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The escalating complexity and scale of software systems have rendered them increasingly susceptible to a variety of defects. To empower maintenance teams to efficiently prioritize and resolve defects, Software Defect Categorization (SDC) models have emerged, offering the classification of software defects into categories such as "high," "medium," or "low." This study embarks on the development of SDC models, based on three critical defect attributes: i) the maintenance effort required to rectify a defect, ii) the change impact on the software induced by defect resolution, and iii) a combined approach that integrates both maintenance effort and change impact. Leveraging the prevailing advancements in computational power and storage capacity, the study present a novel defect categorization model built upon Convolutional Neural Networks (CNNs). Extensive experiments were carried out on defect datasets from five Android operating system application modules, leading to the creation of 60 SDC models (5 datasets x 4 feature sets x 3 approaches). The results underscore the predictive potential of our CNN-based defect categorization model. Furthermore, SDC models rooted in the combined approach exhibit superior performance when compared to models based solely on change impact and remain competitive with those anchored in maintenance effort.

Abstract Customer turnover is a crucial issue in banking since maintained profitability depends on keeping clients. This work aims to categorize consumer turnover in banks by using a new ensemble approach combining many machine learning methods, hence enhancing churn prediction models. Using a comprehensive dataset including demographic, financial, and behavioral data—such as credit score, account balance, tenure, and activity levels—the study employs the goal variable revealing if a customer has left the bank. The study starts with univariate, bivariate, and multivariate feature exploration and subsequently uses the Interquartile Range (IQR) approach to identify outliers thereby improving the data quality. Five models—K-Nearest Neighbors, Support Vector Classifier, Random Forest, Decision Tree, and XGBoost—a Voting Classifier ensemble—are used to estimate project churn. Building upon all the strengths of each model, this approach improves the prediction of classification and provides a balanced and highly robust classification system. The applied approaches are K-Nearest Neighbors (KNN), Support Vector Classifier (SVC), Random Forest, Decision Tree, and XGBoost within a Voting Classifier configuration. The performance of the Voting Classifier without SMOTE yields the following results: Accuracy: 0.87, precision: 0.87, recall: 0.80, and F1-Score: 0.87. The proposed model that extend the base model using SMOTE (Synthetic Minority Over-sampling Technique), yields a higher prediction accuracy of 0.90, precision of 0.90, recall of 0.90 and F1-Score of 0.90. This enhancement is proving the efficiency of SMOTE to handle the class imbalance problem in order to render the churn prediction more balanced and reliable system. The proposed approach assures a reliable solution to the strategies to retain the customers in the banking organisations.

Background: Suicides are among the leading causes of death in the world and pose a major public health challenge. Mental health issues intensified during the COVID-19 pandemic, causing an increase in the number of suicides globally. Contributory factors included social isolation, loneliness, unemployment, grief due to loss of family, fear of death, and financial stress. Aim: To assess the pattern of suicide deaths following the COVID-19 pandemic as compared to pre-COVID-19 in the South and South-east districts of Delhi. Materials and Methods: Pre-COVID-19 suicide data were reviewed from April 2017 to March 2020. We collected data from police inquest papers, medical records, and the evaluation of autopsy reports. Post-COVID-19 data for suicide deaths were collected from April 2020 and March 2023. The close relatives of the deceased were interviewed using a standardized proforma. Data were analyzed using STATA version 16. Results: A total of 1435 and 1462 suicide deaths were reported in the pre- and post-COVID-19 pandemic period, respectively. Suicide deaths among males were significantly higher in the post-COVID-19 period (P = 0.001). The place of suicide was non-residence in a significantly higher number of suicide deaths during the post-COVID-19 period (P = 0.001), while there was no significant difference in terms of alcohol use (P = 0.249), and physical illness (P = 0.28) during pre- and post-COVID-19 period. The most common cause of death was hanging both in the pre-COVID-19 (93.91%) and post-COVID-19 (95.5%) period. Conclusion: There was no significant difference in the number of suicide deaths pre- and post-COVID pandemic. A significantly higher rate among males, non-residence as the place of suicide, and history of psychiatric illness was found in the post-COVID-19 period.

Background: Menopause brings about significant hormonal changes that can affect various aspects of women’s health, including nasal function. However, the specific impact of menopause on nasal health in Indian women remains underexplored. This study aims to compare nasal function using the Nasal Obstruction Symptom Evaluation (NOSE) score between premenopausal and postmenopausal Indian women. Materials and Methods: A comparative cross-sectional study was conducted involving 107 premenopausal and 111 postmenopausal women recruited from a tertiary care hospital in India. Demographic data, medical history, and NOSE scores were collected. Statistical analyses including Wilcoxon rank-sum test, Chi-squared test, logistic regression, and receiver operating characteristic curve analysis were performed. Results: Postmenopausal women were significantly older with higher body mass index (BMI) compared to premenopausal women. Postmenopausal women consistently had higher NOSE scores indicating worse nasal function across various time points. Logistic regression revealed menopausal status as a significant predictor of severe nasal obstruction (odds ratio: 1.45, 95% confidence interval: 1.10–1.90, P = 0.015), independent of age, BMI, and other factors. Conclusion: Menopause is associated with a significant decline in nasal function in Indian women, as evidenced by higher NOSE scores in postmenopausal women. Addressing nasal symptoms in postmenopausal women may improve their quality of life. Further research is needed to develop targeted interventions for managing nasal obstruction in this population.

Abstract The proliferation of Internet of Things (IoT) devices in smart homes has created a demand for efficient computational task management across complex networks. This paper introduces the Dynamic Multi-Criteria Scheduling (DMCS) algorithm, designed to enhance task scheduling in fog-cloud computing environments for smart home applications. DMCS dynamically allocates tasks based on criteria such as computational complexity, urgency, and data size, ensuring that time-sensitive tasks are processed swiftly on fog nodes while resource-intensive computations are handled by cloud data centers. The implementation of DMCS demonstrates significant improvements over conventional scheduling algorithms, reducing makespan, operational costs, and energy consumption. By effectively balancing immediate and delayed task execution, DMCS enhances system responsiveness and overall computational efficiency in smart home environments. However, DMCS also faces limitations, including computational overhead and scalability issues in larger networks. Future research will focus on integrating advanced machine learning algorithms to refine task classification, enhancing security measures, and expanding the framework’s applicability to various computing environments. Ultimately, DMCS aims to provide a robust and adaptive scheduling solution capable of meeting the complex requirements of modern IoT ecosystems and improving the efficiency of smart homes.

