bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkylation Repair Homolog 5 Regulates N(6)-methyladenosine (m6A) Methylation of Mitsugumin 53 to Attenuate Myocardial Infarction by Inhibiting Apoptosis and Oxidative Stress
Authors: Li Dong , Li Lianggang , Dong Shiyong , Yu Yaqun , Zhang Lin , Jiang Shengli 
Published: November 2023

Abstract:
N(6)-methyladenosine (m6A) methylation modification is involved in the progression of myocardial infarction (MI). In this study, we investigated the effects of demethylase alkylation repair homolog 5 (ALKBH5) on cell apoptosis and oxidative stress in MI. The ischemia/reperfusion (I/R) injury mouse model and hypoxia/reoxygenation (H/R) cell model were established. The levels of ALKBH5 and mitsugumin 53 (MG53) were measured by quantitative real-time polymerase chain reaction, immunohistochemical, and immunofluorescence analysis. Apoptosis was evaluated by TUNEL assay, flow cytometry, and western blot. Oxidative stress was assessed by antioxidant index kits. Methylation was analyzed by RNA binding protein immunoprecipitation (RIP), MeRIP, and dual-luciferase reporter assay. We observed that ALKBH5 and MG53 were highly expressed in MI. Overexpression of ALKBH5 inhibited H/R-induced cardiomyocyte apoptosis and oxidative stress in vitro, and it inhibited I/R-induced collagen deposition, cardiac function, and apoptosis in vivo. ALKBH5 could bind to MG53, inhibit m6A methylation of MG53, and increase its mRNA stability. Silencing of MG53 counteracted the inhibition of apoptosis and oxidative stress induced by ALKBH5. In conclusion, ALKBH5 suppressed m6A methylation of MG53 and inhibited MG53 degradation to inhibit apoptosis and oxidative stress of cardiomyocytes, thereby attenuating MI. The results provided a theoretical basis that ALKBH5 is a potential target for MI treatment.
Eyes on the Lid: The Impact of Fibroblast Growth Factor Receptor Targeting Drug on Human Meibomian Gland
Authors: Chen Xiaomin , Liu Yang , Zheng Tian , Zhang Qiuyan , Ren Yaoyao , Shen Yanru , Ke Min 
Published: November 2023

Objective:
To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland.

Methods:
We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries.

Results:
All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors.

Conclusions:
These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.
Organizational Learning in the Morbidity and Mortality Conference
Authors: Batthish Michelle , Kuper Ayelet , Fine Claire , Laxer Ronald M. , Baker G. Ross 
Published: November 2023

ABSTRACT

Introduction:
The focus of morbidity and mortality conferences (M&MCs) has shifted to emphasize quality improvement and systems-level care. However, quality improvement initiatives targeting systems-level errors are challenged by learning in M&MCs, which occurs at the individual attendee level and not at the organizational level. Here, we aimed to describe how organizational learning in M&MCs is optimized by particular organizational and team cultures.

Methods:
A prospective, multiple-case study design was used. Using purposive sampling, three cases covering different medical/surgical specialties in North America were chosen. Data collection included direct observations of the M&MC, semistructured interviews with key M&MC members, and documentary information.

Results:
The role of the M&MC in all cases integrated two key concepts: recognition of system-wide trends and learning from error, at an organizational and team level. All cases provided evidence of double-loop learning and used organizational memory strategies to ensure knowledge was retained within the organization. A patient safety culture was linked to the promotion of open communication, fostering learning from adverse events.

Conclusion:
This study describes three cases of systems-oriented M&MCs that reflected elements of organizational learning theory. The M&MC can therefore provide a context for organizational learning, allowing optimal learning from adverse events.
Prehospital lactate-glucose interaction in acute life-threatening illnesses: metabolic response and short-term mortality
Authors: Usategui-Martín Ricardo , Zalama-Sánchez Daniel , López-Izquierdo Raúl , Delgado Benito Juan F. , del Pozo Vegas Carlos , Sánchez Soberón Irene , Martín-Conty José L. , Sanz-García Ancor , Martín-Rodríguez Francisco 
Published: November 2023

Background and importance
Lactate is an already recognized biomarker for short-term mortality. However, how glycemia and diabetes affect the predictive ability of lactate needs to be revealed.

Objective
To determine how hypoglycemia, normoglycemia, and hyperglycemia modify the predictive ability of lactate for short-term mortality (3 days). The secondary objective was to evaluate the predictive ability of lactate in diabetic patients.

Design, settings and participants
Prospective, observational study performed between 26 October 2018 and 31 December 2022. Multicenter, EMS-delivery, ambulance-based study, considering 38 basic life support units and 5 advanced life support units referring to four tertiary care hospitals (Spain). Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments.

Outcomes measure and analysis
The primary outcome was in-hospital mortality from any cause within the third day following EMS attendance. The main predictors considered were lactate, blood glucose levels and previous diabetes.

