HiC

MOTIVATION: Pre-trained protein language and/or structural models are often fine-tuned on drug development properties (ie, developability properties) to accelerate drug discovery initiatives. However, these models generally rely on a single structural conformation and/or a single sequence as a molecular representation. We present a physics-based model whereby 3D conformational ensemble representations are fused by a transformer-based architecture and concatenated to a language representation to predict antibody protein properties...

Research ethics review committees (ERCs) worldwide faced daunting challenges during the COVID-19 pandemic. There was a need to balance rapid turnaround with rigorous evaluation of high-risk research protocols in the context of considerable uncertainty. This study explored the experiences and performance of ERCs during the pandemic. We conducted an anonymous, cross-sectional, global online survey of chairs (or their delegates) of ERCs who were involved in the review of COVID-19-related research protocols after March 2020...

BACKGROUND: Many mothers in high-income countries (HIC) do not breastfeed to the World Health Organisation's recommendation of two years. This is particularly true for low-income women (LIW). They often face additional socio-structural barriers that encourage early discontinuation and are inadequately supported by current healthcare interventions. Teleinterventions are flexible and widely used following the global pandemic and increase maternal autonomy over intervention delivery. They show promise in improving other maternal conditions in LIW, including postpartum depression...

This session deals with the rational design of viral clearance studies for biopharmaceuticals including recombinant proteins such as monoclonal antibodies and, as new in scope of the symposium, also viral clearance for adeno-associated viral (AAV) vectors. For recombinant proteins, large datasets were accumulated over the last decades and are intended to be used for accelerated product process development and streamlining of viral clearance studies. How to utilize prior knowledge in viral clearance validation and how it can be used in a risk assessment tool to decide whether additional virus clearance studies are necessary during product development is being addressed by three of the presentations of this session...

Extracellular vesicles (EVs) have garnered much interest due to their fundamental role in intracellular communication and their potential utility in clinical diagnostics and as biotherapeutic vectors. Of particular relevance is the subset of EVs referred to as exosomes, ranging in size from 30 to 150 nm, which contain incredible amounts of information about their cell of origin, which can be used to track the progress of disease. As a complementary action, exosomes can be engineered with therapeutic cargo to selectively target diseases...

Co-formulation of multiple drug products is an efficient and convenient approach to simultaneously deliver multiple biotherapeutics with the potentially added benefit of a synergistic therapeutic effect. However, co-formulation also increases the risk of heteromeric interactions, giving rise to unique impurities with unknown efficacy and immunogenicity. Therefore, it is critical to develop methods to evaluate the risk of heteromers as an impurity that could affect potency, efficacy, and/or immunogenicity. The most direct strategy to evaluate antibody heteromers is via specific enrichment...

This study reports a metal- and light-free decarboxylative C-H alkylation of heteroarenes at room temperature. The reaction generates various primary, secondary, and tertiary alkyl radicals and functionalizes seven different privileged scaffolds widely present in bioactive molecules. During this process, one equivalent of hypervalent iodine(III) carboxylates (HICs) plays dual roles as an alkyl radical precursor and an oxidant.

INTRODUCTION: Female participation is lower than males in both acute stroke and stroke rehabilitation trials. However, less is known about how female participation differs across countries and regions. OBJECTIVE: To systematically assess the percentage of female participants in RCTs of post stroke rehabilitation of upper extremity (UE) motor disorders in low-middle-income (LMICs) and high-income countries (HICs) as well as different HIC world regions. MATERIALS & METHODS: CINAHL, Embase, PubMed, Scopus and Web of Science were searched from 1960 to April 1, 2021...

OBJECTIVE: Occupant impact safety is critical for train development. This paper proposes a systematic procedure for developing validated numerical occupant crash scenarios for high-speed trains by integrating experimental, computational, and inverse methods. METHODS: As the train interior is the most potentially injury-causing factor, the material properties were acquired by mechanical tests, and constitutive models were calibrated using inverse methods. The validity of the seat material constitutive model was further verified via drop tower tests...

