bluuebunny/crossref_metadata_2025 huggingface dataset:
Geothermal energy appraisal and subsurface structural mapping of the Rafin Rewa warm spring region, Precambrian basement complex of Nigeria
Authors: Usman Ayatu Ojonugwa , Abraham Ema Michael , Oknonkwo Churchill Chukwunonso , Chinwuko Augustine Ifeanyi , Azuoko George-Best
Published: July 2024

This research work aims at evaluating the geothermal energy potentials of the Rafin Rewa warm spring (RRWS) of the Precambrian Basement Complex in Nigeria as an alternative energy source using integrated aeromagnetic geophysical techniques. Four aeromagnetic dataset were acquired, assemblage, analyzed, and interpreted using integrated geophysical processing techniques of spectral analysis and Euler deconvolution. Qualitative interpretation of the residual anomalous map reveals a distribution of positive anomalies (> 53 nT) majorly in the central and southeastern regions, which are traced to the granitic rocks, while the low anomalies (< − 1.5 nT) have been traced to the RRWS location emanating from the coastal plain sands of the Pliocene, Pleistocene, Oligocene, and Miocene ages. Quantitatively, the depth to the top (DTT) of the anomalous bodies reveals a depression that is almost intersecting with the Curie point depth (CPD) plot at the RRWS location, which indicates high heat flow in the RRWS region. The Spectral Analysis results reveal that the DTT and the CPD in this area ranges from 0.512 to 0.761 km and 6.504 to 10.582 km, respectively while the average CPD is 8.543 ± 0.325 km. It is observed that the DTT and CPD decrease as one move away from the RRWS region. The computed heat flow average was 160.76 ± 19.09 mW/m2 within the RRWS region. The Euler deconvolution result reveals the presence of geological structures, which were interpreted as faults and fractures. The major fractures trend in the east–west (E-W) directions, while the minor fractures trend northeast-southwest (NE-SW) directions. The geochemical result presented shows that iconic compositions impact the convective heat transfer processes associated with geothermal systems. It was conclusively believed that regions with comparable shallow CPDs could be viable for further geothermal energy investigations.
Human proprioceptive gaze stabilization during passive body rotations underneath a fixed head
Authors: Wibble Tobias , Pansell Tony
Published: July 2024

The present study explored the presence of torsional gaze-stabilization to proprioceptive neck activation in humans. Thirteen healthy subjects (6 female, mean age 25) were exposed to passive body rotations while maintaining a head-fixed, gravitationally upright, position. Participants were seated in a mechanical sled, their heads placed in a chin rest embedded in a wooden beam while wearing an eye tracker attached to the beam using strong rubber bands to ensure head stability. The body was passively rotated underneath the head both in darkness and while viewing a projected visual scene. Static torsional gaze positions were compared between the baseline position prior to the stimulation, and immediately after the final body tilt had been reached. Results showed that passive neck flexion produced ocular torsion when combined with a visual background. The eyes exhibited rotations in the opposite direction of the neck’s extension, matching a hypothetical head tilt in the same direction as the sled. This corresponded with a predicted head rotation aimed at straightening the head in relation to the body. No such response was seen during trials in darkness. Altogether, these findings suggest that proprioception may produce a predictive gaze-stabilizing response in humans.
A randomized trial of behavioral interventions yielding sustained reductions in distracted driving
Authors: Ebert Jeffrey P. , Xiong Ruiying A. , Khan Neda , Abdel-Rahman Dina , Leitner Aaron , Everett William C. , Gaba Kristen L. , Fisher William J. , McDonald Catherine C. , Winston Flaura K. , Rosin Roy M. , Volpp Kevin G. , Barnett Ian J. , Wiebe Douglas J. , Halpern Scott D. , Delgado Mucio Kit
Published: July 2024

Distracted driving is responsible for nearly 1 million crashes each year in the United States alone, and a major source of driver distraction is handheld phone use. We conducted a randomized, controlled trial to compare the effectiveness of interventions designed to create sustained reductions in handheld use while driving (NCT04587609). Participants were 1,653 consenting Progressive® Snapshot® usage-based auto insurance customers ages 18 to 77 who averaged at least 2 min/h of handheld use while driving in the month prior to study invitation. They were randomly assigned to one of five arms for a 10-wk intervention period. Arm 1 (control) got education about the risks of handheld phone use, as did the other arms. Arm 2 got a free phone mount to facilitate hands-free use. Arm 3 got the mount
plus
a commitment exercise and tips for hands-free use. Arm 4 got the mount, commitment, and tips
plus
weekly goal gamification and social competition. Arm 5 was the same as Arm 4,
plus
offered behaviorally designed financial incentives. Postintervention, participants were monitored until the end of their insurance rating period, 25 to 65 d more. Outcome differences were measured using fractional logistic regression. Arm 4 participants, who received gamification and competition, reduced their handheld use by 20.5% relative to control (
P
< 0.001); Arm 5 participants, who additionally received financial incentives, reduced their use by 27.6% (
P
< 0.001). Both groups sustained these reductions through the end of their insurance rating period.
A high-light therapy restores the circadian clock and corrects the pathological syndrome generated in restricted-fed mice
Authors: Damara Manohar , Misra Nisha , Chambon Pierre
Published: July 2024

