bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Galaxy 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

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

RNA 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

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

Mycoplasma 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

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

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 (>/= 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

Do 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

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

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.
Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Authors: Arumugam Suyavaran , Li Binghua , Boodapati Sri Lakshmi Tejaswi , Nathanson Michael H. , Sun Beicheng , Ouyang Xinshou , Mehal Wajahat Z.
Published: April 2023

Background and Aims:

TGF-β induces multiple structural and functional changes in quiescent HSCs, including an increase in proliferation, mitochondrial mass, and matrix deposition. HSC transdifferentiation requires significant bioenergetic capacity, and it is not known how TGF-β–mediated transcriptional upregulation is coordinated with the bioenergetic capacity of HSCs.

Approach and Results:

Mitochondria are key bioenergetic organelles, and here, we report that TGF-β induces release of mitochondrial DNA (mtDNA) from healthy HSCs through voltage-dependent anion channels (VDACs), with the formation of an mtDNA-CAP on the external mitochondrial membrane. This stimulates organization of cytosolic cyclic GMP-AMP synthase (cGAS) onto the mtDNA-CAP and subsequent activation of the cGAS-STING-IRF3 pathway. TGF-β is unable to induce conversion of HSCs from a quiescent to a transdifferentiated phenotype in the absence of mtDNA, VDAC, or stimulator of interferon genes (STING). Transdifferentiation by TGF-β is blocked by a STING inhibitor, which also reduces liver fibrosis prophylactically and therapeutically.

Conclusions:

We have identified a pathway that requires the presence of functional mitochondria for TGF-β to mediate HSC transcriptional regulation and transdifferentiation and therefore provides a key link between bioenergetic capacity of HSCs and signals for transcriptional upregulation of genes of anabolic pathways.
Increasing Access to Medical Forensic Care for the Pediatric Patient
Authors: Lechner Megan , Hagedorn Sarah
Published: April 2023

Child sexual abuse is a major public health problem. About one in every four girls and one in every 13 boys in the United States experience sexual abuse. In order to best serve these patients and families, the forensic nurse examiner team from a large urban Level 1 trauma center partnered with the local child advocacy center to provide ready access to educated, competent pediatric examiners who provide developmentally appropriate medical forensic care in a child-friendly environment. Consistent with national best practice standards, this occurs as part of a coordinated, colocated, highly functional multidisciplinary team. These services are provided free of charge and regardless of timeline from abuse. This partnership removes several key barriers to this care, including difficulty coordinating with multiple organizations, cost, lack of knowledge regarding available resources, and decreased ability to provide medical forensic care to nonacute patients.
Environmental sustainability in otolaryngologic surgery
Authors: Dilger Amanda E. , Bergmark Regan W.
Published: April 2023

Purpose of review

Climate change is an urgent public health crisis that significantly impacts disease development, health outcomes, and access to care. The major approaches to climate change are mitigation and adaptation. The purpose of this review is to discuss the effects of climate change on health and health disparities, review the carbon footprint of surgical care and discuss strategies for surgeons to reduce emissions and advocate for sustainability.

Recent findings

Recent studies increasingly demonstrate the direct and indirect health effects of climate change, including the relationship between climate and otolaryngologic disease. Within the domain of otolaryngology, we summarize findings related to climate change and health and healthcare delivery; health disparities; healthcare-associated emissions; and the role of otolaryngologists in mitigating and adapting to the climate crisis. There are many recent studies that identify impactful sustainability opportunities and initiatives for healthcare providers. Climate solutions may also reduce cost and have potential clinical benefits.

Climate change and air pollution directly impact disease burden in otolaryngology patients and are underrecognized social determinants of health. Surgeons can lead on climate change by implementing sustainability initiatives in the operating room and engaging in research and advocacy.
Barriers to head and neck cancer care in high-income and low- and middle-income countries: a scoping review
Authors: Sprow Holly , Heer Baveena , Nuss Sarah , Jashek-Ahmed Farizeh , Wiedermann Joshua , Seguya Amina
Published: April 2023

Purpose of review

Identify patient-perceived barriers to head and neck cancer care and compare differences in barriers by country income status.

Recent Findings

Of the 37 articles, 51% (n = 19) were from low- and middle-income countries (LMICs), while 49% (n = 18) were from high-income countries. Of the papers from high-income countries, unspecified head and neck cancer (HNC) subtype (67%, n = 12) were the most common cancer type, while upper aerodigestive tract mucosal malignancies (58%, n = 11) were more common in LMICs (P = 0.02). Based on World Health Organization barriers, level of education (P =  < 0.01) and alternative medicine use (P = 0.04) were greater barriers in LMICs compared to high-income countries. At least 50% of articles listed barriers at all three ‘Three Delays’ timepoints. There were no significant differences by country income status for the ‘Three Delays’ timepoints of deciding to seek care (P = 0.23), reaching the healthcare facility (P = 0.75), or receiving care (P = 1.00).

