anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.
The present invention relates to a medicine composition of a freezing-drying powder injection and a large injection of antihepatitis medicine and preparation method. The medicine composition of the freezing-drying powder injection comprises 1 part of an effective component of meadowrueleaf corydalis roots and 50 to 500 parts of auxiliary materials. The method comprises the steps that after decocted with water and extracted, the meadowrueleaf corydalis roots are made into meadowrueleaf corydalis root extract products through separation, purification and refining; the meadowrueleaf corydalis root extract products and the auxiliary materials are uniformly mixed, and are dissolved in injecting water; then, the meadowrueleaf corydalis root extract products and the auxiliary materials are filtered, filled, packaged and frozen; the composition of the large injection comprises 1 part of an effective component of meadowrueleaf corydalis roots and 800 to 10000 parts of auxiliary materials. The method comprises the steps that after decocted with water and extracted, the meadowrueleaf corydalis roots are made into meadowrueleaf corydalis root extract products through separation, purification and refining; the meadowrueleaf corydalis root extract products and the auxiliary materials are uniformly mixed and are dissolved in injecting water; the meadowrueleaf corydalis root extract products and the auxiliary materials are filtered, filled and sterilized. The medicine composition is a Chinese herbal medicine with a special folk secret prescription for curing hepatitis, and the injection is extracted and refined by the meadowrueleaf corydalis roots through a modern scientific method. The present invention has the functions of clearing heat, expelling toxin and alleviating pain and is mainly used for patients with oxyhepatitis, chronic hepatitis and dampness and heat in liver and gallbladder. The present invention has good market perspective and social benefit.
Metformin as either immediate- or extended-release formulations can be utilized, and titrated to a maximum daily dose of 2,500 mg. Participants receiving metformin will have insulin added only if they have not achieved euglycemia for at least 30% of glucose values after generally receiving the maximum daily dose of metformin of 2,500 mg, or in select situations in the setting of participant intolerance due to mild gastrointestinal symptoms. Participants will be asked to continue taking metformin after treatment supplementation with insulin.
Prednihexal (Prednisolon), daily oral tablet, 10 mg during week one to four, 7,5 mg during week five to eight. Finally 5 mg for four weeks.
Activating the cGAS-STING pathway of circulating tumor cell clusters (CTC clusters) represents a promising strategy to mitigate metastases. To fully exploit the potential of cholesterol-regulating agents in activating CTCs' STING levels, we developed a nanoparticle (NP) composed of metal complex lipid (MCL). This design includes MCL-miriplatin to increase NP stiffness and loads lomitapide (lomi) modulating cholesterol levels, resulting in the creation of PLTs@Pt-lipid@lomi NPs. MCL-miriplatin not only enhances lomi's eliciting efficacy on STING pathway but also increases NPs' stiffness, thus a vital factor affecting the penetration into CTC clusters to further boost lomi's ability. Demonstrated by cy5 tracking experiments, PLTs@Pt-lipid@lomi NPs quickly attach to cancer cell via platelet membrane anchorage, penetrate deep into the spheres, and reach the subcellular endoplasmic reticulum where lomi regulates cholesterol. Additionally, these NPs have been shown to track CTCs in the bloodstream, a capability not demonstrated by the free drug. PLTs@Pt-lipid@lomi NPs more efficiently activate the STING pathway and reduce CTC stemness compared to free lomi. Ultimately, PLTs@Pt-lipid@lomi NPs reduce metastasis in a post-surgery animal model. While cholesterol-regulating agents are limited in efficacy when being repositioned as immunomodulatory agents, this MCL-composing NP strategy demonstrates the potential to effectively deliver these agents to target CTC clusters.
The invention belongs to the technical field of biomedicine and molecular biology, and particularly relates to application of targeted HIF-1/CBS in triple negative breast cancer. The present invention demonstrates that under hypoxic conditions, TNBC cells are upregulated by HIF-1-induced CBS, thereby providing an alternative source of cysteine for glutathione synthesis and protecting the cells from iron death induced by inhibition of cystine uptake. CBS is overexpressed in BCSCs and mediates resistance of BCSCs to iron death. Genetic or pharmacological inhibition of CBS reduces the number of BCSCs in vitro and in vivo by inducing iron death. Pharmacological inhibition of HIF-1 decreases CBS expression, inhibits tumor initiation, and increases time to tumor recurrence. The above results indicate that targeting HIF-1/CBS may reduce BCSC numbers by inducing iron death, improving the clinical prognosis of TNBC patients.
The CAMS Therapeutic Assessment incorporates low levels of lethal means restriction (see above). Experimental Intervention Component 4 will provide a high level of lethal means restriction that includes the evaluation of the need for a lock box, the provision of a lock box if needed, structured process for evaluating home safety in each room of the house, specific directives to accomplish, follow up with the clinician, and problem-solving barriers to lethal means restriction over two, 30-minute modules delivered across 2 sessions.
