bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of abnormal body weight on mortality and functional recovery in adults after stroke: An umbrella review
Authors: Holland Stephanie A , Wellwood Ian , Kuys Suzanne 
Published: October 2023

Background: Several published systematic reviews have drawn conflicting conclusions on the effect of abnormal body weight (i.e. being underweight, overweight or obese) on outcomes following stroke. The ‘obesity paradox’ seen in several diseases (wherein obesity, often associated with mortality and morbidity, appears to be protective and improve outcomes) may be evident after stroke, but inconsistent results of existing reviews, and the issue of being underweight, are worth investigating further. Aims: To better understand the impact of body weight on prognosis after stroke, we aimed to answer the following research question: What is the effect of abnormal body weight (underweight, overweight, or obesity) on mortality and functional recovery in adults after stroke? Summary of review: We conducted an umbrella review to synthesize existing evidence on the effects of abnormal body weight on stroke outcomes. We searched Cumulated Index to Nursing and Allied Health Literature (CINAHL) Complete, COCHRANE Database of Systematic Reviews, PubMed, Medline, PEDro, and EMBASE Classic + EMBASE, from inception until 28 February 2023. Seven systematic reviews (1,136,929 participants) from 184 primary studies (counting duplicates) were included. While the risk of mortality increases with being underweight (body mass index (BMI) < 18.5 kg/m2), excess body weight (being overweight (BMI = 25–29.9 kg/m2) or obese (BMI > 30 kg/m2)) is associated with reduced mortality. The impact of abnormal body weight on functional recovery is less clear; data from studies of being underweight are associated with poor functional outcomes while those from studies of excess body weight are inconclusive. Conclusion: Abnormal body weight effects post-stroke outcomes and should be considered in clinical decision-making, prognostic research, and clinical trials of rehabilitation interventions. The “obesity paradox” is evident after stroke, and excess body weight is associated with reduced mortality compared to normal body weight. It is recommended that body weight is routinely recorded for stroke patients, and further research, including well-designed cohort studies with reliable weight data, is needed to further investigate the impact of body weight and distribution on post-stroke outcomes.
AMPK activation induces immunogenic cell death in AML
Authors: Mondesir Johanna , Ghisi Margherita , Poillet Laura , Bossong Robert A. , Kepp Oliver , Kroemer Guido , Sarry Jean-Emmanuel , Tamburini Jérôme , Lane Andrew A. 
Published: October 2023

Abstract
Survival of patients with acute myeloid leukemia (AML) can be improved by allogeneic hematopoietic stem cell transplantation (allo-HSCT) because of the antileukemic activity of T and natural killer cells from the donor. However, the use of allo-HSCT is limited by donor availability, recipient age, and potential severe side effects. Similarly, the efficacy of immunotherapies directing autologous T cells against tumor cells, including T-cell recruiting antibodies, chimeric antigen receptor T-cell therapy, and immune checkpoint inhibitors are limited in AML because of multiple mechanisms of leukemia immune escape. This has prompted a search for novel immunostimulatory approaches. Here, we show that activation of adenosine 5′-monophosphate–activated protein kinase (AMPK), a master regulator of cellular energy balance, by the small molecule GSK621 induces calreticulin (CALR) membrane exposure in murine and human AML cells. When CALR is exposed on the cell surface, it serves as a damage-associated molecular pattern that stimulates immune responses. We found that GSK621-treated murine leukemia cells promote the activation and maturation of bone marrow–derived dendritic cells. Moreover, vaccination with GSK621-treated leukemia cells had a protective effect in syngeneic immunocompetent recipients bearing transplanted AMLs. This effect was lost in recipients depleted of CD4/CD8 T cells. Together, these results demonstrate that AMPK activation by GSK621 elicits traits of immunogenic cell death and promotes a robust immune response against leukemia. Pharmacologic AMPK activation thus represents a new potential target for improving the activity of immunotherapy in AML.
Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy: a phase 2 study
Authors: Altman Jessica K. , Zuckerman Tsila , Koprivnikar Jamie , McCloskey James , Kota Vamsi , Keng Michael , Frankfurt Olga , Abaza Yasmin , Bixby Dale L. , Emadi Ashkan , Burch Micah , Bhatnagar Bhavana , Luger Selina M. , Percival Mary-Elizabeth , Wolach Ofir , Craig Michael , Ganzel Chezi , Roboz Gail , Levi Itai , Gourevitch Anna , Flaishon Liat , Tessler Shoshi , Blumberg Chen , Gengrinovitch Stela , Ben Yakar Ruth , Rowe Jacob M. 
Published: October 2023

Abstract
High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study of patients unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. The median age was 75 years; 60.6% of patients had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome, and 10.6% had therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents, and patients with TP53 mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range, 6-15.9) and was not reached among responders. Hematologic recovery was observed in all responding patients by day 26 without prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. These data suggest that aspacytarabine may be an effective regimen with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine. This trial was registered at www.clinicaltrials.gov as #NCT03435848.
Design of low-threshold photonic-crystal surface-emitting lasers with confined gain regions by using selective area intermixing
Authors: Chang Chia-Jui , Chen Lih-Ren , Hong Kuo-Bin , Lu Tien-Chang 
Published: October 2023

AbstractPhotonic-crystal surface-emitting lasers have many promising properties over traditional semiconductor lasers and are regarded as the next-generation laser sources. However, the minimum achievable lasing threshold of PCSELs is still several times larger than that of VCSELs, and limiting its applications especially if the required power is small. Here, we propose a new design that reduces the gain region in the lateral plane by using selective quantum-well intermixing to reduce the threshold current of PCSELs. By performing theoretical calculations, we confirmed that the threshold current can be lowered by a factor of two to three while keeping the PCSEL’s advantage of small divergence angle.
Picky with peakpicking: assessing chromatographic peak quality with simple metrics in metabolomics
Authors: Kumler William , Hazelton Bryna J. , Ingalls Anitra E. 
Published: October 2023

AbstractBackgroundChromatographic peakpicking continues to represent a significant bottleneck in automated LC–MS workflows. Uncontrolled false discovery rates and the lack of manually-calibrated quality metrics require researchers to visually evaluate individual peaks, requiring large amounts of time and breaking replicability. This problem is exacerbated in noisy environmental datasets and for novel separation methods such as hydrophilic interaction columns in metabolomics, creating a demand for a simple, intuitive, and robust metric of peak quality.ResultsHere, we manually labeled four HILIC oceanographic particulate metabolite datasets to assess the performance of individual peak quality metrics. We used these datasets to construct a predictive model calibrated to the likelihood that visual inspection by an MS expert would include a given mass feature in the downstream analysis. We implemented two novel peak quality metrics, a custom signal-to-noise metric and a test of similarity to a bell curve, both calculated from the raw data in the extracted ion chromatogram, and found that these outperformed existing measurements of peak quality. A simple logistic regression model built on two metrics reduced the fraction of false positives in the analysis from 70–80% down to 1–5% and showed minimal overfitting when applied to novel datasets. We then explored the implications of this quality thresholding on the conclusions obtained by the downstream analysis and found that while only 10% of the variance in the dataset could be explained by depth in the default output from the peakpicker, approximately 40% of the variance was explained when restricted to high-quality peaks alone.ConclusionsWe conclude that the poor performance of peakpicking algorithms significantly reduces the power of both univariate and multivariate statistical analyses to detect environmental differences. We demonstrate that simple models built on intuitive metrics and derived from the raw data are more robust and can outperform more complex models when applied to new data. Finally, we show that in properly curated datasets, depth is a major driver of variability in the marine microbial metabolome and identify several interesting metabolite trends for future investigation.
Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2
Authors: Campos-Ruíz Mario Aldair , Illades-Aguiar Berenice , Del Moral-Hernández Oscar , Romo-Castillo Mariana , Salazar-García Marcela , Espinoza-Rojo Mónica , Vences-Velázquez Amalia , Cortés-Sarabia Karen , Luna-Pineda Victor M. 
Published: October 2023

Abstract
Background
The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent immunogen that promotes the production of high-titer antibodies. N protein-derived peptides identified using a bioinformatics approach can potentially be used to develop a new generation of vaccines or diagnostic methods for detecting SARS-CoV-2 and its variants. However, further studies must demonstrate their capacity to be naturally processed by the immune system.

