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Abstract Background Domestic violence (DV) prior to, and during pregnancy is associated with increased risks for morbidity and mortality. As pregnant women routinely attend antenatal care this environment can be used to offer support to women experiencing DV. We have developed a video intervention that focuses on the use of behavioral coping strategies, particularly regarding disclosure of DV experiences. The effectiveness of this intervention will be evaluated through a randomized controlled trial (RCT) and a concurrent process evaluation. Methods All pregnant women between 12–22 weeks of gestation attending routine antenatal care at two tertiary level hospitals in Nepal are invited to participate. DV is measured using the Nepalese version of the Abuse Assessment Screen (N-AAS). Additionally, we measure participants’ mental health, use of coping strategies, physical activity, and food security through a Color-coded Audio Computer Assisted Self Interview (C-ACASI). Irrespective of DV status, women are randomized into the intervention or control arm using a computer-generated randomization program. The intervention arm views a short video providing information on DV, safety improving actions women can take with an emphasis on disclosing the violence to a trusted person along with utilizing helplines available in Nepal. The control group watches a video on maintaining a healthy pregnancy and when to seek healthcare. The primary outcome is the proportion of women disclosing their DV status to someone. Secondary outcomes are symptoms of anxiety and depression, coping strategies, the use of safety measures and attitudes towards acceptance of abuse. Follow-up is conducted after 32 weeks of gestation, where both the intervention and control group participants view the intervention video after completing the follow-up questionnaire. Additionally, a mixed methods process evaluation of the intervention will be carried out to explore factors influencing the acceptability of the intervention and the disclosure of DV, including a review of project documents, individual interviews, and focus group discussions with members of the research team, healthcare providers, and participants. Discussion This study will provide evidence on whether pregnant women attending regular antenatal visits can enhance their safety by disclosing their experiences of violence to a trusted person after receiving a video intervention. Trial registration The study is registered in ClinicalTrial.gov with identifier NCT05199935.

This study culturally adapted and validated a Nepalese version of the Abuse Assessment Screen (AAS) tool for identifying domestic violence among pregnant women in Nepal, creating the Nepalese Abuse Assessment Screen (N-AAS). International and national topic experts reviewed the initial N-AAS version using the Delphi method, and pregnant women participated in cognitive interviews, providing feedback on the N-AAS as user experts. Subsequent pre-testing of a comprehensive questionnaire, which included the translated version of the N-AAS, occurred in two tertiary care hospitals using an electronic format known as Color-Coded Audio Computer-Assisted Self-Interview (C-ACASI). The study assessed the content validity index, compared the concurrent validity of the N-AAS with the gold standard interview, estimated the prevalence of domestic violence from two hospitals, and calculated the Kappa coefficient. The reliability of the entire questionnaire was also evaluated through a test-retest analysis, with content validity rated as "good to excellent" by topic and user experts and high test-retest reliability (91.2-98.9%), indicating consistency across questionnaires completed at two different time points, with 12% of participants reporting any form of violence. The N-AAS demonstrated ≥91.7% specificity for all forms of abuse, accurately identifying non-abuse cases. In addition, moderate to excellent sensitivity was observed for emotional abuse (52.5%) and physical abuse since marriage (50%), while sensitivity for physical abuse in the past 12 months was 100%. Thus, the N-AAS demonstrated reliable test-retest results with a good Kappa coefficient and specificity, as well as showing excellent sensitivity for detecting recent physical abuse and moderate sensitivity for detecting emotional abuse and physical abuse since marriage. Because cultural context often leads women to normalize and tolerate abuse from spouses and family members and women are thus reluctant to report abuse, the results imply that the N-AAS can serve as a valuable screening tool for domestic abuse in antenatal care settings in Nepal.

This study delves into the realm of Explainable Artificial Intelligence (XAI) frameworks, aiming to empower researchers and practitioners with a deeper understanding of these tools. We establish a comprehensive knowledge base by classifying and analyzing prominent XAI solutions based on key attributes like explanation type, model dependence, and use cases. This resource equips users to navigate the diverse XAI landscape and select the most suitable framework for their specific needs. Furthermore, the study proposes a novel framework called XAIE (eXplainable AI Evaluator) for informed decision-making in XAI adoption. This framework empowers users to assess different XAI options based on their application context objectively. This will lead to more responsible AI development by fostering transparency and trust. Finally, the research identifies the limitations and challenges associated with the existing XAI frameworks, paving the way for future advancements. By highlighting these areas, the study guides researchers and developers in enhancing the capabilities of Explainable AI.

