bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network-medicine approach for the identification of genetic association of parathyroid adenoma with cardiovascular disease and type-2 diabetes
Authors: Imam Nikhat , Alam Aftab , Siddiqui Mohd Faizan , Veg Akhtar , Bay Sadik , Khan Md Jawed Ikbal , Ishrat Romana 
Published: February 2023

Abstract
Primary hyperparathyroidism is caused by solitary parathyroid adenomas (PTAs) in most cases (⁓85%), and it has been previously reported that PTAs are associated with cardiovascular disease (CVD) and type-2 diabetes (T2D). To understand the molecular basis of PTAs, we have investigated the genetic association amongst PTAs, CVD and T2D through an integrative network-based approach and observed a remarkable resemblance. The current study proposed to compare the PTAs-associated proteins with the overlapping proteins of CVD and T2D to determine the disease relationship. We constructed the protein–protein interaction network by integrating curated and experimentally validated interactions in humans. We found the $11$ highly clustered modules in the network, which contain a total of $13$ hub proteins (TP53, ESR1, EGFR, POTEF, MEN1, FLNA, CDKN2B, ACTB, CTNNB1, CAV1, MAPK1, G6PD and CCND1) that commonly co-exist in PTAs, CDV and T2D and reached to network’s hierarchically modular organization. Additionally, we implemented a gene-set over-representation analysis over biological processes and pathways that helped to identify disease-associated pathways and prioritize target disease proteins. Moreover, we identified the respective drugs of these hub proteins. We built a bipartite network that helps decipher the drug–target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drug combinations or drug-repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs and give a synergistic effect with better outcomes. This network-based analysis opens a new horizon for more personalized treatment and drug-repurposing opportunities to investigate new targets and multi-drug treatment and may be helpful in further analysis of the mechanisms underlying PTA and associated diseases.
wpLogicNet: logic gate and structure inference in gene regulatory networks
Authors: Malekpour Seyed Amir , Shahdoust Maryam , Aghdam Rosa , Sadeghi Mehdi 
Published: February 2023

Abstract

Motivation
The gene regulatory process resembles a logic system in which a target gene is regulated by a logic gate among its regulators. While various computational techniques are developed for a gene regulatory network (GRN) reconstruction, the study of logical relationships has received little attention. Here, we propose a novel tool called wpLogicNet that simultaneously infers both the directed GRN structures and logic gates among genes or transcription factors (TFs) that regulate their target genes, based on continuous steady-state gene expressions.

Results
wpLogicNet proposes a framework to infer the logic gates among any number of regulators, with a low time-complexity. This distinguishes wpLogicNet from the existing logic-based models that are limited to inferring the gate between two genes or TFs. Our method applies a Bayesian mixture model to estimate the likelihood of the target gene profile and to infer the logic gate a posteriori. Furthermore, in structure-aware mode, wpLogicNet reconstructs the logic gates in TF–gene or gene–gene interaction networks with known structures. The predicted logic gates are validated on simulated datasets of TF–gene interaction networks from Escherichia coli. For the directed-edge inference, the method is validated on datasets from E.coli and DREAM project. The results show that compared to other well-known methods, wpLogicNet is more precise in reconstructing the network and logical relationships among genes.

Availability and implementation
The datasets and R package of wpLogicNet are available in the github repository, https://github.com/CompBioIPM/wpLogicNet.

Supplementary information
Supplementary data are available at Bioinformatics online.
Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model
Authors: Kinnear Hadrian M , Hashim Prianka H , Dela Cruz Cynthia , Chang Alexis L , Rubenstein Gillian , Nimmagadda Likitha , Ramamoorthi Elangovan Venkateswaran , Jones Andrea , Brunette Margaret A , Hannum D Ford , Li Jun Z , Padmanabhan Vasantha , Moravek Molly B , Shikanov Ariella 
Published: February 2023

