bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE
Authors: Yamada Norikazu , Fu Weiguo , Shi Zhenyu , Park Ki-Hyuk , Kim Hyo-Soo , Dai Xiangchen , Lensing Anthonie WA , Pap Akos F , Kohno Tomoko , Tajima Tsubasa , Watakabe Tadashi , Mitsumori Tomoyuki 
Published: June 2024

Abstract
Background
Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented.

Methods
Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6–12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles.

Results
367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding.

Conclusions
Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions.

Trial registration
NCT00439725 and NCT02064439.
The COVID-19 pandemic and the use of benzodiazepines and benzodiazepine-related drugs in Estonia: an interrupted time-series analysis
Authors: Kurvits Katrin , Toompere Karolin , Jaanson Peeter , Uusküla Anneli 
Published: June 2024

Abstract
Background
The COVID-19 pandemic has posed challenges that worsened people’s mental health. We explored the impact of the COVID-19 pandemic on the mental well-being of the population, as indicated by the prevalence rates of benzodiazepine and benzodiazepine-related drug (BDZ) use.

Methods
This population‐based, time‐series analysis included all prescriptions of BDZs dispensed in Estonia between 2012 and 2021. The monthly prevalence rates of BDZ use were calculated. Autoregressive integrated moving average models with pulse and slope intervention functions tested for temporary and long-term changes in monthly prevalence rates after the onset of the COVID-19 pandemic.

Results
Throughout the 10-year study period, a total of 5,528,911 BDZ prescriptions were dispensed to 397,436 individuals. A significant temporary increase in the overall prevalence rate of BDZ use in March 2020 (2.698 users per 1000, 95% CI 1.408–3.988) was observed, but there was no statistically significant long-term change. This temporary increase affected all the examined subgroups, except for new users, individuals aged 15–29 years, and prescribing specialists other than general practitioners and psychiatrists. The long-term increase in BDZ use was confined to females aged 15–29 years (0.056 users per 1000 per month, 95% CI 0.033–0.079), while no significant change was observed among males of the same age (0.009 users per 1000 per month, 95% CI – 0.017 to 0.035). Among females aged 15–29 years, a significant long-term increase in BDZ use was observed for anxiety disorders (0.017 users per 1000 per month, 95% CI 0.010–0.023), depressive disorders (0.021 users per 1000 per month, 95% CI 0.012–0.030), and other mental and behavioral disorders (0.020 users per 1000 per month, 95% CI 0.010–0.030), but not for sleep disorders (– 0.008 users per 1000 per month, 95% CI – 0.018–0.002).

Conclusion
The COVID-19 pandemic led to a short-term increase in BDZ use immediately after the pandemic was declared. In the long term, young females experienced a sustained increase in BDZ use. The prolonged effect on girls and young women suggests their greater vulnerability. These results underscore the need to effectively address the long-term effects of the pandemic among youth.
DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues
Authors: Zhang Xiaohui , Zhao Xiaojing , Wang Jiapo , Zhang Yifang , Chen Jinhong 
Published: June 2024

Abstract
Introduction
Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate.

Methods
Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases.

Results
A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues.

Conclusions
These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.
First identification of Cytauxzoon manul in Eurasian lynx (Lynx lynx) in northwestern China
Authors: Cui Nannan , Su Lixin , Wang Ziqi , Hornok Sándor , Tang Lijuan , Yang Meihua , Zhang Yujiang , Zhao Guoyu , Wang Yuanzhi 
Published: June 2024

Abstract
Background
Multiple species of the genera Cytauxzoon and Hepatozoon can infect wild felines, but the diversity of these and other apicomplexan parasites in Eurasian lynx is scarcely known. The aim of this study was to detect Cytauxzoon and Hepatozoon species with molecular methods in Eurasian lynxes and their ticks in northwestern China.

Methods
DNA was extracted from the heart, liver, spleen, lung, and kidney samples of three Eurasian lynxes as well as from their five ixodid ticks. These DNA samples were screened with polymerase chain reactions (PCRs) for Cytauxzoon with the partial cytochrome b gene (CytB), cytochrome c oxidase subunit I gene (COI), and small subunit ribosomal RNA gene (18S rRNA), and Hepatozoon with three different fragments of small subunit ribosomal RNA gene (18S rRNA). PCR products were sequenced, aligned, and phylogenetically analyzed.

