syedzayyan/paper_mill_benchmark huggingface dataset:
Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss.

Noise-induced hearing loss (nihl) has always been an important occupational hazard, but the exact etiopathogenesis underlying nihl remains unclear.Herein, we aimed to find metabolic biomarkers involved in the development of nihl based on a mouse model using a gas chromatography coupled with mass spectrometry (gc-ms) metabolomics technique.We showed that the auditory brainstem response (abr) thresholds at the frequencies of 4, 8, 12, 16, 24, and 32 k hz were all significantly elevated in the noise-exposed mice.Noise could cause outer hair cell (ohc) loss in the base of the cochlea.A total of 17 differential metabolites and 9 metabolic pathways were significantly affected following noise exposure.Spermidine acting as an autophagy modulator was found to be 2.85-fold higher in the noise-exposed group than in the control group and involved inβ-alanine metabolism and arginine and proline metabolism pathways.Additionally, we demonstrated that lc3b and beclin1 were expressed in the spiral ganglion neurons (sgns), and their m rna levels were increased after noise.We showed that sod activity was significantly decreased in the cochlea of noise-exposed mice.Further experiments suggested that sod1 and sod2 proteins in the sgns were all decreased following noise exposure.The upregulation of spermidine may induce lc3b- and beclin1-mediated autophagy in the cochlear hair cells (hcs) throughβ-alanine metabolism and arginine and proline metabolism and be involved in the nihl.Ros-mediated oxidative damage may be a pivotal molecular mechanism of nihl.Taken together, spermidine can be regarded as an important metabolic marker for the diagnosis of nihl.

Journal: BioMed research international (2022)
Publication types: Journal Article
LC-MS-based urinary metabolite signatures in idiopathic Parkinson's disease.

Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of parkinson's disease (pd).These body fluids include urine; however, the relationship between, specifically, urinary metabolic phenotypes and pd is not fully understood.In this study, urinary metabolites from a total of 401 clinical urine samples collected from 106 idiopathic pd patients and 104 normal control subjects were profiled by using high-performance liquid chromatography coupled to high-resolution mass spectrometry.Our study revealed significant correlation between clinical phenotype and urinary metabolite profile.Metabolic profiles of idiopathic pd patients differed significantly and consistently from normal controls, with related metabolic pathway variations observed in steroidogenesis, fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism, tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism.In the fruit fly drosophila melanogaster, the alteration of the kynurenine pathway in tryptophan metabolism corresponded with pathogenic changes in the alpha-synuclein overexpressed drosophila model of pd.The results suggest that lc-ms-based urinary metabolomic profiling can reveal the metabolite signatures and related variations in metabolic pathways that characterize pd.Consistent pd-related changes across species may provide the basis for understanding metabolic regulation of pd at the molecular level.

Journal: Journal of proteome research (2015)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Providing Housing First services for an underserved population during the early wave of the COVID-19 pandemic: A qualitative study.

We assessed the critical role of housing first (hf) programs and frontline workers in responding to challenges faced during the first wave of the covid-19 pandemic.Method semi-structured interviews were conducted with nine hf frontline workers from three hf programs between may 2020 and july 2020, in toronto, canada.Information was collected on challenges and adjustments needed to provide services to hf clients (people experiencing homelessness and mental disorders).We applied the analytical framework method and thematic analysis to our data.Results inability to provide in-person support and socializing activities, barriers to appropriate mental health assessments, and limited virtual communication due to clients' lack of access to digital devices were among the most salient challenges that hf frontline workers reported during the covid-19 pandemic.Implementing virtual support services, provision of urgent in-office or in-field support, distributing food aid, connecting clients with online healthcare services, increasing harm reduction education and referral, and meeting urgent housing needs were some of the strategies implemented by hf frontline workers to support the complex needs of their clients during the pandemic.Hf frontline workers experienced workload burden, job insecurity and mental health problems (e.g.Distress, worry, anxiety) as a consequence of their services during the first wave of the covid-19 pandemic.Conclusion despite the several work-, programming- and structural-related challenges experienced by hf frontline workers when responding to the needs of their clients during the first wave of the covid-19 pandemic, they played a critical role in meeting the communication, food, housing and health needs of their clients during the pandemic, even when it negatively affected their well-being.A more coordinated, integrated, innovative, sustainable, effective and well-funded support response is required to meet the intersecting and complex social, housing, health and financial needs of underserved and socio-economically excluded groups during and beyond health emergencies.

Journal: PloS one (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care Toward Molecular Medicine.

