bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPV4 mediates IL‐1‐induced Ca2+ signaling, ERK activation and MMP expression
Authors: Wang Qin , Ji Chenfan , Ali Aiman , Ding Isabel , Wang Yongqiang , McCulloch Christopher A.
Published: June 2024

Ca2+ permeation through TRPV4 in fibroblasts is associated with pathological matrix degradation. In human gingival fibroblasts, IL‐1β binding to its signaling receptor (IL‐1R1) induces activation of extracellular regulated kinase (ERK) and MMP1 expression, processes that require Ca2+ flux across the plasma membrane. It is not known how IL‐1R1, which does not conduct Ca2+, generates Ca2+ signals in response to IL‐1. We examined whether TRPV4 mediates the Ca2+ fluxes required for ERK signaling in IL‐1 stimulated gingival fibroblasts. TRPV4 was immunostained in fibroblasts of human gingival connective tissue and in focal adhesions of cultured mouse gingival fibroblasts. Human gingival fibroblasts treated with IL‐1β showed no change of TRPV4 expression but there was increased MMP1 expression. In mouse, gingival fibroblasts expressing TRPV4, IL‐1 strongly increased [Ca2+]i. Pre‐incubation of cells with IL‐1 Receptor Antagonist blocked Ca2+ entry induced by IL‐1 or the TRPV4 agonist GSK101. Knockout of TRPV4 or expression of a non‐Ca2+‐conducting TRPV4 pore‐mutant or pre‐incubation with the TRPV4 inhibitor RN1734, blocked IL‐1‐induced Ca2+ transients and expression of the mouse interstitial collagenase, MMP13. Treatment of mouse gingival fibroblasts with GSK101 phenocopied Ca2+ and ERK responses induced by IL‐1; these responses were absent in TRPV4‐null cells or cells expressing a non‐conducting TRPV4 pore‐mutant. Immunostained IL‐1R1 localized with TRPV4 in adhesions within cell extensions. While TRPV4 immunoprecipitates analyzed by mass spectrometry showed no association with IL‐1R1, TRPV4 associated with Src‐related proteins and Src co‐immunoprecipitated with TRPV4. Src inhibition reduced IL‐1‐induced Ca2+ responses. The functional linkage of TRPV4 with IL‐1R1 expands its repertoire of innate immune signaling processes by mediating IL‐1‐driven Ca2+ responses that drive matrix remodeling in fibroblasts. Thus, inhibiting TRPV4 activity may provide a new pharmacological approach for blunting matrix degradation in inflammatory diseases.
Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake
Authors: Leung Kit‐Yi , Weston Eleanor , De Castro Sandra C. P. , Nikolopoulou Evanthia , Sudiwala Sonia , Savery Dawn , Eaton Simon , Copp Andrew J. , Greene Nicholas D. E.
Published: June 2024

Maternal nutrition contributes to gene–environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo‐inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol‐responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol‐3‐phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d‐chiro‐inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry‐based metabolome analysis. Among inositol‐responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5‐methyltetrahydrolate and tetrahydrofolate in MI‐treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one‐carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.
Comparison of Patients Operated for Lumbar Spinal Stenosis With and Without Spondylolisthesis​​​​​
Authors: Weber Clemens , Hermansen Erland , Myklebust Tor Åge , Banitalebi Hasan , Brisby Helena , Brox Jens I. , Franssen Eric , Hellum Christian , Indrekvam Kari , Harboe Knut , Rekeland Frode , Solberg Tore , Storheim Kjersti , Austevoll Ivar M.
Published: June 2024

Study Design.

Observational cohort study (secondary analysis of two randomized trials).

Objective.

The aim of this study was to investigate whether function, disability, pain, and quality of life before surgery and patient-reported outcome as well as complication and reoperation rates up to 2 years after surgery differ between lumbar spinal stenosis patients with and without spondylolisthesis.

Summary of Background Data.

Lumbar spinal stenosis is a degenerative condition of the spine, which appears with or without degenerative spondylolisthesis often presenting similar signs and symptoms.

Materials and Methods.

This study is a secondary analysis of two randomized trials on patients with lumbar spinal stenosis with and without spondylolisthesis conducted at 16 public Norwegian hospitals. Disability, function, back pain, leg pain, quality of life, complication, and reoperation rates up to 2 years after surgery were compared between the two cohorts.

Results.

A total of 704 patients were included in this study, 267 patients with spondylolisthesis [median age: 67.0 yr (IQR: 61.0–72.0 yr); 68.7% female] and 437 patients without spondylolisthesis [median age: 68.0 yr (IQR: 62.0–73.0 yr); 52.9% female]. In the linear mixed-model analysis there were no significant differences in disability, function, back pain, leg pain, and quality of life scores between the two cohorts of patient with and without spondylolisthesis before surgery or at 2 years of follow-up. The complication rate was 22.9% in patients with spondylolisthesis and 12.1% in patients without spondylolisthesis (P<0.001). There were no significant differences in reoperation rates.

