Search

Abstract The demand for electric power has consistently been on the rise, owing to urbanisation and technological improvements. On the generation side, renewable sources have been favoured over their polluting, exhaustible, non‐renewable counterparts. These changes in the power system have necessitated a system for maintaining the supply‐demand balance, to maintain system stability. A complex power system is also more prone to blackouts and grid failure. Islanding helps in provision of supply to consumers in a microgrid, reducing the possibility of a blackout. Depending on the power demand and generation, loads need to be shed or restored to mitigate power imbalances. A wide area distribution management system (WADMS) is proposed to dynamically shed and restore loads in the islanded mode, with the aid of micro phasor measurement units (µPMUs). A priority and consumer‐based load shedding and restoration (PCLS) algorithm is proposed in the WADMS that preferentially sheds or restores loads based on their assigned load priority indices and number of consumers. The algorithm has been tested on a modified IEEE 13 bus system, incorporated with a solar photovoltaic (PV) system, diesel generators (DGs) and an energy storage system (ESS) in MATLAB Simulink.

Abstract Objectives The main goal of presurgical evaluation in drug‐resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource‐intensive tests available, ictal single‐photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri‐ictal radionuclide administration. Recent studies indicate that geographic and center‐specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri‐ictal injection during inpatient admission) using surgery‐related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center‐specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. Methods We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center‐specific SPECT practices. Results Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non‐Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p

Abstract Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1–3, fibroblast growth factor (FGF) receptors 1–4, platelet‐derived growth factor receptor‐α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whether lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang‐2, Tie‐2, and FGF‐23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients with radioiodine‐refractory differentiated thyroid cancer (RR‐DTC) receiving either lenvatinib or placebo treatment. Lenvatinib PK was best described by a 3‐compartment model with simultaneous first‐ and zero‐order absorption and linear elimination from the central compartment with significant covariates (body weight, albumin ULN, RR‐DTC, RCC, HCC subjects, and concomitant CYP3A inhibitors). Except for body weight, none of the covariates have any clinically meaningful effect on exposure to lenvatinib. Longitudinal biomarker measurements over time were reasonably well defined by a PK/PD model with common EC50, Emax, and a slope for disease progression for all biomarkers. Longitudinal tumor measurements over time were reasonably well defined by a tumor growth inhibition Emax model, which in addition to lenvatinib exposure, included model‐predicted relative changes from baseline over time for Tie‐2 and Ang‐2 as having significant association with tumor response. The developed PK/PD models pave the way for dose optimization and potential prediction of clinical response.

Abstract Identifying individuals is key to estimating population sizes by spatial capture–recapture, but identification errors are sometimes made. The most common identification error is the failure to recognise a previously detected individual, thus creating a ‘ghost’ Johansson. This results in positively biased abundance estimates. Ghosts typically manifest as single detection individuals (‘singletons’) in the capture history. To deal with ghosts, we develop a spatial capture–recapture method conditioned on at least K detections. The standard spatial capture–recapture (SCR) model is the special case of K=1. Ghosts can mostly be excluded by fitting a model with K=2 (SCR‐2). We investigated the effect of ‘singleton’ ghosts on the estimation of the model parameters by simulation. The SCR method increasingly overestimated abundance with increasing percentage of ghosts, with positive bias even when only 10% of the detected individuals were ghosts, and bias between 43% and 71% when 30% were ghosts. Estimates from the SCR‐2 method showed lower bias in the presence of ghosts, at the cost of a loss of precision. The mean squared error of the estimated abundance from the SCR‐2 method was lower in all scenarios with ghosts under high encounter rates and for scenarios with 30% or more ghosts with low encounter rates. We also applied our method to capture histories from camera trap surveys of snow leopards (Panthera uncia) at two sites from Mongolia and find that the SCR method produced higher abundance estimates at both sites. Capture histories are susceptible to errors when generated from passive detectors such as camera traps and genetic samples. The SCR‐2 method can remove bias from ghost capture histories, at the cost of some loss in precision. We recommend using the SCR‐2 method in cases when there may be more than 10% ghosts or surveys with a large number of single detection capture histories, except perhaps when the sample size is very low.

Abstract The global warming crisis, together with environmental concerns, has already led governments to replace traditional fossil‐fuel cars with low‐emission Electric Vehicles (EVs). This replacement has resulted in the addition of a large number of EVs capable of connecting to the grid. A coordinated charging method is needed to promote EVs on a large scale while preventing grid overloading. In this work, EVs are categorized based on their battery capacity, as cars, trucks, and buses. A charging/discharging mechanism based on Real Time Pricing for each hour is developed for a 20‐min block that has been formed. The locations of EV charging stations have been identified using Voltage Stability Index. In the present work, the power loss when Distributed Generator (DG) units are deployed after the EVs are located in the system for charging and discharging is analyzed. The DGs are considered as solar‐based or wind‐based generators for studying the economic benefit of such an investment under two different weather scenarios and topologies on standard test systems. The results thus obtained give an insight into the various technical and economic benefits.

