bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication patterns and potentially inappropriate medication in patients with metastatic breast cancer: results of the BRE-BY-MED study
Authors: Brandstetter Lilly Sophia , Grau Anna , Heuschmann Peter U. , Müller-Reiter Max , Salmen Jessica , Störk Stefan , Wöckel Achim , Reese Jens-Peter 
Published: January 2025

Abstract

Background
The treatment of metastatic breast cancer (mBC) focuses on prolonging patient survival, providing adequate symptom management, and maintaining quality of life (QoL). This includes supportive therapy to prevent or treat potential side effects and handle comorbidities. The combination of mBC therapy, supportive therapy, and treatment for comorbidities increases the risk for polypharmacy, potential drug-drug interactions (pDDI), potentially inappropriate medication (PIM), and potentially missing drugs (pMD). Therefore, the aim of this study was to assess medication patterns of mBC patients in routine care within a cohort study from South Germany.

Methods
Between July 2022 and February 2024 individuals with advanced or mBC, aged ≥ 18 years, living in Bavaria, and who gave written informed consent, were included in the BRE-BY-MED “Breast Cancer Care in Bavaria for Patients with Metastatic Disease” cohort study (DRKS00026601). BRE-BY-MED was carried out at the University Hospital Würzburg with the primary aim of estimating the prevalence of guideline-concordant treatment. For the present analysis cross-sectional data from the baseline assessment was used. Medication was extracted from routine medical records. PIM, pDDI and pMD were assessed using established criteria. Polypharmacy was defined as ≥ 5 concomitantly prescribed drugs.

Results
Ninety-three patients with a median age of 57 years (IQR = 48–64 years), were consecutively enrolled in the BRE-BY-MED study. One patient was male. At baseline, a total of 668 drugs were documented for all patients, including 131 unique substances, of which 44% were mBC therapy, 18% supportive therapy and 38% treatment for comorbidities or supplements. Patients took a median of 6 (IQR = 5–9) concomitant drugs. Polypharmacy (i.e. ≥ 5 concomitant drugs) was observed in 80.6% (n = 75) of the patients. PIM were documented in 9.7% (n = 9), pDDI in 12.9% (n = 12) and pMD in 64.5% (n = 60) of the patients.

Conclusion
We observed a high drug burden in mBC patients, largely due to treatment for comorbidities. These drugs might not only be associated with additional risk for side effects, pDDI, or PIM use, yet might also contribute to low medication adherence, higher medication costs and impaired QoL. Considering the burden of mBC and the predicted life expectancy, mBC patients might benefit from closer monitoring of their medication.
The risks of adverse events with mirtazapine for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis
Authors: Kamp Caroline Barkholt , Petersen Johanne Juul , Faltermeier Pascal , Juul Sophie , Sillassen Christina Dam Bjerregaard , Siddiqui Faiza , Andersen Rebecca Kjaer , Moncrieff Joanna , Horowitz Mark Abie , Hengartner Michael Pascal , Kirsch Irving , Gluud Christian , Jakobsen Janus Christian 
Published: January 2025

Abstract

Background
Mirtazapine is used to treat depression worldwide, and the effects of mirtazapine on depression rating scales are well-known. Our primary objective was to assess the risks of adverse events with mirtazapine for major depressive disorder.

Methods
We searched relevant sources from inception to 7 March 2024 for randomised clinical trials comparing mirtazapine versus placebo in adults with major depressive disorder. The primary outcomes were suicides or suicide attempts, serious adverse events, and non-serious adverse events. Data were synthesised using meta-analysis and Trial Sequential Analysis.

Results
We included 17 trials randomising 2,131 participants to mirtazapine versus placebo. All results were at high risk of bias, and the certainty of the evidence was very low. The included trials assessed outcomes at a maximum of 12 weeks after randomisation. Meta-analysis and Trial Sequential Analysis showed insufficient information to determine the effects of mirtazapine on the risks of suicides or suicide attempts and serious adverse events. Meta-analyses showed that mirtazapine increased the risks of somnolence, weight gain, dry mouth, dizziness, and increased appetite but decreased the risk of headaches.

Conclusions
There is a lack of evidence on the effects of mirtazapine on suicides and serious adverse events. Mirtazapine increases the risks of somnolence, weight gain, dry mouth, dizziness, and increased appetite. Mirtazapine might decrease the risk of headaches. The long-term effects of mirtazapine are unknown.

