Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective Evaluation of the mariPOC Test for Detection of Clostridioides difficile Glutamate Dehydrogenase and Toxins A/B

The objective of this study was to evaluate a novel automated random-access test, mariPOC CDI (ArcDia Ltd., Finland), for the detection of Clostridioides difficile glutamate dehydrogenase (GDH) and toxins A and B directly from fecal specimens. The mariPOC test was compared with both the GenomEra C. difficile PCR assay (Abacus Diagnostica Oy, Finland) and the TechLab C. diff Quik Chek Complete (Alere Inc.; now Abbot) membrane enzyme immunoassay (MEIA). Culture and the Xpert C. difficile assay (Cepheid Inc. ABSTRACT The objective of this study was to evaluate a novel automated random-access test, mariPOC CDI (ArcDia Ltd., Finland), for the detection of Clostridioides difficile glutamate dehydrogenase (GDH) and toxins A and B directly from fecal specimens. The mariPOC test was compared with both the GenomEra C. difficile PCR assay (Abacus Diagnostica Oy, Finland) and the TechLab C. diff Quik Chek Complete (Alere Inc.; now Abbot) membrane enzyme immunoassay (MEIA). Culture and the Xpert C. difficile assay (Cepheid Inc., USA) were used to resolve discrepant results. In total, 337 specimens were tested with the mariPOC CDI test and GenomEra PCR. Of these specimens, 157 were also tested with the TechLab MEIA. The sensitivity of the mariPOC test for GDH was slightly lower (95.2%) than that obtained with the TechLab assay (100.0%), but no toxin-positive cases were missed. The sensitivity of the mariPOC test for the detection of toxigenic C. difficile by analyzing toxin expression was better (81.6%) than that of the TechLab assay (71.1%). The analytical specificities for the mariPOC and the TechLab tests were 98.3% and 100.0% for GDH and 100.0% and 99.2% for toxin A/B, respectively. The analytical specificity of the GenomEra method was 100.0%. The mariPOC and TechLab GDH tests and GenomEra PCR had high negative predictive values of 99.3%, 98.3%, and 99.7%, respectively, in excluding infection with toxigenic C. difficile. The mariPOC toxin A/B test and GenomEra PCR had an identical analytical positive predictive value of 100%, providing highly reliable information about toxin expression and the presence of toxin genes, respectively.
Pathogen-Specific Impacts of the 2011–2012 La Niña-Associated Floods on Enteric Infections in the MAL-ED Peru Cohort: A Comparative Interrupted Time Series Analysis

Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites—Loreto, Peru—were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic E. coli (ST-ETEC) was identified (RR = 1.73 [1.10, 2.71]) along with a decreased risk of enteric adenovirus (RR = 0.36 [0.23, 0.58]). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 [2.70, 10.40]) and sapovirus (RR = 2.47 [1.79, 3.41]) were observed, in addition to increases in transmission of Shigella spp. (RR = 2.86 [1.81, 4.52]) and Campylobacter spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P[4]) strain of the virus. Policy-makers should target interventions towards these pathogens—including vaccines as they become available—in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.
MHC Class II (DRB) Promoter Polymorphism and Its Role in Parasite Control among Malaria Patients

Key Points The genetic variation in the proximal promoter region alters MHCII expression. Lower MHCII-DRB expression leads to poor parasite clearance. MHCII gene regulation determines the immunity to malaria. Visual Abstract MHC class II (MHCII) molecules are cell surface glycoproteins that play an important role to develop adaptive immune responses. MHCII-disease association is not restricted to structural variation alone but also may extend to genetic variations, which may modulate gene expression. The observed variations in class II gene expression make it possible that the association of MHCII polymorphism with diseases may relate to the level of gene expression in addition to the restriction of response to Ag. Understanding the extent of, and the mechanisms underlying, transcription factor DNA binding variation is therefore key to elucidate the molecular determinants of complex phenotypes. In this study, we investigated whether single nucleotide polymorphisms in MHCII-DRB regulatory gene may be associated with clinical outcomes of malaria in Plasmodium-infected individuals. To this end, we conducted a case-control study to compare patients who had mild malaria with those patients who had asymptomatic Plasmodium infection. It demonstrates that GTAT haplotype exerts an increased DRB transcriptional activity, resulting in higher DRB expression and subsequently perturbed Ag presentation and T cell activation, higher TLR-mediated innate immune gene expression, and Ag clearance, so low parasitemia in comparison with haplotypes other than GTAT (GTAC, GGGT). Hence, we hypothesized that DRB gene promoter polymorphism might lead to altered DRB gene expression, which could possibly affect the TLR-triggered innate immune responses in malaria patients. These genetic findings may contribute to the understanding of the pathogenesis of malaria and will facilitate the rational vaccine design for malaria.
Morphoscopic ancestry estimates in Filipino crania using multivariate probit regression models.

