Background: Studies have tried to identify predictors of functional markers of keratoconus progression, whereas structural outcomes of collagen cross-linking have not been properly investigated. Objective: find and set up a combination of diagnostic modalities and measurements to reliably reflect CXL efficiency. Material and methods: We retrospectively reviewed the medical histories of 107 KC patients (131 eyes) who underwent CXL in a medical center from January 2018 to December 2022. The dataset included preoperative examinations and follow-up results, which provided a total of 796 observations. The cases of other corneal diseases, repeated CXL, pregnancy, and observations without follow-up examinations were excluded. Results: The study findings revealed a significant drop in the central and corneal thickness during 14.01±9.98 months of observations. Linear and polynomial equations suggested different trends in pachymetry change after CXL. The linear model showed corneal thinning, and according to the polynomials, pachymetry findings return to baseline values two years after CXL. Conclusion: The most reliable prognosis of postoperative corneal thickness is achieved with the models trained on keratometry readings and topography indices. BAD indices are also reliable predictors of the corneal thickness after CXL. A combination of the aforementioned structural parameters and their derivatives can reliably predict CXL efficiency.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Breast cancer in patients with prior breast augmentation poses unique challenges for detection, diagnosis, and management. Mastectomy rates are increasing, and patients with prior augmen-tation often have a lower body mass index, making autologous techniques unsuitable. This study aims to assess the best reconstructive option in patients with a history of subglandular or dual plane breast augmentation. Materials and methods: a prospective analysis was conducted on pa-tients who underwent breast reconstruction after mastectomy. Patients with subglandular or dual plane breast augmentation were included. Patients were divided into submuscular breast recon-struction (group 2) or prepectoral breast reconstruction (group 1) groups. Demographic and sur-gical data were collected. Results: A total of 47 patients were included, with 23 in Group 1 and 24 in the Group 2. Complications occurred in 11 patients (23.4%), with significant differences be-tween groups. The most common complication was seroma formation. Implant loss occurred in 4.3% of cases in the Group 1, while no implant loss was observed in the Group 2. Patient-reported satisfaction scores were similar between groups at 12 months postoperatively. Conclusions: sub-pectoral breast reconstruction with a tissue expander seems a safer and effective technique for pa-tients with prior breast augmentation. It resulted in fewer complications. This approach should be considered as an option for breast reconstruction after mastectomy in this cohort of patients.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

Aim: The aim of this study is to evaluate the possibility of discriminating between the two sexes through the simultaneous use of cheiloscopy and palatine rugoscopy. Materials and methods: 80 palate and lip impressions (40 male and 40 female) were analyzed. The palate impressions were acquired using both analogue and digital methods. The lip impres-sions were first acquired analogically and then scanned. The morphology of the palatine rugae in the palate impressions was analyzed, with the exclusion of segmental rugae. The lip prints were analyzed in sextants and the morphology of the lip wrinkles was evaluated. Results: Palatine rugoscopy shows that women have more curvy rugae than men and that men have more rugae on the left side than on the right. Cheiloscopy gave no statistically significant re-sults. Discussion: Palatine rugoscopy showed some differences between the sexes, however, these re-sults were not solid enough for reliable sex discrimination. Differences between the results of dif-ferent studies can be attributed to ethnic and methodological variations. Cheiloscopy, on the other hand, did not provide statistically significant results for sex discrimination. Conclusions: Given the scant results obtained from palatine rugoscopy and the lack of statisti-cally relevant results in cheiloscopy, together with a lack of concordance among the data found in literature, it is believed that it is not possible to discriminate between the two sexes by using the two methods contemporarily. Further research is needed.

The art of observing and describing behaviors has driven diagnosis and informed basic science in Psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In Precision Medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes genes’ expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate genes’ expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing the genes’ expressions on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological ones. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g. Autism, Schizophrenia, Depression) through DSM-observation criteria, have strong convergence with well-known neurological ones (e.g. Ataxias, Parkinson), but less overlap with non-neurological ones. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Background: The aim of this experimental work was to evaluate cheiloscopy potential: to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject, with a focus on assessing the method's limitations. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants. All the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, but the absence of a database greatly limits its use. Additionally, its use for sex identification does not seem to be reliable. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Aortic stenosis continues to be still the most frequently valvular pathology in the elderly population of the Western countries. According to the latest guidelines, the therapeutic choice of aortic stenosis depends on the age of the patient (<75 years or >75 years) and the risk class (STS-Prom/ Euroscore II < o > 4%). Therefore, if the surgical indication is clear in young and low risk patients and percutaneous treatment is the gold standard in older and high-risk patients, the therapeutic choice is still debated in intermediate-risk patients. In this group of patients the aortic valve stenosis treatment depends on the patient's global evaluation, on the experience of the center and no less important on the patient's will. Two main therapeutic options are debated: surgical aortic valve replacement with sutureless prosthesis versus transcatheter aortic valve implantation. In addition, the progressive development of mininvasive techniques for aortic valve surgery (right -anterior minitoracotomy) has also reduced the peri and post -operative risk in this group of patients. The goal of our review is to analyze the literature evidence of the best therapeutic choice in intermediate risk patients with severe aortic stenosis.

Background: The aim of this experimental work was to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants, all the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female and the presence of sex-linked features. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, and can be a valid tool in gender determination but the absence of a database greatly limits its use. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision-making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of data sets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.

Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines, and 3D tumor models. To address this goal, a well characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labelled tumor cells were injected into the perivitelline space of 2 days post fertilization zebrafish embryos. At 1 day post-injection xenografts were as-sessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib, and trametinib + luminespib. Subsequently xenografts were euthanized and analysed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n=84) in vivo and with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.