Prospero id
CRD42022315395.
Prevalence of complications and comorbidities associated with obesity: a health insurance claims analysis
Authors: Bae Jay P. , Nelson David R. , Boye Kristina S. , Mather Kieren J. 
Published: January 2025

Abstract

Background
Despite the substantial burden of obesity in the United States (US), data on the comprehensive range of comorbidities in different age groups is limited. This study assessed the prevalence of various comorbidities among people diagnosed with obesity (as per ICD-10 diagnosis code) across age cohorts and compared how they differ from people without obesity.

Methods
This cross-sectional study analyzed individuals from all four regions (Midwest, Northeast, South, and West) of the US who had continuous insurance coverage from 2018 to 2020, using a large health insurance claims database (Merative™ MarketScan®). Identification of disorders relied on ICD-10 diagnosis code in patient claims and their prevalence was calculated.

Results
Of 6,935,911 individuals, people with a diagnosis of obesity accounted for 22.0%, 33.6%, and 34.4% in the 18–39 years, 40–64 years, and ≥ 65 years age groups, respectively. Within age strata, the mean age of people with obesity was comparable with those without obesity. Comorbidity burden was significantly higher among people with obesity, but increased with age in both obesity and non-obesity groups. Comorbidities with highest prevalence in people with obesity included: (i) hypertension (18–39 years: 29.0%, 40–64 years: 66.2%, ≥ 65 years: 89.4%), (ii) dyslipidemia (18–39 years: 28.1%, 40–64 years: 65.4%, ≥ 65 years: 88.0%), (iii) depression or anxiety (18–39 years: 44.1%, 40–64 years: 39.0%, ≥ 65 years: 38.9%), and (iv) prediabetes (18–39 years: 17.1%, 40–64 years: 32.2%, ≥ 65 years: 35.3%). Notably, increased prevalence of cardiometabolic risk factors such as hypertension and dyslipidemia began at an earlier age in people with obesity as compared with those without obesity. Ratio of prevalence between obesity and non-obesity groups was highest for the 18–39 years age group, as compared to older groups. Disorders such as obstructive sleep apnea, osteoarthritis, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, coronary heart diseases (CHD), and chronic kidney diseases also exhibited substantial burden among those with obesity.

Conclusions
In this claims study, hypertension and dyslipidemia were the leading comorbidities in people with obesity, with an increasing prevalence with age. The burden of cardiometabolic comorbidities among the younger age group suggested potential risk for early onset of CHD in later life. Understanding the range of obesity-related comorbidities seen in this claims data may encourage healthcare professionals and healthcare systems to systematically diagnose and better manage these disorders. Further research using additional data sources can offer a more accurate view of the prevalence of obesity and its impact.
Epidemiologic trends of cleft lip and/or palate in Switzerland
Authors: Beyeler Joël , Lauener Anic , Katsaros Christos , La Scala Giorgio C. , Degen Martin 
Published: January 2025

Abstract

Background
Epidemiologic data on the number of cleft lip and/or palate (orofacial cleft (OFC)) births in Switzerland are currently sparse. However, this knowledge is essential for better understanding the etiologies underlying the various cleft phenotypes and providing expectant parents with the best possible healthcare planning and counseling.

Methods
This is the first descriptive study to report data on the prevalence of the various cleft types, their sex, and regional distributions in Switzerland. Data for the years 1998–2021 were obtained from the Swiss Federal Statistical Office. Due to the notable initial underreporting of cleft cases from 1998 to 2006, this period was omitted from the final analyses.

Results
Between 2007 and 2021, the prevalence of all Swiss OFC cases per 10,000 live births was 12.5, with a stable trend. Cleft lip was the least common anomaly. Except for cleft palate, which was more common in females, males were generally more affected by OFC than females. There was no discernible regional trend for any of the malformations, even though the prevalence differed throughout the seven Swiss regions.

