anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In a 2-year carcinogenicity study with oral administration of ribociclib daily in cycles of 3 weeks on/1 week off, ribociclib was not carcinogenic at doses up to 50 mg/kg in male rats and 600 mg/kg in female rats. Systemic exposure in male and female rats were 1.3 and 1.8 times, respectively, the human exposure at the highest recommended dose of 600 mg/day based on AUC.

Ribociclib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in an in vitro human lymphocyte chromosomal aberration assay or an in vivo rat bone marrow micronucleus assay.

In a fertility and early embryonic development study, female rats received oral doses of ribociclib for 14 days prior to mating through the first week of pregnancy. Ribociclib did not affect reproductive function, fertility or early embryonic development at doses up to 300 mg/kg/day (approximately 0.6 times the clinical exposure in patients at the highest recommended dose of 600 mg/day based on AUC).

A fertility study in male rats has not been performed with ribociclib. In repeat-dose toxicity studies with oral administration of ribociclib daily for 3 weeks on/1 week off in rats up to 26 weeks duration and dogs up to 39 weeks duration, atrophic changes in testes were reported. Findings included degeneration of seminiferous tubular epithelia in the testes and hypospermia and luminal cellular debris in the epididymides of rats and dogs and vacuolation of epithelia in the epididymides of rats. These findings were observed at doses ≥ 75 mg/kg in rats and ≥ 1 mg/kg in dogs which resulted in systemic exposures that were 1.4 and 0.03 times the human exposure at the highest recommended daily dose of 600 mg/day based on AUC, respectively. These effects can be linked to a direct anti-proliferative effect on the testicular germ cells resulting in atrophy of the seminiferous tubules and showed a trend towards reversibility in rats and dogs after a four-week non-dosing period.
The present invention provides a means to broadly protect the military and the public from injury from biological warfare weapons, particularly infective agents such as anthrax. Beta (1,3)-glucans, particularly whole glucan particles, PGG-Glucan, and microparticulate glucan, provide general immune enhancement, thereby increasing the body's ability to defend against a wide variety of biological threats. Beta (1,3)-glucans have been shown to increase the resistance to infection by anthrax and other infectious organisms when administered before and after infection. The anti-infective mechanism of β(1,3)-glucan appears to involve stimulation of the innate immune system through increased cytokine release and CR3 receptor activation. Beta (1,3)-glucan is pharmaceutically stable, relatively compact, and can also be used without significant side effects. Beta (1,3)-glucan can also enhance the effectiveness of other medical countermeasures such as antibiotics, vaccines, and immune antibodies.
OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases.
METHODS: The levels of the immunoproteasome β5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome β5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of β5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay.
RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the β5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA.
CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.
The present invention provides a method for manufacturing a hydrogel sheet product. The method for manufacturing a hydrogel sheet product includes: a step of coating a hydrogel forming composite containing a high molecular weight hydrophilic solution including polyacrylic acid or salt thereof, a cross-linking agent, a gelation speed modifier, and water, on a support body; a step of ripening a hydrogel layer for the polyacrylic acid or the salt thereof to be cross-linked by the cross-linking agent; a forming step of cutting the ripened hydrogel sheet in a desired shape; a step of inserting the formed hydrogel sheet into a package bag; a step of impregnating an impregnated liquid into the hydrogel layer by injecting the impregnated liquid formed of water of a hydrophilic solution into the package bag; and a sealing the package bag. According to the present invention, a hydrogel sheet product sufficiently contains active ingredients such as water, polyhydric alcohol, and a moisturizer in hydrogel and when in contact with the skin, these active ingredients are transferred effectively. The hydrogel sheet product has high product satisfaction since users feel relief when the cosmetic ingredients remain on the skin. According to the present invention, the hydrogel sheet product is convenient to use and does not waste cosmetic ingredients since the active ingredients such as water, polyhydric alcohol, and the moisturizer contained in the hydrogel stay in contact with the hydrogel sheet during storage and distribution. The hydrogel sheet product has excellent skin adhesiveness.
Fentanyl Citrate Injection may cause muscle rigidity, particularly involving the muscles of respiration. The incidence and severity of muscle rigidity is dose related. These effects are related to the dose and speed of injection. Skeletal muscle rigidity also has been reported to occur or recur infrequently in the extended postoperative period usually following high dose administration. In addition, skeletal muscle movements of various groups in the extremities, neck, and external eye have been reported during induction of anesthesia with Fentanyl Citrate Injection; these reported movements have, on rare occasions, been strong enough to pose patient management problems.

