bluuebunny/crossref_metadata_2025 huggingface dataset:
Seven classes of rotational variables from a study of 50 000 spotted stars with ASAS-SN, Gaia, and APOGEE
Authors: Phillips Anya , Kochanek C S , Jayasinghe Tharindu , Cao Lyra , Christy Collin T , Rowan D M , Pinsonneault Marc
Published: November 2023

We examine the properties of ∼50 000 rotational variables from the ASAS-SN survey using distances, stellar properties, and probes of binarity from Gaia DR3 and the SDSS APOGEE survey. They have higher amplitudes and span a broader period range than previously studied Kepler rotators. We find they divide into three groups of main sequence stars (MS1, MS2s, MS2b) and four of giants (G1/3, G2, G4s, and G4b). MS1 stars are slowly rotating (10–30 d), likely single stars with a limited range of temperatures. MS2s stars are more rapidly rotating (days) single stars spanning the lower main sequence up to the Kraft break. There is a clear period gap (or minimum) between MS1 and MS2s, similar to that seen for lower temperatures in the Kepler samples. MS2b stars are tidally locked binaries with periods of days. G1/3 stars are heavily spotted, tidally locked RS CVn stars with periods of 10s of days. G2 stars are less luminous, heavily spotted, tidally locked sub-subgiants with periods of ∼10 d. G4s stars have intermediate luminosities to G1/3 and G2, slow rotation periods (approaching 100 d), and are almost certainly all merger remnants. G4b stars have similar rotation periods and luminosities to G4s, but consist of sub-synchronously rotating binaries. We see no difference in indicators for the presence of very wide binary companions between any of these groups and control samples of photometric twin stars built for each group.
Optical intraday variability of the blazar S5 0716+714
Authors: Tripathi Tushar , Gupta Alok C , Takey Ali , Bachev Rumen , Vince Oliver , Strigachev Anton , Kushwaha Pankaj , Elhosseiny E G , Wiita Paul J , Damljanovic G , Dhiman Vinit , Fouad A , Gaur Haritma , Gu Minfeng , Hamed G E , Kishore Shubham , Kurtenkov A , Rastogi Shantanu , Semkov E , Zead I , Zhang Zhongli
Published: November 2023

We present an extensive recent multiband optical photometric observations of the blazar S5 0716+714 carried out over 53 nights with two telescopes in India, two in Bulgaria, one in Serbia, and one in Egypt during 2019 November – 2022 December. We collected 1401, 689, 14726, and 165 photometric image frames in B, V, R, and I bands, respectively. We monitored the blazar quasi-simultaneously during three nights in B, V, R, and I bands; four nights in B, V, and R; two nights in V, R, and I; five nights in B and R; and two nights in V and R bands. We also took 37 nights of data only in R band. Single band data are used to study intraday flux variability and two or more bands quasi-simultaneous observations allow us to search for colour variation in the source. We employ the power-enhanced F-test and the nested ANOVA test to search for genuine flux and colour variations in the light curves of the blazar on intraday time-scales. Out of 12, 11, 53, and 5 nights observations, intraday variations with amplitudes between ∼3 and ∼20 per cent are detected in 9, 8, 31 and 3 nights in B, V, R, and I bands, respectively, corresponding to duty cycles of 75, 73, 58, and 60 per cent. These duty cycles are lower than those typically measured at earlier times. On these time-scales colour variations with both bluer-when-brighter and redder-when-brighter are seen, though nights with no measurable colour variation are also present. We briefly discuss possible explanations for this observed intraday variability.
Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation
Authors: Jensen Axel , Swift Frances , de Vries Dorien , Beck Robin M D , Kuderna Lukas F K , Knauf Sascha , Chuma Idrissa S , Keyyu Julius D , Kitchener Andrew C , Farh Kyle , Rogers Jeffrey , Marques-Bonet Tomas , Detwiler Kate M , Roos Christian , Guschanski Katerina
Published: November 2023