Time-restricted feeding (RF) is known to shift the phasing of gene expression in most primary metabolic tissues, whereas a time misalignment between the suprachiasmatic nucleus circadian clock (SCNCC) and its peripheral CCs (PCC’s) is known to induce various pathophysiological conditions, including a metabolic syndrome. We now report that a unique “light therapy,” involving different light intensities (T
ZT0-ZT12
150–T
ZT0-ZT12
700 lx, T
ZT0-ZT12
75–T
ZT0-ZT12
150 lx, and T
ZT0-ZT12
350–T
ZT0-ZT12
700 lx), realigns the RF-generated misalignment between the SCNCC and the PCC’s. Using such high-light regime, we show that through shifting the SCNCC and its activity, it is possible in a RF and “night-shifted mouse model” to prevent/correct pathophysiologies (e.g., a metabolic syndrome, a loss of memory, cardiovascular abnormalities). Our data indicate that such a “high-light regime” could be used as a unique chronotherapy, for those working on night shifts or suffering from jet-lag, in order to realign their SCNCC and PCC’s, thereby preventing the generation of pathophysiological conditions.
Pieces of Music and Pinches of Salt
Authors: Ridley Aaron
Published: July 2024

Suppose we grant that each musical work has an establishable essence. Suppose we grant, too, that for at least one piece of music philosophers have established what that essence is. The argument of the present essay is that this would have no consequences for the proper performance of that work. More specifically, the claim is that there can be no presumption that a performance that accurately reflects that essence should be preferred to one that does not, nor any generalization about how far a good performance may deviate from that essence, or in what respects. The argument, in short, is that musical metaphysics has little contribution to make to our efforts to understand, to evaluate, or indeed to give, performances of musical works.
On the Musically Possible
Authors: Ridley Aaron
Published: July 2024

It seems natural to suppose that Artur Schnabel’s occasionally inaccurate performance of Beethoven’s Hammerklavier would have been even better had it been accurate throughout. In the present essay I defend this supposition against a sceptical argument which purports to show that we have no good reason to believe it. The sceptical argument, which draws on some plausible-seeming thoughts about aesthetic properties, concludes that, because we cannot know whether this or that (as-yet-unachieved) musical result is so much as possible, we have no good reason to suppose that an accurate version of Schnabel’s performance should be preferred to Schnabel’s own. In attempting to defuse this sceptical argument, I open up, and begin to explore, some new and potentially interesting questions about musical performance and about the species of rationality that it requires and exhibits.
Roseibium algae sp. nov., isolated from a marine alga (Grateloupia sp.)
Authors: Fan Jiwu , Liu Xinqi , Wang Ziwei , Cui Ning , Zhang Yao , Zhang Yanfeng , Song Jiale , Li Tao , Wang Yan
Published: July 2024

A novel Gram-stain-negative, rod-shaped, non-spore-forming, aerobic, motile bacterium with a single polar or subpolar flagellum, designated strain H3510T, was isolated from marine alga collected on sea shore of Yantai, PR China. The organism grew optimally at 28 °C and pH 7.0 and in presence of 3.0 % (w/v) NaCl. The strain exhibited positive catalase activity but negative oxidase and nitrate reduction activities. The predominant cellular fatty acids were C18 : 1
 ω7c and/or C18 : 1
 ω6c, 11-methyl C18 : 1
 ω7c, and C16 : 0. Additionally, the major polar lipids were phosphatidylglycerol, phosphatidylmonomethylethanolamine, diphosphatidylglycerol, and phosphatidylethanolamine; the respiratory quinone was ubiquinone 10 (Q-10). The genomic DNA G+C content of strain H3510T was 54.2%. The novel strain showed the closest relationship with Roseibium polysiphoniae KMM 9699T with 98.2 % 16S rRNA gene sequence similarity. The calculated values for average nucleotide identity and DNA–DNA hybridization between strain H3510T and the phylogenetically related Roseibium species were in the range of 71.3–74.9 % and 13.7–19.9 %, respectively. Based on polyphasic analyses, strain H3510T was identified as representing a novel species of the genus Roseibium, for which the name Roseibium algae sp. nov. is proposed. The type strain is H3510T (=KCTC 8206T=MCCC 1K04325T). The heterologously expressed inositol 2-dehydrogenase gene from strain H3510T displayed high oxidation activity on myo-inositol and showed potential in the production of rare stereoisomers of inositol, such as scyllo-inositol.
Diversity and structure of the deep-sea sponge microbiome in the equatorial Atlantic Ocean
Authors: Williams Sam E. , Varliero Gilda , Lurgi Miguel , Stach James E.M. , Race Paul R. , Curnow Paul
Published: July 2024