Main results
A total of 6341 participants fulfilled the inclusion criteria. 68 years (IQR: 51–80); 41.4% were female. The 3-day in-hospital mortality rate was 3.5%. The predictive capacity of lactate for 3-day mortality was only significantly different between normo-glycemia and hyperglycemia. The best predictive result was for normo-glycemia – AUC = 0.897 (95% CI: 0.881–0.913) – then hyperglycemia – AUC = 0.819 (95% CI: 0.770–0.868) and finally, hypoglycemia – AUC = 0.703 (95% CI: 0.422–0.983). The stratification according to diabetes presented no statistically significant difference, and the predictive results were AUC = 0.924 (95% CI: 0.892–0.956), AUC = 0.906 (95% CI: 0.884–0.928), and AUC = 0.872 (95% CI: 0.817–0.927) for nondiabetes, uncomplicated cases, and end-organ damage diabetes, respectively.

Conclusion
Our results demonstrated that glycemia, but not diabetes, alters the predictive ability of lactate. Therefore, hyperglycemia should be considered when interpreting lactate, since this could improve screening to detect cryptic shock conditions.
Brief Report: HIV Pre-Exposure Prophylaxis Awareness and Use Among Adolescents in Kenya
Authors: Truong Hong-Ha M. , Heylen Elsa , Kadede Kevin , Amboka Sayo , Otieno Beatrice , Odhiambo Hanningtone , Odeny Damaris , Hewa Marion , Opiyo Maurice , Opondo Fidel , Ogolla David , Guzé Mary A. , Miller Lara E. , Bukusi Elizabeth A. , Cohen Craig R. ,   the Maneno Yetu Study Team
Published: November 2023

Background:
HIV pre-exposure prophylaxis (PrEP) is an effective prevention tool; however, use among adolescents is thought to be low. To determine the unmet need and opportunity to expand use, we assessed awareness, prior use, and willingness to take PrEP among Kenyan adolescents.

Methods:
The Maneno Yetu study recruited a community-based sample of adolescents aged 15–19 years (N = 3061) in Kisumu for a survey using respondent-driven sampling.

Results:
Overall, 50% of adolescents had heard of PrEP and 2% had used PrEP. Girls were more likely than boys to have heard of PrEP (53.4% vs. 45.1%; P < 0.001) and used PrEP (3.6% vs. 0.3%; P < 0.001). Among participants, 14% engaged in transactional sex and 21% experienced forced sexual contact. PrEP use was higher among adolescents who engaged in transactional sex (4.8% vs. 0.6%; P < 0.001) and experienced forced sexual contact (2.7% vs. 0.7%; P < 0.001) compared with those who did not. Among adolescents with no prior use, 53% were willing to consider using PrEP, although girls were less willing than boys (49.7% vs. 55.9%; P = 0.001).

Conclusions:
PrEP is an important prevention tool, especially for adolescents whose circumstances potentially expose them to HIV-positive or unknown status sexual partners, yet remains underused, particularly in resource-limited settings. Although many expressed willingness to use PrEP, low awareness and use highlight the need to expand HIV prevention education and services tailored for adolescents. Our finding that boys were more willing to use PrEP suggests campaigns should also be designed to reach male youth to narrow the gender gap and expand uptake in the adolescent population.
Duphaston as a suitable medication for women taking intracytoplasmic sperm injection to treat infertility
Authors: Naserpour Leila , Berjis Katayon , Soleymani Moud Sanaz , Jannatifar Rahil 
Published: November 2023

Objective:
Duphaston is used as an alternative to gonadotropin-releasing hormone (GnRH) antagonists for suppressing premature luteinizing hormone (LH) surges. This study aimed to compare the efficacy of Duphaston protocols with that of Cetrotide in suppressing the LH surge.

Methods:
In this retrospective cross-sectional study, 669 infertile women (aged 25–40 years) were administered recombinant follicle-stimulating hormone (rFSH) from the third day of their menstrual cycle. After the follicular diameter reached 13 to 14 mm, Cetrotide was prescribed orally to the control subjects, also case subjects took Duphaston orally. The retrieved oocytes were fertilized by an intracytoplasmic sperm injection (ICSI).

Results:
The levels of FSH, LH, and estradiol did not differ significantly between the groups (P >0.05). However, the findings indicated that Duphaston led to greater oocyte retrieval than Cetrotide (P = 0.006). However, the number of mature oocytes and viable embryos in the case subjects did not reach a significant difference compared to that in the control subjects (P >0.05). The number of good-quality embryos (stage 1) was significantly higher in the case subjects (P = 0.04). In addition, there is no significant difference in the chemical, clinical pregnancy, implantation rate, and miscarriage rate between both groups (P >0.05).

