anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
One of the most critical axes for cell fate determination is how cells respond to excessive reactive oxygen species (ROS)-oxidative stress. Extensive lipid peroxidation commits cells to death via a distinct cell death paradigm termed ferroptosis. However, the molecular mechanism regulating cellular fates to distinct ROS remains incompletely understood. Through siRNA against human receptor-interacting protein kinase (RIPK) family members, we found that RIPK4 is crucial for oxidative stress and ferroptotic death. Upon ROS induction, RIPK4 is rapidly activated, and the kinase activity of RIPK4 is indispensable to induce cell death. Specific ablation of RIPK4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion. RNA sequencing revealed the dramatically decreased expression of acyl-CoA synthetase medium-chain (ACSM) family members induced by cisplatin treatment which is compromised in RIPK4-deficient mice. Among these ACSM family members, suppression of ACSM1 strongly augments oxidative stress and ferroptotic cell death with induced expression of ACS long-chain family member 4, an important component for ferroptosis execution. Our lipidome analysis revealed that overexpression of ACSM1 leads to the accumulation of monounsaturated fatty acids, attenuation of polyunsaturated fatty acid (PUFAs) production, and thereby cellular resistance to ferroptosis. Hence, knockdown of ACSM1 resensitizes RIPK4 KO cells to oxidative stress and ferroptotic death. In conclusion, RIPK4 is a key player involved in oxidative stress and ferroptotic death, which is potentially important for a broad spectrum of human pathologies. The link between the RIPK4-ASCM1 axis to PUFAs and ferroptosis reveals a unique mechanism to oxidative stress-induced necrosis and ferroptosis.
Testim® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

  1. Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
  2. Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range.



Testim® has not been clinically evaluated in males under 18 years of age.
Described herein are BRCA1 modulating compounds and formulations thereof. In some aspects, the BRCA1 modulating compound is a deubiquitinase. In some aspects, the BRCA1 modulating compound is a deubiquitinase inhibitor. as Also described herein are methods of treating a subject in need thereof with a BRCA1 modulating compound or formulation thereof. In some aspects, the subject in need thereof can have a cancer. In some aspects, the subject in need thereof has one or more BRCA1 mutations.
For incident peritoneal dialysis (PD) patients assigned to the experimental arm, PD is initiated with single daily exchange of 2-liter icodextrin-based dialysis solution. The daily dwell time ranges from 8-24 hours per day, depending on the patient's clinical conditions. Additional exchange(s) of glucose-based dialysis solution will be added to increase uremic toxins and fluid removal if necessary during the follow-up.
Cold compression application was performed using Game Ready for 15 minutes. The target temperature was manually set to 1°C and the pressure was set to high compression (75 mm Hg). Since it is known that the applied pressure increases the effect of cold application and oxygenation in the tissue increases as the compression intensity increases (108), it was applied in the high option. Duration was preferred because the optimal range for the duration of cold applications is given as 11-15 minutes in the literature (120). Pneumatic intermittent compression with a standard ∼3-minute cycle was applied to both lower legs using a thigh wrap. The application was performed with the athletes in the supine semi-recumbent position.
BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity.
METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents.
RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity.
CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.
Chemically-induced seizures, as a result of exposure to a neurotoxic compound, present a serious health concern. Compounds can elicit seizure activity through disruption of neuronal signaling by neurotransmitters, either by mimicking, modulating or antagonizing their action at the receptor or interfering with their metabolism. Benzodiazepines, such as diazepam and midazolam, and barbiturates are the mainstay of treatment of seizures. However, chemically-induced seizures are often persistent, requiring repeated treatment and increased doses of anticonvulsants, which in turn may lead to severe adverse effects such as respiratory depression. Here, we investigated the potential of rational polytherapy consisting of the benzodiazepine midazolam and the selective α2-adrenergic agonist dexmedetomidine as an improved, generically applicable anticonvulsant treatment regimen. Therapeutic efficacy was evaluated against two experimental paradigm compounds that induce persistent seizures in rats, the rodenticide TETS and the nerve agent soman. Following exposure, both TETS and soman elicited profound seizure activity and convulsions, associated with substantial mortality. Treatment with midazolam or dexmedetomidine alone provided no or limited suppression of seizure activity and improvement of survival at 4 h. Polytherapy consisting of midazolam and dexmedetomidine showed excellent anticonvulsant efficacy. Even at low doses, polytherapy showed a profound effect that lasted for the duration of the experiment. Analysis of the dose-response relationships confirmed presence of synergy. Administration of polytherapy in non-exposed animals did not indicate aggravation of adverse effects on respiration or heart rate. Even though more research is needed for the translation to clinical use, polytherapy consisting of midazolam and dexmedetomidine shows promise for the broad-spectrum treatment of (chemically-induced) seizures in emergency situations.
BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalisation, and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore.
METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists, and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase, and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori.
RESULTS: The panellists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide preoperative, and (3) postoperative management of sarcopenia.
CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and postoperative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.
Acute myeloid leukemia (AML) is frequently linked to genetic abnormalities, with the t (8; 21) translocation, resulting in the production of a fusion oncoprotein AML1-ETO (AE), being a prevalent occurrence. This protein plays a pivotal role in t (8; 21) AML's onset, advancement, and recurrence, making it a therapeutic target. However, the development of drug molecules targeting AML1-ETO are markedly insufficient, especially used in clinical treatment. In this study, it was uncovered that Neratinib could significantly downregulate AML1-ETO protein level, subsequently promoting differentiation of t (8; 21) AML cells. Based on "differentiated active" probes, Neratinib was identified as a functional inhibitor against HNRNPA3 through covalent binding. The further studies demonstrated that HNRNPA3 function as a putative m6A reader responsible for recognizing and regulating the alternative splicing of AML-ETO pre-mRNA. These findings not only contribute to a novel insight to the mechanism governing post-transcriptional modification of AML1-ETO transcript, but also suggest that Neratinib would be promising therapeutic potential for t (8; 21) AML treatment.
Cases of acute renal failure have been reported in:

