anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common, chronic, and debilitating condition in women. The underlying cause of IC/BPS remains unknown. We recently published the first functional magnetic resonance imaging (fMRI) study comparing brain function in women with IC/BPS to healthy women. We found that women with IC/BPS have altered resting activity in supplementary motor area (SMA). Specifically, these changes appear in a part of SMA that we have shown to control pelvic floor muscle activity. We call this part of SMA "pelvic-SMA". Our results provide the first potential explanation for extensive published reports of increased pelvic floor muscle activity in women with IC/BPS. We hypothesize that we are observing evidence of an important theory of chronic pain: motor cortical changes occur that are initially beneficial to increase protective muscle activity but are ultimately maladaptive and perpetuate pain. If this theory is true, it should be possible to reduce pain and muscle activity by improving brain activity. The proposed work is to do exactly that. Using non-invasive repetitive transcranial magnetic stimulation (rTMS) directed at pelvic-SMA, we aim to determine if we can reduce pain (Aim 1), improve resting brain activity (fMRI) and resting pelvic floor muscle electromyographic (EMG) activity in IC/BPS (Aim 2), and to link the pain reductions to fMRI/EMG improvements to develop a causal mediation model of IC/BPS symptoms (Aim 3). We will recruit 50 women with IC/BPS to participate in the study, and participants will be randomized to 2 groups of 25: high-frequency (active) or sham (inert). Our preliminary data suggest that high-frequency stimulation is the best stimulation protocol for reducing pain and improving pelvic-SMA activity and resting pelvic floor muscle activity. Our preliminary results agree with a large body of literature suggesting that high-frequency rTMS applied to motor cortex is the best stimulus paradigm to reduce pain, but our proposed work has the potential to greatly innovate the field of non-invasive brain stimulation for pain by providing a mechanism by which the stimulation can improve deficiencies in motor function in chronic pain patients.
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins (see PRECAUTIONS: Drug Interactions and Drug-Laboratory Test Interactions). Thyroid hormones do not readily cross the placental barrier (see PRECAUTIONS: Pregnancy).
Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B).
PURPOSE: Recent literature suggests that tinnitus can impact cognition, but results were varied due to a diversity in investigated aspects of cognition and utilized tests, as well as the possible influence of confounding factors. The purpose of this study was to assess the impact of tinnitus loudness on cognition by use of a within-subjects design in patients with a cochlear implant (CI). In this population, tinnitus loudness can be modulated by switching the CI on or off as CI is known to highly suppress tinnitus.
METHODS: A total of 18 CI users completed two versions of the Repeatable Battery for Assessment of Neuropsychological Status for Hearing Impaired individuals (RBANS-H), once in unaided condition and once in best aided condition. Tinnitus suppression was defined as a difference in score on a visual-analogue scale (VAS) of at least one point out of ten between these two conditions.
RESULTS: No significant differences in RBANS-H scores were found between the suppression and no suppression group, nor for the suppression group alone. No significant correlations between tinnitus loudness and RBANS-H were found, neither for the suppression group alone, nor for the group as a whole.
CONCLUSION: The current study shows no significant effect of tinnitus loudness on cognition, which contradicts previous literature. This discrepancy could be explained by the use of a within-subjects design, which controls for confounding factors. Future research should include a larger and more diverse study sample to draw definitive conclusions on this topic.
Weight loss was noted in nude mice treated with cerulenin, a non-competitive inhibitor of FAS. Sustained reduction of adipocyte mass in humans without toxicity would significantly impact disease prevention worldwide. Aside from psychological and self-esteem improvement, weight loss via reduction of adipocyte mass may: (1) ameliorate hyperglycemia associated with non-insulin-dependent diabetes mellitus thereby reducing diabetic complications such as arterial disease, blindness, cataracts, etc., (2) reduce hypertension, (3) reduce risk of coronary artery vascular disease and stroke, and (4) reduce the risk of other complications of massive obesity such as osteoarthritis, surgical complications, etc. There is also potential use in livestock and poultry to reduce the saturated fat content of meat products. Therefore FAS inhibitors are disclosed herein as novel agents for weight reduction. A family of compounds (η-substituted-α-methylene-β-carboxy-η-butyrolactones) whose synthesis was based on the cerulenin motif is shown herein to inhibit fatty acid synthesis, inhibit growth in certain susceptible tumor cells, and induce weight loss.