Sponges (phylum Porifera) harbour specific microbial communities that drive the ecology and evolution of the host. Understanding the structure and dynamics of these communities is emerging as a primary focus in marine microbial ecology research. Much of the work to date has focused on sponges from warm and shallow coastal waters, while sponges from the deep ocean remain less well studied. Here, we present a metataxonomic analysis of the microbial consortia associated with 23 individual deep-sea sponges. We identify a high abundance of archaea relative to bacteria across these communities, with certain sponge microbiomes comprising more than 90 % archaea. Specifically, the archaeal family Nitrosopumilaceae is prolific, comprising over 99 % of all archaeal reads. Our analysis revealed that sponge microbial communities reflect the host sponge phylogeny, indicating a key role for host taxonomy in defining microbiome composition. Our work confirms the contribution of both evolutionary and environmental processes to the composition of microbial communities in deep-sea sponges.
Ultrastructural diversity of alpha-Synuclein pathology in the post-mortem brain of Parkinson patients: implications for Lewy Body formation
Authors: Lewis Amanda J , van den Heuvel Lukas , di Fabrizio Marta , Burger Domenic , Huisman Evelien , Bol John GJM , van de Berg Wilma DJ , Stahlberg Henning
Published: July 2024

Lewy bodies, the major pathological hallmark of Parkinson’s disease, are intraneuronal inclusions rich in aggregated alpha-synuclein (aSyn). To understand the cellular mechanisms behind the formation of Lewy bodies and the aggregation of aSyn, we used correlative light and electron microscopy and detailed ultrastructural analysis of postmortem brain tissue samples of Parkinson patients. We found that somal aSyn inclusions in dopaminergic neurons were exclusively fibrillar, while membranous-type inclusions were located outside the cell soma and likely compact neuritic aggregates. These neuritic inclusions displayed phenotypic heterogeneity, ranging from predominantly membranous to mixed membranous/fibrillar ultrastructures. Our data suggest that membranous and fibrillar aSyn inclusions form via distinct mechanisms, with membranous neuritic inclusions providing the environment for the initial nucleation of aSyn fibrils, which could then spread via a prion-like mechanism to form somal fibrillar Lewy bodies. This study provides important insight into Lewy body formation and highlights the importance of aSyn and membrane interactions for future therapeutic intervention.
Accurate, fast and memory efficient quantification of immune cell phenotypes in cytometry using machine learning
Authors: Exner Tarik , Hackert Nicolaj S. , Pohl Frederic , Osmanusta Goerkem , Schmidt Fee , Lorenz Hanns-Martin , Wabnitz Guido , Schett Georg , Graw Frederik , Henes Joerg , Grieshaber-Bouyer Ricardo
Published: July 2024

To achieve accurate and reproducible cytometry data analysis, we benchmarked 19 machine learning algorithms for supervised and unsupervised cell classification. The underlying data encompassed 138 million cells from seven independent datasets including conventional flow cytometry, spectral flow cytometry and mass cytometry. We found that tree-based classifiers and in particular Decision Trees, outperformed other approaches in classification accuracy, speed and memory use. High accuracy was achieved even for cell populations rarer than 1% using decision trees. We validated our decision tree-based approach in a clinical setting using diagnostic blood T cell phenotyping of 107 patients. Automatic quantification of CD4 helper T cell phenotypes achieved 99 % accuracy compared to manual expert assessment. Finally, we combined automated data transformation, supervised and unsupervised gating, an application program interface and a user-friendly desktop-application into FACSPy and FACSPyUI, a fast and scalable open-source toolbox for the analysis and visualization of cytometry data.
Influence of gonadal and chromosomal sex on the brain transcriptome in a mouse species with natural sex reversal
Authors: Heitzmann Louise D. , Saunders Paul A. , Perez Julie , Boursot Pierre , Veyrunes Frederic
Published: July 2024

Sex chromosomes are expected to play a role in shaping the transcriptional architecture of sexual dimorphism, through the direct expression of sex-linked genes, by regulating autosomal genes, or in interactions with hormones. Yet, their degree of involvement remains elusive partly because chromosomal sex (XX/XY or ZZ/ZW) and gonadal sex (ovaries or testes) are usually inextricably intertwined. They are however dissociated in the African pygmy mouse,Mus minutoides,in which a feminizing X (X*) has evolved resulting in three female genotypes (XX, XX* and X*Y) and one male genotype (XY). Despite hormonal levels similar to the other females, X*Y females show distinctive phenotypes with greater fertility, divergent maternal care strategies and the masculinization of some traits (e.g. enhanced aggressiveness). By comparing the brain transcriptome of the four sexual genotypes, we show, here, that differential gene expression is mainly linked to gonadal sex (male vs. female) but also and significantly, to chromosomal sex, with expression patterns matching the singularity of X*Y female traits. Genes with such patterns are over-represented on sex and sex-linked chromosomes, and some are strong candidates to explain X*Y-specific behavioral and reproductive traits. We also report the preferential inactivation of the X* chromosome in XX* females, which could explain their trait similarities with XX females. Overall, we show that sex chromosomes have profoundly impacted the brain transcriptome in ways that reflect their new transmission modes and new resulting conflicts. This opens exciting prospects on the evolution of sex differences in relation to the dynamic of sex chromosome evolution.
Comparing efficiencies of population control methods for responding to foreign animal disease threats in wild pigs
Authors: Snow Nathan P. , Smith Benjamin , Lavelle Michael J. , Glow Michael P. , Chalkowski Kayleigh , Leland Bruce R. , Sherburne Sarah , Fischer Justin W. , Kohen Keely J. , Cook Seth M. , Smith Hatton , VerCauteren Kurt C. , Miller Ryan S. , Pepin Kim M.
Published: July 2024

Introductions of foreign animal diseases (FADs) into free-ranging wildlife can be difficult to control and devastating for domestic livestock trade. Combating a new FAD introduction in wildlife with an emergency response requires quickly limiting spread of the disease by intensely removing wild animals and recovering their carcasses for proper disposal. In the case of African swine fever virus (ASFv) in wild pigs (Sus scrofa), which has been spreading in many regions of the world, there is little information on the time- and cost-efficiency of methods for intensively and consistently removing wild pigs and recovering carcasses in an emergency response scenario. We compared the efficiencies of aerial operations, trapping, an experimental toxic bait, and ground shooting in northcentral Texas, USA during two months in 2023. Removing and recovering carcasses of wild pigs averaged a rate of 0.15 wild pigs/person hour and cost an average of $233.04/wild pig ($USD 2023) across all four methods. Aerial operations required the greatest initial investment but subsequently was the most time- and cost-efficient, costing an average of $7,266 to incrementally reduce the population by 10% including recovering carcasses. Aerial operations required a ground crew of ∼7 people/helicopter to recover carcasses. Costs for reducing the population of wild pigs using trapping were similar, although took 13.5 times longer to accomplish. A benefit of trapping was carcass recovery was incorporated. Toxic baiting was less efficient because carcass recovery required substantial time, and we removed very few wild pigs with ground shooting in this landscape. We recommend combining aerial and trapping methodologies to remove wild pigs and their carcasses efficiently and effectively during a FAD response. Overall, our findings can inform the preparation of resources, personnel needs, and deployment readiness for FAD responses involving wild pigs.
Abnormal multisensory facilitation patterns relate to disorganized thinking severity and cognitive decline in schizophrenia
Authors: Rogge-Obando Kimberly K , Coffman Brian A , Stephen Julia M
Published: July 2024

Past research has demonstrated that patients with schizophrenia (SP) have visual processing and multisensory integration deficits. Additional studies report that sensory abnormalities are related to positive symptoms. To further understand how multisensory abnormalities relate to positive symptoms, we administered a multisensory integration task requiring the evaluation of perceived distance from auditory, visual, and multisensory stimuli with varying synchrony as well as clinical and neurocognitive assessments. Overall, patients had greater facilitation than healthy controls and the near synchronous condition had the most facilitation in comparison to other conditions. To further examine how multisensory facilitation relates to symptom severity, we performed a Ward cluster analysis that grouped participants by their multisensory facilitation profile. In contrast to what was expected, none of the Ward clusters were populated by a single group. Patients in cluster 3 had a significantly greater disorganization factor score than those in cluster 1. Our in-depth comparison between Ward clusters and neuropsychological tests reveal patients with greater multisensory facilitation experience the most cognitive deficits. Overall, our results demonstrate that multisensory integration is related to behavioral and cognitive deficits in complex ways. Further research is needed to understand the relationship between multisensory integration and schizophrenia symptomology.

Highlights

Patients with schizophrenia have greater multisensory facilitation in perceived synchronous conditions

Multisensory facilitation patterns are heterogenous across patients with Schizophrenia.

Different multisensory patterns relate to cognitive decline and disorganized thinking in Schizophrenia.
Simple, universal rules predict trophic interaction strengths
Authors: Coblentz Kyle E. , Novak Mark , DeLong John P.
Published: July 2024

Many critical drivers of ecological systems exhibit regular scaling relationships, yet the underlying mechanisms explaining these relationships are often unknown. Trophic interaction strengths, which underpin ecosystem stability and dynamics, are no exception, exhibiting statistical scaling relationships with predator and prey traits that lack causal, evolutionary explanations. Here we propose two universal rules to explain the scaling of trophic interaction strengths through the relationship between a predator’s feeding rate and its prey’s density --- the so-called predator functional response. First, functional responses must allow predators to meet their energetic demands when prey are rare. Second, functional responses should approach their maxima near the highest prey densities that predators experience. We show that independently parameterized mathematical equations derived from these two rules predict functional response parameters across over 2,100 functional response experiments. The rules further predict consistent patterns of feeding rate saturation among predators, a slow-fast continuum among functional response parameters, and the allometric scaling of those parameters. The two rules thereby offer a potential ultimate explanation for the determinants of trophic interaction strengths and their scaling, revealing the importance of ecologically realized constraints to the complex, adaptive nature of functional response evolution.
Automated model discovery for textile structures: The unique mechanical signature of warp knitted fabrics
Authors: McCulloch Jeremy A. , Kuhl Ellen
Published: July 2024

Textile fabrics have unique mechanical properties, which make them ideal candidates for many engineering and medical applications: They are initially flexible, nonlinearly stiffening, and ultra-anisotropic. Various studies have characterized the response of textile structures to mechanical loading; yet, our understanding of their exceptional properties and functions remains incomplete. Here we integrate biaxial testing and constitutive neural networks to automatically discover the best model and parameters to characterize warp knitted polypropylene fabrics. We use experiments from different mounting orientations, and discover interpretable anisotropic models that perform well during both training and testing. Our study shows that constitutive models for warp knitted fabrics are highly sensitive to an accurate representation of the textile microstructure, and that models with three microstructural directions outperform classical orthotropic models with only two in-plane directions. Strikingly, out of 214=16,384 possible combinations of terms, we consistently discover models with two exponential linear fourth invariant terms that inherently capture the initial flexibility of the virgin mesh and the pronounced nonlinear stiffening as the loops of the mesh tighten. We anticipate that the tools we have developed and prototyped here will generalize naturally to other textile fabrics–woven or knitted, weft knit or warp knit, polymeric or metallic–and, ultimately, will enable the robust discovery of anisotropic constitutive models for a wide variety of textile structures. Beyond discovering constitutive models, we envision to exploit automated model discovery as a novel strategy for the generative material design of wearable devices, stretchable electronics, and smart fabrics, as programmable textile metamaterials with tunable properties and functions. Our source code, data, and examples are available athttps://github.com/LivingMatterLab/CANN.
Revamping the Day Hospital Program at North York General Hospital in response to COVID-related changes in patient demographics
Authors: Zhou Carrol , Doval Ishita , Liu Regina
Published: July 2024

Background

The Dynamic Sustainability Framework emphasizes the need for improving programs after implementation in response to the evolving environment. This report illustrates said framework and describes significant changes made to the Psychiatric Day Hospital (DH) at North York General Hospital (NYGH) in response to pandemic-related changes in participant demographic. Patient and staff satisfaction pre- and post-program modification are compared.

Problem

The COVID-19 pandemic resulted in increased DH referral acuity and patient affect dysregulation. The program needed to adapt to these changes and better serve the new DH patient population.

Methods

DH participants and team member feedback was gathered. Five major areas of improvement were identified. Changes were systematically introduced from July 2021 to January 2022. Feedback post-implementation in 2022-2023 from patients and DH team members were gathered for comparison.

Interventions

Dialectical Behavioral Therapy (DBT) was adopted as the theoretical basis of the revamped Day Hospital Program. All Day Hospital staff underwent training in DBT skills, with the creation of new treatment schedules and materials. Two separate streams were created for differing patient illness severity. The program continued to run during implementation of new changes, without disruption to the existing clinical workload.

Results

The program transitioned from a 3-week psychoeducational and rudimentary CBT program to a dual-stream 4-week DBT-based program to address patient acuity and higher prevalence of emotional dysregulation. Quantitative and qualitative feedback from new program participants have been positive.

Conclusions

The Day Hospital Program at NYGH made a successful transition in response to an evolving healthcare landscape.
Multimodal Large Language Model Passes Specialty Board Examination and Surpasses Human Test-Taker Scores: A Comparative Analysis Examining the Stepwise Impact of Model Prompting Strategies on Performance
Authors: Samaan Jamil S. , Margolis Samuel , Srinivasan Nitin , Srinivasan Apoorva , Yeo Yee Hui , Anand Rajsavi , Samaan Fadi S. , Mirocha James , Safavi-Naini Seyed Amir Ahmad , El Kurdi Bara , Soroush Ali , Watson Rabindra , Gaddam Srinivas , Elmore Joann G. , Spiegel Brennan M.R. , Tatonetti Nicholas P.
Published: July 2024

Background

Large language models (LLMs) have shown promise in answering medical licensing examination-style questions. However, there is limited research on the performance of multimodal LLMs on subspecialty medical examinations. Our study benchmarks the performance of multimodal LLM’s enhanced by model prompting strategies on gastroenterology subspeciality examination-style questions and examines how these prompting strategies incrementally improve overall performance.

Methods

We used the 2022 American College of Gastroenterology (ACG) self-assessment examination (N=300). This test is typically completed by gastroenterology fellows and established gastroenterologists preparing for the gastroenterology subspeciality board examination. We employed a sequential implementation of model prompting strategies: prompt engineering, retrieval augmented generation (RAG), five-shot learning, and an LLM-powered answer validation revision model (AVRM). GPT-4 and Gemini Pro were tested.