  * Elderly patients with or without reduced renal function. Caution should be exercised when administering VALTREX to geriatric patients, and dosage reduction is recommended for those with impaired renal function [see Dosage and Administration ( 2.4), Use in Specific Populations ( 8.5)]. 
  * Patients with underlying renal disease who received higher-than-recommended doses of VALTREX for their level of renal function. Dosage reduction is recommended when administering VALTREX to patients with renal impairment [see Dosage and Administration ( 2.4), Use in Specific Populations ( 8.6)]. 
  * Patients receiving other nephrotoxic drugs. Caution should be exercised when administering VALTREX to patients receiving potentially nephrotoxic drugs. 
  * Patients without adequate hydration. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients. 



In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored [see Dosage and Administration ( 2.4), Adverse Reactions ( 6.3)] .
This prospective, double-blind, randomized, placebo-controlled clinical trial will investigate the effects of 4-week B. lactis HN019 supplementation on whole gut transit time and gastrointestinal symptoms in adults with functional constipation. Participants who meet all study entry criteria will enter a 2-week run-in period. Following successful completion of the run-in period, subjects will be randomized to 4-week supplementation with B. lactis HN019 (10 billion cfu), B. lactis HN019 (1 billion cfu), or placebo. The primary outcome of whole gut transit time will be evaluated with abdominal x-rays on days 0 and 28. Secondary outcomes include IBS-specific questionnaires (administered on days 0 and 28); abdominal pain severity, bowel movement frequency, stool consistency, and adverse events (evaluated daily throughout the study); and overall product satisfaction (evaluated at day 28). Physical activity questionnaires and 24-hour food recalls will be completed periodically during the trial.
One aspect is a method for generating an image of a human face expected to have at least one changed perceptive trait. Such method includes encoding an image of a human face into a vector to generate an input image vector. A scaled direction vector is applied to the input image vector to generate a modified input image vector. The modified input image vector is converted into a morphed image of the actual human face. The scaled direction vector is determined using an artificial neural network trained to associate human faces to with ratings of perceptive traits, to determine a unit direction vector. The unit direction vector is based on at least one chosen perceptive trait. An amplitude for scaling the unit direction vector is determined by a limit on change in facial features obtainable by known treatments.
UNLABELLED: Bloodstream infections are associated with high mortality, which can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. This study aimed to evaluate three different direct AST protocols for Gram-negative rods from flagged positive blood culture broths. Blood culture broths showing Gram-negative rods only were subjected to direct AST by Clinical and Laboratory Standards Institute-recommended direct disk diffusion (protocol A). Additionally, automated AST (protocol B) and Kirby-Bauer disk diffusion (protocol C) were performed with standard inoculum prepared from bacterial pellets obtained by centrifuging blood culture broths in serum separator vials. For comparison, conventional AST of isolates from solid media subculture was also performed with Kirby-Bauer disk diffusion (reference standard) and the automated method. Overall, categorical agreements of protocols A, B, and C were 97.6%, 95.7%, and 95.9%, respectively. Among Enterobacterales, minor error, major error, and very major error rates of protocol B were 3.5%, 0.36%, and 0.43%, respectively, whereas minor error, major error, and very major error rates of protocol C were 3.4%, 0.72%, and 0.21%, respectively, and among non-fermenters, protocol B had a minor error rate of 6.5%, and protocol C had a minor error rate of 4.1% and major error rate of 1.9%. All three direct AST protocols demonstrated excellent categorical agreements with the reference method. Performance of protocols B and C between Enterobacterales and non-fermenters was not statistically different.
IMPORTANCE: Bloodstream infections are associated with high mortality that can be reduced by targeted antibiotic therapy in the early stages of infection. Direct antibiotic susceptibility testing (AST) from flagged positive blood cultures may facilitate the administration of early effective antimicrobials much before the routine AST. Clinical and Laboratory Standards Institute-recommended direct AST can be performed with a limited number of antibiotic disks only. On the other hand, using an automated system for direct AST will not only allow effective laboratory workflow with reduced turnaround time but also provide the minimum inhibitory concentration values of tested antibiotics. However, using expensive automated systems for direct AST may not be feasible for resource-limited laboratories. Therefore, in this study, we aimed to evaluate the CLSI-recommended method and two other direct AST protocols (one with an automated system and the other with disk diffusion) for Gram-negative rods from flagged positive blood cultures.
The control group will be invited to an orientation session, where it will be provided detailed information concerning their home base exercise program. Additionally, once in every 4 weeks, the control group will meet for thematic sessions regarding diabetes topics, such as, nutrition, physical activity, and clinical complications. Due to ethical reasons, the control group needs to be provided with a standard counseling approach, as suggested in this research project.
BACKGROUND: Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD).
METHODS: A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication.
RESULTS: The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes.
CONCLUSIONS: The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.
The purpose of this study is to measure neurophysiologic parameters to assess the effect of malnutrition on peripheral nervous system and their response to treatment in three categories (SAM, severe wasting and severe stunting) of childhood malnutrition. The electrophysiological properties of peripheral nerves in malnourished under-5 children before and after correction of severe malnutrition were assed.