Ge'ez has been used in Ethiopian churches for centuries to read and interpret the Bible. As a part of the liturgy and religious ceremonies, it is also utilized in prayer and chanting. Since the language is ancient, plenty of handwritten physical documents are generated. Recognizing handwritten Ge'ez numerals poses significant challenges due to variations in handwriting styles, incomplete or overlapping strokes, noise, and distortion. This study introduces an end-to-end approach for handwritten Ge'ez multiple numeral recognition employing deep neural networks. The proposed method streamlines recognition by eliminating manual feature extraction stages. To enable end-to-end training without explicit alignment, the model uses attention mechanisms and a connectionist temporal classification-based loss function. The proposed model is evaluated on 120,000 handwritten Ge'ez multiple numeral images, which is a syntactically generated dataset. The developed recognition model achieved a character error rate (CER) of 2.81% and a word error rate (WER) of 18.13%. These results highlight the effectiveness of the approach in accurately and reliably recognizing handwritten Ge'ez multiple numerals.

Background/Objectives: The American Urological Association (AUA) vasectomy guidelines’ current recommendation to obtain the first post-vasectomy semen analysis (PVSA) from 8 weeks to 16 weeks post-vasectomy is based predominantly on azoospermia rates. However, non-compliance with semen analysis after vasectomy is a known problem in this patient population. An approach that optimizes clearance and compliance is essential when adopting appropriate post-vasectomy care guidelines, specifically the scheduling of the first PVSA. We aimed to conduct a systematic review and meta-analysis of studies assessing compliance and clearance to determine the optimal time of first PVSA. Methods: Databases (MEDLINE, EMBASE, POPLINE) were searched for studies that contained the following: rate of azoospermia and rare nonmotile sperm (RNMS), compliance, recanalization, persistent RNMS, pregnancies, and incidence of repeat vasectomy. Results: A total of 28 studies were included in this review. The patient compliance was 47–100% and trended downward with increasing time to first PVSA. There was a positive trend in azoospermia rate as post-vasectomy time increased, but this plateaued at 8 weeks. Compliance and post-vasectomy semen analysis clearance (PVSAC) converged at 5.7 weeks, with rates of 74.5% and 74.6%, respectively. A proportion of 1.5% of patients exhibited persistent RNMS. Recanalization events had an incidence rate of 1.5%. Repeat vasectomies were performed in 1.6% of patients. Conclusions: Based on our study optimizing post-vasectomy semen clearance with follow-up compliance, we recommend initial PVSA between 6 to 18 weeks post-vasectomy, as this offers improved compliance over current AUA guidelines which recommend PVSA at 8 to 16 weeks and allows for the identification of instances of “subclinical recanalization” that may be missed at later time points.

In the present study we investigated the impact of the combination of astragalin and rutin (CAR) on restoring gut-microbial dysbiosis and obesity and obesity related disorders. Randomized male C57BL/6J mice were experimentally divided into 5 groups and fed either a normal diet or a high-fat diet (HFD) for 16 weeks. Compared to vehicle treated group (HFD group), CAR could substantially improve selected gut microbiota abundance (Akkermansia, Lactobacillus, Bifidobacteria, Roseburia, Prevotella), reversed the Firmicutes/Bacteroidetes proportions, and inhibited the growth of Escherichia coli, Salmonella, and Klebsiella in obese mice. In addition, CAR-treated mice showed significantly increased total short-chain fatty acid production, reduced body weight gain, organs’ weights, serum lipid profile (except HDL) and insulin resistance. The mRNA expressions of CCAAT/enhancer binding protein-α (C/EBP-α), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ), acetyl-CoA carboxylase (ACC), adipocyte protein 2 (aP2), and fatty acid synthase (FAS) were downregulated (P < 0.05) and the protein expression of PPAR-γ was downregulated while adenosine 5’ monophosphate-activated protein kinase (AMPK) was phosphorylated in CAR-treated HFD-fed mice compared to the HFD control group. Interestingly, CAR-treated HFD-fed mice showed significantly improved tissue architecture in the liver and fatty tissues. In conclusion, the findings suggest that CAR/Moringa oleifera may be beneficial in the treatment of insulin resistance and obesity disorders.

Introduction: Deep bite, a common orthodontic malocclusion, necessitates timely intervention to prevent potential side-effects. If left untreated, a deep bite can lead to increased tooth wear, dental injuries, and Temporomandibular Joint (TMJ) disorders. Various treatment modalities, such as anterior teeth intrusion and posterior teeth extrusion, are employed to correct deep bite. However, selecting the optimal approach requires careful consideration of patient-specific factors and treatment objectives. While anterior teeth intrusion is effective for mild to moderate cases, posterior teeth extrusion may be preferred in severe deep bite scenarios. There are various treatment modalities for deep bite correction such as intrusion arches and mini screw implants. Jayade’s intrusion arch, detailed by A.V. Jayade in “Refined Begg for Modern Times” (2001), is an orthodontic appliance designed to correct vertical dental misalignments by intruding over-erupted anterior teeth. The modified three-piece intrusion arch is an advancement of the traditional intrusion arch technique. It incorporates three distinct segments: two lateral segments and a central segment. This design allows for greater precision and control over the intrusion forces applied to specific teeth or groups of teeth. Need of the Study: Simultaneous intrusion and retraction mechanics in orthodontic treatment are very challenging, and there is a paucity of data regarding the best modalities for achieving these with minimal root resorption. Aim: Comparative evaluation of the rate of intrusion, retraction and amount of periapical root resorption with Jayade’s intrusion arch and the modified three-piece intrusion arch using Cone Beam Computed Tomography (CBCT). Materials and Methods: The present prospective, two-arm parallel interventional study will be conducted in the Department of Orthodontics and Dentofacial Orthopaedics Outpatient Department, Sharad Pawar Dental College, Sawangi (Meghe), Wardha, Maharashtra, India, from September 2024 to February 2026. Study will involve the recruitment of 20 patients and all these patients will be divided into two groups for comparative analysis. The intervention will entail the use of the McLaughlin, Bennett and Trevisi (MBT) bracket system equipped with triple tubes on maxillary teeth, characterised by a slot dimension of 0.022 inches by 0.028 inches, as the standardised starting point for all cases. After initial alignment and leveling, and extractions as per the case, the intrusion arch will be applied. Jayade’s intrusion arch will be given in group A, while the modified three-piece intrusion arch will be given in group B. The assessment of intrusion rate, retraction rate and amount of root resorption will be conducted both prior to the initiation of intrusive and retractive forces, as well as, at intervals of two, four and six months following the application of the intrusion arches.

