Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of porcine respiratory pathogens in slaughterhouses in Shanxi Province, China

Abstract Background Porcine respiratory diseases remain the biggest challenge in pig‐based food production and are a public health concern. Despite control measures, persistent outbreaks have been reported worldwide. Objective To establish an early detection mechanism for pig farm disease outbreaks based on slaughterhouse risk and environmental assessment. Methods We investigated the prevalence and risk factors of porcine respiratory disease‐causing pathogens including Mycoplasma hyopneumoniae (MHP), porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS). Polymerase chain reaction (PCR) was used to analyse the lungs of 491 pigs from 19 slaughterhouses across 11 cities in Shanxi Province, China. Results PCR detected MHP, PCV2, PPRSV and HPS in 76.99%, 67.00%, 11.82% and 19.55% of the samples, respectively; 10.12% were negative for all four pathogens. Co‐positivity rates for two and three pathogens were identified. The results confirmed significant correlations between PCV2 and MHP (p = .001, p < .05), HPS and PCV2 (p = .01, p < .05) and MHP and PRRSV (p = .01, p < .05). No significant correlation was observed between HPS and MHP (p = .067, p > .05). Positive MHP and PCV2 rates were low in areas with high vegetation coverage. The overall pathogen positivity rate was higher in both lower and higher temperature environments. Conclusions Interactions among pathogens may increase disease severity. Furthermore, environmental assessment and pathogen surveillance within pig slaughterhouses can be an effective approach for early detection and mitigation of new disease threats before broad dissemination occurs among a herd.
Local Anti–PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model

Oral cancer is an aggressive disease, with an overall survival rate of 50%. Preinvasive histologic abnormalities such as tongue dysplasia represent an early stage of oral cancer; however, there are no treatments to prevent oral carcinoma progression. Here, we combined biomaterials loaded with an immunotherapeutic agent preventing oral cancer progression. Although the principle of systemic treatment to prevent the progression of oral premalignant lesions (OPL) has been demonstrated, there remains a lack of consensus about an optimal approach that balances clinical efficacy with toxicity concerns. Recent advances in cancer therapy using approaches targeting the tumor immune microenvironment (TIME) including immune-checkpoint inhibitors indicate that these agents have significant clinically activity against different types of cancers, including oral cancer, and therefore they may provide an effective oral cancer prevention strategy for patients with OPLs. Our past work showed that systemic delivery of a monoclonal antibody to the programmed death receptor 1 (PD-1) immune checkpoint can inhibit the progression of OPLs to oral cancer in a syngeneic murine oral carcinogenesis model. Here we report a novel approach of local delivery of a PD-1 immune-checkpoint inhibitor loaded using a hydrogel, which significantly reduces the progression of OPLs to carcinomas. In addition, we detected a significant infiltration of regulatory T cells associated with oral lesions with p53 mutation, and a severe loss of expression of STING, which correlated with a decreased infiltration of dendritic cells in the oral lesions. However, a single local dose of PD-1 inhibitor was found to restore stimulator of interferon response cGAMP interactor 1 (STING) and CD11c expression and increase the infiltration of CD8+ T cells into the TIME irrespective of the p53 mutational status. Overall, we provide evidence for the potential clinical value of local delivery of biomaterials loaded with anti–PD-1 antibodies to prevent malignant progression of OPLs. Prevention Relevance: Oral cancer is an aggressive disease, with an overall survival rate of 50%. Preinvasive histologic abnormalities such as tongue dysplasia represent an early stage of oral cancer; however, there are no treatments to prevent oral carcinoma progression. Here, we combined biomaterials loaded with an immunotherapeutic agent preventing oral cancer progression.
Epigenetic Biomarkers of Prenatal Tobacco Smoke Exposure Are Associated with Gene Deletions in Childhood Acute Lymphoblastic Leukemia

Background: Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases. Methods: Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy—DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score—in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers. Results: We found an association between DNA methylation at AHRR CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02–1.69] for each 0.1 β value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10–1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09–1.57). Conclusions: We provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL. Impact: Analyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.
Protecting children from tobacco smoke exposure: A randomized controlled trial of Project Zero Exposure.