Background Increased vascular CaV1.2 channel function causes enhanced arterial tone during hypertension. This is mediated by elevations in angiotensin II/protein kinase C signaling. Yet, the mechanisms underlying these changes are unclear. We hypothesize that α1C phosphorylation at serine 1928 (S1928) is a key event mediating increased CaV1.2 channel function and vascular reactivity during angiotensin II signaling and hypertension. Methods and Results The hypothesis was examined in freshly isolated mesenteric arteries and arterial myocytes from control and angiotensin II‐infused mice. Specific techniques include superresolution imaging, proximity ligation assay, patch‐clamp electrophysiology, Ca2+ imaging, pressure myography, laser speckle imaging, and blood pressure telemetry. Hierarchical “nested” and appropriate parametric or nonparametric t test and ANOVAs were used to assess statistical differences. We found that angiotensin II redistributed the CaV1.2 pore‐forming α1C subunit into larger clusters. This was correlated with elevated CaV1.2 channel activity and cooperativity, global intracellular Ca2+ and contraction of arterial myocytes, enhanced myogenic tone, and altered blood flow in wild‐type mice. These angiotensin II‐induced changes were prevented/ameliorated in cells/arteries from S1928 mutated to alanine knockin mice, which contain a negative modulation of the α1C S1928 phosphorylation site. In angiotensin II‐induced hypertension, increased α1C clustering, CaV1.2 activity and cooperativity, myogenic tone, and blood pressure in wild‐type cells/tissue/mice were averted/reduced in S1928 mutated to alanine samples. Conclusions Results suggest an essential role for α1C S1928 phosphorylation in regulating channel distribution, activity and gating modality, and vascular function during angiotensin II signaling and hypertension. Phosphorylation of this single vascular α1C amino acid could be a risk factor for hypertension that may be targeted for therapeutic intervention.

Background Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial. Methods and Results Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post–percutaneous coronary intervention population with acute coronary syndrome. Dual‐antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high‐potency, high‐ to low‐potency, low‐dose, and short‐duration DAPT. A network meta‐analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty‐two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high‐ to low‐potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52–0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72–0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06–2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow‐up). Prasugrel (RR, 1.35 [95% CI, 1.09–1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17–1.62]) containing DAPT for 12 months had significantly higher rates, whereas high‐ to low‐potency DAPT (RR, 0.85 [95% CI, 0.63–1.15]) had no significant risk of major bleeding. Conclusions Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post–percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

Key Clinical Message Hepatocellular carcinoma (HCC) is one of the most common types of cancer. More focus is being placed on clinical presentations of distant metastasis from HCC. Head masses should be investigated even when no concerning symptoms are found in patients with prior history of alcohol abuse and liver comorbidities.

Abstract In Numerical Weather Prediction (NWP) models, such as the Weather Research and Forecasting (WRF) model, parameter uncertainty in physics parameterization schemes significantly impacts model output. Our study adopts a Bayesian probabilistic approach, building on prior research that identified temperature (T) and relative humidity (Rh) as sensitive to three key WRF parameters during southeast Australia's extreme heat events. Using Gaussian process regression‐based Bayesian Optimisation (G‐BO), we accurately estimated the optimal distributions for these parameters. Results show that the default values are outside their corresponding optimal distribution bounds for two of the three parameters, suggesting the need to reconsider these default values. Additionally, the robustness of the optimal parameter distributions is validated by their application to an independent extreme heat event, not included in the optimisation process. In this test, the optimized parameters substantially improved the simulation of T and Rh, highlighting their effectiveness in enhancing simulation accuracy during extreme heat conditions.

Abstract Today's industries need to be more productive, especially those that shape and machine materials. As a result, engineers and scientists are seeking for cutting tool materials and technologies that have high hot hardness, chemical stability, wear resistance, and toughness while also improving tool life or contact time. Cryogenic treatment of cutting tools has been proven to be a good way for increasing the contact time of any cutting tool material. This study presents the results of turning alloy steel (EN24 grade) using P20 grade carbide inserts under various conditions under continuous machining. Cutting speeds varied from 100 to 500 m/min (in increments of 100 m/min), with feed rates ranging from 0.1 to 0.4 mm/rev in stages of 0.1 mm/rev and a constant radial depth of cut of 1.5 mm were considered under dry machining conditions. Cryogenic treated/coated inserts are better than other inserts in terms of tool life for optimized parameters such as cutting speed 100 m/min, feed rate 0.1 mm/rev, and depth of cut 1.5 mm, according to the study's findings. Under similar conditions of cutting speed, feed rate, and depth of cut, coated/cryotreated inserts had a tool life increase of about 97.5% over uncoated/untreated inserts, a 50.58% increase over uncoated/crytreated inserts, and a 23.89% increase over coated and untreated inserts, respectively.

Abstract Introduction HIV self‐testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95‐95‐95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community‐based, PLHIV network‐led and private practitioners models, in India. Methods This cross‐sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood‐based or oral‐fluid‐based test kits. Participants were shown a test‐kit usage demonstration video, and pre‐ and post‐test counselling was provided for all. Participants were followed‐up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation. Results Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood‐based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART. Conclusions Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two‐thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first‐time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic.

Abstract Early‐stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non‐invasive and cost‐effective detection method for early‐stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance for early‐stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on‐skin sensor to reduce electrode‐skin contact impedance by increasing double‐layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention‐based deep learning algorithm is introduced to differentiate impedance signals associated with early‐stage NAFLD in high‐fat‐diet‐fed low‐density lipoprotein receptor knockout (Ldlr−/−) mice compared to healthy controls. The integration of an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance and the attention‐based deep learning algorithm significantly enhances the detection accuracy for early‐stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non‐invasive approach for early‐stage NAFLD detection and display a strategy for improved early detection through on‐skin electronics and deep learning.