Participants undergo weight management and health behavior intervention with a combination of 4 components for 16 weeks. TELEPHONE COACHING: Participants receive 1 phone call each week from a coach over 30-45 minutes to discuss diet, physical activity and goal setting. EMAIL COACHING: Participants receive 1 phone call to discuss the process over 10-15 minutes and then receive 1 email each week for 16 weeks. NO COACHING: Participants receive 1 phone call the first week over 10-15 minutes to discuss the process. TEXT MESSAGING: Participants receive 7-12 text messages comprising information about diet and physical activity each week for 16 weeks. SELF-MONITORING: Participants record their food intake and weight directly into the Fitbit website or application 4-7 days each week or 1 day each week for 16 weeks. FAMILY TEAM INTERVENTION: Participants receive 2 group phone calls and join a Facebook group that is monitored by research staff where they can interact with each other and coaches.
INTRODUCTION: Post stroke elbow spasticity (PSES) affects over a third of individuals following stroke and negatively impacts on functional recovery, comfort and quality of life. Drug therapies have limited efficacy and unwanted side effects, botulinum toxin, although effective, is costly, and conventional electrical stimulation therapies are limited long term by habituation. We aim to investigate the efficacy of Sheffield Adaptive Patterned Electrical Stimulation (SHAPES), that delivers temporally and spatially varying pattern of electrical stimulation, against transcutaneous electrical stimulation (TENS) and standard care at reducing PSES.
METHODS AND DESIGN: Overall, 297 people with PSES will be randomised (1:1:1) to one of 3 arms: Standard care (no electrical stimulation), TENS (conventional patterned electrical stimulation) or SHAPES (adaptive patterned electrical stimulation). Both SHAPES and TENS are delivered using a specially designed electrical stimulation sleeve used for 60 min each day for 6-weeks. Outcome measures are completed at baseline, end of treatment (EOT 6 weeks) and then 6-weeks, 12-weeks and 24-weeks after the end of treatment. Efficacy will be determined based on the proportion of participants experiencing meaningful improvement (18%) in the 7-day Numerical Rating Scale (NRS-S) for PSES, compared between both intervention arms and standard care, and between the two intervention groups. Measures of arm motor function (Action Research Arm Test, MRC scale), and quality of life (SQoL-6D, EQ-5D) will also be measured along with a parallel health economic evaluation.
DISCUSSION: The results of the SHAPES trial will inform management of elbow spasticity after stroke. The SHAPES intervention is a low cost, self-administered intervention for the management of spasticity that can be used repeatedly, and if found to be more effective than TENS or control has the potential to be widely implemented in the UK NHS healthcare setting. Furthermore, despite the wide use of TENS in the management of spasticity, this study will provide critically required evidence regarding its efficacy. The trial has been registered with the ISRCTN registry (ISRCTN26060261).
Breech presentation occurs in approximately 3-4% of term pregnancies and leads to one of the most common indications for cesarean delivery. Attempting an external cephalic version (ECV) significantly increases the chance of cephalic presentation at time of delivery and reduces the chance of cesarean section. Since ECV does in fact reduce the rate of cesarean section, many studies have sought to determine the best method to perform the procedure to optimize the chance of success. A recent meta-analysis concluded that administration of neuraxial analgesia significantly increases the success rate of ECV and also increases the incidence of vaginal delivery. However, there have been only 2 prospective studies and no randomized trials that evaluated the success of ECV using neuraxial analgesia only when initial attempt without it has failed. Therefore, the study team designed a randomized controlled trial with two groups: Group 1- patients receiving spinal anesthesia immediately versus Group 2- patients attempting ECV without spinal anesthesia with reattempt using a spinal if first attempt fails. This study will be conducted on labor and delivery at Mount Sinai West hospital. Patients who present to labor and delivery at term for ECV will be approached for enrollment and those who consent to be part of the study would be randomized into a group. ECV will then be attempted and delivery and neonatal outcomes will be collected. Patients will likely be enrolled in the study from time of version (approximately 37 weeks) until postpartum. This study will take approximately 1-2 years given the ECV rate.
BACKGROUND: There are socioeconomic inequalities in the prevalence of multimorbidity and its accumulation across the life course. Estimates of multimorbidity prevalence in English primary care increased by more than two-thirds from 2004 to 2019. We developed a microsimulation model to quantify current and projected multimorbidity inequalities in the English adult population.
