bluuebunny/crossref_metadata_2025_split huggingface dataset:
A sodium/potassium switch for G4-prone G/C-rich sequences
Authors: Luo Yu , Živković Martina Lenarčič , Wang Jiawei , Ryneš Jan , Foldynová-Trantírková Silvie , Trantírek Lukáš , Verga Daniela , Mergny Jean-Louis 
Published: November 2023

Abstract
Metal ions are essential components for the survival of living organisms. For most species, intracellular and extracellular ionic conditions differ significantly. As G-quadruplexes (G4s) are ion-dependent structures, changes in the [Na+]/[K+] ratio may affect the folding of genomic G4s. More than 11000 putative G4 sequences in the human genome (hg19) contain at least two runs of three continuous cytosines, and these mixed G/C-rich sequences may form a quadruplex or a competing hairpin structure based on G-C base pairing. In this study, we examine how the [Na+]/[K+] ratio influences the structures of G/C-rich sequences. The natural G4 structure with a 9-nt long central loop, CEBwt, was chosen as a model sequence, and the loop bases were gradually replaced by cytosines. The series of CEB mutations revealed that the presence of cytosines in G4 loops does not prevent G4 folding or decrease G4 stability but increases the probability of forming a competing structure, either a hairpin or an intermolecular duplex. Slow conversion to the quadruplex in vitro (in a potassium-rich buffer) and cells was demonstrated by NMR. ‘Shape-shifting’ sequences may respond to [Na+]/[K+] changes with delayed kinetics.
Epigenetic profiles guide improved CRISPR/Cas9-mediated gene knockout in human T cells
Authors: Ito Yusuke , Inoue Satoshi , Nakashima Takahiro , Zhang Haosong , Li Yang , Kasuya Hitomi , Matsukawa Tetsuya , Wu Zhiwen , Yoshikawa Toshiaki , Kataoka Mirei , Ishikawa Tetsuo , Kagoya Yuki 
Published: November 2023

Abstract
Genetic modification of specific genes is emerging as a useful tool to enhance the functions of antitumor T cells in adoptive immunotherapy. Current advances in CRISPR/Cas9 technology enable gene knockout during in vitro preparation of infused T-cell products through transient transfection of a Cas9-guide RNA (gRNA) ribonucleoprotein complex. However, selecting optimal gRNAs remains a major challenge for efficient gene ablation. Although multiple in silico tools to predict the targeting efficiency have been developed, their performance has not been validated in cultured human T cells. Here, we explored a strategy to select optimal gRNAs using our pooled data on CRISPR/Cas9-mediated gene knockout in human T cells. The currently available prediction tools alone were insufficient to accurately predict the indel percentage in T cells. We used data on the epigenetic profiles of cultured T cells obtained from transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Combining the epigenetic information with sequence-based prediction tools significantly improved the gene-editing efficiency. We further demonstrate that epigenetically closed regions can be targeted by designing two gRNAs in adjacent regions. Finally, we demonstrate that the gene-editing efficiency of unstimulated T cells can be enhanced through pretreatment with IL-7. These findings enable more efficient gene editing in human T cells.
Epigenetic regulation of asymmetric cell division by the LIBR-BRD4 axis
Authors: Chen Hsiao-Fan , Chang Chia-Ting , Hsu Kai-Wen , Peng Pei-Hua , Lai Joseph Chieh-Yu , Hung Mien-Chie , Wu Kou-Juey 
Published: November 2023

Abstract
Asymmetric cell division (ACD) is a mechanism used by stem cells to maintain the number of progeny. However, the epigenetic mechanisms regulating ACD remain elusive. Here we show that BRD4, a BET domain protein that binds to acetylated histone, is segregated in daughter cells together with H3K56Ac and regulates ACD. ITGB1 is regulated by BRD4 to regulate ACD. A long noncoding RNA (lncRNA), LIBR (LncRNA Inhibiting BRD4), decreases the percentage of stem cells going through ACD through interacting with the BRD4 mRNAs. LIBR inhibits the translation of BRD4 through recruiting a translation repressor, RCK, and inhibiting the binding of BRD4 mRNAs to polysomes. These results identify the epigenetic regulatory modules (BRD4, lncRNA LIBR) that regulate ACD. The regulation of ACD by BRD4 suggests the therapeutic limitation of using BRD4 inhibitors to treat cancer due to the ability of these inhibitors to promote symmetric cell division that may lead to tumor progression and treatment resistance.
Changes in energy and macronutrient intakes during Ramadan fasting: a systematic review, meta-analysis, and meta-regression
Authors: Abdelrahim Dana N , El Herrag Salah Eddine , Khaled Meghit Boumediene , Radwan Hadia , Naja Farah , Alkurd Refat , Khan Moien A B , Zeb Falak , AbuShihab Katia H , Mahrous Lana , Obaideen Khaled , Kalam Faiza , Granata Iv Frank , Madkour Mohamed , Faris MoezAlIslam E 
Published: November 2023