Background: Alcohol and tobacco use are among the major risk factors for causing hypertension in the adult population globally as well as in India. India being a religious country harbor’s large number of Hindu temples which are conventionally managed by a dedicated population of Hindu priests. The prevalence of alcohol and tobacco use in this special population of priests in India is not well established along with the associated risk of hypertension. Aims and Objectives: First, to study the pattern of use of habit-forming substances; tobacco, alcohol, and cannabis derivatives among priests in central India. Second, to find the relationship between the use of tobacco smoking, chewing, and alcohol with hypertension. Materials and Methods: The current study is a cross-sectional survey on Hindu priests of registered temples of a Pilgrimage city in Central India. The study utilizes a pre-tested semi-structured questionnaire for interviewing 440 study participants. It included a sociodemographic profile, history of use of habit-forming substances, the presence of known hypertension, and measurement of blood pressure. Results: Out of 440 study participants; 280 (63.6%) were currently using habit-forming substances, whereas 160 (36.4%) number of participants had never used it. The current study found the prevalence of hypertension to be 31.9%. A statistically significant relationship of hypertension with the use of alcohol (χ2=44.2), tobacco chewing (χ2=106.1), and smoking (χ2=74.3) was found. Conclusion: The current study concludes that the use of Habit-forming substances, especially alcohol, tobacco chewing, and smoking, are prevalent among priests which are known risk factors for hypertension in the general population. Hence all screening/interventions applicable for these risk factors should be applied to this special population of priests.

Abstract Osmotic processes play a crucial role in developing high-quality intermediate moisture food products. This study investigates the role of osmotic dehydration focusing on using natural sweeteners to reduce health risks from refined sugar. Jaggery and honey were used for osmosis of papaya cubes, with a Box-Behnken design to determine optimal conditions: osmosis temperature (30, 40, 50 °C), osmotic solution concentration (40, 50, 60°Brix), and osmosis time (3, 4, 5 h). Simultaneous optimization of these parameters considered responses such as water loss, solid gain, weight reduction, colour change, ascorbic acid content, lycopene content, and phenolic content. The optimized conditions were identified as 49.46 °C, 40°Brix, and 5 h for jaggery osmosed samples and 39.64 °C, 60°Brix, and 4.92 h for honey osmosed samples. Drying the osmosed samples using advanced domestic solar dryer revealed superior quality (total phenolic content and lycopene content) in jaggery osmosed papaya compared to honey osmosed papaya. The study suggests that introducing a new osmotic agent, jaggery, can enhance the nutritional value of osmosed papaya cubes.

Abstract N-butanol is well known to be a flammable and harmful liquid that is a potential threat to human health and property. Therefore, it is important to monitor the concentration of n-butanol in the surroundings. The need for highly efficient toxic gas detection is urgent and has been driving the research on gas sensors for practical applications. Molybdenum disulfide (MoS2) has been attracting significant interest for gas detection at room temperature. Herein, we report biofunctionalized magnetic nanoparticles incorporated MoS2 for sensing n-butanol. The biosynthesized magnetite nanoparticles (CT-Fe3O4) were synthesized by the addition of Cinnamomum Tamala (CT) leaf extract, and subsequently, the nanocomposite was synthesized using a hydrothermal method. Highly sensitive sensors based on MoS2-CT-Fe3O4 were fabricated and tested for sensing different concentrations of n-butanol. The nanocomposites showed a good sensing performance ( $$\Delta$$ Δ R/Rair %) of 72% towards 20 ppm of n-butanol, indicating the potential use of MoS2-CT-Fe3O4 nanocomposite for sensing n-butanol at room temperature.

All 189 World Bank member countries are classified by their capita gross national income into one of four income groups. In this review, we aim to explore the economic burden and management of urologic oncology conditions in low- and middle-income countries (LMICs), emphasizing disparities and challenges in treatment access. The current World Bank classification system highlights economic stratification, showing significant health outcome disparities, particularly in urologic oncology conditions including kidney, bladder, and prostate cancer. First, this review focuses on the management of advanced prostate cancer in Asian LMICs, revealing higher mortality-to-incidence ratios and a greater prevalence of metastatic disease compared to high-income countries (HICs). The prohibitive costs of novel hormonal therapies (NHTs) like abiraterone and enzalutamide limit their use and exacerbate outcome disparities. Second, we review Wilms tumor treatment with chemotherapy in African countries, noting significant price variations for adapted and non-adapted regimens across different economic settings. The cost of chemotherapy agents, particularly dactinomycin, acts as a primary driver of treatment expenses, underscoring the economic challenges in providing high-quality care. Lastly, bladder cancer treatment costs in Brazil and Middle Eastern countries are examined, highlighting how detrimental the economic burden of intravesical therapies, like mitomycin C and Bacillus Calmette–Guérin (BCG), is on treatment accessibility. Overall, this literature review emphasizes the financial strain on healthcare systems and patients, particularly in regions facing economic instability and drug shortages, and underscores the need for international cooperation and effective resource allocation to address the economic barriers to urologic care in LMICs, aiming to improve health outcomes and ensure equitable access to advanced treatments.

Background Atherosclerosis is the most common cause of ischemic cardiovascular disease (CVD). However, approximately 20%–40% of cases of acute myocardial infarction (AMI) in patients aged 18 years who met the universal definition of AMI but excluded those with missing medical records or coronary angiograms. Results In total, 2624 patients with AMI (aged 18–85 years) were included in the study and divided into two groups based on age: ≤45 (n = 1286) and >45 years (n = 1338). Total cholesterol and triglyceride levels were significantly higher in patients aged ≤45 years (5.6 ± 2.1 and 3.2 ± 2.1 mmol/L, respectively, P < 0.007) than in those aged >45 years (6.3 ± 1.8 and 3.1 ± 2.0 mmol/L, respectively, P < 0.001). Overall, 1745 and 879 patients were unvaccinated and fully vaccinated, respectively; severe and critical COVID-19 infections were more common among unvaccinated patients in both age groups. Conclusions Younger patients with AMI were more likely to be smokers with no hypertension, diabetes mellitus, or previous AMI. In contrast, they were more likely to have hypercholesterolemia and hypertriglyceridemia, single-vessel disease, Type C lesions, and a history of drug-eluting stent use.

Migraine, a commonly occurring neurological disorder, disproportionately affects women during their reproductive years, and its symptoms are often intensified by hormonal fluctuations. This narrative review examines the impact of hormonal contraceptives, particularly combined oral contraceptives (COCs), on menstrual migraine (MM). This review assessed the impact of COCs on MM through a literature search in PubMed, Google Scholar, Web of Science, and Scopus using keywords like “menstrual migraine”, “hormone therapy”, and “COCs”. The selection criteria were peer-reviewed studies published between 2014 and 2024, written in English, and focused on MM treatment with COCs. Exclusion criteria were duplicates, editorials, irrelevant articles, and non-English studies. The literature reveals inconsistent results, with some studies reporting aggravation of migraine symptoms with COC use, whereas others indicate a decrease in the frequency and severity of attacks, especially with continuous use. Factors affecting these outcomes include patient age, menstrual cycle characteristics, and migraine type. It is crucial to choose contraceptives that suit individual patient profiles, considering the potential for increased migraine frequency or onset of migraine with aura in some women. Further studies are required to establish clear clinical guidelines. It is recommended to create personalized treatment plans that balance the effectiveness of migraine management with the overall health risks.

