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Brugada syndrome, a rare genetic disease increases the risk of arrhythmias and sudden cardiac death. Various trigger factors has been associated with Brugada syndrome. Arrhythmias have been reported in COVID 19. We report a patient with transient Brugada like pattern in ECG triggered by COVID 19.

Abstract Background Lung cancer is among the top causes of cancer-related mortality in men and is the second most common cancer after breast cancer in women. There are approximately 234,030 new cases of lung cancer and 154,050 deaths from lung cancer in 2018 as per the latest American Cancer Society’s report. Alectinib, a more potent orally active tyrosine kinase inhibitor which was approved by the US Food & Drug Administration for anaplastic lymphoma kinase-positive lung adenocarcinoma, has been shown to have a reasonable safety profile when compared with other anaplastic lymphoma kinase-targeted therapy. As per research studies, grade 1 or 2 renal impairment has been reported but grade 4 renal toxicity due to alectinib has not been reported so far. We report a case of acute renal failure caused by alectinib which necessitated emergency dialysis. This is the first case report describing the severe renal toxicity of alectinib. Case presentation We describe a case of 72-year-old Taiwanese man diagnosed with stage IV anaplastic lymphoma kinase-positive adenocarcinoma of the lung initially treated with crizotinib for over a year, which was switched to alectinib due to disease progression with brain metastasis. Within 6 weeks of starting alectinib, he developed acute renal failure needing emergency dialysis support. His renal failure was secondary to acute tubular necrosis and had a complete reversal within 7–10 days on withdrawing the medication. When he was re-challenged with alectinib, his creatinine started to worsen again which confirmed the renal toxicity of alectinib. Conclusions This case emphasizes the uncommon adverse effect of the anaplastic lymphoma kinase-targeted therapy alectinib causing acute renal failure manifesting as acute tubular necrosis. Recognition of alectinib nephropathy requires a thorough drug history and knowledge of risk factors that lessen its margin of safety at therapeutic ingestions. Frequent monitoring of renal functions and early nephrology referral significantly reduce the mortality and morbidity of these patients.

Hasan Rawashdeh,1,2 Aparna Ramachandran,1 Jenny M Yang,1 Gemma Blain,1 Jon Hyett1,3 1Department of Women and Babies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 2Department of Obstetrics and Gynaecology, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Obstetrics and Gynaecology, Western Sydney University, Sydney, NSW, AustraliaCorrespondence: Hasan Rawashdeh, Department of Obstetrics and Gynaecology, Jordan University of Science and Technology, Irbid, Jordan, Tel +00 962 7 9828 4038, Email hmrawashdeh@just.edu.joBackground: Preterm birth (PTB) is associated with significant neonatal mortality and morbidity. Universal measurement of cervical length has been proposed as a screening tool to direct intervention to prevent PTB.Aim: To assess the impact of the introduction of sonographic mid-trimester cervical length screening on the use of cervical cerclage and PTB.Material and Methods: A retrospective cohort study reviewed two groups of women who underwent cervical cerclage before and after the introduction of universal sonographic cervical length screening. Demographics and outcomes were compared using Student’s t test, Fisher’s Exact test and Kaplan–Meier analysis.Results: Following introduction of universal cervical length screening, the overall rate of cerclage increased from 2.5/1000 births to 6.0/1000 births (p < 0.01). There was a reduction in the proportion of sutures placed purely based on maternal history (50.0% to 30.4%; p < 0.001), while the proportion of sutures placed following ultrasound assessment increased in both high- (21.7 to 36.6%) and low-risk (11.7% to 30.4%) women (p < 0.001). The overall rate of PTB < 37 weeks in women has a cerclage was 25.7% and was highest in women undergoing rescue cerclage (64.3%; p < 0.01). There was no difference in the rate of PTB between high- and low-risk women undergoing history- or ultrasound-indicated cerclage. Mean pregnancy length was most prolonged in low-risk women undergoing ultrasound-indicated cerclage, extending gestation from 33.9 to 38.3 weeks (p < 0.01).Conclusion: Universal cervical length screening results in an increase in the use of cerclage, specifically on the basis of the ultrasound findings. Women who were at low risk but then underwent ultrasound-indicated cerclage experienced most prolongation of pregnancy. Women who were at high risk but had a suture on the basis of ultrasound findings-indicated cerclage represent an alternative method of management with no significant difference in the gestational age of delivery.Keywords: cerclage, premature birth, cervical length measurement, progesterone, ultrasonography

Abstract The CUT and homeodomain are ubiquitous DNA binding elements often tandemly arranged in multiple transcription factor families. However, how the CUT and homeodomain work concertedly to bind DNA remains unknown. Using ONECUT2, a driver and therapeutic target of advanced prostate cancer, we show that while the CUT initiates DNA binding, the homeodomain thermodynamically stabilizes the ONECUT2-DNA complex through allosteric modulation of CUT. We identify an arginine pair in the ONECUT family homeodomain that can adapt to DNA sequence variations. Base interactions by this ONECUT family-specific arginine pair as well as the evolutionarily conserved residues are critical for optimal DNA binding and ONECUT2 transcriptional activity in a prostate cancer model. The evolutionarily conserved base interactions additionally determine the ONECUT2-DNA binding energetics. These findings provide insights into the cooperative DNA binding by CUT-homeodomain proteins.

Abstract The ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBNmidi, a construct that readily expresses from E. coli with high yields as soluble, stable protein without DDB1. We benchmark CRBNmidi for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBNmidi as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics.

Abstract Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Abstract Background This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. Methods This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. Discussion Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. Trial registration Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.

Purpose: While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. Materials and Methods: Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. Results: TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. Conclusions: TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

Abstract Aims New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long‐term HF risk in a large community‐based cohort. Methods and results We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: −0.60 in men and −0.55 in women, P

Context: Plantar fasciitis is one of the most typical causes of heel pain, affecting approximately 10% of the general population. Standard treatment for plantar fasciitis is conservative; however, approximately 10% of patients fail to respond. The rationale for using platelet-rich plasma (PRP) is to increase tendon regenerative abilities with a high content of cytokines and cells in hyperphysiologic doses, which should promote cellular chemotaxis, matrix synthesis, and proliferation. AIMS: Our study aims to analyze the efficacy of the injection of autologous PRP in the treatment of plantar fasciitis. Settings and Design: This study was conducted on patients attending the orthopedics outpatient department, diagnosed with plantar fasciitis satisfying inclusion and exclusion criteria. This is a hospital-based pre- and postinterventional study. MATERIALS AND METHODS: Under aseptic precautions, 2–3 ml of activated autologous PRP will be injected using a 22-gauge needle at the point of maximum tenderness. After the injection, the patient will be followed up regularly at 1 week, 6 weeks, 12 weeks, and 24 weeks. Statistical Analysis Used: Data will be entered in Epi Info version 7.2.2.16 software and analyzed using (SPSS) Software Version 24.0. Results: The majority of the study participants were in the age group of 35–39 years. The mean Visual Analog Scale (VAS) score preinjection was 6.94 ± 0.96, at 1 week 6.48 ± 0.89, at 6 weeks 3.73 ± 0.88, at 12 weeks 0.85 ± 1.61, and 24 weeks 0.27 ± 0.49. Mean roles and Maudsley score preinjection was 3.38 ± 0.63, at 1 week 3.37 ± 0.63, at 6 weeks 1.25 ± 0.52, at 12 weeks 1.00 ± 0.00, and at 24 weeks 1.00 ± 0.00. AOFAS score at preinjection was 48.77 ± 3.29, at 1 week 50.54 ± 3.24, at 6 weeks 77.04 ± 11.46, at 12 weeks 96.31 ± 6.93, and 24 weeks 98.69 ± 2.52. Conclusion: A single PRP injection in chronic plantar fasciitis improved VAS scores and AOFAS scores for heel pain and functional outcomes in a clinically and statistically significant way.

Abstract The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03–2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias.

Abstract Background Nyctanthes arbor-tristis Linn. is a small, sacred ornamental tree used in prayer. It is renowned throughout India for its aromatic white blossoms. The entire plant was widely used for several health applications particularly root and bark were used to treat fever and cough, respectively. Also, the leaf was used for managing fever and diabetes, and its cholagogue, diaphoretic, and anthelmintic properties. Main text The current review aimed to comprehensively analyze the botanical characteristics, phytochemistry, and pharmacology of N. arbor-tristis essential oil (NAEO) and extracts. Additionally, it wants to emphasize the latest advancements in phytochemistry and pharmacology related to this aromatic plant. Depending on the variety, origin, and plant parts used, the NAEO yield ranged from 0.002 to 0.10% on a dry basis. The NAEO has been investigated in only a few research studies and resulted, in the predominant levels of phytol and methyl palmitate chemical compounds. Furthermore, the NAEO was found to have significant volatile chemical constituents, including geranylgeraniol, phytoene, nonadecane, linalool, and various other miscellaneous chemical components. The plant extracts and NAEO have numerous biological properties, including antioxidant, antimicrobial, anticancer, anti-inflammatory, analgesic, larvicidal, and other miscellaneous activities. Conclusion This paper analyzes and summarizes the diverse research potential associated with N. arbor-tristis. The results of the present study suggested that most of the biological and pharmacological investigations were carried out without including dosage, positive controls, and negative controls. Furthermore, several pharmacological investigations were exclusively carried out using cell lines and animal models. Hence, the following research endeavors aimed at assessing the medicinal properties of NAEO and extracts in human subjects would broaden the scope of its utilization. Graphical abstract

In the title compound, C33H29ClN2O2, the two piperidine rings of the diazabicyclo moiety adopt distorted-chair conformations. Intermolecular C—H...π interactions are mainly responsible for the crystal packing. The intermolecular interactions were quantified and analysed using Hirshfeld surface analysis, revealing that H...H interactions contribute most to the crystal packing (52.3%). The molecular structure was further optimized by density functional theory (DFT) at the B3LYP/6–31 G(d,p) level and is compared with the experimentally determined molecular structure in the solid state.