Abstract

Context
Ramadan fasting (RF) is associated with various physiological and metabolic changes among fasting Muslims. However, it remains unclear whether these effects are attributable to changes in meal timing or changes in dietary energy and macronutrient intakes. Furthermore, the literature on the associations between RF, meal timing, and energy and macronutrient intakes is inconclusive.

Objectives
This systematic review aimed to estimate the effect sizes of RF on energy and macronutrient intakes (carbohydrates, protein, fats, dietary fiber, and water) and determine the effect of different moderators on the examined outcomes.

Data Sources
The Cochrane, CINAHL, EMBASE, EBSCOhost, Google Scholar, PubMed/MEDLINE, ProQuest Medical, Scopus, ScienceDirect, and Web of Science databases were searched from inception to January 31, 2022.

Data Extraction
The studies that assessed energy, carbohydrate, protein, fat, fiber, and water intakes pre- and post-fasting were extracted.

Data Analysis
Of the 4776 identified studies, 85 relevant studies (n = 4594 participants aged 9–85 y) were selected. The effect sizes for the studied variables were as follows: energy (number of studies [K] = 80, n = 3343 participants; mean difference [MD]: −142.45; 95% confidence interval [CI]: −215.19, −69.71), carbohydrates (K = 75, n = 3111; MD: −23.90; 95% CI: −36.42, −11.38), protein (K = 74, n = 3108; MD: −4.21; 95% CI: −7.34, −1.07), fats (K = 73, n = 3058; MD: −2.03; 95% CI: −5.73, 1.67), fiber (K = 16, n = 1198; MD: 0.47; 95% CI: −1.44, 2.39), and water (K = 17, n = 772; MD: −350.80; 95% CI: −618.09, 83.50). Subgroup analyses showed age significantly moderated the 6 dietary outcomes, and physical activity significantly moderated water intake. There were significant reductions in energy, carbohydrate, and protein intakes during RF.

Conclusions
The change in meal timing rather than quantitative dietary intake may explain various physiological and health effects associated with RF.
Rifampin Mono-Resistant Tuberculosis in New York City, 2010–2021: A Retrospective Case Series
Authors: Lindsey Joseph A , Easton Alice V , Modestil Herns , Dworkin Felicia , Burzynski Joseph , Nilsen Diana 
Published: November 2023

Abstract

Background
Although relatively rare, rifampin mono-resistant tuberculosis (RMR TB) poses important challenges to effective TB treatment and control. Information on the burden of RMR TB and treatment outcomes is needed to inform diagnosis and management.

Methods
Standardized variables were collected from the New York City (NYC) tuberculosis surveillance system for patients treated for RMR TB in NYC during 2010–2021.

Results
Of 7097 TB cases reported in 2010–2021, 31 (&lt;1%) were treated clinically as RMR TB. Five (16%) of these patients had HIV. Seventeen patients (55%) had TB that was rifampin-resistant by both molecular and phenotypic drug susceptibility testing; 2 (6%) had rifampin resistance by phenotypic tests, and molecular tests were not done; and 12 (39%) were identified based only on molecular tests. Among these 12, 7 were rifampin-sensitive by phenotypic tests, and phenotypic testing could not be done for the other 5. Ten of the 31 (32%) were diagnosed in 2010–2015; the other 21 (including 10/12 diagnosed by molecular tests alone) were diagnosed in 2016–2021. Of the 31 patients, 21 (68%) completed treatment (median treatment duration of 18 months). Although the interval between tuberculosis treatment initiation and change to a non-rifamycin-containing regimen decreased significantly during the study period, the overall duration of treatment did not decrease significantly between 2010 and 2021.