Results

Implementing all prompting strategies improved the overall score of GPT-4 from 60.3% to 80.7% and Gemini Pro’s from 48.0% to 54.3%. GPT-4’s score surpassed the 70% passing threshold and 75% average human test-taker scores unlike Gemini Pro. Stratification of questions by difficulty showed the accuracy of both LLMs mirrored that of human examinees, demonstrating higher accuracy as human test-taker accuracy increased. The addition of the AVRM to prompt, RAG and 5-shot increased GPT-4’s accuracy by 4.4%. The incremental addition of model prompting strategies improved accuracy for both non-image (57.2% to 80.4%) and image-based (63.0% to 80.9%) questions for GPT-4, but not Gemini Pro.

Conclusions

Our results underscore the value of model prompting strategies in improving LLM performance on subspecialty-level licensing exam questions. We also present a novel implementation of an LLM-powered reviewer model in the context of subspecialty medicine which further improved model performance when combined with other prompting strategies. Our findings highlight the potential future role of multimodal LLMs, particularly with the implementation of multiple model prompting strategies, as clinical decision support systems in subspecialty care for healthcare providers.
Evaluating phasic transcutaneous vagus nerve stimulation (taVNS) with pupil dilation: the importance of stimulation intensity and sensory perception
Authors: Ludwig Mareike , Pereira Calida , Keute Marius , Düzel Emrah , Betts Matthew J. , Hämmerer Dorothea
Published: July 2024

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hzand25 Hz) and intensities (3 mAand5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail.
Lentivirus Transduced T Cell Lines Response to Pro-inflammatory and Antiviral Cytokines in the Presence of HIV
Authors: Ventocilla Kevin , Miranda Daniel , Sanchez David Jesse
Published: July 2024

Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.
Immune Modulation in Solid Tumors: A Phase 1b Study of RO6870810 (BET Inhibitor) and Atezolizumab (PD-L1 Inhibitor)
Authors: Marbach Daniel , Brouer-Visser Jurriaan , Brennan Laura , Wilson Sabine , Davydov Iakov I , Staedler Nicolas , Duarte José , Quetglas Iris Martinez , Nüesch Eveline , Cañamero Marta , Chesné Evelyne , Au-Yeung George , Hamilton Erika , Lheureux Stephanie , Richardson Debra L , Spanggaard Iben , Gomes Bruno , Franjkovic Izolda , DeMario Mark , Kornacker Martin , Lechner Katharina
Published: July 2024

Purpose

Bromodomain and extra-terminal domain (BET) inhibitors (BETi) have demonstrated epigenetic modulation capabilities, specifically in transcriptional repression of oncogenic pathways. Preclinical assays suggest that BETi potentially attenuates the PD1/PD-L1 immune checkpoint axis, supporting its combination with immunomodulatory agents.

Patients and Methods

A Phase 1b clinical trial was conducted to elucidate the pharmacokinetic and pharmacodynamic profiles of the BET inhibitor RO6870810, as monotherapy and in combination with the PD-L1 antagonist atezolizumab, in patients with advanced ovarian carcinomas and triple-negative breast cancer (TNBC). Endpoints included maximum tolerated dosages, adverse event profiling, pharmacokinetic evaluations, and antitumor activity. Pharmacodynamic and immunomodulatory effects were assessed in tumor tissue (by immunohistochemistry and RNA-seq) and in peripheral blood (by flow cytometry and cytokine analysis).

Results

The study was terminated prematurely due to a pronounced incidence of immune-related adverse effects in patients receiving combination of RO6870810 and atezolizumab. Anti-tumor activity was limited to 2 patients (5.6%) showing partial response. Although target engagement was confirmed by established BETi pharmacodynamic markers in both blood and tumor samples, BETi failed to markedly decrease tumor PD-L1 expression and had a suppressive effect on anti-tumor immunity. Immune effector activation in tumor tissue was solely observed with the atezolizumab combination, aligning with this checkpoint inhibitor’s recognized biological effects.

Conclusions

The combination of BET inhibitor RO6870810 with the checkpoint inhibitor atezolizumab presents an unfavorable risk-benefit profile for ovarian cancer and TNBC (triple-negative breast cancer) patients due to the increased risk of augmented or exaggerated immune reactions, without evidence for synergistic anti-tumor effects.

Trial registration

ClinicalTrials.govIDNCT03292172
City-wide metagenomic surveillance of food centres reveals location-specific microbial signatures and enrichment of antibiotic resistance genes
Authors: Teo Jonathan J.Y. , Ho Eliza Xin Pei , Ng Amanda Hui Qi , How Shaun Hong Chuen , Chng Kern Rei , Ateş Yiğit Can , Fau’di Muhd Tarmidzi , Aung Kyaw Thu , Nagarajan Niranjan
Published: July 2024

