Miracle-dz/UniFAR-FTUs huggingface dataset:
Antenatal administration of hepatitis B immunoglobulin and hepatitis B vaccine to prevent mother to child transmission in hepatitis B virus surface antigen positive pregnant women

Abstract Background: This study aims at evaluating the benefits and harms of hepatitis B immune globulin (HBIG) and hepatitis B vaccine (HBVac) in preventing mother to child transmission in HBV surface antigen (HBsAg) positive pregnant women during antenatal period. Methods: Seven electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Database, Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), and 3 clinical trial registry platforms were searched from inception date to December 2017. Only randomized controlled trials (RCTs) were included in this study. The Cochrane risk of bias tool was applied to assessing the risk of bias. The outcomes were analyzed by Review Manager 5.3 software. Results: Sixteen RCTs involving 2440 HBsAg positive pregnant women were included in the meta-analysis. Compared with placebo group, HBIG and HBVac group had a significant decrease in the number of newborns who were HBsAg positive (relative risks [RR]: 0.2, 95% confidence interval [CI] [0.18, 0.40], P < .00001) and HBV-DNA positive (RR: 0.25, 95% CI [0.09, 0.71], P = .010), and had a significant increase in the number of anti-HBs positive newborns (RR: 3.95, 95% CI [3.11, 5.00], P < .00001). After 1-year follow up, the number of HBsAg positive newborns continued to decline (RR: 0.09, 95% CI [0.04, 0.20], P < .00001) and the number of anti-HBs positive newborns continued to increase in HBIG and HBVac group (RR: 1.30, 95% CI [1.22, 1.38], P < .00001). Compared with HBIG group, HBIG and HBVac group had no significant difference in the number of HBsAg positive newborns (RR: 1.68, 95% CI [0.66, 4.30], P = .28), and had a significant decrease in the number of HBsAg positive newborns (RR: 0.31, 95% CI [0.12, 0.84], P = .02). Additionally, only 1 study reported 2 swelling cases, 4 studies were reported no adverse events, and 11 studies were not report adverse reaction. Conclusions: HBIG and HBVac could be an effective alternative for HBsAg positive pregnant women to prevent mother to child transmission. However, due to the limitations of the study, the long-term efficacy and safety of HBIG and HBVac still need long-term and high-quality research to confirm.
COVID‐19 infection may cause ketosis and ketoacidosis

The present study included 658 hospitalized patients with confirmed COVID‐19. Forty‐two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0–70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8–33.3] vs. 16.0 [10.0–24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non‐diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID‐19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.
Confirmation of a wear‐compensation mechanism in dental roots of ruminants

Diet affects many factors of an animal's anatomy, but teeth are a specific focus of dietary research, as their durability lends them to record information on a large variety of scales. Abrasive diets like those of grazing herbivores are known to wear down teeth, but how that wear affects tooth growth and the relations between its different morphological components is rarely investigated. Seven pelleted diets varying in abrasive size and concentration were fed over a 17‐month period to 49 sheep (Ovis aries), of which n = 39 qualified for morphology measurements. Using computed tomography, scans of the skulls were made over the course of the experiment, and the impact of diet‐related wear was observed on tooth volume and morphology, including the position of dental burr marks, over time. Digital caliper measurements were applied to 3D renderings of the teeth, and the volume of crown and root segments were investigated separately. We aimed to detect a signal of root growth compensating for wear, and test if this mechanism would be affected by dietary abrasives. Crown‐segment volume loss was correlated to root‐segment volume gain. Height and burr mark measurements indicated a much higher experimental tooth wear than that previously reported for free‐ranging animals. The reason for this is unclear. There was no relationship between tooth height and dentine basin depth. For all parameters, there was no effect of diet; hence, while the measurements corroborate general understanding of tooth wear and compensatory processes, these methods appear not suitable to assess subtle differences between feeding regimes.
A single power stroke by ATP binding drives substrate translocation in a heterodimeric ABC transporter

ATP-binding cassette (ABC) transporters constitute the largest family of primary active transporters, responsible for many physiological processes and human maladies. However, the mechanism how chemical energy of ATP facilitates translocation of chemically diverse compounds across membranes is poorly understood. Here, we advance the quantitative mechanistic understanding of the heterodimeric ABC transporter TmrAB, a functional homolog of the transporter associated with antigen processing (TAP) by single-turnover analyses at single-liposome resolution. We reveal that a single conformational switch by ATP binding drives unidirectional substrate translocation. After this power stroke, ATP hydrolysis and phosphate release launch the return to the resting state, which facilitates nucleotide exchange and a new round of substrate binding and translocation. In contrast to hitherto existing steady-state assays, our single-turnover approach uncovers the power stroke in substrate translocation and the tight chemomechanical coupling in these molecular machines.
Mycotoxins in the human food chain.

