anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Fluorescent nucleobase surrogates capable of Watson-Crick hydrogen bonding are essential probes of nucleic acid structure and dynamics. Their limited brightness and short absorption and emission wavelengths have rendered them unsuitable for single-molecule detection. Herein, we synthesized a new tricyclic pyrimidine nucleoside analogue with a push-pull conjugated system. The resulting C-linked 8-(diethylamino)benzo[b][1,8] naphthyridin-2(1H)-one nucleoside (ABN), exhibits ε442=20,000 M−1 cm−1 and Φem,540=0.39 in water, increasing to Φem=0.50-0.53 when base paired with adenine in duplex DNA oligonucleotides. Single-molecule fluorescence measurements of ABN using both one-photon and two-photon excitation demonstrate its excellent photostability and indicate that the nucleoside is present to >95% in a bright state with count rates of at least 15 kHz per molecule. This new fluorescent nucleobase analogue, which, in duplex DNA, is the brightest and most red-shifted known, is first to offer robust single-molecule fluorescence detection capabilities.
The renin-angiotensin-aldosterone system (RAAS) is a crucial regulator of the cardiovascular system and a target for widely used therapeutic drugs. Dysregulation of RAAS, implicated in prevalent diseases like hypertension and heart failure, has recently gained attention in oncological contexts due to its role in tumor biology and cardiovascular toxicities (CVTs). Thus, RAAS inhibitors (RAASi) may be used as potential supplementary therapies in cancer treatment and CVT prevention. Oncological treatments have evolved significantly, impacting patient survival and safety profiles. However, they pose cardiovascular risks, necessitating strategies for mitigating adverse effects. The main drug classes used in oncology include anthracyclines, anti-HER2 therapies, immune checkpoint inhibitors (ICIs), and vascular endothelial growth factor (VEGF) signaling pathway inhibitors (VSPI). While effective against cancer, these drugs induce varying CVTs. RAASi adjunctive therapy shows promise in enhancing clinical outcomes and protecting the cardiovascular system. Understanding RAAS involvement in cancer and CVT can inform personalized treatment approaches and improve patient care.
The pharmacodynamic effects of ONPATTRO were evaluated in hATTR amyloidosis patients treated with 0.3 mg/kg ONPATTRO via intravenous infusion once every 3 weeks.

Mean serum TTR was reduced by approximately 80% within 10 to 14 days after a single dose. With repeat dosing every 3 weeks, mean reductions of serum TTR after 9 and 18 months of treatment were 83% and 84%, respectively. The mean maximum reduction of serum TTR over 18 months was 88%. Similar TTR reductions were observed regardless of TTR mutation, sex, age, race, or prior liver transplantation. In a dose-ranging study, greater TTR reduction was maintained over the dosing interval with the recommended dosing regimen of 0.3 mg/kg every 3 weeks compared to 0.3 mg/kg every 4 weeks.

Serum TTR is a carrier of retinol binding protein, which is involved in the transport of vitamin A in the blood. Mean reductions in serum retinol binding protein of 45% and serum vitamin A of 62% were observed over 18 months [see Warnings and Precautions (5.2)].
Objectives: This study aimed to evaluate the joint effects of multiple air pollutants including PM2.5, PM10, NO2, and NOx with dementia and examined the modifying effects of genetic susceptibility. Methods: This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance weighted meta-analyses were performed to create a pooled effect. The modifying effect of genetic susceptibility on air pollution score was assessed by genetic risk score and APOE ε4 genotype. Results: The HR (95% CI) of dementia for per interquartile range increase of air pollution score was 1.13 (1.07∼1.18). Compared with the lowest quartile (Q1) of air pollution score, the HR (95% CI) of Q4 was 1.26 (1.13∼1.40) (P trend = 2.17 × 10-5). Participants with high air pollution score and high genetic susceptibility had higher risk of dementia compared to those with low air pollution score and low genetic susceptibility. Conclusion: Our study provides evidence that joint exposure to multiple air pollutants substantially increases the risk of dementia, especially among individuals with high genetic susceptibility.
Degludec is a new generation basal insulin analog with a longer duration of action compared to insulin glargine. Several outpatient trials have reported that treatment with degludec results in comparable improvement in HbA1c levels and in lower rates of hypoglycemia compared to glargine U100 insulin. However, no previous studies have compared the safety and efficacy of the long-acting basal insulin degludec in the inpatient management of patients with diabetes. It is expected that a large number of patients with diabetes will be started on or transitioned to this new insulin formulation so acquiring knowledge on the safety and efficacy of degludec insulin is of great clinical interest. Accordingly, the proposed study will provide novel and clinically useful information on the efficacy (assessed as blood glucose control) and safety (assessed as hypoglycemia) of degludec in the inpatient setting and after hospital discharge in general medicine and surgery patients with Type 2 Diabetes (T2D).

