anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cancer is associated with a high risk of venous thromboembolism (VTE) and its recurrence. There is evidence that the prothrombotic fibrin clot phenotype, involving the formation of denser and stiffer clots relatively resistant to lysis, occurs in cancer patients, which is in part related to enhanced inflammation, oxidative stress, and coagulation activation, along with the release of neutrophil extracellular traps, indicating that fibrin-related mechanisms might contribute to cancer-associated thrombosis (CAT). Multiple myeloma and its therapy have been most widely explored in terms of altered fibrin characteristics, but prothrombotic fibrin clot features have also been reported in patients with active solid cancer, including lung cancer and gastrointestinal cancer. Patient-related factors such as advanced age, smoking, and comorbidities might also affect fibrin clot characteristics and the risk of CAT. Prothrombotic fibrin clot features have been shown to predict the detection of cancer in patients following VTE during follow-up. Cancer-specific therapies and anticoagulation can favorably modify the phenotype of a fibrin clot, which may alter the course of CAT. It is unclear whether the fibrin clot phenotype might help identify patients with CAT who are more likely to experience recurrent events. This narrative review summarizes the current knowledge on the role of fibrin clot structure and function in cancer patients in the context of CAT.
1403139 Antiperspirant aerosols COLGATEPALMOLIVE CO 18 Sept 1973 43699/73 Heading C4X [Also in Division A5] Non-staining, antiperspirant, spray powder compositions comprise a powdered antiperspirant, e.g. an aluminium component, in particular aluminium chlorohydrate, a propellant fluid (preferably a liquefied gas) and a surface active agent which is microencapsulated in a shell which is preferably water-soluble, e.g. of protein, cellulosic or synthetic plastics material. Any conventional surface active agent may be used and the compositions may comprise other conventional ingredients, e.g. a suspending agent such as colloidal silica, perfumes, emollients, bactericides and fungicides. Propellants used in examples are; 60/40 trichlorofluoromethane / dichlorodifluoromethane and a branched chain C 11 -C 13  saturated hydrocarbon.
Each participant follows this sequence: (1) 5-9 weeks waitlist during which no treatment is offered; (2) 4 weekly preparatory sessions. During these sessions the rationale of ImRs will be explained in more detail and a list of painful (childhood) memories to be addressed with ImRs is to be compiled, based on any further input from the patient; and a case conceptualization is made; (3) 12 sessions (45-60 minutes) of ImRs will be offered to participating patients. The ImRs treatment will be based upon the protocol described by Arntz \& Weertman (1999). This protocol can be modified to tailor the needs of this study more specifically. (4) After end of active treatment (ImRs) 4 weeks follow during which only weekly assessments are done.
The cells can be injected intramuscular in several points in the muscle alternatively they can be injected in the motor point of the muscle. A motor point is the point at which the motor branch of the innervating nerve enters the muscle). This injection is repeated every 6 month up to 2 years.
In patients with HIV multidrug resistance, maintaining a failing full-dose HAART regimen usually results in significant drug toxicity and in continued accumulation of resistance mutations that can preclude future therapeutic options. In contrast, treatment interruption provokes the reemergence of wild-type virus with full replicative and pathogenic capacity. The researchers investigated whether a calibrated reduction in drug pressure could stabilize the evolution and the pathogenic potential of resistant virus.

