anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
During the early stages of the development of the living multiorgan systems, genome modifications other than sequence variation occur that guide cell differentiation and organogenesis. These modifications are known to operate as a fetal programming code during this period, and recent research indicates that there are some tissue-specific codes in organogenesis whose effects may persist after birth until adulthood. Consequently, the events that disrupt the pre-established epigenetic pattern could induce shifts in organ physiology, with implications on health from birth or later in adult life. Chronic kidney disease (CKD) is one of the main causes of mortality worldwide; its etiology is multifactorial, but diabetes, obesity, and hypertension are the main causes of CKD in adults, although there are other risk factors that are mainly associated with an individual's lifestyle. Recent studies suggest that fetal reprogramming in the developing kidney could be implicated in the susceptibility to kidney disease in both childhood and adulthood. Some epigenetic modifications, such as genome methylation status, dysregulation of miRNA, and histone coding alterations in genes related to the regulation of the renin-angiotensin axis, a common denominator in CKD, may have originated during fetal development. This review focuses on epigenetic changes during nephrogenesis and their repercussions on kidney health and disease. In addition, the focus is on the influence of environmental factors during pregnancy, such as maternal metabolic diseases and dietary and metabolic conditions, as well as some sex differences in fetal kidney reprogramming during which dysregulation of the renin-angiotensin system is involved.
BACKGROUND: Our previous study has shown that intrahepatic necroinflammation favors the eliminations of HBV integration and clonal hepatocytes. Here, the effect of inflammation on host DNA damage eliminations in liver biopsy tissues from patients with chronic hepatitis B (CHB) was further investigated.
METHODS: DNA damage markers, histone γ-H2AX and phosphorylated heterochromatin protein 1γ (p-HP1γ), and senescent marker p21 were detected using immunohistochemical and immunofluorescent assays in liver biopsy samples from 69 CHB patients and 12 liver cirrhosis (LC) patients. Twenty paired hepatocellular carcinoma (HCC) surgical samples were used as controls.
RESULTS: Both γ-H2AX and p-HP1γ were sensitively detected in nuclear and cytoplasmic/nuclear patterns. Nuclear γ-H2AX was superior as a DNA damage marker in hepatocytes. The level of nuclear γ-H2AX in CHB, comparable to those in LC and HCC, was correlated with liver fibrosis and coexisted with the senescent marker p21. However, hepatocytes carried an alleviated level of DNA damages, which was associated with the level of cytoplasmic γ-H2AX. Cytoplasmic γ-H2AX chiefly occurred in hepatocytes near necroinflammatory foci, was correlated with liver inflammation and usually indicated the decrease or disappearance of nuclear γ-H2AX. The lack of cytoplasmic γ-H2AX together with the high level of nuclear γ-H2AX was associated with the progression from large cell changes/dysplasia to small cell changes/dysplasia.
CONCLUSIONS: Hepatocytes in CHB already carry massive DNA damages and undergo cellular senescence. The DNA damages in those senescent hepatocytes are histopathologically demonstrated to be amended by a novel cytoplasmic γ-H2AX-indicated and inflammation-driven rescue repair mechanism, which may be involved in hepatocarcinogenesis if it works improperly.
Eligible families who provide consent/assent will be enrolled into a five week study. All families will complete assessments at baseline, two weeks and four weeks. Each assessment lasts one week and children will be asked to wear an actigraph on their wrist (to measure sleep) and an accelerometer on their hip (to measure physical activity). At the end of the week families will be scheduled for a visit at the research center first thing in the morning approximately one hour after waking and following an overnight fast. During this visit, actigraphs and accelerometers will be downloaded and data will be reviewed with families. Children will be weighed and measured for height and have their body composition assessed. To measure glucose regulation, children will first have 5 ml of blood drawn in a fasted state. They will then ingest a glucose solution (1.75 g/kg; maximum of 75 g) over 2 minutes, and blood will be drawn (1.5 ml) 120 min after the child consumes the solution. At week 4, 5 ml blood will be drawn fasting; OGTT will not be administered (see note below). Research staff will also complete one-day dietary recalls with participants at each center-based assessment to obtain information on all foods consumed over the previous 24-hour period. In addition, at the baseline assessment only, parents will complete questionnaires on basic demographic information and child sleep. It is anticipated that the total time for each assessment will take approximately 2.5-3 hours (1 hour at 4 weeks). Following eligibility confirmation at the baseline assessment, families will be randomized to one of four protocols: 1) Enhance TIB by 90 min/night; 2) Enhance TIB by 45 min/night; 3) Regularize Sleep Schedule; or 4) Typical Sleep Schedule.

