Miracle-dz/UniFAR-FTUs huggingface dataset:
The rescue intervention strategy for asthma patients under severe air pollution: a single-center prospective randomized controlled trial

Abstract Objective The aim of our study is to provide a novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms for preventing airway damage. Methods This single-center, prospective, randomized and standard treatment parallel control clinical trial recruited adult asthma patients. The patients were randomized into either the rescue intervention strategy (RIS) group or control group. The rescue intervention strategy for the RIS group included budesonide/formoterol plus the original treatment until the severe pollution ended. The control group was maintained on the original treatment. The follow-up observation period was 1 year. Results Overall, 22 participants were enrolled and 20 completed the follow-up (11 in the RIS group and 9 in the control group). Two participants dropped out of the trial for personal reasons before the first follow-up. In the intention-to-treat analysis, the frequency of asthma exacerbations per year was significantly lower in the RIS group than in the control group (RIS vs. control, 0.55 vs. 2.67; risk rate [RR] [95% confidence interval {CI}], 0.21 [0.08-0.50]; p = 0.001). The mean number of unplanned outpatient visits per person per year was also lower in the RIS group than in the control group (RIS vs. control, 0.18 vs. 1.11; RR [95% CI], 0.16 [0.04-0.75]; p = 0.019). Conclusion A novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms may decrease the risk of asthma exacerbations and negative outcomes under severe air pollution conditions. Trial registration ChiCTR, ChiCTR1900026757. http://www.chictr. org.cn.
The effect of carpal tunnel release on health-related quality of life of 2346 patients over a 5-year period

In this prospective cohort study, the health-related quality of life (HRQoL) from a societal perspective of carpal tunnel syndrome (CTS) patients was determined and compared with other diseases. In addition, the effect of carpal tunnel release (CTR) was analysed 6 weeks postoperatively with regard to mean EQ-5D index value improvement, side-effects of surgery and cost per quality adjusted life year (QALY) gained. We found a baseline mean EQ-5D index value of 0.75 (SD: 0.23), comparable with values seen in other disease like breast cancer, diabetes and asthma. Furthermore, we found that CTR improved HRQoL substantially 6 weeks postoperatively (mean + 0.12, SD: 0.22) and significantly reduced symptom reporting (mean −52%, SD: 53) with a cost per QALY gained of €396.05. In conclusion, CTS has a comparable impact on quality of life as compared with other diseases, and CTR has the potential to substantially improve patient’s HRQoL at a fairly modest cost. Level of evidence: III
CLCd and CLCf act redundantly at the TGN/EE and prevent acidification of the Golgi stack

The trans-Golgi network/early endosome (TGN/EE) serves as the central hub in which exo- and endocytic trafficking pathways converge and specificity of cargo routing needs to be achieved. Acidification is a hallmark of the TGN/EE and is maintained by the vacuolar H+-ATPase (V-ATPase) with support of proton-coupled antiporters. We show here that CLCd and CLCf, two distantly related members of the Arabidopsis chloride channel (CLC)-family that colocalize in the TGN/EE act redundantly and are essential for male gametophyte development. Combining an inducible knock-down approach and in vivo pH-measurements, we show here that reduced CLC-activity does not affect pH in the TGN/EE but causes accumulation of the V-ATPase in trans-Golgi cisternae leading to their hyper-acidification. Taken together, our results show that CLC-mediated anion transport into the TGN/EE is essential and affects spatio-temporal aspects of TGN/EE-maturation as well as its functional separation from the Golgi stack.
Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study

Abstract BACKGROUND Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients. RESULTS Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection. Graphical Abstract Graphical Abstract
The OxrA Protein of Aspergillus fumigatus Is Required for the Oxidative Stress Response and Fungal Pathogenesis

