bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to the Diabetes Risk Reduction Diet and Bladder Cancer Risk in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cohort
Authors: Chen Yuanhao , Zeng Song , Jiao Binbin , Zhang He , Li Gao , Zhang Xin , Hu Xiaopeng 
Published: September 2023

Abstract

Background:
This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort.

Methods:
Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire.

Results:
During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53–0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64–0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64–0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics.

Conclusions:
This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer.

Impact:
The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.
Sex‐Specific Comparison Between Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict New‐Onset Hypertension in Middle‐Aged and Older Adults
Authors: Lee Joo Hyung , Heo Seok‐Jae , Kwon Yu‐Jin 
Published: September 2023

Background
Triglyceride and glucose (TyG) index and TyG‐related indices combined with obesity‐related markers are considered important markers of insulin resistance. We aimed to examine the association between the TyG index and modified TyG indices with new‐onset hypertension and their predictive ability stratified by sex.

Methods and Results
We analyzed data from 5414 Korean Genome and Epidemiology Study participants aged 40 to 69 years. Multiple Cox proportional hazard regression analyses were conducted to estimate the hazard ratio (HR) and 95% CI for new‐onset hypertension according to sex‐specific tertile groups after confounder adjustments. To evaluate the predictive performance of these indices for new‐onset hypertension, we calculated Harrell's C‐index (95% CI). Over a 9.5‐year follow‐up period, 1014 men and 1012 women developed new‐onset hypertension. Compared with the lowest tertile (T) group, the adjusted HR and 95% CI for new‐onset hypertension in T3 for TyG, TyG‐body mass index, TyG‐waist circumference, and TyG‐waist‐to‐height ratio were 1.16 (0.95–1.40), 1.11 (0.84–1.48), 1.77 (1.38–2.27), and 1.68 (1.33–2.13) in men and 1.37 (1.13–1.66), 1.55 (1.16–2.06), 1.43 (1.15–1.79), and 1.64 (1.30–2.07) in women, respectively. The C‐indices of TyG‐waist‐to‐height ratio for new‐onset hypertension were significantly higher than those of TyG and TyG‐body mass index in both men and women.

Conclusions
TyG and TyG‐body mass index were significantly associated with new‐onset hypertension only in women. TyG‐waist circumference and TyG‐waist‐to‐height ratio were significantly associated with new‐onset hypertension in both men and women. A sex‐specific approach is required when using TyG and modified TyG indices to identify individuals at risk of incident hypertension.
Reinvigorating the Nineteenth Century Scientific Method: A Peirce-pective on Science
Authors: Pietarinen Ahti-Veikko , Beni Majid D. 
Published: September 2023

Abstract
This paper proposes to recover the topic of the philosophy of scientific method from its late nineteenth-century roots. The subject matter of scientific method sprouted from key inferential ingredients identified by Charles Peirce. In this paper, the historical path is traversed from the viewpoint of contemporary Cognitive Structural Realism (CSR). Peirce’s semiotic theory of methods and practices of scientific inquiry prefigured CSR’s reliance on embodied informational structures and experimentation upon forms of relations that model generic scientific domains. Three results are shown to follow from this convocation: (i) a naturalization of Peirce’s interconnected abductive, deductive and inductive stages of the logic of science, here characterized de novo in terms of CSR. (ii) a perspective to scientific modeling that incorporates processes of abstraction and generalization as originated from Peirce’s logic of science, and (iii) diagrammatic reasoning as a pivotal method in analyzing scientific reasoning in experimental practices.
Toevallige ontmoetingen
Authors: Hens Kristien 
Published: September 2023

