bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank
Authors: Li Panlong , Wang Ying , Tian Dandan , Liu Min , Zhu Xirui , Wang Yanfeng , Huang Chun , Bai Yan , Wu Yaping , Wei Wei , Tian Shan , Li Yuna , Qiao Yuan , Yang Junting , Cao Shanshan , Cong Chaohua , Zhao Lei , Su Jingjing , Wang Meiyun 
Published: February 2024

BACKGROUND:
Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility.

METHODS:
This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS.

RESULTS:

Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m
3
increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33–2.14), 1.24 (0.88–1.70), 1.13 (0.89–1.33), 1.03 (0.98–1.08), and 1.04 (1.02–1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%–189%) greater risk of IS than participants with low polygenic risk score and air pollution score.

CONCLUSIONS:
Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis
Authors: Harris William , Kaiser Jed H. , Liao Vanessa , Avadhani Radhika , Iadecola Costantino , Falcone Guido J. , Sheth Kevin N. , Qureshi Adnan I. , Goldstein Joshua N. , Awad Issam A. , Hanley Daniel F. , Kamel Hooman , Ziai Wendy C. , Murthy Santosh B. 
Published: February 2024

BACKGROUND:
Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood.

METHODS:
We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics.

RESULTS:
Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2–35.7). During a median follow-up of 107 days (interquartile range, 91–140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1–7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7–6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01–1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1–7.2]), compared with those with an ICH volume <17.3 mL.

CONCLUSIONS:
In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.
American crocodile nesting in sediment-nourished habitats on Crocodile Lake National Wildlife Refuge, Florida, USA
Authors: Briggs-Gonzalez Venetia , Godahewa Avishka , Balaguera-Reina Sergio , Dixon Jeremy , Mazzotti Frank 
Published: February 2024

Abstract
The American crocodile (Crocodylus acutus) is the most widely distributed New World crocodile. However, the species has experienced severe declines due to overexploitation. In South Florida, loss of nesting habitat, with coastal degradation from sea level rise and urban development has prompted American crocodiles to nest in novel habitats. Crocodile Lake National Wildlife Refuge (CLNWR) serves as an important nesting site for the South Florida population of American crocodiles and more recently nesting habitat has been supplemented to manage coastal erosion. The goal of this study was to investigate the internal nest biology of American crocodile nests laid in sediment nourished sand mounds on CLNWR. We monitored internal nest temperature and volumetric water content of five live and two control sand nests in 2021 (N = 73 eggs) and 2022 (N = 84 eggs). The metabolic heat generated by incubating eggs in internal nest temperatures ranged from 0.8°C to 2.0°C warmer and more stable than ambient temperatures and reflecting a seasonal pattern. Average clutch size was 31.4 ± 7.09 eggs and incubation period ranged from 78 to 114 days until hatching. These data provide the first insight into thermal regimes of nests laid in novel/supplemented nesting habitat as is the case for a significant proportion of nests in the South Florida population of American crocodiles. Here we provide an opportunity to evaluate the importance of creating artificial nesting habitat for American crocodiles where habitat degradation from climate change threatens species survival.
Extracellular CIRP induces CD4CD8αα intraepithelial lymphocyte cytotoxicity in sepsis
Authors: Akama Yuichi , Murao Atsushi , Aziz Monowar , Wang Ping 
Published: February 2024

Abstract
Background
In sepsis, intestinal barrier dysfunction is often caused by the uncontrolled death of intestinal epithelial cells (IECs). CD4CD8αα intraepithelial lymphocytes (IELs), a subtype of CD4+ T cells residing within the intestinal epithelium, exert cytotoxicity by producing granzyme B (GrB) and perforin (Prf). Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently identified alarmin which stimulates TLR4 on immune cells to induce proinflammatory responses. Here, we hypothesized that eCIRP enhances CD4CD8αα IEL cytotoxicity and induces IEC death in sepsis.

Methods
We subjected wild-type (WT) and CIRP−/− mice to sepsis by cecal ligation and puncture (CLP) and collected the small intestines to isolate IELs. The expression of GrB and Prf in CD4CD8αα IELs was assessed by flow cytometry. IELs isolated from WT and TLR4−/− mice were challenged with recombinant mouse CIRP (eCIRP) and assessed the expression of GrB and Prf in CD4CD8αα by flow cytometry. Organoid-derived IECs were co-cultured with eCIRP-treated CD4CD8αα cells in the presence/absence of GrB and Prf inhibitors and assessed IEC death by flow cytometry.

Results
We found a significant increase in the expression of GrB and Prf in CD4CD8αα IELs of septic mice compared to sham mice. We found that GrB and Prf levels in CD4CD8αα IELs were increased in the small intestines of WT septic mice, while CD4CD8αα IELs of CIRP−/− mice did not show an increase in those cytotoxic granules after sepsis. We found that eCIRP upregulated GrB and Prf in CD4CD8αα IELs isolated from WT mice but not from TLR4−/− mice. Furthermore, we also revealed that eCIRP-treated CD4CD8αα cells induced organoid-derived IEC death, which was mitigated by GrB and Prf inhibitors. Finally, histological analysis of septic mice revealed that CIRP−/− mice were protected from tissue injury and cell death in the small intestines compared to WT mice.

Conclusion
In sepsis, the cytotoxicity initiated by the eCIRP/TLR4 axis in CD4CD8αα IELs is associated with intestinal epithelial cell (IEC) death, which could lead to gut injury.
Cirscan: a shiny application to identify differentially active sponge mechanisms and visualize circRNA–miRNA–mRNA networks
Authors: Fraboulet Rose-Marie , Si Ahmed Yanis , Aubry Marc , Corre Sebastien , Galibert Marie-Dominique , Blum Yuna 
Published: February 2024

Abstract
Background
Non-coding RNAs represent a large part of the human transcriptome and have been shown to play an important role in disease such as cancer. However, their biological functions are still incompletely understood. Among non-coding RNAs, circular RNAs (circRNAs) have recently been identified for their microRNA (miRNA) sponge function which allows them to modulate the expression of miRNA target genes by taking on the role of competitive endogenous RNAs (ce-circRNAs). Today, most computational tools are not adapted to the search for ce-circRNAs or have not been developed for the search for ce-circRNAs from user’s transcriptomic data.

Results
In this study, we present Cirscan (CIRcular RNA Sponge CANdidates), an interactive Shiny application that automatically infers circRNA–miRNA–mRNA networks from human multi-level transcript expression data from two biological conditions (e.g. tumor versus normal conditions in the case of cancer study) in order to identify on a large scale, potential sponge mechanisms active in a specific condition. Cirscan ranks each circRNA–miRNA–mRNA subnetwork according to a sponge score that integrates multiple criteria based on interaction reliability and expression level. Finally, the top ranked sponge mechanisms can be visualized as networks and an enrichment analysis is performed to help its biological interpretation. We showed on two real case studies that Cirscan is capable of retrieving sponge mechanisms previously described, as well as identifying potential novel circRNA sponge candidates.

Conclusions
Cirscan can be considered as a companion tool for biologists, facilitating their ability to prioritize sponge mechanisms for experimental validations and identifying potential therapeutic targets. Cirscan is implemented in R, released under the license GPL-3 and accessible on GitLab (https://gitlab.com/geobioinfo/cirscan_Rshiny). The scripts used in this paper are also provided on Gitlab (https://gitlab.com/geobioinfo/cirscan_paper).
Identification of Campylobacter jejuni and Campylobacter coli genes contributing to oxidative stress response using TraDIS analysis
Authors: Stoakes Emily , Chen Xuanlin , Kalmar Lajos , Baker Dave , Evans Rhiannon , Rudder Steven , Grant Andrew J. 
Published: February 2024

Abstract
Background
Campylobacter jejuni and Campylobacter coli are the major causative agents of bacterial gastroenteritis worldwide and are known obligate microaerophiles. Despite being sensitive to oxygen and its reduction products, both species are readily isolated from animal food products kept under atmospheric conditions where they face high oxygen tension levels.