Epigenetic changes regulate gene expression through histone modifications, chromatin remod-eling and proteins interpreter of these modifications. The PRC1 and PRC2 complexes shape gene repression via histone modifications. Specifically, the CBX protein family aids PRC1 recruitment to chromatin, impacting the progressive multistep process driving chromatin silencing. Among family members, CBX3 is a complex protein involved in aberrant epigenetic mechanisms that drive lung cancer progression. CBX3 promotes lung tumorigenesis by interacting with key pathways such as PI3K/AKT, Ras/KRAS, Wnt/β-catenin, MAPK, Notch, and p53, leading to in-creased proliferation, inhibition of apoptosis, and enhanced resistance to therapy. Given our current lack of knowledge, additional research is required to uncover the intricate mechanisms underlying CBX3 activity, as well as its involvement in molecular pathways and its potential biomarker evaluation. Specifically, the dissimilar roles of CBX3 could be reexamined in order to gain a greater insight into lung cancer pathogenesis. This review aims to provide a clear overview of the context-related molecular profile of CBX3, which could be useful for addressing clinical challenges and developing novel targeted therapies based on personalized medicine.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Cancer is fundamentally a disease of perturbed genes. Although many mutations can be marked in the genome of a cancer or transformed cell, the initiation and progression were shown to be driven by only a few mutational events viz. driver mutations that progressively govern and execute the functional impacts. The driver mutations are thus believed to dictate and dysregulate the subsequent cellular proliferative function/decisions thereby producing a cancerous state. Therefore, identifying the driver events from the genomic alterations in a patient’s cancer cell gained large attention recently for designing better targeting therapies towards paving way for the precision cancer medicine. With rolling advancements in high-throughput omics technologies, analysis of genetic variations and gene expression profiles for cancer patients has become a routine clinical practice. However, it is anticipated that protein structural alterations resulting from such driver mutations can provide more direct and clinically relevant evidence of disease states than genetic signatures alone. This review comprehensively discusses various aspects and approaches that have been developed for the prediction of cancer drivers using genetic signatures and protein structures, and their potential application in developing precision cancer therapies.Keywords:

The makeup of human microbiota has been linked to a number of autoimmune disorders. Recent developments in whole metagenome sequencing and 16S rRNA sequencing technology have considerably aided research into the microbiome and its relationship to disease. Due to the inherent high dimensionality and complexity of data generated by high-throughput platforms, conventional bioinformatics techniques could only provide an inadequate explanation for the most relevant changes and seldom provide correct predictions. Machine learning, on the other hand, is a subset of artificial intelligence applications that enable the untangling of high-dimensional systems and intricate knots in correlation by learning complex patterns and improving automatically from training data without being explicitly programmed. Machine learning is increasingly being utilized to research the influence of microbes on the onset of illness and other clinical features since computer power has increased dramatically in the last few decades. In this review paper, we focused on emerging methodological approaches of supervised machine learning algorithms for identification of autoimmune disorders utilizing metagenomics data, as well as the potential benefits and limitations of machine learning models in clinical applications.

Background: Peripheral Ossifying Fibroma (POF) is a benign gingival tumor generally presenting as a slow-growing mass, usually not ulcerated, and without bleeding. Histopathological exam shows fibrous connective tissue with spots or extensive areas of intralesional calcifications, which can also be detectable on radiograms. Methods and case presentation: We present the case of a 4-year-old male with a retro-incisive swelling of the hard palate, associated with speaking and feeding difficulties. On CT scans, a small intralesional calcification was detected. After conscious sedation, the patient was subjected to diode laser excision (910 nm, 2W, CW, 300 m fiber) with-out post-operative complications. A review was conducted by searching the words “peripheral ossifying fibroma” AND “children” OR “infant” and including manuscripts of the last 15 years. Results: POF is an uncommon lesion of the oral mucosa and may sporadically affect the palatal mucosa in children. Considering its epidemiology and conventional clinical presentation as epu-lis, the pre-operative diagnosis may be relatively difficult. Risk factors could be represented by plaque, calculus, or trauma, all supporting a possible reactive pathogenesis, but a certain etiology is still missing. The main problem of POF is the recurrence rate, which is particularly high (8-20%), thus suggesting that a deep excision is recommended with full extension to the hard tis-sue of bone and to the adjacent periodontal ligament. Diode laser surgery may be recommended for such treatments, especially in pediatric patients, associated with intraoperative conscious se-dation. Data emerging from the relevant literature on POF management in children have been collected and discussed. Conclusions: The authors suggest the use of diode laser for the complete excision of POF, especially in less-compliant patients as children, with a low grade of comorbidi-ties and good outcomes, giving the surgeon a viable alternative to conventional surgery.

BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the homologous recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation called HR deficiency. Since their identification, pathogenic variants and other alterations of BRCA1 and BRCA2 genes have been associated with an increased risk of developing mainly breast and ovarian cancer. Interestingly, HR deficiency is also detected in tumors not carrying BRCA1/2 mutations, a condition termed “BRCAness”. One of the main mechanisms causing the BRCAness phenotype is the methylation of the BRCA1/2 promoters and this epigenetic modification is associated with carcinogenesis and poor prognosis mainly among patients with breast and ovarian cancer. BRCA1 promoter methylation has been suggested as an emerging biomarker of great predictive significance, especially concerning Poly (ADP-ribose) Polymerase inhibitors (PARP inhibitor-PARPi) responsiveness, along with or beyond BRCA1/2 mutations. However, as its clinical exploitation is still insufficient, the impact of BRCA1/2 promoter methylation status needs to be further evaluated. The current review aims to gather the latest findings about the mechanisms that underline BRCA1/2 function as well as the molecular characteristics of tumors associated with BRCA1/2 defects, by focusing on DNA methylation. Furthermore, we critically analyze their translational meaning and the validity of BRCA methylation biomarkers in predicting treatment response and we suggest a diagnostic pipeline that could be implemented in liquid biopsy to aid precision pharmacotherapy in BRCA-associated tumors.

This study extends the CGAN-based MODIS cloud vertical-profile (64×64-scene, about 70km width×15km height) retrieval technique developed by Leinonen et al. (2019) [1] to construct seamless 3D cloud fields for the MODIS granules [2]. Firstly, the accuracy and spatial continuity of the Leinonen et al. [1] retrievals are statistically evaluated. Then, according to the characteristics of the retrieval error, a spatially overlapping-scene ensemble generation method and a bi-directional Ensemble Binning Probability Fusion (CGAN-BEBPF) technique are developed, which improves the CGAN retrieval accuracy and support to construct seamless 3D clouds. The CGAN-BEBPF technique involves three steps: cloud masking, intensity scaling, and optimal value selection. It ensures adequate coverage of the low reflectivity areas while preserving the high reflectivity cloud cores. The technique is applied to retrieve the 3D cloud fields of Typhoon Chaba and a multi-cell convective system. The cloud structures of the CGAN-BEBPF results are highly consistent with the ground-based radar observations. It can retrieve weak clouds at the top levels of convective storms and hurricanes that were missed by ground-based radars and fill the gaps of the ground-based radar lower-level PPI scan. Overall, CGAN-BEBPF can be automated to retrieve the rich informative 3D structures of typhoons and severe convective systems over the oceans along the MODIS swath, which certainly presents great value for improving maritime and near-shore typhoons and convection prediction and other cloud-sensitive applications.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