Conclusions
This study presents the first descriptive epidemiologic profiles for OFCs in Switzerland and emphasizes the importance of nationwide OFC registries with an accurate and reliable reporting system for the benefit of current and future patients with clefts, their parents or caregivers, and society as a whole.
The proof is in the pudding: patient engagement in studying cannabidiol in mild cognitive impairment
Authors: Keck Antonia , Scheuermann Julia-Sophia , Scheerbaum Petra , Graessel Elmar , Müller-Vahl Kirsten R. 
Published: January 2025

Abstract

Background
Patient engagement (PE) in clinical trials has gained importance yet remains uncommon, particularly in patients with mild cognitive impairment (MCI), a critical precursor to Alzheimer’s disease (AD). Cannabidiol (CBD) shows potential in slowing MCI progression due to its neuroprotective and anti-inflammatory properties. In CBD research, PE is underutilized too. To design a study on CBD for MCI, we administered an online survey to individuals with MCI to better understand their preferences for trial setup and outcomes.

Methods
We asked 209 individuals with MCI to complete an online survey assessing (i) willingness to participate in a trial using CBD; (ii) importance of improvements in various domains; (iii) acceptance of adverse events (AEs); (iv) reasons for AE-related dropout; (v) willingness to undergo blood sampling and lumbar puncture to assess AD pathology; and (vi) willingness to participate in a trial with a 50% chance of receiving a placebo. Data were analyzed with descriptive statistics.

Results

N = 118 agreed to participate and N = 88 completed the survey. Participants prioritized improvement in cognitive abilities (87.5%), followed by quality of life (63.6%), daily activities (55.7%), sleep (55.7%), pain (52.3%), mood (52.3%), behavior (48.9%), and anxiety (43.2%). Headache (55.7%) was the least accepted AE followed by nausea (46.6%), fatigue (35.2%), and diarrhea (35.2%). Persistent diarrhea (90.9%) and severe fatigue (84.1%) were the main reasons for potential dropout. While most would undergo blood sampling (67.0%), only a minority (21.6%) would accept lumbar puncture. One-third were ready to participate (34.1%), while 54.5% were interested pending details. Among those in favor of participation, 71.6% would participate even with a 50% chance of placebo.

Conclusions
Our study identified cognitive improvement as highly relevant for patients, indicating cognitive assessment tools as primary endpoints in MCI research. Given concerns about AEs, dose titration should be carefully considered to enhance acceptance and prevent AEs. Blood sampling seems well-accepted for AD biomarker assessment. Despite potential AEs, participation in a trial using CBD for MCI is seen as attractive, even under placebo-controlled conditions. This cross-sectional study emphasizes the importance of patient engagement in designing high-quality trials for using CBD to treat MCI.
Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes
Authors: Almeida Miguel Vasconcelos , Blumer Moritz , Yuan Chengwei Ulrika , Sierra Pío , Price Jonathan L. , Quah Fu Xiang , Friman Aleksandr , Dallaire Alexandra , Vernaz Grégoire , Putman Audrey L. K. , Smith Alan M. , Joyce Domino A. , Butter Falk , Haase Astrid D. , Durbin Richard , Santos M. Emília , Miska Eric A. 
Published: January 2025

Abstract

Background
East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. We set out to bridge this gap and to understand the interactions between TEs and their cichlid hosts.

Results
Here, we describe dynamic patterns of TE expression in African cichlid gonads and during early development. Orthology inference revealed strong conservation of TE silencing factors in cichlids, and an expansion of piwil1 genes in Lake Malawi cichlids, likely driven by PiggyBac TEs. The expanded piwil1 copies have signatures of positive selection and retain amino acid residues essential for catalytic activity. Furthermore, the gonads of African cichlids express a Piwi-interacting RNA (piRNA) pathway that targets TEs. We define the genomic sites of piRNA production in African cichlids and find divergence in closely related species, in line with fast evolution of piRNA-producing loci.

Conclusions
Our findings suggest dynamic co-evolution of TEs and host silencing pathways in the African cichlid radiations. We propose that this co-evolution has contributed to cichlid genomic diversity.
Comparative analysis of NR and NiR gene families reveals nitrite formation mechanisms in two Toona species
Authors: Wei Yi , Dai Jianhua , Fan Yanru , Yin Hengfu , Liu Jun , Han Xiaojiao 
Published: January 2025

Abstract

Background

Toona sinensis and Toona ciliata both belong to the same genus in the Meliaceae family; however, the nitrate and nitrite contents in T. sinensis are significantly higher than those in T. ciliata. Given the growing emphasis on dietary health, it has become imperative to implement breeding strategies to reduce the excessive nitrite levels in T. sinensis. Nitrate reductase (NR) and nitrite reductase (NiR) are crucial enzymes in plant nitrogen metabolism. In this study, we employed a comparative analysis of the NR and NiR gene families in T. sinensis and T. ciliata. By integrating bioinformatics and expression pattern assessments, we aimed to elucidate the underlying factors contributing to the variance in nitrate and nitrite levels between these two species.