In dit rigoureuze en noodzakelijke boek brengt Kristien Hens bio-ethiek en filosofie van de biologie bij elkaar, met het argument dat het ethisch noodzakelijk is om in het wetenschappelijk onderzoek een plaatsje vrij te houden voor de filosofen. Hun rol is behalve ethisch ook conceptueel: zij kunnen de kwaliteit en de coherentie van het wetenschappelijk onderzoek verbeteren door erop toe te zien dat specifieke concepten op een consistente en doordachte manier worden gebruik binnen interdisciplinaire projecten. Hens argumenteert dat toeval en onzekerheid een centrale rol spelen in de bio-ethiek, maar dat die in een spanningsrelatie kunnen raken met de pogingen om bepaalde theorieën ingang te doen vinden als wetenschappelijke kennis: bij het beschrijven van organismen en praktijken creëren we op een bepaalde manier de wereld. Hens stelt dat dit noodzakelijk een ethische activiteit betreft.
Doorheen de verkenning van genetisch onderzoek, biomedische ethiek, autismeonderzoek en het concept ‘risico’ toont Hens aan dat er niet zoiets bestaat als ‘universeel’ of ‘neutraal’ wetenschappelijk of klinisch weten. Integendeel, uitgaan van de gesitueerdheid van individuele ervaringen is essentieel om de wereld rondom ons te begrijpen, om er de beperkingen van in te zien (en die van onszelf) en om een ethische toekomst vorm te geven.
Toevallige ontmoetingen is gericht op een breed publiek van geïnteresseerden in bio-ethiek, filosofie, antropologie en sociologie, en op onderzoekers in biomedische en milieuwetenschappen. Daarnaast is het ook relevant voor beleidsmakers. De artistieke bijdrage van Christina Stadlbauer en Bartaku zal inspirerend zijn voor kunstenaars en schrijvers die zich op het snijvlak bewegen van kunst en wetenschappen.
European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention—part 2: flunarizine
Authors: Deligianni Christina I. , Sacco Simona , Ekizoglu Esme , Uluduz Derya , Gil-Gouveia Raquel , MaassenVanDenBrink Antoinette , Ornello Raffaele , Sanchez-del-Rio Margarita , Reuter Uwe , Versijpt Jan , de Vries Tessa , Hussain Muizz , Zeraatkar Dena , Lampl Christian 
Published: September 2023

Abstract
Objective
Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.

Methods
A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo–controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation.

Results
Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06).

Conclusions
Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large‐scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.
Efficacy and safety of intranasal agents for the acute treatment of migraine: a systematic review and network meta-analysis
Authors: Li Guanglu , Duan Shaojie , Zhu Tiantian , Ren Zhiying , Xia Hui , Wang Ziyao , Liu Lei , Liu Zunjing 
Published: September 2023

Abstract
Background
Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients.

Methods
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results
Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model.

Conclusions
Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects.
Genome sequencing-based transcriptomic analysis reveals novel genes in Peucedanum praeruptorum
Authors: Song Cheng , Zhang Yingyu , Zhang Yunpeng , Yi Shanyong , Pan Haoyu , Liao Ranran , Wang Yuanyuan , Han Bangxing 
Published: September 2023

Abstract
Background
Peucedanum praeruptorum Dunn, a traditional Chinese herbal medicine, contains coumarin and volatile oil components that have clinical application value. However, early bolting often occurs in the medicinal materials of Apiaceae plants. The rhizomes of the medicinal parts are gradually lignified after bolting, resulting in a sharp decrease in the content of coumarins. At present, the link between coumarin biosynthesis and early bolting in P. praeruptorum has not been elucidated.

Results
Combining the genome sequencing and the previous transcriptome sequencing results, we reanalyzed the differential transcripts of P. praeruptorum before and after bolting. A total of 62,088 new transcripts were identified, of which 31,500 were unknown transcripts. Functional classification and annotation showed that many genes were involved in the regulation of transcription, defense response, and carbohydrate metabolic processes. The main domains are the pentatricopeptide repeat, protein kinase, RNA recognition motif, leucine-rich repeat, and ankyrin repeat domains, indicating their pivotal roles in protein modification and signal transduction. Gene structure analysis showed that skipped exon (SE) was the most dominant alternative splicing, followed by the alternative 3’ splice site (A3SS) and the alternative 5’ splice site (A5SS). Functional enrichment of differentially expressed genes showed that these differentially expressed genes mainly include transmembrane transporters, channel proteins, DNA-binding proteins, polysaccharide-binding proteins, etc. In addition, genes involved in peroxisome, hexose phosphate pathway, phosphatidylinositol signaling system, and inositol phosphate metabolism pathway were greatly enriched. A protein-protein interaction network analysis discoverd 1,457 pairs of proteins that interact with each other. The expression levels of six UbiA genes, three UGT genes, and four OMT genes were higher during the bolting stage. This observation suggests their potential involvement in the catalytic processes of prenylation, glycosylation, and methylation of coumarins, respectively. A total of 100 peroxidase (PRX) genes were identified being involved in lignin polymerization, but only nine PRX genes were highly expressed at the bolting stage. It is worth noting that 73 autophagy-related genes (ATGs) were first identified from the KEGG pathway-enriched genes. Some ATGs, such as BHQH00009837, BHQH00013830, and novel8944, had higher expression levels after bolting.

Conclusions
Comparative transcriptome analysis and large-scale genome screening provide guidance and new opinions for the identification of bolting-related genes in P. praeruptorum.
Effect of ammonium stress on phosphorus solubilization of a novel marine mangrove microorganism Bacillus aryabhattai NM1-A2 as revealed by integrated omics analysis
Authors: Lu Zhaomei , He Sheng , Kashif Muhammad , Zhang Zufan , Mo Shuming , Su Guijiao , Du Linfang , Jiang Chengjian 
Published: September 2023

Abstract
Background
Phosphorus is one of the essential nutrients for plant growth. Phosphate-solubilizing microorganisms (PSMs) can alleviate available P deficiency and enhance plant growth in an eco-friendly way. Although ammonium toxicity is widespread, there is little understanding about the effect of ammonium stress on phosphorus solubilization (PS) of PSMs.

