anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Cystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies. We aimed to characterize the fecal microbiota in participants with CF with and without advanced CFLD (aCFLD) before and after ETI.
METHODS: This is an ancillary analysis of stool samples from participants ages ≥12 y/o enrolled in PROMISE (NCT04038047). Included participants had aCFLD (cirrhosis with or without portal hypertension, or non-cirrhotic portal hypertension) or CF without liver disease (CFnoLD). Fecal microbiota were defined by shotgun metagenomic sequencing at baseline and 1 and 6 months post-ETI.
RESULTS: We analyzed 93 samples from 34 participants (11 aCFLD and 23 CFnoLD). Compared to CFnoLD, aCFLD had significantly higher baseline relative abundances of potential pathogens Streptococcus salivarius and Veillonella parvula. Four of 11 aCFLD participants had an initially abnormal fecal calprotectin that normalized 6 months post-ETI, correlating with a significant decrease in S. salivarius and a trend towards decreasing V. parvula.
CONCLUSIONS: These results support an association between dysbiosis and intestinal inflammation in CFLD with improvements in both post-ETI, lending further support to the gut-liver axis in aCFLD.
The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation.
The device will be placed in the vagina during the consultation. It is rinsed in sterile water for lubrification and left in place until delivery or remove at 36 weeks in case of no delivery before. There is no need to use any analgesia. The good position of the pessary is checking in the same time than the placement with digital examination.
PURPOSE OF THE REVIEW: This review discusses the molecular mechanisms involved in the immuno-pathogenesis of atherosclerosis, the pleiotropic anti-inflammatory effects of approved cardiovascular therapies and the available evidence on immunomodulatory therapies for atherosclerotic cardiovascular disease (ACVD). We highlight the importance of clinical and translational research in identifying molecular mechanisms and discovering new therapeutic targets.
RECENT FINDINGS: The CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial was the first to demonstrate a reduction in cardiovascular (CV) risk with anti-inflammatory therapy, irrespective of serum lipid levels. ACVD is the leading cause of death worldwide. Although targeting principal risk factors significantly reduces CV risk, residual risk remains unaddressed. The immunological mechanisms underlying atherosclerosis represent attractive therapeutic targets. Several commonly used and non-primarily anti-inflammatory drugs (i.e. SGLT2i, and PCSK9i) exhibit pleiotropic properties. Otherwise, recent trials have investigated the blockade of primarily inflammatory compounds, trying to lower the residual risk via low-dose IL-2, PTPN22 and CD31 pathway modulation. In the era of precision medicine, modern approaches may explore new pharmacological targets, identify new markers of vascular inflammation, and evaluate therapeutic responses.
OBJECTIVE: Rapamycin, a powerful geroprotective drug, can have detrimental effects when administered chronically. We determined whether intermittent treatment of mice can reduce negative effects while maintaining benefits of chronic treatment.
METHODS: From 6 months of age, male and female C3B6F1 hybrid mice were either continuously fed with 42 mg/kg rapamycin, or intermittently fed by alternating weekly feeding of 42 mg/kg rapamycin food with weekly control feeding. Survival of these mice compared to control animals was measured. Furthermore, longitudinal phenotyping including metabolic (body composition, GTT, ITT, indirect calorimetry) and fitness phenotypes (treadmil, rotarod, electrocardiography and open field) was performed. Organ specific pathology was assessed at 24 months of age.
RESULTS: Chronic rapamycin treatment induced glucose intolerance, which was partially ameliorated by intermittent treatment. Chronic and intermittent rapamycin treatments increased lifespan equally in males, while in females chronic treatment resulted in slightly higher survival. The two treatments had equivalent effects on testicular degeneration, heart fibrosis and liver lipidosis. In males, the two treatment regimes led to a similar increase in motor coordination, heart rate and Q-T interval, and reduction in spleen weight, while in females, they equally reduced BAT inflammation and spleen weight and maintained heart rate and Q-T interval. However, other health parameters, including age related pathologies, were better prevented by continuous treatment.
CONCLUSIONS: Intermittent rapamycin treatment is effective in prolonging lifespan and reduces some side-effects of chronic treatment, but chronic treatment is more beneficial to healthspan.