Objective
We aimed to examine the in vivo processing and recognition of in silico-identified peptides using the serum of immunized animals with the complete protein.

Methods
Recombinant N (Nrec) protein was subcutaneously administered to six Balb/c mice. Enzyme-linked immunosorbent assay (ELISA), western blotting, dot blotting, and immunoprecipitation were performed to evaluate the recognition of the complete protein and in silico-derived peptides.

Results
The serum of immunized mice recognized ~ 62.5 ng/µL of Nrec with high specificity to linear and conformational epitopes. Dot blot analysis showed that peptides Npep2 and Npep3 were the most reactive.

Conclusion
Our data confirm the high immunogenicity of the SARS-CoV-2 N protein and provide evidence on the antigenicity of two peptides located in the N-arm/RNA-binding domain (Npep2) and oligomerization domain/C-tail (Npep3), considered the biologically active site of the N protein.
Entomological longitudinal surveys in two contrasted eco-climatic settings in Cameroon reveal a high malaria transmission from Anopheles funestus associated with GSTe2 metabolic resistance
Authors: Natchema S. Fonkou Brice , Tchouakui Magellan , Menze Benjamin D. , Mugenzi Leon M. J. , Fofie Derrick , Nguiffo-Nguete Daniel , Nkengazong Lucia , Tombi Jeannette , Wondji Charles S. 
Published: October 2023

Abstract
Background
The impact of metabolic resistance to insecticides on malaria transmission remains poorly characterised notably through application of entomological parameters. The lack of resistance markers has been one of the limiting factors preventing a robust assessment of such impact. To this end, the present study sought to investigate how the L119F-Gste2 metabolic gene influences entomological parameters underpinning mosquitos’ propensity to transmit Plasmodium spp.

Methods
Longitudinal studies were carried out in Mibellon and Elende, two different eco-climatic settings in Cameroon and mosquitoes were collected using Human Landing Catch (HLC), Centre for Disease Control Light Trap (CDC-LT) and Pyrethrum Spray Catch (PSC) technics. Plasmodium sporozoite parasites were detected by TaqMan and Nested PCR, and blood meal origin by ELISA. The allele-specific PCR (AS-PCR) method was used to genotype the L119F-GSTe2 marker and association with malaria transmission was established by comparing key transmission parameters such as the Entomological Inoculation Rate (EIR) between individuals with different L119F-GSTe2 genotypes.

Results
An. funestus s.l was the predominant malaria vector collected during the entomological survey in both sites (86.6% and 96.4% in Elende and Mibellon, respectively) followed by An. gambiae s.l (7.5% and 2.4%, respectively). Sporozoite infection rates were very high in both collection sites (8.7% and 11% in Elende and Mibellon, respectively). An. funestus s.s exhibited a very high entomological inoculation rate (EIR) (66 ib/h/month and 792 ib/h/year) and was responsible for 98.6% of all malaria transmission events occurring in both sites. The Human Blood Index was also high in both locations (HBI = 94%). An. funestus s.s. mosquitoes with both 119 F/F (RR) and L119F (RS) genotypes had a significantly higher transmission intensity than their susceptible L/L119 (SS) counterparts (IRR = 2.2, 95%CI (1.1–5.2), p = 0.03; IRR = 2.5, 95% CI (1.2–5.8), p = 0.01 respectively).