Aim: To evaluate the propagation of preexisting dentinal microcracks after instrumentation with ProTaper Universal (PTU), ProTaper Gold (PTG), Twisted File Adaptive (TFA), and Reciproc Blue (RB) instruments by micro-CT imaging. Methods: The mesial roots of 60 mature human mandibular molars were cut out approximately 10 mm from the apex. The roots were then divided randomly into four groups (n = 15) based on file system used: PTU, PTG, TFA, and RB. Before and after canal shaping, roots were scanned with micro-CT. The preinstrumentation cross-sectional slices were examined to ascertain the presence of preexisting dentinal microcracks in apical 10 mm of radicular dentine. Postinstrumentation, the extension of preexisting dentinal microcracks was assessed and compared with corresponding preinstrumentation image to determine the grade of propagation. Postinstrumentation, the propagation of preexisting dentinal microcracks were categorized into three grades: nonpropagated dentinal microcracks (Grade 1), incomplete propagation (Grade 2), and complete propagation (Grade 3). Results: The PTU system showed a significantly higher propagation of preexisting dentinal microcracks compared to PTG, TFA, and RB system (P ≤ 0.05). All the instrumentation systems showed propagation of preexisting dentinal microcracks into Grade 2 cracks. Grade 3 propagation was seen in PTU, PTG, and RB systems. The number of Grade 2 dentinal microcracks were significantly higher than Grade 1 dentinal microcracks for the PTU system (P ≤ 0.05). Conclusion: Root canal instrumentation promotes propagation of preexisting dentinal microcracks. As compared to conventional nickel-titanium file systems, reciprocating and thermally treated file systems may less likely result in propagation of dentinal microcracks.

Background: Contemporary imaging methods and quickly advancing technologies have increased the number of diagnostic tools available in medicine and orthodontics. The current study aimed to determine three-dimensional (3D) space changes that occurred after the extraction of either the maxillary or mandibular primary molars during the mixed dentition period. MATERIALS AND METHODS: The present study was a longitudinal split-mouth study with a study group and a control group. The sample consisted of 20 children aged between 6 and 9 years. Clinical examination, radiological analysis, and 3D digital images of the plaster casts were used sequentially to gather all the data. The dental cast measurements recorded were arch width, arch length, hemi-perimeter, dental space at the extraction site, and angulation of the first permanent molar. The children were recalled for follow-up after 9 months, and all dental cast measurements were repeated using nondestructive 3D computed tomography software. For repeated measurements, the test applied was a paired t-test, and for independent samples, the test was a Student’s t-test. Results: A significant decrease in arch width (P = 0.001), arch length (P < 0.001), hemi-perimeter (P < 0.001), D-space (P < 0.001), and E-space (P = 0.001) was observed following extraction. A significant increase in angulation measurements was observed (P = 0.001). Conclusion: The study revealed a comparative reduction in mandibular arch width, a reduction in arch length in both the maxilla and the mandible, a reduced hemi-perimeter of dental arches, loss of dental extraction space, and a change in angulation of the erupted first permanent molars following premature loss of the primary molar.

Both acute traveler’s diarrhea and sexually transmitted infections are common causes of fever in the returned traveler, with the male sex corresponding to two-fold increased odds of a sexually transmitted infection (STI) diagnosis related to travel. Shigella flexneri is the most common cause of shigellosis in low- and middle-income countries, while within the men who have sex with men (MSM) population, outbreaks of S. flexneri 3a, S. flexneri 2a, and S. sonnei have been reported. We herein present a case of a febrile returned MSM traveler with a predominantly gastrointestinal presentation and proctocolitis whose microbiological work-up confirmed coinfection with S. flexneri and rectal gonorrhea. Based on his travel history and epidemiologic risk factors, it is unclear if food- and waterborne shigellosis versus transmission via sexual contact was the major route of acquisition. This case highlights the broad differential for proctocolitis and the importance of consideration of intercurrent infections.

Diaporthe gulyae and D. helianthi cause Phomopsis stem canker, which is a yield-limiting fungal disease of sunflower (Helianthus annuus L.) in the United States. In this study, the mycovirus population was characterized in D. gulyae and D. helianthi using 52 and 42 isolates, respectively, that were recovered from diseased sunflower plants randomly sampled from commercial sunflower fields in the U.S. states of Minnesota, Nebraska, North Dakota, and South Dakota. Total RNA extracts depleted of rRNA from each fungus were pooled to construct one library for sequencing to obtain 20 GB per library of raw reads using a metatranscriptomics approach. Only the family Mitoviridae was present in both Diaporthe species. Twelve and nine novel viral contigs were discovered infecting D. gulyae and D. helianthi, respectively. Additionally, we detected two of the same viruses infecting D. helianthi, Helianthus annuus leaf-associated partitivirus 3 and 5, that were detected in a direct sunflower metatranscriptome reported before. Interestingly, Qinvirus, which is mostly known as a group of insect viruses, was found in a contig. An ambivirus that is rarely reported in the phylum Ascomycota was also discovered in this study. Besides an understanding of virome diversity, the mycovirome survey provides the first clue of biological molecules that can be further developed for antifungal purposes.

The UK Biobank includes genotype information for about 500,000 patients for over 7000 phenotypes. However, owing to multiple testing correction for approximately 200 billion tests, many clinically and statistically significant associations remain unappreciated. We perform a focused analysis of the UK Biobank for 13 dermatologic conditions, including malignant melanoma, melanoma in situ, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, seborrheic keratosis, psoriasis, lichen planus, systemic lupus erythematosus, hyperhidrosis, pilonidal cyst, sebaceous cyst, and lipoma. We identify 447 sentinel variants, which are enriched for protein-coding variants and an elevated combined annotation-dependent depletion (CADD) score compared with background variants. Through gene ontology enrichment analysis, we identify known pathways involved in melanoma, actinic keratoses, and squamous cell carcinoma and uncover additional pathways. We also uncover 5 protein-coding variants, which, to our knowledge, have not been previously reported, including LRP3 for lipomas, PLCD1 for sebaceous cysts, EIF3CL for lichen planus, TTK for pilonidal cysts, and MAPK15 for systemic lupus erythematosus.