Patients face barriers to care for head and neck cancer regardless of country income status. There is overlap in several barriers and a need for systemic improvement in access. The differences in education and alternative medicine may guide region-specific interventions to improve the provision of head and neck services.
Retrograde intrarenal surgery for stones associated with renal anomalies: caliceal diverticulum, horseshoe kidney, medullary sponge kidney, megacalycosis, pelvic kidney, uretero-pelvic junction obstruction
Authors: Corrales Mariela , Sierra Alba
Published: April 2023

Purpose of review

Nowadays, due to the increase of imaging diagnosis, we identify easily renal anomalies, and we can choose between a wide range of armamentarium to treat symptomatic stones in those challenging cases. However, there is a lack of evidence and consensus on its use. The aim of this narrative review is to collect all the available data about safety and efficacity of retrograde intrarenal surgery (RIRS) in the treatment of kidney stones associated to a renal anomaly.

Recent findings

Renal anomalies are uncommon findings and even more if it has to be associated with renal stones. After a literature review of the past 2 years, there are a small number of studies that compare the outcomes in patients who have been treated with minimally invasive modalities and they are mainly focus on RIRS.

It is of extreme importance to know the advances on the stone treatment in anomalous kidneys. With the development of new laser technologies, RIRS is becoming a more interesting technique with high success rate and safety. Further studies are needed to make an accurate statement about the adequate surgical technique for each renal anomaly and also, clinical trials using new laser technologies.
Spirituality/Religion and Self-Harm Among Patients With Alcohol/Substance Use Versus Other Disorders
Authors: Kaufman Caroline C. , Pirutinsky Steven , Rosmarin David H.
Published: April 2023

Spirituality/religion (S/R) is clinically relevant to recovery from alcohol use disorders (AUDs)/substance use disorders (SUDs) and also associated with less self-injury; however, the interplay of these factors has not been adequately evaluated. Participants (n = 1443) were culled from a larger study among psychiatric patients. We assessed for S/R using self-report measures, and medical records were reviewed for demographics, clinical diagnoses, psychiatric medications, and self-harm engagement. Self-harm engagement was significantly higher among patients without AUD/SUD. S/R distress was higher among participants with AUD/SUD, but S/R community activity and importance of religion were lower. Interest in discussing S/R in treatment did not significantly differ across patients. Religious affiliation, importance of religion, and belief in God were associated with less self-harm, but effects were not moderated by presence of AUD/SUD. S/R factors are associated with lower self-harm, irrespective of the presence or absence of AUD/SUD. In contrast with clinical lore, S/R may be equally salient to psychiatric patients with AUD/SUD versus other disorders.
Measurements of large optical rotary dispersion in the adipose eyelid of Atlantic mackerel (
Scomber scombrus
)
Authors: Jenkinson Euan , Alexander Andrew J. , Camp Philip J.
Published: April 2023

Collagen is the most prevalent of Nature’s structural proteins, and is found in the extracellular matrices of animals. The structures of collagen molecules and aggregates are chiral, which leads to the rotation of transmitted, plane-polarized light. Here, it is shown that the concentrations of chiral molecules and aggregates in the optically transparent, adipose eyelid of Atlantic mackerel (
Scomber scombrus
) can be so high, that plane-polarized light in the visible spectrum is rotated by tens to hundreds of degrees, depending on wavelength (the optical rotatory dispersion (ORD)). This gives rise to intensely coloured images of eyelid samples when illuminated with white light and viewed between crossed polarizers. The ORD in the visible spectrum is measured with monochromatic light sources, and using this dispersion, the variation of optical thickness within a sample (proportional to collagen concentration and path length) is determined. The agreement between observed and simulated white-light images is almost perfect. While collagen provides vital mechanical rigidity to animal tissue, it might also possess optical properties that are useful for vision and camouflage.
Does coat colour influence survival? A test in a cyclic population of snowshoe hares
Authors: Oli Madan K. , Kenney Alice J. , Boonstra Rudy , Boutin Stan , Murray Dennis L. , Peers Michael J. L. , Gilbert B. Scott , Jung Thomas S. , Chaudhary Vratika , Hines James E. , Krebs Charles J.
Published: April 2023

