Miracle-dz/UniFAR-FTUs huggingface dataset:
Which factors predict fertility intentions of married men and women? Results from the 2012 Niger Demographic and Health Survey

Introduction Niger is the country with the highest total fertility rate in the world. In the present study, we investigated factors associated with the desire for more children among married men and women in Niger. Materials and methods We utilised data from the 2012 Niger Demographic and Health Survey. The outcome variable for the study was fertility intentions. The data were analysed with Stata version 14.0. Both descriptive (frequencies and percentages) and inferential (binary logistic regression) analyses were carried out. Results Desire for more children was 97.2% and 87.2% among men and women respectively. Women aged 45–49 were less likely to desire more children, compared to those aged 25–39 [aOR = 0.13, CI = 0.11–0.16]. The odds of desire for more children were high in rural areas, compared to urban areas [aOR = 1.61, CI = 1.20–2.17]. Childbearing women with seven or more births were less likely to desire more children, compared to those with 1–3 births [aOR = 0.09, CI = 0.06–0.14]. Men aged 50–59 were less likely to desire more children, compared to those aged 25–39 [aOR = 0.13, CI = 0.05–0.35]. Men with secondary/higher level of education were less likely to desire more children, compared to those with no formal education [aOR = 0.24, CI = 0.11–0.52]. Childbearing men with seven or more births were less likely to desire more children, compared to those with 1–3 births [aOR = 0.06, CI = 0.01–0.30]. Conclusion This study shows high fertility desire among men and women in Niger. However, the prevalence of fertility desire among men is higher than that of women. A number of socio-economic and demographic factors were found to be associated with desire for more children among men and women in Niger. This calls for a collective effort to educate women and men in Niger on the negative consequences of rapid population growth and large family sizes.
Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

Purpose: Programmed death ligand 1 [PD-(L)1]-targeted therapies have shown modest survival benefit in triple-negative breast cancer (TNBC). PD-L1+ microenvironments in TNBC are not well characterized and may inform combinatorial immune therapies. Herein, we characterized clinicopathologic features, RNA-based immune signatures, and spatially defined protein-based tumor–immune microenvironments (TIME) in early-stage PD-L1+ and PD-L1− TNBC. Experimental Design: From a large cohort of chemotherapy-naïve TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMX) were identified in subsets of PD-L1+ and PD-L1− TNBC, as defined by FDA-approved PD-L1 companion assays. Results: 228 of 499 (46%) TNBC were PD-L1+ (SP142: ≥1% immune cells-positive). Using PD-L1 22C3, 46% had combined positive score (CPS) ≥ 1 and 16% had CPS ≥10. PD-L1+ TNBC were higher grade with higher tumor-infiltrating lymphocytes (TIL; P < 0.05). PD-L1 was not associated with improved survival following adjustment for TILs and other variables. RNA profiles of PD-L1+ TNBC had increased dendritic cell, macrophage, and T/B cell subset features; and decreased myeloid-derived suppressor cells. PD-L1+ stromal and intraepithelial TIMEs were highly enriched in IDO-1, HLA-DR, CD40, and CD163 compared with PD-L1-TIME, with spatially specific alterations in CTLA-4, Stimulator of Interferon Genes (STING), and fibronectin. Macrophage- and antigen presentation–related proteins correlated most strongly with PD-L1 protein. Conclusions: In this early-stage TNBC cohort, nearly 50% were PD-L1+ (SP142 companion assay) while 16% were PD-L1+ with the 22C3 companion assay. PD-L1+ TNBC had specific myeloid-derived and lymphoid features. Spatially defined PD-L1+ TIME were enriched in several clinically actionable immune proteins. These data may inform future studies on combinatorial immunotherapies for patients with PD-L1+ TNBC. See related commentary by Symmans, p. 5446
A Collaborative Intervention Between Emergency Medicine and Infectious Diseases to Increase Syphilis and HIV Screening in the Emergency Department