Nowadays, Multi-needle electrospinning has used to be an efficient method for producing nanofiber membranes. But in the process, the fluctuation errors in electrospinning fluid flow rate have directly influence the membrane quality, which bringing instability and still have not been solved yet. For finding out the solution to the inaccurate flow control in multi-needle, it is necessary to develop a multi-stage flow runner spinneret for large-scale production of nanofiber membrane. At first, the paper uses the finite element software COMSOL to numerically simulate the polymer flow in the runner of spinneret. Based on it, the velocity field distribution curve was draw and the velocity instability coefficient of the polymer flow was attained, which are providing theoretical guidance for the optimal design of spinneret. Next, the response surface analysis method (RSM) was used to establish a regression model between the average diameter of the nanofiber membrane and the process parameters. Then, above regression model used to perform variance data processing between the average diameter and the process parameter configuration. After that, the 2D and 3D response surface profiles and the significance analysis were completed. Finally, the stability of the nanofibers production was improved, which attained the optimal adjustment of process configuration in multi-needle electrospinning.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation, and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarized the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug response prediction. We also explained the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface, through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification, to accelerate personalized treatment and precision medicine.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Herein, we examined the effects of weather parameters and individual clinicodemographic risk factors on hemorrhagic stroke (HS) incidence, severity on admission, and disability at discharge in a harsh desert climate. In a retrospective design we studied patients admitted to a stroke unit in Arab Emirates in 2016-2019. With a distributed lag nonlinear model we explored immediate and delayed effects of weather on stroke incidence. Supervised machine learning was used to build models predictive of scores in NIHSS and mRS scales. We assessed model performance by calculating ROC AUC, F1 scores, specificity, and sensitivity. HS risk increased after a significant change in any weather parameter. The risk was reduced below baseline after 1-week adjustment to environmental changes. Climate input from the previous 3 days yielded reliable classification models. Humidex was a better predictor of severity than air temperature, whereas body mass index, age, and time of day at stroke onset were the strongest clinical predictors. Weather parameters before admission were stronger predictors of disease severity than individual clinical factors. We addressed limitations of previous studies by analyzing a full set of climate parameters: ambient temperature, relative humidity, humidex, atmospheric pressure, and wind speed. Predictive models may help to optimize patient management and develop preventative strategies.

The unravelling of the human genome created new perceptions on the origin and evolution of diseases and for cancer in particular, it established the notion that neoplasia has been a companion of life since its ap-pearance on earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today, begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century, generate new ther-apeutic opportunities with immunotherapy, oncolytic virotherapy and gene transfer, the latter especially in cases of hereditary cancer.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

Diffuse intrinsic pontine gliomas (DIPGs) account for ~15% of pediatric brain tumors, which invariably present with poor survival regardless of treatment mode. Several seminal studies have revealed that 80% of DIPGs harbor H3K27M mutation coded by HIST1H3B, HIST1H3C and H3F3A genes. The H3K27M mutation has broad effects on gene expression and is considered a tumor driver. Determination of the effects of H3K27M on posttranslational histone modifications and gene regulations in DIPG is critical for identifying effective therapeutic targets. Advanced animal models play critical roles in translating these cutting-edge findings into clinical trial development. Here, we review current molecular research progress associated with DIPG. We also summarize DIPG animal models, highlighting novel genomic engineered mouse models (GEMMs) and innovative humanized DIPG mouse models. These models will pave the way towards personalized precision medicine for the treatment of DIPGs.

Introduction. Anesthesia is widely used in various fields of dentistry to reduce patient discomfort when the treatment would be painful. The dentist may need to infiltrate the anesthetic into multiple locations and this is usually done with the same needle which passes through the soft tissues several times to distribute the anesthetic solution over a larger area. The present study aims to evaluate, through a morphological analysis under a scanning electron microscope (SEM), how the beveled tip of a 30G needle, used to inject anesthetic several times into different areas of the vestibular mucosa, changes. Materials and methods. 30G needles with two different brands were tested, in vivo used for a variable number of sequential injections from 1 to 6 on 192 patients. The specimens were analyzed under SEM observation to evaluate any deformations induced by contact with the vestibular soft tissues. Results. The amount of deformation, measured along the axis parallel to the needle, was proportional to the number of injections. The protrusion of deformations, measured on an axis perpendicular to the needle, were maximum on the needles used 3 times. For the needles used 4,5 and 6 injections, no further increase in deformations was noted. Conclusion. From the data it seems that the tested needles are not produced to withstand multiple injections consequently after the first injection on soft tissues, they undergo a deformation which could increase the risk of injury to the mucosa itself or to nerves and vessels with which they come into contact. It would be advisable to use the single needle for a reduced number of injections.

Esophageal cancer is a formidable challenge in the realm of cancer treatment. Conventional methods such as surgery, chemotherapy, and immunotherapy have demonstrated limited success rates in managing this disease. In response, targeted drug therapies have emerged as a promising strategy to improve outcomes for patients. These therapies aim to disrupt specific pathways involved in the growth and development of esophageal cancer cells. This review explores various drugs used to target specific pathways, including cetuximab and monoclonal antibodies (gefitinib) that target the epidermal growth factor receptor (EGFR), trastuzumab that targets human epidermal growth factor receptor 2 (HER-2), drugs targeting the vascular endothelial growth factor receptor (VEGFR), mTOR inhibitors, and cMET inhibitors. Additionally, the article discusses the impact of drug resistance on the effectiveness of these therapies, highlighting factors such as cancer stem cells, cancer-associated fibroblasts, immune-inflammatory cells, cytokines, hypoxia, and growth factors. While drug targeting approaches do not provide a complete cure for esophageal cancer due to drug resistance and associated side effects, they offer potential for improving patient survival rates.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

