bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight loss increases skeletal muscle mitochondrial energy efficiency in obese mice
Authors: Ferrara Patrick J , Lang Marisa J , Johnson Jordan M , Watanabe Shinya , McLaughlin Kelsey L , Alan Maschek John , Verkerke Anthony R P , Siripoksup Piyarat , Chaix Amandine , Cox James E , Fisher-Wellman Kelsey H , Funai Katsuhiko 
Published: April 2023

Abstract
Weight loss from an overweight state is associated with a disproportionate decrease in whole-body energy expenditure that may contribute to the heightened risk for weight regain. Evidence suggests that this energetic mismatch originates from lean tissue. Although this phenomenon is well documented, the mechanisms have remained elusive. We hypothesized that increased mitochondrial energy efficiency in skeletal muscle is associated with reduced expenditure under weight loss. Wildtype (WT) male C57BL6/N mice were fed with high-fat diet for 10 weeks, followed by a subset of mice that were maintained on the obesogenic diet (OB) or switched to standard chow to promote weight loss (WL) for additional 6 weeks. Mitochondrial energy efficiency was evaluated using high-resolution respirometry and fluorometry. Mass spectrometric analyses were employed to describe the mitochondrial proteome and lipidome. Weight loss promoted ~50% increase in the efficiency of oxidative phosphorylation (ATP produced per O2 consumed, or P/O) in skeletal muscle. However, Weight loss did not appear to induce significant changes in mitochondrial proteome, nor any changes in respiratory supercomplex formation. Instead, it accelerated the remodeling of mitochondrial cardiolipin (CL) acyl-chains to increase tetralinoleoyl CL (TLCL) content, a species of lipids thought to be functionally critical for the respiratory enzymes. We further show that lowering TLCL by deleting the CL transacylase tafazzin was sufficient to reduce skeletal muscle P/O and protect mice from diet-induced weight gain. These findings implicate skeletal muscle mitochondrial efficiency as a novel mechanism by which weight loss reduces energy expenditure in obesity.
Exploring the cosmological synergy between galaxy cluster and cosmic void number counts
Authors: Pelliciari D , Contarini S , Marulli F , Moscardini L , Giocoli C , Lesci G F , Dolag K 
Published: April 2023

ABSTRACTGalaxy clusters and cosmic voids, the most extreme objects in our Universe in terms of mass and size, trace two opposite sides of the large-scale matter density field. By studying their abundance as a function of their mass and radius, respectively, i.e. the halo mass function (HMF) and void size function (VSF), it is possible to achieve fundamental constraints on the cosmological model. While the HMF has already been extensively exploited, providing robust constraints on the main cosmological model parameters (e.g. Ωm, σ8, and S8), the VSF is still emerging as a viable and effective cosmological probe. Given the expected complementarity of these statistics, in this work, we aim at estimating the costraining power deriving from their combination. To this end, we exploit realistic mock samples of galaxy clusters and voids extracted from state-of-the-art large hydrodynamical simulations, in the redshift range 0.2 ≤ z ≤ 1. We perform an accurate calibration of the free parameters of the HMF and VSF models, needed to take into account the differences between the types of mass tracers used in this work and those considered in previous literature analyses. Then, we obtain constraints on Ωm and σ8 by performing a Bayesian analysis. We find that cluster and void counts represent powerful independent and complementary probes to test the cosmological framework. In particular, the constraining power of the HMF on Ωm and σ8 improves with the VSF contribution, increasing the S8 constraint precision by a factor of about 60 per cent.
Converting the sub-Jovian desert of exoplanets to a savanna with TESS, PLATO, and Ariel
Authors: Kálmán Szilárd , Szabó Gyula M , Borsato Luca , Bódi Attila , Pál András , Szabó Róbert 
Published: April 2023

