Miracle-dz/UniFAR-FTUs huggingface dataset:
Polygenic Transcriptome Risk Scores 1 Can Translate Genetic Results 2 Between Species 3

Genome-wide association studies have demonstrated that most 35 traits are highly polygenic; however, translating these polygenic signals into 36 biological insights remains diﬃcult. A lack of satisfactory methods for 37 translating polygenic results across species has precluded the use of model 38 organisms to address this problem. Here we explore the use of polygenic 39 transcriptomic risk scores (PTRS) for translating polygenic results across species. 40 Unlike polygenic risk scores (PRS), which rely on SNPs for predicting traits, PTRS 41 use imputed gene expression for prediction, which allows cross-species 42 translation to orthologous genes. We ﬁrst developed RatXcan, which is a 43 framework for transcriptome-wide association studies (TWAS) in outbred rats. 44 Leveraging predicted transcriptome and genotype data from UK Biobank, and 45 the genetically trained gene expression models from RatXcan, we scored more 46 than 3,000 rats using a human-derived PTRS for height. Strikingly, we found that 47 human-derived height PTRS signiﬁcantly predicted body length in rats (P<0.013). 48 The genes included in the PTRS were enriched for biological pathways including 49 skeletal growth and metabolism and were over-represented in tissues including 50 pancreas and brain. This approach facilitates experimental studies in model 51 organisms that examine the polygenic basis of human complex traits and 52 provides an empirical metric by which to evaluate the suitability of speciﬁc 53 animal models and identify their shared biological underpinnings. 54
Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain

The midbrain participates in complex neural information processing in the ascending and descending circuits, but their organization remains unclear due to the lack of comprehensive dissection of the characterization of individual neurons. Combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired the whole-brain dataset with high resolution and reconstructed the detailed morphology of the pontine-tegmental cholinergic neurons (PTCNs). As the main cholinergic system of the midbrain, the individual PTCNs own abundant axons with length up to 60 cm and 5000 terminal branches and innervate multiple brain regions from the spinal cord to cortex in both hemispheres. According to various targeting regions in the ascending and descending circuits, individual PTCNs could be grouped into four types and the axonal fibers of cholinergic neurons in the pedunculopontine nucleus present more divergent while neurons in the laterodorsal tegmental nucleus contain richer axonal fibers and dendrites. In the axonal targeting nuclei, such as in the thalamus or cortex, the individual neurons innervate multiple sub-regions with separate pathways. These results provide the detailed organization characterization of the cholinergic neurons to understand the connection logic of the midbrain.
Multivalency, autoinhibition, and protein disorder in the regulation of interactions of dynein intermediate chain with dynactin and the nuclear distribution protein

Cytoplasmic dynein plays crucial roles in the intracellular transport of organelles and other cargoes. Central to dynein function is the intrinsically disordered N-terminal domain of dynein intermediate chain (IC), which binds the three dimeric dynein light chains at multivalent sites, and dynactin p150Glued and nuclear distribution protein (NudE) at overlapping sites. The disorder in IC has hindered cryo-electron microscopy and X-ray crystallography studies of its structure and interactions. Here we use a suite of biophysical methods to reveal how multivalent binding of the three light chains regulate IC interactions with p150Glued and NudE. Using the N-terminal domain or the full-length IC from Chaetomium thermophilum, a tractable species to interrogate IC interactions, we identify a significant reduction in IC’s binding affinity for p150Glued and a loss of binding to NudE in contrast to the tight binding observed with small IC constructs. We attribute this difference to autoinhibition caused by strong long-range intramolecular interactions that cover IC’s N-terminal single α-helix, the site for p150Glued and NudE binding. Reconstitution of IC subcomplexes demonstrate that autoinhibition is differentially regulated by light chains binding underscoring their importance both in assembly and organization of IC, and in selection between multiple binding partners at the same site.
Increasing Engagement in Kitten Fostering Programs: Lessons Learned From High Kitten Intake Zip Codes in Los Angeles County