Provided are an immune cell targeting probe, a pre-targeting recognition and drug delivery system based on the probe, and a use thereof. A targeting polypeptide and an antibody do not affect their own recognition effects after modification of a pre-targeting binding handle. The targeting polypeptide and the antibody can be self-assembled to form a combined probe, and the self-assembled probe can enhance the recognition capability to immune cells. Different targeting drug delivery strategies such as pre-targeting secondary delivery can be used on the basis of a difference in steric hindrance of binding of a probe to a target. Therefore, an off-target effect during delivery of toxic drugs is avoided or mitigated, and a use range of the toxic drugs is expanded. Due to the fact that a drug delivery ligand and a target recognition function portion can be independently subjected to chemical modification and storage, the drug delivery ligand can further load various drug molecules or modification groups, and has the advantages of high drug loading capacity, convenient synthesis, controllable product quality, etc., and has wide application in the aspects of immune cell imaging, tracing, screening, analysis and targeting drug delivery.
PURPOSE: Transabdominal preperitoneal (TAPP) ventral hernia repair requires incising the peritoneum from within the abdominal cavity, developing a flap, and placing a reinforcing mesh after fascial closure from the preperitoneal space. We present a novel adaptation to this technique that allows placement of preperitoneal mesh without entering the abdominal cavity. The robotic totally extra- and preperitoneal (R-PeTEP) access for ventral hernia repair is best suited for small to moderate sized ventral hernias with concomitant diastasis recti.
METHODS: Our study is a retrospective review of all patients who underwent R-PeTEP from December 2022 to November 2023. A comprehensive description of the surgical technique is included. Patient demographics, hernia characteristics, as well as clinical outcomes are described.
RESULTS: A total of 25 patients underwent R-PeTEP for ventral hernia repair with diastasis recti plication. The median age was 55 years (IQR 43.5-63) and 92% (n = 23) were male. The median ASA score was 2 (IQR 1-2) and the median BMI was 30.4 (IQR 29.3-32.8) with 64% (n = 16) percent having a BMI ≥ 30. Median hernia width was 3 cm (IQR 3-4), with a median diastasis recti width of 4 cm (IQR 2.6-4) and length of 15 cm (IQR 11.8-16). The median operative time was 120 min (IQR 116-134). All repairs were reinforced with permanent mesh. Sixty-eight percent of the patients (n = 17) were discharged on the same day. With a median follow-up of 30 days (IQR 16-107), 8% (n = 2) seromas, 16% (n = 4) developed clinically insignificant hematomas, and one patient (4%) developed ileus that was managed conservatively.
CONCLUSION: This study establishes the feasibility and safety of R-PeTEP, which provides direct access to the preperitoneal space, avoiding disruption to the posterior rectus sheath, possibly reducing neurovascular bundle injuries, and omitting entry to the abdominal cavity. R-PeTEP facilitates wide flap creation for prosthetic overlap and allows for posterior plication of diastasis recti with little to no mesh fixation with overall excellent preliminary clinical outcomes.
PURPOSE: To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany.
METHODS: Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care university hospitals between October 2016 and June 2020 were prospectively evaluated. In vancomycin-resistant enterococci (VRE), the presence of vanA/vanB was confirmed via molecular methods.
RESULTS: In the 4-year study period, 3001 patients with BSI due to Enterococcus spp. were identified. E. faecium was detected in 1830 patients (61%) and E. faecalis in 1229 patients (41%). Most BSI occurred in (sub-) specialties of internal medicine. The pooled incidence density of enterococcal BSI increased significantly (4.0-4.5 cases per 10,000 patient days), which was primarily driven by VRE BSI (0.5 to 1.0 cases per 10,000 patient days). In 2020, the proportion of VRE BSI was > 12% in all study sites (range, 12.8-32.2%). Molecular detection of resistance in 363 VRE isolates showed a predominance of the vanB gene (77.1%).
CONCLUSION: This large multicentre study highlights an increase of BSI due to E. faecium, which was primarily driven by VRE. The high rates of hospital- and ICU-acquired VRE BSI point towards an important role of prior antibiotic exposure and invasive procedures as risk factors. Due to limited treatment options and high mortality rates of VRE BSI, the increasing incidence of VRE BSI is of major concern.
