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Background: Dolutegravir (DTG) is part of a first-line antiretroviral therapy (ART) for HIV management in drug-naïve individuals and is recommended for the treatment of HIV during pregnancy. Robust analytical tools to quantify DTG are necessary to support clinical trials that characterize its multi-compartment drug distribution. Methods: Potassium EDTA (K2EDTA) plasma or whole breast milk was spiked with DTG and an isotopically labeled internal standard. Samples were prepared via protein precipitation prior to LC–MS/MS analysis. The assays were validated in accordance with regulatory recommendations. Results: Analytical measuring ranges for DTG quantitation in plasma and breast milk were 100–10,000 ng/mL and 0.500 to 1000 ng/mL, respectively. Inter-assay precision and accuracy were 2.73 % to 3.41 % and −10.6 % to −5.37 % for plasma, and 4.24 % to 12.4 % and −5.63 % to 7.49 % for breast milk, respectively. DTG was stable for three freeze–thaw cycles and for at least 72 h at room temperature in matrix (plasma or breast milk). Additionally, whole blood was stable for 24 h at room temperature and 2 h under conditions of extended heat and humidity. Matrix effects for DTG in plasma and breast milk ranged from 101 % to 108 % and 78.2 % to 99.3 %, respectively. Quantitation in remnant plasma samples yielded measurable concentrations within the primary linearity of the assay. Conclusions: Methods to quantify DTG in human plasma and breast milk have been developed and validated. These assays were designed to satisfy all criteria for implementation in clinical and clinical trial settings.

Abstract The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, represent alternative therapeutics with clear advantages such as affinity and target selectivity. Here, we describe the nanobody NbE, which selectively binds to the μOR and acts as an antagonist. We functionally characterize NbE as an extracellular and genetically encoded μOR ligand and uncover the molecular basis for μOR antagonism by determining the cryo-EM structure of the NbE-μOR complex. NbE displays a unique ligand binding mode and achieves μOR selectivity by interactions with the orthosteric pocket and extracellular receptor loops. Based on a β-hairpin loop formed by NbE that deeply protrudes into the μOR, we design linear and cyclic peptide analogs that recapitulate NbE’s antagonism. The work illustrates the potential of nanobodies to uniquely engage with GPCRs and describes lower molecular weight μOR ligands that can serve as a basis for therapeutic developments.

Abstract Background & aims Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. Methods A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. Results Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. Conclusion The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Schwannomatosis is a rare neurocutaneous syndrome characterized by the presence of multiple schwannomas along the peripheral nerves, distinctly excluding the vestibular nerves. It is recognized as the third principal form of neurofibromatosis, alongside neurofibromatosis types 1 and 2. In this report, we discuss the case of a 45-year-old woman who initially sought medical attention for low back pain and swelling in her left axilla. Her magnetic resonance imaging revealed multiple enhancing intradural extramedullary lesions, along with a mass in the right upper thoracic region and another in the left axilla, raising suspicions of metastasis. However, a comprehensive analysis that aligned imaging results with histopathological findings confirmed the diagnosis of schwannomatosis. This case highlights the importance of differentiating between various conditions that can cause multiple intradural extramedullary masses, such as nerve sheath tumors, meningiomas, and metastasis. The presence of multiple schwannomas suggests a diagnosis of either neurofibromatosis type 2 or schwannomatosis, making the distinction between these two conditions critical for appropriate management.

Methane is a powerful greenhouse gas with a 25 times higher 100-year warming potential than carbon dioxide and is a target for mitigation to achieve climate goals. To control and curb methane emissions, estimates are required from the sources and sectors which are typically generated using bottom-up methods. However, recent studies have shown that national and international bottom-up approaches can significantly underestimate emissions. In this study, we present three bottom-up approaches used to estimate methane emissions from all emission sectors in the Denver-Julesburg basin, CO, USA. Our data show emissions generated from all three methods are lower than historic measurements. A Tier 1/2 approach using IPCC emission factors estimated 2022 methane emissions of 358 Gg (0.8% of produced methane lost by the energy sector), while a Tier 3 EPA-based approach estimated emissions of 269 Gg (0.2%). Using emission factors informed by contemporary and region-specific measurement studies, emissions of 212 Gg (0.2%) were calculated. The largest difference in emissions estimates were a result of using the Mechanistic Air Emissions Simulator (MAES) for the production and transport of oil and gas in the DJ basin. The MAES accounts for changes to regulatory practice in the DJ basin, which include comprehensive requirements for compressors, pneumatics, equipment leaks, and fugitive emissions, which were implemented to reduce emissions starting in 2014. The measurement revealed that normalized gas loss is predicted to have been reduced by a factor of 20 when compared to 10-year-old normalization loss measurements and a factor of 10 less than a nearby oil and production area (Delaware basin, TX); however, we suggest that more measurements should be made to ensure that the long-tail emission distribution has been captured by the modeling. This study suggests that regulations implemented by the Colorado Department of Public Health and Environment could have reduced emissions by a factor of 20, but contemporary regional measurements should be made to ensure these bottom-up calculations are realistic.

Abstract Wildfire disturbance propagation along fluvial networks remains poorly understood. We use incident, atmospheric, and water-quality data from the largest wildfire in New Mexico’s history to quantify how this gigafire affected surface runoff processes and mobilized wildfire disturbances into fluvial networks after burning 1382 km2. Surface runoff post-fire increased compared to pre-fire conditions, and precipitation events that are frequently observed in the affected watershed (160 km downstream of the burn perimeter. Our findings emphasize the need to incorporate spatially resolved longitudinal sampling designs into wildfire water quality research and highlight the spatiotemporal co-dependency among atmospheric, terrestrial, and aquatic processes in defining the net outcome of wildfire disturbance propagation along impacted fluvial networks.

Abstract Achieving fast gates and long coherence times for superconducting qubits presents challenges, typically requiring either a stronger coupling of the drive line or an excessively strong microwave signal to the qubit. To address this, we introduce on-chip filters of the qubit drive exhibiting a stopband at the qubit frequency, thus enabling long coherence times and strong coupling at the subharmonic frequency, facilitating fast single-qubit gates, and reduced thermal load. The filters exhibit an extrinsic relaxation time of a few seconds while enabling sub-10-ns gates with subharmonic control. Here we show up to 200-fold improvement in the measured relaxation time at the stopband. Furthermore, we implement subharmonic driving of Rabi oscillations with a π pulse duration of 12 ns. Our demonstration of on-chip filters and efficient subharmonic driving in a two-dimensional quantum processor paves the way for a scalable qubit architecture with reduced thermal load and noise from the control line.

