Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of serine/threonine phosphatases in human development: Evidence from congenital disorders

Reversible protein phosphorylation is a fundamental regulation mechanism in eukaryotic cell and organismal physiology, and in human health and disease. Until recently, and unlike protein kinases, mutations in serine/threonine protein phosphatases (PSP) had not been commonly associated with disorders of human development. Here, we have summarized the current knowledge on congenital diseases caused by mutations, inherited or de novo, in one of 38 human PSP genes, encoding a monomeric phosphatase or a catalytic subunit of a multimeric phosphatase. In addition, we highlight similar pathogenic mutations in genes encoding a specific regulatory subunit of a multimeric PSP. Overall, we describe 19 affected genes, and find that most pathogenic variants are loss-of-function, with just a few examples of gain-of-function alterations. Moreover, despite their widespread tissue expression, the large majority of congenital PSP disorders are characterised by brain-specific abnormalities, suggesting a generalized, major role for PSPs in brain development and function. However, even if the pathogenic mechanisms are relatively well understood for a small number of PSP disorders, this knowledge is still incomplete for most of them, and the further identification of downstream targets and effectors of the affected PSPs is eagerly awaited through studies in appropriate in vitro and in vivo disease models. Such lacking studies could elucidate the exact mechanisms through which these diseases act, and possibly open up new therapeutic avenues.
Dynamic changes and early predictive value of branched-chain amino acids in gestational diabetes mellitus during pregnancy

Objective Branched-chain amino acids (BCAAs) are closely associated with type 2 diabetes mellitus, but their roles in gestational diabetes mellitus (GDM) are still controversial. This study aims to explore the dynamic changes of BCAAs during pregnancy and identify potential early biomarkers for GDM. Methods This study is a nested case-control study involved 49 women with GDM and 50 age- and body mass index (BMI)-matched healthy pregnant women. The dynamic changes of valine (Val), isoleucine (Ile), and leucine (Leu) were detected in the first (8-12 weeks) and second trimesters (24-28 weeks) by liquid chromatography-mass spectrometry. Results Serum Val, Ile, and Leu were higher in GDM patients than in controls in the first trimester. Compared with the first trimester, the serum Val, Ile, and Leu in GDM patients were decreased in the second trimester. In addition, Val, Ile, and Leu in the first trimester were the risk factors for GDM, and Ile presented a high predictive value for GDM. Ile + age (≥ 35) + BMI (≥ 24) exhibited the highest predictive value for GDM (AUC = 0.902, sensitivity = 93.9%, specificity = 80%). Conclusion Maternal serum Ile in the first trimester was a valuable biomarker for GDM. Ile combined with advanced maternal age and overweight may be used for the early prediction of GDM.
Cultural resources, academic self-concept, and achievement of chemistry students in senior secondary schools of Calabar Municipality, Cross River State, Nigeria

This paper investigated cultural resources, academic self-concept, and achievement of chemistry students in a senior secondary school in Nigeria. Research questions and hypotheses were formulated to direct the study. A quasi-experimental factorial design was used in this study, which had a sample size of 90 senior secondary chemistry students. The Academic Self-concept Questionnaire (ASCQ) and Chemistry Achievement Test (CAT) were used in this study. The reliability of ASCQ was done using Cronbach Alpha and it was 0.80 while the reliability of CAT was done using Kuder Richardson formula 20 and had a coefficient of 0.79. The results obtained were analyzed using a dependent t-test and analysis of variance (ANCOVA). Analysis of data showed that the academic self-concept of the students increased after using cultural resources and the experimental group gained more than the control. This study found that cultural resources made the learning of chemical concepts easy to comprehend as the materials were things that the learners were familiar with. This study recommends, among others, that teachers use cultural resources in teaching chemistry.
Allele frequency of SLC4A3 (PRA1), TTC8 (PRA2), and PRA-prcd mutations in golden retrievers in Brazil

Progressive retinal atrophy (PRA) is a term used in veterinary medicine to describe inherited and progressive retinal diseases characterized by progressive retinal degeneration and loss of vision. In the Golden Retriever (GR) breed, the mutations associated with PRA have an autosomal recessive inheritance pattern. This study aimed to verify the allele frequencies of PRA1, PRA2, and PRA-prcd in the GR breed in Brazil. A total of 121 GR DNA samples (n = 66 females and n = 55 males) were analyzed. All animals assessed in this study were identified as wild-type (121/121 animals; 100%) for PRA1 and PRA2 mutations; therefore, no carrier or homozygous animals were identified in this population. For the PRA-prcd mutation, 118 animals (118/121 animals; 97.52%) were wild-type. Three animals were genotyped as heterozygous for PRA-prcd (3/121 animals; 2.47%), demonstrating that this mutation is still present in some bloodlines and animals in Brazil, even with a rare prevalence. Five animals (5/121 animals, 4.2%) had a previous eye disease, which was diagnosed by a veterinarian as entropion (2 animals), keratoconjunctivitis sicca (1 animal), corneal ulcer (1 animal), and bilateral blindness (1 animal). This dog with bilateral blindness was identified as wild type homozygous for three mutations assessed in this study; therefore, blindness was not associated with the investigated mutations. In addition, the vast majority (98.3%) of Brazilian breeders assessed in this study were unaware of these mutations as a cause of blindness in the Golden Retriever. Therefore, the present study will serve to disseminate knowledge about PRA and its genetic etiologies, as well as to support future studies with other Brazilian GR populations.
Insights into coastal microbial antibiotic resistome through a meta-transcriptomic approach in Yucatan