Knowledge of ROS detoxification in fungal pathogens is useful in the design of new antifungal drugs and could aid in the study of oxidative stress resistance mechanisms. In this study, we demonstrate that OxrA protein localizes to the mitochondria and functions to protect against oxidative damage. ABSTRACT An efficient reactive oxygen species (ROS) detoxification system is vital for the survival of the pathogenic fungus Aspergillus fumigatus within the host high-ROS environment of the host. Therefore, identifying and targeting factors essential for oxidative stress response is one approach to developing novel treatments for fungal infections. The oxidation resistance 1 (Oxr1) protein is essential for protection against oxidative stress in mammals, but its functions in pathogenic fungi remain unknown. The present study aimed to characterize the role of an Oxr1 homolog in A. fumigatus. The results indicated that the OxrA protein plays an important role in oxidative stress resistance by regulating the catalase function in A. fumigatus, and overexpression of catalase can rescue the phenotype associated with OxrA deficiency. Importantly, the deficiency of oxrA decreased the virulence of A. fumigatus and altered the host immune response. Using the Aspergillus-induced lung infection model, we demonstrated that the ΔoxrA mutant strain induced less tissue damage along with decreased levels of lactate dehydrogenase (LDH) and albumin release. Additionally, the ΔoxrA mutant caused inflammation at a lower degree, along with a markedly reduced influx of neutrophils to the lungs and a decreased secretion of cytokine usually associated with recruitment of neutrophils in mice. These results characterize the role of OxrA in A. fumigatus as a core regulator of oxidative stress resistance and fungal pathogenesis. IMPORTANCE Knowledge of ROS detoxification in fungal pathogens is useful in the design of new antifungal drugs and could aid in the study of oxidative stress resistance mechanisms. In this study, we demonstrate that OxrA protein localizes to the mitochondria and functions to protect against oxidative damage. We demonstrate that OxrA contributes to oxidative stress resistance by regulating catalase function, and overexpression of catalase (CatA or CatB) can rescue the phenotype that is associated with OxrA deficiency. Remarkably, a loss of OxrA attenuated the fungal virulence in a mouse model of invasive pulmonary aspergillosis and altered the host immune response. Therefore, our finding indicates that inhibition of OxrA might be an effective approach for alleviating A. fumigatus infection. The present study is, to the best of our knowledge, a pioneer in reporting the vital role of Oxr1 protein in pathogenic fungi.
Comparison between Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: case reports and literature review

Kimura’s disease (KD) is a rare chronic inflammatory or allergic disease. Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm. Their relationship has always been debated. This article reports two rare cases, one of each disease. One patient was a 48-year-old female that presented with a mass on her right mandible. She also had oedema erythema and wheals on her lower limbs. She was diagnosed with Kimura’s disease complicated with chronic urticaria. The second patient was a 23-year-old female that presented with multiple nodules of unequal size on the scalp. She was diagnosed with angiolymphoid hyperplasia with eosinophilia. The first patient recovered after being treated with surgical resection, glucocorticosteroids, cyclophosphamide and radiotherapy. The second patient underwent the first stage of surgical excision and is currently being followed-up. Comparison of the clinical and histopathological features of these two cases supports the theory that KD and ALHE are two separate disease entities.
Total Chromium Captured by Maize (Zea Mays) Plants is Increased by Phosphate and Iron Supplementation in the Soil

ABSTRACT In this work, a commercial hybrid maize was used, and the effect of selected mineral nutrients [sulfur (S), phosphorus (P), iron (Fe), and nitrogen (N)] on the chromium (Cr) captured by plants was analysed. Seeds were germinated in vitro, and plants were transferred to pots with soil supplemented with a growth inhibitory Cr concentration and different mineral nutrient combinations. Plants were grown for 13 weeks and irrigated with water. In the harvested plants, total Cr was determined considering the Cr concentration in tissues and the biomass as dry weight. The soil supplemented with phosphorus (P) or Fe improved the total Cr captured by plants by a quarter. Bioconcentration values in plant tissues were similar to those of other plants grown in soil with Cr. This information will be useful either for Cr phytoremediation or to protect commercial maize crops cultivated in Cr contaminated soils.
A Synergistic Consortium Involved in rac-Dichlorprop Degradation as Revealed by DNA Stable Isotope Probing and Metagenomic Analysis