Conclusion:
Duphaston could be utilized as a suitable medication rather than a GnRH antagonist in women subjected to controlled ovarian hyperstimulation.
Clinical application of the endometrial microbiota test combined with personalized treatment in patients with repeated implantation failure
Authors: Chen Rou-Zhu , Wang Yan-Fang , Chen Pei-Gen , Fang Cong , Li Ting-Ting 
Published: November 2023

Aims:
To investigate the clinical value of the endometrial microbiota test (EMT) combined with personalized treatment in patients with repeated implantation failure (RIF).

Methods:
From March 2019 to August 2022, the clinical data of patients with RIF at the Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 356 patients underwent the EMT using 16S rRNA sequencing and were included in the EMT group. The SPSS statistical software propensity score was set at 1:1 to match the age, anti-Müllerian hormone (AMH), antral follicle count (AFC), years of infertility, and body mass index (BMI) of the women who had not undergone the EMT; subsequently, 354 patients were classified in the non-EMT group. We compared the clinical characteristics of the two groups and analyzed the clinical pregnancy outcomes after personalized treatment.

Results:
The clinical pregnancy rate (CPR) of the EMT group was significantly higher than that of the non-EMT group (47.81% vs. 13.38%, P<0.05). Among 356 patients who underwent the EMT, 55 patients (15.45%) in Group A with normal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis, 34 patients (9.55%) in Group B with abnormal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis, 35 patients (9.83%) in Group C with normal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis, and 232 patients (65.17%) in Group D with abnormal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis. After administration of probiotics or antibiotic plus probiotics treatment, the pregnancy rates of groups C and D were higher than those of group A (44.00% vs. 20.00% and 55.03% vs. 20.00%, respectively; both P<0.05).

Conclusion:
The EMT combined with personalized treatment in patients with RIF has solid clinical value as a new treatment strategy.
Tropism of AAV.CPP.16 in the respiratory tract and its application for a CRISPR-based gene therapy against SARS-CoV-2
Authors: Yang Zhi , Yao Yizheng , Chen Xi , Madigan Victoria , Fan Xianqun , Pu Jun , Bei Fengfeng 
Published: November 2023

AbstractEfficient gene delivery vectors are essential for developing gene therapies for respiratory diseases. Here, we report that AAV.CPP.16, a novel AAV9-derived adeno-associated virus vector, can efficiently transduce airway epithelium systems and lung parenchyma cells in both mice and non-human primates after intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism to respiratory tract tissues, and can target major cell types in the respiratory tract and the lung. We also report an “all-in-one”, CRISPR-Cas13d-based AAV gene therapy vector that targets the highly conserved RNA-dependent RNA polymerase (Rdrp) gene in SARS-CoV-2, and show the potential of such gene therapy against a broad range of circulating and emergent SARS-CoV-2 variants. Thus, AAV.CPP.16 could be a useful gene delivery vector for treating genetic respiratory diseases and airborne infections including for developing a potential prophilaxis to SARS-CoV-2.
Negative predictive value Of Point-of-care ultrasound normal exam to exclude PneumoniA (NO-PNA)
Authors: Istrail Larry , Chakravorty Shourjo , Stepanova Maria 
Published: November 2023

AbstractPneumonia is one of the most common causes of hospital admission in the United States. Worldwide, the majority of antibiotics are prescribed for upper respiratory infections, much of which could be avoided with highly accurate methods of diagnosing or excluding pneumonia at the bedside. Despite the high prevalence of infectious pneumonia and decades of medical progress, accurately diagnosing or ruling out pneumonia without the use of computed tomography (CT) scanners and distinguishing between viral or bacterial etiologies remains challenging. We enrolled 61 patients in a prospective, blinded study to determine the sensitivity of lung ultrasound (LUS) using a handheld ultrasound probe in patients who had a computed tomography (CT) scan of their chest for any reason. The sensitivity of lung ultrasound to detect patients with evidence of pneumonia as compared to a CT scan was 94.4% (72.7 - 99.9) with a negative predictive value of 96.2% (80.4 - 99.9) when the scan was normal. Due to our broad inclusion criteria and the high prevalence of of non-infectious lung disease at the site of this study, the specificity was 61% (44.5 - 75.8) and positive predictive value was 51.5% (33.5 - 69.2). This simple lung ultrasound scan can be incorporated into the physical exam, has very high sensitivity to detect patients with pneumonia, and can be effectively used to rule out pneumonia if the lung exam is normal.
Whole genome association testing in 333,100 individuals across three biobanks identifies rare non-coding single variant and genomic aggregate associations with height
Authors: Hawkes Gareth , Beaumont Robin N , Li Zilin , Mandla Ravi , Li Xihao , Albert Christine M. , Arnett Donna K. , Ashley-Koch Allison E. , Ashrani Aneel A. , Barnes Kathleen C. , Boerwinkle Eric , Brody Jennifer A. , Carson April P. , Chami Nathalie , Chen Yii-Der Ida , Chung Mina K. , Curran Joanne E. , Darbar Dawood , Ellinor Patrick T. , Fornage Myrian , Gordeuk Victor R. , Guo Xiuqing , He Jiang , Hwu Chii-Min , Kalyani Rita R. , Kaplan Robert , Kardia Sharon L.R. , Kooperberg Charles , Loos Ruth J.F. , Lubitz Steven A. , Minster Ryan L. , Mitchell Braxton D. , Murabito Joanne M. , Palmer Nicholette D. , Psaty Bruce M. , Redline Susan , Benjamin Shoemaker M. , Silverman Edwin K. , Telen Marilyn J. , Weiss Scott T. , Yanek Lisa R. , Zhou Hufeng ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Liu Ching-Ti , North Kari E. , Justice Anne E. , Locke Jon , Owens Nick , Murray Anna , Patel Kashyap , Frayling Timothy M. , Wright Caroline F. , Wood Andrew R. , Lin Xihong , Manning Alisa , Weedon Michael N. 
Published: November 2023

