Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum biomarkers for prediction of mortality in patients with COVID-19

Background There is limited information regarding the role of biomarker levels at predicting mortality in patients with the coronavirus disease (COVID-19) pandemic. The purpose of this study is to determine the differences in serum biomarker levels in adults with COVID-19 who survived hospitalization from those who did not. Methods A comprehensive search was completed on PubMed, EMBASE and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. Results A total of 10 studies with 1584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from coronavirus disease included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukin-6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Lymphocyte count, platelet count and albumin were significantly lower in patients who died. Conclusion This pooled analysis of 10 studies including 1584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited health-care resources.
Incidence and prognosis of COVID‐19 in psoriasis patients on biologic therapy: a multicentre retrospective cohort study

Current guidelines recommend continuing biologic therapy in dermatologic patients who have not tested positive for or exhibited signs/symptoms of COVID-19 and postponing biologic therapy in patients who have tested positive for or exhibited signs/symptoms of COVID-19.1-3 In order to help guide current recommendations, we aimed to investigate the incidence and prognostic outcomes of positive ﻿SARS-CoV-2 infection in psoriasis patients on biologic therapy.
Cryo‐kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase

Effects of isotopic substitution on the rate constants of human dihydrofolate reductase (HsDHFR), an important target for anti‐cancer drugs, have not previously been characterized due to its complex fast kinetics. Here, we report the results of cryo‐measurements of the kinetics of the HsDHFR catalyzed reaction and the effects of protein motion on catalysis. Isotopic enzyme labeling revealed an enzyme KIE (kHLE/kHHE) close to unity above 0 °C; however, the enzyme KIE was increased to 1.72±0.15 at −20 °C, indicating that the coupling of protein motions to the chemical step is minimized under optimal conditions but enhanced at non‐physiological temperatures. The presented cryogenic approach provides an opportunity to probe the kinetics of mammalian DHFRs, thereby laying the foundation for characterizing their transition state structure.
Myocarditis Presenting as Sudden Death in Infants and Children: A Single Centre Analysis by ESGFOR Study Group

Background Acute myocarditis is an inflammatory disease of the heart mostly diagnosed in young people, which can present as sudden death. The etiology includes infectious agents (mostly viruses), systemic diseases and toxins. We aim to characterize infants and children with myocarditis at post-mortem presenting as sudden deaths. Methods Retrospective evaluation of 813 post-mortems in infants and children dying suddenly and unexpectedly between 2009–2019. Data retrieved included histological features, microbiology and clinical history. Results 23 of 813 post-mortems reviewed corresponded to acute myocarditis and 1 to dilated cardiomyopathy related to remote Parvovirus infection. PCR identified enterovirus (7), parvovirus (7 cases, 2 also with HHV6 and 1 case with EVB), Influenza A (1), Parainfluenza type 3 (1). Two cases corresponded to hypersensitivity myocarditis, 1 was Group A Streptococcus and 5 idiopathic myocarditis. Enterovirus was frequent in infants (7/10), and in newborns was associated with meningoencephalitis or congenital myocarditis. More than 50% were less than 2 years of age and all remained clinically unsuspected. Conclusion Myocarditis represents almost 3% of all sudden pediatric deaths. Enterovirus and parvovirus were the most common viruses. This retrospective analysis showed that patients experienced viral symptoms but remained unsuspected, highlighting the need for more clinical awareness of myocarditis.
Powder diffraction data for ferrous gluconate

Synchrotron powder diffraction data have been obtained and indexed for ferrous gluconate, a common supplement used for the treatment and prevention of iron-deficiency anemia. Ferrous gluconate (Fe(C6H11O7)2 · x H2O, Z = 4) crystallizes in a monoclinic cell (space group I2, #5) with lattice parameters a = 19.953 16(9) Å, b = 5.513 92(3) Å, c = 18.470 58(9) Å, and β = 111.3826(3)°. The pattern shows no evidence of impurity reflections.
Intratendinous Strain Variations of the Supraspinatus Tendon Depending on Repair Technique: A Biomechanical Analysis Regarding the Cause of Medial Cuff Failure