Antibiotic resistance (AR) is one of the greatest human and clinical challenges associated with different pathogenic organisms. However, in recent years it has also become an environmental problem due to the widespread use of antibiotics in humans and livestock activities. The ability to resist antibiotics comes from antibiotic resistance genes (ARGs) and our understanding of their presence in coastal environments is still limited. Therefore, the objective of the present study was to explore the presence and possible differences in the microbial resistome of four sites from the Yucatan coast through the evaluation of the composition and abundance of ARGs using a high-throughput analysis of metatranscriptomic sequences. In total, 3,498 ARGs were uncovered, which participate in the resistance to tetracycline, macrolide, rifamycin, fluoroquinolone, phenicol, aminoglycoside, cephalosporin, and other antibiotics. The molecular mechanisms of these ARGs were mainly efflux pump, antibiotic target alteration and antibiotic target replacement. In the same way, ARGs were detected in the samples but showing dissimilar enrichment levels. With respect to the sampling sites, the ARGs were present in all the samples collected, either from preserved or contaminated areas. Importantly, sediments of the preserved area of Dzilam presented the second highest level of ARGs detected, probably as a consequence of the antibiotics dragged to the coast by submarine groundwater discharge. In general, the resistance to a single antibiotic was greater than multiresistance, both at the level of gene and organisms; and multiresistance in organisms is acquired mainly by recruiting different monoresistance genes. To our knowledge, this is the first study that describes and compares the resistome of different samples of the Yucatan coast. This study contributes to generating information about the current state of antibiotic resistance on the Yucatan coasts for a better understanding of ARGs dissemination and could facilitate the management of ARGs pollution in the environment.
Specific imaging features indicate the clinical features of patients with hepatic perivascular epithelioid cell tumor by comparative analysis of CT and ultrasound imaging

Objective The objective of the study was to explore the CT and ultrasound features and clinical significance of perivascular epithelioid cell tumor (PEComa) of the liver. Methods Eleven hepatic PEComa patients treated in our hospital were retrospectively analyzed based on the characteristics of the imaging results of the patients, including conventional ultrasound, CDFI, contrast-enhanced ultrasound (CEUS), and contrast-enhanced CT (CECT). Results CT scans showed that all lesions were hypodense. Ultrasonography showed that lesions were either hyperechoic (4/11, 36.36%), hypoechoic (4/11, 36.36%), isoechoic (1/11, 9.09%), or heterogeneously echoic (2/11, 18.18%). CDFI showed that most of the lesions had an abundant blood supply (9/11, 81.82%). Whether on CT scan or ultrasonography, the margins of the lesions were dominated by clear margins. Ultrasonography revealed more features: hyperechoic patterns around lesions (3/11, 27.27%) and lateral shadow (5/11, 45.45%). The CDFI showed that large blood vessels were observed around the lesions (9/11, 81.82%). CECT shows two enhancement patterns: “fast in and fast out (FIFO)” (8/11, 72.72%) and “fast in and slow out (FISO)” (3/11, 27.27%). CEUS shows that all lesions had the enhancement pattern of “FISO,” which was different from CECT. All lesions displayed rapid enhancement during HAP in CEUS during 7–20 s. Four patients (36.36%) washed out at 60–180 s, another four (36.36%) washed out at 180–300 s, and the remaining three patients (27.27%) showed no signs of washout even at 360 s. Conclusion Some imaging features, such as clear margins, peripheral hyperechoic around the lesion, lateral shadow, the large blood vessels around lesions, and the “FISO” enhancement pattern, may indicate expansive growth of the tumor and be helpful in the diagnosis of PEComa. Ultrasound images may provide more details for clinical reference.
The impact of an exercise intervention using low-cost equipment on functional fitness in the community-dwelling older adults: A pilot study