A prospective pilot study was conducted in patients receiving protease inhibitor-based HAART with a resistance genotype predicting less than two active drugs according to the 2002 ANRS algorithm, CD4 counts over or equal to 100/mm3 and plasma HIV RNA below or equal to 5 log/ml. The treatment was low-dose IDV/RTV (200/100 BID) and 3TC 150mg BID. IDV doses were adjusted at week 4 to ensure a Cmin of 250+/-100ng/ml, which, based on a panel of multi-PI resistant viruses, was calculated to yield an inhibitory quotient (Cmin/IC50) of 0.50. Primary end-points were over 25% decrease in CD4 counts (immunological failure-IF), or over 0.7 log increase in plasma HIV RNA (virological failure-VF) at two consecutive monthly visits during the 24-week study. Inclusions were to stop when the total number of failures (VF+IF) reached 7
BACKGROUND: The prevalence of diabetes and obesity has been continuously rising worldwide over the last three decades, particularly in China. The prevalence varies widely among different ethnicities. In this study, we investigated the prevalence of diabetes and obesity, as well as the associated factors for diabetes in Kazakh adults in Xinjiang to improve diabetes screening.
METHODS: We collected data from the Xinjiang physical examination in 2018, including a total sample of 118,505 Kazakh adults in Altay District. Data on demographic characteristics, medical history, physical examination, fasting plasma glucose (FPG) and serum lipid profiles were collected. The chi-square test was used to examine the differences between multiple variables. Multivariate logistic regression was performed to identify the factors associated with diabetes.
RESULTS: The mean age was 43. 66 years (SD 14.14). 49.3% of the population were women and 75.5% were rural residents. The mean FPG was 5.33 mmol/L (SD 1.22). The prevalence of diabetes was 6.3% and 4.1% received a new diagnosis by FPG. 26.6% were diagnosed with impaired fasting glucose (IFG). The mean body mass index (BMI) was 26.29 kg/m2 (SD 14.14) and the mean waist circumference was 87.69 cm (SD 12.74). 33.2% of the population were overweight, and 33.0% were obese. The prevalence of central obesity was 51.4%. Diabetes was mostly positively associated with hypertension (OR = 3.821, P<0.001), hypertriglyceridemia (OR = 2.757, P<0.001), and hyper-LDL-cholesterolemia (OR = 2.331, P<0.001) in the Kazakh population. The ORs for overweight, obesity and central obesity predictive of diabetes were 1.265, 1.453 and 1.222 ( all P<0.001), respectively.
CONCLUSIONS: Despite having a high prevalence of obesity and central obesity, the Kazakh population had a considerably low prevalence of diabetes. Obesity was not the most important risk factor for diabetes in Kazakh individuals. The awareness of diabetes was low. When screening for diabetes in Kazakhs, those with hypertension or dyslipidemia should receive more attention.
OBJECTIVES: Chronic hepatitis B (CHB) caused by HBV infection greatly increases the risk of liver cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) plays critical roles in the pathogenesis of CHB. HBsAg loss is the key indicator for cure of CHB, but is rarely achieved by current approved anti-HBV drugs. Therefore, novel anti-HBV strategies are urgently needed to achieve sustained HBsAg loss.
DESIGN: We developed multiple chimeric antigen receptors (CARs) based on single-chain variable fragments (scFvs, namely MA18/7-scFv and G12-scFv), respectively, targeting HBV large and small envelope proteins. Their impacts on HBsAg secretion and HBV infection, and the underlying mechanisms, were extensively investigated using various cell culture models and HBV mouse models.
RESULTS: After secretory signal peptide mediated translocation into endoplasmic reticulum (ER) and secretory pathway, MA18/7-scFv and CARs blocked HBV infection and virion secretion. G12-scFv preferentially inhibited virion secretion, while both its CAR formats and crystallisable fragment (Fc)-attached versions blocked HBsAg secretion. G12-scFv and G12-CAR arrested HBV envelope proteins mainly in ER and potently inhibited HBV budding. Furthermore, G12-scFv-Fc and G12-CAR-Fc strongly suppressed serum HBsAg up to 130-fold in HBV mouse models. The inhibitory effect lasted for at least 8 weeks when delivered by an adeno-associated virus vector.
CONCLUSION: CARs possess direct antiviral activity, besides the well-known application in T-cell therapy. Fc attached G12-scFv and G12-CARs could provide a novel approach for reducing circulating HBsAg.
The study will logically build on our previous work and utilize the already established infrastructure and resources of the intra-operative electronic medical record and the AlertWatch® alerting system. In conceptualizing this pilot study, as well as a larger follow-up trial focused on clinical outcomes, we have been mindful of challenges put forward to investigators by the National Institutes of Health, which seek to support low-cost, pragmatic, patient-centered randomized controlled trials. Specifically in relation to ACTFAST, (1) the highly developed, specialized IT infrastructure limits the investment required for embarking on this study; (2) the study will be conducted entirely within the context of routine clinical care, negating the need for dedicated trial-related visits; (3) access to registries with granular data on complications and patient-reported outcomes obviates the need for a new and costly infrastructure to track patient outcomes; (4) inclusion of large numbers of broadly representative patients in this study will be highly efficient with a waiver of informed consent. The design for this pilot proof-of-concept study will be a randomized clinical effectiveness trial. It will include a 6-month pre-intervention period during which time the ACT will be staffed but no alerts will be sent. This will allow for the training of controllers, refinement of alerts, and optimization of processes for obtaining and filtering information from diverse electronic sources. Following this period, the trial will begin and run for 12 months. On a daily basis during the study period (weekdays from 7am to 5pm), each operating room in Barnes-Jewish Hospital (BJH) will be eligible for randomization, which will occur using computer-generated assignment. Anesthesiology teams in ORs allocated to the experimental arm will receive the additional support of the ACT in the form of control-tower alerts that complement the AlertWatch® system. The outcomes of interest in this pilot study will be the usability and usefulness of the ACT, clinician adherence to recommendations for monitoring, documentation and therapeutic interventions, key physiologic variables such as temperature and blood pressure. We will also document patient outcomes including duration of postoperative hospital stay, incidence of postoperative morbidity (myocardial infarction, surgical site infection), functional recovery, and postoperative quality of life. Data on these endpoints will inform the design of a subsequent trial focused on clinically relevant outcomes, which will logically follow the current pilot randomized trial. All of the alerts included in this study will be chosen because they follow proven best intraoperative management practice and are in line with national metrics for quality and safety.
The Mindfulness Based Relapse Prevention (MBRP) intervention is composed of 8 weekly 2-hour sessions delivered in small group format (10-14 participants). Individual sessions will be team-taught by two therapists and will include mindfulness practices targeting craving, Negative affect, and reactivity, as well as discussion about how to implement practice into high-risk situations and in daily life.
Carcinogenesis   
Carcinogenicity studies have not been conducted with oxycodone alone or the oxycodone and naloxone combination.