OBJECTIVES Probit has not been applied to ancestry estimation in forensic anthropology. The goals of this study were to: (1) evaluate the performance of probit analysis as a classification tool for ancestry estimation using ordinal data and (2) expand our current understanding of human cranial variation for an understudied population. METHODS Multivariate probit models were used to classify the ancestral affiliation of Filipino crania using morphoscopic traits. Ancestral reference populations represented Africa, Asia, and Europe in a three-group model, with the addition of Hispanics in a four-group model. Posterior probabilities across these groups were interpreted as admixture proportions of an individual. Model performance was also evaluated for individuals with missing data. RESULTS The overall correct classification rates for the three-group and four-group models were 72.1% and 68.6%, respectively. Filipinos classified as Asian 52.9% of the time using three ancestral reference groups and 48.6% using four groups. A large portion of Filipinos also classified as African. There were no significant differences in classification trends or accuracy rates between complete crania and crania with at least one missing variable. CONCLUSIONS Multivariate probit models using morphoscopic traits perform well when populations are represented in both training and test samples. Probit can also accommodate individuals with missing data. Classifying Filipinos showed only moderate success. Filipinos are more phenotypically similar to Africans than the other Asian samples used here, but still affiliate most closely as Asian. Ancestry methods would benefit from including Filipinos as a reference sample given the additional variation they provide to the continental category of Asian.
Smartphone Biosensor System with Multi-Testing Unit Based on Localized Surface Plasmon Resonance Integrated with Microfluidics Chip

Detecting biomarkers is an efficient method to diagnose and monitor patients’ stages. For more accurate diagnoses, continuously detecting and monitoring multiple biomarkers are needed. To achieve point-of-care testing (POCT) of multiple biomarkers, a smartphone biosensor system with the multi-testing-unit (SBSM) based on localized surface plasmon resonance (LSPR) integrated multi-channel microfluidics was presented. The SBSM could simultaneously record nine sensor units to achieve the detection of multiple biomarkers. Additional 72 sensor units were fabricated for further verification. Well-designed modularized attachments consist of a light source, lenses, a grating, a case, and a smartphone shell. The attachments can be well assembled and attached to a smartphone. The sensitivity of the SBSM was 161.0 nm/RIU, and the limit of detection (LoD) reached 4.2 U/mL for CA125 and 0.87 U/mL for CA15-3 through several clinical serum specimens testing on the SBSM. The testing results indicated that the SBSM was a useful tool for detecting multi-biomarkers. Comparing with the enzyme-linked immunosorbent assays (ELISA) results, the results from the SBSM were correlated and reliable. Meanwhile, the SBSM was convenient to operate without much professional skill. Therefore, the SBSM could become useful equipment for point-of-care testing due to its small size, multi-testing unit, usability, and customizable design.
Exploring the effectiveness of an 18-month weight management intervention in adults with Down syndrome using propensity score matching.