Abstract Aims/Introduction We analyzed patient‐reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence. Materials and Methods In the ongoing International Diabetes Management Practices Study, we collected patient‐reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self‐Management Questionnaire) and free‐text answers to open‐ended questions to assess perceptions of treatment value and side‐effects, as well as barriers to, and enablers for, adherence and self‐management. Free‐text answers were analyzed by natural language processing. Results In 2018–2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin‐treated, glycated hemoglobin (HbA1c) 8.0 ± 1.8%; 30.9% with HbA1c

We present a case of a 29-year-old male who was brought into the hospital due to unresponsiveness and found to have heroin inhalational leukoencephalopathy (HLE). HLE is one component of a broad spectrum of opioid encephalopathies that is associated with heroin inhalation and other opioids. There is considerable overlap of HLE with other toxic and hypoxic-ischemic encephalopathies; however, the specific territories of brain involvement help distinguish it from other cerebral insults. The goal of this study is to help elucidate the findings of HLE and compare these findings to other toxic and hypoxic-ischemic encephalopathies.

AbstractFabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV–visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.

In this era of the latest diagnostic technologies, meticulous clinical examination of the patient still is the golden principle of medical science and will never lose its importance. This case report highlights that detailed physical examination of the patient would have led to the identification of the etiology quite earlier and the significance of evaluating a child as a whole and not based on symptoms alone.

Background: Linear scleroderma (LS) is a variant of localized scleroderma, which is termed as “en coup de sabre” (ECDS) when it involves the head and/or face. Although mainly a dermatological condition, extracutaneous manifestations have been infrequently reported. Clinical Description: A 13-year-old boy presented with fever, altered sensorium with seizures, right hemiparesis, and right-sided upper motor neuron type of facial palsy. He was noticed to have a depression in the left frontoparietal area of the scalp with skin changes. Management and Outcome: The child was initially managed along the lines of acute encephalitis supported with mechanical ventilation. Brain imaging revealed tiny calcification in the left temporal and parietal lobes with altered signal intensities ipsilateral to the scalp lesion. Suspecting an association with the overlying scalp skin lesion, biopsy of the skin lesion was done which confirmed LS. The erythrocyte sedimentation rate was elevated and the antinuclear antibody was positive. The child was started on pulse methylprednisolone following which encephalopathy improved facilitating extubation. Later, he was started on subcutaneous methotrexate and he improved on follow-up. Conclusion: This case creates awareness regarding the association between neurological manifestations and LS EDCS, which responds favorably to immunosuppressives and methotrexate.

In response to the growing need for enhanced energy management in smart grids in sustainable smart cities, this study addresses the critical need for grid stability and efficient integration of renewable energy sources, utilizing advanced technologies like 6G IoT, AI, and blockchain. By deploying a suite of machine learning models like decision trees, XGBoost, support vector machines, and optimally tuned artificial neural networks, grid load fluctuations are predicted, especially during peak demand periods, to prevent overloads and ensure consistent power delivery. Additionally, long short-term memory recurrent neural networks analyze weather data to forecast solar energy production accurately, enabling better energy consumption planning. For microgrid management within individual buildings or clusters, deep Q reinforcement learning dynamically manages and optimizes photovoltaic energy usage, enhancing overall efficiency. The integration of a sophisticated visualization dashboard provides real-time updates and facilitates strategic planning by making complex data accessible. Lastly, the use of blockchain technology in verifying energy consumption readings and transactions promotes transparency and trust, which is crucial for the broader adoption of renewable resources. The combined approach not only stabilizes grid operations but also fosters the reliability and sustainability of energy systems, supporting a more robust adoption of renewable energies.

Abstract Heart rate, a measure of the frequency of the cardiac cycle, reflects the health of the cardiovascular system, metabolic rate, and activity of the autonomic nervous system. Whether changes in resting heart rate are related to lifespan has not yet been explored to our best knowledge. In this study, we examined the association between resting heart rate and lifespan using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study. We used Cox proportional hazards regression to relate changes in heart rate over years to mortality risk. We observed a statistically significant association between increases in resting heart rate over a 5-year period and risk of mortality in the Paris Prospective Study I (HR mortality per 10 bpm increase over time: 1.20; 95% CI: 1.13 to 1.27) and over an 8-year period in the Framingham Heart Study (HR: 1.13; 95% CI: 1.07 to 1.19 for men and HR: 1.09; 95% CI: 1.04 to 1.15 for women), after adjusting for classical risk factors and resting heart rate. Our study shows that men and women who increase their resting heart rate over time increase their risk of mortality.

