them to either the deferoxamine treatment group or the placebo control group. While the control group received the routine treatment plus a placebo, the treatment group received routine treatment conjugated with 7.5 mg/kg of deferoxamine per hour intravenously over the first three days. The study compared hematoma and edema volume, GCS score, and mortality rates between the two groups. Our study employed rigorous randomization and blinding procedures to ensure unbiased results. 3. Results: There was a significant (p<0.05) improvement in patients' GCS up until the fourth day, but no significant difference was noted afterward. In addition, the volume of both edema and hematoma was significantly lower in the intervention group, as well as the length of stay, intubation requirement, and mortality. 4. Discussion: Deferoxamine administration can, at least in a short timeframe, improve neurological and radiological parameters.

Introduction: Treating elbow fracture-dislocation is a challenge, especially in the situation of basal-coronoid trans-ulnar fracture. The study ams to explain whether or not the minimal invasive surgery (MIS) would be feasible in elbow dislocation with coronoid fracture. Materials & Methods: At Taipei Veterans General Hospital, patients who had elbow dislocations with coronoid process fractures underwent single one surgeon’s MIS techniques which included the fluoroscopy-guided ulnar anteromedial (FGUAM) approach in the stage of reducing coronoid process. When there is a proximal ulnar fracture, the posterior incision should be necessary, followed by the incision over the lateral or medial elbow in treating radial fractures or ligament injuries. Results: The Flow Diagram about approach recommendation was established in base of defining MIS as not to do cross-plane dissection. Anteriorly rigid fixation for the coronoid process was also emphasized. Conclusions: MIS can be achieved by multiple limited surgical incisions. However, if there is an unstable ulnar metaphysis or ligament avulsion fracture, the posterior approach has to be extended and the so-called MIS fails to be established.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

The following narrative review embarks on a comprehensive exploration of the pivotal role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing towards promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely frag-ile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage gener-ates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular mi-croscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations par-ticularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

Buttonweed (Cotula coronopifolia) is native to South Africa but invasive in wetlands in Europe, North America, and Australasia, where it excludes native plants. Despite being dry-fruited, field studies suggest migratory waterbirds can disperse its seeds via gut passage (endozoochory), aiding its expansion. To explore the potential for endozoochory in different regions and habitats, we collected seeds from six populations in Spain, Sweden, and the UK. Germination was tested under different salinity levels (0, 5, 10, 15 g/L) and simulated gut passage treatments: scarification, acidification, or both. No germination occurred at 15 g/L. Higher salinity reduced and delayed germination, but full gut passage treatment increased germinability and accelerated germination. Scarification or acid treatment alone resulted in intermediate germination patterns. There were significant salinity x population and gut passage x population interactions on germinability. The acceleration effect of gut passage on germination was stronger at 5-10 g/L than at 0 g/L. This study highlights how migratory birds can facilitate the spread of alien plants introduced by humans. Non-classical endozoochory by waterbirds is an understudied mechanism for the long-distance dispersal of dry-fruited alien plants. Further research on C. coronopifolia, including population genetics, is necessary to understand dispersal mechanisms and facilitate management strategies.

Introduction: Acute rhinosinusitis (ASR) is a common condition in children, which can be burdened by orbital complication (OC) or intracranial complications (IC) that are rare but have potential for serious sequelae; therefore, it needs prompt diagnosis and treatment. The first line of treatment is intravenous antibiotic therapy. In case of failure of clinical improvement after 48 hours, hypovisus or negative prognostic factors (intracranial abscess, large orbital abscess or in intraconic or lateral localization, cavernous sinus thrombosis), surgical treatment is indicated. Objective: the purpose of this work is to describe the clinical profile, treatments and outcome of a series of patients undergoing surgical treatment for complications of ARS at a tertiary referral center. Material and methods: a retrospective analysis of clinical databases was conducted to identify all patients under 16 years of age who underwent surgical treatment for complications of ARS during the 20-year period 2000-2023. Demographic characteristics, clinical data, radiological investigations, surgical treatment, and follow-up performed were reported for each case. Results: 29 patients (20 males and 9 females), mean age 13 years, were included, 69% of whom had OC, 21% had IC, and 7% had both OC and IC. The main symptoms of OC were orbital edema, hypovisus and diplopia; while the main symptoms of IC were headache, fever, comitial seizures and focal neurological symptoms. Mean hospitalization time was 11.75 (± 9.2) days. The mean length of hospital stay (LOS) was 9.1 days for OC, 21 days for IC and 14 days for OC + IC. A single patient manifested a Potts Puffy Tumor, with a LOS of 10 days. Basal CT and gadolinium-enhanced MRI were performed in all cases. Intravenous antibiotic therapy and surgical clearance was undertaken. The majority of patients (76%) underwent endoscopic endonasal approach, 24% external transorbital approach, 1,16% orbital decompression and 0,58% superior eyelid approach. Any complications related to the surgical procedures were found. All patients with hypovisus and diplopia had complete recovery. During follow-up 7 patients (24%) had sinus recurrences, at a time range of 1 to 4 years after surgery. Conclusion: our experience, in agreement with the data reported in the literature, confirmed the importance of appropriate diagnostic-therapeutic management to avoid potentially serious sequelae of complicated ARS.