bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usage and health perception of cannabidiol-containing products among the population in Germany: a descriptive study conducted in 2020 and 2021
Authors: Geppert Johanna , Lietzow Julika , Hessel-Pras Stefanie , Kirsch Fabian , Schäfer Bernd , Sachse Benjamin 
Published: November 2023

Abstract
Background
Cannabidiol (CBD), a non-intoxicating substance of Cannabis sativa L., is gaining consumer attention. Yet, legal regulations in the EU are complex and questions of potential health risks remain partly unanswered. In Germany, little is known about people who use CBD products. The aim of this cross-sectional study was to gain insight into the user group of CBD, reasons for consumption and risk perception towards CBD-containing products.

Methods
The study consisted of two parts: In the first part of the study, the prevalence of CBD awareness and usage in Germany was estimated using a telephone survey and a population-representative sample of n = 1,011 respondents. Based on these results, n = 2,000 participants being aware of CBD were surveyed with an online questionnaire in the second part of the study to examine usage and perception of CBD in users and non-users.

Results
When the study was conducted at the end of 2020 and beginning of 2021, 40.2% of the German participants had already heard of products containing CBD, and 11.4% had actually used them. 42.1% of the users consumed such products regularly, at least once a week, primarily orally via oils or tinctures, and purchased them mainly online. Besides curiosity – addressed especially in young adults – anticipated health benefits including pain and stress relief were main reasons for use. More than half of the study participants perceived the health benefits of CBD use as high or very high. In contrast, the health risks were rated as low or very low by most respondents. Assumptions about official testing for safety as well as physical effects of CBD-containing products varied between users and non-users.

Conclusion
About one in nine people in Germany uses CBD-containing products. Given reasons for consumption and perception of potential health risks and benefits suggest that people are insufficiently informed about CBD-containing products. The results of the study indicate that risk communication is needed to raise awareness for the topic and to inform (potential) users.
PILLAR: ParaspInaL muscLe segmentAtion pRoject - a comprehensive online resource to guide manual segmentation of paraspinal muscles from magnetic resonance imaging
Authors: Anstruther Meagan , Rossini Bianca , Zhang Tongwei , Liang Terrance , Xiao Yiming , Fortin Maryse 
Published: November 2023

Abstract
Background
There is an increasing interest in assessing paraspinal morphology and composition in relation to low back pain (LBP). However, variations in methods and segmentation protocols contribute to the inconsistent findings in the literature. We present an on-line resource, the ParaspInaL muscLe segmentAtion pRoject (PILLAR, https://projectpillar.github.io/), to provide a detailed description and visual guide of a segmentation protocol by using the publicly available ITK-SNAP software and discuss related challenges when performing paraspinal lumbar muscles segmentations from magnetic resonance imaging (MRI).

Methods
T2-weighted and corresponding fat-water IDEAL axial MRI from 3 males and 3 females (2 chronic LBP and 1 control for each sex) were used to demonstrate our segmentation protocol for each lumbar paraspinal muscle (erector spinae, lumbar multifidus, quadratus lumborum and psoas) and lumbar spinal level (L1-L5).

Results
Proper segmentation requires an understanding of the anatomy of paraspinal lumbar muscles and the variations in paraspinal muscle morphology and composition due to age, sex, and the presence of LBP or related spinal pathologies. Other challenges in segmentation includes the presence and variations of intramuscular and epimuscular fat, and side-to-side asymmetry.

Conclusion
The growing interest to assess the lumbar musculature and its role in the development and recurrence of LBP prompted the need for comprehensive and easy-to-follow resources, such as the PILLAR project to reduce inconsistencies in segmentation protocols. Standardizing manual muscle measurements from MRI will facilitate comparisons between studies while the field is progressively moving towards the automatization of paraspinal muscle measurements for large cohort studies.
“We usually see a lot of delay in terms of coming for or seeking care”: an expert consultation on COVID testing and care pathways in seven low- and middle-income countries
Authors: Bonnet Gabrielle , Bimba John , Chavula Chancy , Chifamba Harunavamwe N. , Divala Titus , Lescano Andres G. , Majam Mohammed , Mbo Danjuma , Suwantika Auliya A. , Tovar Marco A. , Yadav Pragya , Corbett Elisabeth L. , Vassall Anna , Jit Mark 
Published: November 2023

AbstractBackgroundRapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023.MethodsWe organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses.ResultsParticipants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab.ConclusionsTesting does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.
Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies
Authors: Fontvieille Emma , Viallon Vivian , Recalde Martina , Cordova Reynalda , Jansana Anna , Peruchet-Noray Laia , Lennon Hannah , Heath Alicia K. , Aune Dagfinn , Christakoudi Sofia , Katzke Verena , Kaaks Rudolf , Inan-Eroglu Elif , Schulze Matthias B. , Mellemkjær Lene , Tjønneland Anne , Overvad Kim , Farràs Marta , Petrova Dafina , Amiano Pilar , Chirlaque María-Dolores , Moreno-Iribas Conchi , Tin Tin Sandar , Masala Giovanna , Sieri Sabina , Ricceri Fulvio , Panico Salvatore , May Anne M. , Monninkhof Evelyn M. , Weiderpass Elisabete , Gunter Marc J. , Ferrari Pietro , Freisling Heinz 
Published: November 2023

Abstract
Background
Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer.