Precision cancer medicine primarily aims to identify individual patient genomic variations and exploit vulnerabilities in cancer cells to select suitable patients for specific drugs. These genomic features are commonly determined by gene sequencing prior to therapy, to identify individuals who would be most responsive. This precision approach in cancer therapeutics remains a powerful tool that benefits a smaller pool of patients, sparing others from unnecessary treatments. A limitation of this approach is that proteins, not genes, are the ultimate effectors of biological functions, and therefore the targets of therapeutics. An additional dimension in precision medicine that considers an individual’s cytokine response to cancer therapeutics is proposed. Cytokine responses to therapy are multifactorial and vary among individuals. Thus, precision is dictated by the nature and magnitude of cytokine responses in the tumor microenvironment exposed to therapy. This review highlights cytokine responses as modules for precision medicine in cancer therapy, including potential challenges. For solid tumors, both detectability of cytokines in tissue fluids and their being amenable to routine sensitive analyses could address the difficulty of specimen collection for diagnosis and monitoring. Therefore, in precision cancer medicine, cytokines offer rational targets that can be utilized to enhance the efficacy of cancer therapy.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and the risk of a major cardiovascular event is highest among those with established disease. Ongoing management of these patients relies on the accurate assessment of their response to any prescribed therapy, and their residual risk, in order to optimize treatment. Recent international guidelines and position statements concur that the plasma concentration of apolipoprotein B (apoB) is the most accurate measure of lipoprotein associated ASCVD risk. This is especially true for the growing number of individuals with diabetes, obesity or the metabolic syndrome, and those on statin therapy. Most guidelines, however, continue to promote LDL-C as the primary risk marker due to uncertainty as to whether the greater accuracy of apoB is sufficient to warrant a paradigm shift. Recommendations regarding apoB measurement vary, and the information provided on how to interpret apoB results is sometimes insufficient, particularly for the non-lipid specialist. Misinformation regarding the reliability of the assays is also frequently repeated despite its equivalent or better standardization than many other diagnostic assays. Thus, demand for apoB testing is relatively low, which means there is little incentive to increase its availability or reduce its cost. In this review, we examine the results of recent clinical outcomes studies and meta-analyses on the relative values of apoB, LDL-C and non-HDL-C as markers of ASCVD risk. Although there is seemingly minimal difference among these markers when only population-based metrics are considered, it is evident from our analysis that, from a personalized or precision medicine standpoint, a great many individuals would benefit, at a negligible total cost, if apoB measurement were better integrated into the diagnosis and treatment of ASCVD.

Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Microscopic vision plays an important role in automated micro-assembly. However, some uncertain factors in the assembly process, such as occlusion and stains can lead to the mistakes of feature extraction. Herein, to solve the problem, the deep learning techniques are introduced into the feature recognition tasks, focusing on the attention mechanism and visualizing CNNs for DL-based microscopic vision. The main contributions are summarized as follows: The CBAM attention mechanism is combined with the YOLOv5 algorithm to improve the accuracy and robustness of feature extraction. The micropart feature occlusion experiment results show that at 70% occlusion degree, YOLOV5-CBAM can reach 97.9% [email protected], which is 4.6% higher than the original one. Visualization analysis of DL-based model is conducted using Grad-CAM to make the decision result more transparent and avoid potential visual detection risks during assembly. The heatmap matching degree between GT area and high-light area is increased by 27.81% on average, which further verify the effectiveness of attention mechanism in micropart feature localization. Additionally, micropart surface stain and droplet quality classification models based on ResNet50 are trained to replace the manual sorting. The visual results are consistent with human eye discernment and judgement, confirming the reliability of parts and droplets sorting.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

The central promise of personalized medicine is individualized treatments that target molecular mechanisms underlying the physiological changes and symptoms arising from disease. We demonstrate a bioinformatics analysis pipeline as a proof-of-principle to test the feasibility and practicality of comparative transcriptomics to classify two of the most popular in vivo diet-induced models of coronary atherosclerosis, apolipoprotein E null mice and New Zealand White rabbits. Transcriptomics analyses indicate the two models extensively share dysregulated genes albeit with some unique pathways. For instance, while both models have alterations in the mitochondrion, the biochemical pathway analysis revealed, Complex IV in the electron transfer chain is higher in mice, whereas the rest of the electron transfer chain components are higher in the rabbits. Several fatty acids anabolic pathways are expressed higher in mice, whereas fatty acids and lipids degradation pathways are higher in rabbits. This reflects the differences between two translational models of atherosclerosis. This study validates transcriptome analysis as a potential method to precisely identify altered cellular and molecular pathways in atherosclerotic disease, which can be used to individualize treatment even in the absence of genetic data.

Tungsten balls with sub-100-μm diameter can function as probe tips for micro-coordinate measuring machines (CMMs) to measure ultraprecise workpieces such as ceramic bearings with a high aspect ratio. A high-precision measuring system was proposed to evaluate the roundness error of the self-made tungsten ball tips. The principles and mathematical models of the measuring system are illustrated, and the fabrication principle of tungsten balls is introduced. An analysis was conducted on the maximum allowable contact force and bending strength of the tungsten ball tips, and the elastic mechanism was designed based on the analysis. A ruby probe with a sphericity error of 130 nm (A-5003-0577, Renishaw Corporation) used as a reference sphere was measured to verify the system's effectiveness. Repeated measurement experiments were performed for two tungsten ball tips. The results show the roundness error of the tungsten ball-A is between 568.3 and 586.2 nm with a standard deviation of 6.6 nm while the tungsten ball-B’s roundness error is between 898.5 and 958.0 nm with a standard deviation of 19.7 nm. The uncertainty is calculated as 125.8 nm. The developed system can stably measure the roundness of the tungsten ball tips.

Recent data has shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. Liquid biopsy’s monitoring for biomarkers of head and neck cancer, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Anemia is a well-developed discipline where the concepts of precision medicine have, in part and being studied extensively. This review discusses the treatment of EPO-deficient anemia and resistance in Chronic Kidney Disease (CKD). Traditionally, erythropoietin-stimulating agents (ESA) and iron supplementation have been used to manage anemia in CKD. However, these treatments have potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron, and erythropoietin-iron combination therapy. Another novel approach is using hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). This review highlights the need for precision medicine targeting genetic components of EPO-deficient anemia in CKD and discusses individual variability of genes such as the erythropoietin gene (EPO), Interleukin-β gene (IL-β), and hypoxia-inducible factor gene (HIF). Pharmacogenomics testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, optimizing treatment outcomes and minimizing resistance and adverse effects. The article concludes by suggesting the potential of receptor modification to revolutionize treatment outcome of erythropoietin deficiency anemia through integration of the mentioned approach.

To achieve a narrow bandwidth optical filter with a wide swept range for new generation optical spectrum analysis (OSA), an optoelectronic equivalent narrowband filter (OENF) is investigated and a swept optical filter with bandwidth of several MHz and swept range of several ten nanometers is built using electric filters and a swept laser as local oscillator (LO). The principle of OENF is introduced and analysis of OENF system is presented. Two electric filters are optimized to be RBW filters for high and medium spectral resolution application. Both simulations and experiments are conducted to verify OENF principle and results show that power uncertainty is less than 1.2% and spectral resolution can reach 6 MHz. Then, a real-time wavelength calibration system consisting of HCN gas cell and FP etalon is proposed to guarantee a wavelength accuracy of ±0.4 pm at C-band and to reduce the influence of phase noise and nonlinear velocity of swept LO. Finally, experiments on OSA of actual spectra of various optical sensors using OENF system are conducted. Experimental results indicate that OENF system has an excellent capacity in analysis of fine spectrum structures.