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.
LncSEA 2.0: an updated platform for long non-coding RNA related sets and enrichment analysis
Authors: Zhang Guorui , Song Chao , Fan Shifan , Yin Mingxue , Wang Xinyue , Zhang Yuexin , Huang Xuemei , Li Ye , Shang Desi , Li Chunquan , Wang Qiuyu
Published: November 2023

Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs.
Plant Reactome Knowledgebase: empowering plant pathway exploration and OMICS data analysis
Authors: Gupta Parul , Elser Justin , Hooks Elizabeth , D’Eustachio Peter , Jaiswal Pankaj , Naithani Sushma
Published: November 2023

Plant Reactome (https://plantreactome.gramene.org) is a freely accessible, comprehensive plant pathway knowledgebase. It provides curated reference pathways from rice (Oryza sativa) and gene-orthology-based pathway projections to 129 additional species, spanning single-cell photoautotrophs, non-vascular plants, and higher plants, thus encompassing a wide-ranging taxonomic diversity. Currently, Plant Reactome houses a collection of 339 reference pathways, covering metabolic and transport pathways, hormone signaling, genetic regulations of developmental processes, and intricate transcriptional networks that orchestrate a plant's response to abiotic and biotic stimuli. Beyond being a mere repository, Plant Reactome serves as a dynamic data discovery platform. Users can analyze and visualize omics data, such as gene expression, gene-gene interaction, proteome, and metabolome data, all within the rich context of plant pathways. Plant Reactome is dedicated to fostering data interoperability, upholding global data standards, and embracing the tenets of the Findable, Accessible, Interoperable and Re-usable (FAIR) data policy.
Ling-Ling Chen: RNA has its own features; don’t study it as a protein
Authors: Zhao Weijie
Published: November 2023

Non-coding RNA (ncRNA) has been a very active research area over the past 30 years. From small ncRNA – the discovery of RNA interference won the lead researchers the Nobel Prize, to long ncRNA (lncRNA), which has attracted much attention in recent years, various ncRNAs participate in all kinds of biological processes and show a variety of biomedical application prospects. Recently, National Science Review (NSR) interviewed Ling-Ling Chen, a professor at the Center for Excellence in Molecular Cell Science (CEMCS) of the Chinese Academy of Sciences (CAS), deputy director of the State Key Laboratory of Molecular Biology and director of the CAS Key Laboratory of RNA Science and Engineering, to talk about the magic world of RNA.

Ling-Ling Chen and her team have been studying ncRNA for more than 10 years, and have witnessed and promoted the development of this field. They discovered unconventional lncRNAs without polyadenylated (polyA) tails or N7-methylguanosine (m7G) caps, including sno-lncRNAs (small nucleolar lncRNAs), SPAs (5' snoRNA capped and 3' polyadenylated RNAs) and circRNAs (circular RNAs), and have made remarkable progress clarifying the biogenetic mechanisms and functions of these RNAs and exploring their biomedical application. Chen said: ‘I am 45 years old. I hope I will not stagnate here, but make new discoveries.’
White adipose tissue‐derived small extracellular vesicles: A new potential therapeutic reagent for accelerating diabetic wound healing
Authors: Zhang Chi , Jiang Tao , Jiang Guoyong , Xu Xiang , Yan Chengqi , Kang Yu , Xiang Xuejiao , Liu Shuoyuan , Nie Pengjuan , Zhang Maojie , Chen Jing , Yuan Meng , Xu Yingpeng , Yang Xiaofan , Chen Zhenbing
Published: November 2023