Background: Double-row (DR) and transosseous-equivalent (TOE) techniques for rotator cuff repair offer more stability and promote better tendon healing compared with single-row (SR) repairs and are preferred by many surgeons. However, they can lead to more disastrous retear patterns with failure at the medial anchor row or the musculotendinous junction. The biomechanics of medial cuff failure have not been thoroughly investigated thus far. Purpose: To investigate the intratendinous strain distribution within the supraspinatus tendon depending on repair technique. Study Design: Controlled laboratory study. Methods: Twelve fresh-frozen cadaveric shoulders were used. The intratendinous strain within the supraspinatus tendon was analyzed in 2 regions—(1) at the footprint at the greater tuberosity and (2) medial to the footprint up to the musculotendinous junction—using a high-resolution 3-dimensional camera system. Testing was performed at submaximal loads of 40 N, 60 N, and 80 N for intact tendons, after SR repair, after DR repair, and after TOE repair. Results: The tendon strain of the SR group differed significantly in both regions from that of the intact tendons and the TOE group at 40 N (P≤ .043) and from the intact tendons, the DR group, and the TOE group at 60 N and 80 N (P≤ .048). SR repairs showed more tendon elongation at the footprint and less elongation medial to the footprint. DR and TOE repairs did not provide significant differences in tendon strain when compared with the intact tendons. However, the increase in tendon strain medial to the footprint from 40 N to 80 N was significantly more pronounced in the DR and TOE group (P≤ .029). Conclusion: While DR and TOE repair techniques more closely reproduced the strains of the supraspinatus tendon than did SR repair in a cadaveric model, they showed a significantly increased tendon strain at the musculotendinous junction with higher loads in comparison with the intact tendon. Clinical Relevance: DR and TOE rotator cuff reconstructions lead to a more anatomic tendon repair. However, their use has to be carefully evaluated whenever tendon quality is diminished, as they lead to a more drastic increase in tendon strain medial to the footprint, putting these repairs at risk of medial cuff failure.
Long-term neurodevelopmental outcome after prenatal exposure to maternal hematological malignancies with or without cytotoxic treatment

ABSTRACT Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18 months, 36 months, 6, 9, 12, 15 and 18 years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child’s general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7 years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7 years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer.
Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell

Abstract Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative end-joining (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that repair of Cas9-induced breaks also involves NHEJ, Alt-EJ, and HR pathways, providing a new format to measure pathway usage. Here, we have developed a simple Cas9-based system with validated repair outcomes that accurately represent each pathway and then converted it to a droplet digital PCR (ddPCR) readout, thus obviating the need for Next Generation Sequencing and bioinformatic analysis with the goal to make Cas9-based system accessible to more laboratories. The assay system has reproduced several important insights. First, absence of the key Alt-EJ factor Pol θ only abrogates ∼50% of total Alt-EJ. Second, single-strand templated repair (SSTR) requires BRCA1 and MRE11 activity, but not BRCA2, establishing that SSTR commonly used in genome editing is not conventional HR. Third, BRCA1 promotes Alt-EJ usage at two-ended DSBs in contrast to BRCA2. This assay can be used in any system, which permits Cas9 delivery and, importantly, allows rapid genotype-to-phenotype correlation in isogenic cell line pairs.
Resistome and microbial profiling of pediatric patient’s gut infected with multidrug-resistant diarrhoeagenic Enterobacteriaceae using next-generation sequencing; the first study from Pakistan

ABSTRACT A high prevalence of multidrug-resistant (MDR) pathogens has been reported in adult and pediatric populations of Pakistan. However, data describing the effect of MDR microbes on the gut microbiota is scarce. We designed a cross-sectional pediatric study to investigate the effect of MDR microbes’ infection on the gut microbiome and its resistome of children using high-throughput next-generation sequencing (NGS). A cross-sectional study was conducted at a tertiary health care hospital in Peshawar Pakistan, between 5 September 2019 to 15 February 2020. Pediatric patients with acute gastroenteritis (n = 200) were enrolled. All the enrolled pediatric patients underwent initial antimicrobial resistance (AMR) screening using the disk diffusion method. Children with MDR infections were identified and selected for gut microbiome and its resistome profiling using NGS. Out of 200 enrolled pediatric patients, 80 (40%) were found infected with MDR diarrheagenic Enterobacteriaceae consisting of 50 (62.5%) infections caused by extended-spectrum beta-lactamase (ESBL) producing E. coli while 30 (37.5%) by MDR Enterobacter specie. A total of 63 and 17 antibiotic-resistant genes (ARGs) conferring resistance to 7 and 5 classes of antibiotics were identified in the resistomes of MDR diarrheagenic Enterobacteriaceae infected and healthy children, respectively. NGS-based gut microbial profiling of MDR Enterobacter spp. , ESBL producing E. coli infected pediatric patients and healthy controls revealed the predominance of Proteobacteria and Actinobacteria, respectively. An increased abundance of several pathogenic gram-negative bacteria namely E. coli, Enterobacter cloacae, and Salmonella enterica was observed in the gut microbiota of children infected with MDR bacterial infections than that of the healthy controls. This work indicates that children with MDR infections have reduced microbial diversity and enriched ARGs than healthy controls. The emergence of MDR bacterial strains and their association with gut dysbiosis needs immediate attention to regulate antibiotics usage in Pakistani children.
The Relationship of the Type of Intracerebral Hemorrhage to Early Disease Evolution and Long-Term Prognosis After r-tPA Thrombolysis

