bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micro-DeMix: a mixture beta-multinomial model for investigating the heterogeneity of the stool microbiome compositions
Authors: Liu Ruoqian , Wang Yue , Cheng Dan 
Published: November 2024

Abstract

Motivation
Extensive research has uncovered the critical role of the human gut microbiome in various aspects of health, including metabolism, nutrition, physiology, and immune function. Fecal microbiota is often used as a proxy for understanding the gut microbiome, but it represents an aggregate view, overlooking spatial variations across different gastrointestinal (GI) locations. Emerging studies with spatial microbiome data collected from specific GI regions offer a unique opportunity to better understand the spatial composition of the stool microbiome.

Results
We introduce Micro-DeMix, a mixture beta-multinomial model that deconvolutes the fecal microbiome at the compositional level by integrating stool samples with spatial microbiome data. Micro-DeMix facilitates the comparison of microbial compositions across different GI regions within the stool microbiome through a hypothesis-testing framework. We demonstrate the effectiveness and efficiency of Micro-DeMix using multiple simulated datasets and the inflammatory bowel disease data from the NIH Integrative Human Microbiome Project.

Availability and implementation
The R package is available at https://github.com/liuruoqian/MicroDemix.
DrugRepPT: a deep pretraining and fine-tuning framework for drug repositioning based on drug’s expression perturbation and treatment effectiveness
Authors: Fan Shuyue , Yang Kuo , Lu Kezhi , Dong Xin , Li Xianan , Zhu Qiang , Li Shao , Zeng Jianyang , Zhou Xuezhong 
Published: November 2024

Abstract

Motivation
Drug repositioning (DR), identifying novel indications for approved drugs, is a cost-effective strategy in drug discovery. Despite numerous proposed DR models, integrating network-based features, differential gene expression, and chemical structures for high-performance DR remains challenging.

Results
We propose a comprehensive deep pretraining and fine-tuning framework for DR, termed DrugRepPT. Initially, we design a graph pretraining module employing model-augmented contrastive learning on a vast drug–disease heterogeneous graph to capture nuanced interactions and expression perturbations after intervention. Subsequently, we introduce a fine-tuning module leveraging a graph residual-like convolution network to elucidate intricate interactions between diseases and drugs. Moreover, a Bayesian multiloss approach is introduced to balance the existence and effectiveness of drug treatment effectively. Extensive experiments showcase the efficacy of our framework, with DrugRepPT exhibiting remarkable performance improvements compared to SOTA (state of the arts) baseline methods (improvement 106.13% on Hit@1 and 54.45% on mean reciprocal rank). The reliability of predicted results is further validated through two case studies, i.e. gastritis and fatty liver, via literature validation, network medicine analysis, and docking screening.

Availability and implementation
The code and results are available at https://github.com/2020MEAI/DrugRepPT.
Gene count estimation with pytximport enables reproducible analysis of bulk RNA sequencing data in Python
Authors: Kuehl Malte , Wong Milagros N , Wanner Nicola , Bonn Stefan , Puelles Victor G 
Published: November 2024

Abstract

Summary
Transcript quantification tools efficiently map bulk RNA sequencing (RNA-seq) reads to reference transcriptomes. However, their output consists of transcript count estimates that are subject to multiple biases and cannot be readily used with existing differential gene expression analysis tools in Python.
Here we present pytximport, a Python implementation of the tximport R package that supports a variety of input formats, different modes of bias correction, inferential replicates, gene-level summarization of transcript counts, transcript-level exports, transcript-to-gene mapping generation, and optional filtering of transcripts by biotype. pytximport is part of the scverse ecosystem of open-source Python software packages for omics analyses and includes both a Python as well as a command-line interface.
With pytximport, we propose a bulk RNA-seq analysis workflow based on Bioconda and scverse ecosystem packages, ensuring reproducible analyses through Snakemake rules. We apply this pipeline to a publicly available RNA-seq dataset, demonstrating how pytximport enables the creation of Python-centric workflows capable of providing insights into transcriptomic alterations.