Sevoflurane (n=29) was compared to isoflurane (n=27) in ASA Class I or II patients for the maintenance of anesthesia during cesarean section. Newborn evaluations and recovery events were recorded. With both anesthetics, Apgar Score averaged 8 and 9 at 1 and 5 minutes, respectively.

Use of sevoflurane as part of general anesthesia for elective cesarean section produced no untoward effects in mother or neonate. Sevoflurane and isoflurane demonstrated equivalent recovery characteristics. There was no difference between sevoflurane and isoflurane with regard to the effect on the newborn, as assessed by Apgar score and Neurological and Adaptive Capacity Score (average=29.5). The safety of sevoflurane in labor and vaginal delivery has not been evaluated.
Background: Individuals with chronic obstructive pulmonary disease (COPD) are often at risk for or have comorbid cardiovascular disease and are likely to die of cardiovascular-related causes. Objectives: To prioritize a list of research topics related to the diagnosis and management of patients with COPD and comorbid cardiovascular diseases (heart failure, atherosclerotic vascular disease, and atrial fibrillation) by summarizing existing evidence and using consensus-based methods. Methods: A literature search was performed. References were reviewed by committee co-chairs. An international, multidisciplinary committee, including a patient advocate, met virtually to review evidence and identify research topics. A modified Delphi approach was used to prioritize topics in real time on the basis of their potential for advancing the field. Results: Gaps spanned the translational science spectrum from basic science to implementation: 1) disease mechanisms; 2) epidemiology; 3) subphenotyping; 4) diagnosis and management; 5) clinical trials; 6) care delivery; 7) medication access, adherence, and side effects; 8) risk factor mitigation; 9) cardiac and pulmonary rehabilitation; and 10) health equity. Seventeen experts participated, and quorum was achieved for all votes (>80%). Of 17 topics, ≥70% agreement was achieved for 12 topics after two rounds of voting. The range of summative Likert scores was -15 to 25. The highest priority was "Conduct pragmatic clinical trials with patient-centered outcomes that collect both pulmonary and cardiac data elements." Health equity was identified as an important topic that should be embedded within all research. Conclusions: We propose a prioritized research agenda with the purpose of stimulating high-impact research that will hopefully improve outcomes among people with COPD and cardiovascular disease.
Colonoscopy is an integral part of the lower bowel care and is generally considered a potentially safe diagnostic and therapeutic procedure performed as a daycare outpatient procedure. Colonoscopy is associated with different complications that are not limited to adverse events related to the bowel preparation solutions used, the sedatives used, but to the procedure related as well including bleeding and perforation. Injuries to the extra-luminal abdominal organs during colonoscopy are uncommon, however, serious complications related to the procedure have been reported infrequently in the literature. Life threatening injuries to the spleen, liver, pancreas, mesentery, and urinary bladder have been reported as early as in mid-1970s. These injuries should not be overlooked by clinicians and endoscopists. Steadily increasing abdominal pain, abdominal distension, and hemodynamic instability in absence of rectal bleeding should raise the possibility of severe organ injury. Splenic and hepatic injury following colonoscopy are usually serious and may be life threatening. Although conservative management may help, yet they usually need interventional radiology or surgical intervention. Acute pancreatitis following colonoscopy is usually mild and is mostly managed conservatively. The mechanism of abdominal organ injuries during colonoscopy is not fully understood, however many risk factors have been identified, which can be classified as- organ related, procedure related, and local abdominal factors. Difficult colonoscopy and prior intra-abdominal adhesions are probably the most relevant risk factors for these injuries. Left lateral position, avoidance of looping and excessive force during the procedure would probably reduce the risk of such injuries.
