anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Hybridization, the process of crossing individuals from diverse genetic backgrounds, plays a pivotal role in evolution, biological invasiveness, and crop breeding. At the transcriptional level, hybridization often leads to complex nonadditive effects, presenting challenges for understanding its consequences. Although standard transcriptomic analyses exist to compare hybrids to their progenitors, such analyses have not been implemented in a software package, hindering reproducibility. We introduce hybridexpress, an R/Bioconductor package designed to facilitate the analysis, visualization, and comparison of gene expression patterns in hybrid triplets (hybrids and their progenitors). hybridexpress provides users with a user-friendly and comprehensive workflow that includes all standard comparative analyses steps, including data normalization, calculation of midparent expression values, sample clustering, expression-based gene classification into categories and classes, and overrepresentation analysis for functional terms. We illustrate the utility of hybridexpress through comparative transcriptomic analyses of cotton allopolyploidization and rice root trait heterosis. hybridexpress is designed to streamline comparative transcriptomic studies of hybrid triplets, advancing our understanding of evolutionary dynamics in allopolyploids, and enhancing plant breeding strategies. hybridexpress is freely accessible from Bioconductor (https://bioconductor.org/packages/HybridExpress) and its source code is available on GitHub (https://github.com/almeidasilvaf/HybridExpress).
This study will investigate the incidence of recreational water illness due to exposure to cyanobacterial blooms and their toxins in four targeted and popular freshwater beaches in Ontario, Manitoba, and Nova Scotia, Canada. A prospective cohort design and One Health approach will be used. On-site recruitment of recreational water users will be conducted at two beaches per year during the summers of 2024 and 2025. The population of interest includes recreational water users of any age and their pet dogs. After enrollment, an in-person survey will determine beach exposures and confounding factors, and a three-day follow-up survey will ascertain any acute illness outcomes experienced by participants or their dogs. The target sample size is 2500 recreational water users. Water samples will be taken each recruitment day and analyzed for cyanobacterial indicators (pigments), cell counts, and toxin levels. Regression analysis will be conducted to estimate the association with water contact, cyanobacterial levels, and risks of different acute illness outcomes.
Patients undergo 60 minute sessions of nutrition education for 12 weeks and behavioral intervention 26 weeks. Patients receive FitBit and undergo physical activity for 30-60 minutes 5 days a week (aerobic activity) and 2 days a week (resistance training).
OBJECTIVE: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone.
METHODS: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform.
RESULTS: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio.
CONCLUSIONS: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs.
TRIAL REGISTRATION NUMBER: NCT02556450.
The researchers will recruit patients with severe liver disease at Parkland Hospital where the procedure will be performed. Age-, gender- and race-matched healthy subjects will be recruited from general population, and the procedure will be performed at the procedure room of the AIRC. Patients at Parkland will be screened and selected by Dr. Jeffrey Browning and Dr. Rodney Infante. After ingestion of 25 mg/kg \[U-13C3\]glycerol plus 25 mg/kg unlabeled glycerol in water (total glycerol dose, 50 mg/kg), blood will be drawn at +60 and +120 min.

Healthy subjects will make two visits to the AIRC for screening and study procedures. The screening visit will take an hour and the study visit will take 3 hours. Volunteers will be made comfortable in the procedure room of the Research Center. All the study procedures at both Parkland and AIRC will be under the direction of the principal investigator, Dr. Jeffrey Browning.
BACKGROUND/AIM: There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs).
PATIENTS AND METHODS: Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively.
RESULTS: Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa.
CONCLUSION: This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction.
Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 μM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 μM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.