Results
In this study, Transposon Directed Insertion-site Sequencing (TraDIS) was used to investigate the ability of one C. jejuni strain and two C. coli strains to overcome oxidative stress, using H2O2 to mimic oxidative stress. Genes were identified that were required for oxidative stress resistance for each individual strain but also allowed a comparison across the three strains. Mutations in the perR and ahpC genes were found to increase Campylobacter tolerance to H2O2. The roles of these proteins in oxidative stress were previously known in C. jejuni, but this data indicates that they most likely play a similar role in C. coli. Mutation of czcD decreased Campylobacter tolerance to H2O2. The role of CzcD, which functions as a zinc exporter, has not previously been linked to oxidative stress. The TraDIS data was confirmed using defined deletions of perR and czcD in C. coli 15-537360.

Conclusions
This is the first study to investigate gene fitness in both C. jejuni and C. coli under oxidative stress conditions and highlights both similar roles for certain genes for both species and highlights other genes that have a role under oxidative stress.
Safety and efficacy of low-dose esketamine in laparoscopic cholecystectomy: a prospective, double-blind randomized controlled trial
Authors: Zhao Lu , Li Zhengyu , Jin Bi , Hou Nina , Yang Heng 
Published: February 2024

Abstract
Background
Esketamine, recognized for its analgesic, sedative, and anti-inflammatory qualities, is integral in multimodal analgesia. However, the potential opioid-sparing effects of intravenous esketamine, along with its impact on inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored.

Methods
In this study, 90 patients scheduled for laparoscopic cholecystectomy were equally randomized into three groups: a normal saline control group (NS), a low-dose esketamine group (LS) and a high-dose esketamine group (HS). Subsequently, we monitored several parameters: hemodynamics, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, and 24-hour postoperative sufentanil requirements. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups.

Results
Compared to their levels 5 minutes prior to anesthesia (T0) and 30 minutes post-operation (T4), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at various time intervals: 5 minutes after the skin incision (T1), 30 minutes post-incision (T2), and at the conclusion of the operation (T3), compared to the LS and HS groups(P < 0.05). Furthermore, the NS group exhibited a greater increase in levels of adrenaline (AD), noradrenaline (NE), endothelin (ET), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) at T1, T2, and T3, more so than the other two groups(P < 0.05). 24 hours after the surgery, patients in the LS group and HS group had significantly higher Montreal Cognitive Assessment (MoCA) scores than those in the NS group(P < 0.05). The LS and HS groups required lower doses of propofol, remifentanil, and sufentanil during surgery (P < 0.05), experienced shorter postoperative recovery times, and had lower incidences of nausea, vomiting, and respiratory depression compared to the NS group (P < 0.05).

Conclusion
The administration of low-dose esketamine has been shown to be safe, effective, and dependable in the context of laparoscopic gallbladder surgery. It has the capacity to stabilize hemodynamic responses, ameliorate both stress and inflammatory reactions from surgery, and hastens anesthesia recovery. Furthermore, it fosters the restoration of postoperative cognitive function. Notably, when combined with nalbuphine, it exhibits opioid-sparing effects, reducing postoperative adverse outcomes.

Trial registration
The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively registered (date of registration: 12/01/2023).
A modified Michaelis-Menten equation estimates growth from birth to 3 years in healthy babies in the USA
Authors: Walters William A. , Ley Catherine , Hastie Trevor , Ley Ruth E. , Parsonnet Julie 
Published: February 2024

Abstract
Background
Standard pediatric growth curves cannot be used to impute missing height or weight measurements in individual children. The Michaelis–Menten equation, used for characterizing substrate-enzyme saturation curves, has been shown to model growth in many organisms including nonhuman vertebrates. We investigated whether this equation could be used to interpolate missing growth data in children in the first three years of life and compared this interpolation to several common interpolation methods and pediatric growth models.

Methods
We developed a modified Michaelis–Menten equation and compared expected to actual growth, first in a local birth cohort (N = 97) then in a large, outpatient, pediatric sample (N = 14,695).

Results
The modified Michaelis–Menten equation showed excellent fit for both infant weight (median RMSE: boys: 0.22 kg [IQR:0.19; 90% < 0.43]; girls: 0.20 kg [IQR:0.17; 90% < 0.39]) and height (median RMSE: boys: 0.93 cm [IQR:0.53; 90% < 1.0]; girls: 0.91 cm [IQR:0.50;90% < 1.0]). Growth data were modeled accurately with as few as four values from routine well-baby visits in year 1 and seven values in years 1–3; birth weight or length was essential for best fit. Interpolation with this equation had comparable (for weight) or lower (for height) mean RMSE compared to the best performing alternative models.