Abstract Introduction Real-world evidence is receiving considerable attention as a way to evaluate the efficacy and safety of medical products for substance use disorders (SUDs). However, the feasibility of using real-world data (RWD) to emulate clinical trials evaluating treatments for SUDs is uncertain. The aim of this study is to identify the number of clinical trials evaluating treatments for SUDs with reported results that could be feasibly emulated using observational data from contemporary insurance claims and/or electronic health record (EHR) data. Methods In this cross-sectional study, all phase 2–4 trials evaluating treatments for SUDs registered on ClinicalTrials.gov with reported results were identified. Each trial was evaluated to determine if the indications, interventions, at least 80% of eligibility criteria, comparators, and primary end points could be ascertained using contemporarily available administrative claims and/or structured EHR data. Results There were 272 SUD trials on ClinicalTrials.gov with reported results. Of these, when examining feasibility using contemporarily available administrative claims and/or structured EHR data, 262 (96.3%) had indications that were ascertainable; 194 (71.3%) had interventions that were ascertainable; 21 (7.7%) had at least 80% of eligibility criteria that were ascertainable; 17 (6.3%) had active comparators that were ascertainable; and 61 (22.4%) had primary end points that were ascertainable. In total, there were no trials for which all 5 characteristics were ascertainable using contemporarily available administrative claims and/or structured EHR data. When considering placebo comparators as ascertainable, there were 6 (2.2%) trials that had all 5 key characteristics classified as ascertainable from contemporarily available administrative claims and/or structured EHR data. Conclusions No trials evaluating treatments for SUDs could be feasibly emulated using contemporarily available RWD, demonstrating a need for an increase in the resolution of data capture within a public health system to facilitate trial emulation.

Abstract Smart elevators provide substantial promise for time and energy management applications by utilizing cutting edge artificial intelligence and image processing technology. In order to improve operating efficiency, this project designs an elevator system that uses the YOLO model for object detection. Compared to traditional methods, our results show a 15% improvement in wait times and a 20% reduction in energy use. Due to the elevator’s increased accuracy and dependability, users’ qualitative feedback shows a high degree of pleasure. These results imply that intelligent elevator systems can make a significant contribution to more intelligent building management. Due to the elevator’s increased accuracy and dependability, users’ qualitative feedback shows a high degree of pleasure. These results imply that intelligent elevator systems can make a significant contribution to more intelligent building management. The successful integration of artificial intelligence (AI) and image processing technologies in elevator systems presents a promising foundation for future research and development. Further advancements in object detection algorithms, such as refining YOLO models for even higher accuracy and real-time adaptability, hold potential to enhance operational efficiency. Integrating smart elevators more deeply into IoT networks and building management systems could enable comprehensive energy management strategies and real-time decision-making. Predictive maintenance models tailored to elevator components could minimize downtime and optimize service schedules, enhancing overall reliability. Additionally, exploring adaptive user interfaces and personalized scheduling algorithms could further elevate user satisfaction by tailoring elevator interactions to individual preferences. Sustainable practices, including energy-efficient designs and integration of renewable energy sources, represent crucial avenues for reducing environmental impact. Addressing security concerns through advanced encryption and access control mechanisms will be essential for safeguarding sensitive data in smart elevator systems.

Abstract Methane emissions from the oil and gas sector are a large contributor to climate change. Robust emission quantification and source attribution are needed for mitigating methane emissions, requiring a transparent, comprehensive, and accurate geospatial database of oil and gas infrastructure. Realizing such a database is hindered by data gaps nationally and globally. To fill these gaps, we present a deep learning approach on freely available, high-resolution satellite imagery for automatically mapping well pads and storage tanks. We validate the results in the Permian and Denver-Julesburg basins, two high-producing basins in the United States. Our approach achieves high performance on expert-curated datasets of well pads (Precision = 0.955, Recall = 0.904) and storage tanks (Precision = 0.962, Recall = 0.968). When deployed across the entire basins, the approach captures a majority of well pads in existing datasets (79.5%) and detects a substantial number (>70,000) of well pads not present in those datasets. Furthermore, we detect storage tanks (>169,000) on well pads, which were not mapped in existing datasets. We identify remaining challenges with the approach, which, when solved, should enable a globally scalable and public framework for mapping well pads, storage tanks, and other oil and gas infrastructure.