Naloxone was tested in two carcinogenicity studies in rats and transgenic mice. Naloxone was not carcinogenic in a 2-year rat bioassay at doses as high as 100 mg/kg/day (24-times the maximum recommended daily dose of 40 mg naloxone/day on a mg/m2 basis).

Naloxone did not produce evidence of carcinogenic potential in the Tg.rasH2 mouse model.

Mutagenesis   
Oxycodone was genotoxic in the mouse lymphoma assay. Clastogenicity was observed with oxycodone in the presence of metabolic activation in one chromosomal aberration assay in human lymphocytes at concentrations greater than or equal to 1250 mcg/mL at 24 but not 48 hours of exposure. In a second chromosomal aberration assay with human lymphocytes, no structural clastogenicity was observed either with or without metabolic activation; however, in the absence of metabolic activation, oxycodone increased numerical chromosomal aberrations (polyploidy). Oxycodone was not genotoxic in the following assays: Ames S. typhimurium and E. coli test with and without metabolic activation at concentrations up to 5000 µg/plate, chromosomal aberration test in human lymphocytes (in the absence of metabolic activation) at concentrations up to 1500 µg/mL, and with activation after 48 hours of exposure at concentrations up to 5000 µg/mL, and in the in vivo bone marrow micronucleus assay in mice (at plasma levels up to 48 µg/mL).

Naloxone was genotoxic in the mouse lymphoma assay. Naloxone produced a non-dose-related increase in chromosomal aberrations in the presence of metabolic activation that was statistically significant at concentrations of 375 and 1500 mcg/mL but not at 750 or 3000 mcg/mL. In contrast, naloxone was not mutagenic in the S. typhimurium/E. coli bacterial mutagenicity test with or without metabolic activation nor was it genotoxic in in vivo mouse bone marrow micronucleus test at a dose of 500 mg/kg.

Impairment of Fertility   
Fertility studies to evaluate the combination of oxycodone and naloxone have not been conducted. In a study of reproductive performance, rats were administered a once daily gavage dose of the vehicle or oxycodone hydrochloride doses up to 8 mg/kg (equivalent to the maximum recommended daily dose of 80 mg/day on a mg/m2 basis). Male rats were dosed for 28 days before cohabitation with females, during the cohabitation and until necropsy (2-3 weeks post-cohabitation). Females were dosed for 14 days before cohabitation with males, during cohabitation and up to Gestation Day 6\. Oxycodone hydrochloride did not affect reproductive function in male or female rats.