Conclusion
This study highlights the major role that An. funestus s.s plays in malaria transmission in Cameroon with an aggravation from GSTe2-based metabolic resistance.
Reducing the rate of central line-associated bloodstream infections; a quality improvement project
Authors: Odada David , Munyi Hellen , Gatuiku Japhet , Thuku Ruth , Nyandigisi Jared , Wangui Anne , Ashihundu Emilie , Nyakiringa Beatrice , Kimeu Jemimah , Musumbi Martin , Adam Rodney D. 
Published: October 2023

Abstract
Background
The burden of central line-associated bloodstream infections is significant and has negative implications for healthcare, increasing morbidity and mortality risks, increasing inpatient hospital stays, and increasing the cost of hospitalization. Efforts to reduce the incidence of central line-associated bloodstream infections have utilized quality improvement projects that implement, measure, and monitor outcomes. However, variations in location, healthcare organization, patient risks, and practice gaps are key to the success of interventions and approaches. This study aims to evaluate interventions of a quality improvement project on the reduction of central line-associated bloodstream infection rates at a university teaching hospital.

Methods
This was a retrospective review of a quality improvement project that was implemented using the Plan-Do-Study-Act quality improvement cycle. Active surveillance of processes and outcomes was performed in the critical care areas; compliance to central line care bundles, and central line-associated bloodstream infections. Interrupted time series was used to analyze trends pre and post-intervention and regression modeling to estimate data segments preceding and succeeding the interventions.

Results
There were 350 central line insertions, 3912 catheter days, and 20 central line-associated bloodstream infection events during the intervention period. Compliance with central line care bundles was at 94%. There was a trend in the reduction of central line-associated bloodstream infections by 18% that did not reach statistical significance (p = 0.252).

Conclusions
Improvement projects to reduce central line-associated bloodstream infections face challenges and complexities associated with implementing interventions in real-world healthcare settings. There is a great need to continuously monitor, evaluate, readjust, and adapt interventions to achieve desired results, sustain improvements in patient outcomes, and investigate reasons for non-adherence as keys to achieving desired outcomes.
Prevalence and factors of urinary incontinence among postpartum: systematic review and meta-analysis
Authors: Dai Sidi , Chen Huating , Luo Taizhen 
Published: October 2023

Abstract
Background
Postpartum urinary incontinence substantially impacts the psychophysical well-being of women. The influencing factors contributing to postpartum urinary incontinence remain a subject of contention in clinical investigation. By elucidating the factors contributing to postpartum urinary incontinence, more efficacious interventions for laboring women can be devised. Consequently, this review endeavored to scrutinize the repercussions of maternal postpartum urinary incontinence to furnish empirical references for the clinical advancement of preventive strategies.

Method
The investigation employed bibliographic databases: Embase, PubMed, Web of Science, Cochrane Library, CBM, VIP, CNKI, and Wan Fang Data for article retrieval. A comprehensive consideration of all study designs was undertaken during the examination of the effects of postpartum urinary incontinence. The temporal limitation was set at all articles prior to February 2023. Studies incorporated laboring mothers experiencing normative labor and parturition. A total of 28,303 women were encompassed in the reviewed investigations.

Results
A total of 5,915 putative citations were identified, from which 32 articles were selected for evaluating the effects of postpartum urinary incontinence. Meta-analyses revealed that the incidence of postpartum urinary incontinence was 26% [95%CI: (21% ~ 30%)]. Twelve pivotal variables were identified to influence postpartum urinary incontinence: cesarean delivery, vaginal delivery, age ≥ 35 years, multiparty (number of deliveries ≥ 2), neonatal weight > 4 kg, perineal dystonia, antecedents of urological incontinence-related pathology, maternal pre-conception BMI ≥ 24 kg/m^2, perineal laceration, instrumental parturition, historical pelvic surgical procedures, and protracted second stage of labor. Among these, cesarean delivery was identified as a protective factor against postpartum urinary incontinence.