Methods
This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI).

Results
In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09–0.47).

Conclusions
Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.
Integrated single-cell and bulk RNA sequencing analysis identifies a neoadjuvant chemotherapy-related gene signature for predicting survival and therapy in breast cancer
Authors: Zhang Xiaojun , Feng Ran , Guo Junbin , Pan Lihui , Yao Yarong , Gao Jinnan 
Published: November 2023

AbstractNeoadjuvant chemotherapy (NAC) is a well-established treatment modality for locally advanced breast cancer (BC). However, it can also result in severe toxicities while controlling tumors. Therefore, reliable predictive biomarkers are urgently needed to objectively and accurately predict NAC response. In this study, we integrated single-cell and bulk RNA-seq data to identify nine genes associated with the prognostic response to NAC: NDRG1, CXCL14, HOXB2, NAT1, EVL, FBP1, MAGED2, AR and CIRBP. Furthermore, we constructed a prognostic risk model specifically linked to NAC. The clinical independence and generalizability of this model were effectively demonstrated. Additionally, we explore the underlying cancer hallmarks and microenvironment features of this NAC response-related risk score, and further assess the potential impact of risk score on drug response. In summary, our study constructed and validated a nine-gene signature associated with NAC prognosis, which was accomplished through the integration of single-cell and bulk RNA data. The results of our study are of crucial significance in the prediction of the efficacy of NAC in BC, and may have implications for the clinical management of this disease.
CDK5: an oncogene or an anti-oncogene: location location location
Authors: Nikhil Kumar , Shah Kavita 
Published: November 2023

AbstractRecent studies have uncovered various physiological functions of CDK5 in many nonneuronal tissues. Upregulation of CDK5 and/or its activator p35 in neurons promotes healthy neuronal functions, but their overexpression in nonneuronal tissues is causally linked to cancer of many origins. This review focuses on the molecular mechanisms by which CDK5 recruits diverse tissue-specific substrates to elicit distinct phenotypes in sixteen different human cancers. The emerging theme suggests that CDK5’s role as an oncogene or anti-oncogene depends upon its subcellular localization. CDK5 mostly acts as an oncogene, but in gastric cancer, it is a tumor suppressor due to its unique nuclear localization. This indicates that CDK5’s access to certain nuclear substrates converts it into an anti-oncogenic kinase. While acting as a bonafide oncogene, CDK5 also activates a few cancer-suppressive pathways in some cancers, presumably due to the mislocalization of nuclear substrates in the cytoplasm. Therefore, directing CDK5 to the nucleus or exporting tumor-suppressive nuclear substrates to the cytoplasm may be promising approaches to combat CDK5-induced oncogenicity, analogous to neurotoxicity triggered by nuclear CDK5. Furthermore, while p35 overexpression is oncogenic, hyperactivation of CDK5 by inducing p25 formation results in apoptosis, which could be exploited to selectively kill cancer cells by dialing up CDK5 activity, instead of inhibiting it. CDK5 thus acts as a molecular rheostat, with different activity levels eliciting distinct functional outcomes. Finally, as CDK5’s role is defined by its substrates, targeting them individually or in conjunction with CDK5 should create potentially valuable new clinical opportunities.
Implications of TDP-43 in non-neuronal systems
Authors: Ke Hao , Liu Kang , Jiao Baowei , Zhao Limin 
Published: November 2023

AbstractTAR DNA-binding protein 43 (TDP-43) is a versatile RNA/DNA-binding protein with multifaceted processes. While TDP-43 has been extensively studied in the context of degenerative diseases, recent evidence has also highlighted its crucial involvement in diverse life processes beyond neurodegeneration. Here, we mainly reviewed the function of TDP-43 in non-neurodegenerative physiological and pathological processes, including spermatogenesis, embryonic development, mammary gland development, tumor formation, and viral infection, highlighting its importance as a key regulatory factor for the maintenance of normal functions throughout life. TDP-43 exhibits diverse and sometimes opposite functionality across different cell types through various mechanisms, and its roles can shift at distinct stages within the same biological system. Consequently, TDP-43 operates in both a context-dependent and a stage-specific manner in response to a variety of internal and external stimuli.
Complement factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis
Authors: Jia Yimeng , Feng Bin , Ji Xin , Tian Xinping , Zhao Lidan , Zhou Jiaxin , Zhang Wen , Li Mengtao , Fei Yunyun , Wu Xunyao 
Published: November 2023

Abstract
Objective
To explore the role and underlying mechanism of Complement Factor H (CFH) in the peripheral and joint inflammation of RA patients.