This study reports that focused collaboration between infectious diseases and emergency medicine providers results in increased identification of patients with syphilis and HIV in the emergency department. Background Sexually transmitted infections (STIs) are a common reason for evaluation in the emergency department (ED). Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should be tested for syphilis and HIV. Syphilis and HIV testing rates in the ED have been reported to be low. The study objective was to examine whether collaboration between emergency medicine (EM) and infectious disease (ID) providers improved syphilis and HIV testing in the ED. Methods A multidisciplinary team of EM and ID providers was formed to identify and address barriers to syphilis and HIV testing in the ED. Syphilis, HIV, chlamydia, and gonorrhea testing and infection rates were calculated and compared during 2 time periods: preintervention (January 1, 2012–December 30, 2017) and postintervention (November 1, 2018–November 30, 2019). We also extracted clinical and laboratory data from patients with positive syphilis and HIV results during the study period. Results The most commonly cited barrier to syphilis and HIV testing was concern about follow-up of positive results. Compared with the preintervention period, syphilis and HIV testing rates increased significantly in the postintervention period (incidence rate ratios, 30.70 [P < 0.0001] and 28.99 [P < 0.0001] for syphilis and HIV, respectively). The postintervention period was also associated with a significant increase in the identification of patients with positive syphilis and HIV results (incidence rate ratios, 7.02 [P < 0.0001] and 2.34 [P = 0.03], respectively). Conclusions Collaboration between EM and ID providers resulted in a significant increase in syphilis and HIV testing and diagnosis in the ED.
Surgeon-performed ultrasound for the staging of acute diverticulitis: Preliminary results of a prospective study

INTRODUCTION Although contrast-enhanced abdominal computed tomography (CEACT) is still considered the criterion standard for the assessment of suspected acute diverticulitis, in recent years, the use of point-of-care ultrasound (POCUS) has been spreading more and more in this setting. The aim of this study was to compare CEACT to POCUS for the diagnosis and staging of suspected acute diverticulitis. METHODS This is a prospective study conducted on 55 patients admitted to the emergency department of two Italian Hospitals with a clinical suspicion of acute diverticulitis between January 2014 and December 2017. All the patients included underwent POCUS first and CEACT immediately afterward, with the diagnosis and the staging reported according to the Hinchey (H) classification modified by Wasvary et al. [Wasvary H, Turfah F, Kadro O, Beauregard W. Same hospitalization resection for acute diverticulitis. Am Surg. 1999;65:632–635. ] Three surgeons performed all the POCUS, and the same two radiologists retrospectively analyzed all the CEACT images. The radiologists were informed of the clinical suspicion but unaware of the POCUS findings. The CEACT was used as the criterion standard for the comparison. RESULTS The final cohort included 30 females (55%) and 25 males (45%). The median age was 62 years (range, 24–88 years), and the median body mass index was 26 kg/m2 (range, 19–42 kg/m2). Forty-six of 55 patients had a confirmed diagnosis of acute diverticulitis on both POCUS and CEACT, whereas, in 7 patients, the diagnosis was not confirmed by both methods. Point-of-care ultrasound sensitivity and specificity were 98% and 88%, respectively. Point-of-care ultrasound positive and negative predictive values were 98% and 88%, respectively. Point-of-care ultrasound accuracy was 96%. Point-of-care ultrasound classified 33 H1a, 11 H1b, 1 H2, and 1 H3 acute diverticulitis. This staging was confirmed in all patients but three (93%) by CEACT. CONCLUSION Point-of-care ultrasound appeared a reliable technique for the diagnosis and the staging of clinically suspected H1 and H2 acute diverticulitis. It could contribute in saving time and resources and in avoiding unnecessary radiation exposure to most patients. LEVEL OF EVIDENCE Diagnostic test, level III.
Individuals co-exposed to sand fly saliva and filarial parasites exhibit altered monocyte function

Background In Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions. Methodology/Principal findings To understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes. Conclusions/Significance Together, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines.
Sex Differences in Neuromuscular Fatigue and Changes in Cost of Running after Mountain Trail Races of Various Distances

Supplemental digital content is available in the text. ABSTRACT Introduction Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). Methods Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (<60 and >100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. Results Compared with men, women displayed a smaller decrease in maximal strength in KE (−36% vs −27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: −10% vs −24%, respectively, P < 0.05). Cr increased similarly in men and women. Conclusions Women experience less neuromuscular fatigue than men after both “classic” and “extreme” prolonged running exercises but this does not impact the degradation of the energy Cr.
Autophagy modulates FSS‐induced epithelial–mesenchymal transition in hepatocellular carcinoma cells