How is protein synthesis initiated locally in neurons? We found that mTOR (mechanistic target of rapamycin) was activated and then up-regulated in injured axons, owing to local translation of mTOR messenger RNA (mRNA). This mRNA was transported into axons by the cell size-regulating RNA-binding protein nucleolin. Furthermore, mTOR controlled local translation in injured axons. This included regulation of its own translation and that of retrograde injury signaling molecules such as importin β1 and STAT3 (signal transducer and activator of transcription 3). Deletion of the mTOR 3' untranslated region (3'UTR) in mice reduced mTOR in axons and decreased local translation after nerve injury. Both pharmacological inhibition of mTOR in axons and deletion of the mTOR 3'UTR decreased proprioceptive neuronal survival after nerve injury. Thus, mRNA localization enables spatiotemporal control of mTOR pathways regulating local translation and long-range intracellular signaling.

Transcriptional events leading to outgrowth of neuronal axons have been intensively studied, but the role of translational regulation in this process is not well understood. Here, we use translatome analyses by ribosome pull-down and protein synthesis characterization by metabolic isotopic labeling to study nerve injury and axon outgrowth proteomes in rodent dorsal root ganglia (DRGs) and sensory neurons. We identify over 1600 gene products that are primarily translationally regulated in DRG neurons after nerve injury, many of which contain a 5'UTR cytosine-enriched regulator of translation (CERT) motif, implicating the translation initiation factor Eif4e in the injury response. We further identified approximately 200 proteins that undergo robust de novo synthesis in the initial stages of axon growth. ApoE is one of the highly synthesized proteins in neurons, and its receptor binding inhibition or knockout affects axon outgrowth. These findings provide a resource for future analyses of the role of translational regulation in neuronal injury responses and axon extension.

Abstract Background Literature is scarce on primary sarcopenia among Indian older adults. This study was aimed to estimate the prevalence of primary sarcopenia among older persons in India using the European Working Group on Sarcopenia in the Older People 2010 (EWGSOP) diagnostic criteria and to elucidate the factors leading to its development. Methodology Two hundred twenty‐seven subjects over 60 years of age attending the geriatric outpatient clinic were recruited for the study. Sarcopenia was diagnosed based on set criteria for gait speed, handgrip, and skeletal muscle mass assessment by dual‐energy x‐ray absorptiometry. Result The prevalence of primary sarcopenia in the study population was 39.2% (n = 89). Male patients were more sarcopenic than women, 47% (n = 72) vs 23% (n = 17). Obese subjects (body mass index > 25 kg/m2) had a lower prevalence of sarcopenia (odds ratio = 0.10; 95% confidence interval = 0.05–0.19). There was no association between sarcopenia and other postulated risk factors like low vitamin D levels, dietary protein or carbohydrate intake, or sedentary lifestyle. Conclusion Contrary to published data, primary sarcopenia appears to be higher among older Indians using presently available guidelines. Community studies with validated cutoffs suited for the Indian subcontinent may yield a lower prevalence of primary sarcopenia.

BACKGROUND: The World Health Organization’s End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. METHODS: We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang. We will recruit 128 people with TB notified to the Nepal National TB Program (NTP) and 40 multisectoral stakeholders including NTP staff, civil-society members, policy-makers, and ASCOT (Addressing the Social Determinants and Consequences of Tuberculosis) team members. People with TB will be randomised 1:1:1:1 to four study arms (n=32 each): control; social support; economic support; and combined social and economic (socioeconomic) support. Social support will be TB education and peer-led mutual-support TB Clubs providing TB education and stigma-reduction counselling. Economic support will be monthly unconditional cash transfers during TB treatment with expectations (not conditions) of meeting NTP goals. At 0, 2, and 6 months following TB treatment initiation, participants will be asked to complete a survey detailing the social determinants and consequences of TB and their feedback on ASCOT. Complementary process evaluation will use focus group discussions (FGD), key informant interviews (KII), and a workshop with multi-sectoral stakeholders to consider the challenges to ASCOT’s implementation and scale-up. A sample of ~100 people with TB is recommended to estimate TB-related costs. Information power is estimated to be reached with approximately 25 FGD and 15 KII participants. CONCLUSIONS: The ASCOT pilot trial will both generate robust evidence on a locally-appropriate, socioeconomic support intervention for TB-affected households in Nepal and inform a large-scale future ASCOT trial, which will evaluate the intervention’s impact on catastrophic costs mitigation and TB outcomes. The trial is registered with the ISRCTN (ISRCTN17025974).