Participants will be randomized to receive either a basal bolus with degludec or glargine U100 once daily during hospitalization. All participants will receive aspart insulin before meals. Participants with poorly controlled diabetes during the inpatient portion of the study will be invited to participate in the outpatient portion of the study. Participants in the outpatient portion of the study will be discharged on their preadmission oral antidiabetic medications plus degludec or glargine once daily, based on the study medication they were randomized to take during the inpatient portion of the study.
Retinal ischemia exists in various ischemic retinopathies including glaucoma, contributing to the death of retinal neurons. Calcium binding protein S100A4 is important in tumors, and our previous study found that S100A4 protects retinal ganglion cells (RGCs) against retinal ischemia-reperfusion (I/R) injury. This study was aimed to further discuss the neuroprotection and mechanisms of S100A4 in retinal I/R of mice. The rAAV-EF1α-s100a4-EGFP-WPRE or rAAV-EF1α-EGFP-WPRE-Pa was injected intravitreally 4 weeks before I/R. S100A4, molecules in TLR4 signaling pathway and endoplasmic reticulum (ER) stress branches, inflammatory molecules, and surviving RGCs and cholinergic amacrine (ChAT) cells were determined by quantitative PCR, western blot, or immunofluorescent staining. The apoptosis and necrosis of retinal neurons induced by I/R were inhibited by overexpressed S100A4. RGCs, ChAT cells, and the retinal function were preserved by S100A4 overexpressing 7 days after I/R. Mechanistically, the beneficial effects of S100A4 may be mediated by inhibiting the activation of TLR4 signaling pathway and alleviating ER stress, leading to the attenuation of inflammatory response of the retina after I/R. Our findings indicated that S100A4 has neuroprotective effect against retinal I/R injury, and promoting S100A4 expression may be an effective strategy to inhibit retinal neurons from degeneration in ischemic retinopathy.
Absorption - Following a single intravaginal application of a suppository containing 240 mg 14C-terconazole to healthy women, approximately 70% (range: 64-76%) of terconazole remains in the vaginal area during the suppository retention period (16 hours); approximately 10% (range: 5-16%) of the administered radioactivity was absorbed systemically over 7 days. Maximum plasma concentrations of terconazole occur 5 to 10 hours after intravaginal application of the suppository. Systemic exposure to terconazole is approximately proportional to the applied dose. The rate and extent of absorption of terconazole are similar in patients with vulvovaginal candidiasis (pregnant or non-pregnant) and healthy subjects.

Distribution - Terconazole is highly protein bound (94.9%) in human plasma and the degree of binding is independent of drug concentration over the range of 0.01 to 5.0 mcg/mL.

Metabolism - Systemically absorbed terconazole is extensively metabolized (>95%).