Results
One adult female of Eurasian lynx (#1, adult female) was co-infected with Cytauxzoon manul and Hepatozoon felis genotype I, while an adult male lynx (#2) was infected with C. manul. Interestingly, H. felis genotype I was both detected in a male cub (#3) and two out of five infesting Hyalomma asiaticum ticks.

Conclusions
For the first time, Cytauxzoon manul is reported here from Eurasian lynx. In addition, H. felis has not been known to occur in this host species in China and Central Asia. Thus, the findings of this study extend our knowledge on the geographical distribution and host range of these haemoprotozoan parasites. Moreover, this is also the first evidence of C. manul and H. felis co-infection in Eurasian lynx.

Graphical Abstract
Epidemiology of sarcoptic mange in a geographically constrained insular red fox population
Authors: Wails Christy N. , Helmke Claire C. , Black Kathleen M. , Ramirez-Barrios Roger , Karpanty Sarah M. , Catlin Daniel H. , Fraser James D. 
Published: June 2024

Abstract
Background
Sarcoptic mange is a skin disease caused by the contagious ectoparasite Sarcoptes scabiei, capable of suppressing and extirpating wild canid populations. Starting in 2015, we observed a multi-year epizootic of sarcoptic mange affecting a red fox (Vulpes vulpes) population on Fire Island, NY, USA. We explored the ecological factors that contributed to the spread of sarcoptic mange and characterized the epizootic in a landscape where red foxes are geographically constrained.

Methods
We tested for the presence of S. scabiei DNA in skin samples collected from deceased red foxes with lesions visibly consistent with sarcoptic mange disease. We deployed 96–100 remote trail camera stations each year to capture red fox occurrences and used generalized linear mixed-effects models to assess the affects of red fox ecology, human and other wildlife activity, and island geography on the frequency of detecting diseased red foxes. We rated the extent of visual lesions in diseased individuals and mapped the severity and variability of the sarcoptic mange disease.

Results
Skin samples that we analyzed demonstrated 99.8% similarity to S. scabiei sequences in GenBank. Our top-ranked model (weight = 0.94) showed that diseased red foxes were detected more frequently close to roadways, close to territories of other diseased red foxes, away from human shelters, and in areas with more mammal activity. There was no evidence that detection rates in humans and their dogs or distance to the nearest red fox den explained the detection rates of diseased red foxes. Although detected infrequently, we observed the most severe signs of sarcoptic mange at the periphery of residential villages. The spread of visual signs of the disease was approximately 7.3 ha/week in 2015 and 12.1 ha/week in 2017.

Conclusions
We quantified two separate outbreaks of sarcoptic mange disease that occurred > 40 km apart and were separated by a year. Sarcoptic mange revealed an unfettered spread across the red fox population. The transmission of S. scabiei mites in this system was likely driven by red fox behaviors and contact between individuals, in line with previous studies. Sarcoptic mange is likely an important contributor to red fox population dynamics within barrier island systems.

Graphical Abstract
DNA methylation and stroke prognosis: an epigenome-wide association study
Authors: Jiménez-Balado Joan , Fernández-Pérez Isabel , Gallego-Fábrega Cristina , Lazcano Uxue , Soriano-Tárraga Carolina , Vallverdú-Prats Marta , Mola-Caminal Marina , Rey-Álvarez Lucía , Macias-Gómez Adrià , Suárez-Pérez Antoni , Giralt-Steinhauer Eva , Rodríguez-Campello Ana , Cuadrado-Godia Elisa , Ois Ángel , Esteller Manel , Roquer Jaume , Fernández-Cadenas Israel , Jiménez-Conde Jordi 
Published: June 2024

Abstract
Background and aims
Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.

Methods and results
To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10–5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs).
After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10–5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery = 1.54·10–6; p-valuereplication = 9.17·10–4; p-valuemeta-analysis = 6.39·10–9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10–9 in all cases).

Discussion
Patients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.
Cost-effectiveness of brentuximab vedotin compared with conventional chemotherapy for relapsed or refractory classic Hodgkin lymphoma in China
Authors: Xie Shitong , Sheng Yanan , Chuang Ling-Hsiang , Wu Jing 
Published: June 2024

Abstract
Background
Relapsed or refractory classic Hodgkin lymphoma (RRcHL) associates with poor prognosis and heavy disease burden to patients. This study evaluated the cost-effectiveness of brentuximab vedotin (BV) in comparison to conventional chemotherapy in patients with RRcHL, from a Chinese healthcare perspective.