Carbon black - materials rich in carbon nanostructures - have been successfully applied as modifiers of electrochemical transducers, rivalling other carbon nanomaterials for cost and ease-of-use. Despite the remarkable promise of this nanomaterial, no study has yet comparatively characterised a wide range of different grades of carbon black for their utility in electrochemical sensors. Here, we explore several commonly-studied carbon black grades (N220, N234, N326, N330, N339, N375, N550, N660 and Lamp Black-101), alongside relatively newer grades (Printex®-200, Printex® G, Printex® XE-2B, and Printex® Zeta) for their application in electrochemical sensors. The effects of coating glassy carbon electrodes with carbon black on electrode performance were studied by cyclic voltammetry using three redox probes: ferri-/ferrocyanide (anionic probe molecules), ferrocenemethanol (neutral) and hexaammineruthenium (cationic). Raman Spectroscopy characterisation of the different grades associated a lower degree of graphitisation with superior electrode modifiers. Generally, modification increased the anodic peak current for ferri-/ferrocyanide probes; and lowered anodic potential for ferri-/ferrocyanide and hexaammineruthenium probes. Increases in peak current and potential observed at ferrocenemethanol are consistent with the increased tendency for this probe to adsorb to the surface of modified electrodes. N330 and Printex® XE-2B displayed the best electrocatalytic properties in terms of enhanced peak currents and lowered anodic overpotentials for the redox probes. CB grades were used to modify screen-printed carbon electrodes and the obtained sensors examined for anodic detection of reduced nicotinamide adenine dinucleotide (NADH) cofactor by cyclic voltammetry. Printex® XE-2B significantly improved the detection of NADH and was further used for chronoamperometric detection of NADH at low overpotentials. Grades N220, N375, N550 and P-G showed their suitability as enzyme scaffolds for sensor fabrication, as determined by their preservation of the activity of a NAD-dependent aldehyde dehydrogenase.

Summary: The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. MIC13 mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in MIC13 KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging. We identified stomatin-like protein 2 (SLP2) as a key MIC13 interaction partner, essential for cristae morphology and CJ formation. SLP2 serves as an interaction hub for MICOS subunits and stabilizes MIC26 by protecting it from YME1L-mediated degradation. Deleting both SLP2 and MIC13 impairs MIC60-subcomplex assembly and its nanoscale organization. Restoring the MIC10-subcomplex in MIC13-SLP2 double KO cells through YME1L depletion reinstates MIC60-subcomplex assembly and cristae morphology. Overall, we propose SLP2 and the MIC10-subcomplex act as a proteolytically controlled ‘seeder’ complex, facilitating MICOS-MIB complex assembly and maintaining mitochondrial integrity.

As health data infrastructure improves, we have the opportunity to link increasing volumes of data in order to investigate important health problems. This is perhaps most pertinent when looking at the experiences and outcomes of our most disadvantaged groups, who are often invisible in data obtained through primary research. Whilst these data offer enormous opportunity, there are also ethical implications in their use, which are less frequently discussed than in relation to their qualitative counterparts. As a diverse group of clinicians and academics working across public health, we share our experience and understanding of how we can improve our reflexivity in health data science and ensure that research in this area is ethically conducted in co-production with the people whose data we are using. We discuss the potential opportunities, challenges and impacts of using administrative data to investigate marginalised populations.

Despite the historical significance of the Ge’ez script, there is a notable scarcity of studies on Ge’ez digit recognition, compounded by the challenges posed by the absence of publicly accessible datasets. The complex structure of Ge’ez digits further complicates the recognition task. In response to this gap, our study addresses the development of a digit recognition model based on deep learning (DL) specifically tailored for printed Ge’ez digits, accompanied by the creation of a comprehensive study dataset. The proposed model architecture seamlessly integrates one input layer, six convolutional layers, and three Max-Pooling layers. To assess the model’s performance, we meticulously curated a Ge’ez digit dataset comprising 72,000 images, well-suited for DL applications using the ocropus-linegen model within OCRopus, a free document analysis tool. Leveraging cutting-edge DL algorithms, our proposed model demonstrates an impressive accuracy of 97.29%. This surpasses the performance of previous Ge’ez digit recognition models, marking a noteworthy advancement in this underexplored domain.

Abstract Outer membrane vesicles (OMVs) produced by Gram-negative bacteria have key roles in cell envelope homeostasis, secretion, interbacterial communication, and pathogenesis. The facultative intracellular pathogen Salmonella Typhimurium increases OMV production inside the acidic vacuoles of host cells by changing expression of its outer membrane proteins and modifying the composition of lipid A. However, the molecular mechanisms that translate pH changes into OMV production are not completely understood. Here, we show that the outer membrane protein PagC promotes OMV production through pH-dependent interactions between its extracellular loops and surrounding lipopolysaccharide (LPS). Structural comparisons and mutational studies indicate that a pH-responsive amino acid motif in PagC extracellular loops, containing PagC-specific histidine residues, is crucial for OMV formation. Molecular dynamics simulations suggest that protonation of histidine residues leads to changes in the structure and flexibility of PagC extracellular loops and their interactions with the surrounding LPS, altering membrane curvature. Consistent with that hypothesis, mimicking acidic pH by mutating those histidine residues to lysine increases OMV production. Thus, our findings reveal a mechanism for sensing and responding to environmental pH and for control of membrane dynamics by outer membrane proteins.

Abstract A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25–100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25–100 µl), and Pseudomonas spp. inoculums (50–150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC–MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8th day. From LC–MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 106 and 210 × 106 CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties.

Abstract Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.

Orbital Aspergillosis is a rare life-threatening fungal infection that is often misdiagnosed due to its nonspecific clinical and radiological appearance. In this case report, we present a case of disseminated aspergillus infection initially presenting as right inferior rectus palsy.

Introduction: Risk management includes identifying various risks, assessing the probability of occurrence, and evaluating the severity of their consequences. As clinical laboratories are integrally involved in patient care, risks in the laboratories could present grave consequences in some instances. This study aimed to utilize simple techniques for risk management in a clinical laboratory. Materials and Methods: All potential risks in the pathology laboratory of a tertiary-level hospital were identified and classified into natural calamity, environmental, manpower-related, pre-analytical, analytical, post-analytical, and laboratory hazard-related risks through a brainstorming session. The probability of occurrence of each risk was estimated from departmental and hospital records. The possible impact of risk (score 1–10) was categorized into catastrophic, critical, serious, minor negligible, and insignificant. The unweighted risk score was calculated by multiplying the probability of occurrence and impact score. Results: Inadequate sample-to-anticoagulant ratio had the highest probability of occurrence (22.85%), followed by quantity insufficient for analysis (7.30%) and laboratory information system (LIS) breakdown (6.58%). The highest unweighted risk score in our study was inadequate sample-to-anticoagulant ratio (score 91.40), followed by improperly labeled samples (score 35.61), manpower competency issues (score 32.88), sample insufficient for analysis (score 29.20), and LIS breakdown (score 26.30). Conclusion: We found that among all the categories, risks involving the pre-analytical phase had the highest risk scores. The other important risks included manpower competency issues requiring continued on-the-job training of staff as a risk reduction strategy. Brainstorming and probability analysis could be easily used for risk management in a clinical laboratory.

Background: Antibiotic resistance is a global threat and recently, World Health Organization (WHO) has declared antimicrobial resistance as one of the top 10 global public health threats. The existing antibiotics are becoming ineffective which results in serious complications and even death of the patients. Natural products have tremendous potential against resistant infections due to their multimodal mechanism of action. However, the exact potential is unclear so far. Aim: Thus, we have conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to determine the role of natural products. Methodology: The relevant studies were searched in PubMed and clinical trial websites till 18th February 2022. Results: Out of 11,869 studies, 361 studies were selected for qualitative analysis as per the defined inclusion and exclusion criteria. The results have indicated the antibacterial potential of natural products in concentration/dose/dosage manner under in-vitro, in-vivo, and clinical conditions via different mechanisms of action Conclusion: Overall, available evidence has indicated the potential of natural products against various types of resistant bacterial strains under in-vitro, in-vivo, and clinical conditions.

Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium seeberi, that affects mostly nasal and nasopharyngeal mucosa. Occurrence at extranasal sites such as cutaneous, subcutaneous, and bone is extremely rare. We hereby report a very rare case of disseminated rhinosporidial osteomyelitis.

Hyponatremia is the most common electrolyte imbalance observed in hospitalized as well as outdoor patients. Antidepressants such as selective serotonin receptor inhibitors and tricyclic antidepressants are reported among the most common drugs causing hyponatremia, especially in the elderly and in patients with known risk factors for hyponatremia. However, there have been only a few case reports of hyponatremia associated with antidepressants such as mirtazapine and flupentixol/melitracen. The exact mechanism of hyponatremia with the use of antidepressants is not known; however, syndrome of inappropriate antidiuretic hormone secretion (SIADH) is presumed to be the reason. Here, we report two cases of antidepressant drug-induced hyponatremia in two postmenopausal females with no other risk factor for hyponatremia: one associated with mirtazapine and the other with flupentixol/melitracen.

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with > 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information. Plain language summary Many babies with epilepsy continue to have seizures (‘fits’), despite taking medicines. These babies are unlikely to make the same developmental progress as babies without epilepsy. Ketogenic diets are high in fat and low in carbohydrate and have been shown to reduce seizures in older children and adults. Babies (age 1–24 months) with epilepsy, who still had seizures despite having tried medicines, either started a ketogenic diet or another medicine. They then stayed on this treatment for 8 weeks. We wanted to know whether there was a difference in the number of seizures in the last 2 weeks of treatments compared to before. Seventy-eight babies started a ketogenic diet and 58 started another medicine. Overall, the number of seizures babies had every day was similar in both groups. A similar number of babies in both groups either had to go to hospital for some reason or stay in hospital for longer. This was mostly because of seizures. Two babies suffered ‘sudden unexpected death in epilepsy’ and another died during a planned surgery. These deaths were not thought to be related to the ketogenic diet. Both the ketogenic diet and the medicines helped to reduce the number of seizures in the babies. Babies in both groups had similar side effects. Doctors could consider starting a ketogenic diet in babies who continue to have seizures even though they have tried medicines to stop their seizures. Scientific summary Background Many infancy-onset epilepsies are poorly responsive to antiseizure medicines (ASMs) with poor prognosis for neurodevelopmental outcome. Ketogenic diets (KDs), which are high-fat, low-carbohydrate diets, have been shown to reduce seizures in older children with drug-resistant epilepsy. No high-quality evidence is available for infants. Objectives In this open-label randomised controlled trial, we compared the efficacy of the classical KD to a further appropriate ASM in infants with drug-resistant epilepsy. The primary outcome was the number of seizures recorded during weeks 6–8, accounting for the baseline rate and randomised group. Secondary outcomes at 8 weeks were the number of infants seizure-free in weeks 6–8 of the intervention period, responder rate (defined as the number showing more than a 50% improvement in seizure frequency compared to baseline), tolerance to KD and relationship between medium-chain fatty acids and seizure control. Secondary outcomes at 12 months were retention on treatment, quality of life and neurodevelopmental outcome. Adverse events were recorded throughout the trial. Serious adverse events were reported to the study sponsor. Methods Infants (age 1–24 months) with epilepsy, with an average ≥ 4 seizures/week and previous trials of ≥ 2 ASMs were recruited from 19 hospitals in the UK. Following a 1- or 2-week observation period, during which there were no changes to regular ASMs (emergency seizure treatments continued as required), participants were randomised to receive a classical KD or a further ASM for 8 weeks, using a computer-generated schedule without stratification. An allocation ratio of 1 : 1.35 was used to account for the therapist effect in the KD group only. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The following assessments were performed in all infants prior to randomisation: medical history, physical examination, administration of the Infant Toddler Quality of Life Questionnaire™ (ITQOL-97; © HealthActCHQ Inc. 2013) and Vineland Adaptive Behaviour Scales (Vineland™-II), and clinical laboratory assessments. Food diaries required for diet calculation were returned from parents/guardians of all participants a maximum of 1 week into the observation period. Parents/carers were asked to keep daily seizure diaries throughout the 8-week treatment periods for participants in both arms. Thereafter, they were requested to reduce seizure recording to at least 1–2 days per week, as clinically indicated, until 28 days before the final 12-month visit, when daily seizure recording recommenced. Follow-up visits were arranged at 4 weeks, 8 weeks, and 6, 9 and 12 months. Assessments included clinical review, physical examination, documentation of seizure frequency from seizure diaries, review of adverse events and concomitant medication, clinical laboratory assessments (8 weeks, and 6 and 12 months) and completion of tolerability questionnaire by parents/carers together with research nurses, the ITQOL-97 (8 weeks and 12 months) and Vineland-II (12 months). After the 8-week assessment, according to the infant’s clinical response to treatment (seizure outcome and tolerability), KD or ASM was then continued or changed; those randomised to the ASM arm then had the opportunity to start KD. Results Of 136 eligible infants, 78 were randomised to KD and 58 to ASM. Of 78 infants who started KD, 67 (86%) continued to 8 weeks, of which 61 (78%) had primary outcome data available; 53 (91% of those randomised to ASM group) started a further ASM, 49 (84%) continued to 8 weeks and 47 (81%) had primary outcome data available. The median number of daily seizures was not significantly different in both groups at 8 weeks [KD 5 (1, 16); ASM 3 (2, 11), incidence rate ratio (IRR) 1.33, 95% confidence interval (CI) 0.84 to 2.11; p = 0.22]. The odds ratio (OR) of achieving ≥ 50% seizure reduction was 1.21 (95% CI 0.55 to 2.65) and 0.88 (0.27 to 2.80) for seizure freedom. A total of 7/63 infants (11%) in the KD group were seizure-free, compared with 6/48 (13%) in the ASM group (OR 0.88, 95% CI 0.27 to 2.80). A higher proportion of infants in the ASM group changed the number or dose of concurrent ASMs during the intervention period [24/48 (50%)] compared to KD [9/66 (14%)]. The side-effect score at 8 weeks was similar in both groups [KD median 40; interquartile range (IQR) 38–42; ASM median 41 IQR 39‒44) and there were no clinically significant differences other than those expected in clinical or laboratory parameters between groups. At 8 weeks, median scores within the ITQOL-97 were numerically higher (suggesting better health) in the KD group for 7 of the 12 concepts. The infant’s pain, its global behaviour, impact on parental time and family cohesion were equal between the two groups, although general perceptions of the infant’s health were numerically higher in the ASM arm. A numerically larger proportion of parents/guardians of infants in the KD group perceived their child’s health to be ‘much better than a year ago’ (10/40, 25%) compared to those in the ASM group (3/32, 9%); numerically more parents/guardians of infants in the ASM group perceived their child’s health to be ‘much worse than a year ago’ (8/32, 25%) compared to those in the KD group (2/40, 5%). Of 66 infants randomised to KD > 12 months before the study end date, 31 (47%) continued the diet to 12 months; of 47 randomised to further ASM > 12 months before the study end date, 21 (45%) continued the ASM to 12 months. For those who reported data, there were no differences between groups for any concept within the ITQOL-97 at 12 months, except for the infant’s temperament and mood (coefficient −6.09, 95% CI −11.63 to −0.54) and the infant getting along with others (coefficient −6.79, 95% CI −12.97 to −0.60), which favoured the ASM group. A similar proportion of parents/guardians of infants in both groups perceived their child’s health to be ‘much better than a year ago’ (12/24 50% ASM; 11/30 37% KD) or ‘much worse than a year ago’ (0/24, 0% ASM; 1/30, 3% KD). Within the Vineland-II there were neither significant differences between groups in the overall standardised score nor domain standard scores at 12 months. The Daily living domain sum of v-scale scores was nominally improved in the ASM group (coefficient 2.23, 95% CI −4.22 to −0.25). A total of 73 serious adverse events (SAEs) were reported in the ASM group and 161 in the KD group. A similar proportion of infants in both groups reported at least 1 SAE (43% ASM; 51% KD) – most commonly seizures. Three infants died in the KD arm, all considered unrelated to treatment. Conclusions There was no evidence that KD was better than further ASM in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and KD appeared safe to use in infants with epilepsy. KD could be a treatment option in infants whose seizures continue despite trial of two standard ASMs. Further trials are needed with larger cohorts at 12-month follow-up and beyond, particularly to look at quality of life and neurodevelopment, perhaps with alternative study design. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Diabetes, a chronic condition characterized by an inability to maintain normal glucose levels significantly accounts for enhancing the cost of healthcare expenditure. Managing diabetes using a standard medication protocol more often leads to progressive failure in effectively treating the associated complications. The recent trends involve understanding of diabetes's genetic architecture and its consequences have provided the background for application of precision medicine for customizing protocols for preventing and managing the diabetes therapy. Further, utilizing the electronic health data and genetic information for assisting care and planning therapeutic protocol for monogenic form of diabetes is well-executed example of genomic medicine. The present write-up emphasized recent advances about the causes and effects of diabetes genetics. This also drive to the need for the further investigation for ensuring the appropriate knowledge to enable patients and healthcare providers to make informed decisions for obtaining the best possible outcome.

