anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Compositions including a polynucleotide combined with a vehicle and methods of their use to induce a suppressive immune response are provided. In some embodiments the compositions induce an increase in expression of indoleamine 2,3 dioxygenase (IDO) enzyme activity in cells. The methods and compositions can be used to inhibit or reduce immune-mediated tissue destruction, to treat autoimmune diseases and inflammatory responses, to promote immune tolerance, to enhance tolerizing vaccines, to treat allergies, to treat asthma, or to enhance mucosal tolerance in subject. Methods and compositions for inducing a suppressive immune response for while minimizing undesirable side effects in the subject are also provided. An exemplary undesirable side effect is systemic release of INFγ. Exemplary compositions that can be used to induce an immune response in a subject without inducing systemic release of INFγ include compositions containing a polynucleotide lacking an immunostimulatory nucleic acid sequence complexed with a carrier.
Saline group, where participants will be given saline solution (4mg) via an identical spray device. Participants will be stratified for sex and then randomized to saline arm (The dose of saline will be (0.1 mL 0.9% sodium chloride intranasally), respectively. Investigators, staff, and participants will be blinded to the treatment options.
Individuals assigned to attachment-based family therapy for sexual and gender minorities will receive a 16-session sequence of family-based therapy delivered via telehealth. This sequence will include sessions with sexual and/or gender minority adult children alone, adult children and parent(s), and parent(s) alone. Sessions will address the quality parent-child relationship in relation to child sexual orientation and gender identity to target mental health disparities.
Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP.
Sport: Prevention Plus Wellness (PPW) is a brief, evidence-based substance use prevention program for youth. PPW consists of a single remote-delivered 45-minute session by a research assistant (RA) trained in PPW that is interactive and intended for use by youth in the home setting. It involves screening youth to increase awareness of their current health behaviors; motivational enhancement for change; and establishing a behavior goal plan.
There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40-628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.
After a 4-week observation of the pressure ulcer under investigation, adhesive elastic tape is applied around it for a 4-week period (the tape is changed twice a week), according to a planned application protocol. The ulcer is then observed for a subsequent follow-up period of 4 weeks.
Prenatal exposure to dibutyl phthalate (DBP) has been reported to cause erectile dysfunction (ED) in adult offspring rats. However, its underlying mechanisms are not fully understood. Previously, we found that DBP activates the RhoA/ROCK pathway in the male reproductive system. This study investigated how prenatal exposure to DBP activates the RhoA/ROCK signalling pathway, leading to ED in male rat offspring. Pregnant rats were stratified into DBP-exposed and NC groups, with the exposed group receiving 750 milligrams per kilogram per day (mg/kg/day) of DBP through gavage from days 14-18 of gestation. DBP exposure activated the RhoA/ROCK pathway in the penile corpus cavernosum (CC) of descendants, causing smooth muscle cell contraction, fibrosis, and apoptosis, all of which contribute to ED. In vitro experiments confirmed that DBP induces apoptosis and RhoA/ROCK pathway activation in CC smooth muscle cells. Treatment of DBP-exposed offspring with the ROCK inhibitor Y-27632 for 8 weeks significantly improved smooth muscle cell condition, erectile function, and reduced fibrosis. Thus, prenatal DBP exposure induces ED in offspring through RhoA/ROCK pathway activation, and the ROCK inhibitor Y-27632 shows potential as an effective treatment for DBP-induced ED.
