bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of aerobic exercise on hippocampal formation volume in people with schizophrenia – a systematic review and meta-analysis with original data from a randomized-controlled trial
Authors: Roell Lukas , Fischer Tim , Keeser Daniel , Papazov Boris , Lembeck Moritz , Papazova Irina , Greska David , Muenz Susanne , Schneider-Axmann Thomas , Sykorova Eliska , Thieme Cristina E. , Vogel Bob O. , Mohnke Sebastian , Huppertz Charlotte , Roeh Astrid , Keller-Varady Katriona , Malchow Berend , Stoecklein Sophia , Ertl-Wagner Birgit , Henkel Karsten , Wolfarth Bernd , Tantchik Wladimir , Walter Henrik , Hirjak Dusan , Schmitt Andrea , Hasan Alkomiet , Meyer-Lindenberg Andreas , Falkai Peter , Maurus Isabel
Published: November 2024

Background

The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications.

Methods

The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes.

Results

Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus.

Conclusions

Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.
The effect of polygenic liability to mental disorders on COVID-19 outcomes in people with depression: the mediating role of anxiety
Authors: Monistrol-Mula Anna , Felez-Nobrega Mireia , Byrne Enda M. , Lind Penelope A. , Hickie Ian B. , Martin Nicholas G. , Medland Sarah E. , Colodro-Conde Lucía , Mitchell Brittany L.
Published: November 2024

Background

Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression.

Methods

Data from three assessments of the Australian Genetics of Depression Study (N = 4405; 52.2 years ± 14.9; 76.2% females) were analyzed. Outcomes included COVID-19 clinical outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and long COVID, noting the low incidence of COVID-19 cases in Australia at that time) and COVID-19 psychological outcomes (COVID-related stress and COVID-19 burnout). Predictors included PRS for depression, bipolar disorder, schizophrenia, and anxiety. The associations between these PRSs and the outcomes were assessed with adjusted linear/logistic/multinomial regressions. Mediation (N = 4338) and moderation (N = 3326) analyses were performed to explore the potential influence of anxiety symptoms and resilience on the identified associations between the PRSs and COVID-19 psychological outcomes.

Results

None of the selected PRS predicted SARS-CoV-2 infection or long COVID. In contrast, the depression PRS predicted higher levels of COVID-19 burnout. Anxiety symptoms fully mediated the association between the depression PRS and COVID-19 burnout. Resilience did not moderate this association.

Conclusions

A higher genetic risk for depression predicted higher COVID-19 burnout and this association was fully mediated by anxiety symptoms. Interventions targeting anxiety symptoms may be effective in mitigating the psychological effects of a pandemic among people with depression.
Diagnostic profiles among suicide decedents with and without borderline personality disorder
Authors: Kaufman Erin A. , Coon Hilary , Shabalin Andrey A. , Monson Eric T. , Chen Danli , Staley Michael J. , Keeshin Brooks R. , Docherty Anna R. , Bakian Amanda V. , DiBlasi Emily
Published: November 2024

Background

Borderline personality disorder (BPD) is a debilitating condition characterized by pervasive instability across multiple major domains of functioning. The majority of persons with BPD engage in self-injury and up to 10% die by suicide – rendering persons with this condition at exceptionally elevated risk of comorbidity and premature mortality. Better characterization of clinical risk factors among persons with BPD who die by suicide is urgently needed.

Methods

We examined patterns of medical and psychiatric diagnoses (1580 to 1700 Phecodes) among persons with BPD who died by suicide (n = 379) via a large suicide death data resource and biobank. In phenotype-based phenome-wide association tests, we compared these individuals to three other groups: (1) persons who died by suicide without a history of BPD (n = 9468), (2) persons still living with a history of BPD diagnosis (n = 280), and (3) persons who died by suicide with a different personality disorder (other PD n = 589).

Results

Multivariable logistic regression models revealed that persons with BPD who died by suicide were more likely to present with co-occurring psychiatric diagnoses, and have a documented history of self-harm in the medical system prior to death, relative to suicides without BPD. Posttraumatic stress disorder was more elevated among those with BPD who died by suicide relative to the other PD group.