Availability and implementation
pytximport is licensed under the GNU General Public License version 3. The source code is available at https://github.com/complextissue/pytximport and via Zenodo with DOI: 10.5281/zenodo.13907917. A related Snakemake workflow is available through GitHub at https://github.com/complextissue/snakemake-bulk-rna-seq-workflow and Zenodo with DOI: 10.5281/zenodo.12713811. Documentation and a vignette for new users are available at: https://pytximport.readthedocs.io.
Drug survival and safety of biosimilars for treating psoriasis compared with originator adalimumab: a multinational cohort study
Authors: Phan Duc Binh , Jourdain Hugo , Descalzo-Gallego Miguel Angel , González-Quesada Alicia , Zureik Mahmoud , Rivera-Díaz Raquel , Sahuquillo-Torralba Antonio , Lunt Mark , Garcia-Doval Ignacio , Sbidian Emilie , Warren Richard B , Yiu Zenas Z N 
Published: November 2024

Abstract

Background
The lack of evidence from routine clinical settings has limited the widespread adoption of adalimumab biosimilars for the treatment of psoriasis.

Objectives
To compare the drug survival and safety of adalimumab biosimilars with Humira® in psoriasis.

Methods
We conducted a prevalent new-user cohort study using data from the French National Health Data System (SNDS), the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and the Spanish Registry of Systemic Therapy in Psoriasis (BIOBADADERM). Adalimumab-naïve patients initiating adalimumab biosimilars (new users) were compared with Humira new users. Patients switching from Humira to biosimilars (switchers) were compared with those who continued Humira treatment. Patients were matched 1 : 1 based on previous adalimumab exposure time to create equal-sized cohorts of biosimilar and Humira users. Co-primary outcomes included drug discontinuation and serious adverse events (SAEs). Hazard ratios (HRs) were calculated using Cox proportional hazard models. Meta-analyses using random-effect models were performed to combine results from the three databases.

Results
In total, 7387 biosimilar new users and 3654 switchers were matched and compared with Humira users. No differences in all-cause discontinuation were found between biosimilar and Humira new users [HR 0.99, 95% confidence interval (CI) 0.94–1.04]. Switching from Humira to biosimilars was associated with a higher discontinuation rate than remaining on Humira (HR 1.35, 95% CI 1.19–1.52). Similar results were observed for discontinuation due to ineffectiveness or adverse events. Risks of SAEs were similar between biosimilar new users and Humira new users [incidence rate ratio (IRR) 0.91, 95% CI 0.80–1.05] or between switchers and continuous Humira users (IRR 0.92, 95% CI 0.83–1.01).

Conclusions
Adalimumab biosimilars can be considered viable alternatives to Humira for new patients, with comparable effectiveness and safety. However, owing to the higher likelihood of discontinuation, patients who switch from Humira to biosimilars may require closer monitoring and support.
Inpatient dermatology referrals: what is the burden? A retrospective review of 14 years of dermatology inpatient referrals
Authors: Cnudde Marie-Julie A M , Thomas Charles , Aldridge Christian 
Published: November 2024

Abstract

Background
The lack of dermatological knowledge by nondermatologists is exposed by the increasing number of requests made for inpatient dermatological consultations. Patients have been commenced on inappropriate treatment because of poor dermatology training.

Objectives
To determine the burden and accuracy of inpatient dermatology referrals.

Methods
A retrospective cohort study using paper inpatient dermatology referrals from one health board (Cwm Taf Morgannwg University Health Board, Wales, UK) between June 2007 and July 2021. Data analysis included timing of referrals, referring specialty, diagnosis and treatment. Descriptive statistics, using Excel, were used for analyses.

Results
The average number of referrals per year was 106 (range 79–166). The most frequent day of referral was Monday (26%). Most referrals were from medical teams (73%).
Differential diagnosis was suggested by the referring team in 59% of referrals. In only 29% of referrals did the dermatology team agree with the differential diagnosis. There was a discrepancy in the correctness of diagnosis in all categories; however, paediatricians were most likely to offer a correct differential (44%). In 44% of referrals, treatment was commenced by the referring team, most commonly antibiotics.

Conclusions
There is an extra burden on dermatology teams to cover inpatients. Our figures highlight two important issues. Firstly, the need for better dermatological education in medical schools to improve diagnostic accuracy and management of conditions. Secondly, the need for an inpatient dermatology service to review inpatient referrals and advise in the diagnosis and management of dermatology cases on the wards and to protect the service from being uncoupled from the main hospital.
Gray values and noise behavior of cone-beam computed tomography machines—an in vitro study
Authors: Oliveira-Santos Nicolly , Gaêta-Araujo Hugo , Spin-Neto Rubens , Dagassan-Berndt Dorothea , Bornstein Michael M , Oliveira Matheus L , Haiter-Neto Francisco , Freitas Deborah Q , Schulze Ralf 
Published: November 2024

Abstract

Objectives
To systematically evaluate the mean gray values (MGVs) and noise provided by bone and soft tissue equivalent materials and air imaged with varied acquisition parameters in 9 cone-beam computed tomography (CBCT) machines.