Collecting data to understand violence against women and children during and after the COVID-19 pandemic is essential to inform violence prevention and response efforts. Although researchers across fields have pivoted to remote rather than in-person data collection, remote research on violence against women, children and young people poses particular challenges. As a group of violence researchers, we reflect on our experiences across eight studies in six countries that we redesigned to include remote data collection methods. We found the following areas were crucial in fulfilling our commitments to participants, researchers, violence prevention and research ethics: (1) designing remote data collection in the context of strong research partnerships; (2) adapting data collection approaches; (3) developing additional safeguarding processes in the context of remote data collection during the pandemic; and (4) providing remote support for researchers. We discuss lessons learnt in each of these areas and across the research design and implementation process, and summarise key considerations for other researchers considering remote data collection on violence.

Abstract Molecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2Å root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking. Gnina, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version of Gnina under an open source license for use as a molecular docking tool at https://github.com/gnina/gnina .

Abstract Background Domestic violence is one of the most common forms of violence against women. Domestic violence during pregnancy is associated with adverse perinatal and maternal outcomes. We aimed to assess whether domestic violence was associated with mode of delivery, low birthweight and preterm birth in two sites in Nepal. Methods In this prospective cohort study we consecutively recruited 2004 pregnant women during antenatal care at two hospitals between June 2015 and September 2016. The Abuse Assessment Screen (modified) was used to assess fear and violence. Having ever experienced either fear or violence was defined as any domestic violence. Obstetric outcomes were obtained from hospital records for 1381 (69%) women, selecting singleton pregnancies only. Mode of delivery was assessed as birth by cesarean section or not. A birthweight of less than 2500 g was defined as low birthweight and preterm birth as birth before completion of 37 weeks gestation. Descriptive and multiple logistic regression analyses were performed to assess associations. Results Twenty percent of the women reported any domestic violence. Among all 1381 women, 37.6% gave birth by cesarean section. Of those women who delivered by cesarean section, 84.7% had an emergency cesarean section. Less than 10% of the babies were born prematurely and 13.5% were born with low birthweight. We found no significant association between exposure to any domestic violence during pregnancy and risk of a low birthweight baby or birth by cesarean section. However, having experienced both violence and fear was significantly associated with giving birth to a preterm infant [aOR 2.33 (95% CI;1.10–4.73)]. Conclusions Domestic violence is common in Nepal. This is a potential risk factor for severe morbidity and mortality in newborns. We found that the risk of having a preterm baby was higher for pregnant women who experienced both fear and violence. This should be recognized by the health sector. In this study, no significant differences were found in the rate of cesarean section nor low birthweight for women who had experienced any domestic violence compared to those who did not.

Abstract Background Child marriage is associated with adverse reproductive health outcomes, and the practice is still alarmingly common. Together with efforts to end child marriage, it is essential to provide adequate health care to already married adolescents. However, to date there has been very limited research on health care-seeking practices among married adolescents in Nepal. Method The study was conducted in a rural part of Dang District situated in the Mid-western region of Nepal. We combined thirteen individual interviews and four focus group discussions with 17–20 years old women who had married before the age of 18 years and individual interviews with 10 key informants. Results Pressure to give birth early, limited autonomy, and little knowledge about reproductive health issues make married adolescents vulnerable to risky pregnancies. Early-married women face a range of barriers to use existing health services including work overload, transport and distance to health care facilities, qualities of services, verbal abuse by health care providers, and shyness and embarrassment. Conclusion Women who marry and become pregnant during adolescence face a number of barriers that limit their access to health care services and they need more attention from the health services and policy makers. More youth friendly health services and education about sexual and reproductive health should be key elements in strategies to address the health issues of early-married women and adolescent girls.

Abstract Individual cell types have characteristic sizes, suggesting that size sensing mechanisms may coordinate transcription, translation, and metabolism with cell growth rates. Two types of size-sensing mechanisms have been proposed: spatial sensing of the location or dimensions of a signal, subcellular structure or organelle; or titration-based sensing of the intracellular concentrations of key regulators. Here we propose that size sensing in animal cells combines both titration and spatial sensing elements in a dynamic mechanism whereby microtubule motor-dependent localization of RNA encoding importin β1 and mTOR, coupled with regulated local protein synthesis, enable cytoskeleton length sensing for cell growth regulation.