Conclusions

We found significant differences among persons with BPD who died by suicide and all other comparison groups. Such differences may be clinically informative for identifying high-risk subtypes and providing targeted intervention approaches.
Exosc10 deficiency in the initial segment is dispensable for sperm maturation and male fertility in mice
Authors: Zhou Meiyang , Yu Junjie , Xu Yu , Li Hong , Feng Yan-Qin , Wang Xiao , Qiu Fanyi , Li Nana , Wang Zhengpin
Published: November 2024

EXOSC10 is an exosome-associated ribonuclease that degrades and processes a wide range of transcripts in the nucleus. The initial segment (IS) of the epididymis is crucial for sperm transport and maturation in mice by affecting the absorption and secretion that is required for male fertility. However, the role of EXOSC10 ribonuclease-mediated RNA metabolism within the IS in the regulation of gene expression and sperm maturation remains unknown. Herein, we established an Exosc10 conditional knockout (Exosc10 cKO) mouse model by crossing Exosc10F/F mice with Lcn9-Cre mice which expressed recombinase in the principal cells of IS as early as post-natal day 17. Morphological and histological analyses revealed that Exosc10 cKO males had normal spermatogenesis and development of IS. Moreover, the sperm concentration, morphology, motility, and frequency of acrosome reactions in the cauda epididymides of Exosc10 cKO mice were comparable with those of control mice. Thus, Exosc10 cKO males had normal fertility. Collectively, our genetic mouse model and findings demonstrate that loss of EXOSC10 in the IS of epididymis is dispensable for sperm maturation and male fertility.
Sinus node dysfunction in children: different aetiologies, similar clinical course in two-centre experience
Authors: Tunca Sahin Gulhan , Kurt Cemil Cihad , Kafali Hasan Candas , Sevinc Sengul Fatma , Haydin Sertac , Ozgur Senem , Guzeltas Alper , Ergul Yakup
Published: November 2024

Aim:

This study aims to evaluate the clinical characteristics and outcomes of children diagnosed with sinus node dysfunction.

Methods:

This was a retrospective review of patients diagnosed with sinus node dysfunction in two tertiary paediatric cardiology centres in Turkey from January 2011 to June 2022.

Results:

In all, 77 patients (50, 64.9% males) were included, with a mean age of 8.2 ± 6.3 years and a mean weight of 28.2 ± 18.8 kg. While age-incompatible bradycardia and pauses were the most common rhythm disturbances, syncope, presyncope, and dizziness (n:33, 43%) were the most frequent initial symptoms. Structural heart disease was present in 58 (75.3%) of the 77 patients, 47 (61%) of whom were congenital. The most commonly associated CHDs were transposition of the great arteries (n:8), atrial septal defect (n:7), and atrioventricular septal defect (n:5). Seven of them also had left atrial isomerism. The remaining 19 patients were isolated. Four patients had SCN5A mutation (two of them were siblings) and two of them had Emery–Dreifuss muscular dystrophy.

Conclusion:

Although sinus node dysfunction is rare in children, it has been diagnosed with increasing frequency with structural heart disease, especially in patients who have undergone corrective cardiac surgery related to atrial tissue. Since sinus node dysfunction can occur at any time postoperatively, these patients should be kept under constant control. If symptomatic sinus node dysfunction is confirmed, permanent pacing is an effective therapeutic modality.
The Matter and Form of Kant’s Moral Law
Authors: Biondi Zachary
Published: November 2024

There is an interpretative puzzle at the centre of Kant’s Groundwork for the Metaphysics of Morals. The text presents the single principle of morality (G, 4: 392), but instead of providing a definitive statement of the principle, we find a three-step sequence of formulas. The puzzle concerns the formula relation: given the contrast between the moral law’s individuality and the plurality of formulas, how do the formulas relate to each other and the moral law? This paper takes the first step towards a new account by focusing on G, 4: 436, a passage in which Kant makes claims about the matter and form of the moral law. By understanding the hylomorphism entailed by these claims, it is possible to achieve new perspectives on common questions about Kant’s ethics, in particular, the role of the formulas in deriving or explaining duties and how the formulas are used in the argument of Groundwork II and its transition from popular moral philosophy to metaphysics of morals.
Asymptotic behavior of bond yields and volatilities for the extended 3/2 model under the real-world measure
Authors: Fergusson Kevin
Published: November 2024

The extended
$3/2$
short rate model is a mean reverting model of the short rate which, for suitably chosen parameters, permits a sensible term structure of bond yields and closed-form valuation formulae of zero-coupon bonds and options. This article supplies proofs of the formulae for the expected present values of future cash flows under the real-world probability measure, known as actuarial valuation. Finally, we give formulae for asymptotic levels of bond yields and formulae for bond option prices for the extended
$3/2$
model, under particular conditions on its parameters.
From dreadful shame to manageable incident: How post-mortem cleaning workers’ narratives change the feeling rules about “lonely deaths” in Japan
Authors: Toyota Mika
Published: November 2024