More than 2 million stroke survivors currently living in the U.S. are obese. Obesity is known to exacerbate age-related declines in function in these individuals and is associated with poorer clinical outcomes and quality of life. Weight-loss interventions are well-studied in neurologically healthy individuals and are shown to be effective for attenuating functional decline and improving quality of life. Despite these established benefits, there is currently an absence of studies investigating the effects of intentional weight loss on physical and/or psychosocial function in individuals following stroke. The investigators propose a trial aimed at Enhancing Mobility and Psychosocial function in Obese Veterans following stroke via Weight loss and ExeRcise (EMPOWER). This trial leverages a 15-week multidisciplinary approach to weight loss, via an existing lifestyle and weight management program, including caloric restriction, with or without concurrent supervised exercise training, as the catalyst by which remediation of physical and psychosocial impairments promote enhanced recovery in obese Veteran survivors of stroke. The investigators posit that successful weight loss will result in improvements in physical and psychosocial function (compared to control subjects) and that concurrent exercise will result in improved outcomes when compared to weight loss alone. The VHA 2010 Management of Stroke Rehabilitation Guidelines recommends that patients receive a formal rehabilitation assessment, the results of which should be used to determine the appropriate level of care and develop evidence-based interventions. However, without information regarding the effects of obesity and weight management on physical and psychosocial function as well as data on the long-term benefits of the program, evidence to guide decisions regarding the most appropriate approach to post-stroke rehabilitation for obese Veteran stroke survivors will remain elusive and recommendations for best available treatment cannot be met. Data from the proposed trial will have important clinical significance by determining the extent to which this type of program improves (or not) physical and psychosocial outcomes in Veterans following stroke and will provide a foundation for future studies aimed at establishing effectiveness of this approach to post-stroke care for Veterans.
Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity.
Obstetric fistula is a hole between the bladder or rectum and the vagina, which develops when obstructed labor is not relieved by cesarean section and results in uncontrollable leaking of urine and/or feces. The only cure for obstetric fistula is surgical repair. Multiple studies have documented the social and psychological impact of obstetric fistula, which includes social isolation, stigma, depression, and mental health dysfunction. The surgical repair setting can be a window of opportunity to address the accumulated mental health distress of living with a fistula. However, to date no intervention studies have evaluated empirically-supported therapies to assist in psychological healing among fistula patients. The proposed study aims to fill this gap by developing and pilot-testing a theoretically informed mental health intervention for women receiving surgical repair for obstetric fistula at KCMC Hospital in Moshi, Tanzania. The study has three specific aims: 1) To develop the nurse-delivered mental health intervention, built on theories of coping and cognitive behavioral therapy, 2) To assess feasibility and acceptability of implementing the intervention in the KCMC fistula ward, considering: intervention fidelity, patient satisfaction, provider feedback and cost of delivery, 3) To assess effectiveness of the intervention by comparing immediate and short term outcomes in 30 women who receive the experimental intervention with 30 women receiving the standard of care counseling, examining differences in primary outcomes (depression, PTSD and somatic symptoms) and secondary outcomes (coping, perceived stigma, social support, social participation, efficacy to engage with providers, adherence to clinical recommendations and social reintegration). The proposed research directly responds to the needs specified by NIH because it expands the "evidence base for improving social outcomes" of women with obstetric fistula and develops a "sustainable intervention" that complements existing local care (PA-11-143). At the completion of this study, it is our expectation that we will have a structured intervention curriculum and supportive preliminary data to inform an R01 application to conduct a multi-site evaluation of the intervention, which, if effective, can be disseminated to fistula repair clinics internationally.
PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM).
RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.
Choroidal neovascularization (CNV) is the principal driver of blindness in neovascular age-related macular degeneration (nvAMD). Increased activity of telomerase, has been associated with endothelial cell proliferation, survival, migration, and invasion in the context of tumor angiogenesis. Expanding on this knowledge, we investigated the role of telomerase in the development of CNV in mouse model. We observed increased gene expression and activity of telomerase in mouse CNV. Genetic deficiency of the telomerase components, telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc) suppressed laser-induced CNV in mice. Similarly, a small molecule inhibitor of TERT (BIBR 1532), and antisense oligonucleotides (ASOs) targeting Tert and Terc reduced CNV growth. Bone marrow chimera studies suggested that telomerase activity in non-bone marrow-derived cells is crucial for the development of CNV. Comparison of BIBR 1532 with VEGF neutralizing therapeutic strategy in mouse revealed a comparable level of angiosuppressive activity. However, when BIBR and anti-VEGF antibodies were administered as a combination at sub-therapeutic doses, a statistically significant suppression of CNV was observed. These findings underscore the potential benefits of combining sub-therapeutic doses of BIBR and anti-VEGF antibodies for developing newer therapeutic strategies for NV-AMD. Telomerase inhibition with BIBR 1532 suppressed induction of multiple cytokines and growth factors critical for neovascularization. In conclusion, our study identifies telomerase as a promising therapeutic target for treating neovascular disease of the eye and thus provides a proof of principle for further exploration of telomerase inhibition as a novel treatment strategy for nvAMD.