The distribution of microorganisms in built environments with high human traffic, such as food centres, can potentially have a significant impact on public health, particularly in the context of increasing worldwide incidence of food and fomite-related outbreaks. In several major Asian cities, public food centres are the main venue for food consumption and yet we lack a baseline understanding of their environmental microbiomes. We conducted city-wide metagenomic surveillance of food-centre microbiomes in Singapore (16 centres, n=240 samples) to provide a detailed map of microbial (bacteria, archaea, fungi, viruses) as well as non-microbial DNA abundances across two timepoints. Food-centre microbiomes were found to be enriched in food-related DNA signatures compared to other environments such as hospitals and offices, with specific food-microbe associations (e.g. Enterobacteriaceae and fish) and food DNA providing a partial explanation for the microbial profiles observed (44% of variation explained). Machine learning analysis identified a small set of microbial species (n=22) that serve as highly accurate (>80%) location-specific signatures for various food centres, some of which persist even after 3 years. Profiling of antibiotic resistance genes (ARGs) and pathogens identified a surprising enrichment of ARGs in food centres relative to other non-healthcare environments (>2.5ξ), and an order of magnitude enrichment of key pathogenic species (e.g.Klebsiella pneumoniae,Enterobacter spp) even compared to hospital environments. These results highlight the contribution of diverse biotic and abiotic factors in shaping the unique microbiome profiles of different food-centre environments, and the potential for using metagenomic surveillance to understand the risk for infections and antibiotic resistance gene transmission.
Mind the Gap: Unraveling Mental Health Disparities in America’s Diverse Landscape
Authors: Fischer Margaret , Swint Jennifer , Zhang Wei , Zhang Xi
Published: July 2024

Background

Mental health disparities persist as a significant public health concern in the United States, with certain populations experiencing disproportionate burdens of mental illness and barriers to care. This systematic review aims to synthesize current evidence on mental health disparities across various demographic groups and identify key factors contributing to these inequities.

Methods

We conducted a comprehensive search of peer-reviewed literature published between 2010 and 2024 using PubMed, PsycINFO, and Scopus databases. Studies examining mental health outcomes, access to care, and treatment efficacy across racial/ethnic, socioeconomic, gender, sexual orientation, and geographic groups in the US were included. Two independent reviewers screened articles, extracted data, and assessed study quality.

Results

Of 2,345 initially identified studies, 127 met inclusion criteria. Consistent disparities were observed across multiple domains, with racial/ethnic minorities, low-income individuals, LGBTQ+ populations, and rural residents experiencing higher rates of mental health disorders, lower access to quality care, and poorer treatment outcomes. Key contributing factors included systemic racism, socioeconomic barriers, stigma, lack of culturally competent care, and inadequate insurance coverage.

Conclusion

This review highlights persistent and multifaceted mental health disparities in the US. Addressing these inequities requires comprehensive policy interventions, increased funding for community-based mental health services, improved cultural competence in healthcare delivery, and targeted research to develop effective, culturally-tailored interventions for underserved populations.
SegColR: Deep Learning for Automated Segmentation and Color Extraction
Authors: Boyko James
Published: July 2024

Citizen science platforms like iNaturalist generate biodiversity data at an unprecedented scale, with observations on the order of hundreds of millions. However, extracting phenotypic information from these images, such as color of organisms, at such a large scale poses unique challenges for biologists. Some of the challenges are that manual extraction of phenotypic information can be subjective and time-consuming. Fortunately, with the maturation of computer vision and deep learning, there is an opportunity to automate large parts of the image processing pipeline. Here, I present SegColR, a user-friendly software package that leverages two state-of-the-art deep learning models - GroundingDINO and SegmentAnything - to enable automated segmentation and color extraction from images. The SegColR package provides an R-based interface, making it more accessible to evolutionary biologists and ecologists who may not have extensive coding experience. The SegColR pipeline allows users to load images, automatically segment them based on text prompts, and extract color information from the segmented regions. The package also includes visualization and data summarization functions to facilitate downstream analysis and interpretation of the results.
Deliberative Behaviors and Prefrontal-Hippocampal Coupling are Disrupted in a Rat Model of Fetal Alcohol Spectrum Disorders
Authors: Rosenblum Hailey L. , Kim SuHyeong , Stout John J. , Klintsova Anna , Griffin Amy L.
Published: July 2024

Fetal alcohol spectrum disorders (FASDs) are characterized by a range of physical, cognitive, and behavioral impairments. Determining how temporally specific alcohol exposure (AE) affects neural circuits is crucial to understanding the FASD phenotype. Third trimester AE can be modeled in rats by administering alcohol during the first two postnatal weeks, which damages the medial prefrontal cortex (mPFC), thalamic nucleus reuniens, and hippocampus (HPC), structures whose functional interactions are required for working memory and executive function. Therefore, we hypothesized that AE during this period would impair working memory, disrupt choice behaviors, and alter mPFC-HPC oscillatory synchrony. To test this hypothesis, we recorded local field potentials from the mPFC and dorsal HPC as AE and sham intubated (SI) rats performed a spatial working memory task in adulthood and implemented algorithms to detect vicarious trial and errors (VTEs), behaviors associated with deliberative decision- making. We found that, compared to the SI group, the AE group performed fewer VTEs and demonstrated a disturbed relationship between VTEs and choice outcomes, while spatial working memory was unimpaired. This behavioral disruption was accompanied by alterations to mPFC and HPC oscillatory activity in the theta and beta bands, respectively, and a reduced prevalence of mPFC-HPC synchronous events. When trained on multiple behavioral variables, a machine learning algorithm could accurately predict whether rats were in the AE or SI group, thus characterizing a potential phenotype following third trimester AE. Together, these findings indicate that third trimester AE disrupts mPFC-HPC oscillatory interactions and choice behaviors.