INTRODUCTION Young children are vulnerable to harm from tobacco smoke exposure (TSE). This study assessed the effect of Project Zero Exposure - an intervention program designed to help parents protect children from TSE - on children's exposure. METHODS Randomized controlled trial of a home-based, theory-driven intervention. Parents of young children (< 8 years) in families with a smoking parent were eligible. The intervention included feedback on child TSE (hair nicotine), and home air quality (PM2.5), with motivational interviewing. Families were randomized to: intervention group (IG,N=69), regular control group (RCG, N=70), or to a secondary enhanced control group, (ECG, N=20). Child hair samples were taken at baseline and follow-up. We report on child TSE in the IG versus RCG at six months. RESULTS Most enrolled families completed the trial (IG:98.6%(68/69), RCG:97.1%(68/70). LHN (ng/mg) decreased in both the IG (Baseline:-1.78±1.91,Follow-up:-2.82±1.87,p=.003) and RCG (Baseline:-1.79±1.54,Follow-up:-2.85±1.73,p=.002), but did not differ between groups at study end (p=.635). Three of five parentally-reported outcomes showed improvement over time in the IG, and one in the RCG. Among IG participants, 90% found hair nicotine feedback useful. CONCLUSIONS No difference between the intervention and control groups was found on the objective biomarker, LHN. Child tobacco smoke exposure decreased during the trial in intervention and control groups. Trial participation, which included hair nicotine monitoring, may have contributed to decreasing exposure in both groups. Concurrent control group improvements may partially explain lack of proven intervention benefit. Biomarker monitoring warrants further investigation for reduction of child tobacco smoke exposure.
Course of renal allograft function after diagnosis and treatment of post‐transplant lymphoproliferative disorders in pediatric kidney transplant recipients

Post‐transplant lymphoproliferative disease (PTLD) is a life‐threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD.
Neurodevelopmental phenotypes in individuals with pathogenic variants in CHAMP1

De novo pathogenic variants in CHAMP1 (chromosome alignment maintaining phosphoprotein 1), which encodes kinetochore-microtubule associated protein on 13q34, cause a rare neurodevelopmental disorder. We enrolled 14 individuals with pathogenic variants in CHAMP1 that were documented by exome sequencing or gene panel sequencing. Medical history interviews, seizure surveys, Vineland Adapted Behavior Scales Second Edition, and other behavioral surveys were completed by primary caregivers of available participants in Simons Searchlight. Clinicians extracted clinical data from the medical record for two participants. We report on clinical features of 14 individuals (ages 2–26) with de novo predicted loss-of-function variants in CHAMP1 and compare them with previously reported cases (total n = 32). At least two individuals have the same de novo variant: p.(Ser181Cysfs*5), p.(Trp348*), p.(Arg398*), p.(Arg497*), or p.(Tyr709*). Common phenotypes include intellectual disability/developmental delay, language impairment, congenital and acquired microcephaly, behavioral problems including autism spectrum disorder, seizures, hypotonia, gastrointestinal issues of reflux and constipation, and ophthalmologic issues. Other rarely observed phenotypes include leukemia, failure to thrive, and high pain tolerance. Pathogenic variants in CHAMP1 are associated with a variable clinical phenotype of developmental delay/intellectual disability and seizures.
Lead nitrate and cadmium chloride induced hepatotoxicity and nephrotoxicity: Protective effects of sesamol on biochemical indices and pathological changes.

Lead nitrate (LN) and cadmium chloride (CdCl2 ), regarded as environmental contaminants, are toxic heavy metals. Sesamol is a dietary phytochemical found in sesame oil. We aimed to analyze the hepatotoxic and nephrotoxic effects of LN and CdCl2 and to evaluate the possible protective effect of sesamol. LN (90 mg/kg bw per day), CdCl2 (3 mg/kg bw per day), and sesamol (50 mg/kg bw per day) were given to rats via gavage for 28 days. Total protein, albumin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, urea, uric acid, creatinine, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, malondialdehyde, acetylcholinesterase, and histopathological changes were investigated in liver and kidney tissues. Lead and cadmium were found to result in decreases in the antioxidant enzymes and acetylcholinesterase activities, increases in malondialdehyde levels, and changes in serum biochemical parameters and various pathological findings. An improvement in all these parameters was observed in the sesamol-treated groups. PRACTICAL APPLICATIONS: Heavy metals are used in many areas of the industry all over the world. Heavy metals which include lead nitrate and cadmium chloride cause cell damage by oxidative stress. Some of the examining parameters for oxidative stress are SOD, GST, MDA, GPx, and CAT. However, some chemicals such as sesamol are well-liked and widely used as antioxidants against xenobiotic toxicity. We also indicate that sesamol has been shown to protective effect against heavy metals caused cell damage.
Modeling temperature effect on dynamic modulus of elasticity of red pine (Pinus resinosa) in frozen and non-frozen states

Abstract The response of dynamic and static modulus of elasticity (MOEdyn and MOEsta) of red pine small clear wood (25.4×25.4×407 mm3) within the temperature range -40 to 40°C has been investigated. The moisture content (MC) of the specimens ranged from 0 to 118%. The MOEdyn was calculated based on measured ultrasonic velocity (V) and wood density. The MOEsta was measured by static bending tests in a climate chamber between -40 and 40°C. The results indicate that both MOEdyn and MOEsta were affected by temperature and the MC. Above freezing point, MOE decreased linearly at a slow rate with increasing temperature. Below freezing point, MOE increased at a rapid rate with decreasing temperature. The MC-level had a significant effect on the MOE-temperature relationships. Temperature effect was much more significant in green wood than in dry wood. Analytical models were developed to predict the change of MOEdyn relative to that at 20°C in the case of acoustic measurements under different temperature conditions.
Evaluation of the relationship between KIM‐1 and suPAR levels and clinical severity in COVID‐19 patients: A different perspective on suPAR