ABSTRACT
There is a lack of exoplanets with sizes similar to Neptune orbiting their host stars with periods ≲3 d – hence the name ‘sub-Jovian/Neptune desert’. Recently, several exoplanets have been confirmed to reside in the desert, transforming it into a ‘savanna’ with several ‘giraffe’ planets (such as LTT 9779 b and TOI-674 b). The most prominent scenarios put forward for the explanation of the formation of the desert are related to the stellar irradiation destroying the primary atmosphere of certain specific exoplanets. We aim to present three targets (LTT 9779 b, TOI-674 b, and WASP-156 b) that, when observed at wide wavelength ranges in infrared (IR), could prove the presence of these processes, and therefore improve the theories of planetary formation/evolution. We simulate and analyse realistic light curves of the selected exoplanets with PLATO/N-CAM and the three narrow-band filters of Ariel (VISPhot, FGS1, and FGS2) based on TESS observations of these targets. We improved the precision of the transit parameters of the three considered planets from the TESS data. We find that the combination of the three narrow-band filters of Ariel can yield an inner precision of ${\lesssim}1.1\ \hbox{per cent}$ for the planetary radii. Data from the three telescopes together will span decades, allowing the monitoring of changes in the planetary atmosphere through radius measurements. The three selected ‘giraffe’ planets can be golden targets for Ariel, whereby the loss of planetary mass due to stellar irradiation could be studied with high precision, multiwavelength (spectro-)photometry.
Identification of RNA Virus–Derived RdRp Sequences in Publicly Available Transcriptomic Data Sets
Authors: Olendraite Ingrida , Brown Katherine , Firth Andrew E 
Published: April 2023

AbstractRNA viruses are abundant and highly diverse and infect all or most eukaryotic organisms. However, only a tiny fraction of the number and diversity of RNA virus species have been catalogued. To cost-effectively expand the diversity of known RNA virus sequences, we mined publicly available transcriptomic data sets. We developed 77 family-level Hidden Markov Model profiles for the viral RNA-dependent RNA polymerase (RdRp)—the only universal “hallmark” gene of RNA viruses. By using these to search the National Center for Biotechnology Information Transcriptome Shotgun Assembly database, we identified 5,867 contigs encoding RNA virus RdRps or fragments thereof and analyzed their diversity, taxonomic classification, phylogeny, and host associations. Our study expands the known diversity of RNA viruses, and the 77 curated RdRp Profile Hidden Markov Models provide a useful resource for the virus discovery community.
Translation regulation of specific mRNAs by RPS26 C-terminal RNA-binding tail integrates energy metabolism and AMPK-mTOR signaling
Authors: Havkin-Solomon Tal , Fraticelli Davide , Bahat Anat , Hayat Daniel , Reuven Nina , Shaul Yosef , Dikstein Rivka 
Published: April 2023

Abstract
Increasing evidence suggests that ribosome composition and modifications contribute to translation control. Whether direct mRNA binding by ribosomal proteins regulates the translation of specific mRNA and contributes to ribosome specialization has been poorly investigated. Here, we used CRISPR–Cas9 to mutate the RPS26 C-terminus (RPS26dC) predicted to bind AUG upstream nucleotides at the exit channel. RPS26 binding to positions −10 to −16 of short 5′ untranslated region (5′UTR) mRNAs exerts positive and negative effects on translation directed by Kozak and Translation Initiator of Short 5′UTR (TISU), respectively. Consistent with that, shortening the 5′UTR from 16 to 10 nt diminished Kozak and enhanced TISU-driven translation. As TISU is resistant and Kozak is sensitive to energy stress, we examined stress responses and found that the RPS26dC mutation confers resistance to glucose starvation and mTOR inhibition. Furthermore, the basal mTOR activity is reduced while AMP-activated protein kinase is activated in RPS26dC cells, mirroring energy-deprived wild-type (WT) cells. Likewise, the translatome of RPS26dC cells is correlated to glucose-starved WT cells. Our findings uncover the central roles of RPS26 C-terminal RNA binding in energy metabolism, in the translation of mRNAs bearing specific features and in the translation tolerance of TISU genes to energy stress.
Prevalence ofMycoplasma penetransin Urogenital Samples From Men Screened for Bacterial Sexually Transmitted Infections
Authors: Gardette Marie , Touati Arabella , Laurier-Nadalié Cécile , Bébéar Cécile , Pereyre Sabine 
Published: April 2023