These effects are related to the dose and speed of injection and its incidence can be reduced by: 1) administration of up to 1/4 of the full paralyzing dose of a non-depolarizing neuromuscular blocking agent just prior to administration of Fentanyl Citrate Injection; 2) administration of a full paralyzing dose of a neuromuscular blocking agent following loss of eyelash reflex when Fentanyl Citrate Injection is used in anesthetic doses titrated by slow intravenous infusion; or, 3) simultaneous administration of Fentanyl Citrate Injection and a full paralyzing dose of a neuromuscular blocking agent when Fentanyl Citrate Injection is used in rapidly administered anesthetic dosages.  
The neuromuscular blocking agent used should be compatible with the patient’s cardiovascular status.
BACKGROUND: Hearing loss (HL) is prevalent in older individuals. It is suggested that there is an association between age-related HL, walking and balance, leading to poorer function and increased risk of falls in older individuals.
RESEARCH QUESTION: Is HL associated with physical performance, gait variability, and postural sway in older adults, and will additional dizziness moderate the effect of HL on balance?
METHODS: In this cross-sectional study we examined 100 older individuals (age ≥70 years, 60 % females), divided in two groups, with or without age-related HL. Physical function and balance were evaluated by the Short Physical Performance Battery (SPPB), postural sway measured on a force platform (posturography), and balance in walking (gait variability) measured with a body-worn sensor. Multiple linear regression was used to examine the relationships between the variables, with physical function and balance as outcomes and HL as a dichotomous exposure (>30 dB). For all analyses, we further tested if associations were modified by self-reported dizziness.
RESULTS: Multiple regression analysis with HL, age, sex, education, diabetes, and cardiovascular disease revealed a significant association between reduced SPPB and HL. Multiple linear regression analysis also showed that HL was associated with increased postural sway on firm surface with eyes open and closed after adjusting for age, sex, education, diabetes, and cardiovascular disease. There was significant association between HL and increased gait variability during dual task walking in all directions after adjusting for age, sex, education, diabetes, and cardiovascular disease. Further, we found that the association between HL and SPPB was significantly stronger in those with dizziness compared with those without dizziness. Dizziness also modified the association of HL with the other SPPB sub-scores but not for the other outcomes of postural sway or gait variability.
SIGNIFICANCE: In this study, age-related HL was associated with worse physical performance as measured by SPPB, postural sway, and gait variability. This relationship illustrates the importance of assessing physical performance in people with HL to prevent risk of falls and disability.
A single-dose, randomized, open-label, two-period, two-sequence, two-treatment, single-centre, crossover bioequivalence study was carried out under fasting conditions in healthy adults, aged 20-60 years. For each period, each subject received a single dose as equivalent to 180 mcg of albuterol of the study drugs according to the pre-determined randomization scheme. Each subject was drawn 22 times over the period of 24 hours. Plasma samples were collected and analyzed for albuterol concentrations by using LC-MS/MS. For each subject, there were 2 dosing periods separated by a 14-day washout period. During the study, standardized meals were provided to all subjects while institutionalized.
To easily know how much a health-related countermeasure product has a countermeasure effect level, and how much countermeasure can be taken against regional weather environment forecast information. A two-dimensional code  1  incorporating countermeasure effect level information for each health-related countermeasure category is attached to a product. On the other hand, there is a mobile terminal device  2  capable of automatically inputting the planned activity amount in exercise and work, the physical condition status, the pulse rate, and the body temperature. The health-related countermeasures information processing equipment  3  connected to the communication network also obtains weather information such as temperature, humidity and heat index, ultraviolet rays, and pollen scattering amount for each region from the weather forecast prediction data transmission device  4 . Then, the necessary countermeasure level is generated. Then, it is determined to be compared with the countermeasure effect level of the product. The result will be useful for selecting the product. In addition, an information system that obtains hindrance occurrence prediction information generated by a deep learning method from the progress history of the above information and related countermeasure product promotion information.
The aim of this study was to develop a novel surgical technique for stifle arthrodesis in dogs using a semicircular saw for tibial and femoral ostectomies through a medial approach. Ten pelvic limbs from five canine cadavers underwent stifle arthrodesis. Prior to the surgical procedure, the limbs were radiographed to rule out musculoskeletal abnormalities. Additionally, the radiographs were used for surgical planning. For the tibial ostectomy, the center of the intercondylar eminences, the cranial limit of the tibial plateau, and the caudal cortex of the tibia were used as landmarks. In the femur, the groove of the insertion of the long digital extensor tendon and the caudal portion of the femoral cortex served as references. The most significant iatrogenic injury during the surgical procedures was the complete rupture of the long digital extensor tendon during the tibial cut in one of the stifles. Dome ostectomies facilitated interfragmentary contact, allowing for adjustment of the angulation between the fragments without the need for additional ostectomies or osteotomies. The medial approach provided a clear view of intra-articular structures without causing extensive damage to surrounding tissues. After the procedures, the limbs were radiographed to calculate angular measurements, and the final angulation (mean) of the knee joints was 134.7 ± 11°.
PURPOSE:To obtain cancer repressor gene coding a specific peptide and useful for cancer research by incorporating Escherichia coli with plasmid containing specific cDNA to make a cloning and by selecting the clone having cancer suppressor activity. CONSTITUTION:Tumor cells or transform cells are incorporated with cDNA manifestation library DNA plasmid having selective marker for animal cell by a method such as transfection. Thence, using the selective marker, cDNA plasmid-incorporated cells are selected and the cell clones deprived of the nature as a tumor cell are isolated. From the resultant cells, cDNA is extracted, and plasmid containing this cDNA is made up and incorporated into Escherichia coli to make a cloning, thus selecting the clone having cancer suppressor activity. Thereby the objective cancer suppressor gene can be obtained. This gene codes a peptide expressed by an amino acid sequence selected from those at 2-184, 2-11, 26-31, 31-45, 61-65, 73-85, 116-121, 145-150, 152-165, and 168-180 this among amino acid sequences of the formula.
The invention discloses a health care seat cushion. The health care seat cushion comprises a sleeve and a medicine bag. Projections are arranged on the surface of the sleeve. The sleeve is filled with the medicine bag. Buckling devices are arranged at the front, back, left and right sides of the medicine bag respectively. The medicine bag is filled with the following dry powdery Chinese traditional medicine ingredients, by weight, 20-30 parts of phyllanthus urinaria L, 20-40 parts of setaria viridis, 20-30 parts of thymifoious euphorbia herb, 20-30 parts of murraya paniculata, 20-30 parts of artemisia vulgaris, 10-20 parts of melastoma dodecandrum lour, 20-30 parts of elephantopus scaber, 10-20 parts of purslane, 10-20 parts of Chinese gall, 10-20 parts of fructus sophorae, 10-20 parts of honeysuckle flower, and 10-20 parts of borneol. A slide fastener is arranged at one side of the sleeve. The health care seat cushion with a hemorrhoid treatment function is provided. The buckling devices are arranged at the front, back, left and right sides of the medicine bag respectively, the medicine bag is prevented from movement during the usage process, the projections are arranged on the surface of the sleeve, a massage function is achieved, and blood circulation is promoted.
The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS). 

