Miracle-dz/UniFAR-FTUs huggingface dataset:
Feasibility of implementing the World Health Organization case management guideline for possible serious bacterial infection among young infants in Ntcheu district, Malawi

Background Neonatal sepsis is a leading cause of mortality, yet the recommended inpatient treatment options are inaccessible to most families in low-income settings. In 2015, the World Health Organization released a guideline for outpatient treatment of young infants (0–59 days of age) with possible serious bacterial infection (PSBI) with simplified antibiotic regimens when referral was not feasible. If implemented widely, this guideline could prevent many deaths. Our implementation research evaluated the feasibility and acceptability of implementing the WHO guideline through the existing health system in Malawi. Methods A prospective cohort study was conducted in 12 first-level health facilities in Ntcheu district. Trained health workers identified and treated young infants with PSBI signs with injection gentamicin for 2 days and oral amoxicillin for 7 days, whereas those with only fast breathing were treated with oral amoxicillin for 7 days. Health Surveillance Assistants (HSAs) were trained to promote care-seeking and to conduct home visits on day 3 and 6 to assess infants under treatment, encourage treatment adherence and remind the caregiver to return for facility follow up. Infants receiving outpatient treatment were followed up at health facility on day 4 and 8. The primary outcome was proportion of outpatient cases completing treatment per protocol. Findings A total of 358 infants received outpatient treatment (202 clinical severe infection, 156 only fast breathing) from February to September 2017. Of these, 92.7% (332/358) met criteria for treatment completion and 88.8% (318/358) completed the day 4 follow-up. Twelve (3.4%) young infants clinically failed treatment with no reported deaths in those treated at outpatient level. This treatment failure rate was lower than those reported for the simplified regimens tested in the SATT (8–10%) and AFRINEST (5–8%) equivalency trials. More than half of infants (58.1%; 208/358) received HSA follow-up visits on days 3 and 6. Conclusion Study results demonstrate the feasibility of outpatient treatment for sick young infants when referral is not feasible in Malawi, which will inform scale-up in other parts of Malawi and countries with similar health system constraints.
A multicenter randomized controlled trial of medium‐chain triglyceride dietary supplementation on epilepsy in dogs

Abstract Background Medium‐chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). Objective To evaluate the short‐term efficacy of MCTs administered as an add‐on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. Animals Twenty‐eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. Methods A 6‐month multicenter, prospective, randomized, double‐blinded, placebo‐controlled crossover trial was completed, comparing an MCT‐DS with a control‐DS. A 9% metabolic energy‐based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. Results Seizure frequency (median 2.51/month [0‐6.67] versus 2.67/month [0‐10.45]; P = .02) and seizure‐day frequency were significantly (1.68/month [0‐5.60] versus 1.99/month [0‐7.42], P = .01) lower when dogs were fed MCT‐DS in comparison with the control‐DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. Conclusions and Clinical Importance These data show antiseizure properties of an MCT‐DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug‐resistant dogs with epilepsy.
Transcriptomic Prediction of Pig Liver-Enriched Gene 1 Functions in a Liver Cell Line

The newly identified liver-enriched gene 1 (LEG1) encodes a protein with a characteristic domain of unknown function 781 (DUF781/LEG1), constituting a protein family with only one member in mammals. A functional study in zebrafish suggested that LEG1 genes are involved in liver development, while the platypus LEG1 homolog, Monotreme Lactation Protein (MLP), which is enriched in the mammary gland and milk, acts as an antibacterial substance. However, no functional studies on eutherian LEG1s have been published to date. Thus, we here report the first functional prediction study at the cellular level. As previously reported, eutherian LEG1s can be classified into three paralogous groups. Pigs have all three LEG1 genes (pLEG1s), while humans and mice have retained only LEG1a. Hence, pLEG1s might represent an ideal model for studying LEG1 gene functions. RNA-seq was performed by the overexpression of pLEG1s and platypus MLP in HepG2 cells. Enrichment analysis showed that pLEG1a and pLEG1b might exhibit little function in liver cells; however, pLEG1c is probably involved in the endoplasmic reticulum (ER) stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus MLP shows antibacterial activity, confirming the functional study in platypus. Therefore, our study showed from the transcriptomic perspective that mammalian LEG1s have different functions in liver cells due to the subfunctionalization of paralogous genes.
Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates

Tenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no data in the scientific literature on the solid state properties of TAF. In our report, we describe the preparation of two novel polymorphs II and III of tenofovir alafenamide monofumarate (TA MF2 and TA MF3). The solid-state structure of these compounds was investigated in parallel to the previously known tenofovir alafenamide monofumarate form I (TA MF1) and tenofovir alafenamide hemifumarate (TA HF). Interestingly, the single-crystal X-ray diffraction of TA HF revealed that this derivative exists as a co-crystal form. In addition, we prepared a crystalline tenofovir alafenamide free base (TA) and its hydrochloride salt (TA HCl), which enabled us to determine the structure of TA MF derivatives using 15N-ssNMR (15N-solid state nuclear magnetic resonance). Surprisingly, we observed that TA MF1 exists as a mixed ionization state complex or pure salt, while TA MF2 and TA MF3 can be obtained as pure co-crystal forms.
Fecal shedding of Salmonella spp., Clostridium perfringens, and Clostridioides difficile in dogs fed raw meat-based diets in Brazil and their owners’ motivation