Abstract Atrial fibrillation (AF) recurrence has become common in patients who have undergone catheter ablation. High neutrophil lymphocyte ratios (NLR) have been linked to an increased risk of recurrent AF. The research is, however, not conclusive. This meta‐analysis addressed the value of easily accessible and affordable pre‐ and postablation NLR levels as indicators of AF recurrence in patients who had undergone ablation. We searched PubMed, SCOPUS, and Google Scholar for pertinent studies through May 2023. Using random effects models, the aggregated odds ratio (OR) of pre‐ and post‐NLR and AF recurrence was estimated. Inter‐study heterogeneity was described using I2 statistics and leave‐one‐out sensitivity analysis. A p‐value

Abstract Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug‐resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty‐two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6–10 new RNS devices per year; all DBS programs implant 50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. Plain language summary We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug‐resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

Abstract Electric Vehicles (EV) have the potential to completely transform the transportation industry, reduce carbon emissions significantly, and pave the road for significant climate progress. According to surveys, worries regarding range and charging accessibility are a significant barrier to EV customer adoption. The electricity grid will be significantly impacted by EV charging. A coordinated charging approach that facilitates EV charging while avoiding the power grid from overloading is required to manage EV charging. In this work, the EVs are classified based on their charging capacity. This classification includes car, truck, and bus. With this a charging discharging scheme has been established using Real Time Pricing for each hour for a 20‐min block. The Voltage Stability Index (VSI) for the system is calculated for the system and the strongest bus is identified for locating the EVs to charge/discharge. Augmenting this, in the present work, the power loss is analyzed when Distributed Generation (DG) units are installed after the EVs are located in the system for charging and discharging. The DG units are installed in each feeder, considering the VSI and Penetration Level (PL) and the power losses incurred due to the presence of EVs. The Monetary benefit of such an investment is analyzed for different topologies of IEEE‐33 and 69 bus systems and compared with the existing methods where DGs are installed before the EVs are located in the system for charging and discharging.

Abstract Treatment modalities for pulmonary arterial hypertension (PAH) improve quality of life and walk distance. However, none of these therapies alter the structural/functional pulmonary vascular integrity that results in vascular remodeling. PAH smooth muscle cells share biological characteristics with cancer cells, which may be potential therapeutic targets for PAH. We present a case of a patient with connective tissue disease (CTD)‐associated PAH treated on triple therapy who developed metastatic lung adenocarcinoma. While on PAH triple‐therapy, she received a combination of carboplatin, pemetrexed, and pembrolizumab. She eventually had a complete pathologic response, no evidence of cancer recurrence, and significant improvement of PAH/overall clinical status. After discontinuation of neoplastic therapy, her clinical status worsened, she eventually passed away, and lung biopsy findings revealed evidence of severe pulmonary smooth muscle cell hypertrophy and pulmonary veno‐occlusive disease. This report suggests that combined chemotherapy and immunotherapy may influence the efficacy of PAH therapies and improve clinical status.

Key Clinical Message Endometriosis may contribute to Mullerian adenosarcoma development but makes diagnosis challenging given similar symptoms. Survival benefit has not been definitively shown for chemotherapy, hormonal therapy, or radiotherapy, consolidating surgery as the mainstay treatment. Local excision may be a treatment option for patients with confined tumors wishing to preserve their fertility.

Abstract Fusarium wilt (FW) is the most severe soil‐borne disease of chickpea that causes yield losses up to 100%. To improve FW resistance in JG 11, a high‐yielding variety that became susceptible to FW, we used WR 315 as the donor parent and followed the pedigree breeding method. Based on disease resistance and yield performance, four lines were evaluated in station trials during 2017–2018 and 2018–2019 at Kalaburagi, India. Further, two lines, namely, Kalaburagi chickpea desi 5 (KCD 5) and KCD 11, which possesses the resistance allele for a specific single‐nucleotide polymorphism marker linked with FW resistance, were evaluated across six different locations (Bidar, Kalaburagi, Raichur, Siruguppa, Bhimarayanagudi and Hagari) over a span of 3 years (2020–2021, 2021–2022 and 2022–2023). KCD 11 exhibited notable performance, showcasing yield advantages of 8.67%, 11.26% and 23.88% over JG 11, and the regional checks Super Annigeri 1 (SA 1) and Annigeri 1, respectively, with enhanced FW resistance in wilt sick plot. Further, KCD 11 outperformed JG 11, SA 1 and Annigeri 1 in multi‐location trials conducted across three seasons in the North Eastern Transition Zone, North Eastern Dry Zone, and North Dry Zones of Karnataka. KCD 11 was also tested in trials conducted by All India Coordinated Research Project on chickpea and was also nominated for state varietal trials for its release as a FW‐resistant and high‐yielding variety. The selected line is anticipated to cater the needs of chickpea growers with the dual advantage of yield increment and disease resistance.

Abstract The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as ‘high risk plants, plant products and other objects’. Taking into account the available scientific information, including the technical information provided by the applicant country, this Scientific Opinion covers the plant health risks posed by the following commodities: Sorbus aucuparia bare‐root plants and rooted plants in pots up to 7 years old and specimen trees in pots up to 15 years old imported into the EU from the UK. A list of pests potentially associated with the commodities was compiled. The relevance of any pest was assessed based on evidence following defined criteria. Three EU quarantine pests (Entoleuca mammata and Phytophthora ramorum (non‐EU isolates), Erwinia amylovora), were selected for further evaluation. For two of the selected pests (E. mammata and P. ramorum), the risk mitigation measures implemented in the UK and specified in the technical dossier were evaluated taking into account the possible limiting factors. For these pests, an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The degree of pest freedom varies between the pests evaluated, with P. ramorum being the pest most frequently expected on the imported S. aucuparia plants. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9812 and 10,000 bare‐root S. aucuparia plants per 10,000 will be free from P. ramorum.