Abstract Achieving fast and precise initialization of qubits is a critical requirement for the successful operation of quantum computers. The combination of engineered environments with all-microwave techniques has recently emerged as a promising approach for the reset of superconducting quantum devices. In this work, we experimentally demonstrate the utilization of a single-junction quantum-circuit refrigerator (QCR) for an expeditious removal of several excitations from a transmon qubit. The QCR is indirectly coupled to the transmon through a resonator in the dispersive regime, constituting a carefully engineered environmental spectrum for the transmon. Using single-shot readout, we observe excitation stabilization times down to roughly 500 ns, a 20-fold speedup with QCR and a simultaneous two-tone drive addressing the e–f and f0–g1 transitions of the system. Our results are obtained at a 48-mK fridge temperature and without postselection, fully capturing the advantage of the protocol for the short-time dynamics and the drive-induced detrimental asymptotic behavior in the presence of relatively hot other baths of the transmon. We validate our results with a detailed Liouvillian model truncated up to the three-excitation subspace, from which we estimate the performance of the protocol in optimized scenarios, such as cold transmon baths and fine-tuned driving frequencies. These results pave the way for optimized reset of quantum-electric devices using engineered environments and for dissipation-engineered state preparation.

Background The flexor hallucis longus (FHL) muscle is crucial in fine motor control of the great toe but the muscle is often sacrificed in free fibula flap (FFF) reconstruction. The aim of this study was to compare great toe movement between complete and partial FHL resection during FFF harvest to see if FHL can be left behind (without undergoing fibrosis) in situ when bulk is not required at the recipient site.

ABSTRACT Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial–viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1β, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial–viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1β, IL7, IP10, MIP1α, MIP1β, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein–protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial–viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs.IMPORTANCEAccurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Abstract Background Treatment of keloids and hypertrophic scars is challenging. The current first‐line treatment is a steroid which has high resistance and recurrence rate along with unacceptable adverse effects. Different studies involving the combination of TAC and 5‐FU that have been done so far showed better treatment outcomes in terms of efficacy and safety. Objective The objective of this study was to compare the efficacy and safety of intralesional triamcinolone acetonide alone and its combination with 5‐fluorouracil in patients with keloids and hypertrophic scars at 12 weeks follow‐up. Methods In this randomized parallel group double‐blinded clinical trial, we enroled 66 cases of keloids and hypertrophic scars randomly allocated into two treatment groups. Patients received an intralesional injection of triamcinolone acetonide (20 mg/mL) in Group A and an intralesional injection of a combination of triamcinolone acetonide (20 mg/mL) and 5‐fluorouracil (25 mg/mL) in Group B for every 2 weeks until 10 weeks and the final evaluation was done at 12 weeks follow‐up. Results There was a reduction in all the parameters at every follow‐up visit in both groups. The ≥50% reduction in height, reduction in the VSS and POSAS scores, and good to excellent subjective improvement reported by both the patients and the observer were significantly greater in the combination group compared to TAC alone group. The response rate was faster and complications were lesser in the combination group as compared to TAC alone group. Limitation Single‐centred, no long‐term follow‐up, and recurrence could not be assessed. Conclusion TAC alone and its combination with the 5‐FU both were effective in keloids and hypertrophic scars. Yet, the TAC and 5‐FU combination treatment was more efficacious with a faster response rate and safer than the TAC alone treatment.

Background: Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. Objectives: The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). Design: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. Data sources and methods: We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. Results: (a) ROS production : Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation : Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance : Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. Conclusion: Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

To evaluate the extent to which pharmacies in Hetauda Sub-metropolitan City, Nepal adhere to the recommended practices outlined in the good pharmacy practice guidelines formulated by International Pharmaceutical Federation and draft developed by Nepal Pharmacy Council. Good Pharmacy Practice evaluates the safety, effectiveness, availability, and accessibility of medicines, ensuring their correct usage which is essential component of community pharmacies. Data was collected by visiting community pharmacies throughout Hetauda sub-metropolitan city. The questionnaire includes 38 questions under 9 sections: premises, personnel, quality policy, services, documentation, procurement, storage, prescription handling, and dispensing. Frequencies and percentages were used to represent all categorical variables, while mean ± standard deviation (SD) was used to represent continuous variables. To determine relationships between categorical data, the Pearson Chi-square test (χ²) was utilized with a significance level set at P

Objective To describe antibiotic prescription patterns in the emergency department (ED) of a tertiary healthcare center in Nepal. Methods This was a descriptive cross-sectional study of hospital records of patients who visited the ED. Results Of the 758 ED patients included in the study, 384 (50.6%) received a total of 536 antibiotic prescriptions. Common indications for antibiotic prescriptions included respiratory infection (37.5%), gastrointestinal infection (19.3%), urinary infection (10.4%), and prophylaxis (29.9%). Antibiotics listed as essential in the National List of Essential Medicines (NLEM) and generic formulations were used in 77.1% and 61.9% of the antibiotic prescriptions, respectively. Injectable antibiotics were prescribed to 54.9% of the 384 patients. Frequently prescribed antibiotics included ceftriaxone (34.1%), metronidazole (18.5%), amoxicillin + clavulanic acid (15.9%), and cefixime (14.3%). Bacterial culture testing was performed in 15.1% of the patients who received antibiotics. Conclusions This study showed that overuse of antibiotics, prescription of branded antibiotics, prescription of antibiotics not listed in the NLEM, prophylactic use of antibiotics, and empirical treatment of suspected infections without isolation of pathogens were all prevalent. We recommend more research to determine the causes underlying these practices and develop interventions to limit such practices.

Abstract Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).

Abstract Superconducting quantum circuits are a natural platform for quantum simulations of a wide variety of important lattice models describing topological phenomena, spanning condensed matter and high-energy physics. One such model is the bosonic analog of the well-known fermionic Kitaev chain, a 1D tight-binding model with both nearest-neighbor hopping and pairing terms. Despite being fully Hermitian, the bosonic Kitaev chain exhibits a number of striking features associated with non-Hermitian systems, including chiral transport and a dramatic sensitivity to boundary conditions known as the non-Hermitian skin effect. Here, using a multimode superconducting parametric cavity, we implement the bosonic Kitaev chain in synthetic dimensions. The lattice sites are mapped to frequency modes of the cavity, and the in situ tunable complex hopping and pairing terms are created by parametric pumping at the mode-difference and mode-sum frequencies, respectively. We experimentally demonstrate important precursors of nontrivial topology and the non-Hermitian skin effect in the bosonic Kitaev chain, including chiral transport, quadrature wavefunction localization, and sensitivity to boundary conditions. Our experiment is an important first step towards exploring genuine many-body non-Hermitian quantum dynamics.