BACKGROUND Down syndrome (DS) is one of the most common birth defects in the USA associated with high levels of overweight and obesity. Unique characteristics of adults with DS that may contribute to the high levels of obesity are high rates of hypothyroidism, poor muscle tone, altered gait and lower resting metabolic rate. Due to these factors, it is unknown if the same weight management interventions that are effective in adults with intellectual or developmental disability (IDD) without DS are as effective in those with DS. Therefore, the purpose of this secondary analysis was to compare changes in weight, diet and physical activity between participants with DS-related and non-DS-related IDD participating in an 18-month weight management trial. METHODS We used propensity score methods to adjust baseline variables of overweight/obese adults with and without DS participating in an 18-month effectiveness trial with 6 months weight loss and 12 months weight maintenance. Participants followed one of two reduced calorie diet plans, obtained 150 min of moderate-vigorous intensity physical activity (MVPA) per week, and logged dietary intake daily. A health educator held monthly at-home visits with participants and a caregiver to give feedback on intervention compliance. RESULTS Out of the 124 participants that met the criteria for inclusion, 21 were diagnosed with DS and 103 with non-DS-related IDD. Twenty out of 21 participants with DS were successfully matched. Clinically significant weight loss was seen at 18 months in participants with DS (-5.2%) and non-DS-related IDD (-6.8%), with no difference between groups (P = 0.53). Significant reductions in energy intake were seen across the 18-month intervention in both DS and non-DS-related IDD groups with between-group differences at 12 months only (1119 vs. 1492 kcal/day, respectively; P = 0.003). Although MVPA did not increase in either group across the intervention, those with non-DS-related IDD had higher levels of MVPA compared with those with DS across 18 months. CONCLUSION Participants with DS lost a clinically significant amount of weight across the 18-month intervention. Compared with those with non-DS-related IDD, those with DS lost similar amounts of weight, had similar decreases in energy intake and participated in less MVPA across the 18-month intervention. Although individuals with DS have physiological factors that may contribute to obesity, weight management interventions designed for individuals with IDD may be equally effective in this population.
A VPS13D spastic ataxia mutation disrupts the conserved adaptor-binding site in yeast Vps13

Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson’s disease and spastic ataxia. Recent evidence suggests that the different VPS13 paralogs transport lipids between organelles at different membrane contact sites. How each VPS13 isoform is targeted to organelles is not known. We have shown that the localization of yeast Vps13 protein to membranes requires a conserved six-repeat region, the Vps13 Adaptor Binding (VAB) domain, which binds to organelle-specific adaptors. Here, we use a systematic mutagenesis strategy to determine the role of each repeat in recognizing each known adaptor. Our results show that mutation of invariant asparagines in repeats 1 and 6 strongly impact the binding all adaptors and block Vps13 membrane recruitment. However, we find that repeats 5 to 6 are sufficient for localization and interaction with adaptors. This supports a model where a single adaptor binding site is found in the last two repeats of the VAB domain, while VAB domain repeat 1 may help maintain domain conformation. Importantly, a disease-causing mutation in VPS13D, which maps to the highly conserved asparagine residue in repeat 6, blocks adaptor binding and Vps13 membrane recruitment when modeled in yeast. Our findings are consistent with a conserved adaptor binding role for the VAB domain and suggests the presence of as-yet-unidentified adaptors in both yeast and humans.
Falls Risk in Relation to Activity Exposure in High-Risk Older Adults

Abstract Background Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME). Methods One hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson’s disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken. Results At baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035). Conclusions This work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs.
Binding of the von Willebrand Factor A Domain of Capillary Morphogenesis Protein 2 to Anthrax Protective Antigen Vaccine Reduces Immunogenicity in Mice

The anthrax toxin PA is the major immunogen in the current anthrax vaccine (anthrax vaccine adsorbed). Improving the anthrax vaccine for avoidance of a cold chain necessitates improvements in the thermodynamic stability of PA. We address how stabilizing PA using sCMG2 affects PA immunogenicity in BALB/c mice. Although the stability of PA is increased by binding to sCMG2, PA immunogenicity is decreased. This study emphasizes that, while binding of a ligand retains or improves conformational stability without affecting the native sequence, epitope recognition or processing may be affected, abrogating an effective immune response. ABSTRACT Protective antigen (PA) is a component of anthrax toxin that can elicit toxin-neutralizing antibody responses. PA is also the major antigen in the current vaccine to prevent anthrax, but stability problems with recombinant proteins have complicated the development of new vaccines containing recombinant PA. The relationship between antigen physical stability and immunogenicity is poorly understood, but there are theoretical reasons to think that this parameter can affect immune responses. We investigated the immunogenicity of anthrax PA, in the presence and absence of the soluble von Willebrand factor A domain of the human form of receptor capillary morphogenesis protein 2 (sCMG2), to elicit antibodies to PA in BALB/c mice. Prior studies showed that sCMG2 stabilizes the 83-kDa PA structure to pH, chemical denaturants, temperature, and proteolysis and slows the hydrogen-deuterium exchange rate of histidine residues far from the binding interface. In contrast to a vaccine containing PA without adjuvant, we found that mice immunized with PA in stable complex with sCMG2 showed markedly reduced antibody responses to PA, including toxin-neutralizing antibodies and antibodies to domain 4, which correlated with fewer toxin-neutralizing antibodies. In contrast, mice immunized with PA in concert with a nonbinding mutant of sCMG2 (D50A) showed anti-PA antibody responses similar to those observed with PA alone. Our results suggest that addition of sCMG2 to a PA vaccine formulation is likely to result in a significantly diminished immune response, but we discuss the multitude of factors that could contribute to reduced immunogenicity. IMPORTANCE The anthrax toxin PA is the major immunogen in the current anthrax vaccine (anthrax vaccine adsorbed). Improving the anthrax vaccine for avoidance of a cold chain necessitates improvements in the thermodynamic stability of PA. We address how stabilizing PA using sCMG2 affects PA immunogenicity in BALB/c mice. Although the stability of PA is increased by binding to sCMG2, PA immunogenicity is decreased. This study emphasizes that, while binding of a ligand retains or improves conformational stability without affecting the native sequence, epitope recognition or processing may be affected, abrogating an effective immune response.
Creatinine versus cystatin C for renal function-based mortality prediction in an elderly cohort: The Northern Manhattan Study