Methods
The levels of CFH in the serum and synovial fluid were determined by ELISA. The pyroptosis of monocytes was determined by western blotting and flow cytometry. The inflammation cytokine release was tested by ELISA. The cell migration and invasion ability of fibroblast-like synoviocytes (FLS) were tested by Wound healing Assay and transwell assay, respectively. The potential target of CFH was identified by RNA sequencing.

Results
CFH levels were significantly elevated in the serum and synovial fluid from RA and associated with high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS28). TNF-α could inhibit CFH expression, and CFH combined with TNF-α significantly decreased cell death, cleaved-caspase 3, gasdermin E N-terminal (GSDME-N), and inflammatory cytokines release (IL-1β and IL-6) of RA-derived monocytes. Stimulated with TNF-α increased CFH levels in RA FLS and CFH inhibits the migration, invasion, and TNF-α–induced production of inflammatory mediators, including proinflammatory cytokines (IL-6, IL-8) as well as matrix metalloproteinases (MMPs, MMP1 and MMP3) of RA FLSs. The RNA-seq results showed that CFH treatment induced upregulation of eukaryotic translation initiation factor 3 (EIF3C) in both RA monocytes and FLS. The migration of RA FLSs was promoted and the expressions of IL-6, IL-8, and MMP-3 were enhanced upon EIF3C knockdown under the stimulation of CFH combined with TNF-α.

Conclusion
In conclusion, we have unfolded the anti-inflammatory roles of CFH in the peripheral and joints of RA, which might provide a potential therapeutic target for RA patients.
Impact of anakinra use on clinical outcomes in children with moderate or severe multisystem inflammatory syndrome in children: a propensity score matched retrospective cohort study
Authors: Akkoyun Esra B. , Most Zachary , Katragadda Harita , Yu Andrew , Nassi Lorien , Oakman Nicole , Ginsburg Sarah , Maamari Mia 
Published: November 2023

Abstract
Background
The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C.

Methods
We included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher’s exact tests.

Results
Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS.

Conclusions
In patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.
Is it possible to extend the dose interval of canakinumab treatment in children with familial Mediterranean fever? PeRA group experience
Authors: Kavrul Kayaalp Gülşah , Çağlayan Şengül , Demirkan Fatma Gül , Guliyeva Vafa , Otar Yener Gülçin , Öztürk Kübra , Demir Ferhat , Özdel Semanur , Çakan Mustafa , Sönmez Hafize Emine , Sözeri Betül , Aktay Ayaz Nuray 
Published: November 2023

Abstract
Background
There is no clear data on the optimal duration of treatment with anti-interleukin-1 drugs in colchicine-resistant familial Mediterranean fever patients, as well as on the dose interval. This study aimed to assess patients whose canakinumab dose interval was adjusted according to a specific protocol, with the objective of evaluating the effectiveness of implementing this protocol for the patient care.

Methods
The files of 45 patients whose canakinumab treatment interval was opened with a standard protocol previously determined by the Delphi method were retrospectively reviewed.

Results
Canakinumab treatment was initiated once a month for all patients. In the sixth month of canakinumab treatment, a dose interval extension was introduced; however, 7 patients (15.5%) experienced an attack, and consequently, no further interval extension was administered to them. For 29 patients, the dose interval was successfully extended to once every three months, as they remained attack-free for a year after the first interval extension. Nine patients continued receiving the drug every 2 months, as they had not yet completed one year since the first extension. The study found no significant correlation between experiencing an attack during the dose interval extension protocol and the number, duration of attacks, or autoinflammatory diseases activity index score.

Conclusion
Extending treatment intervals with canakinumab in colchicine-resistant familial Mediterranean fever shows promise for favorable outcomes.
Mendelian randomization studies of depression: evidence, opportunities, and challenges
Authors: Ma Wang-ran , Zhang Lei-lei , Ma Jing-ying , Yu Fang , Hou Ya-qing , Feng Xiang-rui , Yang Lin 
Published: November 2023

Abstract
Background
Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches.

Methods
In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions.

Results
We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially.

Conclusions
While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.