Oral administration of naloxone to male and female rats at dosages as high as 800 mg/kg/day had no effect on fertility or general reproductive performance (approximately 192-times the maximum recommended daily dose of 40 mg naloxone/day, on a mg/m2 basis).
CD44 is a cell receptor glycoprotein overexpressed in circulating tumor cells (CTCs), with levels linked to an increase in metastatic capacity of several tumors. Hyaluronic acid (HA), the natural ligand of CD44, has primarily been investigated for tumor cell interaction in self-assembled polyelectrolyte multilayer films, with little attention given to the complementary polycation. In this study, we screened sixteen different polyelectrolyte multilayer assemblies of HA and chitosan (CHI) to identify key assembly parameters and surface properties that control and govern CTCs adhesion. Statistics analysis revealed a major role of CHI molecular weight in the adhesion, followed by its combinatorial response either with HA ionization degree or ionic strength. PM-IRRAS analysis demonstrated a correlation between the orientation of HA carboxyl groups on the film surface and CTCs adhesion, directly impacted by CHI molecular weight. Overall, although CTCs binding onto the surface of multilayer films is primarily driven by HA-CD44 interaction, both chitosan properties and film assembly conditions modulate this interaction. These findings illustrate an alternative to modifying the performance of biomaterials with minimal changes in the composition of multilayer films.
"Aan Tafel in 1 2 3 euro" is a project of retailer Colruyt in cooperation with social organizations in Belgium. The project/intervention was launched in 2016 and has been implemented throughout Belgium since. In 2021 about 8000 families have already been subscribed, and the numbers are still growing. Families with a lower SES (vulnerable families) are informed by a social organization (OCMW, CAW, kind \& gezin, etc.) and can voluntarily register for the project. When a family is registered, they receive a recipe booklet every two weeks at home. The booklet consists of six easy, child-friendly recipes with accompanying shopping lists. Recipes are targeted at three people and include fish, meat and veggie dishes. Each recipe is guaranteed to cost no more than one, two or three euros per serving. The participants are registered via the Xtra-card (loyalty card of Colruyt), so that the discount can be offered anonymously and discretely. Since the intervention is an already existing one, we made an overview of the intervention components, behavior change techniques and practical applications, based on the Intervention Mapping Theory (Kok et al., 2015) and the Behavior Change Wheel (Abraham \& Michie, 2008). Based on this overview, we determined goals and outcome measures for our research project.

In the qualitative study (WP1), participants of the intervention, as well as representatives of social organizations will be recruited to participate in an interview and/or focus group interview. Interviews will be conducted until data saturation is reached.

In the interventional study (WP3), participants of the project (intervention condition) will be compared to participants in a control condition who do not participate in the project. A total sample size of 200 participants is calculated, based on an a priori power analysis (two groups, two measurements, α=0.05; power=0.80, ES=0.25). Participants in both conditions will complete a survey in a pre-measurement and a post-measurement, three months after the start of the intervention.

The second effect study (WP2) has a longitudinal pre-post design, and is based on secondary purchase data from 2018 until 2022. The intervention group (i.e., participants of the intervention) will be compared to a control group (i.e., not subscribed in the intervention), by using general customer data. A multilevel growth model will be used to look at each individual's different purchase moments, with data before and during the intervention. The model represents three levels: 1) point of time/purchase, 2) customer, 3) store/location.
BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer.
METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses.
RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases.
CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.
We aim to describe double gonosomal mosaicism in the GRIN2A gene in a mother who passed on two different pathogenic variants at the same nucleotide to her two affected children. We studied a boy with epilepsy and intellectual disability, along with his sister and mother who exhibited language impairment and learning difficulties without epilepsy. We identified in the proband a splice-site variant in GRIN2A (c.1008-1G>A) inherited from his mother. Subsequent testing of his sister revealed a different change at the same nucleotide c.1008-1G>T, which was also present in the mother's DNA at 3.9% allele frequency. The co-occurrence of two mutational events at the same nucleotide is extremely rare. Since a chance occurrence is unlikely, we hypothesise that a base mismatch may introduce instability triggering a second event. In this family, the mother carries three alleles, of which one is at very low frequency. This complex genetic landscape poses diagnostic challenges since low-level mosaicism may escape detection via conventional methods. Applying specific technology becomes crucial, as double mosaicism might prove to be more prevalent than anticipated severely impacting diagnostic accuracy and genetic counselling.
BACKGROUND: Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A2 (TxA2) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA2 responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment.
METHODS: Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O2) or hypoxia (11% O2) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA2 analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA2 receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence.
RESULTS: Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA2 receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels.
CONCLUSIONS: Prenatal hypoxia increased TxA2 vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring.