anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The blood-brain barrier (BBB) is a critical interface that maintains the central nervous system homeostasis by controlling the exchange of substances between the blood and the brain. Disruption of the BBB plays a vital role in the development of neuroinflammation and neurological dysfunction in sepsis, but the mechanisms by which the BBB becomes disrupted during sepsis are not well understood. Here, we induced endotoxemia, a major type of sepsis, in mice by intraperitoneal injection of lipopolysaccharide (LPS). LPS acutely increased BBB permeability, activated microglia, and heightened inflammatory responses in brain endothelium and parenchyma. Concurrently, LPS or proinflammatory cytokines activated the NF-κB pathway, inhibiting Wnt/β-catenin signaling in brain endothelial cells in vitro and in vivo. Cell culture study revealed that NF-κB p65 directly interacted with β-catenin to suppress Wnt/β-catenin signaling. Pharmacological NF-κB pathway inhibition restored brain endothelial Wnt/β-catenin signaling activity and mitigated BBB disruption and neuroinflammation in septic mice. Furthermore, genetic or pharmacological activation of brain endothelial Wnt/β-catenin signaling substantially alleviated LPS-induced BBB leakage and neuroinflammation, while endothelial conditional ablation of the Wnt7a/7b co-receptor Gpr124 exacerbated the BBB leakage caused by LPS. Mechanistically, Wnt/β-catenin signaling activation rectified the reduced expression levels of tight junction protein ZO-1 and transcytosis suppressor Mfsd2a in brain endothelial cells of mice with endotoxemia, inhibiting both paracellular and transcellular permeability of the BBB. Our findings demonstrate that endotoxemia-associated systemic inflammation decreases endothelial Wnt/β-catenin signaling through activating NF-κB pathway, resulting in acute BBB disruption and neuroinflammation. Targeting the endothelial Wnt/β-catenin signaling may offer a promising therapeutic strategy for preserving BBB integrity and treating neurological dysfunction in sepsis.
PROBLEM TO BE SOLVED: To obtain a new anthraquinone-based compound 0089, capable of manifesting excellent physiological activities, especially excellent antitumor actions and useful as an antitumor agent or its pharmaceutically permissible salt. SOLUTION: This new anthraquinone-based compound 0089 is represented by the formula (R is ristosamine, OH or OCH3 ) or its pharmaceutically permissible salt, e.g. a compound 0089-A in which A is the ristosamine. The compound 0089 represented by the formula is obtained by culturing a bacterium, belonging to the genus Nocardia and capable of producing the compound 0089 represented by the formula, especially a new Nocardia brasiliensis IFM0089 strain (FERM BP-5542) in a culture medium and collecting the resultant compound from the cultured product. Furthermore, the compound 0089 is preferably produced under aerobic submerged culturing conditions (e.g. a shaking culture or an aeration spinner culture) when culturing the bacterium. A carbon source and a nitrogen source are preferably used in combination in the culture medium.
Clinical experience with risperidone in patients with certain concomitant systemic illnesses is limited. Patients with Parkinson’s Disease or Dementia with Lewy Bodies who receive antipsychotics, including risperidone, are reported to have an increased sensitivity to antipsychotic medications. Manifestations of this increased sensitivity have been reported to include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with the neuroleptic malignant syndrome. 

Caution is advisable in using risperidone in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Risperidone has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from clinical studies during the product's premarket testing. 

Increased plasma concentrations of risperidone and 9-hydroxyrisperidone occur in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m2), and an increase in the free fraction of risperidone is seen in patients with severe hepatic impairment. A lower starting dose should be used in such patients [see Dosage and Administration (2.4)].
Rationale: Graft-versus-host disease(GVHD) is a common complication of allogeneic bone marrow or hematopoietic stem cell transplantation (HSCT). It affects multiple systems, including skin, gastrointestinal system, liver, lung, and oral cavity, as well as eyes, which contributes to decreased quality of life and increased mortality. About 10% of patients with acute GVHD and 60-90% of those with chronic GVHD develop ocular complications. Dry eye is the most common manifestation of ocular GVHD. The pathogenesis remains unclear. The conjunctival tissue and cornea are the main immunological targets in GVHD. Patients often have punctate hypothesize that the recalcitrant nature of ocular GVHD may be related to corneal nerve damage and sensation changes.