Small extracellular vesicles (sEVs) from adipose‐derived stem cells (ADSCs) have gained great attention and have been widely used in cell‐free therapies for treating diabetic non‐healing wounds in recent years. However, further clinical application of ADSC‐sEVs have been limited due to their unsolvable defects, including cumbersome extraction procedure, high cost, low yield, etc. Thus, we urgently need to find one therapeutic reagent that could not only accelerate diabetic wound healing as ADSC‐sEVs but also overcome these shortcomings. As the extraction process of adipose tissue‐derived sEVs (AT‐sEVs) is quite simple and labor saving, we put our focus on the efficiencies of white adipose tissue‐derived sEVs (WAT‐sEVs) and brown adipose tissue‐derived sEVs (BAT‐sEVs) in diabetic wound repair. After successfully isolating WAT‐sEVs and BAT‐sEVs by ultracentrifugation, we thoroughly characterized them and compared their diabetic wound healing capabilities both in vitro and in vivo. According to our study, AT‐sEVs possess similar competence in diabetic wound healing as compared with ADSC‐sEVs. While the effect of BAT‐sEVs is not as stable as WAT‐sEVs and ADSC‐sEVs, the repair efficiency is also slightly lower than the other two sEVs in some cases. In summary, we are the first to discover that WAT‐sEVs show great potential in diabetic wound repair. With advantages that are specific to tissue‐derived sEVs (Ti‐sEVs) such as time‐ and cost‐saving, high‐yield, and simple isolation procedure, we believe WAT‐sEVs could serve as a novel reliable cell‐free therapy for clinical diabetic wound treatment.
Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma
Authors: Zhang Qian , Liang Zhuokai , Zhang Yingjie , Liu Juzi , Liao Yunjun , Lu Feng , Gao Jianhua , Cai Junrong
Published: November 2023

Adipose tissue transplantation shows great therapeutic potential in reversing localized scleroderma‐associated skin fibrosis. Brown adipose tissue (BAT) can specifically secrete various cytokines against fibrosis, but its therapeutic potential in improving skin fibrosis has not yet been demonstrated. In this study, we have demonstrated the superior therapeutic efficacy of BAT transplantation for sclerotic skin by transplanting two distinct types of adipose tissue. In comparison to the white adipose tissue (WAT) group, mice treated with BAT transplantation exhibited a significant reduction in dermal thickness. BAT transplantation effectively reverses skin sclerosis through mechanisms involving inflammation reduction, promotion of angiogenesis, inhibition of myofibroblast accumulation, and collagen deposition. This therapeutic effect can be attributed to its unique paracrine effects. Furthermore, transcriptome sequencing (RNA‐Seq) revealed upregulation of pathways associated with lipogenesis and fatty acid metabolism in BAT while downregulating pathways are related to transforming growth factor β(TGF‐β), epithelial–mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment.
Representation and the Value of Latino Nurse Leaders
Authors: Kim Kim Ann
Published: November 2023

Building solid recruitment and retention strategies
Picky eating or something more? Differentiating ARFID from typical childhood development
Authors: Silvers Elizabeth , Erlich Kimberly
Published: November 2023

Picky eating is a commonly observed behavior among children that comprises a part of typical development and usually resolves with time. A regular concern for parents, children's picky eating is routinely addressed successfully by pediatric clinicians via anticipatory guidance and basic nutrition education. In some cases, however, a child who is a picky eater may develop a feeding and eating disorder. Avoidant/restrictive food intake disorder (ARFID) is one such disorder that is often marked by an apparent lack of interest in or avoidance of food based on its sensory characteristics or on the individual's fear of possible negative consequences of consumption. ARFID is associated with significant weight loss or failure to achieve expected weight gain; nutritional deficiency; need for supplemental feeding; and/or negative psychosocial effects. The disorder can impact children's overall trajectory of growth and development. Pediatric clinicians must be aware of appropriate monitoring for the milestones of typical development in order to identify any feeding and eating disorder as soon as possible, thereby enabling early intervention and avoiding poor health outcomes. Clinicians must also familiarize themselves with the diagnostic criteria for ARFID, a rare disorder with which many may be unfamiliar.
Routine assessment of anxiety among adolescents in a primary care clinic
Authors: Theiss Michelle R. , Clement Maranda L. , Delaney Beth
Published: November 2023

Background:

Approximately 20% to 25% of all adolescents experience significant symptoms of anxiety, but only half of those adolescents are diagnosed and treated. Recent clinical guidelines recommend routine assessment of adolescent anxiety symptoms in the primary care setting to improve the rates of identification and treatment of anxiety in this population. The objective of this project was to increase early identification and referral for treatment of adolescent anxiety during primary care visits.