Abstract
Some transmasculine individuals may be interested in pausing gender-affirming testosterone therapy and carrying a pregnancy. The ovarian impact of taking and pausing testosterone is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine testosterone therapy to characterize the ovarian dynamics following testosterone cessation. We injected postpubertal 9–10-week-old female C57BL/6N mice once weekly with 0.9 mg of testosterone enanthate or a vehicle control for 6 weeks. All testosterone-treated mice stopped cycling and demonstrated persistent diestrus within 1 week of starting testosterone, while control mice cycled regularly. After 6 weeks of testosterone therapy, one group of testosterone-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of testosterone-treated mice were maintained after stopping testosterone therapy and were sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post testosterone group as compared to both age-matched controls and mice at 6 weeks on testosterone. These clusters exhibited periodic acid–Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian ribonucleic acid-sequencing found upregulation of immune pathways post testosterone as compared to age-matched controls and ovaries at 6 weeks on testosterone. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing testosterone to carry a pregnancy.
Semiparametric efficient G-estimation with invalid instrumental variables
Authors: Sun B , Liu Z , Tchetgen Tchetgen E J 
Published: February 2023

SummaryThe instrumental variable method is widely used in the health and social sciences for identification and estimation of causal effects in the presence of potential unmeasured confounding. To improve efficiency, multiple instruments are routinely used, raising concerns about bias due to possible violation of the instrumental variable assumptions. To address such concerns, we introduce a new class of G-estimators that are guaranteed to remain consistent and asymptotically normal for the causal effect of interest provided that a set of at least $\gamma$ out of $K$ candidate instruments are valid, for $\gamma \leqslant K$ set by the analyst ex ante without necessarily knowing the identities of the valid and invalid instruments. We provide formal semiparametric efficiency theory supporting our results. Simulation studies and applications to UK Biobank data demonstrate the superior empirical performance of the proposed estimators compared with competing methods.
Poorer sleep health is associated with altered brain activation during cognitive control processing in healthy adults
Authors: Smevik Hanne , Habli Sarah , Saksvik Simen Berg , Kliem Elisabeth , Evensmoen Hallvard Røe , Conde Virginia , Petroni Agustin , Asarnow Robert F , Dennis Emily L , Eikenes Live , Kallestad Håvard , Sand Trond , Thompson Paul M , Saksvik-Lehouillier Ingvild , Håberg Asta Kristine , Olsen Alexander 
Published: February 2023

Abstract
This study investigated how proactive and reactive cognitive control processing in the brain was associated with habitual sleep health. BOLD fMRI data were acquired from 81 healthy adults with normal sleep (41 females, age 20.96–39.58 years) during a test of cognitive control (Not-X-CPT). Sleep health was assessed in the week before MRI scanning, using both objective (actigraphy) and self-report measures. Multiple measures indicating poorer sleep health—including later/more variable sleep timing, later chronotype preference, more insomnia symptoms, and lower sleep efficiency—were associated with stronger and more widespread BOLD activations in fronto-parietal and subcortical brain regions during cognitive control processing (adjusted for age, sex, education, and fMRI task performance). Most associations were found for reactive cognitive control activation, indicating that poorer sleep health is linked to a “hyper-reactive” brain state. Analysis of time-on-task effects showed that, with longer time on task, poorer sleep health was predominantly associated with increased proactive cognitive control activation, indicating recruitment of additional neural resources over time. Finally, shorter objective sleep duration was associated with lower BOLD activation with time on task and poorer task performance. In conclusion, even in “normal sleepers,” relatively poorer sleep health is associated with altered cognitive control processing, possibly reflecting compensatory mechanisms and/or inefficient neural processing.
Even in preschools: analysing the preschool and neighbourhood segregation gap in Swedish municipalities
Authors: Alm Fjellborg Andreas , Forsberg Håkan 
Published: February 2023

Abstract
Preschool segregation has not been the focus of research efforts to the same extent as compulsory school segregation. This is at least in part a consequence of the lack of large-scale, registry-based data sources on where children live and where they attend preschool. This paper presents a full-population account of discrepancies between preschool segregation and neighbourhood segregation covering the Swedish population. Data includes preschool children as well as their parents’ income, education, ethnic background, and place of residence. Findings indicate that while preschool segregation does not differ from neighbourhood segregation to the same extent as previous research has shown for school segregation, there are systematic differences affecting the level of segregation across Sweden and in various types of municipalities. Studies on school level show segregation by foreign background and income to be most prominent, whilst preschool segregation mostly concerns parents’ educational attainment. Furthermore, the findings show that the geographical distribution of private and public preschools affects levels of segregation. This conclusion supports the general argument that the free-choice reform in the Swedish school system tends to raise levels of school segregation above the levels of residential segregation—even in preschools.
Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)
Authors: Barbato Emanuele , Azizi Michel , Schmieder Roland E , Lauder Lucas , Böhm Michael , Brouwers Sofie , Bruno Rosa Maria , Dudek Dariusz , Kahan Thomas , Kandzari David E , Lüscher Thomas F , Parati Gianfranco , Pathak Atul , Ribichini Flavio L , Schlaich Markus P , Sharp Andrew S P , Sudano Isabella , Volpe Massimo , Tsioufis Costas , Wijns William , Mahfoud Felix 
Published: February 2023