The impact of mycotoxins in the human foodchain is an important issue worldwide. Ingeneral, consumers perceive less risk frommycotoxins than from other food-related threatssuch as pesticides, additives, heavy metals andmicrobial agents. This is due to the fact that, atleast in developed countries, mycotoxins veryrarely cause acute intoxication outbreaks orhealth emergencies, the impact of which is oftenamplified by the media. Nevertheless, the realdanger of mycotoxins is potentially very high,which is why they have been called 'hiddenkillers'. Mycotoxins are highly undesirablesubstances that should not be present in foodand for which a zero tolerance would be ideal.However, even good agricultural, storage andprocessing practices cannot completely preventcontamination; and it is impossible to achievea truly mycotoxin-free food chain.Consequently, small quantities of mycotoxinsbelieved not to be dangerous are legallytolerated. Despite incomplete toxicological,epidemiological and exposure data needed tofully assess human exposure and health risks,and establish causal relationships betweenmycotoxins in foods and human disease,responsible risk management makes itnecessary to take action (Kuiper-Goodman,1995). For these reasons and in order to achieverealistic goals for mycotoxin management,public authorities of many countries have fixedlegal limits for mycotoxin presence in foods.Worldwide legal limits have been recentlyreviewed by van der Westhuizen
The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma

Multiple myeloma stem‐like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti‐cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient‐derived CD138+ plasma cells are particularly sensitive to the growth‐inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81‐Eme1 endonuclease‐mediated DNA damage in S‐phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co‐treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem‐like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.
SARS‐CoV‐2 infection in beta thalassemia: Preliminary data from the Italian experience

was treated with the same anti-hemorrhagic and immunosuppressive treatment, reaching CR on day +20. In addition, the patient received anti-viral drugs (lopinavir-ritonavir 400 mg/twice daily) and noninvasive mechanical ventilation with oxygen as treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, leading to the resolution of the disease on day +14. In this case, the first reported in literature, the re-appearance of AHA was triggered by acute SARS-Cov-2 infection. This finding is particularly interesting considering the close interaction between SARS-Cov-2 and the hemostatic system. The AHA cases associated with other viral infections, including hepatitis B and C viruses, have also been described. The recent association between immune thrombocytopenic purpura and COVID-19 further strengthens the virus-induced immune dysregulation, which could have played a key role in the pathogenesis of AHA. We therefore recommend a daily coagulation monitoring (APTT) in patients admitted with acute COVID-19 infection and the inhibitor search (through a mixing test) in those cases with otherwise unexplained onset or worsening of the hemorrhagic picture and/or aPTT prolongation.
Assessment of Acute Hospital Use and Transfers for Management of Pediatric Seizures

Key Points Question What is the availability of acute hospital care for pediatric patients with seizures? Findings This cross-sectional study including 57 930 encounters with pediatric patients with seizures found that children with seizures are commonly seen in nearly all acute care hospital emergency departments. Most are treated as outpatients, but admission usually requires transfer to a very small number of high-capability receiving hospitals. Meaning These findings suggest that pediatric seizure care is highly regionalized; therefore, as health systems and insurance products evolve, adequate networks of pediatric care must include both community hospitals and their quaternary referral partners.
On‐Chip Neo‐Glycopeptide Synthesis for Multivalent Glycan Presentation

Abstract Single glycan–protein interactions are often weak, such that glycan binding partners commonly utilize multiple, spatially defined binding sites to enhance binding avidity and specificity. Current array technologies usually neglect defined multivalent display. Laser‐based array synthesis technology allows for flexible and rapid on‐surface synthesis of different peptides. By combining this technique with click chemistry, neo‐glycopeptides were produced directly on a functionalized glass slide in the microarray format. Density and spatial distribution of carbohydrates can be tuned, resulting in well‐defined glycan structures for multivalent display. The two lectins concanavalin A and langerin were probed with different glycans on multivalent scaffolds, revealing strong spacing‐, density‐, and ligand‐dependent binding. In addition, we could also measure the surface dissociation constant. This approach allows for a rapid generation, screening, and optimization of a multitude of multivalent scaffolds for glycan binding.
Persistent atrial fibrillation: When the pulmonary veins are no longer the answer

Clinical Scenario: 67 yo hypertensive overweight woman with recurrent persistent AF having undergone PVI 12 months earlier. Sinus rhythm was maintained for 6 months following PVI with 3 symptomatic recurrences despite the reintroduction of Sotalol, two of which required electrical cardioversion after 7 days duration. An echo demonstrated normal LV systolic function with mild to moderate LA enlargement. A repeat catheter ablation is performed in atrial fibrillation and you find that all pulmonary veins are electrically isolated. This article is protected by copyright. All rights reserved.
The Utility of Cognitive Screeners in the Detection of Dementia Spectrum Disorders in Spanish-Speaking Populations

Increasing rates of dementia spectrum disorders among Spanish-speaking geriatric populations necessitate the development of culturally appropriate cognitive screening tests that can identify neurodegenerative disorders in their earliest stages when emerging disease-modifying treatments are most likely to be effective. This scoping review identified 26 brief Spanish language cognitive screening tools (<20 minutes) by searching academic databases using a combination of search terms. Results suggest that the Mini-Mental Status Examination and Montreal Cognitive Assessment appear to be less valid than other screeners. Instruments such as the 7-Minute Screen and Mini-Cog evidence higher classification rates of dementia, while Phototest detected mild cognitive impairment at higher rates more consistently than other screeners. Different sensitivity and specificity outcomes and cutoffs were observed when the same cognitive screener was evaluated in different countries. Results indicate that it is imperative to increase nation-specific validation and normative data for these instruments to best serve diverse populations.
Computed Tomography–Determined Sarcopenia Is a Useful Imaging Biomarker for Predicting Postoperative Outcomes in Elderly Colorectal Cancer Patients

Purpose This study aimed to establish whether computed tomography (CT)–determined sarcopenia is a useful imaging biomarker for postoperative outcome in elderly colorectal cancer (CRC) patients, and construct sarcopenia-based nomograms to predict individual outcomes after surgery. Materials and Methods CT imaging data of 298 elderly CRC patients who underwent surgery in 2012-2014 were retrospectively analyzed. Skeletal muscle mass was determined by CT, and sarcopenia was diagnosed based on the optimal cutoff value determined by X-tile program. The correlation between sarcopenia and risk of preoperative nutrition and postoperative complications was evaluated. A Cox proportional hazards model was used to determine survival predictors. Sarcopenia-based nomograms were developed based on multivariate analysis, and calibrated using concordance index and calibration curves. Results A total 132 patients (44.3%) had sarcopenia based on the optimum cutoff values (29.9 cm2/m2 for women and 49.5 cm2/m2 for men). Sarcopenia was an independent risk factor for preoperative nutrition (p < 0.001; odds ratio [OR], 3.405; 95% confidence interval [CI], 1.948 to 5.954) and postoperative complications (p=0.008; OR, 2.192; 95% CI, 1.231 to 3.903). Sarcopenia was an independent predictor for poor progression-free survival (p < 0.001; hazard ratio [HR], 2.175; 95% CI, 1.489 to 3.179) and overall survival (p < 0.001; HR, 2.524; 95% CI, 1.721 to 3.703). Based on multivariate analysis, we produced four nomograms that had better predictive performance. Conclusion CT-determined sarcopenia is a useful imaging biomarker for predicting preoperative nutritional risk, postoperative complications, and long-term outcomes in elderly CRC patients. The sarcopenia-based nomograms can provide a scientific basis for guiding therapeutic schedule and follow-up strategies.
Fibronectin Gene Up-regulation by Arnica montana in Human Macrophages: Validation by Real-Time Polymerase Chain Reaction Assay

Abstract Background and Aim Arnica montana L. (Arnica m.) is a popular traditional medicine, used for its therapeutic properties in healing traumas, but little is known about its biological action on tissue formation and repair. This new work tested the effects of Arnica m. homeopathic dilutions on human macrophages, key cells in tissue defence and repair. Materials and Methods Macrophages derived from the THP-1 cell line were differentiated with interleukin-4 to induce a ‘wound-healing’-like phenotype, and treated with various dilutions of Arnica m. centesimal (100 times) dilutions (2c, 3c, 5c, 9c, and 15c) or control solvent for 24 hours. RNA samples from cultured cells were analysed by real-time quantitative polymerase chain reaction in five separate experiments. Results Arnica montana at the 2c dilution (final concentration of sesquiterpene lactones in cell culture = 10−8 mol/L) significantly stimulated the expression of three genes which code for regulatory proteins of the extracellular matrix, namely FN1 (fibronectin 1, % increase of 21.8 ± standard error of the mean 4.6), low-density lipoprotein-receptor-related protein 1 (% increase of 33.4 ± 6.1) and heparan sulphate proteoglycan 2 (% increase of 21.6 ± 9.1). Among these genes, the most quantitatively expressed was FN1. In addition, FN1, unlike other candidate genes, was upregulated in cells treated with higher dilutions/dynamisations (3c, 5c, and 15c) of Arnica m. Conclusion The results support evidence that the extracellular matrix is a potential therapeutic target of Arnica m. , with positive effects on cell adhesion and migration during tissue development and healing.
Clinical significance of high expression of proliferating cell nuclear antigen in non-small cell lung cancer