Some mammal species inhabiting high-latitude biomes have evolved a seasonal moulting pattern that improves camouflage via white coats in winter and brown coats in summer. In many high-latitude and high-altitude areas, the duration and depth of snow cover has been substantially reduced in the last five decades. This reduction in depth and duration of snow cover may create a mismatch between coat colour and colour of the background environment, and potentially reduce the survival rate of species that depend on crypsis. We used long-term (1977–2020) field data and capture–mark–recapture models to test the hypothesis that whiteness of the coat influences winter apparent survival in a cyclic population of snowshoe hares (Lepus americanus) at Kluane, Yukon, Canada. Whiteness of the snowshoe hare coat in autumn declined during this study, and snowshoe hares with a greater proportion of whiteness in their coats in autumn survived better during winter. However, whiteness of the coat in spring did not affect subsequent summer survival. These results are consistent with the hypothesis that the timing of coat colour change in autumn can reduce overwinter survival. Because declines in cyclic snowshoe hare populations are strongly affected by low winter survival, the timing of coat colour change may adversely affect snowshoe hare population dynamics as climate change continues.
Additive and interactive effects of anthropogenic stressors on an insect herbivore
Authors: Halsch Christopher A. , Zullo Dominic J. , Forister Matthew L.
Published: April 2023

The pressures of global change acting on wild plants and animals include exposure to environmental toxins, the introduction of non-native species, and climate change. Relatively few studies have been reported in which these three main classes of stressors have been examined simultaneously, allowing for the possibility of synergistic effects in an experimental context. In this study, we exposed caterpillars of the Melissa blue butterfly (
Lycaeides melissa
) to three concentrations of chlorantraniliprole, under three experimental climates, on a diet of a native or a non-native host plant throughout larval development in a fully factorial experiment. We find that high pesticide exposure and a non-native diet exhibit strong negative effects on caterpillars, resulting in 62% and 42% reduction in survival, respectively, while interactive effects tend to be weaker, ranging from 15% to 22% reduction in survival. Interactive effects have been shown to be strong in other contexts, but do not appear to be universal; however, our study shows that the cumulative effects of stressors acting in isolation (additively) are sufficiently strong to severely reduce survival and by extension population persistence in the wild.
Mass mortality among colony-breeding seabirds in the German Wadden Sea in 2022 due to distinct genotypes of HPAIV H5N1 clade 2.3.4.4b
Authors: Pohlmann Anne , Stejskal Ole , King Jacqueline , Bouwhuis Sandra , Packmor Florian , Ballstaedt Elmar , Hälterlein Bernd , Hennig Veit , Stacker Lina , Graaf Annika , Hennig Christin , Günther Anne , Liang Yuan , Hjulsager Charlotte , Beer Martin , Harder Timm
Published: April 2023

Mass mortality was observed among colony-breeding seabirds in the German Wadden Sea area of the North Sea during the summer months of 2022. Several species’ colonies were affected, most notably sandwich terns (Thalasseus sandvicensis), common terns (Sterna hirundo) and Germany’s only northern gannet (Morus bassanus) colony on the island of Heligoland. Mortality in some tern colonies reached 40%, while other colonies were almost spared. In all cases, infections with the high-pathogenicity avian influenza virus (HPAIV) subtype H5N1 of clade 2.3.4.4b were identified to have caused the epidemic. Phylogenetic analysis of whole-genome sequences revealed that the outbreaks were dominated by two genotypes, Ger-10–21 N1.2 and Ger-10–21 N1.5, previously identified in Germany. Spatiotemporal analyses of phylogenetic data suggested that these viruses could have entered the continental North Sea coastal region via the British Isles. A close linkage of viruses from tern colonies in the German Wadden Sea was evident with further connections to breeding colonies in Belgium and the Netherlands, and further spread to Denmark and Poland. Several of the affected species are endangered, such that negative effects of epizootic HPAIV infections on populations are feared, with uncertain long-term consequences.
Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone inDrosophila
Authors: Fang Hsiao Yu , Forghani Rameen , Clarke Akanni , McQueen Philip G. , Chandrasekaran Aravind , O’Neill Kate M. , Losert Wolfgang , Papoian Garegin A. , Giniger Edward
Published: April 2023

Ena/VASP proteins are processive actin polymerases that are required throughout animal phylogeny for many morphogenetic processes, including axon growth and guidance. Here we use live imaging of morphology and actin organization in the TSM1 axon of the Drosophila wing to dissect the mechanism of Ena action. We find that altering Ena activity has a substantial impact on filopodial morphology in this growth cone, but exerts only modest effects on actin organization. This is in contrast to the main regulator of Ena, Abl tyrosine kinase, which has profound effects on actin and only mild effects on TSM1 growth cone morphology. These data suggest that the primary role of Ena in this axon may be to link actin to morphogenetic processes of the plasma membrane, rather than regulating actin organization itself. These data also suggest that a key role of Ena, acting downstream of Abl, may be to maintain a constant filopodial organization of the growth cone, even as Abl activity varies in response to guidance cues in the environment.

