bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence from recent clinical trials in fibrotic interstitial lung diseases
Authors: Cottin Vincent , Valenzuela Claudia 
Published: August 2024

Purpose of review
Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrosing interstitial lung diseases. It is mirrored by progressive pulmonary fibrosis (PPF), an umbrella term which characterizes disease behavior of various fibrotic interstitial lung diseases with irreversible progression, accounting for loss of lung function, exercise intolerance and respiratory failure leading to early mortality. Pirfenidone and nintedanib halve the decline in lung function but do not halt disease progression.

Recent findings
Since the publication in 2014 of pivotal pirfenidone and nintedanib studies, a number of clinical trials were conducted, many of them did not reach their primary endpoints. In IPF, promising phase 2 trials were followed by large phase 3 trials that did not confirm a favorable efficacy to tolerability favorable profile, including those with ziritaxestat, an autotaxin-1 inhibitor, zinpentraxin-alpha (human recombinant pentraxin-2), and the monoclonal antibody pamrevlumab targeting connective tissue growth factor. Nevertheless, newer compounds that hold promise are currently being evaluated in phase 3 or phase 2b randomized controlled trials, including: nerandomilast, a preferential phosphodiesterase 4B inhibitor; admilparant, a lysophosphatidic acid receptor antagonist; inhaled treprostinil, a prostacyclin agonist; and bexotegrast, a dual-selective inhibitor of αvβ6 and αvβ1 integrins. Nerandomilast, admilparant, inhaled treprostinil, and inhaled AP01 (pirfenidone), are currently studied in patients with PPF.

Summary
Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF.
Impact of COVID-19 and Mpox on Sexual Practices and Disease Mitigation Strategies Over Time Among Men Who Have Sex With Men Affiliated With Collective Sex Venues
Authors: Hazra Aniruddha , Rusie Laura K. , Wasanwala Tasneem , Sachdev Nirmalpal , Guidry Taylor , Tabidze Irina , Mehta Supriya D. 
Published: August 2024

Background
The COVID-19 pandemic and subsequent multinational mpox outbreak significantly disrupted sexual health care delivery, particularly impacting men who have sex with men (MSM). This study investigated these public health emergencies in relation to perceptions, attitudes, and sexual practices among MSM affiliated with a collective sex venue (CSV).

Methods
Electronic surveys were sent to clientele of a high-volume CSV between June 2021 and November 2022 across 3 time periods defined as pre-Omicron, post-Omicron, and mpox. Data collection encompassed sociodemographics, health care access, sexually transmitted infection/HIV status, COVID-19 testing, and sexual behaviors. Multivariable regression analyses identified factors associated with self-reported COVID-19 testing and positivity, and mpox exposure.

Results
Among 1135 responses, demographics were largely cisgender MSM and predominantly White. Increased self-reported COVID-19 positivity was associated with having more sex partners and frequenting bathhouses for meeting sex partners. Confidence in COVID-19 mitigation strategies decreased post-Omicron. Factors linked to mpox exposure included younger age, increased sex partners, sexually transmitted infection positivity, and lower confidence in mitigation strategies.

Discussion
These findings underscore the intersectionality between sexual behaviors and public health responses to COVID-19 and mpox among MSM communities affiliated with a CSV. Decreased confidence in mitigation strategies and changes in sexual behaviors during public health emergencies underscore the need for targeted interventions and messaging. Collaboration between health departments and CSVs can facilitate responses to current and future public health threats and interventions.
Gonorrhea and Chlamydia Opt-Out Screening of Justice-Involved Women During Intake at the Los Angeles County Jail: The Pivotal Role of Correctional Health Systems
Authors: Qureshi Nazia S. , Herrera Sulma J. , Miller Loren G. , Judge Stephen P. , Cardenas Charles M. , Henderson Sean O. 
Published: August 2024

Background
Chlamydia and gonorrhea are 2 of the most common sexually transmitted infections (STIs) worldwide, presenting major public health challenges and resulting in billions of dollars in direct medical costs in the United States. Incarcerated women have a particularly elevated risk of these infections, which can result in serious sequelae if left untreated. On December 13, 2021, the Los Angeles County Jail system began offering opt-out urogenital chlamydia and gonorrhea screening to all newly incarcerated women.

Methods
We retrospectively analyzed electronic health record data for completed urogenital chlamydia/gonorrhea screening among newly incarcerated women between December 13, 2021, and May 31, 2023. We used multivariable logistic regression to examine the association of STIs and treatment non-initiation outcomes with various demographic and self-reported variables.