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment.
All subjects will be administered oral ripilvirine 25mg once daily together with the rest of their oral antiretroviral combination and an etonogestrel single-rod subdermal implant (68mg/rod). Study participants will have both interventions for a period of one year.
Injury-related fear after anterior cruciate ligament reconstruction (ACLR) is associated with secondary ACL injury and slower reaction time. Graded exposure (GE) and mindfulness meditation (MM) have reduced injury-related fear, but has not been explored together in patients post-ACLR. GE and MM delivered via the Headspace application is feasible for individuals post-ACLR. GEMM allows athletic trainers' to easily implement MM into their practice. The aim of this randomized single-blinded clinical trial is to determine the efficacy of 5-weeks of GEMM to decrease injury-related fear and reinjury anxiety and improve reaction time in participants 1 to 5-years post-ACLR. Participants will be randomized into a GEMM group or waitlist control group. Participants will complete the Photographic Series of Sports Activities for ACLR, Reinjury Anxiety Inventory, the Tampa Scale of Kinesiophobia-11 and a lower extremity reaction time task pre and post the 5-week period. The investigators hypothesize that participants in the GEMM group will exhibit decreased injury-related fear and reinjury anxiety and faster reaction time when compared to the waitlist controls.
Patients aged 18-60 years presenting for elective surgery under general anaesthesia will be recruited. They will be randomised to receive remifentanil effect-site target 0, 2 or 4 ng/ml. Then anaesthesia will be induced with propofol. Loss of the eyelash reflex, response to command and response to electrical stimulation will be measured. The raw EEG will be recorded and analysed off-line using our new method and also for BIS values. Anaesthesia will then proceed according to the needs of the patient and the surgery.
Three decades of research on end-of-life care in the United States indicates that people who are dying often spend their final days with a significant burden of pain and other symptoms and receive care they would not choose. Patient-clinician communication about end-of-life care is an important focus for improving patient-centered end-of-life care for three reasons: 1) it is an integral component of clinician skill that affects all other aspects of end-of-life care; 2) physicians and nurses in practice do not demonstrate adequate skills for communicating about end-of-life care; and 3) current training in end-of-life communication is inadequate. Studies have shown that clinicians can improve their communication skills with experiential training, but no studies to date have shown that an intervention to improve clinician communication skill improves patient outcomes. Furthermore, despite widespread knowledge that end-of-life care is best delivered in an interdisciplinary context, most studies do not incorporate interdisciplinary training that includes physicians and nurses.