Elimination - Across various studies in healthy women, after single or multiple intravaginal administration of terconazole, the mean elimination half-life of unchanged terconazole ranged from 6.4 to 8.5 hours. Following a single intravaginal administration of a suppository containing 240 mg 14C-terconazole to hysterectomized or tubal ligated women, approximately 3 to 10% (mean ± SD: 5.7 ± 3.0%) of the administered radioactivity was eliminated in the urine and 2 to 6% (mean ± SD: 4.2 ± 1.6%) was eliminated in the feces during the 7-day collection period.

Multiple Dosing - There is no significant increase in maximum plasma concentration or overall exposure (AUC) after multiple daily applications of the suppositories for 3 days.

Photosensitivity reactions have not been observed in U.S. and foreign clinical trials in patients who were treated with terconazole suppositories.
Genital HPV infection is the most common sexually transmitted infection in the world and may lead to genital warts, anogenital dysplasias, and invasive cancers. HIV infected people and others with compromised immunity are at greater risk for HPV-related complications. In particular, researchers are concerned about the risk of HPV infection to women, who may be infected by their male partners, especially if these partners engage in anal intercourse. HIV infected women tend to have multiple types of HPV (associated with a greater risk of HPV-related disease), are less likely to clear HPV-related conditions, and are more likely to progress to HPV-related disease. The quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine to be tested in this study was safe and generally well tolerated in previous studies conducted in healthy and HPV-exposed adolescents, young adults, and older women. However, it is still unclear if the vaccine will be safe and will elicit a similar immune response in younger children. The purpose of this study is to evaluate the safety and immunogenicity of the novel quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine in HIV infected children 7 to 12 years of age.

This study had two stages and lasted at least 108 weeks. In Stage I, participants were stratified by CD4 percentage (CD4%) nadir and CD4% at study screening (Stratum A: CD4% Nadir \< 15 and CD4% ≥ 15 at screening, Stratum B: CD4% Nadir ≥ 15 and \< 25 and CD4% ≥ 15 at screening, Stratum C: CD4% Nadir ≥ 25 and CD4% ≥ 25 at screening). Within each stratification group, they were randomly assigned to one of two arms. During Stage I, Arm A (QHPV:Quadrivalent human papillomavirus vaccine) participants received 3 doses of vaccine, while Arm B (Placebo/QHPV) participants received 3 doses of placebo. Participants did not know whether they were receiving vaccine or placebo. Participants received their assigned intervention at study entry and Weeks 8 and 24. At Week 96, Stage II began, and all study participants were told if they received vaccine or placebo in Stage I. Arm A participants received an additional dose of vaccine at Week 96; Arm B participants received doses of vaccine at Weeks 96, 104, and 120. Over the course of the study, there were at least 12 study visits. A physical exam and blood collection occurred at most visits; medical history occurred at selected visits.

After each vaccination, participants were observed for at least 30 minutes to monitor for any allergic reactions possibly resulting from the vaccination. For 15 days following vaccination, parents or guardians were asked to complete a "report card" with details of each child's signs and symptoms. Three days after each vaccination, parents or guardians of study participants were contacted by telephone and asked about any adverse events that a child may have experienced.
Imatinib is often associated with edema and occasionally serious fluid retention [see Adverse Reactions (6.1)]. Weigh and monitor patients regularly for signs and symptoms of fluid retention. Investigate unexpected rapid weight gain carefully and provide appropriate treatment. The probability of edema was increased with higher imatinib dose and age greater than 65 years in the CML studies. Severe superficial edema was reported in 1.5% of newly diagnosed CML patients taking imatinib, and in 2% to 6% of other adult CML patients taking imatinib. In addition, other severe fluid retention (e.g., pleural effusion, pericardial effusion, pulmonary edema, and ascites) reactions were reported in 1.3% of newly diagnosed CML patients taking imatinib, and in 2% to 6% of other adult CML patients taking imatinib. Severe fluid retention was reported in 9% to 13.1% of patients taking Imatinib for GIST [see Adverse Reactions (6.1)]. In a randomized trial in patients with newly diagnosed Ph+CML in chronic phase comparing imatinib and nilotinib, severe (Grade 3 or 4) fluid retention occurred in 2.5% of patients receiving imatinib and in 3.9% of patients receiving nilotinib 300 mg twice daily. Effusions (including pleural effusion, pericardial effusion, ascites) or pulmonary edema were observed in 2.1% (none were Grade 3 or 4) of patients in the imatinib arm and 2.2% (0.7% Grade 3 or 4) of patients in the nilotinib 300 mg twice daily arm.
RFA causes tissue destruction through the application of a high frequency alternating current, generating local temperatures above 60°C and leading to coagulative necrosis. The technique has been widely used in many solid organ tumors and has been shown to result in 5-year survival rates comparable to surgery. The technique is currently the standard therapy in hepatocellular carcinoma and colorectal pulmonary metastasis particular in patients that are not suitable for surgery.