Abstract Introduction As access to effective antiretroviral therapy (ART) has improved globally, tobacco‐related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa. Methods In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age‐stratified mortality hazard ratios: 1.2−2.3 (females)/1.1−1.9 (males) for people with current versus never smoking status; and 1.0−1.3 (females)/1.0−1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non‐suppression. In sensitivity analysis, we varied smoking‐associated and HIV‐associated mortality risks. Additionally, we estimated the total life‐years gained if a proportion of all virologically suppressed PWH stopped smoking. Results Forty‐five‐year‐old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life‐years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life‐years. Simulated PWH who continue smoking lose more life‐years from smoking than from HIV (females, 5.3 vs. 3.0 life‐years; males, 3.7 vs. 2.6 life‐years). The impact of smoking and smoking cessation increase as smoking‐associated mortality risks increase and HIV‐associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking‐associated mortality hazard ratio; varying this parameter results in 1.0−5.1 life‐years gained from cessation at age 45y. If 10−25% of virologically suppressed PWH aged 30−59y in South Africa stopped smoking now, 190,000−460,000 life‐years would be gained. Conclusions Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.

Abstract Introduction To achieve epidemic control of infectious diseases, engaging higher‐burden populations with accessible diagnostic services is critical. HIV self‐testing (HIVST) is a promising option. Methods We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self‐reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre‐determined pick‐up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow‐up services. Follow‐up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. Results Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. Conclusions Web‐based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder‐to‐reach populations across India. Assistance from a community‐oriented counsellor proved important to overcome literacy barriers and mistrust in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases.

Abstract We explored the challenges and solutions for managing data within the Whole Health System (WHS), which operates as a Learning Health System and a patient‐centered healthcare approach that combines conventional and complementary approaches. Addressing these challenges is critical for enhancing patient care and improving outcomes within WHS. The proposed solutions include prioritizing interoperability for seamless data exchange, incorporating patient‐centered comparative clinical effectiveness research and real‐world data to personalize treatment plans and validate integrative approaches, and leveraging advanced data analytics tools to incorporate patient‐reported outcomes, objective metrics, robust data platforms. Implementing these measures will enable WHS to fulfill its mission as a holistic and patient‐centered healthcare model, promoting greater collaboration among providers, boosting the well‐being of patients and providers, and improving patient outcomes.

Background Hemoglobin (Hgb) drop without bleeding is common among patients undergoing transcatheter aortic valve replacement; however, the clinical implications of significant Hgb drop have not been fully evaluated. Methods and Results Consecutive patients undergoing transcatheter aortic valve replacement at our institution from 2011 to 2021 were retrospectively reviewed. Three groups were assessed: no Hgb drop and no bleed (NoD‐NoB [reference group]), Hgb drop with bleed, and Hgb drop and no bleed (D‐NoB). Hgb drop was defined as ≥3 g/dL decrease from pre‐ to post‐transcatheter aortic valve replacement. Outcomes of interest were in‐hospital death and 1‐year all‐cause mortality. A total of 1851 cases with complete Hgb data were included: NoD‐NoB: n=1579 (85.3%); D‐NoB: n=49 (2.6%); Hgb drop with bleed: n=223 (12.6%). Compared with NoD‐NoB, the D‐NoB group was older (81.1 versus 78.9 years of age) with higher preprocedure Hgb (12.9 versus 11.7 g/dL). In‐hospital death rate was higher among patients with D‐NoB versus NoD‐NoB (4.5% versus 0.8%, P

Abstract In developing countries such as India, Bengaluru city has experienced extraordinary growth in vehicle traffic on arterial roads, causing intersections to operate over capacity under mixed traffic conditions. The speed on urban streets in central business district areas is lower than 15 kmph during peak hours. One of the main routes connecting the airport to the central business district is also vulnerable to this problem. Therefore, providing an alternative route to divert traffic from the mainstream is critical. This study's main goal is to identify alternate routes from Majestic to the airport using remote sensing and a geographic information system, and then evaluate those alternates using the Fuzzy‐TOPSIS approach. This study has used the GIS Arc software application to select the alternative while taking numerous factors such as time, speed, distance, environmental impact, and economic feasibility into consideration. The video graphic and moving car observer methods have been used for the extraction of data for the inventory of the existing route, while the geo image processing tool has been used to analyze alternative routes in the Bengaluru metropolitan area (BMA). The analysis has shown that the alternative route has a lesser travel time of 2 h 30 min in public transit and 1 h 30 min in private mode. The future scope of the study is to compare the alternative and the most suitable routes to divert traffic. Another public transport route network could be developed to minimize the external incoming vehicles in BMA, particularly to reach the airport on urban roads under heterogeneous traffic conditions.

Abstract A large stretch of the east coast of Australia experienced unprecedented rainfall and flooding over a two‐week period in early 2022. It is difficult to reliably estimate the likelihood of such a rare event from the relatively short observational record, so an alternative is to use data from an ensemble prediction system (e.g., a seasonal or decadal forecast system) to obtain a much larger sample of simulated weather events. This so‐called ‘UNSEEN’ method has been successfully applied in several scientific studies, but those studies typically rely on a single prediction system. In this study, we use data from the Decadal Climate Prediction Project to explore the model uncertainty associated with the UNSEEN method by assessing 10 different hindcast ensembles. Using the 15‐day rainfall total averaged over the river catchments impacted by the 2022 east coast event, we find that the models produce a wide range of likelihood estimates. Even after excluding a number of models that fail basic fidelity tests, estimates of the event return period ranged from 320 to 1814 years. The vast majority of models suggested the event is rarer than a standard extreme value assessment of the observational record (297 years). Such large model uncertainty suggests that multi‐model analysis should become part of the standard UNSEEN procedure.