Nanoencapsulation has emerged as a recent improvement in the delivery of drugs, offering and improving stability and bioavailability, and allowing for the controlled and targeted delivery of substances to specific cells or tissues. However, traditional nanoparticle delivery faces challenges such as short circulation time and immune recognition. To address these issues, cell membrane-coated nanoparticles have been proposed as a promising alternative. The production of cell membrane-coated nanoparticles involves three key stages: cell lysis and membrane fragmentation, membrane isolation, and nanoparticle coating. Typically, cell membranes are fragmented using hypotonic lysis in combination with homogenization or sonication. Subsequent membrane fragments are isolated through multiple centrifugation steps. The coating of nanoparticles can be achieved through extrusion, sonication, or a combination of both methods. This analysis shows the absence of a universally applicable method for nanoparticle coating, as the three stages exhibit notable differences in their procedures. Here we review ongoing developments and approaches to cell membrane-coated nanoparticles that position this technology as a promising alternative for effective targeted drug delivery and many other therapeutic applications.

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

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: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and im-proved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologi-cally confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP. Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n=12 [11.8%]), 14 months in patients with actionable GAs treated with standard therapies (n=17 [16.7%]), and 17 months in patients without actionable GAs treated with standard therapies (n=73 [71.5%]; p=0.26). The absence of liver metastases was associated with better OS (HR=0.471, p=0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

Nutraceuticals have taken the spotlight during the past two decades as evidenced by the exponential publications on them. Long a part of routine in Traditional Medicine Systems, the rise of their mainstream use globally raises both safety concerns and need for better understanding of efficacious dosing. We attempt to answer these questions in this preliminary scoping review by an analysis of current literature on nutraceutical use as a personalized or prescription medicine. Using Covidence, Rayyan, and manual searches of PubMed, 598 unique publications were selected. 32 are systematic reviews, of which we overview the scope. We also overview 30 papers that address adverse drug reactions. To obtain an unbiased landscape of the 598 papers, we analyzed keywords using multiple methods. Expectedly, the most frequent keywords were probiotics and vitamins. Unexpectedly and remarkably, among the highest keyword yield was ‘COVID’. Further exploring this aspect, we review 15 pertinent papers, that not only provide robust evidence for nutraceutical benefits as part of SARS-CoV-2 treatment, but also amplify the notion that nutraceuticals are protective. Overall, the strident note is that further robust targeted research is needed in order to reap the full benefits of nutraceuticals in a safe and efficacious manner.

Life is supported by metabolism, a vital physiological activity. It guarantees enough energy available to power every cellular activity. The primary cellular substrate, glucose, is where the majority of the energy needed by the cell to support all other life activities and the growth of living creatures is derived. The quality of life is greatly impacted by any disease or flaw that alters the metabolism of glucose. There is no known cure for the metabolic illness known as diabetes. As diabetes is so varied, the only effective treatments would be based on precision medicine and a molecular strategy. This review covers a wide range of topics, including the ability to recognize the various forms of diabetes, the anthropogenic and genetic influence of the cause of diabetes, the severity of the various forms of diabetes, its potential existential risk, the disease burden, and clinical methods for diagnosing them. The most recent research goes on to recommend ways to ameliorate the disease, including diet-based management, biotherapies, and other individual lifestyle choices. Futuristic therapy using molecular biology approach was suggested. Recent research found a direct correlation between an individual's lifestyle and the rate of gene mutation in diabetes. There is an existential risk associated with the sickness as the rate of the spread of the disease among population globally is faster than the world's population growth rate. It is possible to think of diabetes as a silent pandemic.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, the pathological mechanisms of depression remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in the experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, it modifies signals connected to depression. The present review emphasizes the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways to produce antidepressant effects, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK. Given the antidepressant effects of ghrelin/GHSR1a system, it is expected to become a potential therapeutic target for the treatment of depression.

High-precision displacement sensing has been widely used across from both scientific researches and industrial applications. The recent interests in developing micro-opto-electro-mechanical systems (MOEMS) have given rise to an excellent platform for miniaturized displacement sensors. Advancement in this field during past years is now yielding integrated high-precision sensors which show great potential in applications ranging from photoacoustic spectroscopy to high-precision positioning and automation. In this review, we briefly summarize different techniques for high-precision displacement sensing based on MOEMS, and discuss the challenges for future improvement.

Introduction: Parkinson’s disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (9 homozygous or compound heterozygous PRKN carriers, 4 Heterozygous PRKN carriers and 3 biallelic PINK1 carriers) were evaluated. Results: The average Levodopa Equivalent daily dose (LEDD) was 806.8±453.5 (range 152-1810) in PRKN carriers and 765±96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of Levodopa. The response to Dopamine Agonists (DA) was often favorable both as initial and longitudinal therapy. 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate Levodopa or DA. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any Levodopa treatment decades after disease initiation. DA or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments will be further discussed.

A PLS-based quality prediction method is proposed for batch processes using two-dimensional extended windows. To realize the adoption of information in the direction of sampling time and batch, a new definition region of support (ROS), k-i-back-extended region of support (KIBROS), is proposed to establish the extended window, which including the data of the previous sampling times in the same batch, the data of the same sampling time in the historical batches, the data of the previous sampling times in the historical batches and the data of the later sampling times in the historical batches. According to these regions of support, extended windows are established, and different models are proposed based on the extended windows for batch processes quality prediction. Further, using a typical batch process as an example, the injection molding process, the proposed quality prediction method is experimentally verified, proving that the proposed methods have higher prediction accuracy than the traditional method and the prediction stability is also improved.

YOLOv8, as an efficient object detection method, can swiftly and precisely identify objects within images. However, traditional algorithms encounter difficulties when detecting small targets in remote sensing images, such as missing information, background noise, and interactions among multiple objects in complex scenes, which may affect performance. To tackle these challenges, we propose an enhanced algorithm optimized for detecting small objects in remote sensing images, named HP-YOLOv8. Firstly, we design the C2f-D-Mixer (C2f-DM) module as a replacement for the original C2f module. This module integrates both local and global information, significantly improving the ability to detect features of small objects. Secondly, we introduce a feature fusion technique based on attention mechanisms, named Bi-Level Routing Attention in Gated Feature Pyramid Network (BGFPN). This technique utilizes an efficient feature aggregation network and reparameterization technology to optimize information interaction between different scale feature maps, and through the Bi-level Routing Attention (BRA) mechanism, it effectively captures critical feature information of small target objects. Finally, we propose the Smooth Mean Perpendicular Distance Intersection over Union (SMPDIoU) loss function. The method comprehensively considers the shape and size of detection boxes, enhances the model's focus on the attributes of detection boxes and provides a more accurate bounding box regression loss calculation method. To demonstrate our approach's efficacy, we conduct comprehensive experiments across the RSOD, NWPU VHR-10, and VisDrone2019 datasets. The experimental results show that the HP-YOLOv8 achieves 95.11%, 93.05%, and 53.49% in the [email protected] metric, and 72.03%, 65.37%, and 38.91% in the more stringent [email protected]:0.95 metric, respectively.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

(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.