Results
In this study, seven PSMs were isolated from mangrove sediments. The soluble phosphate concentration in culture supernatant of Bacillus aryabhattai NM1-A2 reached a maximum of 196.96 mg/L at 250 mM (NH4)2SO4. Whole-genome analysis showed that B. aryabhattai NM1-A2 contained various genes related to ammonium transporter (amt), ammonium assimilation (i.e., gdhA, gltB, and gltD), organic acid synthesis (i.e., ackA, fdhD, and idh), and phosphate transport (i.e., pstB and pstS). Transcriptome data showed that the expression levels of amt, gltB, gltD, ackA and idh were downregulated, while gdhA and fdhD were upregulated. The inhibition of ammonium transporter and glutamine synthetase/glutamate synthase (GS/GOGAT) pathway contributed to reducing energy loss. For ammonium assimilation under ammonium stress, accompanied by protons efflux, the glutamate dehydrogenase pathway was the main approach. More 2-oxoglutarate (2-OG) was induced to provide abundant carbon skeletons. The downregulation of formate dehydrogenase and high glycolytic rate resulted in the accumulation of formic acid and acetic acid, which played key roles in PS under ammonium stress.

Conclusions
The accumulation of 2-OG and the inhibition of GS/GOGAT pathway played a key role in ammonium detoxification. The secretion of protons, formic acid and acetic acid was related to PS. Our work provides new insights into the PS mechanism, which will provide theoretical guidance for the application of PSMs.
In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study
Authors: Thietart Sara , Rozes Antoine , Tubach Florence , Marot Stéphane , Marcelin Anne-Geneviève , Raux Mathieu , Vallet Hélène , Riou Bruno , Boddaert Jacques , Zerah Lorène 
Published: September 2023

Abstract
Background
Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19.

Methods
This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group’s data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type.

Results
Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79–90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21–1.66] and 1.56 [95%CI 1.33–1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants.

Conclusions
Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as “milder” but not “mild”. This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.
Orthogeriatric co-managements lower early mortality in long-lived elderly hip fracture: a post-hoc analysis of a prospective study
Authors: Gao Feng , Liu Gang , Ge Yufeng , Tan Zhelun , Chen Yimin , Peng Weidong , Zhang Jing , Zhang Xinyi , He Jiusheng , Wen Liangyuan , Wang Xianhai , Shi Zongxin , Hu Sanbao , Sun Fengpo , Gong Zishun , Sun Mingyao , Tian Maoyi , Zhu Shiwen , Yang Minghui , Wu Xinbao 
Published: September 2023

Abstract
Objective
To evaluate the clinical effectiveness of orthogeriatric co-management care in long-lived elderly hip fracture patients (age ≥ 90).

Methods
Secondary analysis was conducted in long-lived hip fracture patients between 2018 to 2019 in 6 hospitals in Beijing, China. Patients were divided into the orthogeriatric co-management group (CM group) and traditional consultation mode group (TC group) depending on the management mode. With 30-day mortality as the primary outcome, multivariate regression analyses were performed after adjusting for potential covariates. 30-day mobility and quality of life were compared between groups.

Results
A total of 233 patients were included, 223 of whom completed follow-up (125 in CM group, 98 in TC group). The average age was 92.4 ± 2.5 years old (range 90–102). The 30-day mortality in CM group was significantly lower than that in TC group after adjustments for (2.4% vs. 10.2%; OR = 0.231; 95% CI 0.059 ~ 0.896; P = 0.034). The proportion of patients undergoing surgery and surgery performed within 48 h also favored the CM group (97.6% vs. 85.7%, P = 0.002; 74.4% vs. 24.5%, P < 0.001; respectively). In addition, much more patients in CM group could walk with or without aids in postoperative 30 days than in the TC group (87.7% vs. 60.2%, P < 0.05), although differences were not found after 1-year follow-up. And there was no significant difference in total cost between the two groups (P > 0.05).

Conclusions
For long-lived elderly hip fracture patients, orthogeriatric co-management care lowered early mortality, improved early mobility and compared with the traditional consultation mode.
Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study
Authors: Guillot Pauline , Delamaire Flora , Gacouin Arnaud , Painvin Benoit , Piau Caroline , Reizine Florian , Lesouhaitier Mathieu , Tadié Jean-Marc , Maamar Adel 
Published: September 2023

Abstract
Background
Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT).

Methods
We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality.

Results
Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis.

Conclusion
Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.