anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Carcinogenesis

Carcinogenicity studies were conducted in male and female rats and mice. In the 80-week mouse oral study and in the 104-week rat oral study, no relationship of tumor incidence to tacrolimus dosage was found. The highest dose used in the mouse was 3.0 mg/kg/day (0.9 to 2.2 times the AUC at clinical doses of 0.075 to 0.2 mg/kg/day) and in the rat was 5.0 mg/kg/day (0.265 to 0.65 times the AUC at clinical doses of 0.075 to 0.2 mg/kg/day) [see Warnings and Precautions (5.1)]. 

A 104-week dermal carcinogenicity study was performed in mice with tacrolimus ointment (0.03% - 3%), equivalent to tacrolimus doses of 1.1-118 mg/kg/day or 3.3-354 mg/m2/day. In the study, the incidence of skin tumors was minimal and the topical application of tacrolimus was not associated with skin tumor formation under ambient room lighting. However, a statistically significant elevation in the incidence of pleomorphic lymphoma in high-dose male (25/50) and female animals (27/50) and in the incidence of undifferentiated lymphoma in high-dose female animals (13/50) was noted in the mouse dermal carcinogenicity study. Lymphomas were noted in the mouse dermal carcinogenicity study at a daily dose of 3.5 mg/kg (0.1% tacrolimus ointment). No drug-related tumors were noted in the mouse dermal carcinogenicity study at a daily dose of 1.1 mg/kg (0.03% tacrolimus ointment). The relevance of topical administration of tacrolimus in the setting of systemic tacrolimus use is unknown.

The implications of these carcinogenicity studies to the human condition are limited; doses of tacrolimus were administered that likely induced immunosuppression in these animals, impairing their immune system’s ability to inhibit unrelated carcinogenesis.

Mutagenesis

No evidence of genotoxicity was seen in bacterial (Salmonella and E. coli) or mammalian (Chinese hamster lung-derived cells) in vitro assays of mutagenicity, the in vitro CHO/HGPRT assay of mutagenicity, or in vivo clastogenicity assays performed in mice; tacrolimus did not cause unscheduled DNA synthesis in rodent hepatocytes.

Impairment of Fertility

Tacrolimus, subcutaneously administered to male rats at paternally toxic doses of 2 mg/kg/day (1.6 to 4.3 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day] on a mg/m2 basis) or 3 mg/kg/day (2.4 to 6.4 times the recommended clinical dose range), resulted in a dose-related decrease in sperm count. Tacrolimus, administered orally at 1.0 mg/kg (0.8 to 2.2 times the clinical dose range) to male and female rats, prior to and during mating, as well as to dams during gestation and lactation, was associated with embryolethality and adverse effects on female reproduction. Effects on female reproductive function (parturition) and embryolethal effects were indicated by a higher rate of pre- and post-implantation loss and increased numbers of undelivered and nonviable pups. When administered at 3.2 mg/kg (2.6 to 6.9 times the clinical dose range based on body surface area), tacrolimus was associated with maternal and paternal toxicity as well as reproductive toxicity including marked adverse effects on estrus cycles, parturition, pup viability, and pup malformations.
Sedative, analgesic or anaesthetic compsn. comprises: an effective dose of effective agent (I), capable of being absorbed through mucosal tissue, uniformly dispersed in a soluble matrix (II) which dissolves in the mouth releasing (I), and a holder secured to the drug-contg. matrix configured so as to permit insertion into and removal from the mouth when a desired condition is attained. The compsn. is esp. in the form of a lollipop.
Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing argatroban or by decreasing the argatroban dose. In clinical studies, anticoagulation parameters generally returned from therapeutic levels to baseline within 2 to 4 hours after discontinuation of the drug. Reversal of anticoagulant effect may take longer in patients with hepatic impairment. No specific antidote to argatroban is available; if life-threatening bleeding occurs and excessive plasma levels of argatroban are suspected, discontinue argatroban immediately and measure aPTT and other coagulation parameters. When argatroban was administered as a continuous infusion (2 mcg/kg/min) prior to and during a 4-hour hemodialysis session, approximately 20% of argatroban was cleared through dialysis.  
  