To investigate the relationship of different subtypes of intracerebral hemorrhage (ICH) to early disease evolution and long-term prognosis in patients with acute cerebral infarction after intravenous recombinant tissue plasminogen activator(r-tPA). Seventy ischemic stroke patients treated with intravenous r-tPA who underwent computed tomography (CT) within 24 hours after thrombolysis were divided into 4 types (hemorrhagic infarction type 1 [HI-1], HI-2, parenchymal hemorrhage type 1 [PH-1], or PH-2 which according to the size of the hematoma and the presence or absence of space-occupying effect). Early evolution of the disease was observed by the change in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours after thrombolysis. The long-term prognosis was assessed by the modified Rankin Scale (mRS) score at the third month. There were 17 (24.3%) patients with ICH. Compared with patients in the non-ICH group, HI did not affect early neurological function or clinical outcome at the third month. PH-1 did not increase the risk of early neurological deterioration; however, PH-1 has a tendency to increase the risk of death at the third month (50% vs 11.3%, P = 0.090). PH-2 was significantly related to early neurological deterioration (66.7% vs 3.8%, P < 0.001) and mortality at the third month (50.0% vs 11.3%, P = 0.040). Patients with different subtypes of ICH after thrombolysis have different clinical outcomes. PH-2 is significantly associated with early neurological deterioration and increases mortality at the third month.
Protective antibodies against human parainfluenza virus type 3 infection

ABSTRACT Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. There are currently no effective vaccines or therapeutics available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell repertoires from peripheral blood, tonsils, and spleen from healthy children and adults. These analyses yielded five monoclonal antibodies that potently neutralized HPIV3 in vitro. These HPIV3-neutralizing antibodies targeted two non-overlapping epitopes of the HPIV3 F protein, with most targeting the apex. Prophylactic administration of one of these antibodies, PI3-E12, resulted in potent protection against HPIV3 infection in cotton rats. Additionally, PI3-E12 could also be used therapeutically to suppress HPIV3 in immunocompromised animals. These results demonstrate the potential clinical utility of PI3-E12 for the prevention or treatment of HPIV3 in both immunocompetent and immunocompromised individuals.
Family resilience is a protective buffer in the relationship between infertility-related stress and psychological distress among females preparing for their first in vitro fertilization–embryo transfer

ABSTRACT The present study aimed to evaluate psychological distress and scrutinized whether family resilience plays a moderating role in the association between infertility-related stress and psychological distress among infertile females preparing for their first IVF-ET. A total of 492 infertile females completed self-reported measures including the Kessler 10 Psychological Distress Scale (K10), the fertility problem inventory (FPI), and the Family Resilience Assessment Scale (FRAS). The results showed 21 (65.2%) participants reported moderate or higher levels of psychological distress. While controlling for economic status, we found psychological distress to be positively linked to infertility-related stress (β=0.483, P<0.001), and negatively related to family resilience (β=-0.145, P=0.001). The simple slopes analysis showed that infertility-related stress had a weaker positive association with psychological distress for individuals at 1 SD (β = 0.443, P < 0.001) above the mean on family resilience compared to those at 1 SD (β = 0.537, P < 0.001) below the mean. Thus, it suggests that clinical practice should conduct family resilience–oriented interventions to facilitate family resilience among infertile females preparing for their first IVF-ET, with the goal to reduce psychological distress.
A New Equation Based on the Standard Lipid Panel for Calculating Small Dense Low-Density Lipoprotein-Cholesterol and Its Use as a Risk-Enhancer Test.