Results
Of the 13,739 female entrants offered STI testing, 10,717 (78%) completed screening, with 1151 (11%) having a chlamydial infection, 788 (7%) having a gonococcal infection, and 1626 (15%) having ≥1 infection. Sexually transmitted infection positivity was associated with age 18 to 34 years, reported houselessness, amphetamine use, and history of a positive prior treponemal antibody test result. Sexually transmitted infection treatment non-initiation was associated with shorter jail stay for both chlamydial (adjusted odds ratio, 87.4; 95% confidence interval, 34.2–223.2) and gonococcal (adjusted odds ratio, 9.0; 95% confidence interval, 5.2–15.7) infections.

Conclusion
The STI prevalence among female detainees tested was many-fold higher than that of the general population. The implementation of routine opt-out STI screening in carceral settings provides a unique opportunity to benefit the health of both the correctional population and potentially that of the surrounding community.
Prospective Validation of the Pancreatic Fistula Risk Classification by the International Study Group for Pancreatic Surgery (PARIS trial)
Authors: Schuh Fabian , Yildirim Berk , Klotz Rosa , Pianka Frank , Boskovic Andrea , Werba Alexander , Fink Matthias A. , Wild Caroline , Schwab Constantin , Eckert Christoph , Feisst Manuel , Mihaljevic André L. , Loos Martin , Büchler Markus , Probst Pascal 
Published: August 2024

Objective:
The aim of this study was a prospective validation of the recently established ISGPS pancreas classification as a parenchymal risk classification system for pancreatic fistula after pancreatoduodenectomy.

Summary Background Data:
Postoperative pancreatic fistula (POPF) is the major driver for complications after partial pancreatoduodenectomy (PD). Recently, the International Study Group for Pancreatic Surgery (ISGPS) published a pancreas classification containing the parameters main pancreatic duct diameter (MPD) and pancreatic texture to help assess the risk of POPF development following pancreatoduodenectomy.

Methods:
From January 2020 to July 2021, 271 patients receiving elective PD were included after informed consent. The postoperative course was documented prospectively up to postoperative day 30. Among the pancreas characteristics, MPD and pancreatic texture were assessed intraoperatively at the pancreatic resection margin and the pancreatic glands were assigned to one of the four pancreas classes according to the ISGPS (A to D). The primary endpoint was POPF according to the updated ISGPS definition. Secondary endpoints comprised other post-PD morbidity and mortality.

Results:
Of 271 patients, 264 had available data according to the ISGPS pancreas classification. Of those, 78 were assigned to class A (30%), 53 to class B (20%), 50 to class C (19%) and 83 to class D (31%). POPF occurred in 54 of 271 patients (19.9%). The 30-day mortality was 7/271 (2.6%), with 6/7 having developed POPF (86%). POPF rates within the classes A, B, C and D were 9.0%, 11.3%, 20.0% and 37.4%, respectively (P<0.001). In the univariable regression analysis, only patients in pancreas class D demonstrated a significantly higher risk for POPF when compared to class A (OR 6.05, 95%-CI: 2.6-15.9, P<0.001). In the multivariable regression model, patients in class D had a significantly higher risk for POPF compared to class A (OR 3.45, 95%-CI: 1.15-11.3, P=0.032). The model comprised Body Mass Index, surgery duration, microscopic fibrosis and the ISGPS pancreas classification, demonstrating an AUC-value of approximately 0.82 when tested on the PARIS dataset.

Conclusion:
This prospective trial shows that the ISGPS pancreas classification is valid. Patients in risk class D are prone to POPF independently of other factors. Therefore, all future publications on pancreatic surgery should report the risk class according to the ISGPS pancreas classification to allow for a better comparison of reported cohorts.
The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics
Authors: Welk Blayne , McClure J. Andrew , McArthur Eric , Leong Yvonne 
Published: August 2024

Importance
The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown.

Objective
The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation.

Study Design
Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18–45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs).

Results
We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30–120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40–1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85–1.80; P = 0.26).

Conclusions
Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.
Intrinsic dynamic shapes responses to external stimulation in the human brain
Authors: Nentwich Maximilian , Leszczynski Marcin , Schroeder Charles E. , Bickel Stephan , Parra Lucas C. 
Published: August 2024

SummarySensory stimulation of the brain reverberates in its recurrent neuronal networks. However, current computational models of brain activity do not separate immediate sensory responses from intrinsic recurrent dynamics. We apply a vector-autoregressive model with external input (VARX), combining the concepts of “functional connectivity” and “encoding models”, to intracranial recordings in humans. We find that the recurrent connectivity during rest is largely unaltered during movie watching. The intrinsic recurrent dynamic enhances and prolongs the neural responses to scene cuts, eye movements, and sounds. Failing to account for these exogenous inputs, leads to spurious connections in the intrinsic “connectivity”. The model shows that an external stimulus can reduce intrinsic noise. It also shows that sensory areas have mostly outward, whereas higher-order brain areas mostly incoming connections. We conclude that the response to an external audiovisual stimulus can largely be attributed to the intrinsic dynamic of the brain, already observed during rest.
Desegregation of neuronal predictive processing
Authors: Wang Bin , Audette Nicholas J , Schneider David M , Aljadeff Johnatan 
Published: August 2024