Background: There is scarce knowledge on the use of structured positive psychology interventions for reducing work-stress and improving wellbeing of rural community health workers in India, particularly the Accredited Social Health Activists (ASHAs) who are village-level (resident women, incentivised) lay health workers. This trial will test the effectiveness of a ‘character-strengths’ based coaching intervention compared to routine supervision on wellbeing (‘authentic happiness’) of ASHAs. Methods: This protocol is for a single-blind, parallel group randomized controlled trial comparing the effectiveness of a five-day residential workshop focusing on the use of character-strengths and subsequent 8- to 10-week remote telephonic coaching (weekly) to individually support ASHAs to improve their wellbeing, against routine health system support. The arms are intervention added to routine ASHA supervision (weekly, by the ASHA supervisor), and routine supervision alone (control arm). The target sample comprises 330 rural ASHAs in Madhya Pradesh, India. The primary outcome of mean Authentic Happiness Inventory (AHI) scores will be compared between arms at 3-month follow-up. Secondary outcomes will include an assessment of ASHA's self-reported affect, self-efficacy, flourishing, burnout, motivation, physical health symptoms, quality of life, and routine work performance indicators, and the consequent patient-level outcomes [e.g., service satisfaction and depression remission rates after receiving brief psychological treatment by trained ASHAs]. We will also evaluate the costs of developing and delivering the intervention. Discussion: This trial will determine whether a character-strengths based coaching intervention is an effective and scalable approach for reducing work-stress and improving wellbeing of rural ASHAs in low-resource settings.

Foeniculum vulgare Mill. commonly known as fennel, is a globally recognized aromatic medicinal plant and culinary herb with widespread popularity due to its antimicrobial, antioxidant, carminative, and diuretic properties, among others. Although the phenotypic effects of salinity stress have been previously explored in fennel, the molecular mechanisms underlying responses to elevated salinity in this plant remain elusive. MicroRNAs (miRNAs) are tiny, endogenous, and extensively conserved non-coding RNAs (ncRNAs) typically ranging from 20 to 24 nucleotides (nt) in length that play a major role in a myriad of biological functions. In fact, a number of miRNAs have been extensively associated with responses to abiotic stress in plants. Consequently, employing computational methodologies and rigorous filtering criteria, 40 putative miRNAs belonging to 25 different families were characterized from fennel in this study. Subsequently, employing the psRNATarget tool, a total of 67 different candidate target transcripts for the characterized fennel miRNAs were predicted. Additionally, the expression patterns of six selected fennel miRNAs (i.e. fvu-miR156a, fvu-miR162a-3p, fvu-miR166a-3p, fvu-miR167a-5p, fvu-miR171a-3p, and fvu-miR408-3p) were analyzed under salinity stress conditions via qPCR. This article holds notable significance as it identifies not only 40 putative miRNAs in fennel, a non-model plant, but also pioneers the analysis of their expression under salinity stress conditions.

AbstractA study was conducted from February 2021 to May 2021 to assess the incidence and severity of major diseases of Mandarin and the management practices adopted by mandarin growers in Syangja, Nepal. Data were collected from a total of 90 mandarin-growing farmers and 25 orchards, comprising 10 from Putalibazar, 8 from Bhirkot, and 7 from Waling municipalities. Descriptive statistics such as percentage, mean, standard deviation, and range, as well as inferential statistics like the chi-square test and independent sample t-test, were employed alongside analytical tools like binary logistic regression to analyze the data. The findings revealed the highest incidences of citrus greening (27%) and foot rot (36%) in Putalibazar Municipality and sooty mold (63.75%) in Bhirkot Municipality, whereas the most pronounced severity of citrus greening and sooty mold was observed in Waling Municipality. Training, pruning, and the use of Bordeaux mixture were the major practices adopted by farmers for the management of citrus greening and sooty mold, respectively, whereas for the management of foot rot, both Bordeaux mixture and cow’s urine were used. A significant mean difference was found in average production per plant, nursery height, and marketed yield between trained and non-trained farmers. Factors such as mandarin cultivated area, farming experience, and access to technical assistance were found to influence management practices, including the application of Bordeaux mixture, the use of Jhol-mol, neem-based pesticides, and insect traps. Besides, the findings also indicate the need for targeted training programs and technical support for growers, emphasizing disease-specific management strategies.

Background: Severe asthma pathology encompasses a wide range of pulmonary and extrapulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health-related quality-of-life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. Objective: We sought to examine the impact of pulmonary and extrapulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centers. Methods: Patients’ characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. Results: Patients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extrapulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms, and requirement for maintenance oral corticosteroids were observed. Conclusions: Both pulmonary and extrapulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasizing the importance of early identification and management of severe asthma before comorbidities develop.

An interview-based questionnaire survey was done in 2021 to assess the socio-economic conditions, farming practices adopted, and problems faced by fish farmers and to analyze the cost and benefits of fish farming in the Fish super zone area of Pachrauta Municipality, Bara district. A simple random sampling technique was used to select 60 respondents for the study and the information collected was analyzed and processed by MS-Excel and SPSS. The majority of respondents were male, belonged to the age group of 25–36 years, and had a secondary level of school education. The mean total land holding size was found to be 3.65 ± 2.57 bigha with a total pond area of 1.38 ± 1.08 bigha and a small minority (18 %) practiced contract farming. Most of the farmers were found to have experience of 6–11 years (40 %). The farming system was polyculture and mostly Intensive (60 %). While the use of modern equipment was low (25 %), the majority of farmers (>90 %) practiced regular drying and liming of ponds. Mid-April to Mid-July was the most preferred time of stocking and the big fraction of feed used was locally prepared (70 %). Fertilizer use and Multiple harvesting were also common. Fish farming in the study area was found to fetch an average annual income of 0.95 million NRs. The major problems faced by farmers were Expensive feed (0.67), Lack of quality seeds (0.60), and Lack of proper marketing channels (0.55). Despite the constraints, Economic analysis revealed fish production in the study area as a profitable business with a BC ratio of 2.20 and a high gross margin value (Rs. 1330341.6 per hectare).

Introduction: Measurement of Maximal Static Respiratory Pressures (MSRP) is a non invasive tool to determine global respiratory muscle strength. The unique lifestyle factors in the Himalayan region, prompted the need for establishing normative values. Aim: To establish the typical maximum respiratory pressures in the Himalayan region and, secondarily, to develop a predictive equation based on the normative data collected. Materials and Methods: A cross-sectional observational study was conducted at the Department of Respiratory Medicine, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India. A total of 101 non smokers (78 males, 23 females) aged from 19-70 years were selected after initial screening by a questionnaire and spirometry from the attendants of patients attending Himalayan Hospital from July 2000 to May 2022. Sustained Nasal Inspiratory Pressure (SNIP), Maximal Expiratory Pressure (MEP), and Maximal Inspiratory Pressure (MIP) values were measured using Micro Respiratory Pressure Meter (RPM) following the American Thoracic Society Technical Statement (ATS) standard protocol. The prediction model for the Maximal Respiratory Pressure (MRP) was obtained using regression analysis. Height, age, weight, and Body Mass Index (BMI) were included as variables in the calculations. The statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) program for Windows (Version 22.0). Results: There was a statistically significant difference observed in MIP among males 91.77±29.41 cmH2O and females 65.26±19.55 cmH2O and in MEP among males 86.37±26.96 cmH2O and females 56.04±18.29 cmH2O. Both MIP and MEP averages were more in males than in females. In the present study, there was no significant relationship between height, weight, BMI, and respiratory pressure in females. There was no significant relationship between MIP and MEP plus height, age, weight, or BMI. Weight (r-value=0.24), age (r-value=0.27), and BMI (r-value=0.27) all had a significant association in men. Conclusion: Based on these findings, it can be concluded that there are gender-based disparities in MRP in the Himalayan population, with males exhibiting higher average values than females. Additionally, while there was no significant correlation between anthropometric factors and respiratory pressures in females, in males, weight, age, and BMI showed significant associations with these respiratory parameters.