The goal of the current study was to identify ways to increase awareness and engagement in kitten fostering programs (KFPs) among residents of areas with a high intake of kittens to animal shelters in Southern California (i.e., Los Angeles County). Specifically, we aimed to understand residents': (1) awareness of KFPs and kitten overpopulation issues, (2) interest in fostering kittens with an animal welfare organization, (3) concerns about fostering, (4) perceived ability to meet common KFP requirements, and (5) perceptions of potential KFP marketing/messaging and communication methods. Participants included 283, predominantly Hispanic/Latinx adults aged 18 years or older who resided in Los Angeles County and who lived in one of 12 zip codes with a high rate of kitten shelter intake. Survey results indicated that more than one quarter of participants had engaged in fostering on their own without an animal shelter or rescue program. One-third of the total sample, and more than two-thirds of participants who had already fostered cats and kittens on their own, were open to fostering kittens in partnership with an animal shelter. A majority of individuals who were interested in fostering had not seen advertising for fostering programs; Spanish-language participants were significantly less likely than expected to have encountered program advertisements. The most prevalent concerns about fostering in our sample were centered on the time (79%), cost (78%), and space (77%) required to engage in fostering. Text, email, social media, and mail were among the most preferred methods for marketing and communication, with some variation between Spanish and English language respondents. Opportunities for increasing engagement included, but were not limited to, improving the promotion of program advertisements using animal-welfare and cost-focused messaging approaches and improving the dissemination and marketing of Spanish-language materials. Providing community members with realistic expectations of the time, resources, and support they will get from animal welfare organizations may improve engagement in KFPs, as well as identifying alternative resources and supports (e.g., transportation, in-home veterinary visits) to assist community members in serving animals in their community.
Determining Inaccurate Coordinates in Electronic Data Collection for Surveillance and Immunization Supportive Supervision: A Case Study of Nigeria EPI Supportive Supervision Module

The mobile phone global positioning system (GPS) is used to reconnaissance a mobile phone user's location, e.g., at work, home, shops, etc. Such information can be used to feed data gathering expeditions, the actual position of the interviewer/surveyor using the mobile phone inert settings of location mode via GPS, WIFI, and Mobile networks. Mobile devices are becoming progressively erudite and now integrate diverse and robust sensors. The new generation of smartphones is multi-laden with sensors, including GPS sensors. The study describes and evaluates a data-gathering process used by the World Health Organization (WHO–Nigeria, EPI Program) that uses phone-based in-built GPS sensors to identify the position of users while they undergo supportive supervision. This form of spatial data is collected intrinsically using the Open Data Kit (ODK) GPS interface, which interlaces with the mobile phone GPS sensor to fetch the geo-coordinates during the process. It represents a step in building a methodology of matching places on the map with the geo-coordinates received from the mobile phones to investigate deviation patterns by devices and location mode. The empirical results can help us to understand the variation in geospatial data collation across devices and highlight critical criteria for choosing mobile phones for mobile surveys and data campaigns. This study reviewed the existing data gathered inadvertently from 10 brands of smartphones over 1 year of using the mobile data collection with over 80,000 field visits to predict the deviation pattern for spatial data acquisition via mobile phones by different brands.
Penicillin Allergy and Perioperative Anaphylaxis

Penicillin allergy is the most commonly reported drug allergy, while perioperative anaphylaxis is overall rare. This review covers the epidemiology of both penicillin allergy and perioperative anaphylaxis both separately and taken together. Considerations regarding anaphylaxis to penicillin during pregnancy are also discussed, since penicillin is the drug of choice for Group B Streptococcus prophylaxis. The minimal cross reactivity between penicillins and cephalosporins is addressed, since the vast majority of patients with a penicillin allergy label can receive perioperative cephalosporins. The management of the patient who has experienced perioperative anaphylaxis, including the importance of allergy referral is covered. Approaches to pre-operative penicillin allergy evaluations and opportunities for education are highlighted.
Wind-Driven Mechanisms for the Variations of the Pacific Equatorial Undercurrent Based on Adjoint Sensitivity Analysis

The maintenance and variation of the Pacific Equatorial Undercurrent (EUC) are thought to be controlled by the zonal pressure gradient force (ZPGF). However, a recent study found that a large-scale circulation associated with Rossby waves can also lead to EUC variation, implying that the structures and timing of the influential winds and the underlying wind-driven mechanisms need to be revisited. Here, we use the adjoint-sensitivity method to obtain the crucial winds that can most efficiently influence EUC variations. The obtained adjoint sensitivities (denoting the sensitive winds) are confined to 15°S–15°N and exhibit a funnel-shaped pattern with high symmetry about the equator. The remote winds, which occur 4 to 11 months prior, can lead to EUC variations at the basin scale; in contrast, the near-term winds (occurring not earlier than 4 months) lead only to local EUC variations. Accordingly, we find that wind-initiated equatorial Kelvin waves, equatorial Rossby waves, and the reflected waves at both the western and eastern boundaries superimpose onto each other to result in EUC variations. Specifically, when the travel time is longer than 4 months, the waves can form a negative-positive-negative sea surface height anomaly (SSHA) pattern between 15°S and 15°N in the central-eastern tropical Pacific, indicating the joint effect of both types of waves; they also form a positive SSHA in the western equatorial Pacific, indicating the dominance of the Kelvin wave therein. These mechanisms are complementary to the canonical ZPGF mechanism, which provide a clear theoretical basis for EUC variation studies.
Endogenous Retroviruses (ERVs): Does RLR (RIG-I-Like Receptors)-MAVS Pathway Directly Control Senescence and Aging as a Consequence of ERV De-Repression?