BACKGROUND Increased small dense low-density lipoprotein-cholesterol (sdLDL-C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD) but typically requires advanced lipid testing. We describe two new equations, first one for calculating large buoyant LDL-C (lbLDL-C), based only upon results from the standard lipid panel, and the second one for sdLDL-C. METHODS Equations for sdLDL-C and lbLDL-C were generated with least-squares regression analysis using the direct Denka sdLDL-C assay as reference (n = 20 171). sdLDL-C was assessed as a risk-enhancer test in the National Heart and Nutrition Examination Survey (NHANES), and for its association with ASCVD in the Multi-Ethnic Study of Atherosclerosis (MESA). RESULTS The newly derived equations depend on two terms, namely LDL-C as determined by the Sampson equation, and an interaction term between LDL-C and the natural log of triglycerides (TG). The lbLDL-C equation (lbLDLC=1.43 × LDLC-0.14 ×(ln⁡(TG)× LDLC)- 8.99) was more accurate (R2 = 0.933, slope = 0.94) than the sdLDL-C equation (sdLDLC=LDLC- lbLDLC; R2 = 0.745, slope = 0.73). Using the 80th percentile (46 mg/dL) as a cut-point, sdLDL-C identified in NHANES additional high-risk patients not identified by other risk-enhancer tests based on TG, LDL-C, apolipoprotein B, and nonHDL-C. By univariate survival-curve analysis, estimated sdLDL-C was superior to other risk-enhancer tests in predicting ASCVD events in MESA. After multivariate adjustment for other known ASCVD risk factors, estimated sdLDL-C had the strongest association with ASCVD compared to other lipid parameters, including measured sdLDL-C. CONCLUSIONS Estimated sdLDL-C could potentially be calculated on all patients tested with a standard lipid panel to improve ASCVD risk stratification.
Sweet spheres: Succession and CAZyme expression of marine bacterial communities colonising a mix of alginate and pectin particles.

Polysaccharide particles are important substrates and microhabitats for marine bacteria. However, substrate-specific bacterial dynamics in mixtures of particle types with different polysaccharide composition, as likely occurring in natural habitats, are undescribed. Here, we studied the composition, functional diversity and gene expression of marine bacterial communities colonising a mix of alginate and pectin particles. Amplicon, metagenome and metatranscriptome sequencing revealed that communities on alginate and pectin particles significantly differed from their free-living counterparts. Unexpectedly, microbial dynamics on alginate and pectin particles were similar, with predominance of amplicon sequence variants (ASVs) from Tenacibaculum, Colwellia, Psychrobium and Psychromonas. Corresponding metagenome-assembled genomes (MAGs) expressed diverse alginate lyases, several co-localised in polysaccharide utilisation loci. Only a single, low-abundant MAG showed elevated transcript abundances of pectin-degrading enzymes. One specific Glaciecola ASV dominated the free-living fraction, possibly persisting on particle-derived oligomers through different glycoside hydrolases. Elevated ammonium uptake and metabolism signified nitrogen as important factor for degrading carbon-rich particles, whereas elevated methylcitrate and glyoxylate cycles suggested nutrient limitation in surrounding waters. The bacterial preference for alginate, whereas pectin primarily served as colonization scaffold, illuminates substrate-driven dynamics within mixed polysaccharide pools. These insights expand our understanding of bacterial niche specialisation and the biological carbon pump in macroalgae-rich habitats. This article is protected by copyright. All rights reserved.
Translation, reliability and validity of Persian version of Adolescent/Adult Sensory Profile in dementia

Abstract Our study aimed at the reliability and validity of the Persian version of the Adolescent/Adult Sensory Profile (AASP). This study was conducted on 130 people with dementia as well as 77 healthy elderlies. After translating the AASP into Persian, its content validity was determined based on 9 experts working in the same field. Cronbach’s alpha and the Intraclass correlation coefficient (ICC) were calculated to assess the internal consistency and test–retest reliability of the Persian version of AASP. The two groups of people with dementia and healthy elderlies were compared in terms of scores in the four quadrants by performing an Independent t-test. All items in the Content Validity Ratio (CVR) and Content Validity Index (CVI) received an acceptable score. The Cronbach’s alpha score for different parts of AASP was also calculated (α between 0.894 and 0.916; p < 0.001). The test–retest reliability of sub-tests of AASP was excellent (ICC between 0.885 and 0.948; p < 0.001). There was a statistically significant difference between the healthy Elderlies and dementia persons for low registration, sensory avoiding quadrants (p < 0.05). The Persian version of the AASP questionnaire is a reliable and valid questionnaire for people with dementia in Iran.