Exercise interventions have shown significant improvements in the older adult population regarding functional and cognitive capacity. However, much research has applied exercise protocols that are expensive both for research and participation. Thus, high investments that are made are currently not ecologically efficient. The aim of the study was to determine whether the impact of a 20-week multicomponent exercise intervention using low-cost material could improve physical fitness in community-dwelling older adults. We tested the feasibility of this three times per week exercise protocol using an inclusive approach. Eligibility criteria included age ≥65 years, the ability to stand and walk with or without assistive devices, being physically inactive; medical clearance, and living in the community. Outcomes were muscle resistance measured using the chair-stand test for lower limbs, cardiorespiratory capacity measured using the 6-min walk test, and agility and balance using the Timed-up and Go test. Flexibility was measured using the chair sit and reach for lower limbs and the back scratch for upper limbs using the dominant leg and arm, respectively. Hand grip strength was measured using a dynamometer. Thirty participants (n = 30) were recruited and included in the intention-to-treat analysis. The mean age of participants was 70 years (±3.62 years), 100% were Caucasians, and 50% were female. There was a significant trend toward a clinically important improvement in the chair-stand (t = −5.23; p < 0.001; d = 0.36), arm curl (t = −5.21; p < 0.001; d = 0.74), 6-min walk test (t = −4.69; p = <0.001; d = 0.77), timed-up and go test (t = 8.788; p < 0.001; d = 1.18), and hand grip strength (t = 2.846; p = 0.009; d = 0.23). There were also differences in the back scratch (t = 2.243; p = 0.035; d = 0.29) and chair sit and reach test (t = −3.380; p < 0.001; d = 0.15). This pilot study has provided preliminary evidence that a 20-week community-based low-cost exercise program may be effective in improving overall functional fitness in older people. The pilot trial has provided the necessary data to design future randomized-controlled trials that can be implemented in the community in an ecological feasible manner.
Serum exosomal and serum glypican-1 are associated with early recurrence of pancreatic ductal adenocarcinoma

Background The diagnostic performance and prognostic value of serum exosomal glypican 1 (GPC-1) in pancreatic ductal adenocarcinoma (PDAC) remain controversial. In this study, we detected serum exosomal GPC-1 using enzyme-linked immunosorbent assay (ELISA) and determined whether it serves as a predictor of diagnosis and recurrence for early-stage PDAC. Methods Serum samples were obtained from patients with 50 PDAC, 6 benign pancreatic tumor (BPT), or 9 chronic pancreatitis (CP) and 50 healthy controls (HCs). Serum exosomes were isolated using an exosome isolation kit. Exosomal and serum GPC-1 levels were measured using ELISA. The freeze–thaw process was carried out to analyze the stability of GPC-1. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic value of GPC-1. Kaplan–Meier and multivariate Cox analyses were used to evaluate the prognostic value of GPC-1. Results The average concentrations of serum exosomal and serum GPC-1 were 1.5 and 0.8 ng/ml, respectively. GPC-1 expression levels were stable under repeated freezing and thawing (d1-5 freeze–thaw cycles vs. d0 P > 0.05). Serum exosomal and serum GPC-1 were significantly elevated in patients with PDAC compared with HCs (P < 0.0001) but were slightly higher compared with that in patients with CP and BPT (P > 0.05). The expression levels of exosomal and serum GPC-1 were elevated 5 days after surgery in patients with PDAC, CP, and BPT (P < 0.05). Patients with high levels of exosomal and serum GPC-1 had a shorter relapse-free survival (RFS) (P = 0.006, and P = 0.010). Multivariate analyses showed that serum exosomal and serum GPC-1 were independent prognostic indicators for early RFS (P = 0.008, and P = 0.041). Conclusion ELISA is an effective and sensitive method to detect exosomal and serum GPC-1. The detection of GPC-1 was stable under repeated freezing and thawing cycles and could distinguish early-stage PDAC from HCs but not CP and BPT. Exosomal and serum GPC-1 may be good independent predictors of early recurrence in early-stage PDAC.
HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections

One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host’s immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response.
Sanghuangporus vaninii fruit body polysaccharide alleviates hyperglycemia and hyperlipidemia via modulating intestinal microflora in type 2 diabetic mice