AbstractThe role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N=200,003), TOPMed (N=87,652) and All of Us (N=45,445). We performed rare (<0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal, intergenic and deep-intronic annotation. We observed 29 independent variants associated with height atP< 6 × 10−10after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7cm. We also identified and replicated non-coding aggregate-based associations proximal toHMGA1containing variants associated with a 5cm taller height and of highly-conserved variants inMIR497HGon chromosome 17. We have developed a novel approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.
Glucose-fed microbiota alters intestinal epithelium and increases susceptibility to bacterial pathogens
Authors: Kingsley Samuel F. , Seo Yonghak , Wood Alicia , Wani Khursheed A. , Gonzalez Xavier , Irazoqui Javier , Finkel Steven E. , Tissenbaum Heidi A. 
Published: November 2023

AbstractOverconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota strongly associated with our overall health has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspeciesC. elegans-E. colisystem, whereE. coliare subjected to high sugar, then consumed by the bacterivore hostC. elegansto become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan including locomotion, stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar such as a western diet has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.
Visual cortex anodal tDCS does not alter reading performance for Chinese presented character-by-character to normal peripheral vision
Authors: Lyu Anqi , Silva Andrew E , Thompson Benjamin , Abel Larry , Cheong Allen MY 
Published: November 2023

AbstractVisual cortex transcranial direct current stimulation (tDCS) reduces crowding in normal peripheral vision and may improve reading of English words in patients with macular degeneration. Given the different visual requirements of reading English words and Chinese characters, the effect of tDCS on peripheral reading performance in English might be different from Chinese. This study recruited seventeen participants (59 to 73 years of age) with normal vision and tested the hypothesis that anodal tDCS would improve reading of Chinese characters presented at 10° eccentricity compared with sham stimulation. Chinese sentences of different print sizes and exposure durations were presented one character at a time 10° below or to the left of fixation, and the individual critical print size (CPS) - the smallest print size eliciting the maximum reading speed (MRS) was determined. Reading accuracies for characters presented 0.2 logMAR smaller than the CPS were measured before, during, 5 mins, and 30 mins after receiving active or sham anodal visual cortex tDCS. Participants completed both the active and sham sessions in a random order following a double-blind, within-subject design. No effect of active anodal-tDCS on reading accuracy was observed, implying that a single session of tDCS did not improve Chinese character reading in normal peripheral vision. This may suggest that tDCS does not significantly reduce the crowding elicited within a single Chinese character. However, the effect of tDCS on between-character crowding is yet to be determined.
Seabird nutrient subsidies enrich mangrove ecosystems and are exported to nearby coastal habitats
Authors: Appoo Jennifer , Bunbury Nancy , Jaquemet Sébastien , Graham Nicholas A.J. 
Published: November 2023

SUMMARYEutrophication by human-derived nutrient enrichment is a major threat to mangroves, impacting productivity, ecological functions, resilience and ecosystem services. Natural mangrove nutrient enrichment processes, however, remain largely uninvestigated. Mobile consumers such as seabirds are important vectors of cross-ecosystem nutrient subsidies to islands but how they influence mangrove ecosystems is poorly known. We assessed the contribution, uptake, cycling and transfer of nutrients from seabird colonies in remote mangrove systems free of human stressors. We found that nutrients from seabird guano enrich mangrove plants, reduce nutrient limitations, enhance mangrove invertebrate food webs and are exported to nearby coastal habitats through tidal flow. We show that seabird nutrient subsidies in mangroves can be substantial, improving the nutrient status and health of mangroves and adjacent coastal habitats. Conserving mobile consumers, such as seabirds, is therefore vital to preserve and enhance their role in mangrove productivity, resilience and provision of diverse functions and services.