Prolonged lead (Pb) exposure impairs human health due to its interference with physiological and biochemical processes. Therefore, it is necessary to investigate natural therapeutics to alleviate Pb-induced intoxication. In the current investigation, essential oil extracted from the fresh bulbs of Allium sativum was considered as a natural remedy. Initially, in vitro antioxidant and anti-inflammatory activity of A. sativum essential oil (ASEO) were explored. The results reported that ASEO exhibits potent antioxidant and anti-inflammatory potential. Additionally, an in vivo study was conducted to elucidate its preventive role against Lead-nitrate (LN)-induced hepatic damage in Swiss albino mice. The experimental mice were allocated into six groups: Control, LN-intoxicated group (50 mg/kg), LN + ASEO (50 mg/kg), LN + ASEO (80 mg/kg), LN + Silymarin (25 mg/kg), and LN + vehicle oil control group. The entire duration of the study was of 30 days. From the results, it was determined that LN exposure elevated the Pb content in hepatic tissues which subsequently increased the serum biomarkers, inflammatory cytokines (NF-kB, TNF-α, IL-6) as well as apoptotic factors (caspase-3, BAX), all of which contribute to DNA damage. Meanwhile, it reduced anti-inflammatory (IFN-γ and IL-10) and anti-apoptotic factors (Bcl-2). Furthermore, Pb accumulation in hepatic tissues changed the histological architecture, which was linked to necrosis, central vein dilation, inflammatory cell infiltration and Kupffer cell activation. In contrast to this, ASEO administration decreased the Pb content, which in turn reduced the level of serum biomarkers, inflammatory and apoptotic factors. At the same time, it increased the anti-inflammatory and anti-apoptotic factors, thereby reduced DNA damage and restored the hepatic histology. In conclusion, exhaustive research is of the utmost demand to elucidate the precise defense mechanisms of ASEO against LN-induced hepatotoxicity.
Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.
Provided are anti-wrinkle agents having a novel parent nucleus that are suitable as components for external skin preparations such as cosmetics. The anti-wrinkle agents comprise compounds represented by general formula (1), stereoisomers thereof, or pharmacologically permissible salts thereof. Said anti-wrinkle agents have excellent efficacy in improving wrinkles and sagging that occur as a result of photoaging due to ultraviolet ray exposure that is skin aging with increased age. [In the formula, R1 represents a hydrogen atom or a 1- to 8-carbon straight or branched alkyl group. R2 represents -SH, -SO3H, -S-S-X1, -S-X2, -SO-X3, -SO2-X4, -SO2-NY1-X5 or -SO2-NY2-Y3. X1-X5 independently are hydrogen atoms or 1- to 8-carbon aliphatic hydrocarbon groups or 5- to 12-carbon aromatic parts wherein carbon atoms may be substituted with heteroatoms. Y1-Y3 independently represent hydrogen atoms or 1- to 8-carbon straight or branched alkyl groups. R3 represents a hydrogen atom or acyl group having a 1- to 8-carbon straight or branched alkyl chain. R4 represents a 5- to 12-carbon aromatic group or polycyclic condensed aromatic group that may have unsubstituted or substituted groups. m represents an integer 0-3 and n represents an integer 1 or 2.]
One treatment cycle of 131I-omburtamab consists of one dosimetry dose (2 mCi ) (for subjects enrolled on Version 1-7 of Protocol 101) and one treatment dose (50 mCi) for up to 2 cycles of length 5 weeks (for subjects enrolled on Version 1-7 of Protocol 101) or 4 weeks (for subject enrolled after Version 7 of Protocol 101). For Japan only, the first cycle consisted of one dosimetry dose (2 mCi ) week 1 one treatment dose (50 mCi) week 2. If eligible a second cycle of 50 mCi 131I-omburtamab was given at week 6. For subjects below 3 and 1 years of age, the treatment dose was reduced by 33% and 50%, respectively.
Long-term high-fat diet (HFD) will induce dysbiosis and a disturbance of intestinal homeostasis. Large yellow tea polysaccharide (LYP) has been shown to improve obesity-associated metabolic disease via modulation of the M2 polarization. However, the contribution of LYP to intestinal barrier impairment and improvement mechanisms in obesity caused by an HFD are still not clear. In this study, we evaluated the impacts of LYP on the mucosal barrier function and microbiota composition in HFD-feeding mice. Results exhibited that dietary LYP supplement could ameliorate the physical barrier function via maintaining intestinal mucosal integrity and elevating tight-junction protein production, strengthen the chemical barrier function via up-regulating the levels of glucagon-like peptide-1 and increasing mucin-producing goblet cell numbers, and enhance the intestinal immune barrier function though suppressing immune cell subsets and cytokines toward pro-inflammatory phenotypes. Moreover, LYP reshaped the constitution and metabolism of intestinal flora by enriching probiotics that produce short-chain fatty acids. Overall, LYP might be used as a critical regulator of intestinal homeostasis to improve host health by promoting gut barrier integrity, modulating intestinal immune response, and inhibiting bowel inflammation.