Prostate cancer is the most common cancer diagnosed in men, and is increasingly managed with effective treatment strategies, including surgery. Although active treatment provides excellent cancer control, issues related to the functional and health-related quality of life outcomes following treatment persist. Surgical therapy (radical prostatectomy) is a commonly used treatment but is associated with erectile and sexual dysfunction, in addition to urinary incontinence. Substantial efforts have been made to reduce rates of incontinence and impotence following surgery. Nerve-sparing prostatectomy has been the most successful technique for preserving erectile function in sexually active men; however, issues such as the quality of the nerve-sparing, surgeon experience, and case complexity continue to impact the outcomes of many men treated with radical prostatectomy. In addition, for patients with low-risk, early-stage prostate cancer, there is currently debate regarding the extent of dissection and tissue removal around the prostate. Specifically, the necessity of complete removal of the seminal vesicles (paired structures located adjacent to the prostate and posterior to the base of the bladder that are responsible for the majority of ejaculate volume) is not clear. This is potentially important for functional and health-related quality of life outcomes because the nerves responsible for erectile function course immediately next to the seminal vesicles. Complete dissection and removal therefore risks injury to these nerves, and may decrease the overall quality of nerve sparing during prostatectomy. Our objective is to determine if seminal vesicle-sparing, in addition to nerve-sparing, results in relatively preserved post-surgery functional and health-related quality of life outcomes (erectile function and urinary continence) compared to nerve-sparing alone in select patients with low-risk, early-stage prostate cancer treated surgically with prostatectomy. In order to evaluate this objective, we will randomize a series of men with recently diagnosed, low-risk, early-stage prostate cancer who choose surgical therapy to either standard nerve-sparing prostatectomy or seminal vesicle-sparing prostatectomy. We will then compare sexual and urinary function post-operatively to determine if there is a difference in treatment approach.
1377306 Esters of 3-methyl-quinoxaline-2- carboxylic acid-di-N-oxides PFIZER Inc 31 Jan 1972 [20 April 1971] 4505/72 Addition to 1330151 Heading C2C Novel esters of 3-methyl-2-quinoxaline carboxylic acid, 1,4-dioxide of general Formula I: in which X is a 6- or 7-position substituent selected from hydrogen, chloro, bromo, fluoro, methyl, methoxy or trifluoromethyl A is alkylene of 2-5 C atoms and Z is acyloxy of formula O 2 CR where R is C 4-10  alkyl, C 1-4  alkoxy, C 1-4  alkylamino, C 2-8  carboxyalkyl or substituted C 1-4  alkyl (in which the substituent is chlorine, bromine or di-C 1-3  alkyl-amino) and where appropriate acid addition salts, pharmaceutically acceptable basic salts and C 1-3  alkyl quaternary salts with a pharmaceutically acceptable anion are prepared by (1) reacting a benzofuran of general Formula II: with either CH 3 -CO-CH 2 -O-O-A-Z or CH 3 -CH 2 -CO-CO-O-A-Z in the presence of a base or (2) reacting an ester 2-quinoxaline carboxylic acid, 1,4-di-N-oxide of general Formula III: in which M is alkyl or phenyl or a 2-cyanoquinoxaline-di-N-oxide of general Formula IV: with an alkanol of general Formula HO-A-Z Compounds of general Formula I, in which Z is carboxyacyloxy or acyloxy, may be prepared from compounds III in which M is 2-hydroxyethyl, by reaction with the appropriate anhydride or acid chloride. Compounds of general Formula I in which Z is alkyl carbamoyl may be prepared from compounds III in which M is 2- hydroxyethyl by reaction with the appropriate isocyanate. Compounds of general Formula I in which Z is dialkylaminoacyloxy are prepared by reaction of a secondary amine with a compound of general Formula I in which Z is alkyl substituted by chlorine or bromine. Preferred compounds are 3-methyl-2-quinoxaline carboxylic acid, 2-(3-carboxypropionyloxy)ethyl ester, di - N - oxide; 3 - methyl - 2 - quinoxaline carboxylic acid, 2 - (4 - carboxybutyryloxy)ethyl ester, di - N - oxide; 3 - methyl - 2 - quinoxaline carboxylic acid, 2 - (octanoyloxy)ethyl ester, di - N- oxide; 3 - methyl 2 - quinoxaline carboxylic acid, 2 - [(ethoxycarbonyl)oxy]ethyl ester, di - N - oxide.  Compounds of formula are anti-microbials and may be used in water treatment, paint and wood preservation, as a disinfectant and as an antibiotic. They form with a suitable carrier a pharmaceutical composition which may be administered orally, parenterally or topically. Compounds of Formula I also may be added to an animal feed for promoting growth and improving feed efficiency.
