Miracle-dz/UniFAR-FTUs huggingface dataset:
Mode of delivery is an independent risk factor for maternal mortality: a case-control study

Abstract Background and Objectives In contrast to the global trend, the maternal mortality ratio (MMR) in the United States has increased in recent decades. During this time, the cesarean section rate has concurrently and steadily increased. Herein, we sought to determine whether the mode of delivery is an independent risk factor for maternal in-hospital mortality. Materials and Methods We conducted a retrospective, population-based, 1:1 matched, case-control study on all births recorded in the Health – Care Cost and Utilization Project – Nationwide Inpatient Sample between 2005 and 2014. We compared cases of maternal mortality and survival on a number of clinical characteristics. We conducted two different multivariate logistic regression analysis models, obtaining the adjusted odds ratios to determine the independent effect of mode of delivery on maternal mortality relative to surviving controls. Results We found a total of 617 cases of maternal mortality, which corresponds to an in-hospital MMR of 6.9/100,000 in our cohort. We matched 617 controls to mortality cases by year and geographic location. Relative to surviving controls, cases of maternal mortality were older, more likely to be African American, of lesser income, more likely to use Medicaid as payment, to have prolonged admissions, and more likely to have severe obstetrical complications including preterm delivery, postpartum hemorrhage, eclampsia, peripartum cardiomyopathy, pulmonary emboli, and disseminated intravascular coagulation (DIC). Relative to unassisted vaginal delivery, adjusted logistic regression analysis reveals no excess mortality observed with assisted vaginal delivery: OR 1.35, 95% CI [0.59–3.51]. However, after adjusting for demographic and obstetrical confounders, a significant risk of maternal mortality was observed with cesarean delivery: OR 3.21, 95% CI [2.80–3.61], p-value = . 0001. This risk was more pronounced amongst primary cesarean deliveries: OR 5.72, 95% CI [4.92–6.51], p-value = . 0001. Conclusion Cesarean delivery, and particularly primary cesarean delivery, is an independent risk factor for maternal in-hospital mortality. Measures taken to reduce the cesarean section rate may impact the rising maternal mortality ratio (MMR) in the United States.
Evidence that the fungus cultured by leaf‐cutting ants does not metabolize cellulose

Leaf-cutting ants are a very specialized group of ants that cultivate fungus gardens in their nests, from which they obtain food. The current opinion is that the fungus cultivated by leaf-cutting ants digests cellulose. Here we reassess the cellulose-degrading capability of the fungus by using two complementary approaches tested in four Attini species (genera Atta and Acromyrmex): (1) ability of fungus to grow in cellulose; and (2) lignin/cellulose ratio in the refuse material dumped outside the nest, as an indicator of cellulose consumption. We found that (1) the fungus did not grow in cellulose, and (2) the lignin/cellulose ratio was much lower in the ants' refuse than in material digested by cellulose-digesting organisms, such as brown-rot fungus, termites, and ruminant mammals. This evidence strongly suggests the inability of the fungus to degrade cellulose. Therefore, the fungus–ant symbiosis and the ecological role of leaf-cutting ants need to be reconsidered.
Gendered effects on inflammation reaction and outcome of COVID‐19 patients in Wuhan

The rapid outbreak of coronavirus disease 2019 (COVID‐19) has turned into a public health emergency of international concern. Epidemiological research has shown that sex is associated with the severity of COVID‐19, but the underlying mechanism of sex predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID‐19.
Severe α-Thalassemia Due to Compound Heterozygosity for Hb Adana (α59 Gly>Asp) (HBA1: c.179G > A) and Codon 127 (A > T) (HBA2: c.382A > T) in an Iranian Family

Abstract We describe a novel compound heterozygous genotype which consists of two point mutations named Hb Adana (HBA1: c.179G>A) and codon 127 (HBA2: c.382A>T) in a Kurdish family with two girls affected with severe α-thalassemia (α-thal). Both patients (the proband and her sister) had a history of splenectomy during childhood. Although the proband had no blood transfusion history, her affected sister has had two blood transfusions so far. In conclusion, diagnosing and reporting new genotypes on the α-globin genes will improve our knowledge about complicated genotype-phenotype correlations in α-thal disorder.
EKLF and KLF2 have compensatory roles in embryonic β-globin gene expression and primitive erythropoiesis

The Kruppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Kruppel-like factor (EKLF or KLF1) regulates adult β-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and βh1-, but not adult βglobin, gene expression in mice. Both EKLF and KLF2 play roles in primitive erythroid cell development. To investigate potential interactions between these genes, EKLF/KLF2 double-mutant embryos were analyzed. EKLF−/−KLF2−/− mice appear anemic at embryonic day 10.5 (E10.5) and die before E11.5, whereas single-knockout EKLF−/− or KLF2−/− embryos are grossly normal at E10.5 and die later than EKLF−/−KLF2−/− embryos. At E10.5, Ey- and βh1-globin mRNA is greatly reduced in EKLF−/−KLF2−/−, compared with EKLF−/− or KLF2−/− embryos, consistent with the observed anemia. Light and electron microscopic analyses of E9.5 EKLF−/−KLF2−/− yolk sacs, and cytospins, indicate that erythroid and endothelial cells are morphologically more abnormal than in either single knockout. EKLF−/−KLF2−/− erythroid cells are markedly irregularly shaped, suggesting membrane abnormalities. EKLF and KLF2 may have coordinate roles in a common progenitor to erythroid and endothelial cells. The data indicate that EKLF and KLF2 have redundant functions in embryonic β-like globin gene expression, primitive erythropoiesis, and endothelial development.
Cystic Trophoblastic Tumor in a Primary Central Nervous System Post-Chemotherapy Germ Cell Tumor: The First Case Report

Cystic trophoblastic tumor (CTT) is an uncommon trophoblastic proliferation of germ cell tumor origin, mostly reported in post-chemotherapy metastases of testicular germ cell tumors and rarely primary untreated testicular tumors. To date, we are not aware of occurrence in a non-testicular tumor. A 12-year-old boy presented with limb swelling, increased appetite, weight gain, and precocious puberty. Evaluation revealed right frontal lobe mass and elevated α-fetoprotein and β-human chorionic gonadotrophin. After response to neoadjuvant chemotherapy, the tumor was resected. Microscopically, the resection contained predominantly smooth muscle tissue with scattered small foci of glandular teratoma and CTT. Immunohistochemistry (SALL4, glypican 3) revealed no residual yolk sac tumor. Fluorescence in situ hybridization revealed gain of chromosome 12p. The patient has been disease-free for 13 years. This report expands the spectrum of primary central nervous system germ cell tumors with the occurrence of CTT in this site.
MicroRNA-30a regulates acute cerebral ischemia-induced blood–brain barrier damage through ZnT4/zinc pathway

The mechanism of early blood–brain barrier (BBB) disruption after stroke has been intensively studied but still not fully understood. Here, we report that microRNA-30a (miR-30a) could mediate BBB damage using both cellular and animal models of ischemic stroke. In the experiments in vitro, inhibition of miR-30a decreased BBB permeability, prevented the degradation of tight junction proteins, and reduced intracellular free zinc in endothelial cells. We found that the zinc transporter ZnT4 was a direct target of negative regulation by miR-30a, and ZnT4/zinc signaling pathway contributed significantly to miR-30a-mediated BBB damage. Consistent with these in vitro findings, treatment with miR-30a inhibitor reduced zinc accumulation, increased the expression of ZnT4, and prevented the loss of tight junction proteins in microvessels of ischemic animals. Furthermore, inhibition of miR-30a, even at 90 min post onset of middle cerebral artery occlusion, prevented BBB damage, reduced infarct volume, and ameliorated neurological deficits. Together, our findings provide novel insights into the mechanisms of cerebral ischemia-induced BBB disruption and indicate miR-30a as a regulator of BBB function that can be an effective therapeutic target for ischemic stroke.
Challenges to reduce or replace NaCl by chloride salts in meat products made from whole pieces – a review

Abstract NaCl is fundamental for the development of the physico-chemical, sensorial and microbiological stability in meat products made from whole pieces such as dry-cured lacón, loin, ham, bacon, jerked beef, and pastirma). The substitution of NaCl by other chloride salts (KCl, CaCl2 and MgCl2), in order to minimize changes in the processing steps and insertion of new ingredients, is a major challenge for the elaboration of salted meat products in the context of increasing awareness among consumer about sodium consumption and health. This review aims to discuss the potential use of binary, ternary and quaternary salting mixtures in the processing of salted meat products and their effects on microbiological evolution and safety, sensory properties, oxidative reactions on proteins and lipid, and proteolysis and lipolysis reactions. More specifically, the substitution of NaCl by other chloride salts can influence the growth of microorganisms, the formation of toxic compounds, progression of enzymatic and oxidative reactions, and the sensory attributes. Scientific evidences from a food technological point of view, support the use of KCl to partially replace NaCl while major advances/more sophisticated strategies are still necessary to effectively introduce CaCl2 and MgCl2 as NaCl replacers. Moreover, further studies regarding the shelf-life and economic problems of the alternatively salted products are still necessary.
Human histone H3K79 methyltransferase DOT1L protein binds actively transcribing RNA polymerase II to regulate gene expression.

Histone-modifying enzymes play a pivotal role in gene expression and repression. In human, DOT1L (Dot1-like) is the only known histone H3 lysine 79 methyltransferase. hDOT1L is associated with transcriptional activation, but the general mechanism connecting hDOT1L to active transcription remains largely unknown. Here, we report that hDOT1L interacts with the phosphorylated C-terminal domain of actively transcribing RNA polymerase II (RNAPII) through a region conserved uniquely in multicellular DOT1 proteins. Genome-wide profiling analyses indicate that the occupancy of hDOT1L largely overlaps with that of RNAPII at actively transcribed genes, especially surrounding transcriptional start sites, in embryonic carcinoma NCCIT cells. We also find that C-terminal domain binding or H3K79 methylations by hDOT1L is important for the expression of target genes such as NANOG and OCT4 and a marker for pluripotency in NCCIT cells. Our results indicate that a functional interaction between hDOT1L and RNAPII targets hDOT1L and subsequent H3K79 methylations to actively transcribed genes.
The impact of world assumptions on the association between discrimination and internalizing and substance use outcomes

This study investigated whether core beliefs about the world being safe and predictable (i.e. world assumptions) mediated the association between discrimination and internalizing and substance use problems among individuals from marginalized groups. Path analyses tested mediating effects of four types of world assumptions on the association between discrimination (race-, gender-, and sexual orientation-based) and anxiety, depression, alcohol and cannabis problems in college students (N = 1,181, agemean = 19.50, SD = 1.67). Limited support for mediation by world assumptions was found: among Asian students, race-based discrimination indirectly impacted anxiety symptoms through low perceived controllability of events. Direct effects across groups and discrimination types were also found.
Evaluation of the pharmacokinetic-pharmacodynamic integration of marbofloxacin in combination with methyl gallate against Salmonella Typhimurium in rats

Fluoroquinolone resistance in Salmonella Typhimurium is becoming a major concern. Hence, an intervention to limit the growth in resistance is inevitable. One way to combat this challenge is through combination therapy. The combination of antibiotics with phytochemicals has become an ideal means of preventing antimicrobial resistance. Recently, in an in vitro study, the combination of methyl gallate (MG) with marbofloxacin (MAR) has shown to prevent Salmonella Typhimurium invasion. It is also worth to study the effects of plant extracts on the pharmacokinetics of antibiotics. Hence, the objective of this study was to determine the effect of MG on the pharmacokinetics of MAR and pharmacokinetics/pharmacodynamics integration of MG and MAR. The micro-broth dilution method was used to obtain the minimum inhibitory concentration (MIC), and fractional inhibitory concentration (FIC) of MAR and MG. Whereas, the pharmacokinetic was conducted in rats by administering either MAR alone or combined with MG through oral and/or intravenous routes. The results indicated that the MIC of MAR and MG against standard strain Salmonella Typhimurium (ATCC 14028) was 0.031 and 500 μg/mL, respectively. The FICindex of the combination of MAR and MG was 0.5. For orally administered drugs, the Cmax and AUC24h of MAR were 1.04 and 0.78 μg/mL and 5.98 and 6.11 h. μg/mL when MAR was given alone and in combination with MG, respectively. The intravenous administration of MAR showed a half-life of 3.8 and 3.9 h; a clearance rate of 1.1 and 0.73 L/h/kg and a volume of distribution of 5.98 and 4.13 L/kg for MAR alone and in combination with MG, respectively. The AUC24/MIC for MAR alone and in combination with MG was 192.8 and 381.9 h, respectively. In conclusion, MG has shown to increase the antimicrobial activity of MAR in vitro and ex vivo experiments without affecting the pharmacokinetics of MAR in rats.
The Psychological Change Process of Frontline Nurses Caring for Patients with COVID-19 during Its Outbreak

Abstract Aim: To identify the psychological change process of the registered nurses who worked in the epicenter of the COVID-19 outbreak. Background: The pandemic of COVID-19 has continued to pose an unprecedented threat and challenge to people’s health around the world. Nurses are at high risk because they work within the closest proximity to patients. Understanding nurses’ psychological change process during the care for patients with COVID-19 is imperative for healthcare leaders. Methods: This was a qualitative descriptive study that took place in a hospital in Wuhan, China, the epicenter of the COVID-19 epidemic, from February 9th to March 15th, 2020. Using purposive sampling, we interviewed 23 nurses. Data were analyzed using Colaizzi’s method of data analysis to find, understand, and describe nurses’ experiences. Results: The psychological change process of frontline nurses included three stages, early, middle, and later stages. The psychological characteristics of each period were ambivalence, emotional exhaustion, and energy renewal, respectively. Nurse leaders were anchors in facilitating frontline nurses’ psychological adaptation. Conclusions: In the past month, the psychological characteristics of nurses changed over time. The study indicated the necessity for nurse leaders to implement intervention programs based on nurses’ psychological characteristics in different periods to promote nurses’ health during this critical time period.
Morphometric MRI Analysis: Improved Detection of Focal Cortical Dysplasia Using the MP2RAGE Sequence

