anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families.
METHODS: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women.
RESULTS: We found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward.
CONCLUSION: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.
A method for producing human dendritic cells (DC) for therapeutic purposes using serum-free, animal protein-free medium. The method involves culturing mononuclear cells from peripheral or umbilical cord blood or bone marrow of an individual human donor in a culture container having at least one inner surface of polystyrene in the above described medium containing at least one hematopoietic growth factor, and maintaining the culture to produce a culture enriched for DC. The DC enrichment is evidenced by at least about 10% of the total cells in the culture exhibiting DC processes, or at least 2.5 % of the total cells expressing at least one DC antigen such as CD80, CD86, or CD1a.  The culture method is preferably carried out in a gas-permeable container in a closed fluid path system. The DC so produced can be pulsed with an antigen such as a viral, bacterial, tumor, or cell surface antigen, and the resulting primed dendritic cells can be co-cultured with T cells to produce antigen-specific human T-cells for therapeutic use. Useful for treatment of viral or bacterial infections, useful as a cancer vaccine, useful to induce tolerance when transplant of allo- or xeno-graft cells or organ is intended.
BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure.
METHODS: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function.
RESULTS: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments.
CONCLUSIONS: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.
Participants performed a 12 weeks outpatient pulmonary rehab (PR) according to guidelines. Participants allocated to intervention received PR plus physical activity (PA) counselling. PA counselling was performed using "motivational interviewing" techniques and was provided by two experiences physiotherapists independant to the rehab team. After PR and three months follow-up was evaluated if PA counselling during PR increases PA elvel (primary outcome: steps per day) in daily life.

Furthermore, individual, semi-structured interviews were performed in a subgroup of participants in order to gain more detailed information about barriers and enablers of participation in daily-life activities. Participants were invited to two interviews, one right after PR the other after 3 months follow up. A content analysis was performed.
Since the discovery of the vascular smooth muscle relaxant properties of nitric oxide (NO) over 25 years ago, studies have implicated this molecule in modulating such processes as atherosclerosis, impotence, angina, platelet function, and blood pressure, among others. Through vascular smooth muscle relaxation in both coronary and skeletal muscle arteries, as well as via independent mechanisms, nitric oxide has also been implicated in improvement of exercise capacity. In addition, NO may be involved in the immune system, assist in memory function and sleep regulation, and act as a cellular signaling messenger. Youthful, healthy and athletic individuals generally have a healthier NO system, compared to sedentary, unhealthy and aging individuals. NiteworksTM is a dietary supplement that includes L-arginine, an amino acid that acts as a nitric oxide donor and has been shown to increase levels of this molecule in the body. NiteworksTM has been formulated as a composite mixture along with other supplements, including antioxidants, that may act synergistically with L-arginine in enhancing exercise capacity.
Animal studies have shown that ibandronate is an inhibitor of osteoclast-mediated bone resorption. In the Schenk assay in growing rats, ibandronate inhibited bone resorption and increased bone volume, based on histologic examination of the tibial metaphyses. There was no evidence of impaired mineralization at the highest dose of 5 mg/kg/day (subcutaneously), which is 1000 times the lowest antiresorptive dose of 0.005 mg/kg/day in this model, and 5000 times the optimal antiresorptive dose of 0.001 mg/kg/day in the aged ovariectomized rat. This indicates that ibandronate sodium administered at therapeutic doses is unlikely to induce osteomalacia.  
  