Continuous glucose monitoring In a voluntary subset of randomly selected children (approximately n = 4/group) 72-hour continuous glucose monitoring (CGM) will be performed. If the child and family agree to participate in CGM, they will come to the Center for an additional visit during which a disposable subcutaneous glucose-sensing device connected to a battery-operated recorder will be inserted subcutaneously (a thin tube under the surface of the skin). This sensor measures glucose every ten seconds and records an average value every five minutes.
A time- and attention-matched live online control group. The manualized control intervention developed for the basic group-based opioid treatment group in primary care uses 16 core modules and 8 elective modules that are common to eclectic approach in treatment as usual addiction recovery groups (including engagement and group development activities with a mix of basic CBT skills, twelve-step facilitation, community reinforcement, and motivational interviewing). As an active group control, this method will help to isolate mindfulness as the putative mechanism of action by controlling for the therapeutic aspects of group without any reference to mindfulness.
A processes is provide herein for converting waste bio-product pomace to useful bio-product extracts. The process includes the steps of forming a mixture of water as a solvent and a specified quantity of the waste bio-product pomace. Then optionally adding a suitable quantity of citric acid to the water/waste bio-product mixture. Then heating waste bio-product pomace/water mixture to an elevated temperature below the boiling point of water. Then optionally adding a suitable quantity of sodium metabisulfite to the heated waste bio-product pomace/water mixture. Then stirring heated waste bio-product pomace/water mixture for a suitable time to disperse the waste bio-product uniformly in the water solvent. Then cooling the stirred, heated waste bio-product pomace/water mixture to a suitable lower temperature at a rate of about 60° C per hour. Then removing solids from the stirred waste bio-product pomace/water mixture. Then clarifying the cooled stirred water/ waste bio-product mixture.  Then concentrating the clarifying cooled stirred waste bio-product pomace/water mixture under the influence of a suitable vacuum and at a suitable increased temperature until the concentrate has a BRIX of about 20 to about 22. This provides a concentrated useful bio-product comprising antioxidant-enriched liquids comprised of the natural elements extracted from said waste bio--products.
Chronic intermittent hypoxia (CIH) in rodents mimics the hypoxia-induced elevation of blood pressure seen in individuals experiencing episodic breathing. The brainstem nucleus tractus solitarii (nTS) is the first site of visceral sensory afferent integration, and thus is critical for cardiorespiratory homeostasis and its adaptation during a variety of stressors. In addition, the paraventricular nucleus of the hypothalamus (PVN), in part through its nTS projections that contain oxytocin (OT) and/or corticotropin-releasing hormone (CRH), contributes to cardiorespiratory regulation. Within the nTS, these PVN-derived neuropeptides alter nTS activity and the cardiorespiratory response to hypoxia. Nevertheless, their contribution to nTS activity after CIH is not fully understood. We hypothesized that OT and CRH would increase nTS activity to a greater extent following CIH, and co-activation of OT+CRH receptors would further magnify nTS activity. Our data show that compared to their normoxic controls, 10 days' CIH exaggerated nTS discharge, excitatory synaptic currents and Ca2+ influx in response to CRH, which were further enhanced by the addition of OT. CIH increased the tonic functional contribution of CRH receptors, which occurred with elevation of mRNA and protein. Together, our data demonstrate that intermittent hypoxia exaggerates the expression and function of neuropeptides on nTS activity. KEY POINTS: Episodic breathing and chronic intermittent hypoxia (CIH) are associated with autonomic dysregulation, including elevated sympathetic nervous system activity. Altered nucleus tractus solitarii (nTS) activity contributes to this response. Neurons originating in the paraventricular nucleus (PVN), including those containing oxytocin (OT) and corticotropin-releasing hormone (CRH), project to the nTS, and modulate the cardiorespiratory system. Their role in CIH is unknown. In this study, we focused on OT and CRH individually and together on nTS activity from rats exposed to either CIH or normoxia control. We show that after CIH, CRH alone and with OT increased to a greater extent overall nTS discharge, neuronal calcium influx, synaptic transmission to second-order nTS neurons, and OT and CRH receptor expression. These results provide insights into the underlying circuits and mechanisms contributing to autonomic dysfunction during periods of episodic breathing.