Since the 1990s, Japan has experienced the rise of a phenomenon known as “lonely death” (kodokushi 孤独死): people who die alone and whose death goes unnoticed for a certain period of time. This has triggered public anxiety and moral panic because lonely death is often perceived as a form of “bad death” and a sign of the breakdown of family ties and neighborly relations. In the 2020s, this “feeling rule,” which associates lonely death with shame and fear, has quietly begun to be challenged by a group of post-mortem cleaning workers. By sharing their work experience and feelings through blogs, artworks, and books, the workers’ accounts of how they deal with the remnants of the deceased have turned the public perception of lonely death from an abstract, totalizing, fearful category into an understanding that such incidents have specific causes that can be faced and even prepared for. The cleaners’ emotional labor, especially their mourning for the dead, creates a sense of relatedness to the deceased, a feeling which is conveyed to the public through the cleaners’ narratives. The cleaners thereby change the feeling rules associated with the labor of dealing with the aftermath of a lonely death, turning it from “dirty work” into meaningful social action. This article contributes to an understanding of feeling rules by highlighting how individuals’ efforts, particularly, their reflections on their emotional labor, can change collective feeling rules.
Reintegration of People with Substance Use Disorders into Working Life
Authors: Schlöffel Malgorzata , Bayrhuber Marianne , Armbruster Christoph , Farin-Glattacker Erik
Published: November 2024

Abstract: Aims: Unemployment is a common problem among people with substance use disorders. Aim of this feasibility study is to explore possible positive effects of a new intervention to increase the integration of unemployed people with substance use disorders into the labour market. Methods: A prospective, non-controlled longitudinal study with four measurement points and mixed-methods-design will be conducted to check feasibility of a novel intervention. The primary outcome of the study is the reintegration of job seekers with substance use disorders into working life, secondary outcomes are substance use, point abstinence, work-related self-management and the subjective impairment. Conclusion: The concept of an outpatient work-orientated rehabilitation, with the collaboration of different actors can be successful as a possible way of addiction rehabilitation in practice. Should the intervention turn out to be feasible, then the evaluation should proceed to the next step and an effectiveness study (e. g. randomized controlled trial) should be planned.
Issues Behind the Measurement of Political Orientation
Authors: Lee Ahlam , Eshleman Latimer Samuel R.
Published: November 2024

Abstract: Given the limited research addressing the construct and content validity of single-item and multiple-item measures of political orientation (PO), we investigated the effect sizes in the relationship between PO and variables categorized into multiple dimensions using a meta-analysis of 511 independent effect sizes from 108 articles published from 2012 to 2022. Multiple-item measures of PO that included economic items had a large effect size ( r = .55 ~ .75) in their association with variables in the economic, environmental, and traditionalism dimensions, whereas we found small effect sizes ( r = .23 ~ .24) between single-item PO and variables in the economic and environmental dimensions and a medium effect size ( r = .31) between single-item PO and variables in the traditionalism dimension. Based on the pooled data consisting of all multiple dimensions’ data subsets, we found medium effect sizes ( r = .35 ~ .39) for multiple-item measures of PO and a small effect size ( r = .27) for single-item PO. Our content analysis of 30 multiple-item measures of PO showed that over 80% of multiple-item measures were grounded in US and/or Western countries’ political contexts and samples and 50% of them did not measure economic aspects of PO. We discuss implications for future research.
Postdoc Perspectives on Leadership and Matters of Equity and Inclusion in Polar Science
Authors: Goliber Sophie , Coenen Jason , Fair Heather , Szesciorka Angela R. , Schulz Kirstin , Harning David J. , Fernando Benjamin , Ksenofontov Stanislav Saas , Pacini Astrid , Rivera Marisol Juarez , Calmer Radiance , Conroy John A. , Doting Eva Lisa , Bergelin Marie , Dunmire Devon , Sánchez Montes Maria Luisa , Ravelo Alexandra M. , Sledd Anne , Stinchcomb Taylor R. , Tibbett Emily J. , Dryák‐Vallies Mariama C.
Published: November 2024

In 2023, the first Polar Postdoc Leadership Workshop convened to discuss present and future polar science issues and to develop leadership skills. The workshop discussions fostered a collective commitment to inclusive leadership within the polar science community among all participants. Here, we outline challenges encountered by underrepresented groups in polar sciences, while also noting that progress has been made to improve inclusivity in the field. Further, we highlight the inclusive leadership principles identified by workshop participants to bring to the polar community as we transition into leadership roles. Finally, insights and practical knowledge we gained from the workshop are shared, aiming to inform the community of our commitment to inclusive leadership and encourage the polar community to join us in pursuing action toward our shared vision for a more welcoming polar science future.
3‐D Subsurface Geophysical Modeling of the Charity Shoal Structure: A Probable Late Proterozoic‐Early Paleozoic Simple Impact Structure in Eastern Lake Ontario
Authors: Armour Mary H. , Boyce Joseph I. , Suttak Phillip , Hrvoic Doug
Published: November 2024