IntroductionWhen Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks.MethodsA scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted.ResultsA major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear.DiscussionData on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future.ConclusionThis experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

The energy and industrial sectors' most recent extraordinarily quick expansion has resulted in a substantial rise in stationary CO2 sources. As a result, many questions have been raised concerning how to stop global warming and implement methods to mitigate its effects by 2050 to create a low-carbon and sustainable future. Over the last three decades, India's CO2 emissions have increased at a growth rate of 3.1 % mainly consumption of fossil fuels. In this global and Indian situation, the best method, besides renewable energy sources, is Carbon capture, utilization, and storage (CCUS), which will make it possible to achieve net-zero emissions targets within this century. Given this, a brief review and discussion that aims to study India's development in CCUS deployment and its importance for sustainable development were conducted. The review highlights the current energy scenario of India and the world, the CO2 increase trend, and its consequences globally. Furthermore, a brief discussion on the present status of several areas of carbon capture, utilization, and storage (CCUS) technologies have been done. To clearly define the maturity of each important component of the CCUS system with a commercialization direction route, we focused on determining the technological readiness level (TRL) from India's perspective. Further, we identified important data of different sizes from the biggest R&D schemes, policies, regulations and initiatives taken by the government across the country. Lastly, our study seeks to provide a guide for the successful implementation of CCUS in India.

BackgroundBorderline personality disorder (BPD) is a severe mental disorder that is characterised by a pervasive pattern of instability of interpersonal relationships, self-image, and mood as well as marked impulsivity. BPD has its peak incidence and prevalence from puberty through to emerging adulthood. BPD is a controversial diagnosis in young people. Commonly, young people with BPD are under-diagnosed, untreated, are not in employment or training and are estranged from their families. Yet, they have complex needs and are at high suicide risk.AimTo assess the feasibility of conducting a randomised controlled trial (f-RCT) of a BRIDGE, a brief intervention programme for young people (age 14-24) with BPD symptoms (sub-threshold or threshold) in a community sample from Scotland, UK.MethodForty young people (age 14-24) meeting criteria for BPD symptoms, will be randomised in a 1:1 ratio to receive either a) the BRIDGE intervention plus service-as-usual or b) service-as-usual alone. Follow up will be 12 weeks and 24 weeks post-intervention. The study is carried out between 2021 to 2024.OutcomeThe two primary outcomes of the MQ funded, BRIDGE project (f-RCT) are i. recruitment rates and ii. retention rates. The study will present the acceptability and appropriateness of our putative outcome measures for a future definitive randomised controlled trial (d-RCT).ImpactYoung people with BPD benefit from good clinical care and targeted intervention, however are regularly missed or mislabelled. The community based feasibility trial would provide initial evidence of variable needs of young people with complex needs, who maybe missed or excluded from services as they don’t “fit” a model/diagnosis. Workable multi-agency service model proposed in the trial would be a major advance in understanding care pathways regardless of trial outcome.Clinical Trial RegistrationClinicalTrial.gov, identifier NCT05023447

Cultured meat has the potential to provide a complementary meat industry with reduced environmental, ethical, and health impacts. However, major technological challenges remain which require time-and resource-intensive research and development efforts. Machine learning has the potential to accelerate cultured meat technology by streamlining experiments, predicting optimal results, and reducing experimentation time and resources. However, the use of machine learning in cultured meat is in its infancy. This review covers the work available to date on the use of machine learning in cultured meat and explores future possibilities. We address four major areas of cultured meat research and development: establishing cell lines, cell culture media design, microscopy and image analysis, and bioprocessing and food processing optimization. In addition, we have included a survey of datasets relevant to CM research. This review aims to provide the foundation necessary for both cultured meat and machine learning scientists to identify research opportunities at the intersection between cultured meat and machine learning.