Background Estimated glomerular filtration rate (eGFR) is routinely utilized as a measure of renal function. While creatinine-based eGFR (eGFRcr) is widely used in clinical practice, the use of cystatin-C to estimate GFR (eGFRcys) has demonstrated superior risk prediction in various populations. Prior studies that derived eGFR formulas have infrequently included high proportions of elderly, African-Americans, and Hispanics. Objective Our objective as to compare mortality risk prediction using eGFRcr and eGFRcys in an elderly, race/ethnically diverse population. Design The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3,298 participants recruited between 1993 and 2001, with a median follow-up of 18 years. Participants We included all Northern Manhattan Study (NOMAS) participants with concurrent measured creatinine and cystatin-C. Main measures The eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equations. The performance of each eGFR formula in predicting mortality risk was tested using receiver-operating characteristics, calibration and reclassification. Net reclassification improvement (NRI) was calculated based on the Reynolds 10 year risk score from adjusted Cox models with mortality as an outcome. The primary hypothesis was that eGFRcys would better predict mortality than eGFRcr. Results Participants (n = 2988) had a mean age of 69±10.2 years and were predominantly Hispanic (53%), overweight (69%), and current or former smokers (53% combined). The mean eGFRcr (74.68±18.8 ml/min/1.73m2) was higher than eGFRcys (51.72±17.2 ml/min/1.73m2). During a mean of 13.0±5.6 years of follow-up, 53% of the cohort had died. The AUC of eGFRcys (0.73) was greater than for eGFRcr (0.67, p for difference<0.0001). The proportions of correct reclassification (NRI) based on 10 year mortality for the model with eGFRcys compared to the model with eGFRcr were 4.2% (p = 0.002). Conclusions In an elderly, race/ethnically diverse cohort low eGFR is associated with risk of all-cause mortality. Estimated GFR based on serum cystatin-C, in comparison to serum creatinine, was a better predictor of all-cause mortality.
Adhesive Hydrogels for Maxillofacial Tissue Regeneration Using Minimally Invasive Procedures

Minimally invasive surgical procedures aiming to repair damaged maxillofacial tissues are hampered by its small, complex structures and difficult surgical access. Indeed, while arthroscopic procedures that deliver regenerative materials and/or cells are common in articulating joints such as the knee, there are currently no treatments that surgically place cells, regenerative factors or materials into maxillofacial tissues to foster bone, cartilage or muscle repair. Here, hyaluronic acid (HA)‐based hydrogels are developed, which are suitable for use in minimally invasive procedures, that can adhere to the surrounding tissue, and deliver cells and potentially drugs. By modifying HA with both methacrylate (MA) and 3,4‐dihydroxyphenylalanine (Dopa) groups using a completely aqueous synthesis route, it is shown that MA‐HA‐Dopa hydrogels can be applied under aqueous conditions, gel quickly using a standard surgical light, and adhere to tissue. Moreover, upon oxidation of the Dopa, human marrow stromal cells attach to hydrogels and survive when encapsulated within them. These observations show that when incorporated into HA‐based hydrogels, Dopa moieties can foster cell and tissue interactions, ensuring surgical placement and potentially enabling delivery/recruitment of regenerative cells. The findings suggest that MA‐HA‐Dopa hydrogels may find use in minimally invasive procedures to foster maxillofacial tissue repair.