AbstractMycoplasma penetrans prevalence was assessed in urogenital samples from men screened for Chlamydia trachomatis and Neisseria gonorrhoeae. Prevalence was 3.5% among men who have sex with men and 5.3% among human immunodeficiency virus (HIV)–positive patients, significantly higher than in HIV-negative individuals (0.4%, P = .0016). No association was found between M. penetrans and urogenital symptoms.
Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study
Authors: Icht Oded , Leader Avi , Batat Erez , Yosef Lilach , Shochat Tzippy , Goldstein Daniel A , Dudnik Elizabeth , Spectre Galia , Raanani Pia , Hammerman Ariel , Zer Alona 
Published: April 2023

Abstract

Introduction
There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events.

Methods
A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks.

Results
The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]).

Conclusions
In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC.
Suicidal thoughts and behaviors in patients with chronic pain, with and without co-occurring opioid use disorder
Authors: Cheatle Martin D , Giordano Nicholas A , Themelis Kristy , Tang Nicole K Y 
Published: April 2023

Abstract

Background
Individuals with chronic pain and a co-occurring substance use disorder present higher risk of suicide, but the individual and joint impacts of chronic pain and substance use disorders on suicide risk are not well defined. The objective of this study was to exam the factors associated with suicidal thoughts and behaviors in a cohort of patients with chronic non-cancer pain (CNCP), with or without concomitant opioid use disorder (OUD).

Design
Cross sectional cohort design

Setting
Primary care clinics, pain clinics, and substance abuse treatment facilities in Pennsylvania, Washington, and Utah

Subjects
In total, 609 adults with CNCP treated with long-term opioid therapy (&gt;/= 6 months) who either developed an OUD (cases, n = 175) or displayed no evidence of OUD (controls, n = 434).

Methods
The predicted outcome was elevated suicidal behavior in patients with CNCP as indicated by a Suicide Behavior Questionnaire-Revised (SBQ-R) score of 8 or above. The presence of CNCP and OUD were key predictors. Covariates included demographics, pain severity, psychiatric history, pain coping, social support, depression, pain catastrophizing and mental defeat.

Results
Participants with CNCP and co-occurring OUD had an increased odds ratio of 3.44 in reporting elevated suicide scores as compared to participants with chronic pain only. Multivariable modeling revealed that mental defeat, pain catastrophizing, depression, and having chronic pain, and co-occurring OUD significantly increased the odds of elevated suicide scores.

Conclusions
Patients with CNCP and co-morbid OUD are associated with a 3-fold increase in risk of suicide.
Shared Agency and Mutual Obligations: A Pluralist Account
Authors: Salomone-Sehr Jules 
Published: April 2023

AbstractDo participants in shared activity have mutual obligations to do their bit? This article shows this question has no one-size-fits-all answer and offers a pluralist account of the normativity of shared agency. The first part argues obligations to do one's bit have three degrees of involvement in shared activity. Such obligations might, obviously, bolster co-participants’ resolve to act as planned (degree 1). Less obviously, there also are higher and lower degrees of involvement. Obligations to do one's bit might provide our agency-pooling mechanism. When they do, we act together by virtue of satisfying them (degree 2). Conversely, some shared activities involve no obligation (degree 0). In the second part, I argue shared agency theory is best served by a non-moralistic conception of obligation, one on which co-participants’ obligations need be neither strict-performance obligations, nor directed ones. Overall, my arguments suggest that we can choose how to coordinate normatively our shared activities.
Low Carbon Mutual Funds
Authors: Ceccarelli Marco , Ramelli Stefano , Wagner Alexander F 
Published: April 2023