Hyperbilirubinemia in newborns may progress to acute bilirubin encephalopathy (ABE), posing short- and long-term health risks. Despite extensive research identifying numerous mRNAs, lncRNAs, circRNAs, and miRNAs associated with brain injury, their roles in neonatal bilirubin-induced brain injury remain elusive. This study employed whole-transcriptome sequencing to ascertain the differentially expressed (DE) RNA profiles in a newborn ABE rat model, followed by bioinformatic analysis. A time-series competing endogenous RNA (ceRNA) regulatory network was established, and the expression trends of 9 arbitrarily chosen RNAs were verified through quantitative real-time polymerase chain reaction(qRT-PCR). In comparison with the control group, we identified 595, 888, and 1448 DE mRNAs; 22, 37, and 37 DE miRNAs; 1945, 1869, and 1997 DE lncRNAs; and 31, 28, and 36 DE circRNAs at 6 h, 12 h, and 24 h, respectively. Predominantly, these DERNAs contribute to biological functions and pathways associated with inflammation, immunity, metabolism, cell death, and neurodevelopmental regulation. Moreover, we constructed ceRNA networks of DE lncRNA/circRNA-DE miRNA-DE mRNA based on time series. The qRT-PCR expression trends for the selected 9 RNAs were generally similar to the RNA-seq outcomes. This investigation uniquely delineated the temporal expression patterns of mRNA and non-coding RNA in ABE, establishing ceRNA networks and identifying potential molecular mechanisms underlying bilirubin-induced hippocampal damage. Nonetheless, further studies are warranted to corroborate these findings in humans.
Lamp devices, apparatus, methods of use, and methods of assembly which can be used with a single suspension lamp and/or with a plurality of suspension lamps. Each lamp can have a lamp seat mounted on a tubular member that is fixed to a main body. The lamp seat can be connected electrically to a circuit unit housed in the main body, and is mounted with a lamp bulb. A bowl-shaped upper lamp shade surrounds the lamp seat, is mounted on the tubular member, and is formed with heat-dissipating holes. A lower lamp shade is coupled detachably to a larger-diameter lower open end of the upper lamp shade, and cooperates with the upper lamp shade to define an accommodating space for receiving an assembly of the lamp seat and the lamp bulb. A bowl-shaped water-resistant cover is mounted on the tubular member, and is disposed above the upper lamp shade for covering the upper lamp shade.
INTRODUCTION: The underlying pathophysiology behind a diagnosis of acontractile or underactive detrusor at invasive urodynamics is very heterogeneous. Lack of etiological classification currently limits the possibility of stratifying therapy.
METHODS: This subject was discussed at a think-tank on the subject at the International Consultation on Incontinence-Research Society held in Bristol, June 2023. This manuscript is a result of those deliberations and the subsequent discussions of the think-tank.