Bi-directional transcription of Human Endogenous Retroviruses (hERVs) is a common feature of autoimmunity, neurodegeneration and cancer. Higher rates of cancer incidence, neurodegeneration and autoimmunity but a lower prevalence of autoimmune diseases characterize elderly people. Although the re-expression of hERVs is commonly observed in different cellular models of senescence as a result of the loss of their epigenetic transcriptional silencing, the hERVs modulation during aging is more complex, with a peak of activation in the sixties and a decline in the nineties. What is clearly accepted, instead, is the impact of the re-activation of dormant hERV on the maintenance of stemness and tissue self-renewing properties. An innate cellular immunity system, based on the RLR-MAVS circuit, controls the degradation of dsRNAs arising from the transcription of hERV elements, similarly to what happens for the accumulation of cytoplasmic DNA leading to the activation of cGAS/STING pathway. While agonists and inhibitors of the cGAS–STING pathway are considered promising immunomodulatory molecules, the effect of the RLR-MAVS pathway on innate immunity is still largely based on correlations and not on causality. Here we review the most recent evidence regarding the activation of MDA5-RIG1-MAVS pathway as a result of hERV de-repression during aging, immunosenescence, cancer and autoimmunity. We will also deal with the epigenetic mechanisms controlling hERV repression and with the strategies that can be adopted to modulate hERV expression in a therapeutic perspective. Finally, we will discuss if the RLR-MAVS signalling pathway actively modulates physiological and pathological conditions or if it is passively activated by them.
Role Medium-Chain Fatty Acids in the Lipid Metabolism of Infants

Human breastmilk, the ideal food for healthy infants, naturally contains a high concentration of medium-chain fatty acids (MCFAs, about 15% of total fatty acids). MCFAs are an important energy source for infants due to their unique digestive and metabolic properties. MCFA-enriched oils are widely used in an infant formula, especially the formula produced for preterm infants. Recently, there has been a growing interest in the triglyceride structure of MCFAs in human milk, their metabolism, and their effects on infant health. This study summarized the MCFA composition and structure in both human milk and infant formula. Recent studies on the nutritional effects of MCFAs on infant gut microbiota have been reviewed. Special attention was given to the MCFAs digestion and metabolism in the infants. This paper aims to provide insights into the optimization of formulations to fulfill infant nutritional requirements.
Road Toward a New Model of Care for Idiopathic Pulmonary Fibrosis in the Lazio Region

A timely, confirmed diagnosis of Idiopathic Pulmonary Fibrosis (IPF) has a significant impact on the evolution of the disease. The current model of care in the Lazio region (in Italy) was assessed on the basis of real-world data provided by the four reference centers responsible for diagnosing and treating IPF. The 5-year, population-based, retrospective longitudinal study provided the data that is at the basis of the current proposal for a new clinical and therapeutic pathway (DTCP) and has been shared with regional decision makers. A DTCP must be defined and based on four pillars: GPs, pulmonologists, IPF centers, and telemedicine. Each must play a role within a sort of hub-and-spoke model. IPF centers remain the hubs, while spokes are identified in trained GPs and pulmonologists.
Schizophrenia and Inflammation Research: A Bibliometric Analysis

Background Schizophrenia (SCZ) is a severe psychiatric disorder that involves inflammatory processes. The aim of this study was to explore the field of inflammation-related research in SCZ from a bibliometric perspective. Methods Regular and review articles on SCZ- and inflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to February 19, 2022. R package “bibliometrix” was used to summarize the main findings, count the occurrences of the top keywords, visualize the collaboration network between countries, and generate a three-field plot. VOSviewer software was applied to conduct both co-authorship and co-occurrence analyses. CiteSpace was used to identify the top references and keywords with the strongest citation burst. Results A total of 3,596 publications on SCZ and inflammation were included. Publications were mainly from the USA, China, and Germany. The highest number of publications was found in a list of relevant journals. Apart from “schizophrenia” and “inflammatory”, the terms “bipolar disorder,” “brain,” and “meta-analysis” were also the most frequently used keywords. Conclusions This bibliometric study mapped out a fundamental knowledge structure consisting of countries, institutions, authors, journals, and articles in the research field of SCZ and inflammation over the past 30 years. The results provide a comprehensive perspective about the wider landscape of this research area.
A Qualitative Study of Stakeholders’ Views on Pharmacovigilance System, Policy, and Coordination in Pakistan