The present study aimed to explore the motivations of Brazilian dog owners and their knowledge about the risks related to raw meat-based diets (RMBD) as well as to evaluate important enteropathogens such as Salmonella spp. , C. perfringens, and C. difficile, in feces of dogs fed different diets. The majority of the pet owners (69.3%) reported to have chosen this diet for their dogs, considering it to be more “natural”. A large number of owners declared that RMBD do not pose health risks for their animals (87.9%) or humans (98.8%), even though almost one third of the respondents (34.8%) declared having at least one individual at high risk of infection in contact with RMBD-fed dogs. Stool samples from 46 RMBD-fed dogs and 192 dogs fed commercial dry feed were collected. The present study revealed that dogs fed raw meat diets were almost 30 times more likely to be positive for Salmonella spp. than dogs on a conventional diet. Some of the serovars detected were commonly associated with human salmonellosis, such as S. Typhimurium and S. Saintpaul, and were multidrug resistant. RMBD-fed dogs were more likely to be positive for C. perfringens type A (p = 0.008) and one C. perfringens type F was isolated from these animals. Two toxigenic strains (4.3%) of C. difficile were isolated only from raw meat-fed dogs, all of which were under antibiotic therapy. These toxigenic C. difficile isolates were classified as RT106/ST54 and RT600/ST149, previously associated with infection in dogs and humans. The present work revealed that the owners have a tendency to ignore or are unaware of the risks associated with raw meat diets for dogs. Also, the higher fecal shedding of important enteropathogens in dogs fed RMBD suggests that this diet poses a risk for the animals and the people in contact with them.
The Impact of Posttraumatic Stress Disorder and Moral Injury on Women Veterans' Perinatal Outcomes Following Separation From Military Service.

Posttraumatic stress disorder (PTSD) has been found to lead to several adverse perinatal outcomes in the general population. Preliminary research has found that women veterans with PTSD have an increased prevalence of preterm birth, gestational diabetes, and preeclampsia. Less research has examined the role of moral injury (MI) in perinatal outcomes. This longitudinal survey study examined the impact of PTSD symptoms and MI on prospectively assessed adverse perinatal outcomes among women who became pregnant in the first 3 years after separating from U.S. military service (N = 318). The Moral Injury Events Scale was used to assess the degree to which individuals experienced distress related to transgressions of deeply held moral beliefs, and the Primary Care PTSD Screen for DSM-5 (PC-PTSD) was used to assess PTSD symptoms. Perinatal outcomes included experiencing an adverse pregnancy outcome (e.g., preterm birth, gestational diabetes), postpartum depression and/or anxiety, and perceived difficult pregnancy. Although both PTSD symptoms, adjusted odds ratio (aOR) = 1.16, 95% CI [1.00, 1.35]; and MI, aOR = 1.27, 95% CI [1.06, 1.41], emerged as significant predictors of adverse pregnancy outcomes, only PTSD symptoms were a significant predictor of postpartum depression and/or anxiety, aOR = 1.43, 95% CI [1.22, 1.68], and perception of a difficult pregnancy, β = . 31, when controlling for lifetime trauma exposure, age, socioeconomic status, and ethnic/racial minority status. The results indicate that both PTSD symptoms and MI are associated with adverse perinatal outcomes, supporting the potential need to screen for both PTSD and MI during the perinatal period.
Muscle Activity Detectors—Surface Electromyography in the Evaluation of Abductor Hallucis Muscle

Despite the high availability of surface electromyography (sEMG), it is not widely used for testing the effectiveness of exercises that activate intrinsic muscles of foot in people with hallux valgus. The aim of this study was to assess the effect of the toe-spread-out (TSO) exercise on the outcomes of sEMG recorded from the abductor hallucis muscle (AbdH). An additional objective was the assessment of nerve conduction in electroneurography. The study involved 21 patients with a diagnosed hallux valgus (research group A) and 20 people without the deformation (research group B) who performed a TSO exercise and were examined twice: before and after therapy. The statistical analysis showed significant differences in the third, most important phase of TSO. After the exercises, the frequency of motor units recruitment increased in both groups. There were no significant differences in electroneurography outcomes between the two examinations in both research groups. The TSO exercise helps in the better activation of the AbdH muscle and contributes to the recruitment of a larger number of motor units of this muscle. The TSO exercises did not cause changes in nerve conduction. The sEMG and ENG are good methods for assessing this exercise but a comprehensive assessment should include other tests as well.
Ironic Effects of Thought Suppression: A Meta-Analysis

