Further Development of SAMPDI-3D: A Machine Learning Method for Predicting Binding Free Energy Changes Caused by Mutations in Either Protein or DNA.

Background/objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein-DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein-DNA binding, accurately predicting changes in binding free energy (ΔΔG) is valuable for distinguishing pathogenic mutations from benign ones.

Methods: This study describes the development and optimization of the SAMPDI-3Dv2 machine learning method, which is trained on an expanded database of experimentally measured ΔΔGs.

SAAMBE-MEM: a sequence-based method for predicting binding free energy change upon mutation in membrane protein-protein complexes.

Motivation: Mutations in protein-protein interactions can affect the corresponding complexes, impacting function and potentially leading to disease. Given the abundance of membrane proteins, it is crucial to assess the impact of mutations on the binding affinity of these proteins. Although several methods exist to predict the binding free energy change due to mutations in protein-protein complexes, most require structural information of the protein complex and are primarily trained on the SKEMPI database, which is composed mainly of soluble proteins.

Community health workers' barriers and facilitators to use a novel mHealth tool for motivational interviewing to improve adherence to care among youth living with HIV in rural Nepal.

Adherence to treatment regimens is a common challenge in achieving HIV control, especially among youth. Motivational Interviewing (MI) is an evidence-based intervention to facilitate behavior change (such as adherence to treatment) by focusing on the client's priorities and motivations. Community Health Workers (CHWs), who are well situated to engage clients for care, can use MI but studies have shown that they often lose MI skills.

Addressing Challenges for Psychotherapy Supervision in Global Mental Health: Experiential Learnings From Rural Nepal.

Background: As the field of global mental health grows, many psychotherapy trainees will work across cultures in low-resource settings in high-income countries or in low- and middle-income countries. Faculty members and mentors may face several challenges in providing supervision for psychologists in low-resource settings. As such, there is a need to develop best practices for psychotherapy supervision in global mental health.

Predicting the Effect of Single Mutations on Protein Stability and Binding with Respect to Types of Mutations.

The development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein interaction, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods require a database of experimentally measured folding and binding free energy changes for training. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residues on the above-mentioned thermodynamic characteristics, i.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

Introduction: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed.

The development and roll-out of a new hydrocoele surgery facility assessment tool for the elimination of lymphatic filariasis.

A hydrocoele surgery facility assessment tool (HSFAT) was developed to assess the readiness of hydrocoele surgery services in health facilities prior to implementation of hydrocoele surgical campaigns for the elimination of lymphatic filariasis (LF). A first version of the tool was piloted in Bangladesh, Malawi and Nepal in 2019, then, following feedback from country programme managers, a second version of the tool was rolled out across countries implementing hydrocoele surgery in the Accelerating the Control of Neglected Tropical Diseases (Ascend) West and Central Africa Programme, including Benin, Burkina Faso, Ghana, Guinea, Niger and Nigeria. The HSFAT assessed facilities across 10 domains: background information, essential amenities, emergency patient transfer, laboratory capacity, surgical procedures and trained staff, infection prevention, non-disposable basic equipment, disposable basic equipment, essential medicines and current hydrocoele practices.

Implementing Collaborative Care in Low-Resource Government, Research, and Academic Settings in Rural Nepal.

The collaborative care model (CoCM) is a strategy of integrating behavioral health into primary care to expand access to high-quality mental health services in areas with few psychiatrists. CoCM is multifaceted, and its implementation is accelerating in high-resource settings. However, in low-resource settings, it may not be feasible to implement all CoCM components.

Collaborative care model for depression in rural Nepal: a mixed-methods implementation research study.

Introduction: Despite carrying a disproportionately high burden of depression, patients in low-income countries lack access to effective care. The collaborative care model (CoCM) has robust evidence for clinical effectiveness in improving mental health outcomes. However, evidence from real-world implementation of CoCM is necessary to inform its expansion in low-resource settings.

Cross-cultural adaptation of motivational interviewing for use in rural Nepal.

Background: Motivational Interviewing (MI) has a robust evidence base in facilitating behavior change for several health conditions. MI focuses on the individual and assumes patient autonomy. Cross-cultural adaptation can face several challenges in settings where individualism and autonomy may not be as prominent.

Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs: Results of a multi-country analysis.

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped.

Treatment recommendations made by a consultant psychiatrist to improve the quality of care in a collaborative mental health intervention in rural Nepal.

Background: The Collaborative Care Model (CoCM) for mental healthcare, where a consulting psychiatrist supports primary care and behavioral health workers, has the potential to address the large unmet burden of mental illness worldwide. A core component of this model is that the psychiatrist reviews treatment plans for a panel of patients and provides specific clinical recommendations to improve the quality of care. Very few studies have reported data on such recommendations.

An integrated intervention for chronic care management in rural Nepal: protocol of a type 2 hybrid effectiveness-implementation study.