Results

T. sinensis exhibited higher nitrate and nitrite contents than T. ciliata. Through comprehensive genome-wide analysis, we identified two TsNRs and two TsNiRs in T. sinensis, compared to one TcNiR and two TcNiRs in T. ciliata, suggesting an expansion of NR members in T. sinensis relative to T. ciliata. The NR and NiR proteins in T. sinensis and T. ciliata share high sequence similarity and exhibit close genetic relationships with their counterparts in Populus trichocarpa and Salix purpurea. The exon–intron structures and conserved motifs of these genes were stringently conserved throughout evolutionary history. All the seven NR and NiR genes in both T. sinensis and T. ciliata harbor various cis-regulatory elements within their promoter sequences, which are associated with development, stress response, and hormonal regulation. Furthermore, the expression of TsNiR and TcNiR genes was also found to be tissue-specific. Among them, TcNR1 and TsNR2 exhibited the highest expression observed in mature leaves. Especially, the expression level of TsNR2 in mature leaves was 400-fold higher than in other tissues. In addition, transient overexpression of TsNiR1 and TsNiR2 in T. sinensis significantly reduced nitrite content.

Conclusions
The higher nitrite accumulation in T. sinensis compared to T. ciliata is attributed to its lower nitrite reductase activity, the expansion of the NR gene family, and the elevated expression of TsNR2 in the leaves.

Graphic Abstract
Implementation of national poultry improvement plan in poultry disease control in Africa: current perspectives, challenges, and prospects
Authors: Adesola Ridwan Olamilekan , Idris Ibrahim , Bakre Adetolase Azizat 
Published: January 2025

Abstract
Practical control of poultry diseases in Africa remains a considerable challenge, impacting food security, livelihoods, and public health. National Poultry Improvement Plan (NPIP) is a combined industry, state, and federal initiative to address specific poultry diseases. Implementing an NPIP offers Africa a promising disease management and prevention avenue. This article aims to evaluate the implementation status of the NPIP in diverse African countries, analyze the challenges faced in adopting and executing NPIP strategies within the continent’s poultry industry, and the prospects for enhancing poultry disease control efforts. This review provides more detailed information about the importance of NPIP in fortifying Africa’s poultry industry against diseases, ensuring food security, and driving economic growth. Collaboration among stakeholders, policymakers, and researchers is paramount to realize the full potential of the NPIP and pave the way for a healthier and more resilient poultry sector in Africa.
Can the monocyte/HDL ratio predict ear effusion in adenoid vegetation patients?
Authors: Kaya Çelik Elif , Öner Fatih 
Published: January 2025

Abstract

Background
Since monocytes secrete cytokines, high monocyte counts may indicate subclinical inflammation. HDL-C, a significant component of total cholesterol, may reduce inflammation.

Objectives
This study investigated whether the monocyte/HDL ratio (MHR) could be an independent predictive marker in patients with adenoid vegetation, both with and without otitis media with effusion (OME).

Methods
This cross-sectional study included patients diagnosed with adenoid vegetation, with or without OME, who underwent surgery. The groups consisted of patients who underwent adenoidectomy alone for adenoid vegetation and those who underwent adenoidectomy + ventilation tube for adenoid vegetation with OME (Group 2). Monocyte counts, HDL-C levels, and MHR values were calculated for both groups.

Results
The mean age of Group 1 was 6.95 ± 2.77 years, while Group 2 had a mean age of 6.61 ± 2.98 years. No significant difference was found in monocyte count or percentage between the groups. The HDL-C ratios were lower in Group 2, which OME accompanied, and the difference between the groups was significant (p: 0.027). The MHR was not significantly different between Groups 1 and 2, with values of 10.47 (4.22–29.23) and 12.29 (5.43–99.6), respectively.