Abstract As the quantity and significance of digital pictures in the medical industry continue to increase, Image Quality Assessment (IQA) has recently become a prevalent subject in the research community. Due to the wide range of distortions that Magnetic Resonance Images (MRI) can experience and the wide variety of information they contain, No-Reference Image Quality Assessment (NR-IQA) has always been a challenging study issue. In an attempt to address this issue, a novel hybrid Artificial Intelligence (AI) is proposed to analyze NR-IQ in massive MRI data. First, the features from the denoised MRI images are extracted using the gray level run length matrix (GLRLM) and EfficientNet B7 algorithm. Next, the Multi-Objective Reptile Search Algorithm (MRSA) was proposed for optimal feature vector selection. Then, the Self-evolving Deep Belief Fuzzy Neural network (SDBFN) algorithm was proposed for the effective NR-IQ analysis. The implementation of this research is executed using MATLAB software. The simulation results are compared with the various conventional methods in terms of correlation coefficient (PLCC), Root Mean Square Error (RMSE), Spearman Rank Order Correlation Coefficient (SROCC) and Kendall Rank Order Correlation Coefficient (KROCC), and Mean Absolute Error (MAE). In addition, our proposed approach yielded a quality number approximately we achieved significant 20% improvement than existing methods, with the PLCC parameter showing a notable increase compared to current techniques. Moreover, the RMSE number decreased by 12% when compared to existing methods. Graphical representations indicated mean MAE values of 0.02 for MRI knee dataset, 0.09 for MRI brain dataset, and 0.098 for MRI breast dataset, showcasing significantly lower MAE values compared to the baseline models.

Background: Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Methods: Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Results: Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC)

Complex congenital heart disease (CHD) constitutes a significant non-infectious contributor to childhood morbidity and mortality, particularly prevalent in developing countries with an estimated incidence of nearly 1/100 births. The spectrum of CHD spans from isolated atrial septal defects that necessitate no immediate intervention to intricate structural cardiovascular abnormalities demanding multiple interventions early in the neonatal period. Patients afflicted with complex CHD often manifest symptoms such as respiratory distress, cyanosis of the skin, feeding difficulties, and failure to thrive, becoming evident within the initial 48 h post-birth. In this context, we present an intriguing case of a male child with complex CHD. This case study is accompanied by a concise exploration of the embryology of the heart, shedding light on the intricate developmental processes that may underlie such congenital anomalies.

Abstract Hot electrons and holes generated from the decay of localised surface plasmons in metallic nanoparticles can be harnessed for applications in solar energy conversion and sensing. In this paper, we study the generation of hot carriers in large spherical gold-silver alloy nanoparticles using a recently developed atomistic modelling approach that combines a solution of Maxwell’s equations with large-scale tight-binding simulations. We find that hot-carrier properties depend sensitively on the alloy composition. Specifically, nanoparticles with a large gold fraction produce hot carriers under visible light illumination while nanoparticles with a large silver fraction require higher photon energies to produce hot carriers. Moreover, most hot carriers in nanoparticles with a large gold fraction originate from interband transitions which give rise to energetic holes and ‘cold’ electrons near the Fermi level. Increasing the silver fraction enhances the generation rate of hot carriers from intraband transitions which produce energetic electrons and ‘cold’ holes. These findings demonstrate that alloy composition is a powerful tuning parameter for the design of nanoparticles for applications in solar energy conversion and sensing that require precise control of hot-carrier properties.

Abstract Developing supercapacitor materials that are both efficient and durable, with high cycle life and specific energy, poses a significant challenge due to issues in electrodes such as volume expansion and electrode degradation that occur over time. This work reports a simple, novel, and cost-effective synthesis method to fabricate high surface area “Iron (Fe) doped TiO2 materials” via the metal-organic framework (MOF) route for supercapacitor application. Morphological analysis revealed a disc-like shaped pattern for pristine TiO2 (PT), and a cuboid form for Fe-doped TiO2 (FeT). The electrochemical investigation of MOF-derived PT and FeT electrode materials demonstrated the superior performance of FeT. Cyclic Voltammetry revealed enhanced electrochemical properties in FeT. Galvanostatic charge-discharge measurements confirmed FeT’s higher energy storage capacity, reaching a maximum specific capacitance of 925 Fg− 1. Long-term cycling tests exhibited excellent stability, with FeT retaining 67% of its initial capacitance after 6000 cycles and showing prolonged self-discharge. Overall, the results underscore the potential of Fe-doped TiO2 for high-performance supercapacitors.

Abstract The creation of the National Register of Citizens (NRC) in Assam is indicative of the sharpening tensions surrounding citizenship, belonging and integration in India. Officially aimed at demarcating the “legitimate citizens”, its implementation is believed to have resulted in the partial exclusion of the so-called “Doubtful Voters” and denationalisation of the “illegitimate residents”. These frictions associated with citizenship identity and rights are nowhere as acute as in the northeastern Indian state of Assam, where measures of retroactive revocation, administrative erasure and withdrawal of citizenship rights have been systematically deployed against religious and linguistic minorities. Using new research with some NRC rejected applicants in western Assam and other materials, this article identifies the central aspects of the implementation gap in the crucial, albeit problematic task of locating the rightful “Assamese-Indian” citizens. Linking our work to the idea of the ‘process is the punishment’, we conceptualise these conspicuous inconsistencies in the NRC citizenship determination processes and their results as the “punitive gap”. We have identified the distinctive contours of this gap in terms of the massive economic costs, intensification of social (including gender and religion-based) inequalities, increased control through social suspicion and unpredictable outcomes for the marginal Miya Muslim community. The article highlights how this punitive gap has constantly eroded key components of due process, of procedural and substantive protections of the rights of individuals, during the NRC determination exercise and after the release of the final draft list.

Aim: Temporomandibular disorders (TMD) comprise ailments involving the jaw joint (temporomandibular joint) and its associated anatomical structures. The complexity involved in TMD is primarily due to its broad spectrum of conditions, clinical signs and symptoms variability, and multifactorial etiology. Considering the above, the present study was performed to help understand the prevailing knowledge and awareness of TMD among Indian dentists in the context of the new specialty “orofacial pain”. Settings and Design: Questinnaire study and review. Materials and Methods: The questionnaire was distributed using a web-based portal nationwide among Indian dentists. Dentists were invited to participate, clearly stating that the intent and purpose of the questionnaire was to record the existing knowledge and awareness concerning temporomandibular disorders among Indian dentists. The questionnaire was segregated into three sections: pathogenesis, diagnosis, and management of TMDs. The questions were recorded using a Likert three-point scale (1=agree; 2=disagree; 3=not aware). 310 dentists participated in the survey, among which 105 were general dentists (BDS [Bachelor of Dental Surgery] graduates), and 205 were dentists with specialist training (MDS [Masters of Dental Surgery] graduates). Statistical Analysis Used: The results obtained from the study participants was used to calculate the percentage and frequency, following which tabulations were made based on graduate type and clinical experience. The values obtained from all three sections were recorded, and the responses were analysed using Pearson’s Chi-Square test with statistical significance kept at P < 0.05. Results: Results of the study disclosed that only 58.1% of general dentists and 46.8% of specialists were confident in handling temporomandibular disorder patients. Splint therapy was the preferred treatment modality for general dentists, whereas dentists with specialist training preferred occlusal rehabilitation. Conclusion: The results of the current survey indicate that Indian dentists lack sufficient training in dental schools on all three sections and face difficulty diagnosing and treating TMDs.

Acute kidney injury (AKI) is a common problem in critical care settings and conferred an increased risk of morbidities and mortality. The pendulum has shifted to the increasing number of children with comorbidities exposed to potential kidney damage. AKI is a complex clinical syndrome due to heterogeneous etiology. There has been an evolution in the definition and staging of AKI over the past two decades. However, estimating glomerular filtration rate in rapidly changing kidney function remains challenging. Although biomarkers are promising in AKI identification, timing is crucial in deciding which biomarker to measure. The outcome of AKI is not always recovery, but it is an interconnected syndrome with acute and chronic kidney disease.

Abstract Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body’s defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.

Soybean rust is an economically significant disease caused by the fungus Phakopsora pachyrhizi that negatively impacts soybean (Glycine max [L.] Merr.) production throughout the world. Susceptible plants infected by P. pachyrhizi develop tan-colored lesions on the leaf surface that give rise to funnel-shaped uredinia as the disease progresses. While most soybean germplasm is susceptible, seven genetic loci (Rpp1 to Rpp7) that provide race-specific resistance to P. pachyrhizi (Rpp) have been identified. Rpp3 was first discovered and characterized in the soybean accession PI 462312 (Ankur), and it was also determined to be one of two Rpp genes present in PI 506764 (Hyuuga). Genetic crosses with PI 506764 were later used to fine-map the Rpp3 locus to a 371-kb region on chromosome 6. The corresponding region in the susceptible Williams 82 (Wm82) reference genome contains several homologous nucleotide binding site-leucine rich repeat (NBS-LRR) genes. To identify Rpp3, we designed oligonucleotide primers to amplify Rpp3 candidate (Rpp3C) NBS-LRR genes at this locus from PI 462312, PI 506764, and Wm82 using polymerase chain reaction (PCR). Five Rpp3C genes were identified in both Rpp3-resistant soybean lines, and co-silencing these genes compromised resistance to P. pachyrhizi. Gene expression analysis and sequence comparisons of the Rpp3C genes in PI 462312 and PI 506764 suggest that a single candidate gene, Rpp3C3, is responsible for Rpp3-mediated resistance. [Graphic: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

Abstract Aim There is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma. Methods We conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample. Results In this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%). Conclusion Patients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

Abstract Familial chylomicronemia syndrome (FCS) is a rare inherited disorder characterized by severe hypertriglyceridemia, posing a heightened risk of acute pancreatitis. Recently, Volanesorsen, an APOC3 antisense oligonucleotide, gained approval for FCS treatment in the UK. Caution is advised during pregnancy due to limited safety data, although animal studies show no toxicity/teratogenicity. Two case scenarios are presented: In the first case, a patient with FCS continued Volanesorsen injections without having thrombocytopenia during an unplanned pregnancy until third trimester, maintaining triglyceride control. Upon discovering the pregnancy at 38 weeks, Volanesorsen was ceased, and a low‐fat diet reinstated. Despite a heightened risk of pancreatitis, no episodes of pancreatitis occurred during the pregnancy. In the second case, stopping Volanesorsen before conception led to elevated triglycerides, and an episode of acute pancreatitis at 22 weeks, despite strict very low‐fat diet and fibrate therapy from 14 weeks. At 23 weeks, Volanesorsen was reintroduced concurrently with regular therapeutic plasma exchange. No further episodes of pancreatitis occurred. In both case, fetal health was maintained throughout pregnancy, fetal scans revealed no anomalies, and planned C‐sections delivered healthy babies without congenital issues. Both babies are well and developing normally at 24 and 19 months.