This study is a multi-center prospective study involving four high volume international institutions. Consecutive patients suffering from pancreatic neuroendocrine tumors and pancreatic cancers would be recruited. EUS-guided RFA would be performed using a 19-gauge RFA electrode and a generator. The primary outcome would be the overall adverse events rate. Secondary outcomes include mortality, technical success rate, completion ablation rate, 1 \& 3 year overall and disease-free survival.
Carboplatin starting dose AUC of 4, administered by vein over 60 minutes, Day 1 of 3 Week Cycle. TAS-106 starting dose 2.0 mg/m\^2 by vein over 24 hours, Day 1 of 3 Week Cycle.
A double blind placebo control randomized clinical trial was made to verify the efficacy of the treatment by deactivation of MTP, after 10 sessions, in tinnitus patients by means of comparison with a placebo treatment in a control group. Patients with tinnitus and frequent regional pain for at least 3 months in the head, neck and shoulder girdle were investigated in the Tinnitus Research Group of University of São Paulo Medical School. All of them underwent an interview with the otolaryngologist ("physician researcher"), an audiologist evaluation ("blind researcher"), another blind researcher evaluation for tinnitus and pain and a physiotherapist evaluation and randomization. Both blind researchers evaluated tinnitus and pain in the first, fifth and tenth session. The real treatment was made by a gradual and persistent digital pressure in each MTP previously diagnosed by the blind researcher (8 possible muscles) and some home orientations that included stretch, superficial heat in each treated muscle and watch the correct postures during daily activities and sleeping. In the control group physiotherapist researcher pressed in an adjacent non-tender muscle fibers of the same muscle that have MTP. No other complementary orientation was done.
BACKGROUND: WNT7B is a glycoprotein that plays a crucial role in tumorigenesis. This study aimed to investigate the role of WNT7B in oral squamous cell carcinoma (OSCC).
METHODS: Bioinformatic databases, immunohistochemistry, a real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to detect WNT7B expression in OSCC. The clinical and prognostic importance of WNT7B expression was evaluated. WNT7B expression was examined in oral leukoplakia and carcinoma induced by 4-nitroquinoline 1-oxide in mice. Loss- and gain-of-function analyses were performed to elucidate the role of WNT7B in OSCC cells. Subcutaneous tumor model was established to observe the effects of WNT7B on tumor growth. Co-Immunoprecipitation was used to explore the Frizzled receptors that WNT7B may bind to.
RESULTS: WNT7B upregulated in OSCC and associated with lymph node metastasis, perineural invasion, and an unfavorable prognosis in patients with OSCC. A gradual increased in WNT7B expression during the malignant progression of OSCC. WNT7B promoted cell proliferation, migration, invasion, while silencing WNT7B abolished these effects. Knocking down the expression of WNT7B inhibits tumor growth in vivo. WNT7B functions by binding to the Frizzled 7 receptor and facilitates the nuclear translocation of β-catenin.
CONCLUSIONS: WNT7B contributes to the progression of OSCC by modulating the WNT/β-catenin signaling pathway. These findings highlight the potential of WNT7B as a novel prognostic biomarker and promising therapeutic target for OSCC.
<P>PROBLEM TO BE SOLVED: To provide a skin beautifying agent that manifests tyrosinase-inhibiting activity and exhibits good skin-beautifying effects based on the activity.  <P>SOLUTION: The skin beautifying agent includes Dunaliella tertiolecta exhibiting tyrosinase-inhibiting activity. A dried frond of Dunaliella tertiolecta is obtained by freeze-drying cultivated cells that are obtained by cultivating cells of Dunaliella tertiolecta. Extracts of Dunaliella tertiolecta is prepared by adding an extracting solvent to the dried fond of Dunaliella tertiolecta prepared by the freeze-drying, agitating the mixture to extract effective ingredients, and freeze-drying the extracts. The tyrosinase-inhibiting activities are directly exhibited by applying it on the skin. As the compounding agent for beautifying the skin, at least collagen is incorporated with Dunaliella tertiolecta.  <P>COPYRIGHT: (C)2010,JPO&INPIT