METHODS: We used primary care data for adults in England from the Clinical Practice Research Datalink Aurum database between 2004 and 2019, linked to the 2015 English Index of Multiple Deprivation (IMD), to model time individuals spent in four health states (healthy, one chronic condition, basic multimorbidity [two or more chronic conditions], and complex multimorbidity [three or more chronic conditions affecting three or more body systems]) by sex, age, IMD quintile, birth cohort, and region. We applied these transition times in a stochastic dynamic continuous-time microsimulation model to Office for National Statistics population estimates for adults aged 30-90 years. We calculated projected prevalence and cumulative incident cases from 2019 to 2049 by IMD quintile, age group (younger than 65 years vs 65 years and older), and years to be lived without multimorbidity at age 30 years.
FINDINGS: Under the assumption that all chronic conditions were lifelong, and that once diagnosed there was no recovery, we projected prevalence of multimorbidity (basic or complex) increases by 34% from 53·8% in 2019 to 71·9% (95% uncertainty interval 71·8-72·0) in 2049. This rise equates to an 84% increase in the number of people with multimorbidity: from 19·2 million in 2019 to 35·3 million in 2049 (35·3 million to 35·4 million). This projected increase is greatest in the most deprived quintile, with an excess 1·07 million (1·04 million to 1·10 million) cumulative incident basic multimorbidity cases and 0·70 million (0·67 million to 0·74 million) complex multimorbidity cases over and above the projected cases for the least deprived quintile, largely driven by inequalities in those younger than 65 years. The median expected number of years to be lived without multimorbidity at age 30 years in 2019 is 15·12 years (14·62-16·01) in the least deprived IMD quintile and 12·15 years (11·61-12·60) in the most deprived IMD quintile.
INTERPRETATION: The number of people living with multimorbidity will probably increase substantially in the next 30 years, a continuation of past observed increases partly driven by changing population size and age structure. Inequalities in the multimorbidity burden increase at each stage of disease accumulation, and are projected to widen, particularly among the working-age population. Substantial action is needed now to address population health and to prepare health-care and social-care systems for coming decades.
FUNDING: University of Liverpool and National Institute for Health and Care Research School for Public Health Research.
Eligible patients begin to use apatinib mesylate tablets and PD-1, apatinib mesylate tablets at the recommended dose of 250mg,oral, QD, continuous administration, 4 weeks (28 days) as an observation cycle. Until the disease progressed or unbearable adverse reactions appeared. If missed medication occurs during the medication period, it is confirmed that the next medication time is less than 12 hours, then there will be no replenishment. The recommended dose of PD-1 is 200mg/time, Q2W, intravenous injection, 4 weeks (28 days) as an observation cycle, until disease progression or intolerable toxicity.
Older adults with hearing loss may experience difficulty recognizing speech in noise due to factors related to attenuation (e.g., reduced audibility and sensation levels, SLs) and distortion (e.g., reduced temporal fine structure, TFS, processing). Furthermore, speech recognition may improve when the amplitude modulation spectrum of the speech and masker are non-overlapping. The current study investigated this by filtering the amplitude modulation spectrum into different modulation rates for speech and speech-modulated noise. The modulation depth of the noise was manipulated to vary the SL of speech glimpses. Younger adults with normal hearing and older adults with normal or impaired hearing listened to natural speech or speech vocoded to degrade TFS cues. Control groups of younger adults were tested on all conditions with spectrally shaped speech and threshold matching noise, which reduced audibility to match that of the older hearing-impaired group. All groups benefitted from increased masker modulation depth and preservation of syllabic-rate speech modulations. Older adults with hearing loss had reduced speech recognition across all conditions. This was explained by factors related to attenuation, due to reduced SLs, and distortion, due to reduced TFS processing, which resulted in poorer auditory processing of speech cues during the dips of the masker.
Participants will receive SMS reminders as described in the SMS reminder arm. Additionally, participants will be sent a 150 Kenyan Shillings (KES) incentive to the mobile phone number they provided at enrollment. The incentive will be delivered three days before the child turns nine months (i.e. sent on the same day as the first SMS reminder). Caregivers will receive the mobile-money incentive unconditionally. The intent of the incentive is to help offset the costs associated with transportation to the clinic. The transaction costs associated with mobile-money transactions will be borne by the study such that mothers will receive the full 150 KES.
Use oxycodone when pain is mild level. Start from 10 mg every 12 hours and titrate for appropriate dose.
Seven hundred thirty two (732) patients were treated with Cetrotide® (cetrorelix acetate for injection) in five (two Phase 2 dose-finding and three Phase 3) clinical trials. The clinical trial population consisted of Caucasians (95.5%) and Black, Asian, Arabian and others (4.5%). Women were between 19 and 40 years of age (mean: 32). The studies excluded subjects with polycystic ovary syndrome (PCOS), subjects with low or no ovarian reserve, and subjects with stage III-IV endometriosis.

Two dose regimens were investigated in these clinical trials, either a single dose per treatment cycle or multiple dosing. In the Phase 2 studies, a single dose of 3 mg was established as the minimal effective dose for the inhibition of premature LH surges with a protection period of at least 4 days. When Cetrotide® is administered in a multidose regimen, 0.25 mg was established as the minimal effective dose. The extent and duration of LH-suppression is dose dependent.

In the Phase 3 program, efficacy of the single 3 mg dose regimen of Cetrotide® and the multiple 0.25 mg dose regimen of Cetrotide® was established separately in two adequate and well controlled clinical studies utilizing active comparators. A third non-comparative clinical study evaluated only the multiple 0.25 mg dose regimen of Cetrotide®. The ovarian stimulation treatment with recombinant FSH or human menopausal gonadotropin (hMG) was initiated on day 2 or 3 of a normal menstrual cycle. The dose of gonadotropins was administered according to the individual patient's disposition and response.

In the single dose regimen study, Cetrotide® 3 mg was administered on the day of controlled ovarian stimulation when adequate estradiol levels (400 pg/mL) were obtained, usually on day 7 (range day 5-12). If hCG was not given within 4 days of the 3 mg dose of Cetrotide®, then 0.25 mg of Cetrotide® was administered daily beginning 96 hours after the 3 mg injection until and including the day of hCG administration.

In the two multiple dose regimen studies, Cetrotide® 0.25 mg was started on day 5 or 6 of COS. Both gonadotropins and Cetrotide® were continued daily (multiple dose regimen) until the injection of human chorionic gonadotropin (hCG).

Oocyte pick-up (OPU) followed by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) as well as embryo transfer (ET) were subsequently performed. The results for Cetrotide® are summarized below in Table 2.

In addition to IVF and ICSI, one pregnancy was obtained after intrauterine insemination. In the five Phase 2 and Phase 3 clinical trials, 184 pregnancies have been reported out of a total of 732 patients (including 21 pregnancies following the replacement of frozen-thawed embryos).

In the 3 mg regimen, 9 patients received an additional dose of 0.25 mg of Cetrotide® and two other patients received two additional doses of 0.25 mg Cetrotide®. The median number of days of Cetrotide® multiple dose treatment was 5 (range 1-15) in both studies.

No drug related allergic reactions were reported from these clinical studies.
Treatments with adalimumab and other tumor necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), are usually continued indefinitely. Information concerning the possibility of discontinuing anti-TNF therapy in RA patients who are in remission is limited. This is a pilot study in one country to study the effect of adalimumab discontinuation. The objective is to assess the proportion of patients with established RA in stable remission (Disease Activity Score \[DAS\]28 \<2.6) after treatment with adalimumab in combination with methotrexate, in whom it is possible to discontinue adalimumab and to compare the remission rates among patients on sustained therapy with adalimumab + methotrexate with remission rates among patients who discontinued adalimumab.

Rheumatoid arthritis patients in stable remission (DAS28 \< 2.6) treated with adalimumab + methotrexate were randomized in a 1:1 ratio to continue with adalimumab treatment or discontinue adalimumab treatment for the following 52 weeks. Subsequently an observational extension was conducted to observe patients treated at the discretion of the investigator. The observational extension period lasted until Weeks 105 - 156 (average Week 125) and consisted of one follow-up visit. Participants randomized to discontinue adalimumab therapy will be reinstituted to adalimumab if DAS28-score increases by \>1.2 units from baseline and/or is scored ≥2.6 at any visit during the study and will be followed for an additional 12 weeks.
Exercise sessions performed using eight times (sets) with 4-5 repetitions at 70-75% of the maximal strength. The concentric phase was performed as fast as possible, and the eccentric phase was carried out for 2 s.