The invention discloses an oil control composition and application thereof, and a cosmetic containing the oil control composition and a preparation method thereof. The oil control composition comprises chlorella extract, spiraea extract, mountain withered leaf extract and Norway Yun Binshe extract; the chlorella extract, the spiraea extract, the mountain withered leaf extract and the Norway Yun Binshe extract are combined according to a certain proportion to synergistically increase, so that the composition can effectively inhibit the differentiation of sebaceous gland cells and the activity of 5 alpha-reductase, reduce the excessive secretion of sebum and improve the oil production phenomenon. And simultaneously improve the skin micro-ecological environment and reduce inflammatory reaction. Moreover, each component of the composition is an extract of plant origin, which is very warm and non-irritating. The prepared composition and the cosmetic containing the composition have excellent oil control effect. The preparation method of the oil control composition-containing cosmetic provided by the invention has the advantages that the components are mixed and stirred uniformly according to a certain sequence and conditions, the operation is simple, and the cosmetic stability is good.
Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, irritability, and miosis. With large oral overdoses, reversible cardiac conduction defects or arrhythmias, apnea, coma, and seizures have been reported. As little as 100 mcg of oral clonidine has produced signs of toxicity in pediatric patients.

There is no specific antidote for clonidine overdosage. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension. Hypertension associated with overdosage has been treated with intravenous furosemide, diazoxide or alpha-blocking agents such as phentolamine. Naloxone may be a useful adjunct in the treatment of clonidine induced respiratory depression, hypotension, and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. Dialysis is not likely to significantly enhance the elimination of clonidine.

The largest overdose reported to date involved a 28-year old white male who ingested 100 mg of clonidine hydrochloride powder. This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semi-coma, and premature ventricular contractions. The patient fully recovered after intensive treatment. Plasma clonidine levels were 60 ng/mL after 1 hour, 190 ng/mL after 1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In mice and rats, the oral LD50 of clonidine is 206 and 465 mg/kg, respectively.
BACKGROUND: While soft tissue sarcomas affect younger patients, few studies have assessed the distribution of underlying pathogenic germline variants.
PATIENTS AND METHODS: We retrospectively identified all pediatric and young adult patients (0-22 years) at Haukeland University Hospital, Norway (1981-2019), through clinical and pathological records. We identified n = 46 eligible patients. From these 46 patients, adequate material representing normal tissue was available for n = 41 cases (n = 24 diagnosed with rhabdomyosarcoma, 9 with synovial sarcomas, 2 with Ewing sarcomas, and 6 without further classification), with matching tumor tissue for n = 40. Normal tissue samples were analyzed for germline pathogenic variants (PVs) by targeted sequencing of 360 cancer genes.
RESULTS: Out of the 41 analyzed cases, we found PVs or likely PVs in 7 (17%). These variants were found in TP53, MUTYH, FANCC, DICER1, FANCA, MYO3A, and MYO5B. Supporting the causality of these PVs, four cases revealed loss of heterozygosity (LOH) of the wild-type allele in the tumor tissue, one patient with a PV in DICER1 had a second somatic variant in DICER1, and a patient with a PV in TP53 had the altered allele amplified in the tumor. For three out of five with available family history, a history of other cancers in relatives was recorded. Among genes with variants of uncertain significance, CHD1L was of particular interest, revealing a stop-gain and a missense variant.
INTERPRETATION: A high fraction of young patients with soft tissue sarcoma harbor PVs. Among the genes affected, we substantiate a potential role of MYO5B and propose a potential role for MYO3A.
The comparison group patients were not given the data from the electronic data monitoring feedback data. Instead, they filled out a self report form that all patients fill out. If they indicated in this report that their adherence in the previous was less than 95%, then they were flagged for "enhanced counseling" with a doctor. This counseling was based on the patient's self report. Thus both groups received enhanced counseling if they indicated poor adherence, but only the intervention group were given their electronic data output.