The cytoplasmic dynein motor complex transports essential signals and organelles from the cell periphery to the perinuclear region, hence is critical for the survival and function of highly polarized cells such as neurons. Dynein Light Chain Roadblock-Type 1 (DYNLRB1) is thought to be an accessory subunit required for specific cargos, but here we show that it is essential for general dynein-mediated transport and sensory neuron survival. Homozygous Dynlrb1 null mice are not viable and die during early embryonic development. Furthermore, heterozygous or adult knockdown animals display reduced neuronal growth, and selective depletion of Dynlrb1 in proprioceptive neurons compromises their survival. Conditional depletion of Dynlrb1 in sensory neurons causes deficits in several signaling pathways, including β-catenin subcellular localization, and a severe impairment in the axonal transport of both lysosomes and retrograde signaling endosomes. Hence, DYNLRB1 is an essential component of the dynein complex, and given dynein's critical functions in neuronal physiology, DYNLRB1 could have a prominent role in the etiology of human neurodegenerative diseases.

Aims and Objectives: Altered platelet function and increased bleeding time (BT) can occur with antiplatelet therapy. This study was conducted to evaluate the need for stoppage of dual antiplatelet therapy in patients undergoing dental extractions. Materials and Methods: One hundred and fifty patients indicated for dental extraction were grouped as Group I: Consisted of 75 patients on dual antiplatelet therapy and Group II: Consisted of 75 patients who have discontinued antiplatelet therapy 1 week before dental extraction. BT of all the participants was recorded before extraction procedures. Under local anesthesia, single molar tooth indicated for simple extraction was done in both the groups. Suturing along with pressure pack was done after extraction. BT after extraction was statistically checked between the groups after 1 h and 24 h using Chi-square test with P < 0.05. Results: Postoperatively, none of the patients in both the groups showed active bleeding 1 h and 24 h. No bleeding was seen in 73 patients in Group I and 78 patients in Group II after 24 h. Conclusion: This study concluded that there is no significant difference in BT in both the groups. Antiplatelet monotherapy or even antiplatelet dual therapy needs no alteration or stopped before minor oral surgical procedures. Most of the postoperative bleeding can be easily controlled by local hemostatic measures.

Aim: This study aims to analyze root canal configuration of human permanent mandibular first molars of an indo-Dravidian population based in southern India. Materials and Methods: A total of 1147 mandibular first permanent molars were collected, cleansed, and stored. The number of roots was recorded, access preparations made, pattern of orifices recorded after pulpal floor debridement, dye injected into the canals using apical negative pressure and subjected to a clearing technique. They were then analyzed using a stereo microscope and the canal configurations recorded (Vertucci). The number of roots, the pattern of orifices and canal configuration were recorded. Results: The pattern of orifices was triangular (87.9%), rectangular (8.5%), C-shaped (3.0%), and two orifice pattern (0.6%). About 95.6% of teeth had two roots, and 4.4% had three roots. The most common canal system configuration in mesial root was Vertucci type IV (52.3%), followed by type II (35%). Root canal configuration of the distal root revealed type I configuration in 62.7%, followed by types II (14.5%) and IV (12.4%). The distolingual root had a type I configuration. Conclusion: Awareness of canal configuration, adequate clinical skills, use of specialized techniques of diagnosis, debridement and obturation will pave the way for successful treatment outcomes.

Lecturer Building is a facility that has full of activity and full of people inside from morning until afternoon. The Lecturer Building use in this research has a big problem with electricity utility which the energy source of the building until now still using limited fossil energy in its use. Another problem with the façade building was facing the sun in the morning. Then the temperature building was increasing and make uncomfortable conditions inside. Window integrated Solar PV or solar façade not only reducing incoming solar radiation but generate electricity.