There are a few confocal microscopy studies on corneal nerve changes in GVHD, including increased tortuosity and reduced reflectivity of sub-basal nerves. However, there were very few studies on clinical correlations of those microscopic changes with corneal sensation and ocular surface health. In addition, confocal microscopes are not widely available in clinical practice. It also requires the special expertise of technicians and physicians to obtain and explain the images. It is therefore not feasible to routinely perform confocal microscopy for corneal innervation study.

The investigators plan to study the corneal sensation changes and their correlation with ocular surface staining, tear film breakdown and meibomian gland dysfunction in GVHD patients. The study will shed light on an important aspect of corneal innervation damage in GVHD and may lead to new treatment modalities for those patients, noting that topical recombinant human nerve growth factor cenegermin was recently FDA approved for neurotrophic keratopathy. The investigators intend to identify the ocular characteristics of GVHD patients that may potentially benefit from cenegermin treatment.
Toxicity from barbituratepoisoning includes drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock. 

In acetaminophenoverdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, hypoglycemic coma and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. 

Acute caffeinepoisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia and extrasystoles.
PROBLEM TO BE SOLVED: To obtain a powdery preparation having nucleus small in powder particle diameter and capable of controlling the dissolution of medicine. SOLUTION: This powdery preparation having nucleus is prepared by spray- coating a fine particulate nucleus with a mixture solution containing a water-soluble polymer, such as hydroxypropylcellulose or hydroxypropylmethylcellulose and at least one kind of medicine. The prepared powdery preparation having the nucleus has a particle diameter of substantially <=500μm. The fine particulate nucleus may be spherical and contain crystalline cellulose and a disintegrating agent. The employment of a nucleus containing crystalline cellulose and a saccharide component in the powdery preparation having the nucleus enables to control the dissolution of the medicine. The powdery preparation having the nucleus is used as such or after processed into a granule, tablet or capsule.
Flecainide is a Vaughan Williams class 1c antiarrhythmic used to treat supraventricular and ventricular arrhythmias. It has been described as a rare cause for increased pacemaker capture thresholds. We describe a report of a patient, in her early 80s, presenting with tachy-brady syndrome on a background of permanent atrial fibrillation. She was treated with metoprolol and flecainide by her private cardiologist. Permanent right ventricular chamber pacing was recommended for her slow heart rate. At insertion of her single chamber pacemaker, she was noted to have elevated capture thresholds despite appropriate lead positioning. A flecainide level was elevated at 1.1 µg/mL, and it was subsequently ceased. This was associated with a rapid improvement in her capture threshold. Flecainide should be considered as a cause for elevated pacing thresholds at the time of implant. Particular care should be taken for at-risk groups such as the elderly and patients with renal impairment.
BACKGROUND: People with functional/dissociative seizures (FDS) are at elevated suicidality risk.
OBJECTIVE: To identify risk factors for suicidality in FDS or epilepsy.
METHODS: Retrospective cohort study from the UK's largest tertiary mental healthcare provider, with linked national admission data from the Hospital Episode Statistics. Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01 January 2007 and 18 June 2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (International Classification of Diseases, version 10: X60-X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models.
FINDINGS: In both groups, ethnic minorities had significantly reduced odds of hospitalisation following suicide attempt (OR: 0.45-0.49). Disorder-specific risk factors were gender, age and comorbidity profile. In FDS, both genders had similar suicidality risk; younger age was a risk factor for both outcomes (OR: 0.16-1.91). A diagnosis of depression or personality disorders was associated with higher odds of suicidal ideation (OR: 1.91-3.01). In epilepsy, females had higher odds of suicide attempt-related hospitalisation (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88-1.06). A substance abuse disorder was associated with higher suicidal ideation (OR: 2.67). Developmental disorders lowered the risk (OR: 0.16-0.24).
CONCLUSIONS: This is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.
CLINICAL IMPLICATIONS: Risk factors identified will help identify higher-risk groups in clinical settings.
In orthopedic surgery, peripheral nerve block can be used as an anesthesia adjuvant prior to surgery. In this study, we hypothesized that peripheral nerve blocks may alleviate inflammatory response and reduce the analgesics requirement. Sixty patients undergoing limb orthopedic surgery will be enrolled. Peripheral nerve block was injected with 0.25% bupivacaine under ultrasound guidance. 30 patients (Study group) underwent surgery with nerve blocks and another 30 patients (Control group) underwent surgery with morphine. The anesthetic protocol was standardized for both groups by experienced anesthesiologists. Surgical stress was assessed by blood pressure fluctuation and proinflammatory cytokine. Pain intensity was measured by numeric rating scale (NRS) score for 24 hours
BACKGROUND: Although previous studies have showed that epidural morphine can be used as a complement to local anesthetics for analgesia after postcesarean delivery under spinal anesthesia, there is little known about the analgesic dosage of epidural morphine and hydromorphone for hemorrhoidectomy. Therefore, we conducted this study to examine the potency ratio of hydromorphone to epidural morphine as well as effective analgesic dose for 50% patients (ED50) undergoing elective hemorrhoidectomy.
METHODS: 80 patients under elective hemorrhoidectomy with combined spinal and epidural anesthesia(CSEA) in department of anesthesia, Dongguan Tungwah hospital. To assess the ED50, patients were treated with epidural morphine or epidural hydromorphone randomly using a biased coin method-determined dose with a sequential allocation procedure. Following surgery, standardized multimodal analgesia was administered to all patients. A pain response score of ≤ 3 (on a scale of 0-10) was determined to be the effective dose after 24 h following CSEA. The ED50 in both groups were determined using the probit regression and isotonic regression method. We also measured pain intensity by patient interview using a 10 point verbal numeric rating scale prospectively at 6, 12 and 24 h after CSEA, and adverse effects were also noted.
RESULTS: The ED50 was 0.350 mg (95% CI, 0.259-0.376 mg) in hydromorphone group and 1.129 mg (95% CI, 0.903-1.187 mg) in morphine group, respectively, estimated by isotonic regression method. Regression analysis with the probit, the ED50 of epidural hydromorphone was 0.366 mg (95% CI, 0.276-0.388 mg) and epidural morphine was 1.138 mg (95% CI, 0.910-1.201 mg). Exploratory findings showed that there was no difference between the most frequent dosages of epidural hydromorphone or epidural morphine in the occurrence of nausea, vomiting and pruritus. When administered with epidural opioids at ED50 doses or higher, 97.5% (39/40) of epidural morphine patients and 97.5% (39/40) epidural hydromorphone of patients were satisfied with their analgesia.
CONCLUSION: Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction.
Once Aim 2 is complete and mentors have been trained, caregiver mentees will be matched with mentors by relationship to LBD patient, then by sex and age, as much as possible. The study team will contact mentees once a match is available for them. The mentee will complete baseline primary and secondary outcome assessments online via REDCap, including: mastery and loneliness scales, Short Zarit Burden Interview, Hospital Anxiety and Depression Scale. The team will provide the mentor's contact information and send the PERSEVERE handbook. Mentoring pairs will begin the 16-week peer mentor program. Pairs will be expected to speak for \>15-30 minutes weekly, and to review that week's PERSEVERE topics in the handbook before or during each call to facilitate meaningful conversations. Mentors and mentees will complete online study diaries every 2 weeks. Upon completion of the 16-week mentor program, mentors and mentees will be sent a link to complete postmentoring assessments online.
BACKGROUND & AIMS: Metastases from gastric adenocarcinoma (GAC) lead to high morbidity and mortality. Developing innovative and effective therapies requires a comprehensive understanding of the tumor and immune biology of advanced GAC. Yet, collecting matched specimens from advanced, treatment-naïve patients with GAC poses a significant challenge, limiting the scope of current research, which has focused predominantly on localized tumors. This gap hinders deeper insight into the metastatic dynamics of GAC.
METHODS: We performed in-depth single-cell transcriptome and immune profiling on 68 paired, treatment-naïve, primary metastatic tumors to delineate alterations in cancer cells and their tumor microenvironment during metastatic progression. To validate our observations, we conducted comprehensive functional studies both in vitro and in vivo, using cell lines and multiple patient-derived xenograft and novel mouse models of GAC.
RESULTS: Liver and peritoneal metastases exhibited distinct properties in cancer cells and dynamics of tumor microenvironment phenotypes, supporting the notion that cancer cells and their local tumor microenvironments co-evolve at metastatic sites. Our study also revealed differential activation of cancer meta-programs across metastases. We observed evasion of cancer cell ferroptosis via GPX4 up-regulation during GAC progression. Conditional depletion of Gpx4 or pharmacologic inhibition of ferroptosis resistance significantly attenuated tumor growth and metastatic progression. In addition, ferroptosis-resensitizing treatments augmented the efficacy of chimeric antigen receptor T-cell therapy.
CONCLUSIONS: This study represents the largest single-cell dataset of metastatic GACs to date. High-resolution mapping of the molecular and cellular dynamics of GAC metastasis has revealed a rationale for targeting ferroptosis defense in combination with chimeric antigen receptor T-cell therapy as a novel therapeutic strategy with potential immense clinical implications.
For neonates randomized to HHHFNC, they will be placed on a flow rate equivalent to the pressures of nCPAP they were originally receiving based on a published chart, or stay on the same flow rate prior to randomization. When it is time for oral feeds, the Registered Nurse (RN) will turn the dial of the high flow circuit down to 2 lpm. The baby will then proceed to feed for up to one hour, and afterwards, will be turned back up to the flow rate they were on prior to feeds.
Incarcerated gravid uterus (IGU) is a rare and serious obstetric complication. IGU is defined as the entrapment of the gravid uterus between the pubic symphysis and the sacral promontory. The incidence of IGU is 1 in 3000-10 000 cases. IGU is associated with significant obstetric complications, including preterm labor, intrauterine fetal death, growth restriction, renal failure, uterine ischemia/rupture and thrombosis. Here, we present the case of a primigravida with urinary retention at 14 weeks. On transabdominal ultrasound at 19+5/7 weeks the cervix was difficult to visualize, and the anterior uterine wall appeared thickened. The bladder was elongated superior to the uterus and the placenta was low-lying. Initially the patient was managed with intermittent self-catheterization, and subsequently indwelling catheterization was required from 22 weeks. At 30 weeks, the patient was transferred to a tertiary center and magnetic resonance imaging (MRI) was preformed due to challenging visualization of the cervix on ultrasound and the patient's continued symptoms of constipation and recurrent urinary infections. The MRI found a retroflexed gravid uterus, with vagina and endocervix displaced anteriorly and compressed by the gravid uterus. The findings were consistent with an incarcerated uterus. The patient subsequently had positive urinary cultures for Pseudomonas and rising creatinine. Given the obstructive uropathy and associated morbidity and mortality, a plan for elective pre-term delivery at 33+6/7 weeks was made. Delivery was by midline laparotomy, normal anatomy was restored after manual evacuation of the fundus from below the sacral promontory, and an uncomplicated lower segment transverse uterine cesarean section was performed.
Tumor biopsy at baseline to establish diagnosis and to identify PSMA expression in an ex-vivo setting. Patients with ex-vivo PSMA expression receive a multimodal imaging approach: This includes a PSMA-targeted PET/CT (18F-PSMA) at baseline and conventional imaging.
BACKGROUND: Papillary craniopharyngiomas harbor the BRAF V600E mutation, which paves the way for using BRAF inhibitor molecules to treat tumors refractory to standard therapies. Single case reports confirmed the efficacy of targeted therapy. However, most reports were limited by the short follow-up. We describe the long-term course of a patient treated with dual-agent BRAF and MEK inhibitors and review the available literature.
CASE REPORT: A 75-year-old male patient had recurrence of a papillary craniopharyngioma after transsphenoidal surgery and Gamma Knife radiosurgery. Review of the pathologic specimen confirmed the presence of the BRAF V600E mutation. Because of the few therapeutic options, we decided to initiate BRAF/MEK inhibitor combined therapy for six months. Rapid reduction of the tumor occurred, but three months after quitting combined medical therapy the tumor recurred. BRAF/MEK inhibitor therapy was resumed and the tumor again showed a marked reduction. The second course was maintained for 20 months and the tumor showed another recurrence within three months, which, again, responded to a third course of targeted therapy.
CONCLUSIONS: Our study confirms the excellent response of papillary craniopharyngioma to combined BRAF and MEK inhibitors. However, rapid tumor recurrence is the rule when medical therapy is stopped. Resistance to a second and third course of targeted therapy did not occur, suggesting that tumor mutations affecting the response to drugs seems an uncommon event in papillary craniopharyngioma. The exact role of targeted therapy in the treatment algorithm of papillary craniopharyngiomas has still to be refined.
Participants diagnosed with schizophrenia who switched from oral antipsychotics (OAPs) to Paliperidone Palmitate 1-month formulation (PP1M), with available information concerning the annual schizophrenia-related hospitalizations before and after initiation of PP1M treatment, and who switched to PP1M at least 6-months after it was available for reimbursement in Portugal will be observed. The primary data source for this study will be the medical records of each participant.
Treatment of calcaneal fractures in patients with diabetes mellitus (DM) is challenging. The purpose of this study was to compare post-operative outcomes after open reduction and internal fixation (ORIF) for calcaneus fracture in patients with complicated DM, uncomplicated DM, and patients without DM. A commercially available de-identified database was queried for all calcaneus fracture diagnoses undergoing ORIF from 2010 to 2021. The patients were separated into three groups for analysis: patients without DM (10,951, 82.6%), uncomplicated DM (1,500, 11.3%) and complicated DM (802, 6.1%). At 1 year, post-operative adverse events were assessed among the three groups. The odds of adverse event(s) for each group were compared between the three groups with and without characteristic matching. In the unmatched cohorts, patients with complicated DM, when compared with patients without DM and patients with uncomplicated DM, had significantly higher rates of all adverse events with exception of DVT. Rates of CNA were significantly higher in patients with complicated DM compared with no DM (OR 107.7 (CI 24.83-467.6) p < 0.0001) and uncomplicated DM (OR 44.26 (CI 3.86-507.93) p = 0.0002). After matching, non-union, AKI, sepsis, surgical site infection, and wound disruption were higher in patients with complicated DM compared with patients without DM. There were no significant differences in the three groups with regard to reoperation, DVT, MI, pneumonia, or below the knee amputation. Patients with DM who underwent ORIF for calcaneus fracture experienced higher rates of post-operative adverse events compared with those patients without DM.
Active control condition will be longitudinal. Participants in this arm will be asked to wear a research-grade smartwatch for at least 24 weeks and complete the baseline package as well as two follow-ups over a period of 24 weeks. After completing the baseline package, participants in the active control group will receive a 12 week psychoeducation training on stress and health called the Environmental Education Program.
The present invention provides for computing a quality factor value associated with medical care by receiving data sets associated with medical care and analyzing data of the data sets using a medical event detection routine to determine data relationships. The method and system detects a medical event and a care provider based at least on the plurality of relationships. The method and system detects a second event and a first number of data points in relation to the medical event. The method and system also detects a second number of data points relating to a completed standard-of-care response to the second event. The method and system determines a response timeliness value and a response completeness value based on the data analysis. The quality factor value is calculated based on the response completeness value and the response timeliness value.