Background: In Nepal, the burden of noncommunicable, chronic diseases is rapidly rising, and disproportionately affecting low and middle-income countries. Integrated interventions are essential in strengthening primary care systems and addressing the burden of multiple comorbidities. A growing body of literature supports the involvement of frontline providers, namely mid-level practitioners and community health workers, in chronic care management.

Gender and neglected tropical disease front-line workers: Data from 16 countries.

Background: Delivery of preventive chemotherapy (PC) through mass drug administration (MDA) is used to control or eliminate five of the most common neglected tropical diseases (NTDs). The success of an MDA campaign relies on the ability of drug distributors and their supervisors-the NTD front-line workers-to reach populations at risk of NTDs. In the past, our understanding of the demographics of these workers has been limited, but with increased access to sex-disaggregated data, we begin to explore the implications of gender and sex for the success of NTD front-line workers.

Assessment of Socio-Demographic Factors, Mother and Child Health Status, Water, Sanitation, and Hygienic Conditions Existing in a Hilly Rural Village of Nepal.

In many low income developing countries, socioeconomic, environmental and demographic factors have been linked to around half of the disease related deaths that occur each year. The aim of this study is to investigate the sociodemographic factors, mother and child health status, water, sanitation, and hygienic conditions of a Nepalese community residing in a hilly rural village, and to identify factors associated with mother and child health status and the occurrence of diarrheal and febrile disease. A community-based cross-sectional survey was carried out and 315 households from the village of Narjamandap were included in this study.

Designing and implementing an integrated non-communicable disease primary care intervention in rural Nepal.

Low-income and middle-income countries are struggling with a growing epidemic of non-communicable diseases. To achieve the Sustainable Development Goals, their healthcare systems need to be strengthened and redesigned. The Starfield 4Cs of primary care-first-contact access, care coordination, comprehensiveness and continuity-offer practical, high-quality design options for non-communicable disease care in low-income and middle-income countries.

Gender equity in mass drug administration for neglected tropical diseases: data from 16 countries.

Background: Gender equity in global health is a target of the Sustainable Development Goals and a requirement of just societies. Substantial progress has been made towards control and elimination of neglected tropical diseases (NTDs) via mass drug administration (MDA). However, little is known about whether MDA coverage is equitable.

Transition to active learning in rural Nepal: an adaptable and scalable curriculum development model.

Background: Traditional medical education in much of the world has historically relied on passive learning. Although active learning has been in the medical education literature for decades, its incorporation into practice has been inconsistent. We describe and analyze the implementation of a multidisciplinary continuing medical education curriculum in a rural Nepali district hospital, for which a core objective was an organizational shift towards active learning.

Delivering Collaborative Care in Rural Settings: Integrating Remote Teleconsultation and Local Supervision in Rural Nepal.

The collaborative care model can deliver high-quality mental health care. In rural regions, clinical supervision is conducted remotely rather than in person. The authors implemented a remote teleconsultation model in rural Nepal, where the consulting psychiatrist is over 30 hours away.

The risk of second primary malignancy in patients with stage Ia non-small cell lung cancer: a U.S. population-based study.

Background: Lung cancer is one of the most common cancers worldwide. Patients with early stage lung cancer have improved long-term survival. With the introduction of low-dose CT scan, more patients are going to be diagnosed at an early stage.

Translating mental health diagnostic and symptom terminology to train health workers and engage patients in cross-cultural, non-English speaking populations.

Although there are guidelines for transcultural adaptation and validation of psychometric tools, similar resources do not exist for translation of diagnostic and symptom terminology used by health professionals to communicate with one another, their patients, and the public. The issue of translation is particularly salient when working with underserved, non-English speaking populations in high-income countries and low- and middle-income countries. As clinicians, researchers, and educators working in cross-cultural settings, we present four recommendations to avoid common pitfalls in these settings.

Collaborative Care for Mental Health in Low- and Middle-Income Countries: A WHO Health Systems Framework Assessment of Three Programs.

The collaborative care model is an evidence-based intervention for behavioral and other chronic conditions that has the potential to address the large burden of mental illness globally. Using the World Health Organization Health Systems Framework, the authors present challenges in implementing this model in low- and middle-income countries (LMICs) and discuss strategies to address these challenges based on experiences with three large-scale programs: an implementation research study in a district-level government hospital in rural Nepal, one clinical trial in 50 primary health centers in rural India, and one study in four diabetes clinics in India. Several strategies can be utilized to address implementation challenges and enhance scalability in LMICs, including mobilizing community resources, engaging in advocacy, and strengthening the overall health care delivery system.

Developing a scalable training model in global mental health: pilot study of a video-assisted training Program for Generalist Clinicians in Rural Nepal.

Background: In low- and middle-income countries, mental health training often includes sending few generalist clinicians to specialist-led programs for several weeks. Our objective is to develop and test a video-assisted training model addressing the shortcomings of traditional programs that affect scalability: failing to train all clinicians, disrupting clinical services, and depending on specialists.

Methods: We implemented the program -video lectures and on-site skills training- for all clinicians at a rural Nepali hospital.