Methods
The DIN6868-161 phantom, composed of bone and soft tissue equivalent material and air gap, was scanned in 9 CBCT machines. Tube current (mA) and tube voltage (kV), field of view (FOV) size, and rotation angle were varied over the possible range. The effect of the acquisition parameters on the MGV and contrast-to-noise indicator (CNI) was analyzed by Kruskal Wallis and Dunn-Bonferroni tests for each machine independently (α = 0.05).

Results
Tube current did not influence MGV in most machines. Viso G7 and Veraview X800 presented a decrease in the MGV for increasing kV. For ProMax 3D Max and X1, the kV did not affect the MGV. For the majority of machines, MGV decreased with increasing FOV height. In general, the rotation angle did not affect the MGV. In addition, CNI was lower with lower radiation and large FOV and did not change from 80 kV in all machines.

Conclusions
The MGV and noise provided by the tested phantom vary largely among machines. The MGV is mainly influenced by the FOV size, especially for bone equivalent radiodensity. For most machines, when the acquisition parameters affect the MGV, the MGV decrease with the increase in the acquisition parameters.
Carotid calcifications in panoramic radiographs can predict vascular risk
Authors: Garoff Maria , Ahlqvist Jan , Levring Jäghagen Eva , Wester Per , Johansson Elias 
Published: November 2024

Abstract

Objectives
Carotid artery calcification (CAC) is occasionally detected in panoramic radiographs (PRs). Bilateral vessel-outlining (BVO) CACs are independent risk markers for future vascular events and have been associated with large plaque area. If accounting for plaque area, BVO CACs may no longer be an independent risk marker for vascular events. The aim of this study was to explore the association between BVO CACs and vascular events and its relationship with carotid ultrasound plaque area.

Methods
In this cohort study we prospectively included 212 consecutive participants with CACs detected in PR that were performed to plan and evaluate odontologic treatment. Of these 212, 43 (20%) had BVO CACs. Plaque area was assessed with ultrasound at baseline. Primary outcome was major adverse cardiovascular events (MACEs) during follow-up.

Results
Vessel-outlining CAC was associated with larger plaque area on the same side (P = .03) and BVO CACs were associated with larger total plaque area (both sides summed) than other CAC features (P = .004). Mean follow-up was 7.0 years and 72 (34%) participants had more than 1 MACE. In bivariable analyses, both BVO CACs (HR 2.5, P &lt; .001) and total plaque area (HR 1.8 per cm2, P = .008) were associated with MACE. When entering BVO CACs, plaque area and other relevant co-variates in a multivariable model, BVO CACs were virtually unchanged (HR 2.4, P = .001), but total plaque area was no longer significant (HR 1.0, P = .92).

Conclusion
Present results support the contention that BVO CACs are a stronger predictor for future vascular events than carotid ultrasound plaque area.
A case report of verapamil toxicity leading to haemodynamic compromise in obstructive hypertrophic cardiomyopathy
Authors: Gau Jonathan W , Rader Florian , Mody Behram , Lee Andy Y 
Published: November 2024

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is an inherited condition characterized by left ventricular (LV) hypertrophy unexplained by increased afterload, often with concomitant outflow tract obstruction. Verapamil is commonly used to treat symptomatic patients. However, its potential for adverse effects should be recognized.

Case summary
This report provides a case of cardiogenic shock in HCM, where a patient presented with chief complaint of fatigue and shortness of breath with an acute decline in LV systolic function on echocardiogram. His symptoms were attributed to verapamil toxicity following a recent increase in dosage. He achieved rapid symptom relief after holding his home medications, in addition to conservative management.

Discussion
This case report aims to elucidate the potential for multiple adverse effects involved with verapamil use in patients with obstructive HCM.
Anonymize or synthesize? Privacy-preserving methods for heart failure score analytics
Authors: Johann Tim I , Otte Karen , Prasser Fabian , Dieterich Christoph 
Published: November 2024

Abstract

Aims
Data availability remains a critical challenge in modern, data-driven medical research. Due to the sensitive nature of patient health records, they are rightfully subject to stringent privacy protection measures. One way to overcome these restrictions is to preserve patient privacy by using anonymization and synthetization strategies. In this work, we investigate the effectiveness of these methods for protecting patient privacy using real-world cardiology health records.