RESULTS: There are challenges in defining abnormalities of detrusor contraction with resultant implications for available evidence. Pathology at any level of the neuromuscular pathway can impair or prevent a detrusor voiding contraction. Attempts have been made to identify clinical markers that might predict an underactive detrusor but strong supporting evidence is lacking. Hence, a holistic approach to phenotyping requires specialized neuro-imaging as well as physiological investigations. Several general measures can help individuals with an abnormal detrusor contraction. The search for a molecule to enhance the detrusor voiding contraction remains elusive but there are promising new candidates. Neuromodulation can help select individuals but data is not well stratified by underlying etiology. Manipulation of central neurotransmitters might offer an alternate therapeutic option.
CONCLUSIONS: A better understanding of the underlying pathophysiologies behind an abnormality of the detrusor voiding contraction is needed for improving management. Towards this goal, the think-tank proposes a classification of the underactive detrusor that might help in selecting and reporting more well-defined patient cohorts.
Although neuroinflammation is a significant pathogenic feature of many neurologic disorders, its precise function in-vivo is still not completely known. PET imaging enables the longitudinal examination, quantification, and tracking of different neuroinflammation biomarkers in living subjects. Particularly, PET imaging of Microglia, specialised dynamic immune cells crucial for maintaining brain homeostasis in central nervous system (CNS), is crucial for staging the neuroinflammation. Colony Stimulating Factor- 1 Receptor (CSF-1R) PET imaging is a novel method for the quantification of neuroinflammation. CSF-1R is mainly expressed on microglia, and neurodegenerative disorders greatly up-regulate its expression. The present review primarily focuses on the development, pros and cons of all the CSF-1R PET tracers reported for neuroinflammation imaging. Apart from neuroinflammation imaging, CSF-1R inhibitors are also reported for the therapy of neurodegenerative diseases such as Alzheimer's disease (AD). AD is a prevalent, advancing, and fatal neurodegenerative condition that have the characteristic feature of persistent neuroinflammation and primarily affects the elderly. The aetiology of AD is profoundly influenced by amyloid-beta (Aβ) plaques, intracellular neurofibrillary tangles, and microglial dysfunction. Increasing evidence suggests that CSF-1R inhibitors (CSF-1Ri) can be helpful in preclinical models of neurodegenerative diseases. This review article also summarises the most recent developments of CSF-1Ri-based therapy for AD.
PURPOSE: The impact of hospitalization for acute illness on inspiratory muscle strength in oldest-old patients is largely unknown, as are the potential benefits of exercise and inspiratory muscle training (IMT) during in-hospital stay.
DESIGN AND METHODS: This was a sub-study of a randomized clinical trial that evaluated the efficiency of a multicomponent exercise program in preventing hospitalization-associated disability. Patients were randomized into control (CG) and intervention (IG) groups. The intervention included two daily sessions of supervised walking, squat, balance, and IMT. Baseline and discharge maximal inspiratory pressure (MIP) and inspiratory muscle weakness (IMW) were determined. The effect of the intervention on inspiratory muscle strength was assessed by analyzing (1) the differences between groups in baseline and discharge MIP and IMW, (2) the association, patient by patient, between baseline and discharge MIP, and the improvement index (MIP discharge/baseline) in patients with or without IMW.
RESULTS: In total, 174 patients were assessed (mean age of 87), 57 in CG and 117 in IG. Baseline MIP was lower than predicted in both sexes (women 29.7 vs 44.3; men 36.7 vs 62.5 cmH2O, P < 0.001, baseline vs predicted, respectively). More than 65% of patients showed IMW at admission. In women in IG, the mean MIP was higher at discharge than at admission (P = 0.003) and was the only variable that reached expected reference levels at discharge (Measured MIP 39.2 vs predicted MIP 45 cmH2O, P = 0.883). Patients with IMW on admission showed a statistically significant improvement in MIP after the intervention.
CONCLUSION: IMW is very prevalent in oldest-old hospitalized with acute illness. Patients might benefit from a multicomponent exercise program including IMT, even during short-stay hospitalization.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NTC03604640. May 3, 2018.