Abstract
Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient’s global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.
Increased risk of cardiovascular disease associated with diabetes among adult cancer survivors: a population-based matched cohort study
Authors: Oh Sanghyun , Lee Jihwan , Hong Yoo S , Kim Kyuwoong 
Published: February 2023

Abstract

Aims
Diabetes is a well-established risk factor for cardiovascular disease (CVD), but little is known about the differences in contribution of diabetes to incident CVD between adult cancer survivors and those without history of cancer. The aim of this study was to evaluate the magnitude of association between diabetes and CVD risk among adult cancer survivors and their general population counterparts.

Methods and results
The National Health Insurance Service database was used to abstract data on 5199 adult cancer survivors and their general population controls in a 1:1 age- and sex-matched cohort setting. The Cox proportional hazards model adjusted for socioeconomic status, health status, lifestyle, and clinical characteristics was used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) of incident CVD associated with glycaemic status in adult cancer survivors and the general population. The partial likelihood ratio test was used to compare the magnitude of the association between diabetes and CVD risk in the two groups. Compared to those without diabetes, adult cancer survivors (adjusted HR = 2.30; 95% CI: 1.24–4.30) and their general population controls (adjusted HR = 1.91; 95% CI: 1.02–3.58) with diabetes had a higher risk of incident cardiovascular outcomes. The magnitude of diabetes–CVD association was significantly stronger in adult cancer survivors than that in those without history of cancer (P = 0.011).

Conclusions
The magnitude of association between diabetes and incident CVD was stronger in adult cancer survivors as compared to that in their general population counterparts, supporting evidence for the importance of glycaemic control for prevention of CVD among those with history of cancer diagnosis and treatment.
Conversion of Norway spruce (Picea abies (L.) H. Karst.) tree stem volume to volumes of produced logging residues and wood chips
Authors: Dvořák Jiří , Jankovský Martin , Kormanek Mariusz , Natov Pavel , Straka Pavel 
Published: February 2023

Abstract
As a renewable fuel, logging residues, as well as other dendromass, are in high demand. On the other hand, they can serve as a natural fertilizer and stabilize biodiversity in forest ecosystems. Therefore, they need to be used rationally, with due care for the volumes extracted from a particular stand. The volume of logging residues is difficult to measure; thus, foresters need a tool to estimate it, ideally via a simple method based on easily measurable parameters. Conversion factors, based on tree stem volume can serve this purpose. In this study, we develop such conversion factors for thinnings of Norway spruce (Picea abies (L.) H. Karst.) stands. First, we analyzed the relationship between the tree stem volume (ranging between 0.03 and 0.44 m3 stem−1) and the volumes of related logging residues or wood chips via linear regression and correlation analysis. Then, we assessed the significance of differences between volumes of logging residues or wood chips for trees in the five relevant stem volume classes and determined appropriate conversion factors. The conversion factors for wood chips ranged between 1.37 loose cubic meters of logging residue per cubic meter of timber in the largest stem volume class to 2.17 for the smallest stem volume class. The model, on which the conversion factors were based had a coefficient of determination of 0.88. Conversion to logging residue volume yielded factors ranging from 2.2 stacked cubic meters per cubic meter of timber for the largest stem volume class to 10.2 in the smallest stem volume class. The coefficient of determination of the underlying model was 0.69. The conversion factors are based on sufficiently accurate models and can be used in practical forestry for planning purposes, recordkeeping, and remuneration of loggers.
The Impact of Sample Size and Population History on Observed Mutational Spectra: A Case Study in Human and Chimpanzee Populations
Authors: Ghafoor Suhail , Santos João , Versoza Cyril J , Jensen Jeffrey D , Pfeifer Susanne P 
Published: February 2023

