anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: The clinically high comorbidity between polycystic ovary syndrome (PCOS) and breast cancer (BC) has been extensively reported. However, limited knowledge exists regarding their shared genetic basis and underlying mechanisms.
METHOD: Leveraging summary statistics from the largest genome-wide association studies (GWASs) to date, we conducted a comprehensive genome-wide cross-trait analysis of PCOS and BC. A variety of genetic statistical methods were employed to uncover potential shared genetic causes.
RESULTS: Our analysis revealed genetic overlap between the three trait pairs. After partitioning the genome into 2,495 independent regions, we identified two loci, chr8: 75,011,700-76,295,483 and chr17: 6,305,079-7,264,458, with significant localized genetic correlations. Pleiotropic analysis under a composite null hypothesis identified 1,183 significant pleiotropic single nucleotide polymorphisms (SNPs) across three trait pairs. FUMA mapped 26 pleiotropic loci, with regions 16q12.2 and 6q25.1 duplicated across all three trait pairs, while COLOC detected three loci with colocalization evidence. Gene-based analysis identified 23 unique candidate pleiotropic genes, including the FTO shared by all trait pairs, as well as SER1, RALB, and others in two trait pairs. Pathway enrichment analysis further highlighted key biological pathways, primarily involving the significant biological pathways were the metabolism of regulation of autophagy, regulation of cellular catabolic process, and positive regulation of catabolic process. Latent Heritable Confounder Mendelian randomization (LHC-MR) supported a positive causal relationship between PCOS and both BCALL and ERPBC but not with ERNBC.
CONCLUSION: In conclusion, our genome-wide cross-trait analysis identified a shared genetic basis between PCOS and BC, specific identical genetic mechanisms and causality between PCOS and various BC subtypes, which could better explains the genetics of the co-morbidity of PCOS and ERPBC rather than PCOS and ERNBC. These findings provide new insights into the biological mechanisms underlying the co-morbidity of these two complex diseases, which have important implications for clinical disease intervention, treatment, and improved prognosis.
The present invention discloses a medical preparation which improves blood perfusion of the spongy body to treat male dysfunction (impotence) by the function of vasodilation, particularly an orally disintegrating tablet preparation of phentolamine mesylate and a preparation technology thereof. The present invention aims to make up the defects of the existing preparation of phentolamine mesylate used for treating impotence and provide an orally disintegrating tablet of phentolamine mesylate which has the advantages of rapid absorption, high biological availability, little residue in the intestinal tract, low side effect, first pass effect avoidance to the liver and convenient administration, and a preparation technology thereof for patients and medical workers. Phentolamine mesylate is adopted as a raw material, and bulk additive, disintegrating agents, corrigent, flow aid, lubricating agents, etc. as auxiliary materials. According to different situations, capsule wall materials or coating materials can be used, or a right amount of effervescent can be added according to the situation. The preparation process is carried out by a specific preparation method. A tabletting process is carried out by a tabletting machine, and the orally disintegrating tablet of phentolamine mesylate can be obtained.
Cerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cerebellar tDCS vs. cerebellar tACS in patients with neurodegenerative ataxia, we performed a double-blind, randomized, sham controlled, triple cross-over trial with cerebellar tDCS, cerebellar tACS or sham stimulation in twenty-six participants with neurodegenerative ataxia. Before entering the study, each participant underwent motor assessment with wearable sensors considering gait cadence (steps/minute), turn velocity (degrees/second) and turn duration (seconds), and a clinical evaluation with the scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). After each intervention, participants underwent the same clinical assessment along with cerebellar inhibition (CBI) measurement, a marker of cerebellar activity. The gait cadence, turn velocity, SARA, and ICARS significantly improved after both tDCS and tACS, compared to sham stimulation (all p<0.010). Comparable effects were observed for CBI (p<0.001). Overall, tDCS significantly outperformed tACS on clinical scales and CBI (p<0.01). A significant correlation between changes of wearable sensors parameters from baseline and changes of clinical scales and CBI scores was detected. Cerebellar tDCS and cerebellar tACS are effective in ameliorating symptoms of neurodegenerative ataxias, with the former being more beneficial than the latter. Wearable sensors may serve as rater-unbiased outcome measures in future clinical trials. ClinicalTrial.gov Identifier: NCT05621200.
In a method of treating pain, a patient is administered a pharmaceutical composition of 6-hydroxy oxymorphone in an amount sufficient to induce analgesia. In one embodiment, the pharmaceutical composition is administered orally. Any known or later developed method of oral delivery may be used. To achieve the desired analgesic effect, blood plasma levels of 6-hydroxy oxymorphone are raised to at least approximately 0.2 ng/mL. Most preferably blood plasma levels of 6-hydroxy oxymorphone range at least 0.3 ng/mL during treatment. Administration of compositions containing 6-hydroxy oxymorphone, and one or more carriers, diluents, and excipients in an amount sufficient to induce analgesia is also contemplated.
OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression.
METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression.
RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients.
CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.
Chronic hypertension leads to injury and fibrosis in major organs. Fibroblast activation protein (FAP) is one of key molecules in tissue fibrosis, and 68Ga-labeled FAP inhibitor-46 (FAPI46) PET is a recently developed method for evaluating FAP. The aim of this study was to evaluate FAP expression and fibrosis in a hypertension model and to test the feasibility of 68Ga-FAPI46 PET in hypertension. Methods: Hypertension was induced in mice by angiotensin II infusion for 4 wk. 68Ga-FAPI46 biodistribution studies and PET scanning were conducted at 1, 2, and 4 wk after hypertension modeling, and uptake in the major organs was measured. The FAP expression and fibrosis formation of the heart and kidney tissues were analyzed and compared with 68Ga-FAPI46 uptake. Subgroups of the hypertension model underwent angiotensin receptor blocker administration and high-dose FAPI46 blocking, for comparison. As a preliminary human study, 68Ga-FAPI46 PET images of lung cancer patients were analyzed and compared between hypertension and control groups. Results: Uptake of 68Ga-FAPI46 in the heart and kidneys was significantly higher in the hypertension group than in the sham group as early as week 1 and decreased after week 2. The uptake was specifically blocked in the high-dose blocking study. Immunohistochemistry also revealed FAP expression in both heart and kidney tissues. However, overt fibrosis was observed in the heart, whereas it was absent from the kidneys. The angiotensin receptor blocker-treated group showed lower uptake in the heart and kidneys than did the hypertension group. In the pilot human study, renal uptake of 68Ga-FAPI46 significantly differed between the hypertension and control groups. Conclusion: In hypertension, FAP expression is increased in the heart and kidneys from the early phases and decreases over time. FAP expression appears to represent fibrosis activity preceding or underlying fibrotic tissue formation. 68Ga-FAPI46 PET has potential as an effective imaging method for evaluating FAP expression in progressive fibrosis by hypertension.
BACKGROUND: Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear.
METHODS: We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets.
RESULTS: Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential.
CONCLUSION: Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.
The aim of the JMAC study, an international multicenter Randomized Controlled Trial, is to assess the effectiveness and safety of JointRep®, a second-generation chitosan-based hydrogel for cartilage repair. A total of 185 subjects will be randomized 2:1 to either Microfracture plus JointRep® or Microfracture alone. The follow up will be at 24 months, with a planned interim analysis at 12 months. The primary endpoint is an objectively measured structural one (quantity of new cartilaginous tissue, assessing the percentage of fill) and it will be blindly assessed using a quantitative MRI at 12 and 24 months. Two of the secondary endpoints are also structurally based and blindly measured: quality of the new tissue, quantifying the T2 (which measures the Collagen 2 content and orientation as well as degree of hydration); the upper and lower half of the new tissue T2 measurement will depict the degree of stratification of the new cartilaginous tissue. A semiquantitative MOCART-2 blinded analysis will also be carried out. The clinical outcomes will be measured using KOOS and Tegner, as well as a VAS and an EQ-5 questionnaire. All the secondary endpoints will be analyzed at the same 12 and 24 months timepoints. In addition, subject safety will be assessed through a record of adverse events.
Regulatory B cell (Breg) and gut microbiome treatment can prolong the survival of heart transplant recipient mice, prevent heart transplant rejection, and gut microbiome can enhance the protective effect of Breg on heart transplant rejection. According to the invention, by constructing an allogeneic heart transplantation mouse model, the survival time of a heart transplantation receptor mouse can be remarkably prolonged by virtue of two modes, namely, intravenous injection of Breg separated from spleen and intragastric perfusion for supplementing donor intestinal microorganisms. Breg by reduction of IFN-. Gamma.  +  IL‑2  +  CD4  +  T cells and increased CD4  +  CD25  +  Foxp3  +  T cell induction of transplant tolerance, co-treatment of donor intestinal microbes and BregThe curative effect is obviously better than that of single treatment of Breg. The invention provides a novel method for treating the immunological rejection of heart transplantation, and the invention has practical application value.
Two dose levels of MYCAMINE were evaluated in a randomized, double-blind study to determine the efficacy and safety versus caspofungin in patients with invasive candidiasis and candidemia. Patients were randomized to receive once daily intravenous infusions (IV) of MYCAMINE, either 100 mg/day or 150 mg/day or caspofungin (70 mg loading dose followed by 50 mg maintenance dose). Patients in both study arms were permitted to switch to oral fluconazole after at least 10 days of intravenous therapy, provided they were non-neutropenic, had improvement or resolution of clinical signs and symptoms, had a Candida isolate which was susceptible to fluconazole, and had documentation of 2 negative cultures drawn at least 24 hours apart. Patients were stratified by APACHE II score (20 or less or greater than 20) and by geographic region. Patients with Candida endocarditis were excluded from this analysis. Outcome was assessed by overall treatment success based on clinical (complete resolution or improvement in attributable signs and symptoms and radiographic abnormalities of the Candida infection and no additional antifungal therapy) and mycological (eradication or presumed eradication) response at the end of IV therapy. Deaths that occurred during IV study drug therapy were treated as failures. 

In this study, 111/578 (19.2%) of the patients had baseline APACHE II scores of greater than 20, and 50/578 (8.7%) were neutropenic at baseline (absolute neutrophil count less than 500 cells/mm3). Outcome, relapse and mortality data are shown for the recommended dose of MYCAMINE (100 mg/day) and caspofungin in Table 9. 

In two cases of ophthalmic involvement assessed as failures in the above table due to missing evaluation at the end of IV treatment with MYCAMINE, therapeutic success was documented during protocol-defined oral fluconazole therapy.
TENORETIC may potentiate the action of other antihypertensive agents used concomitantly. Patients treated with TENORETIC plus a catecholamine depletor (e.g., reserpine) should be closely observed for evidence of hypotension and/or marked bradycardia which may produce vertigo, syncope or postural hypotension.

Calcium channel blockers may also have an additive effect when given with TENORETIC. (See WARNINGS.)

Disopyramide is a Type I antiarrhythmic drug with potent negative inotropic and chronotropic effects. Disopyramide has been associated with severe bradycardia, asystole and heart failure when administered with beta-blockers.

Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with beta-blockers.

Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the therapeutic effectiveness of norepinephrine. Thiazides may increase the responsiveness to tubocurarine.

Concomitant use of prostaglandin synthase inhibiting drugs, e.g., indomethacin, may decrease the hypotensive effects of beta-blockers.

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read prescribing information for lithium preparations before use of such preparations with TENORETIC.

Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta-blocker should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.

While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Patients with limited-stage SCLC receive etoposide and cisplatin (carboplatin) for 2 cycles and then receive thoracic radiotherapy (45 Gy/30 fractions) with concurrent EP/EC chemotherapy for 2cycles. Patients who achieve CR or PR then receive prophylactic cranial irradiation (PCI, 25 Gy/10 fractions).
In this work, a fluorescent probe TPB-Cys derived from triphenylamine-benzofuranone was developed for monitoring the cysteine (Cys) level and imaging in living pulmonary cells under hypercapnia condition. A systematic hypoxia module was tried to cover both the in-solution test and pulmonary cellular imaging. The hypoxia condition did not obviously affect the fluorescence response signal during the in-solution test. The fluorescence signal at 540 enhanced in a dose-dependent enhancement along with the increase of the Cys concentration. The probe showed the advantages including relatively long linear range, high sensitivity, high stability, and high selectivity. With low cyto-toxicity, TPB-Cys achieved the monitoring of the endogenous Cys level in living pulmonary cells. Furthermore, it also realized the visualization of the affection of the hypoxia and hypoxia recovered conditions. This work was informative for both the accurate diagnosis and potential medical techniques.
The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a Staphylococcus aureus (S. aureus) infection. The influence of host-pathogen interactions on disease progression remains unclear. It is important to note that S. aureus infections following an HAdV-3E infection are frequently observed in clinical settings, yet the underlying susceptibility mechanisms are not fully understood. This study utilized an A549 cell model to investigate secondary infection with S. aureus following an HAdV-3E infection. The findings suggest that HAdV-3E exacerbates the S. aureus infection by intensifying lung epithelial cell damage. The results highlight the role of HAdV-3E in enhancing the interferon signaling pathway through RIG-I (DDX58), resulting in the increased expression of interferon-stimulating factors like MX1, RSAD2, and USP18. The increase in interferon-stimulating factors inhibits the NF-κB and MAPK/P38 pro-inflammatory signaling pathways. These findings reveal new mechanisms of action for HAdV-3E and S. aureus in secondary infections, enhancing our comprehension of pathogenesis.
Age-related hearing loss is the third-most common chronic condition affecting older adults in the US (data from Healthy People 2020 US Dept of Health and Human Services). This study aims to improve the understanding of attitudes, barriers and facilitators needed to improve hearing health care delivery. Two study cohorts of study participants between the ages of 65 - 75 are proposed.

The first cohort of participants include healthy adults being seen by a primary care provider (PCP) for a routine appointment. Each participating primary care practice is assigned to one of three different telephone hearing screening strategies that include progressive levels of PCP time and guidance to complete telephone-based hearing screening. Those who fail a telephone hearing screening go on to a medical referral study and receive (1) diagnostic audiological testing and (2) determination of the reliability and validity of identification of conditions that should require medical referral prior to hearing aid provision (called FDA 'Red Flag' conditions, including conditions such as sudden hearing loss, cerumen impaction, conductive hearing loss, dizziness, external deformity, ear drainage). We will evaluate the proportion of subjects in Groups 1 and 2 who dial the phone number and complete the telephone hearing test at or within two months of their PCP visit, relative to Group 3, and the proportion of subjects in all groups who: a) schedule and b) complete the visit for diagnostic audiological testing, and subsequently, c) complete a plan for appropriate hearing loss intervention, if indicated, within four months of initial hearing screening. Enrollment in this cohort is complete. 955 subjects were screened for eligibility. Of those, 660 patients were enrolled.

The second cohort includes adults who are being seen for a routine appointment for a complaint of hearing loss at one of several participating Ear, Nose, and Throat (ENT) practices in the CHEER network. Information about Red Flag conditions will be obtained from the patient, audiologist, and ENT provider. This information, along with Red Flag data from the PCP Cohort, will be used to evaluate the accuracy of assessment of medical conditions for which the FDA requires physician evaluation and management prior to hearing aid fitting, and determine which medical conditions should require medical evaluation prior to hearing aid fitting. Enrollment in this cohort is ongoing. The anticipated enrollment goal is 500 subjects.