anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVES: I. Determine the 6-month survival and overall survival of patients with unresectable or metastatic biliary tract carcinoma or gallbladder cancer treated with gemcitabine, fluorouracil, and leucovorin calcium. II. Determine the tumor response in these patients treated with this regimen. III. Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive gemcitabine IV over 30 minutes followed by leucovorin calcium IV and fluorouracil IV over 5-10 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.
The right hemisphere has been underestimated by being considered as the non-dominant hemisphere. However, it is involved in many functions, including movement, language, cognition, and emotion. Therefore, because lesions on this side are usually not resected under awake mapping, there is a risk of unfavorable neurological outcomes. The goal of this study is to compare the functional and oncological outcomes of awake surgery (AwS) versus surgery under general anesthesia (GA) in supratentorial right-sided gliomas. A systematic review of the literature according to PRISMA guidelines was performed up to March 2023. Four databases were screened. Primary outcome to assess was return to work (RTW). Secondary outcomes included the rate of postoperative neurological deficit, postoperative Karnofsky Performance Status (KPS) score and the extent of resection (EOR). A total of 32 articles were included with 543 patients who underwent right hemisphere tumor resection under awake surgery and 294 under general anesthesia. There were no significant differences between groups regarding age, gender, handedness, perioperative KPS, tumor location or preoperative seizures. Preoperative and long-term postoperative neurological deficits were statistically lower after AwS (p = 0.03 and p < 0.01, respectively), even though no difference was found regarding early postoperative course (p = 0.32). A subsequent analysis regarding type of postoperative impairment was performed. Severe postoperative language deficits were not different (p = 0.74), but there were fewer long-term mild motor and high-order cognitive deficits (p < 0.05) in AwS group. A higher rate of RTW (p < 0.05) was documented after AwS. The EOR was similar in both groups. Glioma resection of the right hemisphere under awake mapping is a safer procedure with a better preservation of high-order cognitive functions and a higher rate of RTW than resection under general anesthesia, despite similar EOR.
Bone marrow stromal cells (BMSCs) can promote the growth of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Histone deacetylases (HDACs) play essential roles in the proliferation and apoptosis resistance of Ph + ALL cells. In our previous study, inhibiting histone deacetylase 1 (HDAC1) decreases the proliferation of Ph + ALL cells. However, little is known regarding how HDAC1 in BMSCs of Ph + ALL patients affects the imatinib (IM) resistance. Therefore, the present work examined the roles of HDAC1 in BMSCs. Overexpression of HDAC1 was found in BMSCs of Ph + ALL patients with IM resistance. In addition, the Ph + ALL cell line SUP-B15 was co-cultured with BMSCs after lentivirus transfection for regulating HDAC1 expression. Knockdown of HDAC1 within BMSCs elevated the IM-mediated SUP-B15 cell apoptosis, while increasing HDAC1 expression had an opposite effect. IL-6 in BMSCs, which is an important factor for the microenvironment-associated chemoresistance, showed evident up-regulation in HDAC1-upregulated BMSCs and down-regulation in HDAC1-downregulated BMSCs. While recombinant IL-6 (rIL-6) can reversed the sensitivity of SUP-B15 cells to IM induced by downregulating HDAC1 expression in BMSCs. HDAC1 showed positive regulation on IL-6 transcription and secretion. Moreover, IL-6 secretion induced by HDAC1 in BMSCs might enhance IM resistance in Ph + ALL cells. With regard to the underlying molecular mechanism, NF-κB, an important signal responsible for IL-6 transcription in BMSCs, mediated the HDAC1-regulated IL-6 expression. Collectively, this study facilitated to develop HDAC1 inhibitors based not only the corresponding direct anti-Ph + ALL activity but also the regulation of bone marrow microenvironment.
Controlled Transcranial Magnetic Stimulation (cTMS) will be delivered at 10 Hz, 1500 pulses targeting the hand representation of the left primary motor cortex. cTMS delivery will require \~9 min to complete. This intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.