The Charity Shoal structure is a circular, ∼1.2‐km‐diameter, bedrock‐rimmed shoal in eastern Lake Ontario with a ∼20‐m‐deep central basin. The structure has been proposed as a possible Middle Ordovician impact crater or volcanic intrusion. We conducted marine seismic and magnetic surveys (9‐km2) and 3‐D geophysical modeling to better resolve the Charity Shoal subsurface geology and possible origins. Three models were evaluated: (a) a buried (>450 m) impact structure in Mesoproterozoic basement, (b) a maar‐diatreme, (c) a cylindrical, zoned volcanic plug. Seismic profiles and multi‐beam bathymetry revealed >30 m of Quaternary sediments overlying Middle Ordovician (Trenton Group) carbonate bedrock and complex, 3‐dimensional folding and faulting of the structure rim. Magnetic surveys recorded an annular magnetic high (>600 nT) over the structure rim and a central magnetic low (∼500–600 nT) coincident with a ∼−1.7 mGal Bouguer gravity anomaly. The continuity of Trenton Group strata in seismic profiles rules out a previously proposed Mesozoic maar‐diatreme intruded into Paleozoic strata. The zoned volcanic plug model reproduced the annular magnetic anomaly but was incompatible with Bouguer gravity profiles. The magnetic anomaly was best reproduced by a simple impact structure seated in Mesoproterozoic basement at 450–500 m depth with a rim‐to‐rim diameter of ∼1.2 km and rim height of ∼10–20 m. A 100‐m wide and 50‐m‐deep channel in the Mesoproterozoic basement may record fluvial dissection of the southwestern rim. A buried (>450 m), simple impact crater is most compatible with all available geophysical data at Charity Shoal.
Can Large Strains Be Accommodated by Small Faults: “Brittle Flow of Rocks” Revised
Authors: Zou Xiaoyu , Fialko Yuri
Published: November 2024

Brittle deformation in the upper crust is thought to occur primarily via faulting. The fault length‐frequency distribution determines how much deformation is accommodated by numerous small faults versus a few large ones. To evaluate the amount of deformation due to small faults, we analyze the fault length distribution using high‐quality fault maps spanning a wide range of spatial scales from a laboratory sample to an outcrop to a tectonic domain. We find that the cumulative fault length distribution is well approximated by a power law with a negative exponent close to 2. This is in agreement with the earthquake magnitude‐frequency distribution (the Gutenberg‐Richter law with b‐value of 1), at least for faults smaller than the thickness of the seismogenic zone. It follows that faulting is a self‐similar process, and a substantial fraction of tectonic strain can be accommodated by faults that don't cut through the entire seismogenic zone, consistent with inferences of “hidden strain” from natural and laboratory observations. A continued accumulation of tectonic strain may eventually result in a transition from distributed fault networks to localized mature faults.
Observations Over a Century Underscore an Increasing Likelihood of Compound Dry‐Hot Events in China
Authors: Duan Ruixin , Huang Guohe , Wang Feng , Tian Chuyin , Wu Xinying
Published: November 2024

The impacts of extreme events are seldom caused by a single climatic variable but rather arise from the interaction of multiple climate drivers. This study employs observational data sets with high spatiotemporal resolution to analyze the risk of occurrence of compound dry‐hot events in China over the past 120 years (i.e., 1901–2020). Simultaneously, attribution analysis based on distribution functions explores whether and to what extent human activities influence the occurrence of compound events. The results indicate that over the historical 120‐year period, the frequency of compound dry‐hot events in China has gradually increased, with the highest frequency observed in the most recent 40 years (i.e., 1981–2020). The frequency of compound dry‐hot events during this period is approximately four times that of 1901–1940 and about twice that of 1941–1980. The analysis of the relative importance of different factors reveals that temperature changes contribute more (56%) to the occurrence of compound events than precipitation (23%), and also exceed the interaction between them (21%). The substantial increase in compound dry‐hot events is largely attributed to the influence of human activities. Across seven sub‐regions, human activities have led to an increase in the probability of compound events occurring, ranging from 7.9% to 31.6%. The findings of this study indicate that human activities have significant implications for explaining the observed increase in compound hot and dry events over the past 40 years.
Lunar Nearside‐Farside Mare Basalt Asymmetry: The Combined Role of Global Crustal Thickness Variations and South Pole‐Aitken (SPA) Basin‐Induced Lithospheric Thickening
Authors: Head James W. , Wang Xing , Lark Laura H. , Wilson Lionel , Qian Yuqi
Published: November 2024