The disease of type 2 diabetes mellitus (T2DM) is principally induced by insufficient insulin secretion and insulin resistance. In the current study, Sanghuangporus vaninii fruit body polysaccharide (SVP) was prepared and structurally characterized. It was shown that the yield of SVP was 1.91%, and SVP mainly contains small molecular weight polysaccharides. Afterward, the hypoglycemic and hypolipidemic effects and the potential mechanism of SVP in T2DM mice were investigated. The results exhibited oral SVP could reverse the body weight loss, high levels of blood glucose, insulin resistance, hyperlipidemia, and inflammation in T2DM mice. Oral SVP increased fecal short-chain fatty acids (SCFAs) concentrations of T2DM mice. Additionally, 16S rRNA sequencing analysis illustrated that SVP can modulate the structure and function of intestinal microflora in T2DM mice, indicating as decreasing the levels of Firmicutes/Bacteroidetes, Flavonifractor, Odoribacter, and increasing the levels of Weissella, Alloprevotella, and Dubosiella. Additionally, the levels of predicted metabolic functions of Citrate cycle, GABAergic synapse, Insulin signaling pathway were increased, and those of Purine metabolism, Taurine and hypotaurine metabolism, and Starch and sucrose metabolism were decreased in intestinal microflora after SVP treatment. These findings demonstrate that SVP could potentially play hypoglycemic and hypolipidemic effects by regulating gut microflora and be a promising nutraceutical for ameliorating T2DM.
Atovaquone attenuates experimental colitis by reducing neutrophil infiltration of colonic mucosa

Ulcerative colitis (UC) is a chronic relapsing disease featuring aberrant accumulation of neutrophils in colonic mucosa and the luminal space. Although significant advances in UC therapy have been made with the development of novel biologics and small molecules targeting immune responses, success of most current therapies is still limited, with significant safety concerns. Thus, there is a need to develop additional safe and effective therapies for the treatment of UC. Antimalarial drugs have been safely used for many years to resolve tissue inflammation and the associated pathologies. Atovaquone is a recent FDA-approved antimalarial drug that has shown anti-viral and tumor-suppressive properties in vitro however, its role in mucosal inflammation has not been evaluated. Using pre-clinical murine DSS-induced colitis model combined with complementary in vivo peritonitis and ex vivo human neutrophil activation and chemotaxis assays we investigated functional and mechanistic impacts of atovaquone on disease resolution and neutrophil trafficking. We demonstrate that atovaquone promotes resolution of DSS-induced murine colitis by reducing neutrophil accumulation in the inflamed colonic mucosa. Mechanistically, we show that atovaquone suppressed induction of CD11b expression in neutrophils, reducing their polarization and migratory ability. Thus, our findings identify a new role of atovaquone in promoting resolution of mucosal inflammation, supporting the idea of potential repurposing of this FDA-approved drug as UC therapeutic.
Development of the Japanese version of Staff Attitude to Coercion Scale

Background An important factor in proceeding the efforts to reduce coercion in psychiatry is the attitudes of clinical staff toward its use. We aimed to develop the Japanese version of the Staff Attitude to Coercion Scale (SACS) and clarify its psychometric properties. Methods After the translation and back-translation of the SACS, which includes 15 items consisting of three subscales, we conducted an anonymous self-administered questionnaire survey of clinical staffs working in 17 wards in two psychiatric hospitals. We administered the second survey to some of the participants to confirm the test-retest reliability. Additionally, we obtained information regarding the 17 wards from the institutions. Internal consistency was assessed using Cronbach’s alpha coefficients. Test-retest reliability was assessed using intraclass correlation coefficients (ICC). Structural validity was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). For construct validity, the correlation of the SACS score within wards and its association with the actual use of seclusion/restraints were explored using multilevel multivariate linear regression analyses. Results We used 261 (67.1%) responses, 35 responses of which were also used to examine test-retest reliability. Cronbach’s alpha coefficients (0.761) and ICC (0.738) indicated good reliability. The results of CFA based on the original three-dimensional structure did not indicate a good fit (CFA = 0.830, RMSEA = 0.088). EFA suggested a four-factor structure, two of which were almost consistent with the original two subscales. The correlation of the SACS score within wards was confirmed while a positive association with the actual use of seclusion/restraints was not identified. Conclusion While the original three-dimensional structure was not replicated, construct validity was partially confirmed. Reliability of the total scale was good. In Japan, although using the subscales was not recommended, using the total scale of SACS seemed acceptable.
Bank Monitoring with On-Site Inspections

Although a seminal body of theoretical literature asserts that a key advantage of banks is their ability to monitor borrowers, we are the first paper to empirically examine the theoretical determinants of bank monitoring within non-syndicated loans. Using a proprietary set of transaction-level database of nearly 30,000 multiple-draw construction loans, we observe the frequency at which the bank monitors these loans by conducting on-site inspections, the contents of the reports, and the borrower actions over the life of the loan. Consistent with theoretical predictions, we find evidence that banks tradeoff monitoring with many types of favorable loan origination terms. Monitoring is also less frequent for loans where the bank has a prior relationship with either the borrower or project contractor, suggesting that banks may be transferring information across projects. Furthermore, we show that negative on-site inspection reports are associated with a greater likelihood of banks denying draw requests, indicating that the information that banks collect during the monitoring process is important to their decision-making. In subsequent analysis, we provide a comprehensive analysis on the determinants of construction loan default and show that more monitoring ultimately decreases loan default within an instrumental variable framework.