This is a randomized trial of a communication skills workshop for internal medicine residents and nurse practitioner (NP) students. A total of 373 residents and 128 NP students from two large training programs (UW and MUSC) will be randomized to either the intervention or usual education. The study's primary outcome measure will be the QOC scores on the "communication about end-of-life care" domain. The QOC will be assessed by patients, family members, and nurses before and after the intervention time period for all trainees. Secondary outcome measures are patient symptoms and patient-, family - and nurse-assessed QEOLC scores. Outcome measures will be collected for 5 patients and family members per trainee before the intervention period and 5 patients and family members per trainee after the intervention period. Process measures for both residents and NP students will include pre- and post-intervention assessment of knowledge, attitudes, and behavior regarding communication using standardized patient assessment as well as self-assessment and faculty assessment.
PURPOSE:A nail beautifying cosmetic, containing a polyhydric alcohol and a protein as active constituents, capable of imparting sufficient moisture to the nail plate and exhibiting effect on prevention of drying for a long period and aiming at the repair of acquired damage of the nail plate and protection of normal nail plate. CONSTITUTION:A nail beautifying cosmetic containing 10-40wt%, preferably 10-30wt% polyhydric alcohol, e.g. ethylene glycol, dipropylene glycol, pentaerythritol, maltose or D-gluconic acid, and 0.0005-0.1wt%, preferably 0.01-0.07wt% protein, e.g. soybean protein, cow's milk casein, collagen or keratin, as active constituents. Although nail beautifying effect is not recognized in only the protein, the combination thereof with the polyhydric alcohol exhibits synergistic effect. The dosage form may be any one of a solution, solubilized, emulsified and powder dispersed systems, etc.
Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use carvedilol for a condition for which it was not prescribed. Do not give carvedilol to other people, even if they have the same symptoms you have. It may harm them. 

This leaflet summarizes the most important information about carvedilol. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about carvedilol that is written for healthcare professionals. You can also find out more about carvedilol by visiting the website www.glenmarkgenerics.com or calling 1 (888)721-7115. This call is free.