Methods and results
We implemented anonymization and synthetization techniques for a structure data set, which was collected during the HiGHmed Use Case Cardiology study. We employed the data anonymization tool ARX and the data synthetization framework ASyH individually and in combination. We evaluated the utility and shortcomings of the different approaches by statistical analyses and privacy risk assessments. Data utility was assessed by computing two heart failure risk scores on the protected data sets. We observed only minimal deviations to scores from the original data set. Additionally, we performed a re-identification risk analysis and found only minor residual risks for common types of privacy threats.

Conclusion
We could demonstrate that anonymization and synthetization methods protect privacy while retaining data utility for heart failure risk assessment. Both approaches and a combination thereof introduce only minimal deviations from the original data set over all features. While data synthesis techniques produce any number of new records, data anonymization techniques offer more formal privacy guarantees. Consequently, data synthesis on anonymized data further enhances privacy protection with little impacting data utility. We share all generated data sets with the scientific community through a use and access agreement.
Treatment with PCSK9 monoclonal antibodies is associated with discontinuation of oral lipid lowering therapy
Authors: Engebretsen Ingrid , Ødegaard Kristina Malene , Halvorsen Sigrun , Bugge Christoffer , Kristiansen Ivar Sønbø , Støvring Henrik , Munkhaugen John 
Published: November 2024

Abstract

Aims
Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) are recommended for high-risk patients if the low-density lipoprotein cholesterol targets are not achieved with statins and ezetimibe. We studied persistence and adherence to (i) PCSK9 mAbs and (ii) statins and ezetimibe in a nationwide cohort of incident PCSK9 mAb users.

Methods and results
Information on all PCSK9 mAb users ≤80 years from 2015 through 2023 were extracted from the Norwegian Drug Registry. Discontinuation was defined as a gap in treatment ≥180 days and ≥90 days. Adherence was measured as the proportion of days covered during the initial year of PCSK9 mAb therapy. We analysed adherence of statins and ezetimibe before and after PCSK9 mAb initiation. Of 4784 patients initiating PCSK9 mAbs, the median age was 63 years, 41% were female, 61% had atherosclerotic disease, and 34% had familial hypercholesterolaemia. Within 3 years after initiation, 17% experienced a PCSK9 mAb treatment gap exceeding 180 days. In the 12-month period preceding PCSK9 mAb initiation, 74% dispensed statins whereas 67% dispensed ezetimibe. These numbers were reduced to 35% for statins and 42% for ezetimibe during the 12-month period after PCSK9 mAb initiation. Atherosclerotic disease, using ≥3 statins previously, and older age were significantly associated with discontinuation of statins and ezetimibe.

Conclusion
In this high-risk cohort of incident PCSK9 mAb users, more than 1 out of 2 stopped taking statin treatment whereas 40% discontinued ezetimibe. There is a major potential for improving adherence to oral LLD treatment following initiation of PCSK9 mAb.
Association between warfarin use and thromboembolic events in patients post-Fontan operation: propensity-score overlap weighting analyses
Authors: Maki Wakana , Aso Shotaro , Inuzuka Ryo , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo 
Published: November 2024

Abstract

OBJECTIVES
The appropriate antithrombotic regimen after a Fontan operation is yet to be elucidated. Hence, this study aimed to compare the incidence of thromboembolic events in patients with and without receiving warfarin for thromboprophylaxis in a large post-Fontan population.

METHODS
This retrospective cohort study used data from the Diagnosis Procedure Combination database in Japan between April 2011 and March 2022. We identified all patients who underwent a Fontan operation and excluded those who were born before 2010, died during the hospitalization or received mechanical heart replacement. Propensity score overlap weighting was performed between patients discharged with warfarin (with or without aspirin) and the control group (only aspirin or neither aspirin nor warfarin). Cox and Fine-Gray hazards models compared thromboembolic and bleeding events.