Methods
The lifetime cost and quality adjusted life years (QALYs) were estimated through a partitioned survival model with three health states (progression free, post progression, and death). Two cohorts for each BV arm and chemotherapy arm were built, representing patients with and without transplant after BV or chemotherapy, respectively. Clinical parameters were retrieved from BV trials and the literature. Resource utilization data were mainly collected from local expert surveys and cost parameters were reflecting local unit prices. Utility values were sourced from the literature. A discount rate of 5% was employed according to the Chinese guideline. A series of deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness and uncertainty associated with the model.

Results
Results of the base case analysis showed that the incremental cost-effectiveness ratio (ICER) for BV versus chemotherapy was $2,867 (¥19,774). The main model driver was the superior progression-free and overall survival benefits of BV. The ICERs were relatively robust in a series of sensitivity analyses, all under a conventional decision threshold (1 time of Chinese per capita GDP). With this conventional threshold, the probability of BV being cost-effective was 100%.

Conclusions
Brentuximab vedotin can be considered a cost-effective treatment versus conventional chemotherapy in treating relapsed or refractory classic Hodgkin lymphoma in China.
Emotional intelligence, spiritual intelligence, depression and anxiety, and satisfaction with life among emerging adults in Israel and India: the impact of gender and individualism/collectivism
Authors: Walter Ofra , Kasler Jonathan , Routray Surekha 
Published: June 2024

AbstractMuch research has focused on how emotional and spiritual intelligences promote well-being and help combat mental health issues. This comparative study, which was conducted in Israel and India with emerging adults enrolled in higher education, explored the relationship of emotional intelligence, spiritual intelligence, anxiety and depression, and satisfaction with life. The results in Israel showed a positive correlation of emotional intelligence with satisfaction with life, but in India, only spiritual intelligence correlated positively with satisfaction with life. In both groups, female participants scored higher on all variables than male participants. We offer initial explanations for these results.
Trans-cyclooctene—a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs
Authors: Adhikari Karuna , Vanermen Maarten , Da Silva Gustavo , Van den Wyngaert Tim , Augustyns Koen , Elvas Filipe 
Published: June 2024

Abstract
Background
Trans-cyclooctenes (TCOs) are highly strained alkenes with remarkable reactivity towards tetrazines (Tzs) in inverse electron-demand Diels–Alder reactions. Since their discovery as bioorthogonal reaction partners, novel TCO derivatives have been developed to improve their reactivity, stability, and hydrophilicity, thus expanding their utility in diverse applications.

Main body
TCOs have garnered significant interest for their applications in biomedical settings. In chemical biology, TCOs serve as tools for bioconjugation, enabling the precise labeling and manipulation of biomolecules. Moreover, their role in nuclear medicine is substantial, with TCOs employed in the radiolabeling of peptides and other biomolecules. This has led to their utilization in pretargeted nuclear imaging and therapy, where they function as both bioorthogonal tags and radiotracers, facilitating targeted disease diagnosis and treatment. Beyond these applications, TCOs have been used in targeted cancer therapy through a "click-to-release" approach, in which they act as key components to selectively deliver therapeutic agents to cancer cells, thereby enhancing treatment efficacy while minimizing off-target effects. However, the search for a suitable TCO scaffold with an appropriate balance between stability and reactivity remains a challenge.

Conclusions
This review paper provides a comprehensive overview of the current state of knowledge regarding the synthesis of TCOs, and its challenges, and their development throughout the years. We describe their wide ranging applications as radiolabeled prosthetic groups for radiolabeling, as bioorthogonal tags for pretargeted imaging and therapy, and targeted drug delivery, with the aim of showcasing the versatility and potential of TCOs as valuable tools in advancing biomedical research and applications.
Assessing the effects of plant density and nitrogen on millet yield in Southern Niger using the CERES-millet model
Authors: Garba Maman , Kamara Alpha Y. , Mohamed Ali M. L. , Tofa Abdullahi I. , Mahamane Soulé A. , Salissou Hanarou , Kapran Balkissa I. , Abdoulaye Tahirou , Garba Ismail I. 
Published: June 2024

Abstract

Background
The dryland production environments in Niger Republic (Niger) generate variable crop production risks that reduce crop yields and increase regional food insecurity. Optimal combinations of crop varieties and management are needed to maximize crop water-limited yields in these environments.