Methods:

This project used the Generalized Anxiety Disorder-7 screening tool to assess anxiety symptoms in adolescents in a school-based primary care clinic. Upon arrival to the clinic, adolescent patients completed the brief self-assessment. The provider then used the assessment score to determine the need for further assessment and referral for treatment.

Results:

Of the 51 participants, 21.6% were referred to a mental health provider following assessment, compared with 1.2% of adolescent patients seen in the 6-month period immediately preceding the project.

Conclusion:

The results indicate that screening for symptoms of anxiety in adolescents using a brief self-assessment survey is an effective method for achieving the desired outcome of increased identification and referral for treatment of anxiety symptoms in this population.
Ultrasound-guided Percutaneous Achilles Tendon Repair
Authors: Mazek Jacek , Gnatowski Maciej , Porthos Salas Antonio , Domżalski Marcin , Mazek Mateusz
Published: November 2023

There is no consensus as to the standard treatment of ruptured Achilles tendon. In this paper, we present an innovative method of treating Achilles tendon rupture. Ultrasound-guided percutaneous Achilles tendon repair is a minimally invasive method in the treatment of Achilles tendon rupture. This study aims to assess the feasibility and effectiveness of the procedure in treating ruptured Achilles tendons and in minimizing the complications of surgical percutaneous suturing. Thirty-four patients were treated for Achilles tendon rupture using a percutaneous suturing method under the control of ultrasound. The average follow-up was ~22 months with good and excellent results. As the sural nerve can be easily displayed by high-frequency real-time ultrasonography, the percutaneous repair of the Achilles tendon rupture can be aided by intraoperative ultrasound. The presented method is a quick and efficient surgery, which allows the treatment of torn Achilles tendons in a low-invasive way. The outcomes of this method are promising and enable the reduction of complications of the classic suturing methods.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Role of SGLT2 Inhibitors on Heart Failure Outcomes in Nondiabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kommu Sharath
Published: November 2023

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure (HF). However, studies examining their benefits exclusively in nondiabetic patients on various HF outcomes are limited. By conducting a MEDLINE and ClinicalTrials.gov search for randomized controlled trials, we identified 4 studies on SGLT2i with data on HF outcomes in nondiabetic patients and performed a meta-analysis. There were 10.638 nondiabetic patients, with 5316 patients in the SGLT2i group and 5322 in the placebo group included in this meta-analysis. The composite of worsening HF (hospitalization for HF or urgent visit for HF) or cardiovascular death had 726 events (13.66%) in the SGLT2i group and 907 (17.04%) in the placebo group, with a hazard ratio (HR) of 0.78 and 95% confidence interval (CI) of 0.71–0.86 (P < 0.0001). There were 551 events (10.36%) of hospitalization for HF in the SGLT2i group, compared with 751 (14.11%) in the placebo group with an HR of 0.71 (95% CI, 0.62–0.81; P < 0.0001). Cardiovascular death occurred in 396 patients (7.45%) in the SGLT2i group and 452 (8.49%) in the placebo group, with an HR of 0.88 (95% CI, 0.77–1.00; P = 0.059). All-cause mortality occurred in 552 patients (10.38%) in the SGLT2i group and 586 (11.01%) in the placebo group, with an HR of 0.95 (95% CI, 0.84–1.07; P = 0.37). This study showed that in patients with HF without diabetes mellitus, SGLT2i improve HF outcomes, including a significant decrease in hospitalizations for HF and a favorable response for the outcome of cardiovascular death.
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

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.
The fertility care gap in the Global South: lessons from The Gambia, West Africa, and ways forward to establish fertility care for all
Authors: Balen Julie ,   The Fertility Care in the Global South Network
Published: November 2023

