Miracle-dz/UniFAR-FTUs huggingface dataset:
Interventions for Posttraumatic Stress Disorder Arousal and Reactivity Symptoms in Adults with a History of Childhood Adversity: Scoping Review

Purpose: Adverse Childhood Experiences (ACE) predispose individuals to adult-onset posttraumatic stress disorder (PTSD) with amplified arousal and reactivity symptoms (A&R). This review aimed to identify interventions for reducing A&R symptoms in adults diagnosed with PTSD and a history of ACEs. Method: Systematic scoping review of RCT and quasi-experimental studies in peer-reviewed journals using Arksey and O’Malley’s 5-Stage Framework. Extracted data were analyzed descriptively and thematically. Results: Five articles met inclusion criteria. Skills training in affect and interpersonal regulation (STAIR) with exposure, Cognitive Behavioral Therapy (CBT-PE), Interpersonal Processing Group Therapy (IPG), and Trauma-informed yoga interventions were identified. STAIR (d = −1.45, 95% CI [−2.10, −0.80), CBT-PE (d = −1.21, 95% CI [−1.92, −0.51]), and IPG (d = −1.33, 95% CI [−2.07, −0.58]) had large effects on A&R symptoms. Discussion: CBT exposure-based treatments were supported interventions for reducing A&R symptoms in adults diagnosed with PTSD and a history of ACEs.
‘I play, therefore I can’: Using Drama Activities to Reduce the English speaking Anxiety of College Students

Research on drama and anxiety remains relatively unexplored in applied linguistics and language teaching in the Philippines. This study addresses this need by looking into the effects of drama activities on college students in the Philippines who were observed to have anxiety in speaking. More specifically, the study involves the students in a series of improvisational activities, aiming to improve their confidence in speaking. Student motivation, anxiety, and confidence in speaking English are measured by pretest and post-test survey, interviews, and observations in implementing a workshop that employs drama activities. Drawing from Vygotsky’s (1978) zone of proximal development (ZPD), this study examines the efficiency of drama activities in providing a safe space where they can motivate one another and learn collaboratively. The findings of this study may encourage language teachers to design strategies that scaffold learning activities to minimize anxiety and reinforce positive attitudes towards speaking in English.
Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death

The reactivity of retinal glia in response to oxidative stress has a significant effect on retinal pathobiology. The reactive glia change their morphology and secret cytokines and neurotoxic factors in response to oxidative stress associated with retinal neurovascular degeneration. Therefore, pharmacological intervention to protect glial health against oxidative stress is crucial for maintaining homeostasis and the normal function of the retina. In this study, we explored the effect of azithromycin, a macrolide antibiotic with antioxidant, immunomodulatory, anti-inflammatory, and neuroprotective properties against oxidative stress-induced morphological changes, inflammation, and cell death in retinal microglia and Müller glia. Oxidative stress was induced by H2O2, and the intracellular oxidative stress was measured by DCFDA and DHE staining. The change in morphological characteristics such as the surface area, perimeter, and circularity was calculated using ImageJ software. Inflammation was measured by enzyme-linked immunosorbent assays for TNF-α, IL-1β, and IL-6. Reactive gliosis was characterized by anti-GFAP immunostaining. Cell death was measured by MTT assay, acridine orange/propidium iodide, and trypan blue staining. Pretreatment of azithromycin inhibits H2O2-induced oxidative stress in microglial (BV-2) and Müller glial (MIO-M1) cells. We observed that azithromycin inhibits oxidative stress-induced morphological changes, including the cell surface area, circularity, and perimeter in BV-2 and MIO-M1 cells. It also inhibits inflammation and cell death in both the glial cells. Azithromycin could be used as a pharmacological intervention on maintaining retinal glial health during oxidative stress.
The important role of the eccDNA in tumors