AbstractRecent studies have highlighted variation in the mutational spectra among human populations as well as closely related hominoids—yet little remains known about the genetic and nongenetic factors driving these rate changes across the genome. Pinpointing the root causes of these differences is an important endeavor that requires careful comparative analyses of population-specific mutational landscapes at both broad and fine genomic scales. However, several factors can confound such analyses. Although previous studies have shown that technical artifacts, such as sequencing errors and batch effects, can contribute to observed mutational shifts, other potentially confounding parameters have received less attention thus far. Using population genetic simulations of human and chimpanzee populations as an illustrative example, we here show that the sample size required for robust inference of mutational spectra depends on the population-specific demographic history. As a consequence, the power to detect rate changes is high in certain hominoid populations while, for others, currently available sample sizes preclude analyses at fine genomic scales.
Associations Between Loneliness and Cognitive Resilience to Neuropathology in Older Adults
Authors: Jackson Kathryn L , Luo Jing , Willroth Emily C , Ong Anthony D , James Bryan D , Bennett David A , Wilson Robert , Mroczek Daniel K , Graham Eileen K 
Published: February 2023

AbstractObjectivesLoneliness in the aging population is associated with decreased cognitive function and increased neuropathology; less is understood about the association of loneliness and cognitive resilience (CR), defined as the discordance between a person’s actual and expected cognition given their neuropathology. Here we assess the effect of loneliness and change in loneliness on CR at end of life and across older adulthood.MethodsData were combined from 2 longitudinal studies of older adults. CR proximate to death (CRlast_level) and across time (CRslope) was obtained by independently regressing global cognition and change in cognition onto multiple neuropathology indicators and extracting the resulting residuals. We used a series of simple linear regression models to assess the effect of loneliness level and change on CRlast_level and CRslope.ResultsHigher baseline loneliness was associated with lower CRlast_level (β = −0.11, 95% confidence interval [95% CI; −0.18, −0.04], p &lt; .01); higher baseline loneliness and increasing loneliness over time was associated with lower CRslope (β = −0.13, 95% CI [−0.22, −0.05], p &lt; .01 and β = −0.12, 95% CI [−0.20, −0.04], p &lt; .01, respectively). Results were robust to covariate inclusion and independent of objective social isolation.DiscussionHigher and increasing loneliness was associated with lower CR in the face of neuropathology. These results suggest that some individuals are less resilient to the accumulation of neuropathology than others, and experiencing high/increasing loneliness is a key factor putting some at risk. Interventions aimed at optimizing cognitive function across older adults should include loneliness reduction as a potential area of focus.
Modeling earthquake cycles and wear on rough faults with the mortar finite element method
Authors: Tal Yuval 
Published: February 2023

SUMMARYThis paper presents a mortar-based finite element formulation for modelling earthquake cycles and wear on rough faults governed by rate and state friction. The method allows large sliding on the fault and accounts for all stages in the earthquake cycle, using a variable time step size with a transition between quasi-static and fully dynamic time discretizations. Wear laws with linear and power law forms are discretized and implemented into the mortar method, as well as a minimum level of normal traction constraint to treat fault opening. We examine the effect of wear laws on the slip behaviour and near-fault stresses during simulations of earthquake cycles on rough faults. The simulations demonstrate that the implementation of wear allows more realistic modelling of the earthquake cycle without the development of unrealistically large stresses and with less reduction of earthquake magnitude with total fault slip. Moreover, the method enables to study the effects of roughness and fault slip on the gouge zone thickness.
Co-designing marine science for the ocean we want
Authors: Pendleton Linwood H , Alexandroff Stella J , Clausen Alison , Schmidt Jörn O , Browman Howard I 
Published: February 2023

AbstractThe United Nations Decade of Ocean Science for Sustainable Development requires that all of the Actions it endorses have concrete plans to involve stakeholders in the co-creation of ocean science. As a result, we have a unique opportunity to test different approaches to stakeholder engagement to see what works and what does not. Here, we feature short essays in the “Food for Thought” series in which leaders from Decade-endorsed Actions describe how they plan to incorporate stakeholders in the co-design, co-production, and co-delivery of ocean science and how they will measure whether these approaches were successful. We also invited submissions to the journal’s “Stories from the Front Lines” series, in which authors were asked to share unvarnished accounts of the lessons learned from previous efforts to co-design ocean science. We hope that these initial articles will be the beginning of an ongoing series in which new Decade Actions will also document their plans to implement, monitor, and measure the success or failure of these approaches.