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease.Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition.But the potential of the tracer principle goes beyond the assessment of physiology and function, toward the interrogation of biology and molecular pathways.This is a unique selling point of radionuclide imaging, which has been underrecognized in cardiovascular medicine until recently.Now, molecular imaging methods for the detection of myocardial infiltration, device infection, and cardiovascular inflammation are successfully gaining clinical acceptance.This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecule-targeted procedures, in which specific therapeutic interventions require specific diagnostic guidance toward the most suitable candidates.This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad blockbuster medication, toward a future of novel, individualized molecule-targeted and molecular imaging-guided therapies.

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Chromosomal fusion and life history-associated genomic variation contribute to within-river local adaptation of Atlantic salmon.

Chromosomal inversions have been implicated in facilitating adaptation in the face of high levels of gene flow, but whether chromosomal fusions also have similar potential remains poorly understood.Atlantic salmon are usually characterized by population structure at multiple spatial scales; however, this is not the case for tributaries of the miramichi river in north america.To resolve genetic relationships between populations in this system and the potential for known chromosomal fusions to contribute to adaptation, we genotyped 728 juvenile salmon using a 50 k snp array.Consistent with previous work, we report extremely weak overall population structuring (global fst= 0.004) and failed to support hierarchical structure between the river's two main branches.We provide the first genomic characterization of a previously described polymorphic fusion between chromosomes 8 and 29.Fusion genomic characteristics included high ld, reduced heterozygosity in the fused homokaryotes, and strong divergence between the fused and the unfused rearrangement.Population structure based on fusion karyotype was five times stronger than neutral variation (fst= 0.019), and the frequency of the fusion was associated with summer precipitation supporting a hypothesis that this rearrangement may contribute local adaptation despite weak neutral differentiation.Additionally, both outlier variation among populations and a polygenic framework for characterizing adaptive variation in relation to climate identified a 250-kb region of chromosome 9, including the gene six6 that has previously been linked to age-at-maturity and run-timing for this species.Overall, our results indicate that adaptive processes, independent of major river branching, are more important than neutral processes for structuring these populations.

Journal: Molecular ecology (2019)
Publication types: Journal Article
Hamstring Injury: What Is It? What Should I Do About It? When Can I Get Back to My Sport?

Recently, experts developed a guideline for physical therapists to use when treating hamstring injuries.We explain what the guidelines mean for your hamstring injury and answer questions you might have about how long it takes to recover and when you can play your sport again.j orthop sports phys ther 2022;52(3):129.

Journal: The Journal of orthopaedic and sports physical therapy (2022)
Publication types: Journal Article
Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury.

Traumatic brain injury (tbi) is a complex, life-threatening condition that causes mortality and disability worldwide.No effective treatment has been clinically verified to date.Achieving effective drug delivery across the blood-brain barrier (bbb) presents a major challenge to therapeutic drug development for tbi.Furthermore, the field of tbi biomarkers is rapidly developing to cope with the many aspects of tbi pathology and enhance clinical management of tbi.Exosomes (exos) are endogenous extracellular vesicles (evs) containing various biological materials, including lipids, proteins, micro rnas, and other nucleic acids.Compelling evidence exists that exos, such as stem cell-derived exos and even neuron or glial cell-derived exos, are promising tbi treatment strategies because they pass through the bbb and have the potential to deliver molecules to target lesions.Meanwhile, exos have decreased safety risks from intravenous injection or orthotopic transplantation of viable cells, such as microvascular occlusion or imbalanced growth of transplanted cells.These unique characteristics also create exos contents, especially exos-derived micro rnas, as appealing biomarkers in tbi.In this review, we explore the potential impact of cell-derived exos and exosome-derived micro rnas on the diagnosis, therapy, and prognosis prediction of tbi.The associated challenges and opportunities are also discussed.

Journal: Journal of clinical medicine (2022)
Publication types: Journal Article;Review
UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer.

Bone metastasis is the main site of metastasis and causes the most deaths in patients with prostate cancer (pca).The mechanism of bone metastasis is complex and not fully clarified.By rna sequencing and analysing key pathways in bone metastases of pca, we found that one of the most important characteristics during pca bone metastasis was g1/s transition acceleration caused by low protein levels of p16ink4a (p16).Interestingly, we demonstrated that ube2s bound and degraded p16 through k11- rather than k48- or k63-linked ubiquitination, which accelerated pca tumour cell g1/s transitionin vivoandin vitro.Moreover, ube2s also stabilized β-catenin through k11-linked ubiquitination, leading to enhanced migration and invasion of tumour cells in pca bone metastasis.Based on our cohorts and public databases, ube2s was overexpressed in bone metastases and positively correlated with a high gleason score, advanced nodal metastasis status and poor prognosis in pca.Finally, targeting ube2s with cephalomannine inhibited proliferation and invasionin vitro, and bone metastasis of pcain vivo.This study innovatively discovered that ube2s plays an oncogenic role in bone metastasis of pca by degrading p16 and stabilizing β-catenin via k11-linked ubiquitination, suggesting that it may serve as a multipotent target for metastatic pca treatment.