Abstract This paper investigates the stability and reliability analysis of a non‐isolated high‐gain DC‐DC converter. The proposed DC‐DC converter produces a high gain output voltage with a lower duty ratio and reduced voltage stress on the semiconductor switch. A reliability analysis is performed to predict the failure rate and lifetime of the individual components using the military handbook (MIL‐HDBK‐217F). A state space equation and small signal modeling of the proposed converter are derived to elucidate the performance of the proposed converter through stability analysis. A closed‐loop using PID controller is incorporated to attain the constant regulated output voltage during sudden parameter changes. The validation of the closed‐loop using the PID controller is verified with the wide range of variations in the different parameters, such as input voltage, load value, and reference voltage value. The laboratory‐based prototype is developed for the proposed converter and validated the performance with 250 W. The power density and efficiency of the proposed converter are 1.360 kW/L and 93%, respectively.

Abstract Objective Overlap syndromes have been described between N‐methyl‐ d‐aspartate receptor encephalitis (NMDARE) and other neuroinflammatory conditions, although rarely involving neurosarcoidosis. Molecularly targeted immunotherapy may be helpful in the empiric treatment of these conditions. Methods We describe a 9‐year‐old boy with new‐onset seizures and worsening encephalopathy. Results Initial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin‐converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome. Interpretation Our patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high‐acuity pediatric neuroinflammatory disease with limited diagnostic clarity.

Introduction: Chronic spontaneous urticaria (CSU) is the most commonly diagnosed skin condition in dermatology outpatient departments. Second-generation antihistamines are shown to be effective in the control of CSU. As per the guidelines, a combination of antihistamines is less recommended due to the lack of synergistic effect, though used widely. Exploring effective treatment options are crucial, given the challenges posed by CSU. Aims and Objectives: To assess the safety and efficacy of Bilastine up-dosing versus combination of 20 mg Bilastine with 5 mg Levocetirizine in the treatment of CSU. Materials and Methods: This prospective randomized non-blinded comparative trial involved 62 patients, with 32 in group A and 30 in group B. Group A received Tablet Bilastine 20 mg bd, while Group B received a combination of Tablet Bilastine 20 mg and Tablet Levocetirizine 5 mg. Urticarial Activity Score 7 was performed at baseline and follow-up visits (every 2 weeks for 6 weeks). Results: Both groups had a higher number of male patients in the 20–30 years age group. Angioedema was present in 15.6% of group A and 23.3% in group B. After 6 weeks, both the groups showed a significant improvement in UAS 7 scores (P value

Background: Although studies often report the prevalence of obesity, community-based studies reporting the incidence of overweight or obesity in India are scarce. Such incidence data are crucial for improving projections about the future burden of obesity. Methods: A non-concurrent follow-up study was done in 2015 in urban Vellore, Tamil Nadu, among two groups of women aged 30-40 years, with body mass index (BMI) 25 kg/m2. The incidence of overweight (BMI ≥25 kg/m2) in three years, was 29.2% (24/82), among women with a normal BMI (

COVID-19 pandemic has forced the implementation of a new normal for all businesses leading to an increase in stress levels for many including educators and students. Ethics in education was questioned by professional bodies due to online exams. The objective of this study is to determine the antecedents of student online learning effectiveness and its impact on educational ethics. The study compares Malaysia and India since some Indian educational institutions had been implementing online teaching prior to the pandemic. Data was collected through a survey method. 571 questionnaires from students across Malaysia and India were analyzed using SPSS and PLS-SEM. It was found that physical, psychological, intellectual, and emotional attributes were significant in predicting learning effectiveness which in turn had an impact on educational ethics. Intellectual attributes were the most important predictor of learning effectiveness. The emotional and psychological attributes had a small impact on learning effectiveness. Furthermore, physical attributes had trivial effects on the learning effectiveness. A T test comparing mean differences between the two countries revealed that there were no significant differences in learning effectiveness between students of both countries while educational ethics was more evident among Indian students as compared to Malaysian students. The key implication is the need for educational institutions and educators to develop pedagogies to stimulate students’ intellectual abilities during online teaching to preserve educational ethics. HEIs must support the students psychologically, emotionally and encourage themselves to keep physically active during the phase of online classes. Institutions must take ample steps to ensure that educational ethics is not affected as a result of the new normal failing which could prove detrimental in the long run for students and institutions. This will help to curb unethical practices during online examinations and mitigate academic dishonesty. Our findings regarding various attributes of online learning effectiveness add profoundly to literature and help to understand antecedents contributing to successful learning effectiveness which leads to positive educational ethics in both the countries.

In smart city infrastructure, IP cameras play a pivotal role in crime prevention and detection. However, not much research has been conducted on IP cameras from a cybersecurity and forensics perspective. In this study, we investigate vulnerability assessment and forensic artifacts for Hanwha and Mobotix IP cameras, which are widely used in Saudi Arabia. Saudi Arabia is using IP cameras which are essential for its smart cities. In this paper, we examine IP cameras in two directions. The first is to assess the vulnerability of IP cameras through various attack scenarios such as denial of service (DoS), brute force, and unauthorized access, and we suggest countermeasures. The second shows how analysis for IP cameras can be used to investigate logs for cyberattacks. Through this study, we expect to contribute to research on cyber-attack and forensic perspectives on IP cameras to be used in smart cities.

Abstract Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand promoter (HSP). Herein, we characterize the conformational dynamics of TFAM on promoter and non-promoter sequences using single-molecule fluorescence resonance energy transfer (smFRET) and single-molecule protein-induced fluorescence enhancement (smPIFE) methods. The DNA-TFAM complexes dynamically transition between partially and fully bent DNA conformational states. The bending/unbending transition rates and bending stability are DNA sequence-dependent—LSP forms the most stable fully bent complex and the non-specific sequence the least, which correlates with the lifetimes and affinities of TFAM with these DNA sequences. By quantifying the dynamic nature of the DNA-TFAM complexes, our study provides insights into how TFAM acts as a multifunctional protein through the DNA bending states to achieve sequence specificity and fidelity in mitochondrial transcription while performing mtDNA packaging.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

Abstract Background Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells. Methods Human telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood. Results EVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control. Conclusions This is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.

Abstract Accurate classification of tooth development stages from orthopantomograms (OPG) is crucial for dental diagnosis, treatment planning, age assessment, and forensic applications. This study aims to develop an automated method for classifying third molar development stages using OPGs. Initially, our data consisted of 3422 OPG images, each classified and curated by expert evaluators. The dataset includes images from both Q3 (lower jaw left side) and Q4 (lower right side) regions extracted from panoramic images, resulting in a total of 6624 images for analysis. Following data collection, the methodology employs region of interest extraction, pre-filtering, and extensive data augmentation techniques to enhance classification accuracy. The deep neural network model, including architectures such as EfficientNet, EfficientNetV2, MobileNet Large, MobileNet Small, ResNet18, and ShuffleNet, is optimized for this task. Our findings indicate that EfficientNet achieved the highest classification accuracy at 83.7%. Other architectures achieved accuracies ranging from 71.57 to 82.03%. The variation in performance across architectures highlights the influence of model complexity and task-specific features on classification accuracy. This research introduces a novel machine learning model designed to accurately estimate the development stages of lower wisdom teeth in OPG images, contributing to the fields of dental diagnostics and treatment planning.

Background Studies assessing variability of serum testosterone levels associated with seasonal environmental factors have been contradictory.Design We assessed associations between the seasons and changes (δ) in seasonality indices and male serum total testosterone (δTT) variability.Patients and Measurements Data were collected in 144 men with paired serum TT samples (126 non-fasting/18 fasting) analysed at Walsall Manor Hospital, UK (52.3 degrees North). Seasonal factors (ambient temperature within 15 min of sampling, humidity, precipitation, duration of daylight on the day of sampling, monthly average ambient temperature, and precipitation) were obtained from local weather-station archives. Sign-rank test determined inter-sample differences between TT and seasonality indices. Linear regression analyses studied associations between δTT and δ seasonal indices in the total cohort and subgroups (stratified by medians of age, TT and men with paired non-fasting samples). Sign-rank determined whether serum TT differed between the seasons.Results Median inter-sample interval was 63 days. No significant inter-sample differences were evident regarding serum TT levels and seasonality indices. No associations were noted between δTT and δ seasonality indices in the total cohort and subgroups stratified by age and TT. Interestingly, δ ambient temperature (p = 0.012) and daylight duration (p = 0.032) were inversely associated with δTT in the 126 men in the non-fasting group (dependent variable). Only a small degree of the variability in the δTT was accounted by the above-mentioned independent variables. The seasons did not appear to influence serum TT values.Conclusions No relation was shown between seasonality and serum TT in the total cohort, thus possibly eliminating a confounding variable that could affect laboratory and clinical practice. It may be that seasonal variation in length of day is too modest at this latitude to demonstrate significant associations, hence our findings are latitude specific. We suggest that further data analysis to address this question in areas with greater seasonal variation would be appropriate.