As life expectancy continues to increase, age-related kidney diseases are becoming more prevalent. Chronic kidney disease (CKD) is not only a consequence of aging but also a potential accelerator of aging process. Here we report the pivotal role of podocyte ERCC1, a DNA repair factor, in maintaining glomerular integrity and a potential effect on multiple organs. Podocyte-specific ERCC1-knockout mice developed severe proteinuria, glomerulosclerosis, and renal failure, accompanied by a significant increase in glomerular DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). ERCC1 gene transfer experiment in the knockout mice attenuated proteinuria and glomerulosclerosis with reduced DNA damage. Notably, CD44+CD8+ memory T cells, indicative of T-cell senescence, were already elevated in the peripheral blood of knockout mice at 10 weeks old. Additionally, levels of senescence-associated secretory phenotype (SASP) factors were significantly increased in both the circulation and multiple organs of the knockout mice. In older mice and human patients, we observed an accumulation of DSBs and an even greater buildup of SSBs in glomeruli, despite no significant reduction in ERCC1 expression with age in mice. Collectively, our findings highlight the crucial role of ERCC1 in repairing podocyte DNA damage, with potential implications for inflammation in various organs.
This study aims to associate the incidence of postoperative vasoplegia and short-term survival to the implantation of various left ventricular assist devices differing in hemocompatibility and flow profiles. The overall incidence of vasoplegia was 25.3% (73/289 patients) and 30.3% (37/122), 25.0% (18/72), and 18.9% (18/95) in the axial flow (AXF), centrifugal flow (CF), and centrifugal flow with artificial pulse (CFAP) group, respectively. Vasoplegia was associated with longer intensive care (ICU) and hospital length of stay (LOS) and mortality. ICU and in-hospital LOS and 1-year mortality were the lowest in the CFAP group. Post hoc analysis resulted in a p-value of 0.43 between AXF and CF; 0.35 between CF and CFAP; and 0.06 between AXF and CFAP. Although there is a trend in diminished incidence of vasoplegia, pooled logistic regression using flow profile and variables that remained after feature selection showed that flow profile was not an independent predictor for postoperative vasoplegia.
PURPOSE: Hemipelvis reduction in the setting of AO/OTA 61-C1.2 (APC3) pelvic injuries can be challenging. A common strategy is to provisionally reduce or fix the anterior ring prior to definitive fixation of the posterior ring. In this scenario, it is difficult to assess whether residual sacroiliac joint (SIJ) widening is due to hemipelvis flexion/extension or lateral displacement. This simulation sought to identify a radiographic marker for posterior ilium flexion or extension malreduction in the setting of a reduced anterior ring.
METHODS: Symphyseal and both anterior and posterior SIJ ligaments were cut in 8 cadaveric pelvis. The symphysis was reduced and wired. One centimeter of posterior flexion or extension at the SIJ was created to mimic the clinical scenario of hemipelvis flexion or extension malreduction, and a lateral compressive force was applied. SIJ widening and the direction of anterior or posterior ileal displacement relative to the contralateral joint were assessed via inlet views. SIJ widening and the direction of cranial or caudal ileal displacement were assessed using outlet views. Comparisons between flexion and extension models used Fisher's exact test.
RESULTS: On outlet views, all flexed hemipelvis demonstrated caudal ileal translation at the superior SIJ, in contrast to all extended hemipelvis demonstrated cranial translation (p < 0.0005); the scenarios were easily distinguishable. Conversely, inlet imaging was unable to identify the direction of malreduction. Flexion/extension scenarios resulted in similar amounts of SIJ widening.
CONCLUSION: Residual flexion and extension hemipelvis malreductions in APC3 injuries after provisional anterior fixation can be differentiated by the direction of ileal displacement at the superior SIJ on the outlet view.
Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.