Hepatocellular carcinoma is a highly fatal disease and threatens human health seriously. Fluid shear stress (FSS), which is caused by the leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage, has been identified as contributing pathologically to cancer metastasis. Autophagy and epithelial–mesenchymal transition (EMT) are both reported to be involved in cancer cell migration and invasion, but little has been revealed about the interaction between autophagy and EMT under a tumor mechanical microenvironment. Here, we identified that exposure to 1.4 dyne/cm2 FSS could promote the formation of autophagosomes and significantly increase the expressions of autophagy‐related markers of beclin1 and ATG7, and the ratio of LC3Ⅱ/Ⅰ in both of HepG2 and QGY‐7703 cells. The FSS loading also elevated the levels of mesenchymal markers N‐cadherin, Vimentin, Twist, Snail, and β‐catenin, while the epithelial markers E‐cadherin showed a decrease. Once the autophagy was blocked by 3‐methyladenine (3‐MA) or knocking ATG5 down, the occurrence of FSS‐induced EMT was inhibited dramatically according to the expression and translocation of E‐cadherin, N‐cadherin, and β‐catenin. Given the effect of EMT on cell migration, we observed that inhibition of autophagy could impede FSS‐induced cell migration. Collectively, this study demonstrated that autophagy played a crucial role in FSS‐induced EMT and cell migration in hepatocellular carcinoma.
The clinical impact of maternal weight on offspring health: lights and shadows in breast milk metabolome

ABSTRACT Introduction Pre-pregnancy overweight and obesity, depending on maternal nutrition and metabolic state, can influence fetal, neonatal, and long-term offspring health, regarding cardio-metabolic, respiratory, immunological, and cognitive outcomes. Thus, maternal weight can act, through mechanisms not fully understood, on the physiology and metabolism of some fetal organs and tissues, to adapt themselves to the intrauterine environment and nutritional reserves. These effects can occur by modulating gene expression, neonatal microbiome, and through breastfeeding. Areas Covered In this paper, we investigated the potential effects of metabolites found altered in breast milk (BM) of overweight/obese mothers, through an extensive review of metabolomics studies, and the potential short and long-term clinical effects in the offspring, especially overweight, glucose homeostasis, insulin resistance, oxidative stress, infections, immune processes, neurodevelopment. Expert Opinion Metabolomics seems the ideal tool to investigate BM variation depending on maternal or fetal/neonatal factors. In particular, BM metabolome alterations according to maternal conditions were recently pointed out in cases of gestational diabetes, preeclampsia, intrauterine growth restriction and maternal overweight/obesity. In our opinion, even if BM is the food of choice in neonatal nutrition, the deepest comprehension of its composition in overweight/obese mothers could allow targeted supplementation, to improve offspring health and metabolic homeostasis.
Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray

Significance Depression is a serious disease afflicting an increasing number of people, including adolescents. Animal studies indicate that the neuropeptide galanin and its three receptors, GalR1 to 3, are involved in depression-like behavior, evidenced by increased GalR1 transcript levels in the ventral periaqueductal gray of “depressed” rats. Here, we show coexistence of Scratch2 and GalR1, identifying a possible mechanism underlying control of GalR1 expression in this region: the transcription factor Scratch2 lowers, via binding to an E-box in the GalR1 promoter, expression of the GalR1 receptor. This may represent a further role for Scratch2, earlier associated with embryonic development, cell migration, and neurogenesis. Because GalR1 seems involved in major depression, we discuss whether or not Scratch2 also may play a role in the human disease. Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from −250 to −220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.
Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes

Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14). MUN14 B cells efficiently infiltrated the CNS within one week and produced neurological pathologies. We compared the gene expression profiles of viral and cellular genes using RNA-Seq and identified one viral (EBNA1) and several cellular gene candidates, including secreted phosphoprotein 1/osteopontin (SPP1/OPN), neuron navigator 3 (NAV3), CXCR4, and germinal center-associated signaling and motility protein (GCSAM) that were selectively upregulated in MUN14. ATAC-Seq and ChIP-qPCR revealed that these gene expression changes correlated with epigenetic changes at gene regulatory elements. The neuroinvasive phenotype could be attenuated with a neutralizing antibody to OPN, confirming the functional role of this protein in trafficking EBV+ B cells to the CNS. These studies indicate that B-cell trafficking to the CNS can be acquired by epigenetic adaptations and provide a new model to study B-cell neuroinvasion associated CNS lymphoma and autoimmune disease of the CNS, including multiple sclerosis (MS).
Increased body fat content in horses alters metabolic and physiological exercise response, decreases performance, and increases locomotion asymmetry

This study examined the effect of altered body weight (BW) and body fat content on exercise performance and recovery. Nine horses were divided into two groups, and changes in BW and fat content were induced by feeding a high (HA) or restricted (RA) energy allowance for 36 days in a cross‐over design. In the last week of each treatment, BW and body condition score (BCS) were recorded, body fat percentage was estimated using ultrasound, and a standardized incremental treadmill exercise test (SET) and competition‐like field test were performed (scored by judges blinded to treatments). Blood samples were collected, and heart rate (HR), rectal temperature (RT), and respiratory rate (RR) were also recorded. Objective locomotion analyses were performed before and after the field test. Body weight, body fat percentage, and BCS were higher (5–8%) in HA than in RA horses (p < 0.05). In SET, HA horses showed higher HR, plasma lactate concentration, RR, and RT than RA horses (p < 0.05), and lower VLa4, hematocrit (Hct), plasma glucose, and plasma NEFA concentrations (p < 0.05). Hct was also lower in HA horses in the field test, while RA horses showed higher scores (p < 0.05). After both tests, resting plasma lactate concentrations were reached faster in RA than in HA horses (p < 0.05). Objective locomotion asymmetry was higher in HA than in RA (p < 0.05). These results clearly show that increased BW and body fat content in horses lower physiological fitness in terms of VLa4, plasma lactate removal, Hct levels, plasma glucose availability and reduce true performance evaluated by blinded judges.
Enterococcal PrgU Provides Additional Regulation of Pheromone-Inducible Conjugative Plasmids

Bacteria utilize type 4 secretion systems (T4SS) to efficiently transfer DNA between donor and recipient cells, thereby spreading genes encoding antibiotic resistance as well as various virulence factors. Regulation of expression of the T4SS proteins and surface adhesins in Gram-positive bacteria is crucial, as some of these are highly toxic to the cell. ABSTRACT Efficient horizontal gene transfer of the conjugative plasmid pCF10 from Enterococcus faecalis depends on the expression of its type 4 secretion system (T4SS) genes, controlled by the PQ promoter. Transcription from the PQ promoter is tightly regulated, partially to limit cell toxicity caused by overproduction of PrgB, a T4SS adhesin. PrgU plays an important role in regulating this toxicity by decreasing PrgB levels. PrgU has an RNA-binding fold, prompting us to test whether PrgU exerts its regulatory control through binding of prgQ transcripts. We used a combination of in vivo methods to quantify PrgU effects on prgQ transcripts at both single-cell and population levels. PrgU function requires a specific RNA sequence within an intergenic region (IGR) about 400 bp downstream of PQ. PrgU interaction with the IGR reduces levels of downstream transcripts. Single-cell expression analysis showed that cells expressing prgU decreased transcript levels more rapidly than isogenic prgU-minus cells. PrgU bound RNA in vitro without sequence specificity, suggesting that PrgU requires a specific RNA structure or one or more host factors for selective binding in vivo. PrgU binding to its IGR target might recruit RNase(s) for targeted degradation of downstream transcripts or reduce elongation of nascent transcripts beyond the IGR. IMPORTANCE Bacteria utilize type 4 secretion systems (T4SS) to efficiently transfer DNA between donor and recipient cells, thereby spreading genes encoding antibiotic resistance as well as various virulence factors. Regulation of expression of the T4SS proteins and surface adhesins in Gram-positive bacteria is crucial, as some of these are highly toxic to the cell. The significance of our research lies in identifying the novel mechanism by which PrgU performs its delicate fine-tuning of the expression levels. As prgU orthologs are present in various conjugative plasmids and transposons, our results are likely relevant to understanding of diverse clinically important transfer systems.