Journal: International journal of biological sciences (2022)
Publication types: Journal Article
Colloidal fibers and rings by cooperative assembly.

Janus colloids with one attractive patch on an otherwise repulsive particle surface serve as model systems to explore structure formation of particles with chemically heterogeneous surfaces such as proteins.While there are numerous computer studies, there are few experimental realizations due to a lack of means to produce such colloids with a well-controlled variable janus balance.Here, we report a simple scalable method to precisely vary the janus balance over a wide range and selectively functionalize one patch with dna.We observe, via experiment and simulation, the dynamic formation of diverse superstructures: colloidal micelles, chains, or bilayers, depending on the janus balance.Flexible dimer chains form through cooperative polymerization while trimer chains form by a two-stage process, first by cooperative polymerization into disordered aggregates followed by condensation into more ordered stiff trimer chains.Introducing substrate binding through depletion catalyzes dimer chains to form nonequilibrium rings that otherwise do not form.

Journal: Nature communications (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.

Androgen receptor (ar) is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology.Although low expression of stromal ar is clinically associated with advanced cancer stage and worse outcome, whether stromal ar inhibits or promotes prostate cancer progression remains controversial.Here, we specifically delete ar in smooth muscle cells of the adult mouse prostate under two tumorigenic conditions, namely, the hi-myc genetic model and the t + e2 hormonal carcinogenesis model.Histology analyses show that stromal ar deletion exacerbates tumor progression phenotypes in both models.Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal ar deletion, as they transition to a cellular state of potentiated pi3k-m torc1 activities.Our results suggest that stromal ar normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy.

Journal: Cell reports (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Biomechanical Investigation of Lumbar Interbody Fusion Supplemented with Topping-off Instrumentation Using Different Dynamic Stabilization Devices.

Study design a biomechanical comparison study using finite element method.Objective the aim of this study was to investigate effects of different dynamic stabilization devices, including pedicle-based dynamic stabilization system (pbdss) and interspinous process spacer (isp), used for topping-off implants on biomechanical responses of human spine after lumbar interbody fusion.Summary of background data topping-off stabilization technique has been proposed to prevent adjacent segment degeneration following lumbar spine fusion.Pbdss and isp are the most used dynamic stabilizers for topping-off instrumentation.However, biomechanical differences between them still remain unclear.Methods a validated, normal fe model of human lumbosacral spine was employed.Based on this model, rigid fusion at l4-l5 and moderately disc degeneration at l3-l4 were simulated and used as a comparison baseline.Subsequently, bioflex and diam systems were instrumented at l3-l4 segment to construct pbdss-based and isp-based topping-off models.Biomechanical responses of the models to bending moments and vertical vibrational excitation were computed using fe static and random response analyses, respectively.Results results from static analysis showed that at l3-l4, the response parameters including annulus stress and range of motion were decreased by 41.6% to 85.2% for pbdss-based model and by 6.3% to 67% for isp-based model compared with rigid fusion model.At l2-l3, these parameters were lower in isp-based model than in pbdss-based model.Results from random response analysis showed that topping-off instrumentation increased resonant frequency of spine system but decreased dynamic response of annulus stress at l3-l4.Pbdss-based model generated lower dynamic stress than isp-based model at l3-l4, but the dynamic stress was higher at l2-l3 for pbdssbased model.Conclusion under static and vibration loadings, the pbdssbased topping-off device (bioflex) provided a better protection for transition segment, and likelihood of degeneration of supraadjacent segment might be relatively lower when using the ispbased topping-off device (diam).level of evidence: 5.

Journal: Spine (2021)
Publication types: Journal Article
Generation of optical Bessel beams with arbitrarily curved trajectories using a magnetic-liquid deformable mirror.

We propose a new strategy to curve the trajectory of the central lobe of a zero-order bessel beam and a first-order bessel beam along their propagation axis.Our method involves modifying the phase of a beam that is incident on an adaptive mirror.As examples, we show that the most intense lobe of the beam can follow a parabolic trajectory, a cubic trajectory, or a trajectory made by a combination of these orders.By using a phase correction emulating the effect of cylindrical mirrors, the central lobe always preserves its symmetry.Theoretical simulations were reproduced in the laboratory using a magnetic-liquid deformable mirror.The parabolic trajectory of the 60-μm central spot of a zero-order bessel beam exhibits a 0.6-mm off-axis shift after 30-cm-length propagation.