Single intravenous doses of argatroban at 200, 124, 150, and 200 mg/kg were lethal to mice, rats, rabbits, and dogs, respectively. The symptoms of acute toxicity were loss of righting reflex, tremors, clonic convulsions, paralysis of hind limbs, and coma.
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a high mortality rate due to limited treatment options. Current therapies cannot effectively reverse the damage caused by IPF. Research suggests that promoting programmed cell death (apoptosis) in myofibroblasts, the key cells driving fibrosis, could be a promising strategy. However, inducing apoptosis in healthy cells like epithelial and endothelial cells can cause unwanted side effects. This project addresses this challenge by developing a targeted approach to induce apoptosis specifically in myofibroblasts. We designed liposomes (LPS) decorated with peptides that recognize VCAM-1, a protein highly expressed on myofibroblasts in fibrotic lungs. These VCAM1-targeted LPS encapsulate Venetoclax (VNT), a small molecule drug that inhibits BCL-2, an anti-apoptotic protein. By delivering VNT directly to myofibroblasts, we hypothesize that VCAM1-VNT-LPS can selectively induce apoptosis in these cells, leading to reduced fibrosis and improved lung function. We successfully characterized VCAM1-VNT-LPS for size, surface charge, and drug loading efficiency. Additionally, we evaluated their stability over three months at different temperatures. In vitro and in vivo studies using a bleomycin-induced mouse model of lung fibrosis demonstrated the therapeutic potential of VCAM1-VNT-LPS. These studies showed a reduction in fibrosis-associated proteins (collagen, α-SMA, VCAM1) and BCL-2, while simultaneously increasing apoptosis in myofibroblasts. These findings suggest that VCAM1-targeted delivery of BCL-2 inhibitors using liposomes presents a promising and potentially selective therapeutic approach for IPF.
OBJECTIVES: I. Determine whether the addition of octreotide pamoate to tamoxifen alone or to tamoxifen and chemotherapy improves the disease free survival of patients with primary invasive breast cancer with estrogen receptor (ER) positive tumors and histologically negative axillary lymph nodes or histologically negative sentinel lymph nodes if participating in NSABP B-32. II. Determine whether the rate of endometrial cancer associated with tamoxifen is altered by the concurrent administration of octreotide pamoate. III. Determine whether the addition of octreotide pamoate to tamoxifen decreases the rate of opposite breast cancer more than tamoxifen alone. IV. Evaluate the incidence of gallstone formation (including the development of symptoms and complications of biliary tract disease), hyper and hypoglycemia, hypothyroidism, and vitamin B12 deficiency in patients treated with octreotide pamoate in comparison with patients not treated with octreotide pamoate.

OUTLINE: This is a randomized study. Patients are randomized into one of four treatment arms. Arm I: Patients receive oral tamoxifen (TMX) daily continously for 5 years. Lumpectomy patients receive breast radiotherapy following recovery from surgery. Arm II: Patients receive TMX as in Arm I and octreotide pamoate (SMS 201-995 pa LAR) intramuscularly (IM) every 21 days for 4 doses, followed by octreotide pamoate IM for 28 days for 23 additional doses. Lumpectomy patients receive breast radiotherapy following recovery from surgery. Arm III: Patients receive doxorubicin (DOX) IV and cyclophosphamide (CTX) IV every 3 weeks for 4 courses and TMX as in Arm I. Lumpectomy patients receive breast radiotherapy after recovery from chemotherapy. Arm IV: Patients receive DOX and CTX as in Arm III, TMX as in Arm I, and octreotide pamoate as in Arm II. Patients receive TMX and octreotide pamoate on day 1 of first course of chemotherapy. Lumpectomy patients receive breast radiotherapy after recovery from chemotherapy.

PROJECTED ACCRUAL: Total accrual of 3,000 patients will be acrrued for this study over 5 years.
PURPOSE:To obtain the subject new physiologically active substances, having suppressing actions on the growth of a mammalian cell and useful as an active ingredient of an anticancer agent by culturing a microorganism, belonging to the genus Streptomyces and having the ability to produce the physiologically active substances NKl48198A and NK148198B. CONSTITUTION:This method for producing new physiologically active substances, NK148198A and NK148198B is to culture a microorganism, belonging to the genus Streptomyces and having the ability to produce the physiologically active substance, NK148198A or NK148198B [e.g. Streptomyces sp. NK148198 strain (FERM P-13962)] in a culture medium, produce and accumulate the formed product in the resultant culture and collect the prepared product. The physiologically active substances assume a white waxy appearance, are soluble in lower alcohols, chloroform and ethyl acetate and manifest the positivity to color reactions such as phosphomolybdic acid- sulfuric acid and ninhydrin reactions. Furthermore, the resultant physiologically active substances comprise the NK148198A expressed by the rational formula, C14H31N and the NK148198B expressed by the rational formula, C15H33N and are useful as an active ingredient of an anticancer agent.
High risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, followed by cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle and cabozantinib PO, methotrexate IV, and doxorubicin IV for two additional 35-day cycles. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additonal time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.
The control group of parents will be made up of another five successive groups of 8 to 10 families who will receive 12 sessions weekly 90 minutes. In these sessions these families will be encouraged to discuss their thoughts and share their experiences in a non-directive environment. The therapist will not be allowed to provide specific psychotherapy, psychoeducation or psychosocial techniques, nor any additional comments or information, but rather to guide the groups and allow everyone to express and give their personal point of view. The use of an active control group will ensure that the observed benefits are primarily due to the digitally supported psychosocial program only.
Patients receive fludeoxyglucose F 18 IV. Approximately 1 hour later, patients undergo positron emission tomography imaging. Some patients may undergo a repeat scan in 4-6 months.
PURPOSE:To provide a compact solid/liquid separation device having a simple structure inexpensively by utilizing the volume filtration phenomenon. CONSTITUTION:Solid matters are separated from a liquid sample basing on the volume filtration phenomenon, i.e. the phenomenon of holding solid matters in the whole volume of a filtration layer utilizing a three dimensional structure of the layer itself effectively. The solid/liquid separation equipment is constructed of a hollow supporting member 100 consisting of an impermeable material for liquid provided with a liquid inlet port A at one end and a liquid outlet port B at another end, and a volume filtration layer 1 extending in the inside space of the member 100 to separate the space into a liquid inlet port A side and a liquid outlet port B side, consisting of a fibrous material fixed to said member 100 and having >=about 90% void. After feeding a liquid sample contg. solid matters, for example, whole blood sample, is fed from the inlet port A to the volume filtration layer 1, the sample is compressed to hold the blood corpuscle component in the inside of said layer 1 three dimensionally, and only liquid components such as blood serum and blood plasma are moved quickly toward the outlet port B.
Neointimal hyperplasia is the main cause of vascular graft failure in the medium term. Vitamin D receptor activation modulates the biology of vascular smooth muscle cells and has been reported to protect from neointimal hyperplasia following endothelial injury. However, the molecular mechanisms are poorly understood. We have now explored the impact of the selective vitamin D receptor activator, paricalcitol, on neointimal hyperplasia, following guidewire-induced endothelial cell injury in rats, and we have assessed the impact of paricalcitol or vehicle on the expression of key cell stress factors. Guidewire-induced endothelial cell injury caused neointimal hyperplasia and luminal stenosis and upregulated the expression of the growth factor growth/differentiation factor-15 (GDF-15), the cytokine receptor CD74, NFκB-inducing kinase (NIK, an upstream regulator of the proinflammatory transcription factor NFκB) and the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Immunohistochemistry confirmed the increased expression of the cellular proteins CD74 and NIK. Paricalcitol (administered in doses of 750 ng/kg of body weight, every other day) had a non-significant impact on neointimal hyperplasia and luminal stenosis. However, it significantly decreased GDF-15, CD74, NIK and MCP-1/CCL2 mRNA expression, which in paricalcitol-injured arteries remained within the levels found in control vehicle sham arteries. In conclusion, paricalcitol had a dramatic effect, suppressing the stress response to guidewire-induced endothelial cell injury, despite a limited impact on neointimal hyperplasia and luminal stenosis. This observation identifies novel molecular targets of paricalcitol in the vascular system, whose differential expression cannot be justified as a consequence of improved tissue injury.
Patients undergoing implantation of a durable left ventricular assist devices (LVAD) or a heart transplantation are at increased risk for cardiac vasoplegia. Vasoplegia, during or following cardiac surgery, is a life-threatening condition that is characterized by poor organ perfusion and may progress to multi-organ failure. The prognosis is especially poor for patients with refractory hypotension, despite high doses of vasopressors. Existing data point to total catecholamine dose, cumulative time spent with hypotension, volume overload, need for blood transfusion as contributing factors. Catecholamine vasopressors and vasopressin, which are often used as first line vasopressor therapy, are also independent risk factors for end organ dysfunction. Data comparing mortality with the use of different classes of vasopressors, in various types of shock, have been equivocal to date. In addition, data comparing the use of different classes of vasopressors for vasoplegia during or after heart transplantation and LVAD implantation are lacking. In patients with distributive shock in the intensive care unit, angiotensin II has been shown to reduce total catecholamine dose over 24 hours and the cumulative time spent with hypotension. This study will evaluate, as the primary endpoint, whether first line use of angiotensin II affects total catecholamine vasopressor dose in the first 24 hours after vasoplegia is first. Secondary endpoints include cumulative time spent with mean arterial pressure \< 70 mmHg within the first 24 hours after distributive shock is first diagnosed, need for vasoplegia rescue therapies (methylene blue, vitamin B12, Vitamin C, steroids), incidence of acute kidney injury and stroke, time to extubation, incidence of new tachyarrhythmias, need for blood transfusion and fluid overload within the first 24 hours, ICU and hospital length of stay, 30-day mortality and allograft rejection (for heart transplant recipients).
NEW MATERIAL:An antibody having specificity to human pancreas phospho lipase A2. USE:Reagent for determination of human pancreas phospholipase A2 and useful for the diagnosis of acute pancreatitis, etc. PREPARATION:An experimental animal such as mouse is immunized by using purified human pancreas phospholipase A2 as an immunogen and a B lymphocyte is collected from the immunized animal. The lymphocyte is fused with a myeloma cell of permanent myeloma cell system. The obtained hybridoma is screened e.g. by enzyme immunoassay to select a hybridoma capable of producing the objective antibody. Finally, the hybridoma is monoclonized and the monoclonal cell strain of said hybridoma is cultured in the peritoneal cavity of the animal used in immunization. The objective antibody can be separated from the ascites of the animal.
OBJECTIVE: Klebsiella oxytoca can cause nosocomial infections, affecting vulnerable newborns. There are few studies describing nosocomial outbreaks in the neonatal intensive care units (NICU). In this study, a systematic review of the literature was carried out to know the main characteristics of these outbreaks and the evolution of one is described.
METHODS: We conducted a systematic review in the Medline database up to July 2022, and present a descriptive study of an outbreak with 21 episodes in the NICU of a tertiary hospital, between September 2021 and January 2022.
RESULTS: 9 articles met the inclusion criteria. The duration of outbreaks was found to be variable, of which 4 (44.4%) lasted for a year or more. Colonization (69%) was more frequent than infections (31%) and the mortality rate was 22.4%. In studies describing sources, the most frequent was the environmental origin (57.1%). In our outbreak there were 15 colonizations and 6 infections. The infections were mild conjunctivitis without sequelae. Molecular typing analysis made it possible to detect 4 different clusters.
CONCLUSIONS: There is an important variability in the evolution and results of the published outbreaks, highlighting a greater number of colonized, use of PFGE (pulsed-field gel electrophoresis) techniques for molecular typing and implementation of control measures. Finally, we describe an outbreak in which 21 neonates were affected with mild infections, resolved without sequelae and whose control measures were effective.
This is a double-blind randomized controlled trial to test effects of mHealth mobile neurofeedback on the outcomes of pain, enrolling 150 adult participants (18 years of age or older) with chronic low backpain. Participants will be scheduled for a baseline interview at Dr. Elbogen's research office at Duke after a preliminary telephone screen. After providing informed consent, participants will complete an eligibility assessment, a physical function test, self-report questionnaire on pain interference including clinical interviews for health outcomes of pain; self-report questionnaire on pain interference, pain self-efficacy, drug and alcohol use, opioid use, drug/alcohol use; a physical function test; and an EEG. Participants will be be randomly assigned to either an experimental (mobile neurofeedback) or placebo-control (sham neurofeedback) group. All participants will receive a portable Muse EEG headset and an iPod Touch with a mobile app named 'Mobile Neurofeedback' and be asked to complete 10-minute sessions at least 4 days per week for 12 weeks. Participants will be asked to report their current level of pain, stress, and anger before and after each session. The experimental condition involves a mobile app that provides auditory feedback signaling EEG alpha power above a threshold level, denoting a physiologically relaxed state. The control condition involves a visually identical mobile app yoked to a pre-recorded set of actual neurofeedback sessions (i.e., placebo). Study coordinators will conduct 6 check in calls in the intervening period, the study team will to reinforce training, troubleshoot technical problems, and assess any risk/safety issues (weeks 1,3,5,7,9, and 11). Follow-up data will be collected upon completion of the intervention at 12 weeks, 24 weeks and 36 weeks. During all follow-up visits, participants will complete self-report questionnaires, a physical function test, and an EEG. Data will be collected at baseline, 3, 6, and 9 months.
FIELD: biochemistry, endocrinology. SUBSTANCE: invention relates to method of preparing growth hormones or growth hormone derivatives, human growth hormone or their derivative crystals and pharmaceutical preparation as pharmaceutically acceptable growth hormone crystal suspension. Growth hormone crystals are grown in solution containing an organic solvent or combination of organic solvents in the presence of zinc cations at pH solution 5.0-6.8 and temperature 0-30 C. Grown crystals are isolated by the known methods. Grown growth hormone crystals has zinc cations preferably at molar ratio 0.2-10. EFFECT: improved method of preparing. 22 cl, 2 tbl
The evaluation of speech production is based on the characteristics of the pressure signal (time and frequency) and the acoustic signal after synchronization during time using duplicate with up to 8 sensors.

To reach the first objective, the investigators will focus on the patients who wear new complete denture during the first session of recording. They will first analyze the characteristics of the acoustic and pressure signals of the production of consonants. They shall select from 8 sensors, 3 sensors for the inferential analysis: a previous sensor in the alveolar zone, a median sensor in the palatal zone and a posterior sensor in the palatal area (on the border of the beginning of the soft palate). These 3 sensors will be selected on the basis of the amplitude of the variations of pressure during the task. This sensor's triplet will be specific to every patient. The investigators shall thus have after 3 sensors called: previous, median, posterior. They shall do, for every sensor's measurements and for the acoustic measures, an inferential statistical analysis based on one model shelf spaces generalized in mixed effects, in which the variable to be explained will be one of moderate variables, the fixed effects will be the session (just after wearing the prosthesis for the first time, 3 weeks later, 3 months later), the consonant, the index of the sensor (1 - 3, from the front to the back) and the index of the repetition (from 1 to 15), and where the random effect will be the patient.