Abstract
Climate change poses new challenges for portfolio management. In our not-yet-low carbon world, investors face a trade-off between minimizing their exposure to climate risks and maximizing the benefits of portfolio diversification. This article investigates how investors and financial intermediaries navigate this trade-off. After the release of Morningstar’s novel carbon risk metrics in April 2018, mutual funds labeled as “low carbon” experienced a significant increase in investor demand, especially those with high risk-adjusted returns. Fund managers actively reduced their exposure to firms with high carbon risk scores, especially stocks with returns that correlated more with the funds’ portfolios and were thus less useful for diversification. These findings shed light on whether and how climate-related information can re-orient capital flows in a low carbon direction.
Copresence Was Found to Be Related to Some Pupil Measures in Persons With Hearing Loss While They Performed a Speech-in-Noise Task
Authors: Pielage Hidde , Plain Bethany J. , Saunders Gabrielle H. , Versfeld Niek J. , Lunner Thomas , Kramer Sophia E. , Zekveld Adriana A. 
Published: April 2023

Objectives:
To assess if a manipulation of copresence was related to speech-in-noise task performance, arousal, and effort of persons with hearing loss. Task-related arousal and effort were measured by means of pupillometry.

Design:
Twenty-nine participants (mean age: 64.6 years) with hearing loss (4-frequency pure-tone average [4F-PTA] of 50.2 dB HL [SD = 8.9 dB] in the right ear and 51.3 dB HL [SD = 8.7 dB] in the left ear; averaged across 0.5, 1, 2, and 4 kHz) listened to and repeated spoken Danish sentences that were masked by four streams of continuous speech. Participants were presented with blocks of 20 sentences, during which copresence was manipulated by having participants do the task either alone or accompanied by two observers who were recruited from a similar age group. The task was presented at two difficulty levels, which was accomplished by fixing the signal-to-noise ratio of the speech and masker to match the thresholds at which participants were estimated to correctly repeat 50% (difficult) or 80% (easy) of the sentences in a block. Performance was assessed based on whether or not sentences were repeated correctly. Measures of pupil size (baseline pupil size [BPS], peak pupil dilation [PPD], and mean pupil dilation [MPD]) were used to index arousal and effort. Participants also completed ratings of subjective effort and stress after each block of sentences and a self-efficacy for listening-questionnaire.

Results:
Task performance was not associated with copresence, but was found to be related to 4F-PTA. An increase in BPS was found for copresence conditions, compared to alone conditions. Furthermore, a post-hoc exploratory analysis revealed that the copresence conditions were associated with a significantly larger pupil size in the second half of the task-evoked pupil response (TEPR). No change in PPD or MPD did was detected between copresence and alone conditions. Self-efficacy, 4F-PTA, and age were not found to be related to the pupil data. Subjective ratings were sensitive to task difficulty but not copresence.

Conclusion:
Copresence was not found to be related to speech-in-noise performance, PPD, or MPD in persons with HL but was associated with an increase in arousal (as indicated by a larger BPS). This could be related to premobilization of effort and/or discomfort in response to the observers’ presence. Furthermore, an exploratory analysis of the pupil data showed that copresence was associated with greater pupil dilations in the second half of the TEPR. This may indicate that participants invested more effort during the speech-in-noise task while in the presence of the observers, but that this increase in effort may not necessarily have been related to listening itself. Instead, other speech-in-noise task-related processes, such as preparing to respond, could have been influenced by copresence.
IGFBP-3 promotes cachexia-associated lipid loss by suppressing insulin-like growth factor/insulin signaling
Authors: Wang Xiaohui , Li Jia , Zhang Wei , Wang Feng , Wu Yunzi , Guo Yulin , Wang Dong , Yu Xinfeng , Li Ang , Li Fei , Xie Yibin 
Published: April 2023

Abstract

Background:
Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood.

Methods:
The yki-gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1, Acly, and Fasn et al .

Results:
In this study, we revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. We uncovered that IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocyted. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila. Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients.

Conclusion:
Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
Challenges in Therapeutic Drug Monitoring: Optimizing Biological Treatments in Patients With Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases
Authors: Papamichael Konstantinos , Stocco Gabriele , Ruiz del Agua Ainhoa 
Published: April 2023

Background:
Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective.

Methods:
This narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review.

Results:
Proactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti–tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times.

Conclusions:
Despite several knowledge gaps regarding proactive TDM of anti–tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future.