Conclusions.

In patients with lumbar spinal stenosis the symptom burden before surgery and the clinical outcome up to 2 years after surgery were similar independently of a concomitant spondylolisthesis.

Level of Evidence.

II.
One-Hour Suicide Prevention Training Makes a Difference!
Authors: Lyon Nour R. , Thomas Robi , Kwasky Andrea N.
Published: June 2024

Nurses and other healthcare workers in the United States are at increased risk of suicide compared to non-healthcare workers. College students also experience high suicide risk. To impact suicide prevention in these populations, a Question, Persuade, Refer (QPR) 1-hour gatekeeper suicide prevention training program was implemented at the University of Detroit Mercy for faculty, staff, and administrators in the College of Health Professions (N = 43). Knowledge in seven areas of suicide significantly increased after the training (p < .001). Sixteen attitudes about suicide improved; however, only two showed a statistically significant change. Results support that 1-hour QPR training can be effectively implemented in a large organization.
Jumps and Plyometric Exercises in the Return to Play After Sports Injuries
Authors: Arias-Vázquez Pedro Iván , Quezada-González Héctor Ricardo , Loeza-Magaña Pavel , Castillo-Ávila Rosa Giannina , Hernández-Gil Karen del Carmen , Poblete-Magaña Jesus
Published: June 2024

Background:

Jumps and plyometric exercises represent a fundamental component of high-intensity sports activities and must be included in the return to play programs after a sports injury. However, the scientific literature focused on the prescription methodology of these activities in the return to play programs is limited.

Objective:

The aim of this manuscript was to provide an overview of the aspects related to the incorporation of jumps and plyometric exercises in the return to play programs.

Results:

Some clinical criteria that the athlete must meet to be incorporated into jump work and plyometric exercises in return to play programs are capacity of the injured tissue to support the load, absence of symptoms, complete joint mobility, previous acquisition of basic motor patterns of the lower limbs, adequate level of strength and muscular balance and technically consolidated jump gesture. The methodological prescription of jumps and plyometric exercises in return to play programs must consider variables such as the type of jumps, intensity, volume, and execution surface, to guarantee adequate progression and minimize the risk of injury recurrence.

Conclusions:

Jumps and plyometric exercises are frequently included in intermediate and advanced phases of return to play programs but the information on their prescription in this area is scarce; we establish a methodological guide that can be useful for the prescription of jumps and plyometric exercises in return to play programs, based mainly on biomechanical studies that evaluate various aspects of the joint load during its execution.
Act or Wait? Presentation Delay in Symptomatic Breast Cancer in China
Authors: An Jinghua , Steffen Alana D. , Collins Eileen G. , Molina Yamilé , Li Xiaomei , Ferrans Carol E.
Published: June 2024

Background

In Western countries, factors contributing to breast cancer presentation delay have been identified, but little is known about presentation delay in China, where culture and healthcare systems are quite different.

Objective

To describe the delay interval among newly diagnosed breast cancer patients in China and to identify factors influencing delay, including the COVID-19 pandemic.

Methods

Using a cross-sectional design, we recruited 154 participants within 3 months of pathological diagnosis of breast cancer. Data were collected using standardized scales and open-ended questions.

Results

We found 44.8% of participants delayed ≥1 month, and 24.7% delayed ≥3 months before presentation, after self-discovery of symptoms. Logistic regression analysis showed that factors associated with longer delay (≥1 month) included preferring female physicians for breast examination, fewer negative emotions (afraid, anxious, distressed) regarding breast symptoms, more competing priorities, believing folk therapy can help treat lumps, and visiting a secondary or tertiary hospital instead of primary healthcare providers (P< .05 for all). Interaction tests showed perceived seriousness of symptoms significantly predicted delay of ≥1 month only when perceived healthcare access or trust in physicians was low. Patients (14%) reported delaying due to fear of COVID-19 infection and inability to leave home.

Conclusions

Presentation delays were substantial and multilevel barriers to timely presentation were identified, which would be expected to contribute to later-stage cancer at diagnosis.

Implications for practice

Findings suggest that nursing interventions and improved health policies are urgently needed in China, including breast cancer education to increase awareness.
Extended and Long-term Cancer Survivorship of Childhood Survivors
Authors: Leite Ana Carolina Andrade Biaggi , Nascimento Lucila Castanheira , Neris Rhyquelle Rhibna , Soto-Ruiz Nelia , Escalada-Hernández Paula , Martín-Rodríguez Leticia San , García-Vivar Cristina
Published: June 2024

Background

With the increasing survival rates of childhood cancer, nurses’ familiarity with published evidence has become crucial to care for this population and their families throughout the survival process.

Objective

To systematically identify and conduct a bibliometric analysis of nursing-related evidence concerning extended and long-term survival of childhood survivors.

Methods

A scoping review was conducted using bibliometric analysis with searches performed in the PubMed, CINAHL, SCOPUS, and Web of Science databases. A total of 300 studies on childhood cancer survival within the nursing field were included.

Results

The first study on this topic was published in 1975. American and Chinese researchers lead study publications, primarily publishing in nursing journals such as Cancer Nursing. Quantitative designs were prevalent, and the majority of the studies focused on physical late effects, overall quality of life, and survivor follow-up care.

Conclusions

This study has allowed us to map and synthesize the bibliometric evidence pertaining to the extended and long-term survivorship of childhood cancer survivors in the nursing field. Consequently, it identifies gaps in knowledge, research trends, and areas necessitating further exploration.

Implications for Practice

The evidence presented in this review can facilitate academic and clinical discussions, offering a comprehensive synthesis of the published knowledge. More research needs to be developed on the topic, particularly in Central and Latin America, Africa, Southern and Eastern Europe, and in some regions of Asia. Furthermore, the scope of studies should extend beyond late effects and quality of life, encompassing the experience of surviving childhood cancer, including psychosocial and spiritual dimensions.
Dispelling the Myths of Isotretinoin and Implications for Rhinoplasty
Authors: Blough Jordan T. , Rohrich Rachel , Wyles Saranya P. , Rohrich Rodney J.
Published: June 2024

Despite concerns from 1980s case reports, oral isotretinoin, a derivative of Vitamin A, has largely proven to be safe in surgical procedures with the exception of deep skin resurfacing. Isotretinoin modulates thinning skin and internal scarring in select rhinoplasty patients who may otherwise have poor definition and excessive scarring. A review of patients undergoing surgical interventions including rhinoplasty in the setting of concomitant isotretinoin was performed to examine safety and therapeutic potential. Forty-nine studies were reviewed. Isotretinoin use appears to be safe in a wide variety of surgical procedures relying on internal scar formation. In rhinoplasty, studies utilized oral isotretinoin to thin skin and improve appearance, patient and surgeon satisfaction. As such, the clinical potential for using oral isotretinoin in select rhinoplasty candidates such as those with thick glaborous sebaceous skin, ethnic, male, and/or revision patients, could mitigate internal scarring processes. Further studies examining the optimal dosing regimen and long-term benefits are warranted.
Modeling the HIV cascade of care using routinely collected clinical data to guide programmatic interventions and policy decisions
Authors: Bakoyannis Giorgos , Elul Batya , Wools-Kaloustian Kara K. , Brown Steven , Semeere Aggrey , Castelnuovo Barbara , Diero Lameck , Nakigozi Gertrude , Lyamuya Rita , Yiannoutsos Constantin T. ,   for the East Africa IeDEA Regional Consortium
Published: June 2024

Background:

The HIV care cascade is a framework to examine effectiveness of HIV programs and progress toward global targets to end the epidemic but has been conceptualized as a unidirectional process that ignores cyclical care patterns. We present a dynamic cascade that accounts for patient “churn,” and apply novel analytic techniques to readily available clinical data to robustly estimate program outcomes and efficiently assess progress towards global targets.

Methods:

Data were assessed for 35,649 people living with HIV and receiving care at 78 clinics in East Africa between 2014-2020. Patients were aged >15 years and had >1 viral load measurements. We used multi-state models to estimate the probability of being in 1 of 5 states of a dynamic HIV cascade: (1) in HIV care but not on antiretroviral therapy (ART); (2) on ART; (3) virally suppressed; (4) in a gap-in-care; and (5) deceased; and compared these among subgroups. To assess progress towards global targets, we summed those probabilities across patients and generated population-level proportions of patients on ART and virally suppressed in mid-2020.

Results:

One year following enrollment, 2.8% of patients had not initiated ART, 86.7% were receiving ART, 57.4% were virally suppressed,10.2% were disengaged from care, and 0.3% had died. At 5 years, the proportion on ART remained steady but viral suppression increased to 77.2%. Of those aged 15-25, >20% had disengaged from care and <60% were virally suppressed. In mid-2020, 90.1% of the cohort was on ART, 90.7% of whom had suppressed virus.

Conclusion:

Novel analytic approaches can characterize patient movement through a dynamic HIV cascade and, importantly, by capitalizing on readily available data from clinical cohorts, offer an efficient approach to estimate population-level proportions of patients on ART and virally suppressed. Significant progress towards global targets was observed in our cohort but challenges remain among younger patients.
Deep Learning Reconstructed New-Generation 0.55 T MRI of the Knee—A Prospective Comparison With Conventional 3 T MRI
Authors: Donners Ricardo , Vosshenrich Jan , Segeroth Martin , Seng Magdalena , Fenchel Matthias , Nickel Marcel Dominik , Bach Michael , Schmaranzer Florian , Todorski Inga , Obmann Markus M. , Harder Dorothee , Breit Hanns-Christian
Published: June 2024

Objectives

The aim of this study was to compare deep learning reconstructed (DLR) 0.55 T magnetic resonance imaging (MRI) quality, identification, and grading of structural anomalies and reader confidence levels with conventional 3 T knee MRI in patients with knee pain following trauma.

Materials and Methods

This prospective study of 26 symptomatic patients (5 women) includes 52 paired DLR 0.55 T and conventional 3 T MRI examinations obtained in 1 setting. A novel, commercially available DLR algorithm was employed for 0.55 T image reconstruction. Four board-certified radiologists reviewed all images independently and graded image quality, noted structural anomalies and their respective reporting confidence levels for the presence or absence, as well as grading of bone, cartilage, meniscus, ligament, and tendon lesions. Image quality and reader confidence levels were compared (P < 0.05, significant), and MRI findings were correlated between 0.55 T and 3 T MRI using Cohen kappa (κ).

Results

In reader's consensus, good image quality was found for DLR 0.55 T MRI and 3 T MRI (3.8 vs 4.1/5 points, P = 0.06). There was near-perfect agreement between 0.55 T DLR and 3 T MRI regarding the identification of structural anomalies for all readers (each κ ≥ 0.80). Substantial to near-perfection agreement between 0.55 T and 3 T MRI was reported for grading of cartilage (κ = 0.65–0.86) and meniscus lesions (κ = 0.71–1.0). High confidence levels were found for all readers for DLR 0.55 T and 3 T MRI, with 3 readers showing higher confidence levels for reporting cartilage lesions on 3 T MRI.

Conclusions

In conclusion, new-generation 0.55 T DLR MRI provides good image quality, comparable to conventional 3 T MRI, and allows for reliable identification of internal derangement of the knee with high reader confidence.
Enhanced long-term potentiation in the anterior cingulate cortex of tree shrew
Authors: Song Qian , Li Xu-Hui , Lu Jing-Shan , Chen Qi-Yu , Liu Ren-Hao , Zhou Si-Bo , Zhuo Min
Published: June 2024

Synaptic plasticity is a key cellular model for learning, memory and chronic pain. Most previous studies were carried out in rats and mice, and less is known about synaptic plasticity in non-human primates. In the present study, we used integrative experimental approaches to study long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of adult tree shrews. We found that glutamate is the major excitatory transmitter and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid (AMPA) receptors mediate postsynaptic responses. LTP in tree shrews was greater than that in adult mice and lasted for at least 5 h.
N
-methyl-
d
-aspartic acid (NMDA) receptors, Ca
2+
influx and adenylyl cyclase 1 (AC1) contributed to tree shrew LTP. Our results suggest that LTP is a major form of synaptic plasticity in the ACC of primate-like animals.

This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
NeuroNella: A Robust Unsupervised Algorithm for Identification of Neural Activity from Multielectrode Arrays
Authors: Germer C. , Farina D. , Baker S.N. , Del Vecchio A.
Published: June 2024

We introduce NeuroNella, an automated algorithm developed for the identification of neuronal activity from multichannel electrode arrays. In evaluations conducted on recordings from implanted probes in the nervous system of rodents and primates, the algorithm demonstrated remarkable accuracy, showcasing an error rate of less than 1% compared to ground-truth patch clamp signals. Notably, the proposed algorithm handles large datasets efficiently without the necessity of a GPU system. The results highlighted the algorithm’s efficacy in detecting sources in a wide amplitude range and its adaptability in accommodating minor probe shifts. Moreover, the high robustness exhibited by the algorithm in decomposing recordings lasting up to 30 minutes underscores its potential for enabling longitudinal studies and prolonged recording sessions, thus opening new avenues for future brain/machine interface applications.
Decreased scene-selective activity within the posterior intraparietal cortex in amblyopic adults
Authors: Malladi Sarala N , Skerswetat Jan , Tootell Roger BH , Gaier Eric D , Bex Peter , Hunter David G , Nasr Shahin
Published: June 2024

Amblyopia is a developmental disorder associated with reduced performance in visually guided tasks, including binocular navigation within natural environments. To help understand the underlying neurological disorder, we used fMRI to test the impact of amblyopia on the functional organization of scene-selective cortical areas, including the posterior intraparietal gyrus scene-selective (PIGS) area, a recently discovered region that responds selectively to ego-motion within naturalistic environments (Kennedy et al., 2024). Nineteen amblyopic adults (10 female) and thirty age-matched controls (12 female) participated in this study. Amblyopic participants spanned a wide range of amblyopia severity, based on their interocular visual acuity difference and stereoacuity. The visual function questionnaire (VFQ-39) was used to assess the participants perception of their visual capabilities. Compared to controls, we found weaker scene-selective activity within the PIGS area in amblyopic individuals. By contrast, the level of scene-selective activity across the occipital place area (OPA), parahippocampal place area (PPA), and retrosplenial cortex (RSC)) remained comparable between amblyopic and control participants. The subjects scores on general vision (VFQ-39 subscale) correlated with the level of scene-selective activity in PIGS. These results provide novel and direct evidence for amblyopia-related changes in scene-processing networks, thus enabling future studies to potentially link these changes across the spectrum of documented disabilities in amblyopia.
Parkinson’s LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress
Authors: Guevara Christopher A. , Alloo Kumayl , Gupta Swati , Thomas Romario , del Valle Pamela , Magee Alexandra R. , Benson Deanna L. , Huntley George W.
Published: June 2024