This study fabricated piezoelectric fibers of polyvinylidene fluoride (PVDF) with graphene using near-field electrospinning (NFES) technology. A uniform experimental design table U*7 (7^4 ) was applied, considering weight percentage (1-13 wt%), distance between needle and disk collector (2.1-3.9 mm), and applied voltage (14.5-17.5 kV). We optimized the parameters using electrical property measurements and the Kriging response surface method. Adding 13 wt% graphene significantly improved electrical conductivity, increasing from 17.7 μS/cm for pure PVDF to 187.5 μS/cm. The fiber diameter decreased from 21.4 μm in PVDF/1% graphene to 9.1 μm in PVDF/13% graphene. Adding 5 wt% graphene increased the β-phase content by 6.9%, reaching 65.4% compared to pure PVDF fibers. Material characteristics were investigated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), contact angle measurements, and tensile testing. Optimal parameters included 3.47 wt% graphene, yielding 15.82 mV voltage at 5 Hz and 5 N force (2.04 times pure PVDF). Force testing showed a sensitivity (S) of 7.67493 log(mV/N). Fibers were attached to electrodes for piezoelectric sensor applications. Results affirmed enhanced electrical conductivity, piezoelectric performance, and mechanical strength. The optimized piezoelectric sensor could be applied to measure physiological signals, such as attaching it to the throat under different conditions to measure the output voltage. The force-to-voltage conversion facilitated subsequent analysis.

Ideas about Artificial Intelligence appeared about half a century ago, but only now is it becoming an essential element of everyday life. The data provided is getting bigger and bigger and, in this case, we need artificial intelligence that helps us with superhuman powers. The interaction with medicine is getting closer and closer, medicine being a field that continues to be perfected. Machine learning, deep learning, neural networks, computer vision are some of the mechanisms that are already applied in medicine, becoming a trend in healthcare worldwide. Artificial intelligence will be the thing that will change contemporary medicine. Developed countries such as Japan, France, Germany have already implemented artificial intelligence in their medical systems. The help is in medical diagnosis, patient monitoring, personalized therapy, and workflow optimization. Artificial intelligence will help surgeons to perfect their skills, to standardize techniques, to choose the best surgical technique. The goal is to predict complications, reduce diagnostic time, diagnose complex pathologies, guide the surgeon intraoperatively and reduce medical errors. We are at the beginning but the potential is enormous.

This study uses machine learning to identify key factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) from user ratings and prices, we analyzed data from Amazon. The findings indicate that FSA/HSA eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were found to be cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

The Range–Doppler (R-D) model is extensively employed for the geometric processing of Synthetic Aperture Radar (SAR) images. Refining the sensor motion state and imaging parameters is the most common method for achieving high-precision geometric processing using the R-D model, comprising a process that involves numerous parameters and complex computations. In this study, we introduce a novel approach to improve the positioning accuracy of the R-D model, implementing a low-order polynomial to compensate for the original imaging errors without altering the initial positioning parameters. We also design low-order polynomial compensation models with different parameters. The models are evaluated on various SAR images from different platforms and bands, including spaceborne TerraSAR-X and GF3-C images, manned airborne SAR-X images, and unmanned aerial vehicle-mounted miniSAR-Ku images. Furthermore, image positioning experiments involving the use of different polynomial compensation models and various numbers and distributions of Ground Control Points (GCPs) are conducted. The experimental results demonstrate that geometric processing accuracy comparable to that of the classical rigorous positioning method can be achieved even when applying only an affine transformation model to the images. Compared to classical refinement models, however, the proposed image-compensated R-D model is much simpler and easy to implement. Thus, this study provides a convenient, robust, and widely applicable method for the geometric positioning processing of SAR images, offering a potential approach for the joint-positioning processing of multi-source SAR images.

In recent times, the application areas of unmanned aerial vehicles (UAVs) are expanding, and autonomous functions are becoming increasingly prominent, eliminating the need for remote pilot control. Certain applications require the drone to use a docking station autonomously, even for wireless charging. This involves performing autonomous takeoff and landing, where high preci-sion is demanded. These maneuvers can be significantly influenced by environmental factors. The effectiveness of the precision landing function of the DJI Mavic 2 Pro UAV in strong winds is in-vestigated in this article based on experimental measurements conducted outdoors. New findings on the precision landing capabilities of the DJI Mavic 2 Pro UAV are presented in this paper, par-ticularly under windy conditions. The efficiency of precision landing is compared in cases when the precision landing function is enabled versus when it is disabled. It is investigated whether there is a statistically significant difference between the two landing modes in strong winds and it is examined whether the DJI Mavic 2 Pro can perform precision landing on a surface of a specific size in windy conditions. This helps to predict the suitability of the DJI Mavic 2 Pro for precise landing and wireless charging at a docking station in strong winds and high gusts.

This study presents an advanced defect detection approach for solar cells using the YOLOv10 deep learning model. Leveraging a comprehensive dataset of 10,500 solar cell images, annotated with 12 distinct defect types, our model integrates Compact Inverted Blocks (CIB) and Partial Self-Attention (PSA) modules to enhance feature extraction and classification accuracy. Training on the Viking cluster with state-of-the-art GPUs, our model achieved remarkable results, including a mean Average Precision ([email protected]) of 98.5%. Detailed analysis of the model's performance revealed exceptional precision and recall rates for most defect classes, notably achieving 100% accuracy in detecting black core, corner, fragment, scratch, and short circuit defects. Even for challenging defect types such as thick line and star crack, the model maintained high performance with accuracies of 94% and 96%, respectively. The recall-confidence and precision-recall curves further demonstrate the model's robustness and reliability across varying confidence thresholds. This research not only advances the state of automated defect detection in photovoltaic manufacturing but also underscores the potential of YOLOv10 for real-time applications. Our findings suggest significant implications for improving the quality control process in solar cell production.