The disclosure provides substituted aryl thioureas and related compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein the variables A1, A2, R1, R2, X, Y, and Z are as defined in the specification. The compounds of formula (I) described herein possess potent antiviral activity. The disclosure particularly provides compounds of formula (I) that are potent and/or selective inhibitors of Hepatitis C virus replication. The disclosure also relates to pharmaceutical compositions containing one or more compound of formula (I), or a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The disclosure further relates to the use of the compounds of formula (I) in the manufacture of a medicament for treating patients suffering from certain infectious diseases. These infectious diseases include viral infections, particularly HCV infections.
BACKGROUND AND OBJECTIVE: The impairments and duration of PASC (post-acute sequelae of COVID-19) symptoms in mental health have, to date, not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course.
METHODS: The mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID Syndrome Score), depression (Patient Health Questionnaire-9), somatic symptoms (Patient Health Questionnaire-15), anxiety (Generalized Anxiety Disorder-7), fatigue (Fatigue Severity Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional Malaise Screening) was conducted in the home environment.
RESULTS: In total, 80% of patients experienced severe PASC at follow-up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% of patients, respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained at an unchanged high level. The risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre.
CONCLUSIONS: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for the mental health implications of PASC is needed for the planning of health services and disease prevention.
BACKGROUND: Previous studies investigating environmental and behavioral drivers of chronic disease have often had limited temporal and spatial data coverage. Smartphone-based digital phenotyping mitigates the limitations of these studies by using intensive data collection schemes that take advantage of the widespread use of smartphones while allowing for less burdensome data collection and longer follow-up periods. In addition, smartphone apps can be programmed to conduct daily or intraday surveys on health behaviors and psychological well-being.
OBJECTIVE: The aim of this study was to investigate the feasibility and scalability of embedding smartphone-based digital phenotyping in large epidemiological cohorts by examining participant adherence to a smartphone-based data collection protocol in 2 ongoing nationwide prospective cohort studies.
METHODS: Participants (N=2394) of the Beiwe Substudy of the Nurses' Health Study 3 and Growing Up Today Study were followed over 1 year. During this time, they completed questionnaires every 10 days delivered via the Beiwe smartphone app covering topics such as emotions, stress and enjoyment, physical activity, access to green spaces, pets, diet (vegetables, meats, beverages, nuts and dairy, and fruits), sleep, and sitting. These questionnaires aimed to measure participants' key health behaviors to combine them with objectively assessed high-resolution GPS and accelerometer data provided by participants during the same period.
RESULTS: Between July 2021 and June 2023, we received 11.1 TB of GPS and accelerometer data from 2394 participants and 23,682 survey responses. The average follow-up time for each participant was 214 (SD 148) days. During this period, participants provided an average of 14.8 (SD 5.9) valid hours of GPS data and 13.2 (SD 4.8) valid hours of accelerometer data. Using a 10-hour cutoff, we found that 51.46% (1232/2394) and 53.23% (1274/2394) of participants had >50% of valid data collection days for GPS and accelerometer data, respectively. In addition, each participant submitted an average of 10 (SD 11) surveys during the same period, with a mean response rate of 36% across all surveys (SD 17%; median 41%). After initial processing of GPS and accelerometer data, we also found that participants spent an average of 14.6 (SD 7.5) hours per day at home and 1.6 (SD 1.6) hours per day on trips. We also recorded an average of 1046 (SD 1029) steps per day.
CONCLUSIONS: In this study, smartphone-based digital phenotyping was used to collect intensive longitudinal data on lifestyle and behavioral factors in 2 well-established prospective cohorts. Our assessment of adherence to smartphone-based data collection protocols over 1 year suggests that adherence in our study was either higher or similar to most previous studies with shorter follow-up periods and smaller sample sizes. Our efforts resulted in a large dataset on health behaviors that can be linked to spatial datasets to examine environmental and behavioral drivers of chronic disease.