The subject will be placed on 1.5x maintenance IVF with the fluids to which they are randomized. Fluid Management will be the intervention.
BACKGROUND: α-Tocopherol (αT) deficiency causes several neurologic disorders, such as spinocerebellar ataxia, peripheral neuropathy, and myopathy. Furthermore, decreased antibody production, impaired ex vivo T cell function, and elevated cytokine production are observed in humans and mice with αT deficiency. Although modeling αT deficiency in animals is challenging, αT depletion can be more readily achieved in α-tocopherol transfer protein-null (Ttpa-/-) mice than wild-type (WT) mice. Thus, the Ttpa-/- mouse model is a useful tool for studying metabolic consequences of low αT status. Optimizing this mouse model and selecting the reliable indicators/markers of deficiency are still needed.
OBJECTIVE: Our objective was to assess whether αT depletion alters lipopolysaccharide (LPS)-induced inflammatory response in the brain and/or grip strength used as a proxy for fatigue.
METHODS: WT and Ttpa-/- weanling littermates (n = 37-40/genotype) were fed an αT deficient diet ad libitum for 9 wk. Mice were then injected with LPS (10 μg/mouse) or saline (control) intraperitoneally and killed 4 h later. Concentrations of αT in diet and tissues were measured via high-pressure liquid chromatography. Grip strength was evaluated via a grip strength meter apparatus 2 d before and 3.5 h after LPS injection. Cerebellar and serum interleukin-6 (IL-6) concentrations were measured via enzyme-linked immunosorbent assay.
RESULTS: αT concentrations in the liver, heart, and adipose tissue of WT mice were higher than Ttpa-/- mice. Although αT was detected in the brain, muscle, and serum of WT mice, it was undetectable in these tissues of Ttpa-/- mice. Cerebellar and serum concentrations of IL-6 were increased in LPS-treated groups but were not significantly affected by genotype. Grip strength was reduced in LPS-treated groups, an effect that was more pronounced in Ttpa-/- mice.
CONCLUSIONS: Systemic LPS administration caused an acute inflammatory response with a concomitant decline in grip strength, especially in Ttpa-/- mice. αT depletion appears to exacerbate reductions in grip strength brought on by systemic inflammation.
PURPOSE: To compare the consistency of 3 instruments for sexual function evaluation in healthy young women before and after a pelvic floor muscle training. Methods: Thirty-one healthy young women were enrolled in an 8-week training program, consisting of bipedal exercises performed at home. The PERFECT and Peritron methods were used to estimate the efficacy of the intervention on pelvic muscles. Three questionnaires (FSFI, SQ-F and GRISS) were applied to assess sexual function. Both procedures were performed on three occasions: before, 4 and 8 weeks after the start of the training program. ANOVA for repeat measures and Tukey's post hoc were applied to analyze PERFECT and Peritron results, as well as individual domains and total scores of the questionnaires. The accuracy measured by the area under the ROC curve (AUC) for individual domains of each questionnaire and cross-validated pairwise comparison of the three instruments were also analyzed.
BACKGROUND: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity.
METHODS: We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro.
RESULTS: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model.
CONCLUSION: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.
Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.
There is a significant unmet medical need to develop new therapies aimed at preventing chronic recurrent hypoglycemia in congenital HI, the most common cause of persistent hypoglycemia in children. RZ358 is a human mAb that allosterically attenuates excessive insulin action on target cells. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as congenital HI. This is a Phase 2, multicenter, open label clinical study designed to assess the safety and efficacy of four progressively higher doses of RZ358 in separate groups of patients with hyperinsulinemic hypoglycemia due to Congenital HI, not adequately controlled with or without current standard of care. A screening period of up to 5 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered bi-weekly over 8 weeks, and then patients will complete a post-treatment follow-up period of 13 weeks.
Periodontal pockets that received periodontal debridement associated with placebo (members took with placebo 500 mg b.i.d. for 3 days).
All eligible mechanically ventilated patients, FiO2 titration and SpO2 goal range will be based on the correlation between SpO2 and arterial oxygen saturation (SaO2). E-alerts will be sent in the intervention arm as reminders for FiO2 titration.