Coronavirus disease 2019 (COVID‐19) is one of the most pressing health problems of this century, but our knowledge of the disease is still limited. In this study, we aimed to examine serum‐soluble urokinase plasminogen activator receptor (suPAR) and kidney injury molecule 1 (KIM‐1) levels based on the clinical course of COVID‐19. Our study included 102 patients over the age of 18 who were diagnosed as having COVID‐19 between September 2020 and December 2020 and a control group of 50 health workers over the age of 18 whose severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) PCR results were negative. KIM‐1 was measured by ELISA and suPAR by suPARnostic™ assay. Analysis of previously identified variables of prognostic significance in COVID‐19 revealed high neutrophil to lymphocyte ratio, lactose dehydrogenase, prothrombin time, C‐reactive protein, PaO2/FiO2, D‐dimer, ferritin, and fibrinogen levels in patients with severe disease (p < 0.05 for all). KIM‐1 and suPAR levels were significantly higher in COVID‐19 patients compared to the control group (p = 0.001 for all). KIM‐1 level was higher in severe patients compared to moderate patients (p = 0.001), while suPAR level was lower (p = 0.001). KIM‐1, which is believed to play an important role in the endocytosis of SARS‐CoV‐2, was elevated in patients with severe COVID‐19 and may be a therapeutic target in the future. SuPAR may have a role in defense mechanism and fibrinolysis, and low levels in severe patients may be associated with poor prognosis in the early period.
Human milk 3’-Sialyllactose is positively associated with language development during infancy

ABSTRACT Background Genetic polymorphisms leading to variations in human milk oligosaccharide (HMO) composition have been reported. Alpha-Tetrasaccharide (A-tetra), an HMO, has been shown to only be present (>limit of detection; A-tetra+) in the human milk (HM) of women with blood type A, suggesting genetic origins determining the presence or absence (A-tetra-) of A-tetra in HM. Objectives This study aimed to determine whether associations exist between HMO concentrations and cognitive development, and whether the associations vary between A-tetra+ and A-tetra- groups in children (<25 months old). Methods We enrolled typically developing children (2–25 months old; mean, 10 months old) who were at least partially breastfed at the study visit. The Mullen Scales of Early Learning (MSEL) were used as the primary outcome measure to assess early cognitive development. Linear mixed effects models were employed by stratifying children based on A-tetra levels (A-tetra+ or A-tetra-) to assess associations between age-removed HMO concentrations and both MSEL composite scores and the 5 subdomain scores. Results A total of 99 mother-child dyads and 183 HM samples were included (A-tetra+: 57 samples, 33 dyads; A-tetra-: 126 samples, 66 dyads). No significant association was observed between HMOs and MSEL when all samples were analyzed together. The composite score and 3’-sialyllactose (3’-SL) levels were positively associated [P = 0.002; effect size (EF), 13.12; 95% CI, 5.36–20.80] in the A-tetra + group. This association was driven by the receptive (adjusted P = 0.015; EF, 9.95; 95% CI, 3.91–15.99) and expressive (adjusted P = 0.048; EF, 7.53; 95% CI, 2.51–13.79) language subdomain scores. Furthermore, there was an interaction between 3’-SL and age for receptive language (adjusted P = 0.03; EF, -14.93; 95% CI, -25.29 to -4.24). Conclusions Our study reports the association of 3’-SL and cognition, particularly language functions, in typically developing children who received HM containing detectable A-tetra during infancy.
Post‐transplant cyclophosphamide limits reactive donor T cells and delays the development of graft‐versus‐host disease in a humanized mouse model