AbstractNeural circuits construct internal ‘world-models’ to guide behavior. The predictive processing framework posits that neural activity signaling sensory predictions and concurrently computing prediction-errors is a signature of those internal models. Here, to understand how the brain generates predictions for complex sensorimotor signals, we investigate the emergence of high-dimensional, multi-modal predictive representations in recurrent networks. We find that robust predictive processing arises in a network with loose excitatory/inhibitory balance. Contrary to previous proposals of functionally specialized cell-types, the network exhibits desegregation of stimulus and prediction-error representations. We confirmed these model predictions by experimentally probing predictive-coding circuits using a rich stimulus-set to violate learned expectations. When constrained by data, our model further reveals and makes concrete testable experimental predictions for the distinct functional roles of excitatory and inhibitory neurons, and of neurons in different layers along a laminar hierarchy, in computing multi-modal predictions. These results together imply that in natural conditions, neural representations of internal models are highly distributed, yet structured to allow flexible readout of behaviorally-relevant information. The generality of our model advances the understanding of computation of internal models across species, by incorporating different types of predictive computations into a unified framework.
MUC2 Expression Modulates Immune Infiltration in Colorectal Cancer
Authors: Raynaud Christophe M. , Jabeen Ayesha , Ahmed Eiman I. , Hubrack Satanay , Sanchez Apryl , Sherif Shimaa , Al-Shaibi Ahmad A , Roelands Jessica , Lo Bernice , Bedognetti Davide , Hendrickx Wouter 
Published: August 2024

AbstractIntroductionColorectal cancer (CRC) is a prevalent malignancy with significant morbidity and mortality worldwide. A deeper understanding of the interaction of cancer cells with other cells in the tumor microenvironment is crucial for devising effective therapeutic strategies. MUC2, a major component of the protective mucus layer in the gastrointestinal tract, has been implicated in CRC progression and immune response regulation.MethodIn this study, we sought to elucidate the relationship between MUC2 expression and immune infiltration within CRC, usingin-vitromodels involving two well-established cell lines, HT-29 and LS-174T. By employing CRISPR-mediated MUC2 knockout, we investigated the influence of MUC2 on tumor immune infiltration and its interplay with T cells and NK cells enriched peripheral blood mononuclear cells (PBMCs) in 3D spheroid cultures.ResultsWhile MUC2 was more abundant in LS-174T cell lines compared to HT-29, its knockout resulted in increased immune infiltration solely in the HT-29 cell line, but not in LS-174T. We revealed that the removal of MUC2 protein was compensated in LS-174T by the expression of other gel forming mucin proteins (Muc6, Muc5B) commonly expressed in gastrointestinal epithelium, while this was not observed in HT-29 cell line.DiscussionWe propose that the role of MUC2 documented in CRC progression can partially be explained by impairing immune infiltration due to physical barrier established by the gel forming proteins such as MUC2 in mucinous CRC. On the other hand, the removal of MUC2 expression can be compensated by alternative gel forming mucin proteins, thereby impeding any increase in tumor immune infiltration.
Meta-analysis of Public RNA-sequencing Data of Drought and Salt Stresses in Different Phenotypes ofOryza sativa
Authors: Shintani Mitsuo , Bono Hidemasa 
Published: August 2024

AbstractEnvironmental stresses, such as drought and salt, adversely affect plant growth and crop productivity. While many studies have focused on established components of stress signaling pathways, research on unknown elements remains limited. In this study, we collected RNA sequencing (RNA-Seq) data fromOryza sativaregistered in public databases and conducted a meta-analysis integrating multiple studies. We analyzed 105 paired RNA-Seq datasets from resistant or susceptibleOryza sativacultivars under salt and drought conditions to identify novel stress-responsive genes with common expression changes across these datasets. A meta-analysis identified 10 genes specifically upregulated in resistant cultivars and 12 specifically upregulated in susceptible cultivars under both drought and salt conditions. Furthermore, by comparing previously identified stress-responsive genes inArabidopsis thaliana, we explored genes potentially involved in stress response mechanisms that are conserved across plant species. The genes identified in this data-driven study may serve as targets for future research and genome editing.
Touch inhibits cold: non-contact cooling reveals a novel thermotactile gating mechanism
Authors: Ezquerra-Romano Ivan , Chowdhury Maansib , Haggard Patrick 
Published: August 2024

AbstractSkin stimuli reach the brain via multiple neural channels specific for different stimulus types. These channels interact in the spinal cord, typically through inhibition. Interchannel interactions can be investigated by selectively stimulating one channel and comparing the sensations that result when another sensory channel is or is not concurrently stimulated. Applying this logic to thermal-mechanical interactions proves difficult, because most existing thermal stimulators involve skin contact. We used a novel non-tactile stimulator for focal cooling (9mm2) by using thermal imaging of skin temperature as a feedback signal to regulate exposure to a dry ice source. We could then investigate how touch modulates cold sensation by delivering cooling to the human hand dorsum in either the presence or absence of light touch. Across three signal detection experiments, we found that sensitivity to cooling was significantly reduced by touch. This reduction was specific to touch, since it did not occur when presenting auditory signals instead of the tactile input, making explanations based on distraction or attention unlikely. Our findings suggest that touch inhibits cold perception, recalling interactions of touch and pain previously described by Pain Gate Theory. We show, for the first time, a thermotactile gating mechanism between mechanical and cooling signals.
The neurophysiology of healthy and pathological aging: A comprehensive systematic review
Authors: Fernández-Rubio Gemma , Vuust Peter , Kringelbach Morten L. , Bonetti Leonardo 
Published: August 2024

AbstractAs the population of older adults grows, so does the prevalence of neurocognitive disorders such as mild cognitive impairment (MCI) and dementia. While biochemical, genetic, and neuroimaging biomarkers have accelerated early detection and diagnosis, neurophysiological measures are absent from daily medical use. Electroencephalography (EEG) and magnetoencephalography (MEG) are two non-invasive techniques that measure neurophysiological signals in the brain and convey information about signal strength at different frequency bands, event-related activity, signal complexity, and temporal correlation between spatially remote brain regions. Here we conducted a pre-registered, comprehensive systematic review of 942 studies using EEG, MEG, and combined MEG and EEG to characterise the neurophysiology of healthy aging, MCI, and dementia under resting-state and task conditions. To complement our search, we also reviewed 51 past reviews in the field. Relevant features of these papers were extracted to present a detailed overview of the current state of evidence. Overall, neurophysiological measures show great promise as diagnostic tools and could prove invaluable in predicting healthy and pathological aging trajectories. However, to reach this potential in clinical practice, it is crucial to adopt longitudinal designs, standardise methodologies, and identify biomarkers at the individual rather than group level.
Hierarchical optimization of biochemical networks
Authors: Viswan Nisha Ann , Tribut Alexandre , Gasparyan Manvel , Radulescu Ovidiu , Bhalla Upinder S. 
Published: August 2024

AbstractBiological signalling systems are complex, and efforts to build mechanistic models must confront a huge parameter space, indirect and incomplete data, and frequently encounter multiscale and multiphysics phenomena. We present HOSS, a framework for Hierarchical Optimization of Systems Simulations, to address such problems. HOSS operates by breaking down extensive systems models into individual pathway blocks organized in a nested hierarchy. At the first level, dependencies are solely on signalling inputs, and subsequent levels rely only on the preceding ones. We demonstrate that each independent pathway in every level can be efficiently optimized. Once optimized, its parameters are held constant while the pathway serves as input for succeeding levels. We develop an algorithmic approach to identify the necessary nested hierarchies for the application of HOSS in any given biochemical network. Furthermore, we devise two parallelizable variants that generate numerous model instances using stochastic scrambling of parameters during initial and intermediate stages of optimization. Our results indicate that these variants produce superior models and offer an estimate of solution degeneracy. Additionally, we showcase the effectiveness of the optimization methods for both abstracted, event-based simulations and ODE-based models.Author summaryBiochemical pathway models integrate quantitative and qualitative data to understand cell functioning, disease effects, and to test treatments in silico. Constructing and optimizing these models is challenging due to the complexity and multitude of variables and parameters involved. Although hundreds of biochemical models have been developed and are available in repositories, they are rarely reused. To enhance the utilization of these models in biomedicine, we propose HOSS, an innovative hierarchical model optimization method. HOSS takes advantage of the modular structure of pathway models by breaking down large mechanistic computational models into smaller modules. These modules are then optimized progressively, starting with input modules and following causality paths. This method significantly reduces the computational burden as each step involves solving a simpler problem. By making the optimization process more manageable, HOSS accelerates the lifecycle of biochemical models and promotes their broader use in biomedical research and applications.