Summary statement

We dissect the function of the actin polymerase, Enabled, in axon growth by live-imaging of actin dynamics and axon morphology of the TSM1 neuron in its native environment in vivo.
Enhancer architecture and chromatin accessibility constrain phenotypic space during development
Authors: Galupa Rafael , Alvarez-Canales Gilberto , Borst Noa Ottilie , Fuqua Timothy , Gandara Lautaro , Misunou Natalia , Richter Kerstin , Alves Mariana R. P. , Karumbi Esther , Perkins Melinda Liu , Kocijan Tin , Rushlow Christine A. , Crocker Justin
Published: April 2023

Developmental enhancers are DNA sequences that when bound to transcription factors dictate specific patterns of gene expression during development. It has been proposed that the evolution of such cis-regulatory elements is a major source of adaptive evolution; however, the regulatory and evolutionary potential of such elements remains little understood, masked by selective constraints, drift and contingency. Here, using mutation libraries inDrosophila melanogasterembryos, we observed that most mutations in classical developmental enhancers led to changes in gene expression levels but rarely resulted in novel expression outside of the native cell- and tissue-types. In contrast, random sequences often acted as developmental enhancers, driving expression across a range of levels and cell-types, in patterns consistent with transcription factor motifs therein; random sequences including motifs for transcription factors with pioneer activity acted as enhancers even more frequently and resulting in higher levels of expression. Together, our findings suggest that the adaptive phenotypic landscapes of developmental enhancers are constrained by both enhancer architecture and chromatin accessibility. We propose that the evolution of existing enhancers is limited in its capacity to generate novel phenotypes, whereas the activity ofde novoelements is a primary source of phenotypic novelty.

QUOTE

“Chance and chance alone has a message for us.” Milan Kundera,The Unbearable Lightness of Being
Robust enhancement of motor sequence learning with 4mA transcranial electric stimulation
Authors: Hsu Gavin , Shereen A. Duke , Cohen Leonardo G. , Parra Lucas C.
Published: April 2023

Background and Objectives

Motor learning experiments with transcranial direct current stimulation (tDCS) at 2mA have produced mixed results. We hypothesize that tDCS will boost motor learning provided sufficiently high field intensity on the motor cortex.

Methods

In a single-blinded, between-subject design, 72 healthy right-handed participants received either anodal or cathodal tDCS at 4mA while they learned to perform a sequence of key presses using their non-dominant hand for about 12 minutes. Cathodal stimulation served as an active control for sensation. A separate sham-stimulation group established baseline performance. Gains during practice and rest periods were analyzed (called micro-online and -offline learning). The target for stimulation was identified on the motor cortex using fMRI. After optimization with individual current flow models, we selected a single montage for all 108 participants with 4 frontal and 4 parietal electrodes each drawing 1mA.

Results

We found significant gains in performance with anodal stimulation (Cohen’s d=0.7). The boost in performance persisted for at least one hour. Subsequent learning for a new sequence and the opposite hand also improved. Concurrent tDCS enhanced micro-offline learning, while subsequent learning relied on micro-online gains. Sensation ratings were comparable in the active groups and did not exceed moderate levels. The new electrode montage achieved a better tradeoff between stimulation intensity and sensations on the scalp as compared to alternative montages.

Conclusion

The present paradigm shows reliable behavioral effects at 4mA and is well-tolerated. It may serve as a go-to experiment for future studies on motor learning and tDCS.

Highlights

tDCS resulted in a lasting boost of concurrent learning with effect size of Cohen’s d=0.7.

Subsequent learning was also improved, indicating a form of meta-learning.

Detailed analysis of behavior suggests an effect of tDCS on sequence consolidation.

A novel electrode montage with 1mA through each of 4+4 electrodes was well-tolerated.
Bayesian Phylogenetic Inference of HIV Latent Lineage Ages Using Serial Sequences
Authors: Nagel Anna , Rannala Bruce
Published: April 2023

HIV evolves rapidly within individuals, allowing phylogenetic studies to infer the history of viral lineages on short time scales. Latent HIV sequences are an exception to this rapid evolution, as their transcriptional inactivity leads to negligible mutation rates in comparison to non-latent HIV lineages. Latent sequences are of keen interest as they provide insight into the formation, persistence, and decay of the latent reservoir. Different mutation rates in latent versus active HIV lineages generate potential information about the times at which sequences entered the latent reservoir. A Bayesian phylogenetic method is developed to infer integration times of latent HIV sequences. The method uses informative priors to incorporate biologically sensible bounds on inferences (such as requiring sequences to become latent before being sampled) that many existing methods lack. A new simulation method is also developed, based on widely-used epidemiological models of within-host viral dynamics, and applied to evaluate the new method, showing that point estimates and credible intervals are often more accurate by comparison with existing methods. Accurate estimates of latent integration dates are crucial in dating the formation of the latent reservoir relative to key events during HIV infection, such as the initiation of antiretroviral treatment. The method is applied to analyze publicly-available sequence data from 4 HIV patients, providing new insights regarding the temporal pattern of latent HIV integration events.

Significance Statement

Phylogenetic studies are increasingly being used to characterize within-host HIV evolution and the temporal dynamics of the HIV latent reservoir in particular, which is not targeted by current treatment methods and thus prevents a cure for HIV. Phylogenetic methods currently used to analyze HIV sequences suffer from conceptual and statistical problems that degrade their performance. A new Bayesian inference method to estimate the ages of latent sequences and a new simulation method based on within-host viral dynamics are developed. The new inference method outperforms existing methods, particularly in characterizing uncertainty. Understanding how the latent HIV reservoir changes overtime will allow researchers to better understand the nature of HIV infection and develop strategies for a cure.
Increasing the Field-of-View in Oblique Plane Microscopy via optical tiling
Authors: Chen Bingying , Chang Bo-Jui , Zhou Felix , Daetwyler Stephan , Sapoznik Etai , Gihana Gabriel M. , Castro Lizbeth Perez , Sorrell Maralice Conacci , Dean Kevin M. , Millett-Sikking Alfred , York Andrew G. , Fiolka Reto
Published: April 2023

Fast volumetric imaging of large fluorescent samples with high-resolution is required for many biological applications. Oblique plane microscopy (OPM) provides high spatiotemporal resolution, but the field of view is typically limited by its optical train and the pixel number of the camera. Mechanically scanning the sample or decreasing the overall magnification of the imaging system can partially address this challenge, albeit by reducing the volumetric imaging speed or spatial sampling, respectively. In this Letter, we introduce a novel dual-axis scan unit for OPM that enables rapid and high-resolution volumetric imaging throughout a volume of 800 × 500 × 200 microns. This enables imaging of model organisms, such as zebrafish embryos, with subcellular resolution. Furthermore, we combined this microscope with a real-time and multi-perspective projection imaging technique to increase the volumetric interrogation rate to more than 10 Hz.
Interplay of Human Metabolome and Gut Microbiome in Major Depression
Authors: Amin Najaf , Liu Jun , Bonnechere Bruno , MehmoudianDehkordi Siamak , Arnold Matthias , Batra Richa , Chiou Yu-Jie , Fernandes Marco , Ikram M. Arfan , Kraaij Robert , Krumsiek Jan , Newby Danielle , Nho Kwangsik , Radjabzadeh Djawad , Saykin Andrew J , Shi Liu , Sproviero William , Winchester Laura , Yang Yang , Nevado-Holgado Alejo J , Kastenmüller Gabi , Kaddurah-Daouk Rima F , van Duijn Cornelia M
Published: April 2023

The pathogenesis of depression is complex involving the interplay of genetic and environmental risk factors including diet, lifestyle and the gut microbiome. Metabolomics studies may shed light on the interplay of these factors. We study over 63,000 individuals including 8462 cases with a lifetime major depression and 5403 cases with recurrent major depression from the UK Biobank profiled for nuclear magnetic resonance (NMR) spectroscopy based metabolites with the Nightingale platform. We identify 124 metabolites that are associated with major depressive disorder (MDD), including 49 novel associations. No differences were seen between the metabolic profiles of lifetime and recurrent MDD. We find that metabolites involved in the tricarboxylic acid (TCA) cycle are significantly altered in patients with MDD. Integrating the metabolic signatures of major depression and the gut microbiome, we find that the gut microbiome might play an important role in the relationship between these metabolites, lipoproteins in particular, and MDD. The orderClostridiales, and the phylaProteobacteriaandBacteroideteswere the most important taxa, which link the lipoprotein particles to MDD. Our study shows that at the molecular level energy metabolism is disturbed in patients with MDD and that the interplay between the gut microbiome and blood metabolome may play a key role in the pathogenesis of MDD.