Participants will receive subdermal injection of HAC20L to the nasolabial folds on Day 1 followed by an optional touch-up treatment on Day 30 if applicable. Participants will then be eligible to receive optional repeat treatment at Month 12 if applicable.
The disclosure is directed to apparatus and techniques that deliver an active agent, such as an antibiotic age nt or loosening agent to a patient by diffusion. An element of the medical device deployed proximate to the cells or host tissue includes a diffusible material, which comprises a lumen. An agent introduced into the lumen diffuses through the diffusible material to the cells or host tissue or tissues. The invention can be applied to medical devices that are placed partially inside a patient, as well as those that are fully implanted. Some embodiments support moving the internal element of a medical device proximate to targeted cells, such as a tumor, and administering an active agent to the targeted cells by diffusion. The disclosure also encompasses a testing system that helps test and develop apparatus and techniques for delivering an agent by diffusion.
Preparation

Prepare the solution for infusion, using aseptic technique, as follows: 

  * Reconstitute Kepivance lyophilized powder with Sterile Water for Injection, USP (not supplied) by slowly injecting 1.2 mL of Sterile Water for Injection, USP to yield a final concentration of 5 mg/mL. 
  * Swirl the contents gently during dissolution. Do not shake or vigorously agitate the vial. Dissolution of Kepivance can take up to 3 minutes. 
  * Visually inspect the solution for discoloration and particulate matter before administration. The reconstituted solution should be clear and colorless. Do not administer Kepivance if discoloration or particulates are observed. Do not filter the reconstituted solution during preparation or administration. Do not freeze the reconstituted solution. Protect from light. 



Administration

  * Administer Kepivance by intravenous bolus injection. If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after Kepivance administration [see Drug Interactions ( 7)]. 
  * The reconstituted solution contains no preservatives and is intended for single use only. Discard any unused portion. 
  * Following reconstitution, it is recommended that the product be used immediately. If not used immediately, the reconstituted solution of Kepivance may be stored refrigerated in its carton at 2° to 8°C (36° to 46°F) for up to 24 hours. 
  * Prior to injection, allow Kepivance to reach room temperature for a maximum of 1 hour protected from light. Discard Kepivance left at room temperature for more than 1 hour.
Currently, standard treatment of HIT involves the transition from a direct thrombin inhibitor (a type of anticoagulant or "blood thinner") to warfarin, a different type of anticoagulant. Direct thrombin inhibitors (DTIs) require IV administration and frequent blood draws for dose adjustments, which can lead to prolonged hospitalization. DTIs also affect blood test measurements, making it difficult to determine proper dosages of warfarin.

Fondaparinux is a drug that is approved by the FDA for the treatment of blood clots in deep veins and in the lungs. Fondaparinux is not FDA approved for the treatment of HIT. However, an increasing number of doctors are using fondaparinux instead of DTIs to treat HIT. Although fondaparinux appears to be more convenient and predictable than DTI medications, more research is needed to support its use as a treatment for HIT.
This pilot study will examine esophageal manometry in patients emerging from routine general anesthesia. Manometry of the esophagus is not a standard part of surgery or general anesthesia. The investigators will be using standard solid state high resolution manometry. One of the authors (JPC) evaluates all routine manometry for patients undergoing such procedures at both UCSF and SFGH. The use of manometry in patients recovering from anesthesia will permit the investigators to assess the recovery of a normal swallowing mechanism. An adequate determination of return of normal swallowing sequence is likely to determine the safe time for extubation. The investigators propose to, as a research study, investigate esophageal motor function using standard high resolution esophageal manometry in 10 patients recovering from general anesthesia. These studies are likely to document that the return of normal pharyngoesophageal function will coordinate with verbal commands to initiate swallowing. This pilot study will help clarify the precise timing of the return of normal function in the oropharynx and the proximal esophagus and thus determine the safe time for removal of the endotracheal or nasotracheal intubation.