Significance statement

Fetal alcohol spectrum disorders (FASDs) occur at an alarmingly high rate worldwide. Prenatal alcohol exposure leads to significant perturbations in brain circuitry that are accompanied by cognitive deficits, including disrupted executive functioning and working memory. These deficits stem from structural changes within several key brain regions including the prefrontal cortex, thalamic nucleus reuniens, and hippocampus. To better understand the cognitive deficits observed in FASD patients, we employed a rodent model of alcohol exposure during the third trimester, a period when these regions are especially vulnerable to alcohol-induced damage. We show that alcohol exposure disrupts choice behaviors and prefrontal-hippocampal functional connectivity during a working memory task, identifying the prefrontal-hippocampal network as a potential therapeutic target in FASD treatment.
From circuits to lifespan: translating mouse and human timelines with neuroimaging based tractography
Authors: Cottam Nicholas C. , Ofori Kwadwo , Bryant Madison , Rogge Jessica R. , Hekmatyar Khan , Sun Jianli , Charvet Christine J.
Published: July 2024

Age is a major predictor of developmental processes and disease risk, but humans and model systems (e.g., mice) differ substantially in the pace of development and aging. The timeline of human developmental circuits is well known. It is unclear how such timelines compare to those in mice. We lack age alignments across the lifespan of mice and humans. Here, we build upon our Translating Time resource, which is a tool that equates corresponding ages during development. We collected 477 time points (n=1,132 observations) from age-related changes in body, bone, dental, and brain processes to equate corresponding ages across humans and mice. We acquired high-resolution diffusion MR scans of mouse brains (n=12) at sequential stages of postnatal development (postnatal day 3, 4, 12, 21, 60) to trace the timeline of brain circuit maturation (e.g., olfactory association pathway, corpus callosum). We found heterogeneity in white matter pathway growth. The corpus callosum largely ceases to grow days after birth while the olfactory association pathway grows through P60. We found that a P3 mouse equates to a human at roughly GW24, and a P60 mouse equates to a human in teenage years. Therefore, white matter pathway maturation is extended in mice as it is in humans, but there are species-specific adaptations. For example, olfactory-related wiring is protracted in mice, which is linked to their reliance on olfaction. Our findings underscore the importance of translational tools to map common and species-specific biological processes from model systems to humans.

Significance statement

Mice are essential models of human brain development, but we currently lack precise age alignments across their lifespan. Here, we equate corresponding ages across mice and humans. We utilize high-resolution diffusion mouse brain scans to track the growth of brain white matter pathways, and we use our cross-species age alignments to map the timeline of these growth patterns from mouse to humans. In mice, olfactory association pathway growth continues well into the equivalent of human teenage years. The protracted development of olfactory association pathways in mice aligns with their specialized sense of smell. The generation of translational tools bridges the gap between animal models and human biology while enhancing our understanding of developmental processes generating variation across species.
MitoNEET reduces the mitochondrial oxidative phosphorylation during epithelial-mesenchymal transition
Authors: Handa Haruka , Onodera Yasuhito , Oikawa Tsukasa , Takada Shingo , Ueda Koji , Setoyama Daiki , Yokota Takashi , Yamasaki Miwako , Watanabe Masahiko , Fumoto Yoshizuki , Hashimoto Ari , Hata Soichiro , Murakami Masaaki , Sabe Hisataka
Published: July 2024

Mitochondrial functions range from catabolic to anabolic, which are tightly coordinated to meet cellular demands for proliferation and motility. MitoNEET is a mitochondrial outer membrane protein with a CDGSH domain and is involved in mitochondrial function. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose their epithelial characteristics and acquire mesenchymal traits, such as motility, which is a vital step for organism development and wound-healing. Cellular motility is associated with high ATP consumption owing to lamellipodia formation, which is supported by upregulated oxidative phosphorylation (OXPHOS) capacity. However, how mitoNEET is involved in the regulation of OXPHOS capacity and subsequent cellular motility remains unclear. Here we show that loss of mitoNEET regulation during EMT impairs both OXPHOS enhancement and cell motility in non-transformed NMuMG mouse mammary gland epithelial cells. We found that mitoNEET is downregulated during EMT, and that the aberrant expression of mitoNEET abolishes the upregulation of OXPHOS, leading to the inhibition of cell motility. Furthermore, we found that mitoNEET topology may be crucial for the regulation of the mitochondrial electron transfer chain, suggesting an additional regulatory pathway for OXPHOS capacity. Our results demonstrate that mitochondrial OXPHOS capacity during EMT is partly regulated by the dynamics of the outer membrane protein. We believe that our findings are the first step towards understanding the mechanisms by which mitochondrial outer membrane protein topology affects organelle functions.