Journal: Applied optics (2018)
Publication types: Journal Article
A deep crowd density classification model for Hajj pilgrimage using fully convolutional neural network.

This research enhances crowd analysis by focusing on excessive crowd analysis and crowd density predictions for hajj and umrah pilgrimages.Crowd analysis usually analyzes the number of objects within an image or a frame in the videos and is regularly solved by estimating the density generated from the object location annotations.However, it suffers from low accuracy when the crowd is far away from the surveillance camera.This research proposes an approach to overcome the problem of estimating crowd density taken by a surveillance camera at a distance.The proposed approach employs a fully convolutional neural network (fcnn)-based method to monitor crowd analysis, especially for the classification of crowd density.This study aims to address the current technological challenges faced in video analysis in a scenario where the movement of large numbers of pilgrims with densities ranging between 7 and 8 per square meter.To address this challenge, this study aims to develop a new dataset based on the hajj pilgrimage scenario.To validate the proposed method, the proposed model is compared with existing models using existing datasets.The proposed fcnn based method achieved a final accuracy of 100%, 98%, and 98.16% on the proposed dataset, the ucsd dataset, and the jhu-crowd dataset, respectively.Additionally, the res net based method obtained final accuracy of 97%, 89%, and 97% for the proposed dataset, ucsd dataset, and jhu-crowd dataset, respectively.The proposed hajj-crowd-2021 crowd analysis dataset and the model outperformed the other state-of-the-art datasets and models in most cases.

Journal: PeerJ. Computer science (2022)
Publication types: Journal Article
RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge.

Multiple sars-co v-2 variants are identified with higher rates of transmissibility or greater disease severity.Particularly, recent emergence of omicron variant with rapid human-to-human transmission posts new challenges to the current prevention strategies.In this study, following vaccination with an m rna vaccine encoding sars-co v-2 receptor-binding domain (rbd-m rna), we detected serum antibodies that neutralized pseudoviruses expressing spike (s) protein harboring single or multiple mutations, as well as authentic sars-co v-2 variants, and evaluated its protection against sars-co v-2 infection.The vaccine induced durable antibodies that potently neutralized prototypic strain and b.1.1.7 lineage variant pseudoviruses containing n501y or d614g mutations alone or in combination with a n439k mutation (b.1.258 lineage), with a l452r mutation (b.1.427 or b.1.429 lineage), or a l452r-e484q double mutation (b.1.617.1 variant), although neutralizing activity against b.1.1.7 lineage variant containing 10 amino acid changes in the s protein was slightly reduced.The rbd-m rna-induced antibodies exerted moderate neutralization against authentic b.1.617.2 and b.1.1.529 variants, and pseudotyped b.1.351 and p.1 lineage variants containing k417n/t, e484k, and n501y mutations, the b.1.617.2 lineage variant harboring l452r, t478k, and p681r mutations, and the b.1.1.529 lineage variant containing 38 mutations in the s protein.Particularly, rbd-m rna vaccine completely protected mice from challenge with a virulent mouse-adapted sars-co v-2 variant.Among these lineages, b.1.1.7, b.1.351, p.1, b.1.617.2, and b.1.1.529 belong to alpha, beta, gamma, delta, and omicron variants, respectively.Our observations reveal that rbd-m rna vaccine is promising and highlights the need to design novel vaccines with improved neutralization against current and future pandemic sars-co v-2 variants.

Journal: Translational research : the journal of laboratory and clinical medicine (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural
Polyhedral oligosilsesquioxane-modified boron nitride enhances the mechanical properties of polyimide nanocomposites.

A novel high-strength polyimide (pi) nanocomposite film was designed and constructed by the copolymerization of epoxidized polyhedral oligomeric silsesquioxane-modified hexagonal boron nitride and polyamic acid (paa).The composite filler (epposs@gh-bn) was composed of silane coupling agent kh550 modified hexagonal boron nitride (gh-bn) and epoxidized polyhedral oligomeric silsesquioxanes (epposs), which improved not only the dispersion of the h-bn but also the effective interfacial stress transfer, leading to an enhanced mechanical strength of the resultant pi nanocomposite film of 114 mpa even with a slight epposs@gh-bn loading of 0.30 wt%, and the storage modulus was increased by more than 30% to 4 gpa compared to pure pi.Meanwhile, the pi/epposs@gh-bn nanocomposite has better heat transfer performance, higher hydrophobicity, lower dielectric properties, and higher heat stability than pure pi, and is therefore expected to provide an ideal platform for the development of highly flexible electronics in the future.

Journal: RSC advances (2022)
Publication types: Journal Article