(1) Background: In a society with an advancing aging rate, medical systems are coming under pressure due to an increasing flow of elderly patients with multiple somatic diseases, exacerbated by their fragile psychological and sociological backgrounds. We aimed to investigate the relationship be-tween frailty and loneliness in elderly people. Our research question was “Is there a link between the loneliness and frailty in elderly people?” (2) Methods: To assess the link between loneliness and frailty, we conducted a search accessing Index Medicus and PubMed; the timeframe of our research was from 2013 till 2023. Data regarding the study population, as well as loneliness and fragility assessments and approaches, were extracted. (3) Results: A positive relationship between loneliness and the appearance and progression of frailty in elderly people is argued for. (4) Conclusions: Maintaining a balance in the body’s functionality for as long as possible requires the diagnosis and periodic assessment of health status at any age and, due to the various socio-financial and emotional implications, is particularly imperative for elderly patients. Frailty can be prevented, and it appears that it could even be reversed if early diagnosis and appropriate interventions are made. Therefore, knowledge of relevant risk factors—most likely including loneliness—is an absolute necessity to slow down, stop, and even reverse the frailty process.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of pulsatilla decoction (BEPD) of the traditional Chinese medicine herbal formula has been shown to be effective in treating UC. We aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL)1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. Our results showed that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduce the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

Background/Objectives: Peritoneal dialysis as a form of renal function sub-stitution is not as widespread as hemodialysis. However, it has recognized advantages such as preservation of the residual renal func-tion, no need for vascular access , can be performed at home, but requires a proper in-sertion of a peritoneal dialysis (PD) catheter and maintaining its patency. Methods: We presented a 10-year retrospective study on a group of 133 patients hos-pitalized for peritoneal dialysis catheter insertion/replacement. We routinely implant the catheter laparoscopically, but there were cases in which the insertion was performed open route. We analyzed the patient group by age and gender criteria, number of complications and time when they appeared, duration of surgical intervention and the surgical technique used (126 were performed laparoscopically and 7 were inserted via open route). The open technique was performed mainly in patients with contraindications of general anesthesia. Results: We encountered a number of 23 complications in 18 patients, in only 1 case the patient was switched to permanent hemodialysis (at his own wish). We highlighted in the study the indisputable advantages of laparoscopy, supported by the results obtained: correct placement of the catheter, the possibility of adhesiolysis, preservation of the peritoneal surface through minor op-erative trauma, low number of complications(bleeding, migration, hernia 0,8%, leakage 4%, lower than those found in the literature). Even if infection was the most frequent complication (peritonitis 35%, catheter exit site infection 30.4%), only 1 case appered in the pretraining period. All complications were managed by medical treatment or by temporary cessation of peritoneal lavage, except of two cases that required reimplantation of the catheter. Conclusions: Laparoscopic catheter insertion for PD is a safe method, with reduced post-procedural complications, thus ensuring a long duration of the functionality of the catheter.

The global food production system faces several challenges, including significant environmental impacts due to traditional agricultural practices. The rising demands of consumers for food products that are safe, healthy, and have animal welfare standards have led to an increased interest in alternative proteins and the development of the cellular agriculture field. Within this innovative field, precision fermentation emerges as a promising technological solution to produce proteins with reduced ecological footprints. This review provides a summary of the environmental impacts related to the current global food production, and explore how precision fermentation can contribute to address these issues. Additionally, we will report on the main animal-derived proteins produced by precision fermentation, with a particular focus on those used in the food and nutraceutical industries. The general principles of precision fermentation will be explained, including strain and bioprocess optimization. Examples of efficient recombinant protein production by bacteria and yeasts, such as milk proteins, egg-white proteins, structural and flavoring proteins, will also be addressed, along with case examples of companies producing these recombinant proteins in a commercial scale. Through these examples, we will explore how precision fermentation supports sustainable food production and holds the potential for significant innovations in the sector.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Background: The incidence of various types of cancer, for example papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diag-nostic biomarkers must be identified and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs sus-pected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis along with identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulat-ing blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, miR-1, miR-206, and miR-221, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG), and from the culture medium of a PTC cell line (MDAT32) and were duly characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes were associated to the molecular pathogenesis of PTC. Conclusions: Thus, our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

Hyperspectral images (HSI) contain abundant spectral information. Efficient extraction and utilization of this information for image classification remain prominent research topics. Previously, hyperspectral classification techniques primarily relied on statistical attributes and mathematical models of spectral data. Deep learning classification techniques have recently been extensively utilized for hyperspectral data classification, yielding promising outcomes. This study proposes a deep learning approach that uses polarization feature maps for classification. Initially, the polar coordinate transformation method is employed to convert the spectral information of all pixels in the image into spectral feature maps. Subsequently, the proposed Deep Context Feature Fusion Network (DCFF-NET) is utilized to classify these feature maps. The model is validated using three open-source hyperspectral datasets: Indian Pines, Pavia University, and Salinas. The experimental results indicated that DCFF-NET achieves excellent classification performance. Experimental results on three public HSI datasets demonstrate that the proposed method accurately recognizes different objects with an overall accuracy (OA) of 86.68%, 94.73%, and 95.14% based on the pixel method, and 98.15%, 99.86%, and 99.98% based on the pixel-patch method.

Malocclusions have a continuously increasing prevalence from a generation to another as a result of climate changes, soil, atmosphere and water pollution. All of these aspects have unfavorable consequences on the nutritional scheme. Thus, nutrition together with other etiopathogenic factors contribute to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren from Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female) and place of origin (rural and urban). For Angle class I malocclusions we recorded the highest prevalence (48,78% from the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45,85% from the total number of schoolchildren with malocclusions) and for Angle class III malocclusions we found the lowest prevalence (5,37% from the total number of schoolchildren with malocclusions).According to gender, we found the highest prevalence in female gender (29,90% from the total number of female subjects), while in male gender we recorded a prevalence of 27,70% from the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in the urban areas (29,16%). The study subgroup included 140 children randomly selected from the total number of subjects from the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking and salivary aspects. It is also aimed to compare the results obtained with similar ones from the specialized literature.