The present invention describes a unique antiviral screen system. The assay is based on quantitatively monitoring viral activation of host cell beta-interferon (IFN-β) gene expression in a HEK293-derived reporter cell line expressing a firefly luciferase gene under the control of a human IFN-β promoter. Unlike the traditional high throughput antiviral assays that measure either the reduction of viral components/yields or cytopathic effect, the readout of the reporter assay in the present invention is the virus-induced host cellular innate immune response. Hence, the assay allows for identification of compounds that inhibit virus infection. In addition, because induction of IFN is one of the most common attributes of viruses, the assay is applicable to all the viruses that are able to infect the reporter cell line and induce IFN-β expression. Compounds that interfere with viral mediated activation of the interferon pathway in a primary screen, can be further screened with virus-specific assay to confirm their antiviral activity.
Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5' and 3', being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified.
The invention relates to the technical field of cosmetics, in particular to a mask and a preparation method thereof. The mask is prepared from, by weight, 15-50 parts of goat milk and 0.5-20 parts of lemon extracts. The preparation method of the mask includes the following steps that raw materials are preprocessed, goat milk whey essence is prepared and sterilization is conducted. Raw material components are reasonably matched, skin protecting effects of the components have a synergistic effect, no preservative is added in the raw materials, and the effect that the shelf life of goat milk reaches 60 days or longer is achieved. The mask is mild and free of irritation and harmful components. Lemons are used for removing water-insoluble casein in goat milk, no preservative is added in the whole processing process, pregnant women and people with sensitive skin can use the mask, the mask is safe and effective, and quality inspection meets national quality standards.
Traumatic brain injury (TBI) remains a leading cause of death and disability in people with injuries and constitutes a major public health concern both in developed and developing countries. There are multiple clinical trials of hypothermia therapy for TBI conducted, however, with conflicting results. Subgroup analysis of most meta-analysis showed that therapeutic effect was significant when hypothermia was maintained more than 48 hours. We have previously reported a multicenter trial of mild hypothermia (33-35℃) for severe traumatic brain injury, in which 215 patients was randomized to long-term mild hypothermia group (n = 108) for 5 ±1.3 days mild hypothermia therapy and short-term mild hypothermia group ( n = 107) for 2±0.6 days mild hypothermia therapy. The results shown improved outcomes in patients with long-term mild hypothermia and similar frequency of complications. Therefore we concluded that long-term hypothermia, which maintains at 33-35℃ for 5 days, could be considered in the management of severe traumatic brain injury.

Hypothermia therapy was recommend as the level III evidence by the 2007 Brain Trauma Foundation's guideline and this treatment is currently used in our department and other large neurosurgical centers across China, with the aim to decrease the high intracranial pressure (ICP) and improve the functional outcome of TBI patients. When the decision was made, the injured patients would be placed on cooling blankets, tracheotomized and ventilated. The patients would receive continuous infusions of a paralytic drug (Tracrium 10-40 mg/hour) and chlorpromazine (5-10 mg/hour) administered using an infusion pump to prevent shivering. The dosage was given according to each patient's temperature, blood pressure, heart rate, and muscular tone. Once the patient's rectal temperature reached 33˚C, it was kept at approximately that temperature (33-35˚C) 5 to 7 days. Then the patients were passively rewarmed to a temperature of 37 to 38˚C at a rate no greater than 1˚C/hour, by gradual adjustment of the blanket thermostat.

The present multi-center, randomized controlled trials is designed to investigate the efficacy and safety of long-term (5 days) mild hypothermia versus normothermia on the outcome of patients following severe traumatic brain injury. The primary outcome is the neurological function assessed at 1, 6 months post injury with the Glasgow Outcome Score (GOS). Additionally, the following data will also be recorded and compared: the baseline data, Glasgow Coma Score,imaging examination (e.g. CT scan), need of surgery, intracranial pressure, laboratory tests (e.g. blood routine test, liver and kidney function, blood gas analysis, etc), the complications (e.g. pneumonia, significant bleeding) and so on.
We propose to model certain aspects of the dynamics of a macrophage that moves randomly in a one dimensional space in arterial wall tissue and grows by accumulating localized lipid particles, thus reducing its motility. This phenomenon has been observed in the context of atherosclerotic plaque formation. For this purpose, we use a system of stochastic differential equations satisfied by the position and diffusion coefficient of a Brownian particle whose diffusion coefficient is modified at each visit to the origin and with a dumping coefficient. The novelty of the model, with respect to Bénichou et al. (Phys Rev E 85(2):021137, 2012), Meunier et al. (Acta Appl Math 161:107-126, 2019), is to include offloading of lipids through the dumping term. We find explicit necessary and sufficient conditions for macrophage trapping in the locally enriched region.