Background: Women are less likely than men to use cardiac rehabilitation (CR); thus, women-focused (W-F) CR was developed. Implementation of W-F CR globally was investigated, as well as barriers and enablers to its delivery. Methods: In this cross-sectional study, a survey was administered to CR programs via Research Electronic Data Capture (REDCap) from May to July, 2023. Potential respondents were identified via the International Council of Cardiovascular Prevention and Rehabilitation’s network. Results: A total of 223 responses were received from 52 of 111 countries (46.8% country response rate) in the world that have any CR, across all 6 World Health Organization regions. Thirty-three programs (14.8%) from 30 countries reported offering any W-F programming. Programs commonly did offer elements preferred by women and recommended, namely, the following: patient choice of session time (n = 151; 70.6%); invitations for informal care providers and/or partners to attend sessions (n = 121; 57.1%); CR staff that have expertise in women and heart diseases (n = 112; 53.3%); separate changerooms for women (n = 38; 52.8%); and discussion of CR referral with patients (n = 112; 52.1%). Main barriers to delivery of W-F exercise were physical resources (n = 33; 14.8%), space (n = 30; 13.5%), and staff time (n = 26; 11.7%) and expertise (n = 33; 10.3%). Main barriers to delivery of W-F education were human resources (n = 114; 51.1%), educational resources (n = 26; 11.7%), and expertise in the content (n = 74; 33.2%). Enablers of W-F education delivery were availability of materials, in multiple modalities, as well as educated staff and financial resources. Conclusions: Despite the benefits, W-F CR is not commonly offered globally. Considering the barriers and enablers identified, the International Council of Cardiovascular Prevention and Rehabilitation is developing resources to expand delivery. Résumé: Contexte: Les femmes étant moins susceptibles que les hommes d’avoir recours à la réadaptation cardiaque (RC), il convient d’élaborer des programmes de RC qui sont mieux adaptés à leurs besoins. Le recours à de tels programmes dans le monde a fait l’objet d’une étude, laquelle portait également sur les obstacles à leur prestation et les facteurs qui les favorisent. Méthodologie: Dans cette étude transversale, un sondage a été mené auprès de programmes de RC via la REDCap (Research Electronic Data Capture) de mai à juillet 2023. Les participants potentiels au sondage ont été sélectionnés par le réseau de l’International Council of Cardiovascular Prevention and Rehabilitation. Résultats: Au total, 223 réponses ont été reçues de 52 pays sur 111 qui ont un programme de RC (taux de réponse des pays de 46,8 %), dans les 6 régions de l’Organisation mondiale de la Santé. Selon les résultats, trente-trois programmes (14,8 %) de 30 pays offrent des services axés sur les femmes. Les programmes offraient habituellement des éléments privilégiés par les femmes et recommandaient notamment des séances au moment choisi par les patientes (n = 151; 70,6 %); la possibilité de se faire accompagner par un aidant naturel et/ou un(e) partenaire (n = 121; 57,1 %); du personnel de RC possédant une expertise auprès des femmes et en matière de maladies cardiaques (n = 112; 53,3 %); des vestiaires réservés aux femmes (n = 38; 52,8 %); et une discussion avec les patientes sur leur orientation vers des spécialistes en RC (n = 112; 52,1 %). Les principaux obstacles à la prestation de services pour les femmes étaient les ressources physiques (n = 33; 14,8 %), l’espace (n = 30; 13,5 %) ainsi que la disponibilité du personnel (n = 26; 11,7 %) et son expertise (n = 33; 10,3 %). Les principaux obstacles à l’éducation destinée aux femmes étaient les ressources humaines (n = 114; 51,1 %), les ressources éducatives (n = 26; 11,7 %) et l’expertise liée au contenu (n = 74; 33,2 %). Les facteurs qui favorisent l’éducation destinée aux femmes étaient la disponibilité du matériel, sous plusieurs formes, de même que le personnel formé et les ressources financières. Conclusions: En dépit des bienfaits, la RC axée sur les femmes n’est pas couramment offerte dans le monde. En tenant compte des obstacles et des facteurs favorisant la prestation des services cités, l’International Council of Cardiovascular Prevention and Rehabilitation s’affaire à concevoir des ressources pour élargir la portée des programmes destinés aux femmes.

Abstract Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ( $${{\text{M}}}_{{\text{paU}}-{\text{Net}}})$$ M paU - Net ) and 3d full resolution of nnU-Net ( $${{\text{M}}}_{{\text{nnU}}-{\text{Net}}})$$ M nnU - Net ) to determine the best architecture ( $${\text{BA}})$$ BA ) . BA was used with vessels ( $${{\text{M}}}_{{\text{Vess}}})$$ M Vess ) and spleen ( $${{\text{M}}}_{{\text{seg}}+{\text{spleen}}})$$ M seg + spleen ) to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ( $${{\text{C}}}_{{\text{RTTrain}}}$$ C RTTrain ), 40 ( $${{\text{C}}}_{{\text{RTVal}}}$$ C RTVal ), 33 ( $${{\text{C}}}_{{\text{LS}}}$$ C LS ), 25 (CCH) and 20 (CPVE) CECT of LC patients. $${{\text{M}}}_{{\text{nnU}}-{\text{Net}}}$$ M nnU - Net outperformed $${{\text{M}}}_{{\text{paU}}-{\text{Net}}}$$ M paU - Net across all segments with median differences in Dice similarity coefficients (DSC) ranging 0.03–0.05 (p 0.05), however, both were slightly better than $${{\text{M}}}_{{\text{Vess}}}$$ M Vess by DSC up to 0.02. The final model, $${{\text{M}}}_{{\text{seg}}+{\text{spleen}}}$$ M seg + spleen , showed a mean DSC of 0.89, 0.82, 0.88, 0.87, 0.96, and 0.95 for segments 1, 2, 3, 4, 5–8, and spleen, respectively on entire test sets. Qualitatively, more than 85% of cases showed a Likert score $$\ge$$ ≥ 3 on test sets. Our final model provides clinically acceptable contours of liver segments and spleen which are usable in treatment planning.