The protection of cochlear cells is one of the main concerns of cochlear implant surgery. New electrode designs or additional molecules have been used for this purpose. The aim of the study is to test the effect of dexamethasone in two different application methods. Participants who will have cochlear implant surgery will be divided into three groups. Group 1 will have intracochlear dexamethasone after the incision of the round window membrane. Group 2 will have intratympanic dexamethasone after the incision of the round window membrane. Group 3 will serve as a control group. All participants will be tested after a week, a month, 3, and 6 months. Impedance and threshold measurements will be compared.
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Heparan sulfate (HS) is a linear polysaccharide that plays a key role in cellular signaling networks. HS functions are regulated by its 6-O-sulfation, which is catalyzed by three HS 6-O-sulfotransferases (HS6STs). Notably, HS6ST2 is mainly expressed in the brain and HS6ST2 mutations are linked to brain disorders, but the underlying mechanisms remain poorly understood. To determine the role of Hs6st2 in the brain, we carried out a series of molecular and behavioral assessments on Hs6st2 knockout mice. We first carried out strong anion exchange-high performance liquid chromatography and found that knockout of Hs6st2 moderately decreases HS 6-O-sulfation levels in the brain. We then assessed body weights and found that Hs6st2 knockout mice exhibit increased body weight, which is associated with abnormal metabolic pathways. We also performed behavioral tests and found that Hs6st2 knockout mice showed memory deficits, which recapitulate patient clinical symptoms. To determine the molecular mechanisms underlying the memory deficits, we used RNA sequencing to examine transcriptomes in two memory-related brain regions, the hippocampus and cerebral cortex. We found that knockout of Hs6st2 impairs transcriptome in the hippocampus, but only mildly in the cerebral cortex. Furthermore, the transcriptome changes in the hippocampus are enriched in dendrite and synapse pathways. We also found that knockout of Hs6st2 decreases HS levels and impairs dendritic spines in hippocampal CA1 pyramidal neurons. Taken together, our study provides novel molecular and behavioral insights into the role of Hs6st2 in the brain, which facilitates a better understanding of HS6ST2 and HS-linked brain disorders.
Stroke is the leading cause of adult disability in the United States. One of the most debilitating impairments resulting from stroke is aphasia, a language disorder caused by damage to the left hemisphere of the brain. While evidence shows that aphasia therapy improves speech production and communicative quality of life in persons with chronic (\>6 months) stroke-induced aphasia, the amount of therapy provided to patients in the United States is typically far less than what is probably necessary to maximize recovery. There are a few important reasons underlying this discrepancy. For example, considerable emphasis is placed on acute and subacute stroke recovery with less therapy focus on the chronic period, when recovery is usually slower. Also, access to rehabilitation services can be limited by the availability of providers (e.g., in rural regions) or by difficulties with transportation logistics related to disabilities and the physical sequelae of stroke. One way to increase access to aphasia therapy is to rely on telerehabilitation (a.k.a., aphasia remote therapy; ART). So far, telerehabilitation in stroke has primarily focused on physical therapy, with only a handful of smaller studies involving aphasia therapy. The purpose of this study is to compare aphasia therapy administered via ART to aphasia therapy administered in person (In-Clinic Therapy; I-CT). We will conduct the first phase II, non-inferiority trial of telerehabilitation for aphasia therapy that is exclusively administered by a speech-language pathologist. Participants with chronic aphasia will be randomized to either a telerehabilitation or aphasia remote therapy (ART) group or an in-clinic therapy (I-CT) group relying on the same therapy approach currently used in our ongoing POLAR study. The outcome measure will focus on speech production and combines correct naming on the Philadelphia Naming Test and correct words produced per minute (CWPM) during discourse. The primary endpoint is change in the outcome measure at 6 months compared to baseline. The non-inferiority margin will be set so that if ART leads to less than 50% improvement than the improvement following I-CT, it will be considered inferior for therapy delivery. Neuroimaging will be used to evaluate how aphasia is shaped by the stroke lesion in combination with residual brain integrity.