Participants will receive text-message based assessment during shift work (intra-shift) and between shifts (inter-shift). Participants in the experimental group that report high levels of fatigue, sleepiness, or difficulty with concentration during shift work (intra-shift) will receive tailored text-messages promoting adoption of behaviors that can improve alertness. Participants will also receive a summary of their sleep debt once a week and suggestions for paying back sleep debt. Participants will also have access to a graphic summary of their sleep hours over previous 30-days.
The pelvic bones are the key structures that connect the trunk to the lower extremities, support the body's weight and transfer the load to the lower extremities. The symmetrical orientation of the pelvis about the horizontal plane determines the morphology of the pelvis during static standing posture. When the symmetry of the pelvis is disturbed, its effect on gait parameters is unclear. In clinical practice, the pelvis functionally has 3 basic rotational movements during a gait activity. These are associated with upward (positive) or downward (negative) movement of the pelvis in the coronal plane; forward or backward movement in the sagittal plane; and internal (positive) or external (negative) movement in the horizontal plane. Although these angles are determined by the balance of muscle and ligament forces acting between the pelvis and adjacent segments, they can also be affected by changes in pelvic morphology. If the height of the iliac crest in the coronal plane is significantly different on the right and left, this indicates a pelvic oblique asymmetry. On the other hand, pelvic asymmetries can also be seen in the sagittal plane. Here, the pelvic tilt angles on the right and left are usually significantly different from each other. In the literature, morphologic analyses of the pelvis in static standing posture or dynamically during a gait activity have been performed separately. However, to our knowledge, there is no study on the extent to which pelvic asymmetries seen during gait are affected by the morphology of the pelvis in static standing posture. In this study, the pelvis of young adults aged 19-29 years will be evaluated in two stages. In the first stage, pelvic orientation (pelvic tilt, pelvic obliquity and pelvic rotation) will be measured during static standing using a PALM (palpation meter pelvic inclinometer) inclinometer and leg length will be measured using a tape measure. In the second stage, spatio-temporal parameters and pelvic parallels will be assessed during walking using a wearable inertial sensor. With the data obtained, it is aimed to classify the pelvic morphology of the participants as symmetrical and asymmetrical in the literature and to reveal the effects of pelvis types specific to this classification on the parameters during walking. The results of this study will accurately and precisely measure the orientation of the pelvis with objective tools under static and dynamic conditions, which may increase the reasoning skills and understanding of rehabilitation strategies to be developed for pathologies related to this region. In addition, this study will elucidate the effect of pelvic asymmetries on the kinetic and kinematics of the pelvis on gait quality.
The invention is a kind of Chinese patent drug, quick-acting hemorrhoids suppository. It is made up according to the secret recipe handed down from generation to generation. Chinese catalpa leaves, sophora flower, lemahui, snake liver, snake and snake oil is purified and cleaned, they are put into high grade table water and boiled for 3-6 hours according to the proportion of 95:3:0.7:0.3:0.5:0.5, then the drug residues are fished out, the soup in the boiler is filtered and boiled into ointment, then gets the product. The medicine can clear heat, diminish inflammation, stanch and stop pain. According to the different condition of internal hemorrhoid, external hemorrhoid and compound hemorrhoids, uses ointmoent and suppository to cure. The invention is convenient, quick-acting, radical cure and low price.
Women with polycystic ovary syndrome (PCOS) have an impaired fertility and significant higher complication rates during infertility treatment, pregnancy and the perinatal period. Complications include the occurrence of multiple gestations, ovarian hyper stimulation syndrome, early pregnancy loss, gestational diabetes, pregnancy-induced hypertension, pre-eclampsia and need for caesarean section. Moreover, their infants are more frequently born preterm, have higher perinatal mortality rates and are more often admitted to a neonatal intensive care unit. The etiology of PCOS is not particularly mapped, but a genetic background can be assumed by analyzing PCOS families. In utero androgen excess has also been suspected to be an important risk factor. Animal studies have demonstrated that intrauterine hyperandrogenic environment affects the offspring by leading to biochemical and morphological features of PCOS. Sex differences in prenatal androgen levels have been observed and testosterone levels in umbilical cord blood and in amniotic fluid are higher in healthy male babies than in healthy female babies. There are just a few reporting on the relation between maternal androgen levels during pregnancy and the respective offspring. The aim of this clinical study is to determine maternal androgen metabolism and the impact of androgen disorders on mothers and infants.