Lunar mare basalts represent melting of mantle material, buoyant ascent in dikes, and eruption onto <20% of the surface. Global mare distribution is distinctly asymmetrical, with a paucity on the farside, plausibly interpreted to be related to thicker farside low‐density crust inhibiting buoyant magma rise to the surface. Challenging this hypothesis is the presence of the huge, ancient farside South Pole‐Aitken (SPA) basin, site of the thinnest crust and deepest depression observed on the Moon. We hypothesize that an oblique impact stripped the farside crust within the SPA basin, permitting early mare basalt emplacement as cryptomaria due to thin/absent crust. However, removal of the SPA thermally insulating megaregolith/crust accelerated lithosphere thickening beneath the basin. This deepening rheological barrier inhibited buoyant rise of mantle diapirs below SPA, resulting in early abatement of mare basalt extrusions compared to the nearside, and retention of the deep, underfilled SPA impact basin observed today.
A Critical Core Size for Dynamo Action at the Galilean Satellites
Authors: Trinh K. T. , Bierson C. J. , O’Rourke J. G.
Published: November 2024

Ganymede is the only known moon with an active dynamo. No mission has discovered intrinsic magnetism at the other Galilean satellites: Io, Europa, and Callisto. A dynamo requires a large magnetic Reynolds number, which in turn demands, for these moons, a large metallic core that is cooling fast enough for convection. Here we quantify these requirements to construct a regime diagram for the Galilean satellites. We compute the internal heat fluxes that would sustain a dynamo over the wide ranges of plausible radii for their metallic cores. Below a critical radius, no plausible heat flux will sustain a dynamo. Europa likely sits on the opposite side of this limit than Ganymede and Io. We predict that future missions may confirm a small (or absent) core, meaning that Europa could not sustain a dynamo even if its interior were cooling as quickly as Ganymede's core.
Seasonal Upwelling Forecasts in the California Current System
Authors: Amaya Dillon J. , Jacox Michael G. , Alexander Michael A. , Bograd Steven J. , Jia Liwei
Published: November 2024

Coastal upwelling plays a vital role in the support and maintenance of productive marine ecosystems throughout the California Current System (CCS). Here, we evaluate upwelling forecast skill using ∼30 years of seasonal reforecasts from four global climate models contributing to the North American Mulitmodel Ensemble (NMME). The models skillfully predict upwelling intensity throughout much of the CCS in boreal winter, and in the South‐Central CCS in spring/summer. The models also skillfully predict various aspects of upwelling phenology, including the timing of the spring transition, as well as the total vertical transport integrated over the course of the upwelling season. Climatic sources of forecast skill vary with season, with contributions from the El Niño‐Southern Oscillation in winter‐spring, and the North Pacific Oscillation and the North Pacific Meridional Mode in the winter‐summer. Our results highlight the potential of seasonal climate forecasts to inform management of upwelling‐sensitive marine resources.
Limited Preservation of Strike‐Slip Surface Displacement in the Geomorphic Record
Authors: Reitman Nadine G. , Klinger Yann , Briggs Richard W. , Gold Ryan D.
Published: November 2024

Offset geomorphic markers are commonly used to interpret slip history of strike‐slip faults and have played an important role in forming earthquake recurrence models. These data sets are typically analyzed using cumulative probability methods to interpret average amounts of slip in past earthquakes. However, interpretation of the geomorphic record to infer surface slip history is complicated by slip variability, measurement uncertainty, and modification of offset features in the landscape. To investigate how well geomorphic data record surface slip, we use offset measurements from recent strike‐slip surface ruptures (n = 39), faults with geomorphic evidence of multiple strike‐slip earthquakes (n = 29), and synthetic slip distributions with added noise (n10,000) to examine the constraints of the geomorphic record and the underlying assumptions of the cumulative offset probability distribution analysis method. We find that the geomorphic record is unlikely to resolve more than two paleo‐slip distributions, except in specific cases with low slip variability, high slip‐per‐event, and semiarid climate. In cases where site‐specific conditions allow for interpretation of more than two earthquakes, lateral extrapolation along a fault is not straightforward because on‐fault displacement and distributed deformation may be spatially variable in each earthquake. We also find that average slip in modern earthquakes is adequately recovered by probability methods, but the reported prevalence of strike‐slip faults with characteristic slip history is not supported by geomorphic data. We also propose updated methods to interpret slip history and construct uncertainty bounds for paleo‐slip distributions.
Matching patients to clinical trials with large language models
Authors: Jin Qiao , Wang Zifeng , Floudas Charalampos S. , Chen Fangyuan , Gong Changlin , Bracken-Clarke Dara , Xue Elisabetta , Yang Yifan , Sun Jimeng , Lu Zhiyong
Published: November 2024

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.
Molecular profiles, sources and lineage restrictions of stem cells in an annelid regeneration model
Authors: Stockinger Alexander W. , Adelmann Leonie , Fahrenberger Martin , Ruta Christine , Özpolat B. Duygu , Milivojev Nadja , Balavoine Guillaume , Raible Florian
Published: November 2024