ABSTRACT Background Previous meta‐analyses have shown mixed results regarding the association between eating disorders (EDs) and type 1 diabetes mellitus (T1DM). Our paper aimed to analyse different EDs and disordered eating behaviours that may be practiced by patients with T1DM. Methods A literature search of PubMed, Scopus and Web of Science was conducted on 17 January 2023, using the key terms “T1DM,” “Eating Disorders” and “Bulimia.” Only observational controlled studies were included. The Revman software (version 5.4) was used for the analysis. Results T1DM was associated with increased risk of ED compared with nondiabetic individuals (RR = 2.47, 95% CI = 1.84–3.32, p‐value

Abstract Ecological research and monitoring need to be able to rapidly convey information that can form the basis of scientifically sound management. Automated sensor systems, especially if combined with artificial intelligence, can contribute to such rapid high‐resolution data retrieval. Here, we explore the prospects of automated methods to generate insights for seabirds, which are often monitored for their high conservation value and for being sentinels for marine ecosystem changes. We have developed a system of video surveillance combined with automated image processing, which we apply to common murres Uria aalge. The system uses a deep learning algorithm for object detection (YOLOv5) that has been trained on annotated images of adult birds, chicks and eggs, and outputs time, location, size and confidence level of all detections, frame‐by‐frame, in the supplied video material. A total of 144 million bird detections were generated from a breeding cliff over three complete breeding seasons (2019–2021). We demonstrate how object detection can be used to accurately monitor breeding phenology and chick growth. Our automated monitoring approach can also identify and quantify rare events that are easily missed in traditional monitoring, such as disturbances from predators. Further, combining automated video analysis with continuous measurements from a temperature logger allows us to study impacts of heat waves on nest attendance in high detail. Our automated system thus produces comparable, and in several cases significantly more detailed, data than those generated from observational field studies. By running in real time on the camera streams, it has the potential to supply researchers and managers with high‐resolution up‐to‐date information on seabird population status. We describe how the system can be modified to fit various types of ecological research and monitoring goals and thereby provide up‐to‐date support for conservation and ecosystem management.

Abstract Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600–mutant kinase approved for patients with BRAF‐mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug–drug interactions when co‐administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P‐gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50‐mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUCinf) and maximum plasma concentration (Cmax) geometric mean for encorafenib increased by 183% and 68.4%, respectively, when co‐administered with posaconazole. Apparent encorafenib clearance decreased from 26.0 to 9.2 L/h when coadministered with posaconazole, and plasma terminal half‐life (t½) of encorafenib increased from 4.3 to 7.3 h. The AUCinf and Cmax geometric mean for encorafenib increased by 83.0% and 44.7%, respectively, when co‐administered with diltiazem. Similarly, the apparent encorafenib clearance decreased from 29.0 to 16.0 L/h when co‐administered with diltiazem, and plasma t½ of encorafenib increased from 6.6 to 7.9 h. There were no deaths, serious adverse events (AEs), or patient discontinuations due to AEs in parts 1 or 2. The most frequently reported treatment‐related AEs were erythema (n = 14; 88%) and headache (n = 11; 69%) in part 1 and headache (n = 7; 44%) in part 2. The results of this study indicate that co‐administration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

Abstract Aims Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex‐specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR). Methods and results Sex‐specific uncorrelated genome‐wide significant (P

Abstract The European Commission requested the EFSA Panel on Plant Health to evaluate the probability of entry of pests (likelihood of pest freedom at entry), including both regulated and non‐regulated pests, associated with unrooted cuttings of the genera Petunia and Calibrachoa produced under physical isolation in Kenya. The relevance of any pest for this opinion was based on evidence following defined criteria, based on the methodology used for High‐Risk Plants adapted for the specificity of this assessment. Fourteen EU‐regulated pests (Bemisia tabaci, cowpea mild mottle virus, Liriomyza huidobrensis, Liriomyza sativae, Liriomyza trifolii, potato leafroll virus, potato spindle tuber viroid, Ralstonia pseudosolanacearum, R. solanacearum, Scirtothrips dorsalis, tomato mild mottle virus, tomato spotted wilt virus, tomato yellow leaf curl virus and Xanthomonas vesicatoria) and six EU non‐regulated pests (Aleurodicus dispersus, pepper veinal mottle virus, Nipaecoccus viridis, Phenacoccus solenopsis, Tetranychus neocaledonicus and tomato yellow ring virus) fulfilled all relevant criteria and were selected for further evaluation. For these pests, the risk mitigation measures proposed in the technical dossier from Kenya were evaluated, taking into account the possible limiting factors. Additionally, an expert judgement is given on the likelihood of pest freedom, taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The estimated degree of pest freedom varies among the pests evaluated, with T. neocaledonicus being the pest most frequently expected on the imported cuttings. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9942 and 10,000 bags containing unrooted cuttings of Petunia spp. and Calibrachoa spp. per 10,000 would be free of T. neocaledonicus.