Graft‐versus‐host disease (GVHD) is a major complication of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) that develops when donor T cells in the graft become reactive against the host. Post‐transplant cyclophosphamide (PTCy) is increasingly used in mismatched allo‐HSCT, but how PTCy impacts donor T cells and reduces GVHD is unclear. This study aimed to determine the effect of PTCy on reactive human donor T cells and GVHD development in a preclinical humanized mouse model. Immunodeficient NOD‐scid‐IL2Rγnull mice were injected intraperitoneally (i.p.) with 20 × 106 human peripheral blood mononuclear cells stained with carboxyfluorescein succinimidyl ester (CFSE) (day 0). Mice were subsequently injected (i.p.) with PTCy (33 mg kg−1) (PTCy‐mice) or saline (saline‐mice) (days 3 and 4). Mice were assessed for T‐cell depletion on day 6 and monitored for GVHD for up to 10 weeks. Flow cytometric analysis of livers at day 6 revealed lower proportions of reactive (CFSElow) human (h) CD3+ T cells in PTCy‐mice compared with saline‐mice. Over 10 weeks, PTCy‐mice showed reduced weight loss and clinical GVHD, with prolonged survival and reduced histological liver GVHD compared with saline‐mice. PTCy‐mice also demonstrated increased splenic hCD4+:hCD8+ T‐cell ratios and reduced splenic Tregs (hCD4+ hCD25+ hCD127lo) compared with saline‐mice. This study demonstrates that PTCy reduces GVHD in a preclinical humanized mouse model. This corresponded to depletion of reactive human donor T cells, but fewer human Tregs.
Last-minute cancellation of adult patients scheduled for cardiothoracic surgery in a large Dutch tertiary care centre

Abstract OBJECTIVES Unanticipated cancellation of a surgical procedure is a common problem, causing distress to the patient and increases in healthcare costs. However, limited evidence exists on the effects of last-minute cancellations of cardiothoracic surgical procedures in particular. The goal of this study was to gain insight into the prevalence of and the reasons for last-minute cancellations and to examine whether cancellation is associated with adverse medical outcomes. METHODS Patients who were scheduled for elective cardiothoracic surgical procedures between January 2017 and June 2019 were evaluated. The reasons for the cancellations were assigned to the categories medically related or process related. We examined the differences in patient characteristics between those designated as no cancellation, medically related cancellations and process-related cancellations. Lastly, we examined the outcomes of patients who experienced a last-minute cancellation of a scheduled operation. RESULTS A total of 2111 patients were included; of these, 301 (14.3%) had last-minute cancellations. In 78 (26%) cases, the cancellations were attributable to medical reasons (e.g. infection, comorbidities); 215 (71%) of the cancellations were process related (e.g. another patient in more urgent need of surgery, lack of staff). Almost 99% of the operations with a process-related cancellation were rescheduled compared to only 71.8% of the medically related cancelled operations (P < 0.001). Patients with a medically related cancellation had significantly higher 1-year mortality than patients who had no cancellation (unadjusted hazard ratio 2.50; 95% confidence interval, 1.30–4.78; P = 0.006); after adjustment for the EuroSCORE II, this effect remained significant. CONCLUSIONS Last-minute cancellations were commonly seen in our cohort, and the reasons for cancellation were significantly related to adverse medical outcomes.
Machine-learning interatomic potential for W–Mo alloys

In this work, we develop a machine-learning interatomic potential for W x Mo1−x random alloys. The potential is trained using the Gaussian approximation potential framework and density functional theory data produced by the Vienna ab initio simulation package. The potential focuses on properties such as elastic properties, melting, and point defects for the whole range of W x Mo1−x compositions. Moreover, we use all-electron density functional theory data to fit an adjusted Ziegler–Biersack–Littmarck potential for the short-range repulsive interaction. We use the potential to investigate the effect of alloying on the threshold displacement energies and find a significant dependence on the local chemical environment and element of the primary recoiling atom.
Alteration of vaginal microbiota in patients with recurrent miscarriage

Abstract The aim of this study was to characterise the structure of vaginal microbiota in unexplained recurrent miscarriage (RM). The vaginal bacterial communities of 16 patients with RM and 20 healthy volunteers were sampled. Then, the microbiomes of bacterial profiles of RM patients and healthy volunteers were compared by sequencing the V3–V4 regions of the bacterial 16S ribosomal RNA gene using the Illumina MiSeq platform (Illumina, San Diego, CA). Taxonomic analysis demonstrated that abundance of Lactobacillus and Gardnerella were significantly different between the RM and control groups. Furthermore, at the genus level, Lactobacillus was the most dominant genus in the two groups. Statistically significant differences were observed in three genera between RM and control groups. In the control group, two bacterial taxa were significantly more abundant (Lactobacillus and Gardnerella), while only one taxon was overrepresented in the RM group (Atopobium). These present findings provide experimental evidence supporting vaginal microbiota dysbiosis in women with RM. Impact statement What is already known on this subject? Currently, bacterial vaginosis is thought to be mainly due to the vaginal dysbacteriosis, which can induce unexplained recurrent miscarriage, premature rupture of membranes, low birth weight premature birth, premature birth, chorioamnionitis and series of diseases. What do the results of this study add? The current study demonstrated that Lactobacillus and Gardnerella were significantly decreased in RM patients compared to healthy control, while Atopobium was overrepresented in the RM group. What are the implications of these findings for clinical practice and/or further research? Clinically, women with RM might benefit from vaginal microbiota treatment, adjuvant therapy with Lactobacillus-based live biotherapeutics.