Palliative radiotherapy (RT) effectively relieves pain in patients with bone metastases (BMs). Furthermore, several clinical trials, in most cases conducted in high-income countries (HICs), proved that single-fraction RT is equally effective compared to multi-fractionated RT. However, the evidence is scarce regarding low/middle-income countries (LMICs), where the diagnosis of BMs could be later and RT techniques less advanced. Therefore, we conducted a systematic literature review to evaluate the efficacy of palliative RT of BMs in the LMIC setting...

BACKGROUND: Perforation of peptic ulcer (PPU) is the most morbid complication of peptic ulcer disease (PUD) with scant recent reports from sub-Saharan Africa. The aim of this study was to describe a PPU series from a single centre in South Africa and contrast the findings with other recent reports from sub-Saharan Africa. METHODS: A retrospective study of PPU at Kalafong Hospital in Pretoria was performed. The relationship of patient demographics, risk factors, ulcer pathology and severity scores to mortality were analysed...

BACKGROUND: How pediatric medulloblastoma patients fare in Lower Middle-Income Country (LMICs) in South America is not well understood. Correspondingly, the aim of this study was to summarize the pediatric neurosurgical experience of an institution in La Paz, and compare outcomes to that of a generalized High Income Country (HIC) United States (US) experience. METHODS: A retrospective review of all pediatric neurosurgical medulloblastoma patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr...

BACKGROUND: Health research that significantly impacts global clinical practice and policy is often published in high-impact factor (IF) medical journals. These outlets play a pivotal role in the worldwide dissemination of novel medical knowledge. However, researchers identifying as women and those affiliated with institutions in low- and middle-income countries (LMIC) have been largely underrepresented in high-IF journals across multiple fields of medicine. To evaluate disparities in gender and geographical representation among authors who have published in any of five top general medical journals, we conducted scientometric analyses using a large-scale dataset extracted from the New England Journal of Medicine (NEJM) , Journal of the American Medical Association (JAMA) , The British Medical Journal (BMJ) , The Lancet , and Nature Medicine ...

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC)...

While low- and middle-income countries (LMICs), especially in Southern and Eastern Africa, bear the largest burden of the HIV globally, investigators working on the front lines in these regions are leading a limited number of research efforts, particularly related to HIV cure. Conducting HIV cure research in high-burden HIV LIMCs provides an unparalleled opportunity to formulate innovative research strategies, design trials tailored to the local context, evaluate clinical outcomes within key and vulnerable populations, meaningful involvement of stakeholders, and to shape policies in areas where HIV prevention and cure interventions can yield the most significant impact...

Background Immigrants to the United States, on average, accumulate cardiovascular risk after resettlement, including obesity. There is a need to co-create interventions to address these disparities, and mood may be an important mediating factor. Methods The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion...

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities. Therefore, in this analysis we aimed to reappraise gaps and evaluate progress in diagnosis and treatment equity in high-income (HIC) versus low- and middle-income countries (LMICs). METHODS: Estimates of the global CF population were made in 158 countries using patient registries, systematic literature searches, and an international survey of 14 CF experts...

BACKGROUND AND OBJECTIVES: Transfusion safety may be becoming dependent on the financial resources made available for transfusion structures and may vary between high-income countries (HIC) and low-to-middle-income countries (LMIC). To assess whether there is a difference in the reported TR between these two groups of countries, we examined TR reported in Tunis the capital of Tunisia, a LMIC, and compared their frequency with reported TR in HIC. MATERIALS AND METHODS: Data of TR were collected from transfusion incident report (TIR) forms declared by healthcare facilities in Tunis between 2015 and 2019...

IMPORTANCE: Scientific publication is an important tool for knowledge dissemination and career advancement, but authors affiliated with institutions in low- and middle-income countries (LMICs) are historically underrepresented on publications. OBJECTIVE: To assess the country income level distribution of author affiliations for publications resulting from National Cancer Institute (NCI)-supported extramural grants between 2015 and 2019, with international collaborating institutions exclusively in 1 or more LMICs...

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders...