anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Compositions containing three compounds which have, respectively, isothiocyanate, thiocarbamate, and thiourea groups attached to benzene rings, are new. The compsns. are obtd. from extracts of Pentadiplandra Brazzeana, and contain propyl 2-anisyl-1-methyl isothiocyanate (I), ethyl N-benzyl thiocarbamate (II) and N,N-dibenzyl thiourea (III). USE - As a syrup, the compositions are useful in the treatment of functional metrorrhagia and as a powerful venous tonic. As a pomade the compositions may be used to trap free radicals.
Although strokes are frequent and severe, treatment options are scarce. Plasminogen activators, the only FDA-approved agents for clot treatment (tissue plasminogen activators (tPAs)), are used in a limited patient group. Moreover, there are few approaches for handling the brain's inflammatory reactions to a stroke. The orphan G protein-coupled receptor 55 (GPR55)'s connection to inflammatory processes has been recently reported; however, its role in stroke remains to be discovered. Post-stroke neuroinflammation involves the central nervous system (CNS)'s resident microglia activation and the infiltration of leukocytes from circulation into the brain. Additionally, splenic responses have been shown to be detrimental to stroke recovery. While lymphocytes enter the brain in small numbers, they regularly emerge as a very influential leukocyte subset that causes secondary inflammatory cerebral damage. However, an understanding of how this limited lymphocyte presence profoundly impacts stroke outcomes remains largely unclear. In this study, a mouse model for transient middle cerebral artery occlusion (tMCAO) was used to mimic ischemia followed by a reperfusion (IS/R) stroke. GPR55 inactivation, with a potent GPR55-specific antagonist, ML-193, starting 6 h after tMCAO or the absence of the GPR55 in mice (GPR55 knock out (GPR55ko)) resulted in a reduced infarction volume, improved neurological outcomes, and decreased splenic responses. The inhibition of GPR55 with ML-193 diminished CD4+T-cell spleen egress and attenuated CD4+T-cell brain infiltration. Additionally, ML-193 treatment resulted in an augmented number of regulatory T cells (Tregs) in the brain post-tMCAO. Our report offers documentation and the functional evaluation of GPR55 in the brain-spleen axis and lays the foundation for refining therapeutics for patients after ischemic attacks.
The prevalence of obesity is increasing throughout the world. General Anesthesia for obese patients is associated with increased risk of difficult/failed tracheal intubation and aspiration of gastric contents. These life-threatening complications can be avoided by use of regional anesthesia. Other potential advantages of regional anesthesia include improved pain control, less incidence of nausea and vomiting, early ambulation, decreased pulmonary complications, shorter hospital stay. On the other hand, regional anesthesia in obese patients can be challenging because of loss in anatomical landmarks. However, the availability of high-resolution ultrasound imaging has decreased the reliance on anatomical landmarks as the vascular, nervous and musculoskeletal structures can be directly visualized. Ultrasound imaging also allows real time needle visualization and local anesthetic can be deposited more precisely allowing faster onset anesthesia and reduced incidence of complications. Brachial plexus can be anaesthetized at various levels along its course to provide anesthesia for elbow, forearm and hand surgery. Axillary region is ideal site for targeting brachial plexus in obese patients as the plexus is superficial in this region and the likelihood of causing serious complications (e.g. pleural puncture) is low. Study of 188 patients by Chan et al showed that use of ultrasound increases the success rate of axillary brachial plexus block from 63% to 80% when compared with nerve stimulation technique. A recent study (Hanouz et al) showed that obesity increases the failure rate and immediate complications of axillary brachial plexus block but ultrasound was not used for performing the block. In current era, we consider ultrasound-guidance as a standard of care. We hypothesize that the block performance time, success rate and incidence of acute complications are similar in obese and non-obese patients when ultrasound-guidance is used to perform brachial plexus block in axillary region.
This study is a randomized, double-blind, placebo-controlled, combined single and multiple ascending dose (SAD and MAD) trial. Up to one hundred fifty two (152) subjects aged 18-55, who fulfill the inclusion/exclusion criteria, may be enrolled in this study. Up to a total of 17 SAD and 2 MAD cohorts of eight subjects each will be examined. Subjects in each cohort will be randomized 3:1 to receive SPR994 at doses ranging from 100 mg to 900 mg or placebo in various immediate and timed release formulations. One SAD control cohort, Cohort 12, may be enrolled in which eight subjects will receive a single dose of Orapenem® at 300 mg in a fed and fasted state. Dosing is complete in SAD Cohorts 1-3, 6 and 7. Subjects in Cohorts 1-3 received a single dose of SPR994 and subjects in food effect Cohorts 6 and 7 each received 2 doses. Subjects enrolled in SAD Cohorts 8 and beyond will receive a single dose of SPR994 or placebo in a fasted state and a second dose following a standardized meal to investigate food effect on the pharmacokinetics of SPR994 and TBPM. SAD Cohorts 8 through 10 may run in a staggered or concurrent manner before enrollment of further cohorts. Blinded pharmacokinetic data will be reviewed at the conclusion of Cohort 10 (300 mg fasted \& fed). Should the PK be optimized in one of the various time released formulations, the Sponsor may decide to proceed to enrollment of the 600 mg Cohorts using the optimal formulation; other timed release formulations may also be explored at 300 mg dose in a staggered or concurrent manner until an optimal formulation(s) is identified. When an optimal formulation(s) is identified, the 600 mg Cohorts may run in a staggered or concurrent manner. SAD Cohorts 16 (100 mg fasted) and 17 (900 mg fasted) may run prior to or in a staggered or concurrent manner with MAD Cohorts 4 (300 mg) and 5 (600 mg). During the MAD part of the study, subjects will receive 27 doses of SPR994 or placebo over a period of 14 days. Based on the observed PK of SPR994 in prior cohorts, the total number of doses may be increased to 40 doses of SPR994 or placebo administered TID over 14 days; only one dose will be administered on Day 14 to allow for PK sample collection In both SAD and MAD parts of the study, the Cohorts will be exposed to increasing doses of SPR994. Each part (SAD and MAD) of the study will consist of 3 periods: a screening period, a treatment period, and a follow-up period. The safety and tolerability of SPR994 will be assessed based on the types and frequency of adverse events (AEs) reported; concomitant medication usage; and changes from baseline in physical examination, weight, vital signs, ECG, and standard clinical laboratory tests. A Safety Management Group (SMG) will review the data of cohorts prior to escalating to the next dose level.
The purpose of this study is to assess the safety, tolerability, and immunogenicity of immunization with 2 doses of the PfCSP DNA vaccine (given 1 month apart) followed by a single dose of MVA.CSO (given either 1 month or 6 months later) when administered to healthy, malaria semi-immune adult volunteers. This Phase 1, randomized study conducted at Tetteh Quarshie Memorial Hospital will enroll 48 healthy volunteers, ages 18 to 50 years. Twenty four volunteers will initially be recruited and randomized to Groups 1 and 2. During Months 4 and 5 of the study, another 24 volunteers will be recruited and randomized to Groups 3 and 4. Group 1 will receive the DNA malaria vaccine intramuscularly (IM) at months 0 and 1, and the MVA malaria vaccine intradermally (ID) at month 7. Group 2 will receive a rabies vaccine IM at months 0 and 1, and a normal saline injection ID at month 7. Group 3 will receive the DNA malaria vaccine IM at months 5 and 6, and the MVA malaria vaccine ID at month 7. Group 4 will receive the rabies vaccine IM at months 5 and 6, and a normal saline injection ID at month 7. Blood samples will be collected at intervals for safety and immunogenicity studies. Vaccine safety will be monitored until 10 months after the final dose. At the conclusion of the study, volunteers randomized to Groups 1 and 3 will have the option of receiving the rabies vaccine. The primary study objectives are to: (1) assess the safety and tolerability of immunization with two doses of PfCSP DNA followed by one dose of MVA.CSO in healthy, malaria semi-immune adult volunteers when given at intervals of 0, 1, and 2 months or at 0, 1, and 7 months; (2) evaluate whether the PfCSP DNA/MVA.CSO prime/boost vaccine regimen induces PfCSP-specific immune responses, as assessed by IFN-gamma ELISPOT assay, over background responses; and (3) evaluate whether extending the interval between the second dose of PfCSP DNA and MVA.CSO from 1 month to 6 months is associated with higher levels of PfCSP specific T cell responses in semi-immune adults. The secondary study objective is to evaluate whether extending the interval between the second dose of PfCSP DNA and MVA.CSO from 1 month to 6 months is associated with higher levels of humoral immunity by ELISA and IFAT in semi-immune adults. The principal outcome measure will be the incidence of any vaccine related adverse event, abnormal lab values, and local or systemic reactions. An additional outcome variable for the remaining primary objectives is the results of the IFN-gamma ELISPOT assay at 1 week after administration of MVA.CSO. This study is planned to be the first of multiple clinical trials designed to test malaria vaccines in adults, children, and infants in endemic regions of Ghana.
TH-302 in combination with Pemetrexed. 500 mg/m2 of Pemetrexed is administered IV over 10 minutes on Day 1 of a 21-day cycle.
Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO during screening as clinically indicated, sigmoidoscopy/colonoscopy, anoscopy/proctoscopy or digital rectal exam and CT throughout the study as well as blood sample collection during screening and EOT.
Carcinogenesis 

Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). The doses used in these carcinogenicity studies were approximately 16 (mouse) and 26 (rat) times the MHRD for VMS. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown.

Mutagenesis 

Paroxetine produced no genotoxic effect in a battery of 5 in vitro and 2 in vivo assays that included the following: bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats.

Impairment of Fertility 

A reduced pregnancy rate was found in reproduction studies in rats at a paroxetine dose of 15 mg/kg/day, which is 19 times the MRHD for VMS on an mg/m2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (65 times and 32 times the MHRD for VMS on an mg/m2 basis, respectively).
The main purpose of this study is to evaluate the effectiveness of a parenting enhancement training (PET) for parents with children diagnosed with Attention Deficit-/Hyperactivity Disorder (ADHD) already medicated with methylphenidate (MPH). This particular PET was developed at the Department of Child and Adolescent Psychiatry and Psychotherapy at the University of Cologne and has already been evaluated in several studies. MPH treatment has been proven to be efficacious in the reduction of ADHD symptoms. However, despite optimal titration a substantial percentage of children still suffer from residual symptoms and impairment in psychosocial functioning. Therefore, there is still room for improvement in satisfaction with medication. Moreover, a substantial rate of patients with good treatment effects fails to comply with medication during the course of treatment. This parenting enhancement training (PET) mainly conducted via written materials and telephone support will be introduced in patients already treated with MPH. Effects are expected on symptoms of ADHD as well as on comorbid oppositional symptoms. Further outcome parameters are satisfaction with medication and medication compliance of MPH treatment, psychosocial functioning as well as parenting skills. Parenting skills are a main focus of the PET and ADHD symptoms shall be improved through improving parenting skills. Besides focusing on symptoms, recent research often focuses on improvement of quality of life and impairment in psychosocial functioning (e. g. family, school, leisure time) as well. Not only suffer patients from the main symptoms. Many patients suffer as well from the symptoms' consequences, which is often an overall impairment. Satisfaction with medication and medication compliance are fundamental conditions for the success of a long term medical therapy. However, many studies show a lack of compliance.
Pancreatic cancer (PC) is the most lethal of all major cancers with a five year survival rate of 5 %. While stage I and II tumors leads to an improvement in survival, almost all PCs are currently diagnosed at more advanced non-resectable stages since minimally invasive technique which is capable of screening early-stage PC does not exist. Serum CA19-9 is not recommended as a screening technique because of its low sensitivity and specificity. Imaging modalities such as MRI, CT, EUS and ERCP are more accurate but are not appropriate screening tools due to their high cost, discomfort and complications. Therefore, there is a strong demand for a screening tool with high sensitivity and specificity which is highly acceptable for the patient. The investigators would like to look at the spectroscopy technique for pancreatic cancer diagnosis via an upper endoscopy. A definite diagnosis of the patient is made with histology, cytology or imaging diagnosis. Therefore this study can be positioned as a feasibility study.
The safety and efficacy of nelarabine in adult patients were studied in a clinical trial which included 39 treated patients, 28 who had T-ALL or T-LBL that had relapsed following or was refractory to at least two prior induction regimens. A 1,500-mg/m2 dose of nelarabine was administered intravenously over 2 hours on Days 1, 3, and 5 repeated every 21 days. Patients who experienced signs or symptoms of Grade 2 or greater neurologic toxicity on therapy were to be discontinued from further therapy with nelarabine. Seventeen patients had a diagnosis of T-ALL and 11 had a diagnosis of T-LBL. For patients with ≥ 2 prior inductions, the age range was 16 to 65 years (mean: 34 years) and most patients were male (82%) and Caucasian (61%).Patients with central nervous system (CNS) disease were not eligible. 

Complete response (CR) in this trial was defined as bone marrow blast counts ≤ 5%, no other evidence of disease, and full recovery of peripheral blood counts. Complete response without complete hematologic recovery (CR*) was also assessed. The results of the trial for patients who had received ≥ 2 prior inductions are shown in Table 5. 

Table 5. Efficacy Results in Adult Patients With ≥ 2 Prior Inductions Treated With 1,500 mg/m2 of Nelarabine Administered Intravenously Over 2 Hours on Days 1, 3, and 5 Repeated Every 21 Days

Abbreviations: CR, complete response; CI, confidence interval; CR*, complete response without hematologic recovery.

a Does not include 1 patient who was transplanted (duration of response was 156+ weeks). 

The mean number of days on therapy was 56 days (range of 10 to 136 days). Time to CR plus CR* ranged from 2.9 to 11.7 weeks.
Probiotics are live micro-organisms which when administered in adequate amounts can exert a health benefit on the host. This health-promoting effects have been extensively studied in the gastrointestinal niche but it becomes more and more clear that other niches are also interesting for the potential of probiotics. Recent breakthroughs in 'next generation sequencing' (NGS) technologies are making it now possible to map the microbiota after DNA extraction, which is very interesting for bacteria that are not or difficult to cultivate. The research into the microbiota of the skin with such new NGS technologies currently limited, but shows that there is also an equilibrium in the skin composition of the microbiota and that there is a disturbance of the skin microbiota in acne (Murillo \& Raoult, 2013). In acne vulgaris it is known that the condition is multifactorial and that both hormonal triggers and environmental factors play a role. However, it is also known that Propionibacterium acnes play an important role in the inflammation of the sebaceous gland follicles. Probiotic strains with antipathogenic activity against this bacterium and suitable for application to the skin is thus potentially able to restore the balance of the skin microbiota and reduce acne symptoms.
Rationale: Surgery and radiation are often used as treatments for brain metastases, or tumors in the brain that originate from other parts of the body. It is currently unknown whether patient survival or time to progression would experience additional benefits through the addition of chemotherapy. Previous research does appear to suggest that a chemotherapy regimen may improve outcomes of patients with brain metastases previously treated with radiation. The current study further evaluates this research question by providing patients with recurrent or symptomatic residual brain metastases with carboplatin and temozolomide, two chemotherapy agents. Temozolomide has demonstrated clinical antitumor efficacy against malignant gliomas and has been tested with some efficacy against several other types of cancer. This drug appears to have less adverse effects compared to other commonly used cancer drugs. Recent research indicates that temozolomide also has some efficacy against brain metastases. In addition, previous research indicates carboplatin's lack of severe toxicity in patients with this disease.

Treatment: Study participants will be treated with carboplatin and temozolomide. Carboplatin will be administered through intravenous infusions. Temozolomide will be given through oral pills. Before these drugs are administered, study participants will undergo a pre-treatment evaluation with physical and neuropsychological examinations, neuro-imaging, laboratory tests, quality of life assessment, and other procedures. Carboplatin will be given for two consecutive days. Temozolomide will be taken by study participants daily for five consecutive days. Both of these treatment schedules will be repeated every 28 days. Several tests and exams will be given throughout the study to closely monitor patients. Study treatments will be discontinued due to disease growth or unacceptable adverse events.
Approximately 13% of COPAXONE 20 mg per mL patients in the 5 placebo-controlled studies compared to 6% of placebo patients, and approximately 2% of patients exposed to COPAXONE 40 mg per mL in a placebo-controlled trial compared to 1% of placebo patients, experienced at least one episode of transient chest pain. While some of these episodes occurred in the context of the Immediate Post-Injection Reaction described above, many did not. The temporal relationship of this chest pain to an injection was not always known. The pain was usually transient, often unassociated with other symptoms, and appeared to have no clinical sequelae. Some patients experienced more than one such episode, and episodes usually began at least 1 month after the initiation of treatment. The pathogenesis of this symptom is unknown.
The purpose of the study is to evaluate Onzurf probe (microdialysis probe) as a monitoring method for the early diagnosis of complications after surgery in the gastrointestinal tract. Samples taken with Onzurf probe will be analyzed and then compared with routine clinical data on surgical procedures in gastrointesinala tract. These parameters are: Patient general condition, endoscopy, radiology and routine clinical samples (global) as CRP (C-reactive protein), white blood cells, blood gases.The patients are their own controls when the purpose is to see if you can detect early complications with Onzurf probe and also identify how many people gets complications after surgery in the gastrointestinal tract. The patients' clinical routine tests (blood tests, etc.) will serve as control samples, which then will be compared with results from sampling of Onzurf probe. No interventions will be carried out on the patient.
Enhanced expression of methyltransferase-like 3 (METTL3) promotes the m6A modification of specific mRNAs, contributing to breast tumorigenesis. While the mRNA substrates targeted by METTL3 are well characterized, the factors dictating the selection of these specific mRNA remain elusive. This study aimed to examine the regulatory role of the transcription factor STAT5B in METTL3-induced m6A modification. METTL3 specifically interacts with STAT5B in response to mitogenic stimulation by epidermal growth factor (EGF). Chromatin immunoprecipitation and CRISPR/Cas9 mutagenesis showed that STAT5B recruits METTL3 to gene promoters like CCND1, where METTL3 interacts with RPB1, dependent on CDK9-mediated RPB1 (Ser2) phosphorylation during transcription elongation. Inhibition and depletion of either STAT5B or CDK9 prevented the EGF-induced m6A modification of CCND1. The translation efficiency of CCND1 was increased following m6A modification, thereby increasing cell proliferation. STAT5B facilitated METTL3-induced tumor formation by increasing CCND1 expression in an orthotopic mouse model. In clinical context, a positive correlation was observed between p-STAT5B and METTL3 expression in high-grade breast tumors. This study elucidates a novel mechanism that underlies the specificity of m6A modification in breast cancer cells, thereby underscoring its potential therapeutic value.
The CBT-I treatment condition will be delivered in a one-hour per week group format (10 participants) occurring over the course of six-weeks. Four total CBT-I groups occurring over the course of two years will be implemented, with at total of 40 participants enrolled for the CBT-I condition.