Anxiety is a psychiatric non-motor symptom of Parkinson’s that can appear in the prodromal period, prior to significant loss of brainstem dopamine neurons and motor symptoms. Parkinson’s-related anxiety affects females more than males, despite the greater prevalence of Parkinson’s in males. How stress, anxiety and Parkinson’s are related and the basis for a sex-specific impact of stress in Parkinson’s are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2G2019S) andLrrk2WTcontrol mice. In humans,LRRK2G2019Ssignificantly elevates the risk of late-onset Parkinson’s. To assess within-sex differences betweenLrrk2G2019Sand control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design wherebyLrrk2G2019SandLrrk2WTcontrol mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, maleLrrk2G2019Smice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact onLrrk2G2019Smice while significantly increasing latency to feed inLrrk2WTcontrol mice. FemaleLrrk2G2019Smice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and femaleLrrk2G2019Smice was generally lower compared to stressedLrrk2WTmice, except for the nucleus accumbens of maleLrrk2G2019Smice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that theLrrk2G2019Smutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in stress-related brain regions.
EEG Responses to Upper Limb Pinprick Stimulation in Acute and Early Subacute Motor and Sensorimotor Stroke
Authors: Tedesco Triccas L , Van Hoornweder S , Camilleri TC , Boccuni L , Peeters A , Van Pesch V , Meesen R , Mantini D , Camilleri KP , Verheyden G
Published: June 2024

Background

Electroencephalography (EEG) during pinprick stimulation has the potential to unveil neural mechanisms underlying sensorimotor impairments post-stroke. This study explored event-related peak pinprick amplitude and oscillatory responses in healthy controls, in people with motor and sensorimotor in acute and early subacute stroke, their relationship and to what extent EEG somatosensory responses can predict sensorimotor impairment.

Methods

In this study, involving 26 individuals, 10 people with a (sub-)acute sensorimotor stroke, 6 people with a (sub)acute motor stroke and 10 age-matched controls, pinpricks were applied to the dorsa of the impaired hand to collect somatosensory evoked potentials. Time(-frequency) analyses of somatosensory evoked potential (SEP) data at electrodes C3 and C4 explored peak pinprick amplitude and oscillatory responses across the three groups. Also, in stroke, (sensori-)motor impairments were assessed at baseline Fugl Meyer Assessment Upper Extremity (FMA-UE) and Erasmus modified Nottingham Sensory Assessment (EmNSA) at baseline and 7 to 14 days later including Fugl Meyer Assessment Upper Extremity (FMA-UE) and Erasmus modified Nottingham Sensory Assessment (EmNSA). Mixed model analyses were used to address objectives.

Results

It was demonstrated that increased beta desynchronization magnitude correlated with milder motor impairments (R2=0.213), whereas increased beta resynchronization and delta power were associated to milder somatosensory impairment (R2=0.550). At the second session, larger peak-to-peak SEP amplitude and beta band resynchronization at baseline were related to greater improvements in EMNSA and FMA-UE score, respectively, in sensorimotor stroke group.

Conclusions

These findings highlight the potential of EEG combined with somatosensory stimuli to differentiate between sensorimotor and motor impairments in stroke, offering preliminary insights into both diagnostic and prognostic aspects of upper limb recovery.
Control of heat and oxidative stress adaptation by the DJ-1 paralogs inArabidopsis thaliana
Authors: Kataria Priyanka , Pullagurla Naga Jyothi , Laha Debabrata , D’ Silva Patrick
Published: June 2024

Plant growth and development are highly regulated processes and are majorly controlled by various environmental factors, whose extreme exposures lead to chronic stress conditions promoting reactive oxygen species (ROS) and carbonyl species (RCS) production. ROS and RCS extensively damage cellular biomolecules and organelles, affecting plant’s viability and development. Emerging reports highlight that the multi-stress responding DJ-1 superfamily proteins are critical in attenuating cytotoxic effects associated with abiotic stress. The current report, validated in yeast and plant models, shows thatAtDJ-1C andAtDJ-1E are robust antioxidants that scavenge ROS and improve survival under oxidative stress. Although they lack conventional glyoxalases and do not attenuate the glycation of proteins,AtDJ-1C andAtDJ-1E preserve the GSH pool and regulate redox homeostasis. Moreover, transcriptome profiling indicates that levels ofAtDJ-1CandAtDJ-1Eare rapidly established to counter heat and oxidative stress conditions. Notably, the knockdown ofAtDJ-1CandAtDJ-1Epromotes detrimental alterations such as reduced chlorophyll retention, impaired root morphogenesis, and induced sensitivity to heat stress due to ROS elevation. Contrastingly, overexpression ofAtDJ-1C andAtDJ-1E improved plant height and rosette formation under physiological conditions. In conclusion, our study unravels the pivotal functions ofArabidopsis thalianaDJ-1C and DJ-1E in governing plant health and survival under heat and oxidative stress conditions.
Whole-genome DNA methylomes of Tree shrew brains reveal conserved and divergent roles of DNA methylation on sex chromosome regulation
Authors: Son Dongmin , Kong Yifan , Tan Yulian , Hu Ting , Shi Lei , Yi Soojin V.
Published: June 2024