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. This study investigates whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted at the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant group based on the bacteria’s susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from peak to end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 hours (p = 0.0057); and 0%, 29 vs. 54 hours (p = 0.0475). Conclusions: In septic shock with bacteraemia, faster catecholamine dose reduction indicates bacterial susceptibility to initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of appropriate initial empiric therapy.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

The COVID-19 pandemic struck unexpectedly, emergency services and chronic care institutions, including dialysis centers, were overloaded. An important problem was the care of positive COVID patients, but also the care of chronically dialyzed patients who presented emergencies. In our Hospital, which has become a COVID support for dialysis patients with severe forms of the disease, we had to care for PD patients with dialysis-related emergencies. We presented 2 cases of patients managed on an outpatient basis or 1 day hospitalization, treated successfully and without compromising the quality of the care provided. We used remote monitoring, we worked in a multidiscipli-nary team, we shortened the hospitalization of patients (and implicitly the risk of contact). In pandemic conditions, the advantage of PD was represented by the possibility of patient isolation, so that in the first 6 months of the pandemic, we recorded no deaths in this category of patients. In case of hemodialysis patients, in-fection and mortality rates were high. Although we expected an increase in the number of peritoneal dialysis patients in the post-pandemic period, this did not happen. We continue to plead for the popularization of the PD method among patients and doctors, which has proven its advantages under the conditions of the pandemic.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p < 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

This paper presents the PEnsemble 4 model, a sophisticated machine learning framework that integrates IoT-based environmental data to accurately forecast maize yield. With the projected significant growth in global maize demand over the next decade, the inherent risks posed by the crop’s dependence on weather conditions necessitate improved prediction capabilities. The PEnsemble 4 model, developed with high accuracy, incorporates comprehensive datasets encompassing soil attributes, nutrient composition, weather conditions, and UAV-captured vegetation imagery. By employing a combination of Huber and M estimates, the PEnsemble 4 model effectively analyzes temporal patterns in vegetation indices, specifically CIre and NDRE, which serve as reliable indicators of canopy density and plant height. In addition, this research significantly contributes to precision agriculture by offering an efficient and sustainable alternative to conventional farming practices through precise yield predictions. Notably, the PEnsemble 4 model enables earlier estimation, advancing the timeline for yield prediction from the conventional day 100 in the R6 stage to day 79 in the R2 stage. This improvement enhances decision-making processes in farming operations. The remarkable accuracy rate of 91% underscores the importance of adopting a multifaceted data approach that harnesses IoT-derived environmental insights. Additionally, the PEnsemble 4 model extends its benefits beyond yield prediction, facilitating the detection of water and crop stress, as well as disease monitoring in broader agricultural contexts. Ultimately, the PEnsemble 4 model establishes a new standard in maize yield prediction, revolutionizing crop management and protection through the synergistic utilization of IoT and machine learning technologies.

IBD, encompassing CD and UC, are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The bidirectional communication between the gut and the brain, known as the GBA, is disrupted in IBD, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBD affects the brain's inflammatory response system, hormonal axis, and BBB integrity, influencing gut microbiota and clinical responses to probiotics. This review aims to explore the links between dysregulations in the GBA, serum biomarkers, and the development of MCI and NDDs. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on NDDs. Studies suggest a potential link between IBD and extraintestinal complications such as MCI and NDDs. Mechanisms include systemic inflammation, BBB dysfunction, autoimmune responses, GBA dysfunction, medication effects, and comorbidities. Serum biomarkers, including vitamin D3, C-reactive protein, high-sensitivity C-reactive protein, vitamin B12, homocysteine, serum amyloid, neuron-specific enolase, neurofilament light chain, S100 proteins, brain-derived neurotrophic factor, IL-6, LP-2 associated phospholipase, prostaglandin E2, IL-1β, and TNF-α, have been investigated for their potential to predict MCI but current results are lacking clarity.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local proinflammatory Th1 and Th17 subpopulations along with a decrease in Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are needed to ascertain the benefit of microbiota modulation in RPL.

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

To date, the percentage composition of the lung microbiome in bronchopulmonary cancer has not been summarized. Existing studies on identifying the lung microbiome in bronchopulmonary cancer through 16S rRNA sequencing have shown variable results regarding the abundance of bacterial taxa. Objectives: To identify the predominant bacteria in the lung microbiome of bronchopulmonary cancer from samples collected through bronchoalveolar lavage and to assess their potential role in the diagnosis of bronchopulmonary cancers. Data Sources: A systematic review of English articles using MEDLINE, Embase, and Web of Science. Search terms included lung microbiome, lung cancer, bronchoalveolar lavage. Study Selection: Randomized clinical trials that investigated the lung microbiome in bronchopulmonary cancer with samples collected via bronchoalveolar lavage. Data Extraction: Independent extraction of articles using predefined data fields, including study quality indicators. Data Synthesis: Nine studies met the inclusion criteria, focusing on those that utilized a percentage expression of the microbiome at the phylum or genus level. There was noted heterogeneity between studies, both in terms of phylum and genus, with a relatively constant percentage of the Firmicutes phylum and the genera Streptococcus and Veillonella being mentioned. Significant differences were also observed regarding the inclusion criteria for study participants, the method of sample collection, and data processing. Conclusions: To date, there is no consistent percentage pattern at the phylum or genus level in bronchopulmonary cancer, with the predominance of a phylum or genus varying across different patient cohorts, resulting in non-overlapping outcomes.

Background: Bioaerosol can represent a danger to the health. During SARS-CoV-2 pandemic, portable devices were used in different environments and considered a valuable prevention tool. This study has evaluated the effectiveness of the air treatment device “AEROK 1.0” in reducing microbial, particulate and pollen airborne contamination indoors, during normal activity. Methods: In an administrative room, airborne microbial contamination was measured using active (DUOSAS 360 and MD8) and passive sampling; a particle counter was used to evaluate particle concentrations; a Hirst-type pollen trap was used to assess airborne pollen and Alternaria spores. Statistical analysis was performed using SPSS 26.0; p values <0.05 were considered statistically significant. Results: The airborne bacterial contamination assessed by the two different samplers decreased by 55.54% and 69.13%, respectively. The airborne bacterial contamination assessed by passive sampling decreased by 44.16%. For fungi, the reduction was 38.7% by active sampling. Airborne particles (diameters ≥ 1.0, 2.0 μm) and the ratio of indoor/outdoor concentrations of total pollen and Alternaria spp spores significantly decreased. Conclusions: The results highlight the effectiveness of AEROK 1.0 in reducing airborne contamination. The approach carried out represents a contribution to the definition of a standardized model for evaluating the effectiveness of this type of devices.

Background: Removable prostheses have seen a fundamental change recently because of advances in polymer materials, allowing improved durability and performance. Despite these advancements, notable differences still occur amongst various polymer materials and processing technologies, requiring a thorough grasp of their mechanical, physical, and therapeutic implications. Methods: Fours different processing techniques, all utilizing Polymethyl methacrylate (PMMA) as the main material, were used to construct complete dentures. The specimens underwent a mechanical test. Results: All the specimens broke under the influence of a certain force, rather than yielding through flow, as is characteristic for plastic materials. For each specimen, the maximum force (N) was recorded (figure 4), as well as the breaking energy, Conclusions: The best results were obtained in the case of the thermoplastic injection system and, surprisingly and contrary to those in the specialized literature, the worst results were recorded in the case of 3D printed samples.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.