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2022;10(15):844 | https://dx.doi. org/10.21037/atm-22-1750 We would like to thank Qian et al. for their interest in our published work about the potential function of extrachromosomal circular DNA (eccDNA) in esophageal squamous cell carcinoma (ESCC) (1). We have read their article revealing the characterization of the eccDNA in acute myeloid leukemia (AML) with great interest (2). In the article, the authors did not mention the total amount of detected eccDNAs in their samples and showed only 298 up-regulated and 71 down-regulated eccDNAs in AML patients compared to healthy controls, which is far less than the number in our work (1,2). Maybe it is due to tumor specificity or different sequencing methods. The authors identified a cluster of up-regulated eccDNAs derived from the mitochondrial genome, however, our work detected no such eccDNAs. Additionally, the study observed altered biological processes related to up-regulated eccDNAs and no process or network related to downregulated eccDNAs. Nevertheless, our work demonstrated various biological processes playing key roles in ESCC progression by analysis of either up-regulated or downregulated eccDNAs (1,2). These differences may be caused by less amount of differently expressed eccDNAs. We think maybe the optimized methods in eccDNA extraction and amplification or sequencing with higher sensitivity and specificity is possible to have more conclusive results in AML study. Since the discovery, eccDNAs have been reported to contribute to many malignancies (3). As far as we know, there are several mechanisms for their potential function in tumors. Firstly, long-size eccDNAs containing the sequence of oncogenes can lead to oncogene amplification and participate in tumors. Oncogene transcription is more efficient in eccDNA amplification compared to matched linear DNA (4). Secondly, Zhu et al. (5) recently demonstrated that eccDNAs can contact with specific chromosomal genes through RNA polymerase II— mediated chromatin interaction and function as a mobile enhancer to activate the expression of genes relevant to oncogenesis pathways. Thirdly, eccDNAs with limited size rarely carrying full length of protein-coding sequence can encode regulatory short RNAs, such as microRNA and siRNA, to modulate gene expression and participate in tumor biology (6). Fourthly, eccDNAs with limited size possibly function as sponges for transcription factors to regulate gene expression indirectly (7). Of course, other possible mechanisms, such as immune response to naked DNA from eccDNAs, remain to be elucidated. To be noted, our work and previous reports have shown that the length of differently expressed eccDNAs in tumors varies and they are unevenly distributed in different genomic regions, such as 5'and 3'-untranslated regions (UTRs), CpG island regions, exons etc. (1,8). Maybe different categories of eccDNAs function by different mechanisms. The important role of eccDNAs in tumors still needs to be investigated in further studies.
Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure

(1) Background: The development of mitochondrial medicine has been severely impeded by a lack of effective therapies. (2) Methods: To better understand Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-like episodes (MELAS) syndrome, neuronal cybrid cells carrying different mutation loads of the m.3243A > G mitochondrial DNA variant were analysed using a multi-omic approach. (3) Results: Specific metabolomic signatures revealed that the glutamate pathway was significantly increased in MELAS cells with a direct correlation between glutamate concentration and the m.3243A > G heteroplasmy level. Transcriptomic analysis in mutant cells further revealed alterations in specific gene clusters, including those of the glutamate, gamma-aminobutyric acid pathways, and tricarboxylic acid (TCA) cycle. These results were supported by post-mortem brain tissue analysis from a MELAS patient, confirming the glutamate dysregulation. Exposure of MELAS cells to ketone bodies significantly reduced the glutamate level and improved mitochondrial functions, reducing the accumulation of several intermediate metabolites of the TCA cycle and alleviating the NADH-redox imbalance. (4) Conclusions: Thus, a multi-omic integrated approach to MELAS cells revealed glutamate as a promising disease biomarker, while also indicating that a ketogenic diet should be tested in MELAS patients.
Vertical Transmission, Risk Factors, and Antimicrobial Resistance Patterns of Group B Streptococcus among Mothers and Their Neonates in Southern Ethiopia

Background Group B Streptococcus (GBS) contributes to maternal and neonatal morbidity and mortality by increasing intrauterine infection or vertical transmission at the time of birth. Despite many efforts to reduce the potential risk of vertical transmission, GBS remains the main cause of serious disease (neonatal sepsis, meningitis, and/or pneumonia) in vulnerable newborns during the first week of life. This study aimed to assess vertical transmission, risk factors, and antimicrobial resistance patterns of GBS among pregnant women and their neonates. Methods A facility-based cross-sectional study was conducted among mothers and their neonates from February to May 2021. A total of 201 pregnant women with their neonates participated in this study. A well-designed questionnaire was used to collect sociodemographic and clinical data. A vaginal swab from mother before delivery and neonatal nasal and ear canal swab samples were taken as soon as after delivery within 30 minutes. Vaginal swabs, neonatal ear canal, and nasal swabs were placed into Todd–Hewitt broth and incubated at 37°C for 18–24 hours at 35–37°C in 5% CO2 conditions and then subcultured on 5% sheep blood agar for 18–48 hours. Presumptive identification of GBS was made by morphology, Gram stain, catalase, and hemolytic activity on sheep blood agar plates. CAMP and bacitracin susceptibility tests were used as confirmatory tests for GBS. Data were analyzed using SPSS version 21. P value ≤0.05 was considered statistically significant. Results Vertical transmission rates of GBS (mother to neonates) were 11.9%. The prevalence of GBS among pregnant women and newborns was 24/201 (11.9%) (95% CI = 7.5–16.9) and 11/201 (5.5%) (95% CI = 2.5–9.0), respectively. The history of prolonged rupture of membranes (AOR = 3.5, CI = 2.2–18.8) and urinary tract infection (AOR = 2.9, CI = 1.7–16.3) were associated factors for maternal GBS colonization. Gestational age of <37 weeks (p=0.008), low birth weight of <2.5 kg (p=0.001), and maternal history of vaginal discharge (p=0.048) were associated factors for neonatal GBS colonization. Low antibiotic resistance was observed for erythromycin 8.6%, clindamycin 5.7%, and chloramphenicol 2.9%. Conclusion In this study, high vertical transmission (mother to neonates) rate was observed. The prevalence of vaginal GBS colonization of women at delivery was 11.9% and significantly associated with the history of prolonged rupture of membranes and urinary tract infections. Gestational age of <37 weeks, low birth weight of <2.5 kg, and maternal history of vaginal discharge were associated with neonatal GBS colonization. Hence, there is a need for antenatal culture-based GBS screening, risk factor-based interventions, and regular follow-up of drug resistance patterns for proper treatment and management of GBS.
Can financial capability improve entrepreneurial performance? Evidence from rural China

The capability of individuals to manage their finances is essential to the outcomes of their entrepreneurial activities. Using panel data from the China Household Finance Survey (C.H.F.S.) in 2013, 2015 and 2017, this article examines how financial capability affects entrepreneurial performance in rural China. The results demonstrate that financial capability is positively correlated with the scale, profitability and sustainability of entrepreneurship, which is robust in consideration of endogeneity. The effects of financial capability are heterogeneous for different entrepreneurs. Furthermore, technology, labour and land act as the mediating variables through which financial capability improves entrepreneurial performance. Therefore, to facilitate entrepreneurial success, it is important to provide entrepreneurs with financial education. Meanwhile, improvements to the financial environment should also be considered. Additionally, financial institutions should combine financial services with factors, such as technology, land and labour, to improve entrepreneurial performance.
MiTF/TFE Translocation Renal Cell Carcinomas: From Clinical Entities to Molecular Insights

MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC representing the most prevalent RCC in the pediatric population (up to 40%) and making up 4% of all RCCs in adults. It is characterized by translocations involving either TFE3 (TFE3-tRCC), TFEB (TFEB-tRCC) or MITF, all members of the MIT family (microphthalmia-associated transcriptional factor). TFE3-tRCC was first recognized in the World Health Organization (WHO) classification of kidney cancers in 2004. In contrast to TFEB-tRCC, TFE3-tRCC is associated with many partners that can be detected by RNA or exome sequencing. Both diagnoses of TFE3 and TFEB-tRCC are performed on morphological and immunohistochemical features, but, to date, TFE break-apart fluorescent in situ hybridization (FISH) remains the gold standard for diagnosis. The clinical behavior of tRCC is heterogeneous and more aggressive in adults. Management of metastatic tRCC is challenging, especially in the younger population, and data are scarce. Efficacy of the standard of care-targeted therapies and immune checkpoint inhibitors remains low. Recent integrative exome and RNA sequencing analyses have provided a better understanding of the biological heterogeneity, which can contribute to a better therapeutic approach. We describe the clinico-pathological entities, the response to systemic therapy and the molecular features and techniques used to diagnose tRCC.
Quantitative Profiling of Bile Acids in Feces of Humans and Rodents by Ultra-High-Performance Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry

A simple, sensitive, and reliable quantification and identification method was developed and validated for simultaneous analysis of 58 bile acids (BAs) in human and rodent (mouse and rat) fecal samples. The method involves an extraction step with a 5% ammonium–ethanol aqueous solution; the BAs were quantified by high-resolution mass spectrometry (ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, UPLC–Q-TOF). The recoveries were 80.05–120.83%, with coefficient variations (CVs) of 0.01–9.82% for three biological species. The limits of detection (LODs) were in the range of 0.01–0.24 μg/kg, and the limits of quantification (LOQs) ranged from 0.03 to 0.81 μg/kg. In addition, the analytical method was used to identify and quantify BAs in end-stage renal disease (ESRD) patients, C57BL/6 mice, and Sprague-Dawley (SD) rats. The fecal BA profile and analysis of BA indices in these samples provide valuable information for further BA metabolic disorder research.
Impact of KRAS Mutation Subtypes and Co-Occurring Mutations on Response and Outcome in Advanced NSCLC Patients following First-Line Treatment

(1) Background: The purpose was to systematically assess the impact of KRAS subtypes and co-mutations on responses of first-line treatment and outcomes by genetic classification in advanced KRAS mutant NSCLC. (2) Methods: Molecular pathology was confirmed with NGS; Kaplan–Meier analysis and Cox multivariate model were used to analyze the efficacy of first-line treatment and prognosis in KRAS subgroups. (3) Results: Advanced KRAS mutant NSCLC was confirmed among 183 patients, who received first-line therapy. The most common KRAS subtype and co-mutation were G12C (29.5%) and TP53 (59.6%). ICIs/CHE group prolonged PFS to 16.9 m, vs. (CHE)4.6 m vs. (CHE/BEV)7.0 m (p < 0.0001); mOS (ICIs/CHE)37.1 m vs. (CHE)19.8 m vs. [CHE/BEV] 20.7 m (p = 0.024). PFS benefited to different degrees after first-line ICI-based treatment in each genetic classification. KRAS G12D even benefited from OS (p = 0.045). CHE/BEV prolonged mPFS of KRAS/STK11 co-mutation (p = 0.043), but decreased mPFS in G12A subtype (p = 0.026). Multivariate analysis indicated that heavy smoking history (≥20 pack-years) (HR = 0.45, p = 0.039) predicts optimistic prognosis; PS score 1 (HR = 3.604, p = 0.002) and KRAS/SMAD4 co-mutation (HR = 4.293, p = 0.027) remained as independent predictors of shorter OS. (4) Conclusions: First-line treatment with ICI benefited KRAS-mutant-NSCLC patients and resulted in non-negative predictive value for any genetic classification. Bevacizumab should be cautiously chosen for patients with KRAS G12A subtype but is recommended for KRAS/STK11 patients. KRAS/SMAD4 is a new co-mutation genotype that displayed independent risk prognostic factors in patients with advanced KRAS-mutant NSCLC.
The Analysis of the Human Megakaryocyte and Platelet Coding Transcriptome in Healthy and Diseased Subjects

Platelets are generated and released into the bloodstream from their precursor cells, megakaryocytes that reside in the bone marrow. Though platelets have no nucleus or DNA, they contain a full transcriptome that, during platelet formation, is transported from the megakaryocyte to the platelet. It has been described that transcripts in platelets can be translated into proteins that influence platelet response. The platelet transcriptome is highly dynamic and has been extensively studied using microarrays and, more recently, RNA sequencing (RNA-seq) in relation to diverse conditions (inflammation, obesity, cancer, pathogens and others). In this review, we focus on bulk and single-cell RNA-seq studies that have aimed to characterize the coding transcriptome of healthy megakaryocytes and platelets in humans. It has been noted that bulk RNA-seq has limitations when studying in vitro-generated megakaryocyte cultures that are highly heterogeneous, while single-cell RNA-seq has not yet been applied to platelets due to their very limited RNA content. Next, we illustrate how these methods can be applied in the field of inherited platelet disorders for gene discovery and for unraveling novel disease mechanisms using RNA from platelets and megakaryocytes and rare disease bioinformatics. Next, future perspectives are discussed on how this field of coding transcriptomics can be integrated with other next-generation technologies to decipher unexplained inherited platelet disorders in a multiomics approach.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide–specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs. Description Blocking a range of coronaviruses Seven coronaviruses cause human disease, and three have caused serious outbreaks in the past 20 years. The potential for future coronavirus outbreaks in humans and the ongoing resistance of severe acute syndrome coronavirus 2 (SARS-CoV-2) variants to existing antibodies make it important to identify cross-reactive antibodies that can be the basis of therapeutics and can guide vaccine design. Low et al. and Dacon et al. isolated antibodies from convalescent individuals that show broad neutralizing activity against a range of coronaviruses, including Omicron variants of SARS-CoV-2. The antibodies target a conserved region of the viral spike protein known as the fusion peptide and may act by preventing the cell fusion that is required for infection of new host cells. —VV A class of broadly reactive antibodies target a cryptic fusion peptide epitope exposed upon coronavirus spike protein binding to ACE2.
Weakly Supervised Object Detection With Class Prototypical Network

In this paper, we aim to devise a new framework to compel the network to be equipped with the capability of detecting objects using image-level class labels as supervision. The challenge of such a weakly supervised setting mainly lies in how to make the network accurately understand both semantics and objectness of a given proposal without bounding box annotations. To this end, we contribute a concise framework, named Class Prototypical Network (CPNet). Concretely, our CPNet defines a set of learnable class prototypes to help classify object proposals. To endow the prototypes be not only discriminative for classes but also sensitive for proposals' objectness, we conduct both class-aware cross-attention and location-aware cross-attention between the feature embeddings of the learnable prototypes and the proposals. The learned attention scores are then used to form the proposal-level category information into the image-level one, making the entire framework be trained without any bounding box annotations. Besides, by applying these two kinds of attention mechanisms, the knowledge from both proposals' location and its class information can be successfully transferred into the corresponding prototypes. With the help of prototypes, our CPNet detects true positive object proposals. In addition, the CPNet further introduces a multi-head detection head to perform complementary training, preventing the model from falling into local discriminative parts and improving the model's performance on challenging non-rigid categories. We examine our CPNet on popular benchmarks, i.e., PASCAL VOC 2007, 2012 and MS COCO 2014. Extensive experiments show our CPNet is a simple and effective framework.