The present report explores the use of self-ligating brackets in treating Class I malocclusion with mild crowding and a constricted maxillary arch. Self-ligating brackets, designed as an alternative to expansion appliances, prove effective in expanding the maxillary arch by allowing larger archwires. The benefits include reduced friction, potentially faster and more comfortable tooth movement, and easier dental hygiene. While commonly associated with non extraction orthodontics, self-ligating brackets are adaptable to cases requiring tooth extraction for severe crowding. This assessment guides a personalised treatment plan, which may involve extraction, with careful placement of self-ligating brackets on remaining teeth. Hereby, the authors present a case report of 15-year-old female patient showchasing a unique technique for dealing with such cases, in which the advantages of self-ligating brackets are utilised to alleviate crowding with much simpler movement while also enhancing confidence.

Abstract Background Vitamin A deficiency (VAD) is a major public health problem in India, where approximately 62% of children under five have low retinol levels (

Abstract Background For healthcare delivery to be optimally effective, health systems must possess adequate levels and we must ensure a fair distribution of human resources aimed at healthcare facilities. We conducted a scoping review to map the current state of human resources for health (HRH) in India and the reasons behind its shortage. Methods A systematic search was conducted in various electronic databases, from the earliest available date till February 2024. We applied a uniform analytical framework to all the primary research reports and adopted the “descriptive-analytical” method from the narrative paradigm. Inductive thematic analysis was conducted to arrange the retrieved data into categories based on related themes after creating a chart of HRH problems. Results A total of 9675 articles were retrieved for this review. 88 full texts were included for the final data analysis. The shortage was addressed in 30.6% studies (n = 27) whereas 69.3% of studies (n = 61) addressed reasons for the shortage. The thematic analysis of data regarding reasons for the shortage yielded five kinds of HRH-related problems such as inadequate HRH production, job dissatisfaction, brain drain, regulatory issues, and lack of training, monitoring, and evaluation that were causing a scarcity of HRH in India. Conclusion There has been a persistent shortage and inequitable distribution of human resources in India with the rural expert cadres experiencing the most severe shortage. The health department needs to establish a productive recruitment system if long-term solutions are to be achieved. It is important to address the slow and sporadic nature of the recruitment system and the issue of job insecurity among medical officers, which in turn affects their other employment benefits, such as salary, pension, and recognition for the years of service.

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient’s cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology.

Abstract Ubiquitin modifications alter protein function and stability, thereby regulating cell homeostasis and viability, particularly under stress. Ischemic stroke induces protein ubiquitination at the ischemic periphery, wherein cells remain viable, however the identity of ubiquitinated proteins is unknown. Here, we employed a proteomics approach to identify these proteins in mice undergoing ischemic stroke. The data are available in a searchable web interface ( https://hochrainerlab.shinyapps.io/StrokeUbiOmics/ ). We detected increased ubiquitination of 198 proteins, many of which localize to the postsynaptic density (PSD) of glutamatergic neurons. Among these were proteins essential for maintaining PSD architecture, such as PSD95, as well as NMDA and AMPA receptor subunits. The largest enzymatic group at the PSD with elevated post-ischemic ubiquitination were kinases, such as CaMKII, PKC, Cdk5, and Pyk2, whose aberrant activities are well-known to contribute to post-ischemic neuronal death. Concurrent phospho-proteomics revealed altered PSD-associated phosphorylation patterns, indicative of modified kinase activities following stroke. PSD-located CaMKII, PKC, and Cdk5 activities were decreased while Pyk2 activity was increased after stroke. Removal of ubiquitin restored kinase activities to pre-stroke levels, identifying ubiquitination as the responsible molecular mechanism for post-ischemic kinase regulation. These findings unveil a previously unrecognized role of ubiquitination in the regulation of essential kinases involved in ischemic injury.

Monoterpenes, such as Geraniol (G), Geranyl acetate (GA), Citral (CT), Limonene (LN), and Linalool (LL), are the most widely used phytochemicals in the aroma, food, and pharmaceutical industries. Here, we screened several bacteria and fungi to assess their potential to biotransform the selected monoterpenes (G, GA, CT, LN, and LL) through the substrate toxicity test. Three bacteria Pseudomonas fluorescens MTCC2421, Streptococcus mutans MTCC497, and Escherichia coli were found to be resistant to G, GA, and LN while two P. aeruginosa, and S. epidermidis MTTC 435 to GA and LN. In general, all fungal strains did not show resistance to any of the monoterpenes used, except Candida albicans and Fusarium oxysporum, which were slightly resistant to lower concentrations (0.05-0.1%) of GA. Interestingly, none of the bacteria and fungi showed any resistance to CT. The maximum concentrations of monoterpenes to which bacteria exhibited resistance ranged from 0.05-0.2%. The growth and biomass profiles of bacteria revealed that P. fluorescens and S. mutans grew well in the presence of monoterpenes GA and LN. Based on this, Pseudomonas fluorescens was capable of biotransforming GA and LN, while S. mutans only LN. The biotransformation of GA by P. fluorescens produced G and LL on the day 5th and 7th of the incubation. Hence, the study revealed the three potential bacteria, which may be useful in producing new aromatic derivatives from selected monoterpenes through biotransformation.

A 2D imine-linked covalent organic framework (COF) with good biocompatibility was synthesized using o-Dianisidine and 1,3,5-Triformylbenzene. The synthesized COF was characterized by using the Fourier transform infrared (FTIR), thermogravimetry analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The synthesized COF was subsequently utilized for the delivery of gemcitabine (Gem), an FDA-approved drug for the treatment of pancreatic cancer. The COF demonstrated a remarkable drug loading of 30 µg/mg and better drug release at pH 5.0. The biocompatibility of the COF was evaluated in the L929 (mouse fibroblast) cell line, while the cytotoxicity of the Gem-loaded COF (COF-Gem) was evaluated against the MIA-PaCa-2 and PANC-1 (pancreatic cancer) cell lines using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The results indicated that the COF was safe at concentrations up to 200 µg/mL, while the COF-Gem led to superior cytotoxicity as compared to native Gem, with IC50 values of 8.1 ± 1.2 µM in MIA-PaCa-2 cells and 6.0 ± 1.3 µM in PANC-1 cells after 48 h. This study offers a new perspective of utilizing COF as a promising delivery system for Gem delivery.

Artificial intelligence (AI) has gained significant traction in medical image analysis, including dentistry, aiding clinicians in making timely and accurate diagnoses. Radiographs, such as orthopantomograms (OPGs) and intraoral radiographs, along with clinical photographs, are the primary imaging modalities employed for AI-powered analysis in the dental field. In this review, we discuss the most recent research and product developments concerning the clinical application of AI as a visual aid in dentistry and introduce the concept of Observational Diagnostics (ODs) as a structured method to standardise image analysis. ODs serve as foundational elements for AI-driven diagnostic aids and have the potential to improve the consistency and reliability of diagnostic data used in treatment planning. We provide illustrative examples to demonstrate how ODs not only represent a significant advancement towards more precise diagnostic aids but also provide the basis for the generation of evidence-based treatment recommendations. These OD-based algorithms have been integrated into chairside AI applications to streamline clinical workflows to improve consistency, accuracy, and efficiency.