This is an exploratory study conducted in icddr,b, Dhaka, Bangladesh. 83 under-5 children from three categories of undernourished groups- severe stunting (length-for-age Z-scores \<-3), SAM (weight-for-length Z-scores \<-3, and/or mid-upper-arm circumference \<11.5 cm, with or without nutritional edema) and wasting (weight-for-length Z-scores (WLZ) \<-2) were enrolled. A total of 45 age-matched healthy children selected as controls. Participants were identified from urban/peri-urban areas of Dhaka city. After enrolment, participants were brought to icddr,b Dhaka Hospital and data on socio-economic status, weaning practice, morbidity, and dietary intake were collected. Nerve electro physiologic parameters assessed by motor (median, ulnar, fibular and tibial) and sensory (median, ulnar and sural) nerve conduction studies (NCS) on enrollment.

SAM were treated with appropriate nutritional therapy/treatment that included supplementation of high calorie diet; i.e., F-100 milk and khichuri-halwa for nutritional rehabilitation. Egg-milk and micronutrient supplementation were provided for 2 months for recovery from severe stunting (following standard guidelines for facility based management and recently conducted community based nutrition intervention studies). As per national guidelines, children suffering from severe wasting with medical complications were treated with specialized therapeutic milks (F-75) and those without medical complications treated with a suitable local Nutritional Management (NM) \& routine medicines to treat simple medical conditions at community nutrition center (CNC) with weekly follow up. Children were monitored in the community for 2 months. Monthly anthropometry had been done. On day 60 or 2 months of intervention, children with weight-for-length/height Z-scores ≥-1 and MUAC \>115 mm were again brought to icddr, b for nerve conduction test.
In patients assigned to the SPAL group, the management of the soft tissues will be performed according to the SPAL technique as originally described by Trombelli et al. (2018). Implant site preparation will be performed using a set of calibrated guided surgery steel burs under copious sterile saline irrigation. Implants will be placed, and a healing abutment will be positioned and screwed. The space underneath the periosteal layer will be then filled with a deproteinized bovine bone mineral (DBBM) graft. A sterile viscoelastic gel (SVG) based on polynucleotides and hyaluronic acid (REGENFAST®, Mastelli Srl, Sanremo, Italia) will be combined with the bone graft. The periosteal layer will be then secured to the oral flap by mean of 6/0 resorbable internal mattress sutures. SVG wil be placed underneath the mucosal layer and the latter will be coronally advanced and stabilized a using 6/0 resorbable internal mattress and sling sutures.
Perioperative vision loss following non-ophthalmic surgical procedures represents a rare but potentially serious complication. Although its occurrence in urology is infrequent, the consequences for patients and legal implications are significant. We present the case of a 53-year-old woman with no notable medical history, treated for renal lithiasis. Following the ureteroscopy, the patient experienced a sudden reduction in visual acuity. The diagnosis made was that of posterior ischemic optic neuropathy. This case illustrates a rare complication associated with ureteroscopy, highlighting the importance of increased awareness and rigorous postoperative monitoring, especially in patients with risk factors such as anemia or hypertension. Fortunately, the patient's rapid and complete recovery is encouraging, suggesting that early identification and appropriate management can lead to a favorable prognosis.