Methods

In this study, we calibrated and validated the CERES-Millet model using data from field experiments. Seasonal analysis (1984–2020) was carried out in 18 selected sites across the three agroecological zones (AEZs) to test the effects of plant density and N fertilization on grain yield. The treatment included five different plant densities (1.5, 3, 6, 9, and 12 plants m
−2
) and four N rates (0, 20, 40, and 60 kg N ha
−1
). Three millet varieties (CHAKTI, HKP, and SOSAT-C88) were compared. Millet production risk was assessed at each AEZ using cumulative probability distribution graphs. The acceptable grain yield required to compensate for the minimum production cost of millet in Niger was set to 975 kg ha
−1
(75th percentile of the simulated data).

Results

The CERES-Millet model reasonably reproduced number of days to flowering (
d
-index > 0.50; RMSE < 2 days), number of days to maturity (
d-
index > 0.50; RMSE < 2 days), and grain yield
d-
index > 0.78; RMSE < 100 kg ha
−1
) for all the three varieties. The results showed that there was significant response to N (40 – 110% yield increase following N application) and plant density (30–80% yield increase by increasing density above 1.5 plants m
−2
) in all the AEZs depending on variety. The SOSAT was the most responsive variety to N application and plant density in all AEZs. Under low N application (0–20 kg ha
−1
) and low (1.5—3 plants m
−2
) to moderate plant density (6 plants m
−2
), CHAKTI and HKP had the highest production risks. Increasing N application above 20 kg ha
−1
mitigate these risks where grain yield was above the 975 kg ha
−1
threshold representing the minimum production cost for millet in more than 50% of the years under all plant densities except in Sahel where this threshold was only achieved in < 20% of the years. In all AEZs, increasing plant density above 6 plants m
−2
increases this risk under low to moderate N application, but the downside risk was mitigated when N was applied at high rates.

Conclusion
This study demonstrated N application rate and plant density recommendations must be tailored to specific variety and AEZs to maximize grain yield and reduce volatility in Niger.
Concurrent self-administered transcranial direct current stimulation and attention bias modification training in binge eating disorder: feasibility randomised sham-controlled trial
Authors: Flynn Michaela , Campbell Iain C. , Schmidt Ulrike 
Published: June 2024

Background
Binge eating disorder (BED) is a common and disabling condition, typically presenting with multiple psychiatric and obesity-related comorbidities. Evidence-based treatments are either resource-intensive (psychotherapies) or have side-effects (medications): these achieve remission in around 50% of cases. Novel treatments are needed.

Aims
This randomised sham-controlled trial aimed to assess feasibility, acceptability and preliminary efficacy of at-home, self-administered transcranial direct current stimulation (tDCS) and attention bias modification training (ABMT) in adults with binge eating disorder.

Method
Eighty-two participants with binge eating disorder were randomly allocated to real tDCS with ABMT, sham tDCS with ABMT, ABMT only or waitlist control. Intervention groups received ten sessions of their allocated treatment over 2–3 weeks. tDCS (2 mA, 20 min) was self-administered using a bilateral (anode right/cathode left) montage targeting the dorsolateral prefrontal cortex. Outcomes were assessed at baseline, post-treatment and 6-week follow-up.

Results
Prespecified feasibility criteria (recruitment ≥80 participants and retention rate ≥75%) were exceeded, and treatment completion rates were high (98.7%). All interventions reduced binge eating episodes, eating disorder symptoms and related psychopathology between baseline and follow-up, relative to waitlist control (medium-to-large between-group effect sizes for change scores). Small-to-medium effect sizes for change scores favoured real tDCS with ABMT versus comparators, suggesting the verum intervention produces superior outcomes.

Conclusions
At-home, self-administered tDCS with ABMT is feasible and acceptable, and preliminary data on efficacy are promising. This approach could be a useful and scalable alternative or adjunct to established treatments for binge eating disorder. Confirmatory trials can, and should, be pursued.