Conclusions
A modified Michaelis–Menten equation accurately describes growth in healthy babies aged 0–36 months, allowing interpolation of missing weight and height values in individual longitudinal measurement series. The growth pattern in healthy babies in resource-rich environments mirrors an enzymatic saturation curve.
Associations between self-care advice and healing time in patients with venous leg ulcer– a Swedish registry-based study
Authors: Rosenburg Marcus , Tuvesson Hanna , Lindqvist Gunilla , Brudin Lars , Fagerström Cecilia 
Published: February 2024

Abstract
Background
Venous leg ulcers take time to heal. It is advocated that physical activity plays a role in healing, and so does the patient’s nutritional status. Additionally, malnutrition influences the inflammatory processes, which extends the healing time. Therefore, the staff’s advising role is important for patient outcomes. Thus, this study aimed to investigate the associations between given self-care advice and healing time in patients with venous leg ulcers while controlling for demographic and ulcer-related factors.

Methods
The sample consisted of patients registered in the Registry of Ulcer Treatment (RUT) which includes patient and ulcer-related and healing variables. The data was analyzed with descriptive statistics. Logistic regression models were performed to investigate the influence of self-care advice on healing time.

Results
No associations between shorter healing time (less than 70 days) and the staff´s self-care advice on physical activity was identified, whilst pain (OR 1.90, CI 1.32–2.42, p < 0.001) and giving of nutrition advice (OR 1.55, CI 1.12–2.15, p = 0.009) showed an association with longer healing time.

Conclusions
Neither self-care advice on nutrition and/or physical activity indicated to have a positive association with shorter healing time. However, information and counseling might not be enough. We emphasize the importance of continuously and systematically following up given advice throughout ulcer management, not only when having complicated ulcers.
Patterns of psychotropic drug prescriptions and general practice consultations among community-dwelling older people with dementia during the first two years of the COVID-19 pandemic
Authors: Du Jiamin , Burger Huibert , Kupers Thijmen , Sulim Karina , Homburg Maarten T. , Muris Jean W. M. , olde Hartman Tim C. , Zuidema Sytse U. , Peters Lilian L. , Janus Sarah I. M. 
Published: February 2024

Abstract
Background
The COVID-19 pandemic and subsequent lockdown measures had serious implications for community-dwelling older people with dementia. While the short-term impacts of the pandemic on this population have been well studied, there is limited research on its long-term impacts. Quantifying the long-term impacts may provide insights into whether healthcare adaptations are needed after the acute phase of the pandemic to balance infection prevention measures with healthcare provision. This study aims to examine patterns of psychotropic drug prescriptions and general practice consultations in community-dwelling older people with dementia during the first two years of the pandemic.

Methods
We utilised routine electronic health records from three Dutch academic general practice research networks located in the North, East, and South, between 2019 and 2021. We (1) compared the weekly prescription rates of five groups of psychotropic drugs and two groups of tracer drugs, and weekly general practice consultation rates per 1000 participants, between the first two years of the pandemic and the pre-pandemic phase, (2) calculated changes in these rates during three lockdowns and two relaxation phases relative to the corresponding weeks in 2019, and (3) employed interrupted time series analyses for the prescription rates. Analyses were performed for each region separately.

Results
The study population sizes in the North, East, and South between 2019 and 2021 were 1726 to 1916, 93 to 117, and 904 to 960, respectively. Data from the East was excluded from the statistical analyses due to the limited sample size. During the first two years of the pandemic, the prescription rates of psychotropic drugs were either lower or similar to those in the pre-pandemic phase, with differences varying from -2.6‰ to -10.2‰. In contrast, consultation rates during the pandemic were higher than in the pre-pandemic phase, increasing by around 38‰.

Conclusions
This study demonstrates a decrease in psychotropic drug prescriptions, but an increase in general practice consultations among community-dwelling older people with dementia during the first two years of the pandemic. However, reasons for the decrease in psychotropic drug prescriptions are unclear due to limited information on the presence of neuropsychiatric symptoms and the appropriateness of prescribing.