BACKGROUND: Stress during pregnancy is detrimental to maternal health, pregnancy and birth outcomes and various preventive relaxation interventions have been developed. This systematic review and meta-analysis aimed to evaluate their effectiveness in terms of maternal mental health, pregnancy and birth outcomes.
METHOD: The protocol for this review is published on PROSPERO with registration number CRD42020187443. A systematic search of major databases was conducted. Primary outcomes were maternal mental health problems (stress, anxiety, depression), and pregnancy (gestational age, labour duration, delivery mode) and birth outcomes (birth weight, Apgar score, preterm birth). Randomized controlled trials or quasi-experimental studies were eligible. Meta-analyses using a random-effects model was conducted for outcomes with sufficient data. For other outcomes a narrative review was undertaken.
RESULT: We reviewed 32 studies comprising 3,979 pregnant women aged 18 to 40 years. Relaxation interventions included yoga, music, Benson relaxation, progressive muscle relaxation (PMR), deep breathing relaxation (BR), guided imagery, mindfulness and hypnosis. Intervention duration ranged from brief experiment (~10 minutes) to 6 months of daily relaxation. Meta-analyses showed relaxation therapy reduced maternal stress (-4.1 points; 95% Confidence Interval (CI): -7.4, -0.9; 9 trials; 1113 participants), anxiety (-5.04 points; 95% CI: -8.2, -1.9; 10 trials; 1965 participants) and depressive symptoms (-2.3 points; 95% CI: -3.4, -1.3; 7 trials; 733 participants). Relaxation has also increased offspring birth weight (80 g, 95% CI: 1, 157; 8 trials; 1239 participants), explained by PMR (165g, 95% CI: 100, 231; 4 trials; 587 participants) in sub-group analysis. In five trials evaluating maternal physiological responses, relaxation therapy optimized blood pressure, heart rate and respiratory rate. Four trials showed relaxation therapy reduced duration of labour. Apgar score only improved significantly in two of six trials. One of three trials showed a significant increase in birth length, and one of three trials showed a significant increase in gestational age. Two of six trials examining delivery mode showed significantly increased spontaneous vaginal delivery and decreased instrumental delivery or cesarean section following a relaxation intervention.
DISCUSSION: We found consistent evidence for beneficial effects of relaxation interventions in reducing maternal stress, improving mental health, and some evidence for improved maternal physiological outcomes. In addition, we found a positive effect of relaxation interventions on birth weight and inconsistent effects on other pregnancy or birth outcomes. High quality adequately powered trials are needed to examine impacts of relaxation interventions on newborns and offspring health outcomes.
CONCLUSION: In addition to benefits for mothers, relaxation interventions provided during pregnancy improved birth weight and hold some promise for improving newborn outcomes; therefore, this approach strongly merits further research.
Consistent CGM use in youth with T1D has been difficult to sustain historically. Youth with T1D and their families have routinely felt burden related to the introduction of this technology into their care management. Additionally, there can be difficulties with calibration, skin irritation, frequent skips, excessive or nuisance alarms and inaccurate readings which often lead to diminished use or discontinuation entirely. The purpose of this protocol is to implement and evaluate a family-focused behavioral teamwork intervention aimed at overcoming barriers to sustained CGM use in youth with T1D. In this 2-year RCT, we will assess the long-term acceptability and durability of CGM use and its associated glycemic and psychological outcomes in youth with T1D and their families. We will randomize 120 families to one of two groups: (1) CGM implemented according to usual care (CGM-Usual Care, CGM-UC) or (2) CGM implemented with a family teamwork intervention (CGM-Teamwork, CGM-TW). This intervention will allow participants and families to overcome barriers to sustained CGM use and achieve glycemic benefits that have been afforded to adults using CGM as demonstrated in other research. In year 1, all CGM supplies will be provided and covered by study resources. In year 2, study participants will be asked to cover the costs associated with sensor use and any costs associated with replacement of CGM components in a manner consistent with routine clinical care as the investigators believe that it is important to assess durability of CGM use in clinical practice.