The tree shrew (Tupaia belangeri) is a promising emerging model organism in biomedical studies, notably due to their evolutionary proximity to primates. To enhance our understanding of how DNA methylation is implicated in regulation of gene expression and the X chromosome inactivation (XCI) in tree shrew brains, here we present their first genome-wide, single-base-resolution methylomes integrated with transcriptomes from prefrontal cortices. We discovered both divergent and conserved features of tree shrew DNA methylation compared to that of other mammals. DNA methylation levels of promoter and gene body regions are negatively correlated with gene expression, consistent with patterns in other mammalian brains studied. Comparing DNA methylation patterns of the female and male X chromosomes, we observed a clear and significant global reduction (hypomethylation) of DNA methylation across the entire X chromosome in females. Our data suggests that the female X hypomethylation does not directly contribute to the gene silencing of the inactivated X chromosome nor does it significantly drive sex-specific gene expression of tree shrews. However, we identified a putative regulatory region in the 5’ end of the X inactive specific transcript (Xist)gene, a key gene for XCI, whose pattern of differential DNA methylation strongly relate to its differential expression between male and female tree shrews. We show that differential methylation of this region is conserved across different species. Moreover, we provide evidence suggesting that the observed difference between human and tree shrew X-linked promoter methylation is associated with the difference in genomic CpG contents. Our study offers novel information on genomic DNA methylation of tree shrews, as well as insights into the evolution of X chromosome regulation in mammals.
A Hybrid Simulation Model of HIV Program Interventions: From Transmission Behavior to Macroeconomic Impacts
Authors: Crown William , Britton Erin , Razavi Moaven , Luan Yiqun , Veerunaidu Senthil , Kates Jennifer , Gaumer Gary , Jordan Monica , Hurley Clare L. , Nandakumar A.K.
Published: June 2024

While several studies have examined the public health effects of HIV investments, there is a smaller literature that examines the macroeconomic impacts of such investments. The most recent efforts have utilized econometric analyses of country-level panel data, as well as demographic simulations of HIV spending. However, there are no studies that examine the linkages between the behavioral responses to public health investments, demographic changes, and, ultimately, macroeconomic performance. This study demonstrates the feasibility of such a linkage. We develop an agent-based simulation model (ABM) of a Peer Navigator Program to support engagement in HIV therapy in Tanzania. Results from the ABM are weighted to reflect the Tanzania population and fed into the SPECTRUM model. This generates detailed demographic forecasts that are translated into macroeconomic impacts using labor force participation rates from the International Labor Organization, along with an econometric model of gross domestic product (GDP). Although the simulated effects of the Peer Navigator Program in Tanzania are small, the paper demonstrates the feasibility of linking behavioral ABM simulations of program impacts to subsequent demographic effects and, finally, macroeconomic performance.
Principal component analysis revisited: fast multi-trait genetic evaluations with smooth convergence
Authors: Ahlinder Jon , Hall David , Suontama Mari , Sillanpää Mikko J
Published: June 2024

A cornerstone in breeding and population genetics is the genetic evaluation procedure, needed to make important decisions on population management. Multivariate mixed model analysis, in which many traits is considered jointly, utilizes genetic and environmental correlations between traits to improve the accuracy. However, the number of parameters in the multi-trait model grows exponentially with the number of traits which reduces its scalability. Here, we suggest using principal component analysis (PCA) to reduce the dimensions of the response variables, and then using the computed principal components (PC) as separate responses in the genetic evaluation analysis. As PCs are orthogonal to each other, multivariate analysis is no longer needed and separate univariate analyses can be performed instead. We compared the approach to traditional multivariate analysis in terms of computational requirement and rank lists according to predicted genetic merit on two forest tree datasets with 22 and 27 measured traits respectively. Obtained rank lists of the top 50 individuals were in good agreement.

Interestingly, the required computational time of the approach only took a few seconds without convergence issues, unlike the traditional approach which required considerably more time to run (seven and ten hours respectively). Our approach can easily handle missing data and can be used with all available linear mixed models software as it does not require any specific implementation. The approach can help to mitigate difficulties with multi-trait genetic analysis in both breeding and wild populations.
Transcranial Brain Atlas Based on Photon Measurement Density Function in a Triple-Parameter Standard Channel Space
Authors: Wei Lijiang , Zhao Yang , Liu Farui , Chen Yuanyuan , Xu Yilong , Li Zheng , Zhu Chaozhe
Published: June 2024

Functional near-infrared spectroscopy (fNIRS) is a widely used transcranial brain imaging technique in neuroscience research. Nevertheless, its lack of anatomical information poses challenges for designing appropriate optode montage and localizing fNIRS signals to underlying anatomical regions. The photon measurement density function (PMDF) is often employed to address these issues, as it accurately measures the sensitivity of a fNIRS signal channel to perturbations of absorption coefficients at any brain locations. However, existing PMDF-based localization methods have two limitations: a limited channel space, and PMDF estimation based on single standard head models, which differ anatomically from individual subjects. To overcome these limitations, this study proposes a continuous fNIRS standard channel space and constructs a PMDF-based transcranial brain atlas (PMDF-TBA) by calculating PMDFs based on MRI images of 48 adults. PMDF-TBA contains group-averaged sensitivities of channels to gray matter and brain regions of atlases, such as Brodmann, AAL2, and LPBA40. Through leave-one-out cross-validation, we evaluated the prediction ability of PMDF-TBA for sensitivity of unseen individuals and found that it outperformed PMDFs based on single standard head models. Thus, PMDF-TBA serves as a more generalizable fNIRS spatial localization tool. Therefore, PMDF-TBA can be utilized to optimize optode montage design, improve channel sensitivity to target brain regions, and assist in the source localization of fNIRS data, thereby promoting the application of fNIRS in neuroscience research.
Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation
Authors: Miller Rachael , Paquette Joseph , Barker Alexandra , Sapp Ellen , McHugh Nicholas , Bramato Brianna , Yamada Nazomi , Alterman Julia , Echeveria Dimas , Yamada Ken , Watts Jonathan K , Anaclet Christelle , DiFiglia Marian , Khvorova Anastasia , Aronin Neil
Published: June 2024

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection. Electroencephalography (EEG) and electromyography (EMG) in awake mice demonstrated seizures. Using ion chromatography, we show that siRNAs can tightly bind Ca2+ and Mg2+ up to molar equivalents of the phosphodiester (PO)/phosphorothioate (PS) bonds independently of the structure or phosphorothioate content. Optimization of the formulation by adding high concentrations (above biological levels) of divalent cations (Ca2+ alone, Mg2+ alone, or Ca2+ and Mg2+) prevents seizures with no impact on the distribution or efficacy of the oligonucleotide. The data here establishes the importance of adding Ca2+ and Mg2+ to the formulation for the safety of CNS administration of therapeutic oligonucleotides.
RESPAN: A Deep Learning Pipeline for Accurate and Automated Restoration, Segmentation, and Quantification of Dendritic Spines
Authors: Garcia Sergio B. , Schlotter Alexa P. , Pereira Daniela , Recupero Aleksandra J , Polleux Franck , Hammond Luke A
Published: June 2024

Quantification of dendritic spines is essential for studying synaptic connectivity, yet most current approaches require manual adjustments or the combination of multiple software tools for optimal results. Here, we present Restoration Enhanced SPine And Neuron Analysis (RESPAN), an open-source pipeline integrating state-of-the-art deep learning for image restoration, segmentation, and analysis in an easily deployable, user-friendly interface. Leveraging content-aware restoration to enhance signal, contrast, and isotropic resolution further enhances RESPAN robust detection of spines, dendritic branches, and soma across a wide variety of samples, including challenging datasets such as those from live imaging and in vivo 2-photon microscopy with limited signal. Extensive validation against expert annotations and comparison with other software demonstrates RESPAN superior accuracy and reproducibility across multiple imaging modalities. RESPAN offers significant improvements in usability over currently available approaches, streamlining and democratizing access to a combination of advanced capabilities through an accessible resource for the neuroscience community.
Antarctic geothermal soils exhibit an absence of regional habitat generalist microorganisms
Authors: Noell Stephen E , Abbaszadeh Jaber , Richards Huw , Labat Saint Vincent Marie , Lee Charles K , Herbold Craig W , Stott Matthew B , Cary S Craig , McDonald Ian R
Published: June 2024

Active geothermal systems are relatively rare in Antarctica and represent metaphorical islands ideal to study microbial dispersal. In this study, we tested the macroecological concept that high dispersal rates result in communities being dominated by either habitat generalists or specialists by investigating the microbial communities on four geographically separated geothermal sites on three Antarctic volcanoes (Mts. Erebus, Melbourne and Rittman). We found that the microbial communities at higher temperature (max 65℃) sites (Tramway Ridge on Erebus and Rittmann) were unique from each other and were dominated by a variety of novel Archaea from class Nitrososphaeria, while lower temperature (max 50℃) sites (Western Crater on Erebus and Melbourne) had characteristically mesophilic communities (Planctomycetes, Acidobacteriota, etc) that were highly similar. We found that 97% of the detected microbial taxa were regional habitat specialists, with no generalists, with community assembly driven by high dispersal rates and drift (25 and 30% of community assembly, respectively), not environmental selection. Our results indicate that for microbial communities experiencing high dispersal rates between isolated communities, habitat specialists may tend to out-compete habitat generalists.
Critical assessment of missense variant effect predictors on disease-relevant variant data
Authors: Rastogi Ruchir , Chung Ryan , Li Sindy , Li Chang , Lee Kyoungyeul , Woo Junwoo , Kim Dong-Wook , Keum Changwon , Babbi Giulia , Martelli Pier Luigi , Savojardo Castrense , Casadio Rita , Chennen Kirsley , Weber Thomas , Poch Olivier , Ancien François , Cia Gabriel , Pucci Fabrizio , Raimondi Daniele , Vranken Wim , Rooman Marianne , Marquet Céline , Olenyi Tobias , Rost Burkhard , Andreoletti Gaia , Kamandula Akash , Peng Yisu , Bakolitsa Constantina , Mort Matthew , Cooper David N. , Bergquist Timothy , Pejaver Vikas , Liu Xiaoming , Radivojac Predrag , Brenner Steven E. , Ioannidis Nilah M.
Published: June 2024

Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity of missense variants is necessary to evaluate their clinical and research utility and suggest directions for future improvement. Here, as part of the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, we assess missense variant effect predictors (or variant impact predictors) on an evaluation dataset of rare missense variants from disease-relevant databases. Our assessment evaluates predictors submitted to the CAGI6 Annotate-All-Missense challenge, predictors commonly used by the clinical genetics community, and recently developed deep learning methods for variant effect prediction. To explore a variety of settings that are relevant for different clinical and research applications, we assess performance within different subsets of the evaluation data and within high-specificity and high-sensitivity regimes. We find strong performance of many predictors across multiple settings. Meta-predictors tend to outperform their constituent individual predictors; however, several individual predictors have performance similar to that of commonly used meta-predictors. The relative performance of predictors differs in high-specificity and high-sensitivity regimes, suggesting that different methods may be best suited to different use cases. We also characterize two potential sources of bias. Predictors that incorporate allele frequency as a predictive feature tend to have reduced performance when distinguishing pathogenic variants from very rare benign variants, and predictors supervised on pathogenicity labels from curated variant databases often learn label imbalances within genes. Overall, we find notable advances over the oldest and most cited missense variant effect predictors and continued improvements among the most recently developed tools, and the CAGI Annotate-All-Missense challenge (also termed the Missense Marathon) will continue to assess state-of-the-art methods as the field progresses. Together, our results help illuminate the current clinical and research utility of missense variant effect predictors and identify potential areas for future development.
Serosurveillance of dengue infection and correlation with mosquito pools for dengue virus positivity during the COVID-19 pandemic in Tamil Nadu, India – A state-wide cross-sectional cluster randomized community-based study
Authors: Selvavinayagam Sivaprakasam T. , Sankar Sathish , Yong Yean K. , Anshad Abdul R. , Chandramathi Samudi , Somasundaram Anavarathan , Palani Sampath , Kumarasamy Parthipan , Azhaguvel Roshini , Kumar Ajith B. , Subramaniam Sudharshini , Malathi Manickam , Vijayalakshmi Venkatachalam , Rajeshkumar Manivannan , Kumaresan Anandhazhvar , Pandey Ramendra P. , Muruganandam Nagarajan , Gopalan Natarajan , Kannan Meganathan , Murugesan Amudhan , Balakrishnan Pachamuthu , Byrareddy Siddappa N. , Dash Aditya P. , Larsson Marie , Velu Vijayakumar , Shankar Esaki M. , Raju Sivadoss
Published: June 2024

Background

Dengue is a vector-borne viral disease impacting millions across the globe. Nevertheless, akin to many other diseases, reports indicated a decline in dengue incidence and seroprevalence during the COVID-19 pandemic (2020-22). This presumably could be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to vectors due to lockdowns. Scientific evidence on dengue virus (DENV) disease during the COVID-19 pandemic is limited globally.

Methods

A cross-sectional, randomized cluster sampling community-based survey was carried out to assess anti-dengue IgM and IgG and SARS-CoV-2 IgG seroprevalence across all 38 districts of Tamil Nadu, India. The prevalence of DENV in the Aedes mosquito pools during 2021 was analyzed and compared with previous and following years of vector surveillance for DENV by real-time PCR.

Findings

Results implicate that both DENV-IgM and IgG seroprevalence and mosquito viral positivity were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3·76% of mosquito pools were positive for DENV. In the human sera, 4·12% were positive for DENV IgM and 6·4% were positive for DENV IgG. The anti-SARS-CoV-2 antibody titres correlated with dengue seropositivity with a significant association whereas vaccination status significantly correlated with dengue IgM levels.

Interpretation

Continuous monitoring of DENV seroprevalence, especially with the evolving variants of the SARS-CoV-2 virus and surge in COVID-19 cases will shed light on the transmission and therapeutic attributes of dengue infection.