anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This study is a Phase 1, double blind, single and multiple rising dose tolerance study of EMB-001 (metyrapone/oxazepam combination) in otherwise healthy adults who have tobacco use disorder. There will be 3 cohorts, each with 8 subjects (6 active: 2 placebo), for a total of 24 subjects. During the treatment period, subjects will receive a single dose of EMB 001 on Day 1, followed 24 hours later by the start of multiple doses twice daily for 7 days, and then a final morning dose on the last dosing day (Day 9). This design allows for characterization of EMB-001 single dose PK for 24 hours, followed by assessment of repeat dose PK in the multiple-dose phase. Safety will be assessed after the single dose and repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at the end of repeated dosing. Later studies may also assess the efficacy of this drug combination in treating cocaine use disorder, tobacco use disorder, and/or other disorders.
OBJECTIVE: Syphilis-related stillbirths (SRSBs) disproportionately affect marginalized women with 11% of all local stillbirths having maternal syphilis as a contributory factor in 2020. This study describes the incidence and perinatal factors associated with SRSB.
METHODS: This was a retrospective cohort study of all stillbirths occurring from 1 January 2017 to 31 December 2020, at a single tertiary-level referral hospital in Winnipeg, Manitoba. Cases that met criteria for SRSB were identified from hospital records and included in the final analysis. Maternal demographics, comorbidities, prenatal care attendance, sexually transmitted infection testing, treatment, and diagnostic investigations at time of stillbirth were collected from hospital charts using a standardized data collection form. Descriptive statistics were performed to present the results.
RESULTS: The proportion of SRSB increased over the period of study from 0%-11%. Eleven cases were identified as SRSB, with diagnosis occurring intrapartum in 7 cases and antenatally in 4 cases. Of the 4 antenatal cases, only 2 had identifiable treatment responses indicated by microbiological and pathology workup. Commonly identified risk factors for SRSB were homelessness, mental illness, substance use, sexually transmitted co-infections, and lack of prenatal care.
CONCLUSIONS: Cases of SRSB are rising in Winnipeg with 11% of all stillbirths having maternal syphilis as a contributory factor by 2020. SRSBs disproportionately affect marginalized women. The dramatic and rapid changes in the epidemiology of syphilis in Winnipeg are likely shared by other Canadian regions and warrant increased prevention strategies to improve outcomes.
BACKGROUND: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression.
MATERIAL AND METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy.
RESULTS: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation.
CONCLUSION: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.
Bimaxillary surgery is a painful invasive procedure in plastic surgery. Pain control is typically achieved using intravenous analgesics. We aimed to investigate the efficacy of a novel temperature-responsive hydrogel, PF72, mixed with ropivacaine, as a local pain management solution when applied directly to the surgical site following orthognathic surgery. The study was conducted from October 2022 to July 2023 and included a cohort of 40 candidates for orthognathic surgery, encompassing LeFort I maxillary ostectomy and sagittal split ramus osteotomy. The participants were divided into an Injection group (n = 20), where PF72 was administered at the surgical site before the orthognathic surgery, and a Control group (n = 20), which relied solely on intravenous analgesics. Pain was evaluated at 3, 6, 24, 48, and 72 h after surgery using a numerical rating scale (NRS). The mean NRS scores at 24 h were 6.35 and 4 for the Control and Injection groups, respectively. The mean NRS scores at 72 h were 3.4 and 2.55 for the Control and Injection groups, respectively. Patients who received PF72 experienced less pain than those who received intravenous analgesics. These findings underscore the potential of PF72 as an effective alternative for enhancing pain management in patients undergoing orthognathic surgery.Level of Evidence III Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
In younger populations, risk factors from psychologically-focused theoretical models have become accepted as primary drivers behind the persistence of low back pain (LBP), but these risk factors have not been thoroughly assessed in older adult populations (60-85 years). To address this knowledge gap, we sought to examine longitudinal associations between both general and pain-related psychological risk factors and future pain intensity, LBP-related disability, and physical function (gait speed) outcomes in older adults with chronic LBP (n = 250). Questionnaires for general (ie, depressive symptoms) and pain-related psychological risk factors (ie, fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were collected at baseline. Questionnaire values were entered into principal component analysis to yield a combined psychological component score. LBP intensity (pain thermometers), LBP-related disability (Quebec Back Pain Disability Scale), and gait speed were measured at baseline and 12-month follow-up. Multiple linear regression was used to examine adjusted associations between baseline psychological component scores and each prospective outcome. The baseline psychological component score failed to independently predict 12-month LBP-related disability and gait speed after adjustment for baseline outcomes. Though the psychological component score was associated with 12-month LBP intensity after adjusting for baseline LBP intensity, this association diminished with full adjustment for other baseline characteristics. Cumulatively, general and pain-related psychological risk factors did not independently predict longitudinal pain, disability, and physical function outcomes in this cohort. Compared to younger populations with this condition, general and pain-related psychological risk factors may have less influence on the maintenance of chronic LBP in older adults. PERSPECTIVE: This article failed to establish consistent independent relationships between psychological factors and worse longitudinal pain, disability, and physical function outcomes in older adults with chronic LBP. The findings highlight a need to determine other age-specific biopsychosocial risk factors that may impact the maintenance of chronic pain in this patient population.