Conclusions
Molecular drug susceptibility tests identified cases of RMR TB that were not detected by phenotypic testing and helped enable timely adjustment of tuberculosis treatment regimens. Short-course regimens are needed to reduce duration of treatment for RMR TB.
Socio-demographic variation in adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations within the UK Biobank prospective cohort study
Authors: Malcomson Fiona C , Parra-Soto Solange , Lu Liya , Ho Frederick , Celis-Morales Carlos , Sharp Linda , Mathers John C 
Published: November 2023

Abstract

Background
The 2018 (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are evidence-based lifestyle recommendations which aim to reduce the risk of cancer worldwide. Sociodemographic factors modulate lifestyle behaviours, and both cancer incidence and survival are socio-economically patterned. We investigated adherence to these recommendations and examined patterns of adherence across sociodemographic subgroups in the UK Biobank cohort.

Methods
We included 158 415 UK Biobank participants (mean age 56 years, 53% female). Total adherence scores were derived from dietary, physical activity and anthropometric data using the 2018 WCRF/AICR standardized scoring system. One-Way analysis of variance (ANOVA) was used to test for differences in total scores and in values for individual score components according to sociodemographic factors and Pearson’s Χ2 test to investigate associations between sociodemographic factors according to tertiles of adherence score.

Results
Mean total adherence score was 3.85 points (SD 1.05, range 0–7 points). Higher total scores were observed in females, and older (&gt;57 years), Chinese or South Asian, and more educated participants. We found significant variations in adherence to individual recommendations by sociodemographic factors including education, Townsend deprivation index and ethnicity.

Conclusions
Identifying and understanding lifestyle and dietary patterns according to sociodemographic factors could help to guide public health strategies for the prevention of cancers and other non-communicable diseases.
Deficits in brain default mode network connectivity mediate the relationship between poor sleep quality and anxiety severity
Authors: Shen Zhifu , Yang Xue , She Tianwei , Zhao Guangli , Dou Zeyang , Luo Yucai , Lin Wenting , Dang Wantai , Yu Siyi 
Published: November 2023

AbstractStudy ObjectivesChronic insomnia disorder (CID) is a prevalent sleep disorder that frequently cooccurs with anxiety. The association between insomnia and anxiety has been established; however, the neurobiological basis of this relationship remains unclear. This study aimed to investigate the neural markers of CID patients with and without anxiety and to determine whether specific neural connectivity mediates the relationship between insomnia and anxiety.MethodsThis study included 180 participants, comprising CID patients with anxiety (CID-A), CID patients without anxiety (CID-NA), and good sleep controls. All participants completed self-reported measures of sleep quality and anxiety severity and underwent functional magnetic resonance imaging. Brain functional integration was measured using functional connectivity density (FCD) and resting-state functional connectivity (rsFC). Correlation and mediation analyses were used to examine the relationships among brain connectivity, sleep quality, and anxiety severity.ResultsThe CID-NA and CID-A groups showed decreased local FCD in the medial prefrontal cortex (mPFC) and disrupted rsFC between the precuneus and other brain regions. Only the CID-A group exhibited altered long-range FCD in the precuneus and the rsFC between the anterior default mode network (DMN, e.g. mPFC) and posterior DMN (e.g. precuneus). Mediation analysis revealed DMN dysconnectivity underlying the association between poor sleep quality and anxiety symptoms.ConclusionsThis study identified shared and distinct brain circuit disruptions in the CID-NA and CID-A groups, with deficits in DMN connectivity as a potential neural mechanism through which disrupted sleep augments anxiety. These findings may facilitate the development of personalized therapies for insomnia and associated anxiety problems.
Macrophage migration inhibitory factor (MIF) promotes intervertebral disc degeneration through theNF‐κBpathway, and theMIFinhibitorCPSI‐1306 alleviates intervertebral disc degeneration in a mouse model
Authors: Zhang Yejin , Zheng Lin , Fang Jiawei , Ni Kainan , Hu Xingyu , Ye Lin , Lai Hehuan , Yang Tao , Chen Zhenzhong , He Dengwei 
Published: November 2023

AbstractLumbar intervertebral disc degeneration(IDD) is a prevalent inflammatory disease caused by many proinflammatory factors, such as TNF and IL‐1β. Migration inhibitory factor (MIF) is an upstream inflammatory factor widely expressed in vivo that is associated with a variety of inflammatory diseases or malignant tumors and has potential therapeutic value in many diseases. We explored the role of MIF in intervertebral disc degeneration by regulating the content of exogenous MIF or the expression of MIF in cells. Upon inducing degeneration of nucleus pulposus (NP) cells with IL‐1β, we found that the increase in intracellular and exogenous MIF promoted the catabolism induced by proinflammatory factors in NP cells, while silencing of the MIF gene alleviated the degeneration to some extent. In a mouse model, the intervertebral disc degeneration of MIF‐KO mice was significantly less than that of wild‐type mice. To explore the treatment of intervertebral disc degeneration, we selected the small‐molecular MIF inhibitor CPSI‐1306. CPSI‐1306 had a therapeutic effect on intervertebral disc degeneration in the mouse model. In summary, we believe that MIF plays an important role in intervertebral disc degeneration and is a potential therapeutic target for the treatment of intervertebral disc degeneration.
Minoxidil-associated pericardial effusion and impending tamponade
Authors: Lew Michelle J. , Amato Jordan 
Published: November 2023

ABSTRACT
A patient with a large pericardial effusion and impending tamponade exhibited clinical improvement with urgent pericardiocentesis. Further workup ruled minoxidil to be the likely cause of the effusion. After discontinuation of minoxidil, the effusion did not recur.
Six tips for successful grant writing
Authors: Mines Ashley 
Published: November 2023

ABSTRACT
Physician associates/assistants (PAs) are poised to be excellent grant writers for local projects that can improve access to quality care and improve the finances of historically underserved, urban, and rural healthcare communities. Because grant writing focuses on the dream of what is possible with funding, it contrasts with other forms of medical writing, which focus on past findings. This article aims to introduce PAs to six steps that can help them with grant writing, with a goal of improving patient care or starting community outreach projects.
Recurrent Severe Maternal Morbidity in an Obstetric Population With a High Comorbidity Burden
Authors: McIlwraith Claire , Sanusi Ayodeji , McGwin Gerald , Battarbee Ashley , Subramaniam Akila 
Published: November 2023

OBJECTIVE:
To evaluate the risk of severe maternal morbidity (SMM) in subsequent pregnancies in patients who experienced SMM in a previous pregnancy compared with those who did not.

METHODS:
We conducted a retrospective cohort study of patients with two or more deliveries at 23 or more weeks of gestation at a single Southeastern U.S. tertiary care center between 2015 and 2018. The primary exposure was SMM including transfusion (transfusion SMM) in a previous pregnancy, as defined by the Centers for Disease Control and Prevention, using International Classification of Diseases, Ninth or Tenth Revision codes. The primary outcome was transfusion SMM in any subsequent pregnancy in the study time frame. Generalized estimating equation models were used to estimate the relative risk (RR) and associated 95% CIs of transfusion SMM in patients with transfusion SMM in a prior pregnancy compared with patients without transfusion SMM in a previous pregnancy. Severe maternal morbidity without transfusion (nontransfusion SMM) and cross-analysis to determine risk of a different type of SMM after a history of SMM were analyzed similarly.

RESULTS:
Of 852 included patients, transfusion SMM and nontransfusion SMM occurred in 90 (10.6%) and 18 (2.1%), respectively, in the first captured pregnancy and in 79 (9.3%) and 9 (1.1%), respectively, in subsequent pregnancies. Anemia (34.6–40.0%), obesity (33.4–40.4%), substance use disorder (14.2–14.6%), and preeclampsia (12.0–11.4%) were the most prevalent morbidities at first captured and subsequent pregnancies, respectively. There was a 16-fold higher risk of transfusion SMM in a subsequent pregnancy after experiencing transfusion SMM in the first captured pregnancy (57.8% vs 3.5%, RR 16.3 95% CI, 10.8–24.6). Nontransfusion SMM was similarly higher in patients with nontransfusion SMM in their first captured pregnancy compared with those without (16.7% vs 0.7%, RR 23.2 95% CI, 6.3–85.4). Additionally, patients who experienced transfusion SMM in their first captured pregnancies were at sixfold higher risk of developing nontransfusion SMM in a subsequent pregnancy (RR 6.2, 95% CI, 1.7–22.6). However, in cross-analysis of patients who experienced nontransfusion SMM, the risk of transfusion SMM in a subsequent pregnancy was not statistically significant.

CONCLUSION:
The risks of SMM in subsequent pregnancies after previous SMM are extremely high and are higher than previous estimates. Future studies should estimate the contributions of comorbidities and other structural determinants including social vulnerability to help design interventions to reduce subsequent pregnancy risks.
Critical and non-critical coronavirus disease 2019 patients: which is the most predictive biomarker for disease severity and outcome?
Authors: Montrucchio Giorgia , Balzani Eleonora , Sales Gabriele , Bolla Cesare , Sarda Cristina , Della Selva Andrea , Perotto Massimo , Pomero Fulvio , Ravera Enrico , Rumbolo Francesca , Callegari Tiziana , Fanelli Vito , Mengozzi Giulio , Brazzi Luca 
Published: November 2023

BACKGROUND
Severe acute respiratory syndrome-coronavirus-2 in coronavirus disease 2019 (COVID-19) patients leads to a wide range of clinical manifestations. The evaluation of mid-regional pro-adrenomedullin (MR-proADM) as a prognostic biomarker in noncritical wards (NON-ICU) and intensive care units (ICU), may have a potential in predicting disease severity and outcomes.