Objectives: Due to the absence of necessary rules, poor coordination, and various challenges, the pharmacovigilance system of Pakistan is not optimally functional at all levels of the health system. The objective of the study was to assess the stakeholders’ perceptions of the current ADR reporting system and to identify the pharmacovigilance policy issues and problems of effective coordination. Methodology: Stakeholders from a broad range of disciplines, academia, regulatory authorities, the pharmaceutical industry, international health organizations, as well as pharmacovigilance experts, and healthcare professionals were included in the study. A total of 25 stakeholders throughout Pakistan were interviewed during exploratory semi-structured interviews. The interviews were recorded digitally, transcribed, coded, compared, and grouped according to their similarity of themes. Participants provided insights into gaps, limitations, and challenges of Pakistan’s current ADR reporting system, issues with proposed pharmacovigilance rules, and coordination difficulties. Results: The majority of the participants considered the ADR reporting system in Pakistan to be improving but in a nascent phase. The identified gaps, challenges, limitations of the system, and barriers to reporting were labeled as reasons for limited functioning. Almost all stakeholders were aware of the existence of draft pharmacovigilance rules; however, participants in the industry were familiar with the contents and context of draft pharmacovigilance rules. Bureaucratic red tape and lack of political will appeared to be the top reasons for delaying the approval of the pharmacovigilance rules. Wider consultation, advocacy, and awareness sessions of policymakers and HCPs were suggested for early approval of rules. Participants unanimously agreed that the approval of rules shall improve the quality of life and reduce the economic burden along with morbidity and mortality rates. The need for greater and collaborative coordination among the stakeholders in promoting medicines’ safety was highlighted. All participants suggested the use of media and celebrities to disseminate the safety information. Conclusion: Participants showed partial satisfaction with the way pharmacovigilance in Pakistan is moving forward. However, stakeholders believed that engagement of multi-stakeholders, approval of pharmacovigilance rules, and the establishment of pharmacovigilance centers in provinces, hospitals, and public health programs (PHPs) shall support in achieving the desired results.
Intermittent Caloric Restriction Promotes Erythroid Development and Ameliorates Phenylhydrazine-Induced Anemia in Mice

Background Dietary restriction has a profound effect in altering immune system and promoting metabolic health and aging. However, how dietary restriction impacts erythroid system is largely unknown. We found that a short-term caloric restriction (CR) stimulates expression of KLF1, a master regulator of erythroid development, in the spleen of mouse, and thus explored the potential effect of CR on erythropoiesis. Methods We analyzed the effects of intermittent CR and continuous CR for different lengths of time on parameters of peripheral blood and erythroid profiles in the spleen and bone marrow in C57BL/6 mice. We next assessed how different types of CR affect phenylhydrazine-induced anemia in the mice. Colony formation assay was also used to analyze LK + progenitors and BFU-E in the bone marrow. Results Intermittent CR for 2 weeks raised the number of reticulocytes in the blood, while continuous CR for 2 weeks elevated red blood cells and hemoglobin level. Intermittent CR for 2 weeks promoted extramedullary hematopoiesis in the spleen, while continuous CR mainly promoted erythropoiesis in the bone marrow. Interestingly, a short-term intermittent CR but not continuous CR was able to ameliorate phenylhydrazine-induced anemia. Intermittent CR reduced early-stage erythroblasts and increased late-stage erythroblasts/mature RBCs in the spleen, indicating an accelerated transition from early-stage to late-stage erythroblasts/mature red blood cells. Furthermore, a short-term intermittent CR elevated LK + progenitors and the committed erythroid progenitor cells BFU-E in the bone marrow. Conclusion Our study demonstrated that a short-term intermittent CR, but not continuous CR, has a significant effect to promote hematopoiesis and such activity can ameliorate phenylhydrazine-induced acute anemia in the mouse.
The Effect of Rye-Based Foods on Postprandial Plasma Insulin Concentration: The Rye Factor

Consumption of whole grain has been associated with lower incidence of type-2 diabetes, cardiovascular disease and their risk factors including improved glycemic control. In comparison with other whole grain products, rye bread has been shown to induce lower insulin response in the postprandial phase, without affecting the glucose response. This phenomenon has been referred to as the “rye factor” and is being explored in this review where we summarize the findings from meal and extended meal studies including rye-based foods. Overall, results from intervention studies showed that rye-based foods vs. (wheat) control foods had positive effect on both insulin and glucose responses in the postprandial phase, rather than on insulin alone. Mechanistic studies have shown that the rye factor phenomenon might be due to slowing of the glucose uptake in the intestine. However, this has also been shown for wheat-based bread and is likely an effect of structural properties of the investigated foods rather than the rye per se. More carefully controlled studies where standardized structural properties of different cereals are linked to the postprandial response are needed to further elucidate the underlying mechanisms and determinants for the effect of specific cereals and product traits on postprandial glycemic control.