Conclusion
The study corroborated that anamnestic factors pertinent to urinary incontinence, vaginal parturitions, and neonates with a weight exceeding 4 kg serve as significant risk factors for postpartum urinary incontinence. Cesarean delivery emerged as a protective factor against postpartum urinary incontinence. Based on the prevalence of postpartum urinary incontinence, proactive intervention is requisite to mitigate the risk of postpartum urinary incontinence in postpartum women possessing these risk factors.

Trial registration
CRD42023412096.
First-line treatment with TKI plus brain radiotherapy versus TKI alone in EGFR-mutated non-small cell Lung cancer with brain metastases: a systematic review and meta-analysis
Authors: Song Yaowen , Lin Shuiyu , Chen Jun , Dang Jun 
Published: October 2023

Abstract
Background
It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone for EGFR-mutated non-small cell lung cancer with newly diagnosed brain metastases (BMs). Therefore, we performed a meta-analysis to address this issue.

Methods
We searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published until February 28, 2023. The primary outcomes of interest were overall survival (OS) and intracranial progression-free survival (iPFS), reported as hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
Twenty-four retrospective studies with 3184 patients were included. First- or second-generation EGFR-TKIs were used in each study. Upfront brain RT plus EGFR-TKIs significantly prolonged OS (HR = 0.75, 95% CI: 0.64–0.88) and iPFS (HR = 0.61, 95% CI: 0.52–0.72) compared to EGFR-TKIs alone. There were no significant differences in OS and iPFS benefits from the combination therapy between asymptomatic and symptomatic patients, patients with exon 19 and 21 mutations, patients with 1–3 and > 3 BMs, and males and females, respectively (HRs interaction, P > 0.05 for each subgroup comparison).

Conclusions
First-line treatment with upfront brain RT plus EGFR-TKIs is likely to be more effective than EGFR-TKIs alone. The benefits of combination therapy did not appear to be significantly affected by BM-related symptoms, EGFR mutation subtype, number of BMs, or sex.
Quality of antibiotic prescribing for pediatric community-acquired Pneumonia in outpatient care
Authors: Saatchi Ariana , Haverkate Manon R. , Reid Jennifer N. , Shariff Salimah Z. , Povitz Marcus , Patrick David M. , Silverman Michael , Morris Andrew M. , McCormack James , Marra Fawziah 
Published: October 2023

Abstract
Background
Antibiotics remain the primary treatment for community acquired pneumonia (CAP), however rising rates of antimicrobial resistance may jeopardize their future efficacy. With higher rates of disease reported in the youngest populations, effective treatment courses for pediatric pneumonia are of paramount importance. This study is the first to examine the quality of pediatric antibiotic use by agent, dose and duration.

Methods
A retrospective cohort study included all outpatient/primary care physician visits for pediatric CAP (aged < 19 years) between January 1 2014 to December 31 2018. Relevant practice guidelines were identified, and treatment recommendations extracted. Amoxicillin was the primary first-line agent for pediatric CAP. Categories of prescribing included: guideline adherent, effective but unnecessary (excess dose and/or duration), under treatment (insufficient dose and/or duration), and not recommended. Proportions of attributable-antibiotic use were examined by prescribing category, and then stratified by age and sex.

Result(s)
A total of 42,452 episodes of pediatric CAP were identified. Of those, 31,347 (76%) resulted in an antibiotic prescription. Amoxicillin accounted for 51% of all prescriptions. Overall, 27% of prescribing was fully guideline adherent, 19% effective but unnecessary, 10% under treatment, and 44% not recommended by agent. Excessive duration was the hallmark of effective but unnecessary prescribing (97%) Macrolides accounted for the majority on non-first line agent use, with only 32% of not recommended prescribing preceded by a previous course of antibiotics.

Conclusion(s)
This study is the first in Canada to examine prescribing quality for pediatric CAP by agent, dose and duration. Utilizing first-line agents, and shorter-course treatments are targets for stewardship.