Abstract Although proliferating cell nuclear antigen (PCNA) plays an important role in tumor proliferation and its expression level is closely related to the biological activity of tumor cells, PCNA expression in non-small cell lung cancer (NSCLC) has been seldom reported. In this study, we aimed to investigate the significance of PCNA expression in NSCLC tissues. PCNA expression in NSCLC and adjacent tissues were assessed by immunohistochemistry (IHC), western blotting, and reverse transcription polymerase chain reaction. Single factor analysis was used to study the relationship between the expression of PCNA and clinicopathological features of NSCLC. Multi-factor Cox survival analysis was used to evaluate the relationship between the expression of PCNA and overall survival of postoperative NSCLC patients. The areas under the receiver operating characteristics were calculated to evaluate the value of PCNA expression level in predicting the 3-year survival of NSCLC patients. IHC analysis showed that the positive expression rates of PCNA protein in NSCLC and adjacent tissues were 91.79% (257/280) and 25.83% (31/120), respectively. Western blotting confirmed that PCNA protein level was significantly higher in NSCLC tissues than in the adjacent tissues (P < .05). Reverse transcription polymerase chain reaction showed that the positive rate of PCNA mRNA in NSCLC was 88.93% (249/280), which was significantly higher than that in adjacent tissues 29.17% (35/120) (P < .05). Both PCNA mRNA and protein levels were correlated with tumor differentiation, size, metastasis, and stage in NSCLC. Patients exhibiting higher PCNA protein expression had a significantly shorter disease-specific survival rate than the other patients. PCNA protein level and tumor pathological type, metastasis, differentiation degree, and stage were independent factors affecting the overall survival of postoperative patients. The areas under the receiver operating characteristics of PCNA mRNA for predicting the 3-year survival of NSCLC patients was 0.89 (0.79–0.98), with a sensitivity and specificity of 0.84 and 0.76, respectively. In conclusion, high PCNA protein and mRNA levels may be associated with the occurrence, development, and prognosis of NSCLC.
Body Composition Measurements from Birth through 5 Years: Challenges, Gaps, and Existing & Emerging Technologies—A National Institutes of Health workshop

Body composition estimates are widely used in clinical research and field studies as measures of energy‐nutrient balance, functionality and health. Despite their broad relevance and multiple applications, important gaps remain in techniques available for accurately and precisely quantifying body composition in infants and children from birth through 5 years. Identifying these gaps and highlighting research needs in this age group were the topics of a National Institutes of Health workshop held in Bethesda, MD, USA, 30–31 May 2019. Experts reviewed available methods (multicompartment models, air‐displacement plethysmography, dual‐energy X‐ray absorptiometry, weight‐length and height indices, bioimpedance analysis, anthropometry‐skinfold techniques, quantitative magnetic resonance, optical imaging, omics and D3‐creatine dilution), their limitations in this age range and high priority research needs. A summary of their individual and collective workshop deliberations is provided in this report.
MicroRNA Networks in Pancreatic Islet Cells: Normal Function and Type 2 Diabetes

Impaired insulin secretion from the pancreatic β-cells is central in the pathogenesis of type 2 diabetes (T2D), and microRNAs (miRNAs) are fundamental regulatory factors in this process. Differential expression of miRNAs contributes to β-cell adaptation to compensate for increased insulin resistance, but deregulation of miRNA expression can also directly cause β-cell impairment during the development of T2D. miRNAs are small noncoding RNAs that posttranscriptionally reduce gene expression through translational inhibition or mRNA destabilization. The nature of miRNA targeting implies the presence of complex and large miRNA–mRNA regulatory networks in every cell, including the insulin-secreting β-cell. Here we exemplify one such network using our own data on differential miRNA expression in the islets of T2D Goto-Kakizaki rat model. Several biological processes are influenced by multiple miRNAs in the β-cell, but so far most studies have focused on dissecting the mechanism of action of individual miRNAs. In this Perspective we present key islet miRNA families involved in T2D pathogenesis including miR-200, miR-7, miR-184, miR-212/miR-132, and miR-130a/b/miR-152. Finally, we highlight four challenges and opportunities within islet miRNA research, ending with a discussion on how miRNAs can be utilized as therapeutic targets contributing to personalized T2D treatment strategies.