RESULTS
We identified 2007 eligible patients, including 1670 warfarin users and 337 non-users. The mean follow-up duration was 2.1 years. The crude proportions of thromboembolic events were 3.0% and 3.0% and those of bleeding events were 0.4% and 0.3% in the warfarin and control groups, respectively. There was no significant difference in thromboembolic events between the groups (sub-distribution hazard ratio: 0.77; 95% confidence interval 0.39–1.51; P = 0.45) or bleeding events (sub-distribution hazard ratio: 0.78; 95% confidence interval 0.09–7.03; P = 0.83).

CONCLUSIONS
Warfarin use at discharge after a Fontan operation may not be necessary for thromboembolism prophylaxis in paediatric patients, based on large-scale real-world data, with a mean postoperative follow-up duration of 2.1 years. There is room for further studies to reconsider routine warfarin use in patients post-Fontan operation.
Non-bacterial thrombotic endocarditis: a clinical and pathophysiological reappraisal
Authors: Ahmed Omair , King Nicholas E , Qureshi Muhammad Ahmad , Choudhry Abira Afzal , Osama Muhammad , Zehner Carl , Ali Abdelrahman , Hamzeh Ihab R , Palaskas Nicolas L , Thompson Kara A , Koutroumpakis Efstratios , Deswal Anita , Yusuf Syed Wamique 
Published: November 2024

Abstract
Non-bacterial thrombotic endocarditis (NBTE), formerly recognized as marantic endocarditis, represents a rare cardiovascular pathology intricately linked with hypercoagulable states, notably malignancy and autoimmune disorders. Characterized by the development of sterile vegetations comprised of fibrin and platelets on cardiac valves, NBTE poses a diagnostic challenge due to its resemblance to infective endocarditis. Therapeutic endeavours primarily revolve around addressing the underlying aetiology and instituting anticoagulant regimens to forestall embolic events, with surgical intervention seldom warranted. Non-bacterial thrombotic endocarditis frequently coexists with malignancies and autoimmune conditions, such as lupus and antiphospholipid antibody syndrome, and, more recently, has been associated with COVID-19. Its pathogenesis is underpinned by a complex interplay of endothelial dysfunction, hypercoagulability, hypoxia, and immune complex deposition. Clinical manifestations typically manifest as embolic phenomena, particularly cerebrovascular accidents, bearing substantial mortality rates. Diagnosis necessitates a high index of suspicion and meticulous exclusion of infective endocarditis, often facilitated by advanced cardiac imaging modalities. Anticoagulation, typically employing low molecular weight heparin or warfarin, constitutes the cornerstone of pharmacological intervention. Surgical recourse may be warranted in instances of refractory heart failure or recurrent embolic events. Given its multifaceted nature, the management of NBTE mandates a multidisciplinary approach, with prognosis contingent upon individual clinical intricacies. Future endeavours should prioritize further research to refine therapeutic strategies and enhance patient outcomes.
Prevalent findings on low-dose CT scan lung cancer screening: a French prospective pilot study
Authors: Grenier Philippe A , Arutkin Maxence , Brun Anne Laure , Métivier Anne-Cécile , Sage Edouard , Haziza Franck , Ackermann Félix , Mellot François , Vallée Alexandre 
Published: November 2024

Abstract
Despite significant therapeutic advances, lung cancer remains the biggest killer among cancers. In France, there is no national screening program against lung cancer. Thus, in this perspective, the Foch Hospital decided to implement a pilot and clinical low-dose CT screening program to evaluate the efficiency of such screening. The purpose of this study was to describe the prevalent findings of this low-dose CT screening program. Participants were recruited in the screening program through general practitioners (GPs), pharmacists, and specialists from June 2023 to June 2024. The inclusion criteria included male or female participants aged 50 to 80 years, current smokers or former smokers who had quit less than 15 years prior, with a smoking history of over 20 pack-years. Chest CT scans were conducted at Foch Hospital using a low-dose CT protocol based on volume mode with a multi-slice scanner (≥60 slices) without contrast injection. In total, 477 participants were recruited in the CT scan screening, 235 (49%) were males with a median age of 60 years [56–67] and 35 smoke pack-years [29–44] and 242 females (51%) with a median age of 60 years [55–60] and 30 smoke pack-years [25–40]. Eight participants showed positive nodules on CT scan, as a 1.7% rate. 66.7% of diagnosed cancers were in early stages (0-I). It is feasible to implement structured lung cancer screening using low-dose CT in a real-world setting among the general population. This approach successfully identifies most early-stage cancers that could be treated curatively.