The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.
Subjects will receive a single infusion of ex vivo expanded umbilical cord blood derived Treg product (2 x 10\^6). Dose escalation of liraglutide up to 1.2 mg will be started 3 days after Treg infusion only if no severe side effects showed. Subjects continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as a routine therapy.
Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.
It was planned that this Phase 2a, open-label, safety and efficacy study to be performed at 5 sites in the US and 1 site in the United Kingdom.

The study was to enroll \~30 boys with nonsense mutation DMD/BMD (nmDBMD) who have been nonambulatory for at least 1 year. Enrollment was to be stratified to ensure evaluation of \~15 participants who were receiving chronic corticosteroid therapy and of \~15 participants who were not receiving chronic corticosteroid therapy. Participants were to take ataluren 3 times per day (at breakfast, lunch, and dinner) for 48 weeks (\~1 year). Study assessments were to be performed at clinic visits during screening, every 6 weeks for 2 visits and then every 12 weeks until the end of the study. Additional safety laboratory testing was to be required 4 times during the course of the study; this could have been performed at the investigational site, at an accredited local laboratory or clinic, or in the participant's home using a nursing service. When the blind for a similar study (PTC124-GD-007-DMD; NCT00592553) was revealed, the results indicated lack of efficacy for the high dose. Therefore, even though an independent data monitoring committee (DMC) agreed that both ataluren dose levels were well tolerated by the participants, the DMC recommended discontinuing ongoing studies with participants with nmDBMD receiving high-dose ataluren.
PEG linker compounds and biologically active conjugates thereof having mixed functional group linkages attached to at least one PEG moeity, and a coupling group for attaching a biologically active molecule. The PEG mixed linkages can be the combinations of stable, or labile, or releasable, or stable and labile, or stable and releasable, or releasable and labile covalent linkages. The mixed functional linkages of the PEG linker compounds consist of different organic functional groups, which have non-equivalent half-life in plasma and, hence, they have different release rates in blood. The present invention also provides for attachment of novel PEG linker compounds with mixed functional linkages for Pegylation of biologically active molecules to produce Probiomolecule-PEG constructs. The Probiomolecule-PEG construct is the prodrug of biomolecule-PEG conjugate or biomolecule. The Probiomolecule-PEG conjugate will gradually lose portions (or all) of its PEG polymers in vivo to convert into smaller size biomolecule-PEG conjugate (or biologically active molecule), thereby increasing their biological activity in vivo.
OBJECTIVE: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response.
METHODS: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity.
RESULTS: After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients.
CONCLUSION: Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA.
Actinic keratoses are premalign skin lesions with increasing prevalence, causing a rising burden on the health care system. In this blinded controlled study we assess the efficacy of pulsed dye-laser- mediated photodynamic therapy compared to conventional photodynamic therapy and fractional-laser assisted daylight photodynamic therapy to daylight photodynamic therapy. It is a prospective, randomized and blinded split-head comparative study during the years 2016- 2024. 120 patients are recruited based on referral or from patients attending the clinic, with 2 or more actinic keratoses on the head, 60 to the pulsed dye-laser study and 60 to the fractional laser study. Follow-up appointments are 6 months, 1 year and 2 years post treatment. Patient reported maximal pain during treatment is documented.