Regeneration of missing body parts can be observed in diverse animal phyla, but it remains unclear to which extent these capacities rely on shared or divergent principles. Research into this question requires detailed knowledge about the involved molecular and cellular principles in suitable reference models. By combining single-cell RNA sequencing and mosaic transgenesis in the marine annelid Platynereis dumerilii, we map cellular profiles and lineage restrictions during posterior regeneration. Our data reveal cell-type specific injury responses, re-expression of positional identity factors, and the re-emergence of stem cell signatures in multiple cell populations. Epidermis and mesodermal coelomic tissue produce distinct putative posterior stem cells (PSCs) in the emerging blastema. A novel mosaic transgenesis strategy reveals both developmental compartments and lineage restrictions during regenerative growth. Our work supports the notion that posterior regeneration involves dedifferentiation, and reveals molecular and mechanistic parallels between annelid and vertebrate regeneration.
Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease
Authors: Barbehenn Alton , Shi Lei , Shao Junzhe , Hoh Rebecca , Hartig Heather M. , Pae Vivian , Sarvadhavabhatla Sannidhi , Donaire Sophia , Sheikhzadeh Caroline , Milush Jeffrey , Laird Gregory M. , Mathias Mignot , Ritter Kristen , Peluso Michael J. , Martin Jeffrey , Hecht Frederick , Pilcher Christopher , Cohen Stephanie E. , Buchbinder Susan , Havlir Diane , Gandhi Monica , Henrich Timothy J. , Hatano Hiroyu , Wang Jingshen , Deeks Steven G. , Lee Sulggi A.
Published: November 2024

Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.
Chromatin compaction during confined cell migration induces and reshapes nuclear condensates
Authors: Zhao Jessica Z. , Xia Jing , Brangwynne Clifford P.
Published: November 2024

Cell migration through small constrictions during cancer metastasis requires significant deformation of the nucleus, with associated mechanical stress on the nuclear lamina and chromatin. However, how mechanical deformation impacts various subnuclear structures, including protein and nucleic acid-rich biomolecular condensates, is largely unknown. Here, we find that cell migration through confined spaces gives rise to mechanical deformations of the chromatin network, which cause embedded nuclear condensates, including nucleoli and nuclear speckles, to deform and coalesce. Chromatin deformations exhibit differential behavior in the advancing vs. trailing region of the nucleus, with the trailing half being more permissive for de novo condensate formation. We show that this results from increased chromatin heterogeneity, which gives rise to a shift in the binodal phase boundary. Taken together, our findings show how chromatin deformation impacts condensate assembly and properties, which can potentially contribute to cellular mechanosensing.
Mechanistic basis of atypical TERT promoter mutations
Authors: Elliott Kerryn , Singh Vinod Kumar , Bäckerholm Alan , Ögren Linnea , Lindberg Markus , Soczek Katarzyna M. , Hoberg Emily , Luijts Tom , Van den Eynden Jimmy , Falkenberg Maria , Doudna Jennifer , Ståhlberg Anders , Larsson Erik
Published: November 2024

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases −124 and −146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process. Canonical TERTp mutations create de novo binding sites for ETS family transcription factors that induce favourable conditions for DNA damage formation by UV light, thus creating a hotspot effect but only after a first mutational hit. In agreement, atypical TERTp mutations co-occur with canonical driver mutations in large cancer cohorts and arise subclonally specifically on the TERTp driver mutant chromosome homolog of melanoma cells treated with UV light in vitro. Our study gives an in-depth view of TERTp mutations in cancer and provides a mechanistic explanation for atypical TERTp mutations.
A modular platform for bioluminescent RNA tracking
Authors: Halbers Lila P. , Cole Kyle H. , Ng Kevin K. , Fuller Erin B. , Chan Christelle E. T. , Callicoatte Chelsea , Metcalfe Mariajose , Chen Claire C. , Barhoosh Ahfnan A. , Reid-McLaughlin Edison , Kent Alexandra D. , Torrey Zachary R. , Steward Oswald , Lupták Andrej , Prescher Jennifer A.
Published: November 2024

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs. The RNA tags are engineered to recruit light-emitting luciferase fragments (termed RNA lanterns) upon transcription. Robust photon production is observed for RNA targets both in cells and in live animals. Importantly, only a single copy of the tag is necessary for sensitive detection, in sharp contrast to fluorescent platforms requiring multiple repeats. Overall, this work provides a foundational platform for visualizing RNA dynamics from the micro to the macro scale.
Tailoring superstructure units for improved oxygen redox activity in Li-rich layered oxide battery’s positive electrodes
Authors: Liu Hao , Hua Weibo , Kunz Sylvia , Bianchini Matteo , Li Hang , Peng Jiali , Lin Jing , Dolotko Oleksandr , Bergfeldt Thomas , Wang Kai , Kübel Christian , Nagel Peter , Schuppler Stefan , Merz Michael , Ying Bixian , Kleiner Karin , Mangold Stefan , Wong Deniz , Baran Volodymyr , Knapp Michael , Ehrenberg Helmut , Indris Sylvio
Published: November 2024