BACKGROUND AND PURPOSE: Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. MATERIALS AND METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. RESULTS: Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). CONCLUSIONS: In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.
De-Escalation After DE-ESCALATE and RTOG 1016: A Head and Neck Cancer InterGroup Framework for Future De-Escalation Studies

Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) is increasing rapidly. The younger age, significantly improved prognosis, and relative morbidity of the standard-of-care cisplatin and radiotherapy in this population have led to the popularization of the concept of treatment de-escalation. The recent results of the first 3 randomized de-escalation trials, however, have shown a clear detriment in survival when cisplatin is omitted or substituted. In view of these results, the Head and Neck Cancer International Group identified the need to issue guidance regarding future de-escalation studies for patients with HPV-positive head and neck cancer to avoid the possibility of patients being harmed. We review the current state of the literature regarding HPV de-escalation trials and present a framework and guidance on future and existing clinical trials for treatment de-escalation of HPV-positive OPC. De-escalation paradigms of HPV-positive OPC should be evaluated in phase II studies, and results should be awaited before proceeding to phase III studies. Implementation into clinical practice before high-level evidence is available should not be undertaken in this context. Finally, harm-minimization techniques should also be evaluated as an alternative to de-escalation of treatment in these patient groups.
The viability of akinetes of blue-green algae recovered from the sediments of Rostherne Mere

Akinetes from species of blue-green algae were recovered from the recent sediments of Rostherne Mere. Gas vacuolate populations of Aphanizomenon and Anabaena were cultured from sediment up to 18 and 64 years old respectively. Akinetes of blue-green algae may not only have a temporary, or overwintering, function but may also ensure long term survival.
Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody–drug Conjugate (ARX788) for Breast Cancer Treatment

Conventional antibody–drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The nonspecific conjugation results in a mixture with variable drug-to-antibody ratios (DAR), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent antitubulin cytotoxic drug-linker, AS269. The site-specific conjugation is achieved by first incorporating the nonnatural amino acid, para-acetyl phenylalanine (pAF), into the antibody, followed by covalent conjugation of AS269 to the pAF to form a highly stable oxime bond resulting in a DAR 2 ADC. ARX788 exhibits significant, dose-dependent antitumor activity against HER2- expressing breast and gastric xenograft tumors. Pharmacokinetic (PK) studies in multiple species showed the highly stable nature of ARX788 with overlapping PK profiles for the intact ADC and total antibody. Metabolism studies demonstrated that pAF-AS269 was the sole major metabolite of ARX788, with no evidence for the release of free drug often observed in conventional ADCs and responsible for adverse side effects. Furthermore, ARX788 demonstrated a favorable safety profile in monkeys with a highest nonseverely toxic dose of 10 mg/kg, which was well above the efficacious dose level observed in preclinical tumor models, thus supporting clinical development of ARX788.
Karyotype Analysis and Ploidy Determination Using Flow Cytometry in African Bitter Milk Plant "Utazi", Gongronema latifolium Benth

Availability of basic genetic information on a plant species is the first pre-requisite in designing any genetic improvement programme for the species. This study was therefore carried out to determine the karyotype of Gongronema latifolium to obtain basic knowledge on ploidy level and karyotype as a first step in understanding the genetics of this spice plant. Karyotype and flow cytometry (FCM) studies were carried out on 4 accessions of G. latifolium collected from the humid forest vegetation in Abia, Akwa Ibom, Cross River and Imo States of Nigeria. Chromosome number of Abia accessions were 2n=20 and 22 with karyotype formulae, 3m+4sm+2a+1t and 2m+4sm+ 2a+3t, respectively; Akwa Ibom accessions, 2n=18 with formula: 3m+5sm+1a; Cross River accessions, 2n=18 and 22 with formulae: 2m+4sm+2a+1t and 3m+4sm+3a+1t, respectively; Imo accessions, 2x=22 and 24 with formulae: 1m+5sm+3a+2t and 2m+7sm+2a+1t, respectively. Results obtained revealed cytotype variation and the occurrence of 4 cytotypes, 2n=18, 20, 22 and 24. We therefore conclude that G. latifolium is a diploid species with variable basic numbers. Four basic numbers, n=9, 10, 11 and 12, were therefore proposed for G. latifolium. FCM showed the presence of 2C and 4C DNA content and provided evidence for endoreduplication, a likely evolutionary survival mechanism in this climbing vegetable plant species. This is the first report of karyotype analysis in Gongronema latifolium, an important indigenous African vegetable spice plant with huge medicinal value.