Abstract Objectives Although countries like Japan and South Korea have implemented nationwide endoscopic screening programs, there is limited evidence on the effectiveness of endoscopy for diagnosing early gastric cancer (EGC) in developing countries such as India. In the present study, we aimed to determine the feasibility of endoscopic detection of EGC from India. Methods The data was prospectively collected for all patients ≥40 years who underwent a diagnostic upper endoscopy from April to September 2021. A single endoscopist who performed the endoscopic procedures completed 1‐month training in advanced endoscopy in Japan. Following the training, the endoscopist continued to engage in internet‐based discussions regarding his cases encountered. Prior to this training, the endoscopist had not detected any EGC cases during his 12‐year gastroenterology practice. Results A total of 1033 patients were included in the study, with males accounting for 65.4% and a mean age 52 years. The average procedural time was 7.13 ± 4.8 min. A total of 25 patients (2.4%) were found to have GC, including 6 patients (0.6%) with EGC. Two patients had synchronous EGC lesions. All EGC patients were males, with an average age of 66 years. All EGCs were detected in the distal stomach in the presence of Helicobacter pylori infection and severe atrophic gastritis. Conclusion Our findings showed that the endoscopic detection of EGC is feasible in India. Optimal training on endoscopic diagnosis of EGC can improve the detection of such lesion. Further studies are warranted to assess the optimization and implementation of an endoscopic screening program for EGC in India.

Abstract Background Parkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics. Methodology A thorough examination was performed utilizing the PubMed, Medline, Scopus, and Web of Science databases. The search utilized specific keywords like “Parkinson's disease,” “Parkinson's plus syndrome,” “Lewy body dementia,” “Alzheimer's dementia,” “progressive supranuclear palsy,” and “multiple system atrophy.” The selection criteria were aimed at English‐language literature, with a particular focus on examining the connection between PD and associated disorders or dementias. Results and Discussion Parkinson's plus syndromes, such as PSP, MSA, CBD, and VaP, exhibit unique clinical characteristics, imaging results, and diverse reactions to levodopa. This makes it difficult to distinguish them from PD. LBD is characterized by Lewy bodies containing α‐synuclein, which leads to both motor and cognitive deficits. PD and Alzheimer's disease (AD) exhibit a complex interaction, including common pathogenic processes, genetic predispositions, and clinical characteristics of dementia. Conclusion The interrelatedness of PD, Parkinson's plus syndromes, LBD, and AD highlights the significance of comprehending shared disease‐causing processes. Aberrant protein clumping, impaired functioning of mitochondria, increased oxidative stress, and inflammation in the brain are common factors which can be addressed for specific treatments. More research is essential for understanding complicated connections and developing effective therapies for these sophisticated neurological illnesses.

Abstract Background Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti‐centromere antibodies, and anti‐topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Abstract Colorectal cancer (CRC) ranks as the third leading cause of cancer‐related deaths in the United States (U.S.). Our study aims to analyze CRC mortality patterns in the U.S., focusing on gender and age groups from 1999 to 2022. We analyzed Age‐Adjusted Mortality Rates (AAMRs) for CRC‐related deaths using the CDC Wide‐ranging Online Data for Epidemiologic Research (CDC WONDER) database and assessed differences between age and sex. CRC‐related mortality decreased significantly from 1999 to 2011 (−2.81% APC) and from 2011 to 2020 (−1.95% APC) but a not significant uptrend from 2020 to 2022 (2% APC). Males experienced a more significant decrease. Among age groups, crude mortality decreased until 2020, except in age group 45–54, which showed an annual increase in mortality of 0.9% from 2004 to 2022. Furthermore, individuals aged 75–84 and 85+ saw a nonsignificant annual increase of 1.8% and 4.5% from 2020 to 2022, respectively. Our study highlights a significant decline in age and gender‐specific CRC‐related mortality from 1999 to 2020. However, the worrisome uptrend observed in the younger age group of 45–54 emphasizes the importance of implementing targeted public health measures and evidence‐based interventions.

Abstract The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as ‘high risk plants, plant products and other objects’. Taking into account the available scientific information, including the technical information provided by the applicant country, this Scientific Opinion covers the plant health risks posed by the following commodities: Cornus alba and Cornus sanguinea bare‐root plants and rooted plants in pots up to 7 years old imported into the EU from the UK. A list of pests potentially associated with the commodities was compiled. The relevance of any pest was assessed based on evidence following defined criteria. Four EU quarantine pests (Meloidogyne fallax, Phytophthora ramorum (non‐EU isolates), tobacco ringspot virus, and tomato ringspot virus) and one EU non‐regulated pest (Discula destructiva), were selected for further evaluation. For the selected pests, the risk mitigation measures implemented in the technical dossier from the UK were evaluated taking into account the possible limiting factors. For these pests, an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The degree of pest freedom varies among the pests evaluated, with P. ramorum being the pest most frequently expected on the imported C. alba and C. sanguinea plants. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9823 and 10,000 bare‐root C. alba and C. sanguinea plants per 10,000 will be free from P. ramorum.

Abstract The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies.

Abstract Despite the attractive properties of tetrafluorosulfanyl (SF4) compounds in drug discovery, medicinal research on SF4 molecules is hindered by the scarcity of suitable synthetic methodologies. Drawing inspiration from the well‐established Sonogashira cross‐coupling of terminal alkynes under Pd‐catalysis, it is envisioned that SF4‐alkynes can serve as effective coupling partners. To overcome the challenges associated with the electron‐deficient nature of SF4‐alkynes and the lability of the SF4 unit under transition‐metal catalysis, an aryl radical mediated Csp–Csp3 cross‐coupling reaction is successfully developed under Cu catalysis. This methodology facilitates the coupling of SF4‐alkynes with alkyl iodides, leading to the immediate synthesis of SF4‐attached drug‐like molecules. These findings highlight the potential impact of SF4‐containing molecules in the drug industry, paving the way for further research in this emerging field.