OBJECTIVE
To assess the difference in the prognostic power of MR-proADM in NON-ICU wards and in ICUs in a prospective multicentre cohort study.

DESIGN
From January to July 2021, all adult COVID-19 patients requiring admission for more than 48 h.

SETTING
One primary centre and two secondary centre hospitals.

PATIENTS
One hundred and twenty-three ICU and 77 NON-ICU patients.

INTERVENTION
MR-proADM, lymphocyte subpopulations and immunoglobulins were measured within 48 h and on days 3 and 7. A Log-rank test was used to compare survival curves, using a MR-proADM cut-off value of 1.5 nmol l−1. The predictive ability for mortality was compared using the area under the curve and 95% confidence interval (CI) of different receiver-operating characteristic curves.

MAIN OUTCOME MEASURES
The first 48 h MR-proADM values were significantly higher in the ICU group (median value 1.10 [IQR, 0.80 to 1.73] pg ml−1 vs. 0.90 [0.70 to 1.20] pg ml−1, P = 0.020), and statistically significant changes were observed over time for MR-proADM, CD3+, CD4+ and CD56+. In univariate analysis, MR-proADM was the only biomarker that significantly predicted mortality (P = 0.006). The logistic regression model showed an odds ratio for mortality equal to 1.83 (95% CI, 1.08 to 3.37) P = 0.035 for MR-proADM, 1.37 (1.15 to 1.68) P = 0.001 for MuLBSTA and 1.11 (1.05 to 1.18) P less than 0.001 for SAPS II.

CONCLUSION
MR-proADM admission values and trends over time appear to be a suitable marker of illness severity and a patient's risk of mortality in both ICU and NON-ICU settings. Lymphocyte subpopulation dysfunction seems to play a role in defining the severity of COVID-19 but is limited to ICU setting.

TRIAL REGISTRATION
on clinicaltrials.gov, NCT04873388 registered on March 2020.
Bacterial and Candida Colonization of Neonates in a Regional Hospital in South Africa
Authors: Mabena Fikile C. , Olwagen Courtney P. , Phosa Matshie , Ngwenya Innocent K. , Van der Merwe Lara , Khan Aaliyah , Mwamba Tshiama M. , Mpembe Ruth , Magobo Rindidzani E. , Govender Nelesh P. , Velaphi Sithembiso C. , Madhi Shabir A. 
Published: November 2023

Background:
Neonatal colonization with multidrug-resistant (MDR) Enterobacter spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterococcus faecium (ESKAPE) and Candida spp. often precedes invasive hospital-acquired infections. We investigated the prevalence and dynamics of neonatal ESKAPE and Candida spp. colonization from hospital admission until discharge (or death) and followed up for invasive disease.

Methods:
Prospective longitudinal surveillance for neonatal ESKAPE and Candida spp. colonization was conducted over 6 months at a South African regional hospital. Neonates enrolled at birth had swabs (nasal, 2× skin and rectal) collected within 24 hours and every 48–96 hours thereafter, until discharge or death. ESKAPE and Candida spp. were cultured for and antimicrobial susceptibility was performed on bacterial isolates. Whole-genome sequencing was undertaken on paired samples with the same bacterial species from colonizing and invasive disease episodes in the same child.

Results:
Of 102 enrolled neonates, 79% (n = 81) were colonized by ≥1 ESKAPE organism by time of discharge or death. Forty-four percent (36/81) were colonized within 24 hours of birth. Common colonizers were K. pneumoniae (70%; n = 57) and Enterobacter spp. (43%; n = 35). Almost all MDR organisms (93%) were Gram-negative. Forty-two (45%, 42/93) newborns acquired Candida spp. (skin only) colonization, commonly Candida parapsilosis (69%; n = 29). For 2 children with K. pneumoniae colonization and sepsis, the bloodstream and colonizing isolates were genetically different, whereas the single A. baumannii colonizing and blood isolate pair were genetically identical.

Conclusions:
We report a high prevalence of MDR ESKAPE and Candida spp. colonization in a regional neonatal unit. Interventions to reduce the high incidence of hospital-acquired neonatal infections should include reducing high colonization rates.