Understanding of the key microbial consortium involved in the degradation of the phenoxyalkanoic acid herbicide rac-dichlorprop is pivotal for design of synergistic consortia used for enhanced bioremediation of herbicide-contaminated sites. However, the composition of the microbial consortium and the interactions between community members during the biodegradation of rac-dichlorprop are unclear. ABSTRACT rac-Dichlorprop, a commonly used phenoxyalkanoic acid herbicide, is frequently detected in environments and poses threats to environmental safety and human health. Microbial consortia are thought to play key roles in rac-dichlorprop degradation. However, the compositions of the microbial consortia involved in rac-dichlorprop degradation remain largely unknown. In this study, DNA stable isotope probing (SIP) and metagenomic analysis were integrated to reveal the key microbial consortium responsible for rac-dichlorprop degradation in a rac-dichlorprop-degrading enrichment. OTU340 (Sphingobium sp.) and OTU348 (Sphingopyxis sp.) were significantly enriched in the rac-[13C]dichlorprop-labeled heavy DNA fractions. A rac-dichlorprop degrader, Sphingobium sp. strain L3, was isolated from the enrichment by a traditional enrichment method but with additional supplementation of the antibiotic ciprofloxacin, which was instructed by metagenomic analysis of the associations between rac-dichlorprop degraders and antibiotic resistance genes. As revealed by functional profiling of the metagenomes of the heavy DNA, the genes rdpA and sdpA, involved in the initial degradation of the (R)- and (S)-enantiomers of dichlorprop, respectively, were mostly taxonomically assigned to Sphingobium species, indicating that Sphingopyxis species might harbor novel dichlorprop-degrading genes. In addition, taxonomically diverse bacterial genera such as Dyella, Sphingomonas, Pseudomonas, and Achromobacter were presumed to synergistically cooperate with the key degraders Sphingobium/Sphingopyxis for enhanced degradation of rac-dichlorprop. IMPORTANCE Understanding of the key microbial consortium involved in the degradation of the phenoxyalkanoic acid herbicide rac-dichlorprop is pivotal for design of synergistic consortia used for enhanced bioremediation of herbicide-contaminated sites. However, the composition of the microbial consortium and the interactions between community members during the biodegradation of rac-dichlorprop are unclear. In this study, DNA-SIP and metagenomic analysis were integrated to reveal that the metabolite 2,4-dichlorophenol degraders Dyella, Sphingomonas, Pseudomonas, and Achromobacter synergistically cooperated with the key degraders Sphingobium/Sphingopyxis for enhanced degradation of rac-dichlorprop. Our study provides new insights into the synergistic degradation of rac-dichlorprop at the community level and implies the existence of novel degrading genes for rac-dichlorprop in nature.
A single dose of the Biontech/Pfizer BNT162b2 vaccine protected elderly residents from severe COVID‐19 during a SARS‐coronavirus‐2 outbreak in a senior citizen home in Germany

Background: A total of 62/66 (93.9%) residents in a senior citizen home in Bremen, Germany, received the first dose of the Biontech/Pfizer vaccine BNT162b2 on December 27th 2020. After routine severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antigen tests showed positive results on January 5th, all residents and staff were tested by RT‐PCR.
Maternal B cell signaling orchestrates fetal development in mice.

B cell participation in early embryo/fetal development and the underlying molecular pathways have not been explored. To understand whether maternal B cell absence or impaired signaling interferes with placental and fetal growth, we paired CD19-deficient (CD19-/-) mice, females with B cell-specific MyD88 (BMyD88-/-) or IL-10 (BIL-10-/-) deficiency as well as WT and MyD88-/- controls on C57Bl/6 background with BALB/c males. Pregnancies were followed by ultrasound and Doppler measurements. Implantation number was reduced in BMyD88-/- and MyD88-/- mice. Loss of MyD88 or B cell-specific deletion of MyD88 or IL-10 resulted in decreased implantation areas at gestation days (gd)5, 8 and 10, accompanied by reduced placental thickness, diameter and areas at gd10. Uterine artery resistance was enhanced in BIL-10-/- dams at gd10. Challenge with 0.4mg LPS/kg BW at gd16 revealed that BMyD88-/-, BIL-10-/- and CD19-/- mothers delivered preterm while controls maintained their pregnancy. B cell specific MyD88 and IL-10 expression is essential for appropriate in utero development. IL-10+B cells are involved in uterine blood flow regulation during pregnancy. Finally, B cell-specific CD19, MyD88 and IL-10 expression influences susceptibility towards preterm birth.
Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition

Significance There is abundant evidence that environmental insults, such as exposure to anesthetics, at early-life stages impair brain functions in later life, but the underlying mechanisms are poorly understood. Neural stem cells (NSCs) express inhibitory neurotransmitter γ-aminobutyric acid type A receptors that are the main target of most anesthetics, including midazolam (MDZ). We found that early-life exposure to MDZ persistently alters chromatin accessibility and global transcription to reinforce long-lasting NSC dormancy in the mouse hippocampus until adulthood, resulting in reduced neurogenesis and cognitive decline. Furthermore, a simple physical activity, running, could overcome these adverse outcomes by normalizing MDZ-induced transcriptomic alterations. Our study provides insights for further understanding and developing therapeutic strategies for neurological disorders induced by early-life exposure to anesthetics. Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis, normalized the MDZ-perturbed transcriptome, and ameliorated cognitive ability in MDZ-exposed mice. Our findings thus explain how pediatric anesthesia provokes long-term adverse effects on brain function and provide a possible therapeutic strategy for countering them.
“It’s a Bit of a Double-Edged Sword”: Motivation and Personal Impact of Bereaved Mothers’ Advocacy for Drug Policy Reform

North America’s overdose crisis is an urgent public health issue that has resulted in thousands of deaths. As the crisis began to take hold across Canada in 2016, bereaved parents, mainly mothers, emerged as vocal advocates for drug policy reform and harm reduction, using their stories to challenge the stigma of drug-related death. In 2017, we launched a qualitative research partnership with leading family organizations in Canada, conducting interviews with 43 mothers whose children had died from substance use, to understand their experiences of drug policy advocacy. Our findings showed that participants’ motivations for engaging in advocacy were rooted in their experiences of grief, and that advocacy led to feelings of empowerment and connection to others. Our research suggests that advocacy can be cathartic and associated with healing from grief, but that “going public” in sharing a family story of substance use death can also have a considerable personal cost.
Genome‐wide association studies of survival in 1520 cancer patients treated with bevacizumab‐containing regimens

Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta‐analysis of genome‐wide association studies (GWAS) was conducted in 1,520 patients from Phase III trials (CALGB 80303, 40503, 80405 and ICON7), where bevacizumab was randomized to treatment without bevacizumab. We aimed to identify genes and single nucleotide polymorphisms (SNPs) associated with survival independently of bevacizumab treatment or through interaction with bevacizumab. A cause‐specific Cox model was used to test the SNP‐OS association in both arms combined (prognostic), and the effect of SNPs‐bevacizumab interaction on OS (predictive) in each study. The SNP effects across studies were combined using inverse variance. Findings were tested for replication in advanced colorectal and ovarian cancer patients from The Cancer Genome Atlas (TGCA). In the GWAS meta‐analysis, patients with rs680949 in PRUNE2 experienced shorter OS compared to patients without it (P = 1.02 × 10−7, hazard ratio [HR] = 1.57, 95% confidence interval [CI] 1.33‐1.86), as well as in TCGA (P = .0219, HR = 1.58, 95% CI 1.07‐2.35). In the GWAS meta‐analysis, patients with rs16852804 in BARD1 experienced shorter OS compared to patients without it (P = 1.40 × 10−5, HR = 1.51, 95% CI 1.25‐1.82) as well as in TCGA (P = 1.39 × 10−4, HR = 3.09, 95% CI 1.73‐5.51). Patients with rs3795897 in AGAP1 experienced shorter OS in the bevacizumab arm compared to the nonbevacizumab arm (P = 1.43 × 10−5). The largest GWAS meta‐analysis of bevacizumab treated patients identified PRUNE2 and BARD1 (tumor suppressor genes) as prognostic genes of colorectal and ovarian cancer, respectively, and AGAP1 as a potentially predictive gene that interacts with bevacizumab with respect to patient survival.
The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma

Purpose: Marginal zone lymphoma (MZL) is an uncommon non–Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL. Patients and Methods: Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111–214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. Results: Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. Conclusions: Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.