Infertility is a neglected global public health issue affecting an estimated 56–72 million couples worldwide. The prevention and management of infertility was recognized as a basic component of sexual and reproductive health at the landmark 1994 International Conference on Population and Development, yet progress in this area remains limited. Interdisciplinary research has been conducted in The Gambia, West Africa, since 2016, with communities, women’s organizations, clinicians, and health policy and systems stakeholders, to identify key gaps in fertility care, and to better understand the delivery of infertility services. A partnership between the Ministry of Health, Safe Haven Foundation, and international researchers helped create The Gambia’s National Infertility Awareness Campaign and gave birth to the Fertility Care Policy Dialogue supporting the inclusion of infertility in The Gambia’s new 10-year National Health Policy. It also helped to establish the White Rose Interdisciplinary Network on Fertility Care in the Global South. To date, the network has more than 60 members globally, including researchers, health workers, policy makers, and activists who work together on infertility awareness raising, policy change, and system strengthening, with the aim of improving equitable access to fertility care for all. Here, we introduce the network and draw on key lessons from ongoing infertility-related research in The Gambia.
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.
Cytotoxicity of dihydropyridone and dihydropyrimidone curcumin derivatives against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines
Authors: Smits Rufus , Domracheva Ilona , Turovska Baiba
Published: November 2023

Breast cancer is the most common invasive cancer and colorectal cancer (CRC) the second most diagnosed malignancy in women worldwide. In men CRC is the third most common cancer. Despite the recent advances in targeted therapy, the clinical efficacy is often limited, noncurative, with a high toxicity profile, and exorbitant costs. Therefore, there is a growing interest in identifying natural compounds that are safe and affordable as adjunctive treatments to the conventional therapy currently offered for these patients. Curcumin from the roots of the Curcuma longa, is one such compound that has become one of the leading and most studied natural medicines for its role in cancer prevention and powerful antioxidant activity. However, its fast metabolism, low bioavailability, and the lack of specificity call for curcumin analogues to be synthesized with increased potency and higher specificity. In search of lead compounds in the present study the cytotoxic effects of curcumin and 14 heterocyclic curcumin derivatives have been screened using the MTT assay on two cancer cell lines HCT-116 and MDA-MB-231 and also on the normal GM08402 (human fibroblast) cell line. Electrochemical oxidation potentials were determined for selected compounds to reveal their electron-donating capacity and as a general indicator of their radical scavenging ability. Two dihydropyridone lead compounds have been identified which compared to curcumin have higher cytotoxicity on both cancer cell lines and at the same time with reduced cytotoxicity on the normal cell line.
Organizational Learning in the Morbidity and Mortality Conference
Authors: Batthish Michelle , Kuper Ayelet , Fine Claire , Laxer Ronald M. , Baker G. Ross
Published: November 2023

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

Efficient 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

Pneumonia 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

The 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

Overconsumption 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

Visual 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

Eutrophication 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.
CR1variants contribute to FSGS susceptibility across multiple populations
Authors: Skitchenko Rostislav , Modrusan Zora , Loboda Alexander , Kopp Jeffrey B. , Winkler Cheryl A. , Sergushichev Alexey , Gupta Namrata , Stevens Christine , Daly Mark J. , Shaw Andrey , Artomov Mykyta
Published: November 2023

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome with an annual incidence in the United States in African-Americans compared to European-Americans of 24 cases and 5 cases per million, respectively. Among glomerular diseases in Europe and Latin-America, FSGS was the second most frequent diagnosis, and in Asia the fifth. We expand previous efforts in understanding genetics of FSGS by performing a case-control study involving ethnically-diverse groups FSGS cases (726) and a pool of controls (13,994), using panel sequencing of approximately 2,500 podocyte-expressed genes. Through rare variant association tests, we replicated known risk genes –KANK1,COL4A4,andAPOL1. A novel significant association was observed for the gene encoding complement receptor 1 (CR1). High-risk rare variants inCR1in the European-American cohort were commonly observed in Latin-and African-Americans. Therefore, a combined rare and common variant analysis was used to replicate theCR1association in non-European populations. TheCR1risk variant, rs17047661, gives rise to the Sl1/Sl2 (R1601G) allele that was previously associated with protection against cerebral malaria. Pleiotropic effects of rs17047661 may explain the difference in allele frequencies across continental ancestries and suggest a possible role for genetically-driven alterations of adaptive immunity in the pathogenesis of FSGS.