The high-voltage oxygen redox activity of Li-rich layered oxides enables additional capacity beyond conventional transition metal (TM) redox contributions and drives the development of positive electrode active materials in secondary Li-based batteries. However, Li-rich layered oxides often face voltage decay during battery operation. In particular, although Li-rich positive electrode active materials with a high nickel content demonstrate improved voltage stability, they suffer from poor discharge capacity. Here, via physicochemical and electrochemical measurements, we investigate the correlation between oxygen redox activity and superstructure units in Li-rich layered oxides, specifically the fractions of LiMn6 and Ni4+-stabilized LiNiMn5 within the TM layer. We prove that an excess of LiNiMn5 hinders the extraction/insertion of lithium ions during Li metal coin cell charging/discharging, resulting in incomplete oxygen redox activity at a cell potential of about 3.3 V. We also demonstrate that lithium content adjustment could be a beneficial approach to tailor the superstructure units. Indeed, we report an improved oxygen redox reversibility for an optimized Li-rich layered oxide with fewer LiNiMn5 units.
Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development
Authors: Krenger Pascal S. , Roques Magali , Vogt Anne-Cathrine S. , Pardini Alessandro , Rothen Dominik A. , Balke Ina , Schnider Sophie T. , Mohsen Mona O. , Heussler Volker T. , Zeltins Andris , Bachmann Martin F.
Published: November 2024

RTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain. However, neither RTS,S nor R21 targets this junction domain. To test the potential of the NPDP junction domain and other sites of PfCSP as innovative vaccine targets, we developed multiple vaccine candidates based on cucumber mosaic virus-like particles (CuMVTT-VLPs). These candidates vary in several aspects: the number of targeted NANP repeats, the presence or absence of the junction domain, the cleavage site, and up to three NVDP repeats within the target sequence. Immunogenicity and efficacy studies were conducted in BALB/c mice, utilizing chimeric Plasmodium berghei (Pb) sporozoites, in which the endogenous CSP has been replaced by PfCSP (Pb/PfCSP). We observed a positive association between the number of targeted NANP repeats and the induction of specific IgM/IgG antibodies. Elevated humoral responses led to enhanced protection against parasitemia after Pb/PfCSP sporozoite challenge. Especially high-avidity/affinity antibody formation and vaccine protection were NANP repeat-dependent. Intriguingly, vaccine efficacy was not enhanced by targeting sites on PfCSP other than the NANP repeats. Our data emphasize the dominant role of the NANP repeat region for induction of protective antibodies. Furthermore, we present here novel malaria vaccine candidates with an excellent immunogenic profile that confer sterile protection in mice, even in absence of adjuvants.
Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts
Authors: Manghi Paolo , Bhosle Amrisha , Wang Kai , Marconi Roberta , Selma-Royo Marta , Ricci Liviana , Asnicar Francesco , Golzato Davide , Ma Wenjie , Hang Dong , Thompson Kelsey N. , Franzosa Eric A. , Nabinejad Amir , Tamburini Sabrina , Rimm Eric B. , Garrett Wendy S. , Sun Qi , Chan Andrew T. , Valles-Colomer Mireia , Arumugam Manimozhiyan , Bermingham Kate M. , Giordano Francesca , Davies Richard , Hadjigeorgiou George , Wolf Jonathan , Strowig Till , Berry Sarah E. , Huttenhower Curtis , Spector Tim D. , Segata Nicola , Song Mingyang
Published: November 2024