Partial restoration will be performed, and its apical margin will be placed 1 mm beyond the estimated position of the cementoenamel junction. Patients enrolled in this group will receive a coronally advanced flap (CAF) associated with a volume-stable collagen matrix (VCMX). Two horizontal incisions will be performed at the papilla base united by an intrasulcular incision around the tooth. In sequence, releasing incisions will be designed and a split-full-split flap will be raised beyond the mucogingival junction. In sequence, VCMX will be cut according to the recession defect and moistened with saline solution. The biomaterial will be placed at the cementoenamel junction level and stabilized in the adjacent surgery papillae by interrupted sutures. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions.
Systems and methods of treating a subject are provided. A first data set is obtained that includes time-stamped autonomous glucose measurements of a subject during a first time. A second data set is also obtained that is associated with the subject's resident insulin regimen during the first time period and includes an insulin medication record. Each record includes: a time-stamped injection event comprising an amount and type of insulin medication injected into a subject by an insulin pen. The first and second data sets are used to calculate a blood glucose risk measure and an insulin sensitivity factor for the subject during a first time period, which are used to obtain a basal titration schedule and a model of the fasting blood glucose profile of the subject during a subsequent second time period. The model predicts a fasting blood glucose level in the subject based on an amount of basal insulin drug injected into the subject.
Take an appropriate amount of Vaseline and mix thoroughly with 1% of the original ingredient, starch, and pigment. Take an appropriate amount of medication and place it in the center of the acupoint patch (8cm x 8cm). Press the medication evenly into a circular hole with a diameter of about 4cm and a depth of about 3mm, and align the patch.
Multiple sclerosis (MS), an inflammatory and neurodegenerative disorder of the central nervous system (CNS), is the most common cause of progressive neurologic dysfunction in early to middle adulthood. People with MS are a markedly high risk for sleep disturbance. Estimates of the lifetime prevalence of sleep disturbance in MS reach 50%; sleep disturbance is also associated with excess MS-associated morbidity and diminished quality of life. Despite the high burden of impaired sleep and its contribution to adverse MS outcomes, effective approaches to treat and ameliorate disturbed sleep in people with MS remain poorly understood. There is unmet need to develop safe and effective rehabilitative alternatives to mitigate sleep disturbance in MS. Prior research supports the use of timed bright light therapy (LT) as one such approach for insomnia and sleepiness in those with sleep disorders or other neurologic diseases. Yet, the safety and potential effectiveness of timed LT have yet to be tested in MS. The goal of the proposed study is to conduct a detailed intervention study testing if timed bright LT in people with MS is 1) safe (primary outcome) and 2) potentially effective for reducing sleep disturbance (specifically, reducing insomnia, fatigue and improving sleep efficiency, quantity and quality as secondary outcomes). The study will also explore whether LT stimulates a novel subtype of retinal ganglion cells which are central to the regulation of circadian rhythms and sleep.
Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-α, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H2 O2 levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the α7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via α7nAChR and M3AChR.