Abstract Solid state chemistry has produced a plethora of materials with properties not found in nature. For example, high-temperature superconductivity in cuprates is drastically different from the superconductivity of naturally occurring metals and alloys and is frequently referred to as unconventional. Unconventional superconductivity is also found in other synthetic compounds, such as iron-based and heavy-fermion superconductors. Here, we report compelling evidence of unconventional nodal superconductivity in synthetic samples of Rh17S15 (T c = 5.4 K), which is also found in nature as the mineral miassite. We investigated the temperature-dependent variation of the London penetration depth Δλ(T) and the disorder evolution of the critical superconducting temperature T c and the upper critical field H c2(T) in single crystalline Rh17S15. We found a T − linear temperature variation of Δλ(T) below 0.3T c , which is consistent with the presence of nodal lines in the superconducting gap of Rh17S15. The nodal character of the superconducting state is supported by the observed suppression of T c and H c2(T) in samples with a controlled level of non-magnetic disorder introduced by 2.5 MeV electron irradiation. We propose a nodal sign-changing superconducting gap in the A 1g irreducible representation, which preserves the cubic symmetry of the crystal and is in excellent agreement with the derived superfluid density. To the best of our knowledge, this establishes miassite as the only mineral known so far that reveals unconventional superconductivity in its clean synthetic form, though it is unlikely that it is present in natural crystals because of unavoidable impurities that quickly destroy nodal superconductivity.

In the last two decades, chaos-based signals have achieved much popularity due to their useful waveform properties such as non-periodicity, wide-band nature, and robustness against eavesdropping by intruders. In this paper, we utilize differential chaos shift keying (DCSK) for free space optical (FSO) communication systems to improve their performance under the combined influence of atmospheric turbulence (AT) and non-zero boresight pointing errors (PEs). We employ the generalized Malaga distribution for modeling the channel gain under all turbulence regimes from weak to strong. Moreover, we utilize the modified Rayleigh distribution to incorporate the effect of jitter and boresight PEs. The computation of the exact average bit error rate (ABER) expression for the proposed FSO system using DCSK is quite tedious. Therefore, we propose two approximations for ABER of the proposed system which show a tight match with the exact analysis and are also valid for the homodyne detection (HMD), heterodyne detection (HD), and intensity modulation/direct detection (IM/DD) techniques. We also observe the impact of different AT parameters $(\alpha,\beta)$ , spreading factor $(M)$ , and non-zero boresight PE parameters $(k_{x},k_{y})$ on the ABER performance of the DCSK-based FSO system. Further, we derive asymptotic ABER expression to obtain insightful observations into the FSO system performance. We also compare the ABER performance of the proposed DCSK-based FSO system with an FSO system employing, correlation delay shift keying (CDSK), binary phase shift keying (BPSK), and code division multiple access (CDMA). We also derive the generalized ergodic capacity (EC) for the considered FSO communication system and show the effect of the spreading factor and boresight on the EC of the DCSK FSO communication system. We derive closed form expression of the average secrecy capacity (ASC) under the combined effect of AT and nonzero boresight PEs for the considered DCSK FSO system.

While user authentication happens before initiating or resuming a login session, de-authentication detects the absence of a previously-authenticated user to revoke her currently active login session. The absence of proper de-authentication can lead to well-known lunchtime attacks, where a nearby adversary takes over a carelessly departed user’s running login session. The existing solutions for automatic de-authentication have distinct practical limitations, e.g., extraordinary deployment requirements or high initial cost of external equipment. In this paper, we propose “DE-authentication using Ambient Light sensor” (DEAL), a novel, inexpensive, fast, and user-friendly de-authentication approach. DEAL utilizes the built-in ambient light sensor of a modern computer to determine if the user is leaving her work-desk. DEAL, by design, is resilient to natural shifts in lighting conditions and can be configured to handle abrupt changes in ambient illumination (e.g., due to toggling of room lights). We collected data samples from 4800 sessions with 120 volunteers in 4 typical workplace settings and conducted a series of experiments to evaluate the quality of our proposed approach thoroughly. Our results show that DEAL can de-authenticate a departing user within 4 seconds with a hit rate of 89.15% and a fall-out of 7.35%. Finally, bypassing DEAL to launch a lunchtime attack is practically infeasible as it requires the attacker to either take the user’s position within a few seconds or manipulate the sensor readings sophisticatedly in real-time.

Abstract Background Chronic subdural hematoma (cSDH) is a collection of old blood in the subdural space and has a relatively high estimated incidence, especially among the elderly and men, possibly due to falls, anticoagulant use, or age as independent factors. The subdural evacuating port system (SEPS) offers a minimally invasive solution for cSDH treatment. Objective The objective of our meta-analysis is to review the literature and assess the safety and efficacy of SEPS as a first-line treatment for cSDH. Method We conducted an exhaustive literature search to explore outcomes resulting from the implementation of SEPS as the initial treatment for cSDH. The main focus was on treatment success, comprising both symptom improvement and the absence of additional operating room interventions. Supplementary outcomes encompassed factors such as discharge arrangements, length of hospital stay (LOS), recurrence of hematoma, and any associated complications. Result A total of 15 studies, involving 1146 patients who underwent SEPS placement, satisfied the inclusion criteria. The combined rate of achieving a successful outcome stood at 0.79 (95% CI 0.75–0.83). The occurrence of delayed hematoma recurrence was found to be 0.155 (95% CI 0.101–0.208). Meanwhile, the aggregated inpatient mortality rate was 0.017 (95% CI 0.007–0.031). In terms of complications, the rates were 0.02 (95% CI 0.00–0.03) for any acute hemorrhage, 0.01 (95% CI 0.00–0.01) for acute hemorrhage necessitating surgery, and 0.02 (95% CI 0.01–0.03) for seizures. Notably, SEPS placement is associated with a success rate of 79% and exceptionally low incidences of acute hemorrhage and seizure. Conclusion SEPS is a viable first-line treatment for cSDH, supported by its minimally invasive nature, avoidance of general anesthesia, high success rate, and favorable safety profile.

As the scientific, technical, and economic developments of the world continue to advance, there will be an increased requirement for Distribution Generation(DG) technology. There is a widespread disruption in the primary power grid, the procedure known as islanding involves the construction of a power island that operates in a manner analogous to a section of the utility system. The Islanding Detection (ID), in which the development of islanding, actions carried out during islanding, and the approaches utilized to recognize islanding are detailed, is entirely necessary for this study. In this paper the author used reinforcement learning method which is a technique for introducing machines to learn by rewarding appropriate conduct and/or penalizing inappropriate behavior. The Remote technique, the Local approach, and the Hybrid approach were all observable in the Islanding detection methodologies. Passive islanding detection algorithms for inverter-oriented distributed generation systems based on Variational Mode Decomposition (VMD) and the microgrid approach are implemented throughout this research attempt. According to the comparison results of the study, the proposed system is more reliable and better than the compared technique. The comparison results show the detection time of suggested model which is 0.06 s. In​ contrast to active techniques, it is capable of functioning normally and without disrupting the usual operation of the system. As a result, it can be used effectively for real-time applications.

Secondary metabolites are bioactive compounds believed to contribute to the pharmacological properties of plants. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in post-transcriptional regulation and are thought to play an important role in regulating secondary metabolism biosynthesis. Nevertheless, the extent of miRNA involvement in secondary metabolism remains minimal. Nigella sativa (black cumin/black seed) is a popular medicinal and culinary plant known for its pharmaceutical properties; however, its genomic information is scarce. In this study, next-generation sequencing (NGS) technology was employed to obtain the miRNA profile of N. sativa, and their involvement in secondary metabolite biosynthesis was explored. A total of 25,139,003 unique reads ranging from 16 to 40 nucleotides were attained, out of which 240 conserved and 34 novel miRNAs were identified. Moreover, 6083 potential target genes were recognized in this study. Several conserved and novel black cumin miRNAs were found to target enzymes involved in the terpenoid, diterpenoid, phenylpropanoid, carotenoid, flavonoid, steroid, and ubiquinone biosynthetic pathways, among others, for example, beta-carotene 3-hydroxylase, gibberellin 3 beta-dioxygenase, trimethyltridecatetraene synthase, carboxylic ester hydrolases, acetyl-CoA C-acetyltransferase, isoprene synthase, peroxidase, shikimate O-hydroxycinnamoyltransferase, etc. Furthermore, sequencing data were validated through qPCR by checking the relative expression of eleven randomly selected conserved and novel miRNAs (nsa-miR164d, nsa-miR166a, nsa-miR167b, nsa-miR171a, nsa-miR390b, nsa-miR396, nsa-miR159a, nsa-miRN1, nsa-miRN29, nsa-miRN32, and nsa-miRN34) and their expression patterns were found to be corroborated with the sequencing data. We anticipate that this work will assist in clarifying the implications of miRNAs in plant secondary metabolism and aid in the generation of artificial miRNA-based strategies to overproduce highly valuable secondary metabolites from N. sativa.

We demonstrate a surprising connection between pure steady-state entanglement and relaxation time scales in an extremely broad class of Markovian open systems, where two (possibly many-body) systems, A and B, interact locally with a common dissipative environment. This setup also encompasses a broad class of adaptive quantum dynamics based on continuous measurement and feedback. As steady-state entanglement increases, there is generically an emergent strong symmetry that leads to a dynamical slow-down. Using this, we can prove rigorous bounds on relaxation times set by steady-state entanglement. We also find that this time must necessarily diverge for maximal entanglement. To test our bound, we consider the dynamics of a random ensemble of local Lindbladians that support pure steady states, finding that the bound does an excellent job of predicting how the dissipative gap varies with the amount of entanglement. Our work provides general insights into how dynamics and entanglement are connected in open systems and has specific relevance to quantum reservoir engineering.

Modern power systems present opportunities and challenges when integrating distributed generation and electric vehicle charging stations into unbalanced distribution networks. The performance and efficiency of both Distributed Generation (DG) and Electric Vehicle (EV) infrastructure are significantly affected by global temperature variation characteristics, which are taken into consideration in this study as it investigates the effects of these integrations. This scenario is further complicated by the unbalanced structure of distribution networks, which introduces inequalities that can enhance complexity and adverse effects. This paper analyzes the manner in which temperature changes influence the network operational voltage profile, power quality, energy losses, greenhouse harmful emissions, cost factor, and active and reactive power losses using analytical and heuristic techniques in the IEEE 69 bus network in both three-phase balance and modified unbalanced load conditions. In order to maximize adaptability and efficiency while minimizing the adverse impacts on the unbalanced distribution system, the findings demonstrate significant variables to take into account while locating the optimal location and size of DG and EV charging stations. To figure out the objective, three-phase distribution load flow is utilized by the particle swarm optimization technique. Greenhouse gas emissions dropped by 61.4%, 64.5%, and 60.98% in each of the three temperature case circumstances, while in the modified unbalanced condition, they dropped by 57.55%, 60.39%, and 62.79%. In balanced conditions, energy loss costs are reduced by 95.96%, 96.01%, and 96.05%, but in unbalanced conditions, they are reduced by 91.79%, 92.06%, and 92.46%. The outcomes provide valuable facts that electricity companies, decision-makers, along with other energy sector stakeholders may utilize to formulate strategies that adapt to the fluctuating patterns of electricity distribution during fluctuations in global temperature under balanced and unbalanced conditions of network.

Electric power is crucial for economic growth and the overall development of any country. The efficient planning of distribution system is necessary because all the consumers mainly rely on the distribution network to access the power. This paper focuses on addressing distribution system challenges and meeting consumers’ fundamental needs, such as achieving an improved voltage profile and minimizing costs within an environmentally sustainable framework. This work addressed the gap in the existing research by analysing the performance of both balanced and unbalanced systems within the same framework, specifically using the IEEE 33-bus and IEEE 118-bus test systems. Unlike prior studies that focused solely on either balanced or unbalanced systems, this work redistributed balanced loads into three-phase unequal unbalanced loads to create a more challenging unbalanced distribution network. The primary objective is to compare the effects of balanced and unbalanced loads on system the performances and to identify strategies for mitigating unbalanced load issues in each phase. Six optimization methods (PSO, TLBO, JAYA, SCA, RAO, and HBO) were employed to minimize losses, voltage variations, and other multi-objective function factors. Additionally, the study compared the cost of energy loss (CEL), emission factors, costs associated with distributed clean energy resources (DCER), and active and reactive power losses. Phase angle distortions due to unbalanced loads were also analysed. The results showed that among the optimization techniques tested (PSO, TLBO, JAYA, SCA, RAO, and HBO), the HBO method proved to be the most effective for the optimal allocation of distributed clean energy resources, yielding the lowest PFMO values and favourable outcomes across the technical, economic, and environmental parameters.

Polycystic Ovary Syndrome (PCOS) presents multifaceted challenges affecting women’s reproductive, metabolic, and psychological systems, consequently impacting their psychological and emotional well-being. The utilization of meditation and mindfulness interventions (MMIs) is found to be increasing for the management of PCOS. This scoping review systematically explored the current literature to identify the type and application of MMIs for PCOS management. A systematic search of literature was conducted using CINAHL, PsycINFO, Scopus, MEDLINE, and PubMed databases for identifying studies conducted on the usage of MMIs in women diagnosed with PCOS, irrespective of age. The comprehensive search identified 14 trials (comprising 17 citations) meeting inclusion criteria, involving 723 participants across various age groups. Among these, nine were randomized controlled trials (RCTs), while the remaining comprised non-RCTs. Several types of MMIs, including Rajayoga of Brahmakumaris, Yoga Nidra, OM cyclic meditation, unspecified forms of meditation, mindfulness-based stress reduction programs, mindful yoga, and mindfulness-based activities, were used. Outcomes were predominantly assessed in psychological domains (n=11), followed by anthropometric (n=9), quality of life (n=7), and metabolic metrics (n=7). The review findings suggest the integration of meditation with conventional treatment modalities. Preliminary data indicate that MMIs have the potential to improve psychosocial well-being and quality of life among PCOS-affected women. However, adequately powered studies with extended follow-up periods are required to investigate the mechanisms and therapeutic efficacy of MMIs, particularly concerning reproductive outcomes and weight management. Furthermore, diligent monitoring and reporting of adverse events and adherence are essential for a comprehensive understanding of MMI utilization in PCOS management.

PURPOSEDesmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India.PATIENTS AND METHODSThis study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018.RESULTSThere were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT—151, 77—local treatment, 9—tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars.CONCLUSIONThe novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Voice assistants (VAs) are increasingly integrated into everyday activities and tasks, raising novel challenges for users and researchers. One emergent research direction concerns proactive VAs, who can initiate interaction without direct user input, offering unique benefits including efficiency and natural interaction. Yet, there is a lack of review studies synthesizing the current knowledge on how proactive behavior has been implemented in VAs and under what conditions proactivity has been found more or less suitable. To this end, we conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched for articles in the ACM Digital Library, IEEExplore, and PubMed, and included primary research studies reporting user evaluations of proactive VAs, resulting in 21 studies included for analysis. First, to characterize proactive behavior in VAs we developed a novel conceptual model encompassing context, initiation, and action components: Activity/status emerged as the primary contextual element, direct initiation was more common than indirect initiation, and suggestions were the primary action observed. Second, proactive behavior in VAs was predominantly explored in domestic and in-vehicle contexts, with only safety-critical and emergency situations demonstrating clear benefits for proactivity, compared to mixed findings for other scenarios. The paper concludes with a summary of the prevailing knowledge gaps and potential research avenues.

Thoracic endovascular aortic repair (TEVAR) has been widely adopted as a standard for treating complicated acute and high-risk uncomplicated Stanford Type-B aortic dissections. The treatment redirects the blood flow towards the true lumen by covering the proximal dissection tear which promotes sealing of the false lumen. Despite advances in TEVAR, over 30% of Type-B dissection patients require additional interventions. This is primarily due to the presence of a persistent patent false lumen post-TEVAR that could potentially enlarge over time. We propose a novel technique, called slit fenestration pattern creation, which reduces the forces for re-apposition of the dissection flap (i.e., increase the compliance of the flap). We compute the optimal slit fenestration design using a virtual design of experiment (DOE) and demonstrate its effectiveness in reducing the re-apposition forces through computational simulations and benchtop experiments using porcine aortas. The findings suggest this potential therapy can drastically reduce the radial loading required to re-appose a dissected flap against the aortic wall to ensure reconstitution of the aortic wall (remodeling).

Background: Hypertension is a prevalent chronic condition that affects a substantial proportion of the world's population. Medications are commonly prescribed for hypertension management, but non-pharmacological interventions like yoga are gaining popularity. Objective: The purpose of this systematic review and meta-analysis is to assess the efficacy of Yoga Nidra (YN) for the management of hypertension. Methods: A systematic review and meta-analysis of clinical trials, i.e., non-randomized and randomized controlled trials (RCTs) was conducted to investigate the effects of YN on hypertension. PubMed, the Cochrane Library, SCOPUS, and EBSCO were searched for relevant studies published up to September 2022. The quality of the included studies was assessed using the Cochrane risk of bias tool. The primary outcome measure was the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after YN intervention, analyzed as weighted mean difference (WMD), in comparison to control groups. The random-effects model was used for the meta-analysis. Risk of bias was assessed for RCTs and non-RCTs using Cochrane's RoB-2 and ROBINS-I tools, respectively. Results: Five RCTs and three Non-RCTs involving a total of 482 participants (239 for YN vs 243 for controls) were included in this review. The meta-analysis indicated that YN significantly reduced SBP (WMD = 12.03 mm Hg, 95% CI [7.12, 16.93], Z = 4.80, p

Abstract In vitro biopanning platforms using synthetic phage display antibody libraries have enabled the identification of antibodies against antigens that were once thought to be beyond the scope of immunization. Applying these methods against challenging targets remains a critical challenge. Here, we present a new biopanning pipeline, RAPID (Rare Antibody Phage Isolation and Discrimination), for the identification of rare high-affinity antibodies against challenging targets. RAPID biopanning uses fluorescent labeled phage displayed fragment antigen-binding (Fab) antibody libraries for the isolation of high-affinity binders with fluorescent activated sorting. Subsequently, discriminatory hit screening is performed with a biolayer interferometry (BLI) method, BIAS (Biolayer Interferometry Antibody Screen), where candidate binders are ranked and prioritized according to their estimated kinetic off rates. Previously reported antibodies were used to develop the methodology, and the RAPID biopanning pipeline was applied to three challenging targets (CHIP, Gαq, and CS3D), enabling the identification of high-affinity antibodies.

Abstract Background Traumatic brain injury has a crippling impact on sufferers’ quality of life, and numerous therapy techniques are being researched to address this problem. In this study, we compared the superiority of HS against mannitol as one such element of treating TBI patients. Objective To compare the efficacy of hypertonic saline and mannitol and demonstrate superiority of one group over the other. Method Our meta-analysis included only randomized controlled trials that compared the efficacy of mannitol and hypertonic saline in the treatment of traumatic brain injury. The literature search was done using a variety of databases, like Google Scholar, PubMed, and the Cochrane Library. From each of the included RCTs, accurate data extraction, bias risk assessment, and statistical analysis were carried out. Result There are 748 patients among the 15 RCTs. Our primary outcomes are mortality and functional outcomes, and our secondary outcomes include treatment failure, osmolality, intracerebral pressure (ICP), cerebral perfusion pressure (CPP), serum sodium (Na), partial pressure of oxygen in brain tissue (PBTO2), duration of elevated ICP, mean arterial pressure, hematocrit level, and central venous pressure. The comparison showed non-significant results for mortality (RR = 0.73, 95% CI 0.49–1.08; p = 0.12) and functional outcome (RR = 1.15, 95% CI = 0.74–1.80; p = 0.53). HS is linked to higher Na levels (RR = 4.55, 95% CI 1.34–7.76, P = 0.005, I2 = 96%). Despite performing a sensitivity analysis due to the heterogeneities in our various outcomes, the findings were still unreliable. Conclusion Our study revealed inconsequential trends for HS and mannitol, and no conclusion was made. We believe the two medications to be equally effective, but there is still opportunity for improvement as more studies are carried out. Eventually, a conclusive decision can be reached in the future.

Abstract Increased innovation on finding new ways to generate energy from different sources to meet the growing demand of consumers has led to various challenges in controlling the power network when it faces different disruptions. To address these challenges, a new approach has been proposed in this research paper, which combines a controller with a soft computing technique called Particle Swarm Optimization (PSO). The study considers a power system with four units, where three different energy sources are utilized and distributed across two areas. Each area has two power sources, with one area having a combination of thermal and gas power plants, and the other area consisting of a nuclear power plant and a gas power plant. Transmitting power from the nuclear power plant is particularly complex due to its high sensitivity to disturbances. Therefore, an intelligent and efficient controller is needed to ensure robust control in this type of power network that includes nuclear power. The paper also conducts a thorough analysis of the harmful emissions associated with electricity generation from the different power plants considered. The goal is to reduce the carbon footprint associated with power generation. The proposed work and analysis in the paper are implemented using the MATLAB/SIMULINK environment.

Thermally induced moisture flow in unsaturated soils involves complex coupled thermal–hydro processes with the moisture flow in both the vapor and liquid phases. The accurate measurement of the moisture flow in unsaturated sands remains a challenging task due to low moisture migration, the temperature effect on moisture sensors, and the gravity effect on moisture flow. This study aims to accurately measure transient moisture flow, heat transfer, and thermal conductivity in a silty sand with 35% non-plastic fines in a closed heat cell with a controlled 1-D temperature gradient. The heat cell consists of two temperature-controlled heat exchanger plates, heat flux sensors, moisture sensors, thermocouples, and thermal conductivity sensors. The soil moisture sensors were calibrated in the test soil at room temperature and then at elevated incremental temperatures. Soil samples compacted at various initial moisture contents were tested under a constant 1-D temperature gradient of 4 °C/cm. Soil moisture redistribution, temperature, and thermal conductivity profiles were determined from the test results. Transient temperature responses indicated that a lower initial moisture content led to a higher temperature drop after reaching the peak, or a more concaved temperature profile in a steady state due to enhanced moisture migration driven by the temperature gradients. Dry soils exhibited uniform thermal properties, while moist soils showed varying thermal conductivity profiles. A critical moisture content was identified when the maximum moisture migration occurred. Thermal conductivity in soils increased with the distance from the heat source due to thermally induced moisture migration. These findings provide valuable insights into coupled moisture–heat flow dynamics in unsaturated sands.

Establishing limits of entanglement in open quantum systems is a problem of fundamental interest, with strong implications for applications in quantum information science. Here, we study the limits of entanglement stabilization between remote qubits. We theoretically investigate the loss resilience of driven-dissipative entanglement between remote qubits coupled to a chiral waveguide. We find that by coupling a pair of storage qubits to the two driven qubits, the steady state can be tailored such that the storage qubits show a degree of entanglement that is higher than what can be achieved with only two driven qubits coupled to the waveguide. By reducing the degree of entanglement of the driven qubits, we show that the entanglement between the storage qubits becomes more resilient to waveguide loss. Our analytical and numerical results offer insights into how waveguide loss limits the degree of entanglement in this driven-dissipative system, and they offer important guidance for remote entanglement stabilization in the laboratory, for example using superconducting circuits.

Abstract Noise is an ever-present challenge to the creation and preservation of fragile quantum states. Recent work suggests that spatial noise correlations can be harnessed as a resource for noise mitigation via the use of spectator qubits to measure environmental noise. In this work we generalize this concept from spectator qubits to a spectator mode: a photonic mode which continuously measures spatially correlated classical dephasing noise and applies a continuous correction drive to frequency-tunable data qubits. Our analysis shows that by using many photon states, spectator modes can surpass many of the quantum measurement constraints that limit spectator qubit approaches. We also find that long-time data qubit dephasing can be arbitrarily suppressed, even for white noise dephasing. Further, using a squeezing (parametric) drive, the error in the spectator mode approach can exhibit Heisenberg-limited scaling in the number of photons used. We also show that spectator mode noise mitigation can be implemented completely autonomously using engineered dissipation. In this case no explicit measurement or processing of a classical measurement record is needed. Our work establishes spectator modes as a potentially powerful alternative to spectator qubits for noise mitigation.

Abstract We propose an autonomous quantum error correction scheme using squeezed cat (SC) code against excitation loss in continuous-variable systems. Through reservoir engineering, we show that a structured dissipation can stabilize a two-component SC while autonomously correcting the errors. The implementation of such dissipation only requires low-order nonlinear couplings among three bosonic modes or between a bosonic mode and a qutrit. While our proposed scheme is device independent, it is readily implementable with current experimental platforms such as superconducting circuits and trapped-ion systems. Compared to the stabilized cat, the stabilized SC has a much lower dominant error rate and a significantly enhanced noise bias. Furthermore, the bias-preserving operations for the SC have much lower error rates. In combination, the stabilized SC leads to substantially better logical performance when concatenating with an outer discrete-variable code. The surface-SC scheme achieves more than one order of magnitude increase in the threshold ratio between the loss rate κ 1 and the engineered dissipation rate κ 2. Under a practical noise ratio κ 1/κ 2 = 10−3, the repetition-SC scheme can reach a 10−15 logical error rate even with a small mean excitation number of 4, which already suffices for practically useful quantum algorithms.

Abstract Background Curated databases of genetic variants assist clinicians and researchers in interpreting genetic variation. Yet, these databases contain some misclassified variants. It is unclear whether variant misclassification is abating as these databases rapidly grow and implement new guidelines. Methods Using archives of ClinVar and HGMD, we investigated how variant misclassification has changed over 6 years, across different ancestry groups. We considered inborn errors of metabolism (IEMs) screened in newborns as a model system because these disorders are often highly penetrant with neonatal phenotypes. We used samples from the 1000 Genomes Project (1KGP) to identify individuals with genotypes that were classified by the databases as pathogenic. Due to the rarity of IEMs, nearly all such classified pathogenic genotypes indicate likely variant misclassification in ClinVar or HGMD. Results While the false-positive rates of both ClinVar and HGMD have improved over time, HGMD variants currently imply two orders of magnitude more affected individuals in 1KGP than ClinVar variants. We observed that African ancestry individuals have a significantly increased chance of being incorrectly indicated to be affected by a screened IEM when HGMD variants are used. However, this bias affecting genomes of African ancestry was no longer significant once common variants were removed in accordance with recent variant classification guidelines. We discovered that ClinVar variants classified as Pathogenic or Likely Pathogenic are reclassified sixfold more often than DM or DM? variants in HGMD, which has likely resulted in ClinVar’s lower false-positive rate. Conclusions Considering misclassified variants that have since been reclassified reveals our increasing understanding of rare genetic variation. We found that variant classification guidelines and allele frequency databases comprising genetically diverse samples are important factors in reclassification. We also discovered that ClinVar variants common in European and South Asian individuals were more likely to be reclassified to a lower confidence category, perhaps due to an increased chance of these variants being classified by multiple submitters. We discuss features for variant classification databases that would support their continued improvement.