In controlled trials with all clobetasol propionate formulations, the following adverse reactions have been reported: burning/stinging, pruritus, irritation, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, tenderness in the elbow, skin atrophy, and telangiectasia. The incidence of local adverse reactions reported in the trials with clobetasol propionate cream-emollient was <2% of patients treated with the exception of burning/stinging, which occurred in 5% of treated patients.

Cushing syndrome has been reported in infants and adults as a result of prolonged use of other topical clobetasol propionate formulations.

The following additional local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with super-high potency corticosteroids such as clobetasol propionate cream-emollient. These reactions are listed in an approximately decreasing order of occurrence: dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria.

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are common side effects, classified according to timing and severity. Conventional agents such as dexamethasone are effective but have various side effects. For moderately emetogenic chemotherapy, dexamethasone-sparing antiemetic therapies have been developed to minimize these side effects. This systematic review evaluated the efficacy and safety of dexamethasone-sparing antiemetic therapy for highly emetogenic chemotherapy (HEC).
METHODS: We performed a thorough literature search for studies related to dexamethasone-sparing antiemetic therapy with neurokinin-1 antagonists (NK1RA) for HEC using the PubMed, Cochrane Library, and Ichushi-Web databases. A qualitative analysis of the combined data was performed and risk differences with confidence intervals were calculated.
RESULTS: Two reviewers independently assessed the 425 records and 12 full-text articles were evaluated for eligibility. Two studies were included in the qualitative and meta-analyses. These studies included anthracycline-cyclophosphamide (AC) regimens and cisplatin-based regimens, with palonosetron as the serotonin receptor antagonist. In the two studies, no difference was found in the prevention of vomiting (delayed complete response). However, non-inferiority was not demonstrated in the subgroup that received cisplatin-containing regimens. Delayed complete control showed different results for nausea prevention; however, there was no significant difference in the meta-analysis. Only one report has shown non-inferiority for delayed total control. Although the strength of evidence for individual outcomes varied, there was no difference in the duration of dexamethasone administration.
CONCLUSIONS: This systematic review and meta-analysis revealed that dexamethasone-sparing antiemetic therapy with NK1RA and palonosetron can be used to prevent CINV in HEC, limited to AC combination therapy.
Sub-millimeter scale three-dimensional (3D) structures are disclosed with customizable chemical properties and/or functionality. The 3D structures are referred to as drop-carrier particles. The drop-carrier particles allow the selective association of one solution (i.e., a dispersed phased) with an interior portion of each of the drop-carrier particles, while a second non-miscible solution (i.e., a continuous phase) associates with an exterior portion of each of the drop-carrier particles due to the specific chemical and/or physical properties of the interior and exterior regions of the drop-carrier particles. The combined drop-carrier particle with the dispersed phase contained therein is referred to as a particle-drop. The selective association results in compartmentalization of the dispersed phase solution into sub-microliter-sized volumes contained in the drop-carrier particles. The compartmentalized volumes can be used for single-molecule assays as well as single-cell, and other single-entity assays.
The subject will participate in 16 in-person hours that are broken into sessions for the Mindfulness-Based Cognitive Therapy intervention. The intervention will be facilitated by 1-2 instructors who are trained in clinical psychology/ social work and are also trained in MBCT. This intervention will include mindfulness activities, didactic learning, homework assignments and group dialogue. This adapted MBCT intervention will follow the empirically-based MBCT intervention for depression structure with fidelity.
Cancer and its metastases arise from mutations of genes, drivers that promote a tumor's growth. Analyses of driver events provide insights into cancer cell history and may lead to a better understanding of oncogenesis. We reviewed 27 metastatic research studies, including pan-cancer studies, individual cancer studies, and phylogenetic analyses, and summarized our current knowledge of metastatic drivers. All of the analyzed studies had a high level of consistency of driver mutations between primary tumors and metastasis, indicating that most drivers appear early in cancer progression and are maintained in metastatic cells. Additionally, we reviewed data from around 50,000 metastatic cancer patients and compiled a list of genes altered in metastatic lesions. We performed Gene Ontology analysis and confirmed that the most significantly enriched processes in metastatic lesions were the epigenetic regulation of gene expression, signal transduction, cell cycle, programmed cell death, DNA damage, hypoxia and EMT. In this review, we explore the most recent discoveries regarding genetic factors in the advancement of cancer, specifically those that drive metastasis.