Long-term daily or once-monthly intermittent administration of ibandronate to ovariectomized rats or monkeys was associated with suppression of bone turnover and increases in bone mass. In both rats and monkeys, vertebral BMD, trabecular density, and biomechanical strength were increased dose-dependently at doses up to 15 times the recommended human daily oral dose of 2.5 mg, or cumulative monthly doses up to 8 times (rat) or 6 times (monkey) the recommended human once-monthly oral dose of 150 mg, based on body surface area (mg/m2) or area under the curve (AUC) comparison. In monkeys, ibandronate maintained the positive correlation between bone mass and strength at the ulna and femoral neck. New bone formed in the presence of ibandronate had normal histologic structure and did not show mineralization defects.
Postmarketing cases of bowel obstruction have occurred with WELCHOL [see Adverse Reactions (6.2)] . Because of its constipating effects, WELCHOL is not recommended in patients with gastroparesis, other gastrointestinal motility disorders, and in those who have had major gastrointestinal tract surgery and who may be at risk for bowel obstruction. WELCHOL is contraindicated in patients with a history of bowel obstruction [see Contraindications (4)] . Instruct patients to promptly discontinue WELCHOL and seek medical attention if severe abdominal pain or severe constipation occurs. 

Because of the tablet size, WELCHOL tablets can cause dysphagia or esophageal obstruction. For patients with difficulty swallowing tablets, use WELCHOL for oral suspension.
BACKGROUND: Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will need to target the specific biology of tumour recurrence, but our current understanding of the underlying mechanisms is limited. Significantly, there is a lack of available methods and models that are tailored to the examination of tumour recurrence.
METHODS: NOD-SCID mice were orthotopically implanted with luciferase-labelled donor U87MG or MU20 glioblastoma cells. Four days later, an unlabelled recipient tumor was implanted on the contralateral side. The mice were euthanised at a humane end-point and tissue and blood samples were collected for ex vivo analyses.
RESULTS: The ex vivo analyses of the firefly-labelled MU20 tumours displayed extensive invasion at the primary tumour margins, whereas the firefly-labelled U87MG tumours exhibited expansive phenotypes with no evident invasions at the tumour margins. Luciferase signals were detected in the contralateral unlabelled recipient tumours for both the U87MG and MU20 tumours compared to the non-implanted control brain. Remarkably, tumour cells were uniformly detected in all tissue samples of the supratentorial brain region compared to the control tissue, with single tumour cells detected in some tissue samples. Circulating tumour cells were also detected in the blood samples of most of the xenografted mice. Moreover, tumour cells were detected in the lungs of all of the mice, a probable event related to haematogenous dissemination. Similar results were obtained when the U87MG cells were alternatively labelled with gaussian luciferase.
CONCLUSIONS: These findings describe a systemic disease model for glioblastoma which can be used to investigate recurrence biology and therapeutic efficacy towards recurrence.
OBJECTIVE: The goal of this study was to compare rates of dysphagia and patient-reported outcomes (PROs) following long-segment (≥ 3 levels) anterior cervical spinal fusion (ACF) and posterior cervical spinal fusion (PCF) at 3 and 12 months postoperatively. PROs were also compared for patients with dysphagia versus those without dysphagia.
METHODS: A prospectively collected quality improvement database was used to identify patients who had a long-segment cervical spinal fusion. Cohorts were divided into ACF and PCF groups. Eating Assessment Tool-10 scores and PROs were obtained for all patients preoperatively and at 3 and 12 months postoperatively to compare. Multivariate analysis was also performed to evaluate risk factors for dysphagia.
RESULTS: A total of 132 patients met the inclusion criteria, 77 of whom had undergone ACF and 55 of whom had undergone PCF. Dysphagia rates between ACF and PCF cohorts were similar at baseline (13.0% vs 18.2%, p = 0.4). New-onset dysphagia rates were also comparable at 3-month follow-up (39.7% vs 23.1%, p = 0.08) and 12-month follow-up (32.6% vs 32.4%, p > 0.99). Patients who underwent PCF had worse Neck Disability Index (NDI) scores at 3 months than did patients with ACF (13.67 ± 9.49 vs 10.55 ± 6.24, respectively; p = 0.03). There were significantly higher NDI scores for patients with dysphagia at 3 months in both the ACF and PCF groups and at 12 months for those in the PCF group. Analogously, EuroQol-5 Dimensions scores were worse for patients with dysphagia; however, this was only significant for patients in the ACF group at 3 months. There were no significant risk factors for the development of dysphagia found on multivariate analysis.
CONCLUSIONS: Similar rates and severity of dysphagia were seen following ACF and PCF at 3- and 12-month follow-up. This suggests that long-term dysphagia following cervical fusion surgery may be due to structural changes from the fusion rather than the surgical approach. However, the ACF cohort was significantly younger, and this may have partially accounted for the findings. PROs were also compared for patients with and without dysphagia, demonstrating worsened outcomes in some domains for patients who presented with dysphagia at 3- and 12-month follow-up. This suggests that dysphagia may be associated with a decreased quality of life after cervical fusion.
Hematologic: ACTOS may cause decreases in hemoglobin and hematocrit. The fall in hemoglobin and hematocrit with ACTOS appears to be dose related. Across all clinical studies, mean hemoglobin values declined by 2% to 4% in patients treated with ACTOS. These changes generally occurred within the first 4 to 12 weeks of therapy and remained relatively stable thereafter. These changes may be related to increased plasma volume associated with ACTOS therapy and have rarely been associated with any significant hematologic clinical effects.

Serum Transaminase Levels: During all clinical studies in the U.S., 14 of 4780 (0.30%) patients treated with ACTOS had ALT values ≥ 3 times the upper limit of normal during treatment. All patients with follow-up values had reversible elevations in ALT. In the population of patients treated with ACTOS, mean values for bilirubin, AST, ALT, alkaline phosphatase, and GGT were decreased at the final visit compared with baseline. Fewer than 0.9% of patients treated with ACTOS were withdrawn from clinical trials in the U.S. due to abnormal liver function tests.

In pre-approval clinical trials, there were no cases of idiosyncratic drug reactions leading to hepatic failure (see PRECAUTIONS, General, Hepatic Effects).

CPK Levels: During required laboratory testing in clinical trials, sporadic, transient elevations in creatine phosphokinase levels (CPK) were observed. An isolated elevation to greater than 10 times the upper limit of normal was noted in 9 patients (values of 2150 to 11400 IU/L). Six of these patients continued to receive ACTOS, two patients had completed receiving study medication at the time of the elevated value and one patient discontinued study medication due to the elevation. These elevations resolved without any apparent clinical sequelae. The relationship of these events to ACTOS therapy is unknown.
Adjuvant-free recombinant influenza candidate vaccine based on the Nucleoprotein (NP) of the influenza virus. One single administration intramuscularly of a 90µg dose on Day 1.
PURPOSE: To determine the clinical outcomes of endoscopic submucosal dissection (ESD) for colorectal tumors in older patients and predictors of mortality.
METHODS: We retrospectively evaluated 207 lesions in 195 consecutive older patients aged ≥ 75 years who underwent ESD for colorectal tumors between January 2007 and December 2018. Outcomes of ESD were evaluated, and the prognosis was assessed in terms of both curability and the patient's baseline physical condition as determined by several indices. Cox regression analyses were performed to identify factors associated with reduced overall survival (OS).
RESULTS: Treatment outcomes included a median procedure time of 55 min, en bloc resection rate of 97%, histological en bloc resection rate of 92%, postoperative bleeding rate of 2.4%, and intraoperative perforation rate of 3.4%. Postoperative bleeding and intraoperative perforation could be treated conservatively. Delayed perforation occurred in one patient and required emergency surgery. Three-year OS was 99.4% and 5-year OS was 95.8%. Overall, three patients experienced recurrence (one local, two distant metastasis), and one patient died of primary cancer. Multivariate analysis identified the Charlson Comorbidity Index (CCI) score ≥ 3 as the only independent predictor of reduced OS (hazard ratio 4.26; 95% confidence interval 1.60-11.38; P = 0.004).
CONCLUSION: Our results suggest that colorectal ESD is safe and effective in older patients aged ≥ 75 years. There was a significant independent association of reduced OS with high CCI score, but not with curability by ESD. The CCI score should be considered when determining the indications for ESD in older patients.
BACKGROUND: Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death.
METHODS: This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores.
RESULTS: Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (β = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores.
CONCLUSIONS: Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner.
Patients in the home-based BFRE group will be carefully instructed in how to perform the exercise program with four weekly sessions for 12 weeks (48 training sessions within an 84-day period). Each session will consist of one lower-limb resistance training exercise: sit-to-stand from a \~43 cm high chair. The exercise will consist of four rounds interspaced by a 30-seconds rest pause. The first, second, and third round will consist of 30, 15, 15 repetitions, while the fourth round will be performed until volitional fatigue. The patients will be instructed to perform both the eccentric and concentric contractions at a steady 2-sec pace with, preferably, no time for relaxation in the transition from eccentric to concentric phase (i.e. the bottom is only "kissing" the chair before reversing the movement upwards). When a patient can perform more than 25 repetitions in the last round, they are encouraged to add external resistance corresponding to around 5 kg.
Terazosin Hydrochloride administered as capsules is essentially completely absorbed in man. Administration of capsules immediately after meals had a minimal effect on the extent of absorption. The time to reach peak plasma concentration however, was delayed by about 40 minutes. Terazosin has been shown to undergo minimal hepatic first-pass metabolism and nearly all of the circulating dose is in the form of parent drug. The plasma levels peak about one hour after dosing, and then decline with a half-life of approximately 12 hours. In a study that evaluated the effect of age on terazosin pharmacokinetics, the mean plasma half-lives were 14.0 and 11.4 hours for the age group ≥ 70 years and the age group of 20 to 39 years, respectively. After oral administration the plasma clearance was decreased by 31.7% in patients 70 years of age or older compared to that in patients 20 to 39 years of age.

The drug is 90 to 94% bound to plasma proteins and binding is constant over the clinically observed concentration range. Approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces. The remainder is eliminated as metabolites. Impaired renal function had no significant effect on the elimination of terazosin, and dosage adjustment of terazosin to compensate for the drug removal during hemodialysis (approximately 10%) does not appear to be necessary. Overall, approximately 40% of the administered dose is excreted in the urine and approximately 60% in the feces. The disposition of the compound in animals is qualitatively similar to that in man.
Adult patients (18 years of age or older) taking a TNF-alpha inhibitor as defined by the NIH and missing teeth will be recruited to receive dental implant placement according to standard of care for ideal dental restoration. Patients must have been taking a stable dose of the drug for at least 6 months and have no contra-indications to implant placement (regular tobacco use in the last year, periodontal disease, pathology in the jaw bone(s), history of head and neck radiation, history of antiresorptive or antiangiogenic agents, uncontrolled diabetes, pregnancy, other medical conditions that preclude safe delivery of outpatient medical care) to be eligible for enrollment in the study.
Animals have been domesticated and kept as a source of milk for tens of thousands of years, When humans keep animals for their ability to produce milk, the animals are usually kept in confined spaces. As a result of this confinement the animals are exposed to high levels of urine and fecal matter which originated with the animals which are being kept. This exposure contaminates the animal and in particular the udder and teats of the animal, with bacteria. In the milking process this bacteria can further contaminate the milk which is destine for human consumption. The bacteria can further cause mastitis in the bovine. The above set forth problems are eliminated in the subject invention wherein the udder and teat areas of the bovine are sanitized with a solution of trichloromelamine.
Participants will undergo a bone marrow aspirate procedure. Participants will receive a single subchondral injection of NGRM-001 on treatment day.
Visit 1 screening will determine eligibility and obtain informed consent. At visit 2, 3 and 4 subjects inhale 1 dose of 45U TI Inhalation Powder. At visit 3 subjects inhale 2 puffs (200mcg) Albuterol prior to dosing. Only asthmatic subjects undergo visit 4 where a methacholine challenge test (MCT) is performed followed by inhalation of Albuterol then administration of TI Inhalation Powder. Each visit's dosing will occur during a hyperinsulinemic euglycemic clamp. Visit 5 is the follow up visit.