Conclusion
Reduced MHR ratios may indicate elevated inflammatory levels in the body and may be linked to certain medical conditions. However, we found no significant difference in the parameters’ ability to predict OME in children with adenoid vegetation. Therefore, a simple, low-cost marker to predict middle ear effusion in children is needed.
Patterns of Preoperative Tumor Markers Can Predict Resectability and Prognosis of Peritoneal Metastases: A Clustering Analysis
Authors: Enblad Malin , Cashin Peter , Ghanipour Lana , Graf Wilhelm 
Published: January 2025

Abstract

Background
Prediction of open–close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open–close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).

Patients and Methods
All patients accepted for CRS and HIPEC for PMP or colorectal PM at Uppsala University Hospital in 2013–2021 were included. The tumor markers CEA, CA19-9, CA125, CA72-4, and CA15-3 were clustered using the k-means algorithm; the average silhouette width determined the optimal numbers of clusters.

Results
Clustering of patients with PMP (n = 138) and colorectal PM (n = 213) resulted in two clusters each. PMPCluster-1 (n = 124) had a 5-year overall survival (OS) of 77% (95% CI 69−85%), 11 (9%) open–close surgeries, and a median peritoneal cancer index (PCI) of 17. PMPCluster-2 (n = 14) patients had poorer prognosis (36%, 95% CI 15–85%, p = 0.003), more often open–close (n = 6, 43%, p = 0.002), and higher PCI (median 36, p < 0.001). ColorectalCluster-1 (n = 191) had a 5-year OS of 28% (95% CI 21–37%), median PCI of 11, and 38 (20%) open–close surgeries. ColorectalCluster-2 (n = 22) had poorer prognosis (10%, 95% CI 3–36%, p = 0.02), higher PCI (median 26, p < 0.001), higher completeness of cytoreduction score (p = 0.005), but no difference in open–close surgery (n = 6, 27%, p = 0.411). PMPCluster-2 and ColorectalCluster-2 were characterized by markedly elevated tumor markers. Open–close surgery was unusual in cases of normal CA72-4.

Conclusions
Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open–close. CA72-4 deserves increased attention.
Optimal Correlated Equilibria in General-Sum Extensive-Form Games: Fixed-Parameter Algorithms, Hardness, and Two-Sided Column-Generation
Authors: Zhang Brian Hu , Farina Gabriele , Celli Andrea , Sandholm Tuomas 
Published: January 2025

We study the problem of finding optimal correlated equilibria of various sorts in extensive-form games: normal-form coarse correlated equilibrium (NFCCE), extensive-form coarse correlated equilibrium (EFCCE), and extensive-form correlated equilibrium (EFCE). We make two primary contributions. First, we introduce a new algorithm for computing optimal equilibria in all three notions. Its runtime depends exponentially only on a parameter related to the information structure of the game. We also prove a fundamental complexity gap between NFCCE and the other two concepts. Second, we propose a two-sided column generation approach for use when the runtime or memory usage of the previous algorithm is prohibitive. Our algorithm improves upon an earlier one-sided approach by means of a new decomposition of correlated strategies which allows players to reoptimize their sequence-form strategies with respect to correlation plans which were previously added to the support. Experiments show that our techniques outperform the prior state of the art for computing optimal general-sum correlated equilibria. Funding: This work was supported by National Institutes of Health [Grant A240108S001]; Vannevar Bush Faculty Fellowship [Grant ONR N00014-23-1-2876]; National Science Foundation [Grants CCF-173355, IIS-190140, RI-1901403, RI-2312342]; and Army Research Office [Grants W911NF2010081, W911NF2210266].
Coordinate Partitioning for Difficult Euclidean Max-Sum Diversity Problems
Authors: Spiers Sandy , Bui Hoa T. , Loxton Ryan 
Published: January 2025

Divide and Conquer: Solving the Euclidean Diversity Problem Through Coordinate Partitioning A common technique for solving difficult optimization problems is to break them into easier-to-manage pieces, yet it is rarely obvious how to do so. This is especially true for the Euclidean max-sum diversity problem, which becomes increasingly difficult as the number of coordinates grows despite the problem size remaining the same. In “Coordinate Partitioning for Difficult Euclidean Max-Sum Diversity Problems,” Spiers, Bui, and Loxton use an old result by Schoenberg to transform Euclidean distances into their squared counterparts, enabling a functional decomposition of the problem’s objective. The authors introduce novel partitioning strategies as well as a globally convergent cutting-plane algorithm, which can effectively solve high-dimension instances. They also present a new class of challenging instances characterized by locations on the surface of a hyperball.