Abstract Background The application of high throughput technologies has enabled unravelling of unique differences between healthy mares and mares with endometritis at transcriptomic and proteomic levels. However, differences in the uterine microbiome are yet to be investigated. Objectives The present study was aimed at evaluating the differences in uterine microbiome between healthy mares and mares with endometritis. Methods Low‐volume lavage (LVL) samples were collected from the uterus of 30 mares classified into healthy (n = 15) and endometritis (n = 15) based on their reproductive history, intrauterine fluid accumulation, gross appearance of LVL samples, endometrial cytology and bacterial culture. The samples were subjected to 16S rRNA sequencing. Results Notable differences in the uterine microbiome were observed between healthy mares and mares with endometritis at various taxonomic levels. In healthy mares, the most abundant phylum, class, order and family were Firmicutes, Bacilli, Bacillales and Paenibacillaceae, respectively. In contrast, the most abundant corresponding taxonomic levels in mares with endometritis were Proteobacteria, Gammaproteobacteria, Enterobacterales and Enterobacteriaceae, respectively. At the genus level, Brevibacillus and Paenibacillus were more abundant in healthy mares, whereas Escherichia, Salmonella and Klebsiella were more abundant in mares with endometritis. In healthy mares, Brevibacillus brevis was the most abundant species, followed by Brevibacillus choshinensis and Paenibacillus sp JDR‐2. However, in mares with endometritis, Escherichia coli was the most abundant species, followed by Salmonella enterica and Klebsiella pneumoniae. Conclusions These results confirmed the previously reported presence of a uterine microbiome in healthy mares and helped unravel some alterations that occur in mares with endometritis. The findings can potentially help formulate new approaches to prevent or treat equine endometritis.

Abstract Background and Aim Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping dyspepsia, but data regarding this is lacking. Methods This single‐center, prospective study evaluated the efficacy and safety of 6‐week treatment with fixed‐drug combination (FDC) of pantoprazole (PPI) and itopride (prokinetic) in 50 patients with ≥3 month history of GERD and overlapping dyspepsia refractory to pantoprazole. Efficacy was assessed as reduction in GERD symptom assessment scale (GSAS) distress score for 15 symptoms from baseline to week 6. Adverse events (AEs) were monitored up to week 6. Results Although heartburn was the most common symptom at week 6 (26.8%), its frequency significantly decreased from baseline (84.0%; P

Background The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right‐sided obstructive lesions. We have shown that capillary rarefaction occurs early in the pressure‐loaded RV. Here we test the hypothesis that microRNA (miR)‐34a, which is induced in RV hypertrophy and RV failure (RVF), blocks the hypoxia‐inducible factor‐1α‐vascular endothelial growth factor (VEGF) axis, leading to the attenuated angiogenic response and increased susceptibility to RV failure. Methods and Results Mice underwent pulmonary artery banding to induce RV hypertrophy and RVF. Capillary rarefaction occurred immediately. Although hypoxia‐inducible factor‐1α expression increased (0.12±0.01 versus 0.22±0.03, P=0.05), VEGF expression decreased (0.61±0.03 versus 0.22±0.05, P=0.01). miR‐34a expression was most upregulated in fibroblasts (4‐fold), but also in cardiomyocytes and endothelial cells (2‐fold). Overexpression of miR‐34a in endothelial cells increased cell senescence (10±3% versus 22±2%, P

Abstract The current study presents research investigations and developments related to the homogeneous charge compression ignition (HCCI) engine. Research investigations and recent advances, including the role of various operating conditions on HCCI engine combustion phenomena, emissions, and performance, are discussed. There is growing research interest in investigating HCCI engines with diesel fuel to study combustion, emissions, and performance characteristics due to their association with low NOx emissions. In the published literature, research investigations are also conducted with different fuels ranging from biomass to diesel to gasoline in the HCCI engine showing its capability for utilizing various fuels in coming years. The challenges associated with HCCI combustion are reviewed, and the details of excessive carbon monoxide and unburnt hydrocarbon emissions are discussed. The major parameters affecting the hydrogen addition in HCCI diesel engines are also discussed. Overall, adding hydrogen to a diesel‐fueled HCCI engine improves combustion phasing and can potentially increase thermal efficiency while lowering emissions. In addition, the strength, weaknesses, opportunities, and threat analysis is provided and discussed thoroughly.

Abstract Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial‐killing effects is one of the strategies to combat antibiotic tolerance. In this study, we discovered a coumarin–chalcone conjugate C9, which can inhibit the biofilm formation of three common pathogens that cause nosocomial infections, namely, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, with the best antibiofilm activity against P. aeruginosa. Further investigations indicate that C9 decreases the synthesis of the key biofilm matrix exopolysaccharide Psl and bacterial second messenger cyclic‐di‐GMP. Meanwhile, C9 can interfere with the regulation of the quorum sensing (QS) system to reduce the virulence of P. aeruginosa. C9 treatment enhances the sensitivity of biofilm to several antibiotics and reduces the survival rate of P. aeruginosa under starvation or oxidative stress conditions, indicating its excellent potential for use as an antibiofilm‐forming and anti‐QS drug.