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components. Here we conducted a multi-cohort, multi-omic analysis of US and UK populations with detailed dietary information from a total of 22,867 participants, which we then integrated with public data from 211 cohorts (N = 54,198). The link between coffee consumption and microbiome was highly reproducible across different populations (area under the curve of 0.89), largely driven by the presence and abundance of the species Lawsonibacter asaccharolyticus. Using in vitro experiments, we show that coffee can stimulate growth of L. asaccharolyticus. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and L. asaccharolyticus. This study reveals a metabolic link between a specific gut microorganism and a specific food item, providing a framework for the understanding of microbial dietary responses at the biochemical level.
Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment
Authors: Li Ruoyan , Strobl Johanna , Poyner Elizabeth F. M. , Balbaa Aya , Torabi Fereshteh , Mazin Pavel V. , Chipampe Nana-Jane , Stephenson Emily , Ramírez-Suástegi Ciro , Shanmugiah Vijaya Baskar Mahalingam , Gardner Louis , Olabi Bayanne , Coulthard Rowen , Botting Rachel A. , Zila Nina , Prigmore Elena , Gopee Nusayhah H. , Chroscik Marta A. , Kritikaki Efpraxia , Engelbert Justin , Goh Issac , Chan Hon Man , Johnson Harriet F. , Ellis Jasmine , Rowe Victoria , Tun Win , Reynolds Gary , Yang Dexin , Foster April Rose , Gambardella Laure , Winheim Elena , Admane Chloe , Rumney Benjamin , Steele Lloyd , Jardine Laura , Nenonen Julia , Pickard Keir , Lumley Jennifer , Hampton Philip , Hu Simeng , Liu Fengjie , Liu Xiangjun , Horsfall David , Basurto-Lozada Daniela , Grimble Louise , Bacon Chris M. , Weatherhead Sophie C. , Brauner Hanna , Wang Yang , Bai Fan , Reynolds Nick J. , Allen Judith E. , Jonak Constanze , Brunner Patrick M. , Teichmann Sarah A. , Haniffa Muzlifah
Published: November 2024

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.
A multilevel analysis of factors associated with wasting in children one to two years old in Hamadan city
Authors: Manoochehri Sara , Manoochehri Zohreh , Asadi Fatemeh Torkaman , Soltanian Ali Reza
Published: November 2024

The study aimed to identify risk factors for childhood wasting in 1–2 year-olds in Hamadan city, focusing on this age group due to infection and malnutrition risks. Unlike previous cross-sectional studies on children under 5 years old, this longitudinal study tracked weight-to-height changes over time. Data were analyzed from 455 mother-child pairs, aged 1–2 years, collected from health centers and recorded in the Integrated Electronic Health System (SIB). The weight-for-height index, an ordinal response with three categories (wasting, normal, and overweight), was measured several times. A two-level longitudinal ordinal model was used to identify factors associated with wasting. The analysis of data from 230 girls and 225 boys identified several factors associated with wasting: lower birth weight (Adjusted Odds Ratio (AOR) = 0.77), age 12–15 months (AOR = 1.15), lack of health insurance (AOR = 3.09), mother-child residence (AOR = 3.80), maternal height (AOR = 0.92), and age at pregnancy < 24 years (AOR = 4.71). The results of this study showed that most of the factors contributing to childhood wasting can be controlled and prevented. Therefore, implementation of targeted policies and appropriate interventions for mothers before, during, and after pregnancy could reduce the burden of childhood wasting.
Modeling linear and nonlinear viscoelastic oscillatory rheometric stress-strain hysteresis of asphalt binders
Authors: Diab Aboelkasim , You Lingyun , Topa Ameen , Saboo Nikhil , Sukhija Mayank , Awed Ahmed
Published: November 2024

Understanding the complex stress-strain hysteresis behavior of asphalt binders under varied conditions is critical for optimizing pavement performance. This study addresses the challenge by analyzing and modeling asphalt binder responses in oscillating shear mode across different aging states (unaged, short-term aged, and long-term aged), stretch amplitudes, frequencies, and temperatures. Fifty-three stress-strain hysteresis loops were meticulously analyzed, revealing distinct stress paths relative to applied stretch levels. A nine-parameter parallel rheological framework model was developed, integrating a four-parameter eight-chain (FEC) hyperelastic model in one network and a FEC hyperelastic model with a linear viscoelastic flow element in series in another. This constitutive model was implemented in LS-DYNA finite element simulations to predict experimentally-measured stress-strain hysteresis loops accurately. The research demonstrates the model’s capability to simulate both linear and nonlinear viscoelastic responses of asphalt binders across a wide range of environmental and loading conditions. This approach significantly enhances our ability to capture and understand the stress-strain behavior critical for asphalt pavement durability and performance optimization.
A low-cost perfusion heating system for slice electrophysiology
Authors: Dorst Matthijs , Vervaeke Koen
Published: November 2024

Temperature-critical applications, such as patch-clamp electrophysiology, require constant perfusion at a fixed temperature. However, maintaining perfusate at a specific temperature throughout various applications requires heaters or coolers with integrated feedback systems, which has historically increased complexity and cost. This makes such systems prohibitively expensive in research environments with lower funding rates, particularly in developing countries. We developed a custom temperature control system that relies on off-the-shelf components and few custom parts, which can be easily produced with common tools. Our system can be built for less than $30 and maintains a set perfusate temperature within 0.4 °C while introducing negligible electrical interference. Using this system, we demonstrate that Striatal Medium Spiny Neurons exhibit increased membrane resistance, longer membrane time constants, lower firing rates, and increased rheobase current at room temperature compared to physiological temperature.