The ironic effect of thought suppression refers to the phenomenon in which individuals trying to rid their mind of a target thought ironically experience greater levels of occurrence and accessibility of the thought compared with individuals who deliberately concentrate on the thought (Wegner, 1994, doi:10.1037/0033-295X.101.1.34). Ironic effects occurring after thought suppression, also known as rebound effects, were consistently detected by previous meta-analyses. However, ironic effects that occur during thought suppression, also known as immediate enhancement effects, were found to be largely absent. In this meta-analysis, we test Wegner’s original proposition that detection of immediate enhancement effects depends on the cognitive load experienced by individuals when enacting thought suppression. Given that thought suppression is an effortful cognitive process, we propose that the introduction of additional cognitive load would compete for the allocation of existing cognitive resources and impair capacity for thought suppression. Studies (k = 31) consistent with Wegner’s original thought-suppression paradigm were analyzed. Consistent with our predictions, rebound effects were observed regardless of cognitive load, whereas immediate enhancement effects were observed only in the presence of cognitive load. We discuss implications in light of ironic-process theory and suggest future thought-suppression research.
Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.
Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program

The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program’s response to the demands of COVID-19 during this uncertain time in health care.
Design and Experiments of a Water Color Remote Sensing-Oriented Unmanned Surface Vehicle

Integrated and intelligent in situ observations are important for the remote sensing monitoring of dynamic water environments. To meet the field investigation requirements of ocean color remote sensing, we developed a water color remote sensing-oriented unmanned surface vehicle (WC-USV), which consisted of an unmanned surface vehicle platform with ground control station, data acquisition, and transmission modules. The WC-USV was designed with functions, such as remote controlling, status monitoring, automatic obstacle avoidance, and water and meteorological parameter measurement acquisition, transmission, and processing. The key data acquisition module consisted of four parts: A floating optical buoy (FOBY) for collecting remote sensing reflectance (Rrs) via the skylight-blocked approach; a water sample autocollection system that can collect 12 1-L bottles for analysis in the laboratory; a water quality measurement system for obtaining water parameters, including Chlorophyll-a (Chl-a), turbidity, and water temperature, among others; and meteorological sensors for measuring wind speed and direction, air pressure, temperature, and humidity. Field experiments were conducted to validate the performance of the WC-USV on 23–28 March 2018 in the Honghu Lake, which is the seventh largest freshwater lake in China. The tests proved the following: (1) The WC-USV performed well in terms of autonomous navigation and obstacle avoidance; (2) the mounted FOBY-derived Rrs showed good precision in terms of the quality assurance score (QAS), which was higher than 0.98; (3) the Chl-a and suspended matters (SPM) as ocean color parameters measured by the WC-USV were highly consistent with laboratory analysis results, with determination coefficients (R2) of 0.71 and 0.77, respectively; and (4) meteorological parameters could be continuously and stably measured by WC-USV. Results demonstrated the feasibility and practicability of the WC-USV for automatic in situ observations. The USV provided a new way of thinking for the future development of intelligent automation of the aquatic remote sensing ground verification system. It could be a good option to conduct field investigations for ocean color remote sensing and provide an alternative for highly polluted and/or shallow high-risk waters which large vessels have difficulty reaching.
Multifaceted Role of PRDM Proteins in Human Cancer

The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.
Genes and Diet in the Prevention of Chronic Diseases in Future Generations

Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.
The neuronal receptor tyrosine kinase Alk is a target for longevity

Inhibition of signalling through several receptor tyrosine kinases (RTKs), including the insulin‐like growth factor receptor and its orthologues, extends healthy lifespan in organisms from diverse evolutionary taxa. This raises the possibility that other RTKs, including those already well studied for their roles in cancer and developmental biology, could be promising targets for extending healthy lifespan. Here, we focus on anaplastic lymphoma kinase (Alk), an RTK with established roles in nervous system development and in multiple cancers, but whose effects on aging remain unclear. We find that several means of reducing Alk signalling, including mutation of its ligand jelly belly (jeb), RNAi knock‐down of Alk, or expression of dominant‐negative Alk in adult neurons, can extend healthy lifespan in female, but not male, Drosophila. Moreover, reduced Alk signalling preserves neuromuscular function with age, promotes resistance to starvation and xenobiotic stress, and improves night sleep consolidation. We find further that inhibition of Alk signalling in adult neurons modulates the expression of several insulin‐like peptides, providing a potential mechanistic link between neuronal Alk signalling and organism‐wide insulin‐like signalling. Finally, we show that TAE‐684, a small molecule inhibitor of Alk, can extend healthy lifespan in Drosophila, suggesting that the repurposing of Alk inhibitors may be a promising direction for strategies to promote healthy aging.