Abstract Background Mutations in kinases are the most frequent genetic alterations in cancer; however, experimental evidence establishing their cancerous nature is available only for a small fraction of these mutants. Aims Predicition analysis of kinome mutations is the primary aim of this study. Further objective is to compare the performance of various softwares in pathogenicity prediction of kinase mutations. Materials and methods We employed a set of computational tools to predict the pathogenicity of over forty‐two thousand mutations and deposited the kinase‐wise data in Mendeley database (Estimated Pathogenicity of Kinase Mutants [EPKiMu]). Results Mutations are more likely to be drivers when being present in the kinase domain (vs. non‐kinase domain) and belonging to hotspot residues (vs. non‐hotspot residues). We identified that, while predictive tools have low specificity in general, PolyPhen‐2 had the best accuracy. Further efforts to combine all four tools by consensus, voting, or other simple methods did not significantly improve accuracy. Discussion The study provides a large dataset of kinase mutations along with their predicted pathogenicity that can be used as a training set for future studies. Furthermore, a comparative sensitivity and selectivity of commonly used computational tools is presented. Conclusion Primary‐structure‐based in silico tools identified more cancerous/deleterious mutations in the kinase domains and at the hot spot residues while having higher sensitivity than specificity in detecting deleterious mutations.

Abstract Objective Patients with advanced laryngeal cancer are typically presented with divergent treatment options, namely chemoradiation versus total laryngectomy. This study aims to understand general perspectives of the factors involved in this decision‐making process. Methods Surveys were constructed using specialized conjoint analysis software. Seven attributes integral to the decision‐making process for advanced laryngeal cancer treatment were included. Results Three hundred one healthy adult volunteers completed the decision‐making program. The relative impact of each treatment attribute on decision making across all participants was scored with an average importance score (standard deviation) as follows: Lifespan 22.2% (±8.5), Voicing 21.4% (±5.9), Swallowing 19.1% (±7.3), Cancer Cure 14.9% (±6.2), Mode of Breathing 11.0% (±3.7), Self‐Image 6.7% (±2.9), and Treatment Type 4.8% (±3.0). Conclusions General public opinion ranked lifespan, voicing, and swallowing aspects as similarly important, and all were ranked more important than probability of cure. These data demonstrate a variety of priorities among participants and the need for tailored discussions when determining treatment choice for advanced laryngeal cancer. Level of Evidence Level 4.

Abstract Direct torque control (DTC) is one of the most prominent control techniques used by permanent magnet synchronous motor (PMSM) drives in industry applications. Nevertheless, the presence of hysteresis controllers and inaccurate voltage switching table in traditional DTC results in higher torque and flux ripple. This study proposes an enhanced DTC functioned Surface‐mounted PMSM (S‐PMSM) drive with mitigation of torque and flux ripple. The operation relies on generating the reference voltage vector (VV) in a stationary reference frame, which supports control of torque and flux without hysteresis controllers. The reference VV generation is simple and does not affect control robustness. The position of reference VV in a sector is used to build the voltage vector (VV) switching table. As a result, the application of nearest discrete VV to reference VV produces optimal torque and flux control. Moreover, redundant switching combinations of null VV are effectively used for possible minimization of switching frequency of two‐level voltage source inverter (VSI) supplied S‐PMSM drive. Therefore, proposed DTC gains improved S‐PMSM drive response along with switching frequency reduction. In dSPACE‐RTI 1104 platform, experimental response of S‐PMSM drive under various operating conditions have been depicted to highlight the proficiency of proposed DTC in comparison with existing DTC.

We have recently shown that IFNγ, produced during cancer therapy, induces expression of the Bcl3 proto‐oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation, migration, and invasion, but the mechanisms are unknown. Here, we demonstrate that the IFNγ‐induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFκB. Furthermore, the IFNγ‐induced Bcl3 expression is associated with an increased occupancy of Ser‐727 phosphorylated STAT1 and acetylated histone H3 at the Bcl3 promoter. Our data indicate that Bcl3 promotes expression of the pro‐inflammatory chemokine interleukin‐8 (IL‐8) in OC cells. These findings identify Bcl3 as a novel target of IFNγ/JAK1/STAT1 signaling and suggest that targeting the JAK1/STAT1 pathway may suppress IFNγ‐induced Bcl3 expression in OC.

Abstract Background While the incidence of cholangiocarcinoma is rising, little is known about young‐onset disease. We compared clinical characteristics and outcomes between patients with young‐onset cholangiocarcinoma, diagnosed between the ages of 18 and

Momordica charantia is well known for its medicinal properties. It has exhibited various pharmacological activities, such as antidiabetic, anti-inflammatory, and antimicrobial activities. Although this plant is used worldwide as a vegetable and medicinal ingredient in herbal medicines, its toxicity studies have not been conducted to date. This study attempts to understand its toxicity. The present study examined the activity of two enzymes, acetylcholinesterase and succinate dehydrogenase, as well as histopathological variations in the liver, intestine, and gills of zebrafish. The results of the acetylcholinesterase assay showed that the concentrations of 40 mg/L and 60 mg/L of the four extracts (leaf and fruit extracts of both varieties) exhibited increased enzyme activity. Interestingly, the leaves of the green fruit variety at a concentration of 60 mg/L showed the highest activity, with a value of 2.824 ± 0.0682 micromoles/min compared to the control value of 1.8347 ± 0.0046 micromoles/min. On the other hand, the succinate dehydrogenase assay revealed that the concentrations of 40 mg/L and 60 mg/L of the extracts decreased the enzyme activity. The highest inhibition was observed in the concentration of 60 mg/L of the leaves of the white-fruited variety and the green-fruited variety, with values of 1.884 ± 0.0482 micromoles/min compared to the control value of 2.747 ± 0.0046 micromoles/min. The studies on histopathological changes also demonstrated abnormalities in the brain, liver, intestine, and gills of zebrafish after the exposure to the extracts of M. charantia. The severity of the damage varied from low to high concentraions. In general, this study sheds light on the safety profile of Momordica charantia and highlights its potential toxicity in animal models. The findings suggest that more research is needed to fully understand the toxicity of this plant and its implications for human use.