Candidate subjects will undergo a temporal bone Computed Tomography (CT) scan, contrast enhanced head Magnetic Resonance Imaging (MRI), audiogram with immittance testing, pitch and level matching of tinnitus, Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Response (ABR) testing prior to promontory stimulation. Head MRI, DPOAE, audiogram and immittance testing are considered clinically routine for assessment of asymmetric tinnitus. Temporal bone CT, ABR, tinnitus pitch, level matching, masking levels and residual inhibition testing are not standard clinical assessments for asymmetric tinnitus. In addition, subjects will complete the Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI) and Visual Analog Scale (VAS) questionnaires three separate times within the week prior to promontory stimulation testing. Additional testing for comorbid anxiety and depressive conditions will be a screening Generalized Anxiety Disorder (GAD7), Patient Health Questionnaire (PHQ8), and short Health Anxiety Inventory (HAI-S). The NEO Personality Inventory (NEO PI) will be administered to provide baseline information. The initial session of promontory stimulation will define optimal stimulation parameters (i.e., location, current level, pulse-width, phase polarity), where maximal tinnitus suppression occurs with minimal or no auditory percept. After these parameters are established, the patient will complete the THI, TFI, and VAS immediately prior to stimulation, during stimulation, and following completion of stimulation at 10-minutes, 1-hour, 24-hours, 48-hours, and 1-week following completion of stimulation. In addition, pitch and level matching of tinnitus will be completed immediately upon completion of each promontory stimulation session. Each patient will undergo three successive treatments separated by 1-week. Prior to each treatment, the patient will receive an audiogram and DPOAE testing to document interval safety. At the conclusion of the study, subjects will be asked about their willingness to undergo surgical implantation of a device capable of long-term scheduled or on-demand electrical stimulation for tinnitus suppression
Studies in healthy adult volunteers reveal that intravenous lorazepam in doses up to 3.5 mg/70 kg does not alter sensitivity to the respiratory stimulating effect of carbon dioxide and does not enhance the respiratory-depressant effects of doses of meperidine up to 100 mg/70 kg (also determined by carbon dioxide challenge) as long as patients remain sufficiently awake to undergo testing. Upper airway obstruction has been observed in rare instances where the patient received greater than the recommended dose and was excessively sleepy and difficult to arouse (see WARNINGS and ADVERSE REACTIONS).

Clinically employed doses of lorazepam injection do not greatly affect the circulatory system in the supine position or employing a 70-degree tilt test. Doses of 8 mg to 10 mg of intravenous lorazepam (2 to 2-1/2 times the maximum recommended dosage) will produce loss of lid reflexes within 15 minutes.

Studies in 6 healthy young adults who received lorazepam injection and no other drugs revealed that visual tracking (the ability to keep a moving line centered) was impaired for a mean of 8 hours following administration of 4 mg of intramuscular lorazepam and 4 hours following administration of 2 mg intramuscularly with considerable subject variation. Similar findings were noted with pentobarbital, 150 and 75 mg. Although this study showed that both lorazepam and pentobarbital interfered with eye-hand coordination, the data are insufficient to predict when it would be safe to operate a motor vehicle or engage in a hazardous occupation or sport.
There is strong evidence to support that community-dwelling older adults who are able to maintain their involvement in social, recreational, spiritual and physical activities experience positive effects on their health and quality of life. While winter creates challenges to community participation for many Manitobans, these difficulties are magnified for older adults and particularly for older adults who use wheelchairs. The aim of this study is to explore ways to improve or maintain community participation of community-dwelling older adults who use wheelchairs in the winter. Using a single-subject design, five older adult Manitobans who are wheelchair users will each select three community-based participation goals to work on throughout the winter months. Each older adult participant will work with an occupational therapist to receive individually-focused interventions aimed at increasing his or her community participation. The investigators will use a client-centered outcome measure designed to detect changes in performance and satisfaction in the goals that the individual has self-identified as being important to him or her, yet difficult to perform. The findings of this study will help determine the feasibility of conducting a larger scale study that would include a greater number of older adult Manitobans. Older adult wheelchair users in Manitoba bear a disproportionate burden in the winter when aging, mobility limitations, and weather coincide to create conditions that make community participation exceedingly difficult. It is important to the health and well-being of older adult Manitobans to find effective ways to promote community engagement throughout the winter months.
Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.