Background: Domestic violence during pregnancy has detrimental effects on the health of the mother and the newborn. Antenatal care provides a ‘window of opportunity’ to identify and assist victims of domestic violence during pregnancy. Little is known about the experience, needs, and expectations from the women's perspective in relation to domestic violence in Nepal. Objective: Our study aims to explore how women who have experienced domestic violence evaluate their antenatal care and their expectations and needs from health centers. Design: Twelve in-depth interviews were conducted among women who had experienced domestic violence during pregnancy and utilized antenatal care. The women were recruited from two different organizations in Nepal. Results: Women in our study concealed their experience of domestic violence due to fear of being insulted, discriminated, and negative attitudes of the health care providers. The women wished that the health care providers were compassionate and asked them about their experience, ensured confidentiality and privacy, and referred them to services that is free of cost. Conclusions: Findings from our study may help the health care providers to change their attitudes toward women survivors of domestic violence. Identifying and assisting these women through antenatal care could result in improved services for them and their newborns.

How can cells sense their own size to coordinate biosynthesis and metabolism with their growth needs? We recently proposed a motor-dependent bidirectional transport mechanism for axon length and cell size sensing, but the nature of the motor-transported size signals remained elusive. Here, we show that motor-dependent mRNA localization regulates neuronal growth and cycling cell size. We found that the RNA-binding protein nucleolin is associated with importin β1 mRNA in axons. Perturbation of nucleolin association with kinesins reduces its levels in axons, with a concomitant reduction in axonal importin β1 mRNA and protein levels. Strikingly, subcellular sequestration of nucleolin or importin β1 enhances axonal growth and causes a subcellular shift in protein synthesis. Similar findings were obtained in fibroblasts. Thus, subcellular mRNA localization regulates size and growth in both neurons and cycling cells.

OBJECTIVE:This study aimed to evaluate if domestic violence affected women's ability to prepare for childbirth. Birth preparedness and complication readiness (BP/CR) includes saving money, arranging transportation, identifying a skilled birth attendant, a health facility, and a blood donor before childbirth. During data collection, Nepal experienced two earthquakes and therefore it was possible to examine associations between domestic violence, women's BP/CR and effects of the earthquakes. METHODS:Women who were between 12 and 28 weeks of gestation participated in a descriptive cross-sectional study at a hospital antenatal clinic in Nepal, where they completed a structured questionnaire on sociodemographic characteristics, obstetric history, experiences of domestic violence, and BP/CR. The 5-item Abuse Assessment Screen was used to assess prevalence of domestic violence, and a questionnaire on safe motherhood obtained from Jhpiego was used to assess BP/CR status. The participants self-completed the questionnaire on a tablet computer. Those who reported at least three out of five BP/CR activities were considered prepared for childbirth. RESULTS:A total of 1011 women participated in the study: 433 pre-earthquakes and 578 post-earthquakes. With respect to BP/CR, 78% had identified a health facility for childbirth and 65% had saved money prior to childbirth. Less than 50% had identified a birth attendant to assist with the delivery, transportation to a health facility, or arranged for a potential blood donor. Prior to the earthquakes, 38% were unprepared; by contrast, almost 62% were not prepared after the earthquakes. A significant association was found between exposure to violence and not being prepared for childbirth (AOR = 2.3, 95% CI: 1.4-3.9). The women with increased odds of not being prepared for childbirth were illiterate (AOR = 9.9, 95% CI:5.7-17), young (AOR = 3.4, 95% CI:1.6-7.2), from the most oppressed social classes (AOR = 3.0, 95% CI:1.2-7.6), were married to illiterate husbands (AOR = 2.5, 95% CI:1.2-5.2), had attended fewer than four antenatal visits (AOR = 2.0, 95% CI: 1.4-2.6), had low incomes (AOR = 1.7, 95% CI:1.1-2.9) or lived in rural settings (AOR = 1.5, 95% confidence interval CI:1.2-2.1). CONCLUSION:The paper identifies vulnerable women who require extra care from the health system, and draws attention to the need for interventions to reduce the harmful effects of domestic violence on women's preparations for childbirth.

Size homeostasis is fundamental in cell biology, but it is not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors in intracellular length sensing. Computational simulations suggest that spatial information can be encoded by the frequency of an oscillating retrograde signal arising from a composite negative feedback loop between bidirectional motor-dependent signals. The model predicts that decreasing either or both anterograde or retrograde signals should increase cell length, and this prediction was confirmed upon application of siRNAs for specific kinesin and/or dynein heavy chains in adult sensory neurons. Heterozygous dynein heavy chain 1 mutant sensory neurons also exhibited increased lengths both in vitro and during embryonic development. Moreover, similar length increases were observed in mouse embryonic fibroblasts upon partial downregulation of dynein heavy chain 1. Thus, molecular motors critically influence cell-length sensing and growth control.