anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is a single-arm, open-label, phase II trial to evaluate the efficacy and safety of anti-PD-1 antibody MK-3475 (pembrolizumab) in combination with standard of care gemcitabine and cisplatin chemotherapy in women with recurrent platinum-resistant ovarian cancer (encompasses ovarian, peritoneal and fallopian tube cancer). Subjects will receive 2 cycles of gemcitabine and cisplatin chemotherapy followed by 4 cycles of gemcitabine and cisplatin combined with pembrolizumab in 21-day treatment cycles. Subjects will continue to receive single-agent pembrolizumab every 21 days as maintenance therapy for up to 2 year until progression or the subject meets withdrawal criteria. Tumor imaging with CT scan will occur at baseline and every 6 weeks (after each second cycle) during chemotherapy treatment and every 9 weeks thereafter. The primary endpoint is efficacy as defined overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). Secondary endpoints for efficacy include progression free survival at 6 and 12 months, time to progression, duration of response and overall survival. Safety and tolerability of the regimen will be determined by assessing the frequency and intensity of adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE v.4). Quality of life will be measured using the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30).
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.
The invention relates to UV emitting nanoparticles for radiation therapy purposes. If the nanoparticles are brought indirectly or directly to the diseased tissue, excitation with high energy radiation leads to VUV or UV-C emission. This UV radiation is absorbed by the surrounding organic matrix, resulting in decomposition of the material. The nanoparticles can also be modified by attaching antibodies to the particles by chemical linking or coating. Preferably these antibodies bind specifically to the cell membrane of cancer cells leading to a localised destruction of diseased tissue with a high efficacy and a lower level of destruction of surrounding healthy tissue. Endoscopic detection of the UV emission can be used as a medical imaging technique to locate and study diseased tissue.
The subjects in this arm will receive four high intensity (80% of peak work rate) four-minute interval exercises for the abduction movement in the plane of the scapula (m. supraspinatus), supervised three times per week. In addition they will perform the exercise program described for the control group.
Participants will generate positive future events they are looking forward to at five time points in the future (1 day, 1 week, 1 month, 3 months, 1 year, 5 years, and 25 years). Participants will be reminded of these events using cues throughout the study and instructed to think about these cues as they make their decisions.
Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo buccal swab sample collection at cycle 1 day 0 and blood sample collection and bone marrow aspiration and biopsy throughout the study.
BACKGROUND: Non-communicable diseases are an increasing threat in sub-Saharan Africa (SSA), and overweight and obesity are affecting people across all socioeconomic groups. Some studies suggest that big body sizes may be perceived as desirable among women in SSA and that high prevalence of obesity and overweight are especially present in low socioeconomic societies. This study explores the role of socioeconomic factors in the perception of the ideal body among Kenyan women and whether perceptions and beliefs about the ideal body should be considered relevant when targeting the prevention of obesity and overweight.
METHOD: In-depth interviews were conducted with 8 Kenyan women with varying educational backgrounds, aged between 21 and 48, using a qualitative study design. The interviews were conducted in December 2022 and January 2023 in Nairobi, audio-recorded, transcribed and analysed through qualitative content analysis and a coding system using deductive and inductive codes.
RESULTS: The participants reported that conclusions about a person's health and wealth status are drawn based on different body sizes. Furthermore, traditional views about the ideal body size, societal pressure, as well as the women's own experience with their body size play a role in the perception of an ideal body.
CONCLUSION: Small-sized women desire to gain weight as society may view them as weak and sick. Big-sized women aim to reduce weight primarily due to health complications. Nevertheless, traditionally, a big-sized woman is considered strong and wealthy, creating external pressure on women to fulfil this body image-these findings emphasise traditional aspects in designing culturally sensitive prevention and intervention methods to address overweight and obesity.
Americans are increasingly seeking care from massage therapists for relief of chronic back pain. However, while initial studies suggest that massage is beneficial for back pain, we have no information about which of the many types of massage is most helpful. We will be conducting a study that compares two distinct therapeutic massage protocols with each other and with usual care for treating chronic back pain. This study is designed to determine which of these massage protocols will be most effective in reducing pain and increasing functionality in people with low back pain. 399 Group Health members with non-specific low back pain lasting at least 3 months will be randomized to one of the two massage groups or to a control group that receives no treatment beyond their usual care. Massage therapists will provide each participant with 10 treatments over 10 weeks. The primary outcomes, function and bothersomeness of low back pain, will be assessed before treatment begins and 10, 26 and 52 weeks after randomization by interviewers who do not know which treatment the participant received. The results of this study will clarify the value of two different types of massage for treating one of the most common, challenging, and expensive health problems plaguing developed countries. The findings will help physicians make informed and confident referrals, consumers and insurers make safe and cost-effective choices, and massage schools make responsible curriculum decisions.
FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, namely to cardiology and angiology, and deals with correction of functions of vascular walls in patients with arterial hypertension of I-II degree with metabolic syndrome, after thrombosis of eye vessels. For this purpose indices of anti-aggregate, anti-coagulant and fibrinolytic activity of vascular wall are determined. On the basis of said indices calculated is total anti-thrombotic potential of vessels and if its value is 0.069 and lower, complex treatment, including application of individually selected hypocaloric diet, dosed physical load, pioglitazone 30 mg 1 time per day and valsartan 160 mg 1 time per day in the morning during 4 months, is administered. ^ EFFECT: complex of drug and non-drug therapy in combination with empirically selected duration of treatment ensures correction of functions of vascular wall and, thus, reduction, of risk of thrombotic complications in said group of patients due to potentiation of therapeutic effect of separate components of therapeutic complex. ^ 1 ex, 1 dwg
Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle atrophy. Increased skeletal muscle mitochondrial reactive oxygen species (ROS) is a contributing factor to loss of muscle mass in cachectic patients. Mice inoculated with Lewis lung carcinoma (LLC) cells lose weight, muscle mass, and have lower muscle sirtuin-1 (sirt1) expression. Nicotinic acid (NA) is a precursor to nicotinamide dinucleotide (NAD+) which is exhausted in cachectic muscle and is a direct activator of sirt1. Mice lost body and muscle weight and exhibited reduced skeletal muscle sirt1 expression after inoculation with LLC cells. C2C12 myotubes treated with LLC-conditioned media (LCM) had lower myotube diameter. We treated C2C12 myotubes with LCM for 24 h with or without NA for 24 h. C2C12 myotubes treated with NA maintained myotube diameter, sirt1 expression, and had lower mitochondrial superoxide. We then used a sirt1-specific small molecule activator SRT1720 to increase sirt1 activity. C2C12 myotubes treated with SRT1720 maintained myotube diameter, prevented loss of sirt1 expression, and attenuated mitochondrial superoxide production. Our data provides evidence that NA may be beneficial in combating cancer cachexia by maintaining sirt1 expression and decreasing mitochondrial superoxide production.
Wheat is the predominant crop worldwide, contributing approximately 20% of protein and calories to the human diet. However, the yield potential of wheat faces limitations due to pests, diseases, and abiotic stresses. Although conventional breeding has improved desirable traits, the use of modern transgenesis technologies has been limited in wheat in comparison to other crops such as maize and soybean. Recent advances in wheat gene cloning and transformation technology now enable the development of a super wheat consistent with the One Health goals of sustainability, food security, and environmental stewardship. This variety combines traits to enhance pest and disease resistance, elevate grain nutritional value, and improve resilience to climate change. In this review, we explore ways to leverage current technologies to combine and transform useful traits into wheat. We also address the requirements of breeders and legal considerations such as patents and regulatory issues.
Necrotizing enterocolitis (NEC) is a rare but life-threatening diagnosis in infants presenting with bilious emesis, abdominal distension, or bloody stools. Ultrasonography has been advocated as an alternative initial imaging modality to abdominal radiography, and may be superior in the evaluation of NEC. We describe the use of point-of-care ultrasound (PoCUS) in the evaluation of suspected NEC in the emergency department (ED) when the ability to obtain immediate abdominal x-ray (AXR) was delayed due to pandemic conditions. A pre-term infant with history of bowel resection presented with non-bilious emesis, bloody stools, and slight abdominal distension. Evaluation with PoCUS identified pneumatosis intestinalis and pneumoperitoneum, which were confirmed on subsequent AXR. Pneumatosis intestinalis in a neonate is highly suggestive of NEC, but seen by itself, can be associated with milk protein allergy and Food Protein Induced Enterocolitis syndrome (FPIES). Pneumoperitoneum is considered an indication for operative intervention for NEC. The infant was re-admitted to the NICU for suspected NEC. NEC is a rare, but potentially surgical diagnosis in infants as can be FPIES, but not milk protein allergy. NEC can be identifiable using PoCUS to search for a constellation of findings that include pneumatosis intestinalis, pneumoperitoneum, free peritoneal fluid, and portal venous gas. These findings have been previously described in the PoCUS literature for other diseases, but not for a case of suspected NEC presenting to the ED.
Patients receive venetoclax PO QD and enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Although many cytokine pathways are important for dendritic cell (DC) development, it is less clear what cytokine signals promote the function of mature dendritic cells. The signal transducer and activator of transcription 4 (STAT4) promotes protective immunity and autoimmunity downstream of proinflammatory cytokines including IL-12 and IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), Stat4-/- mice are resistant to the development of inflammation and paralysis. To define whether STAT4 is required for intrinsic signaling in mature DC function, we used conditional mutant mice in the EAE model. Deficiency of STAT4 in CD11c-expressing cells resulted in decreased T cell priming and inflammation in the central nervous system. EAE susceptibility was recovered following adoptive transfer of wild-type bone marrow-derived DCs to mice with STAT4-deficient DCs, but not adoptive transfer of STAT4- or IL-23R-deficient DCs. Single-cell RNA-sequencing (RNA-seq) identified STAT4-dependent genes in DC subsets that paralleled a signature in MS patient DCs. Together, these data define an IL-23-STAT4 pathway in DCs that is key to DC function during inflammatory disease.
Subjects with PG will be treated with 100 mg every 4 weeks of guselkumab for 28 weeks in addition to starting stable dose (at least 2 weeks) of prednisone at 20 mg daily. Prednisone will be tapered based on a pre-established algorithm assessed by investigator.
INTRODUCTION: Detection of critical colonization is gaining importance in wound management, but its pathophysiology remains unclear. We previously clarified that a dysbiotic wound microbiota differing from skin commensal microbiota may be involved in critical colonization and that such wounds contain fewer Forkhead box protein P3 (FOXP3)-positive cells in the tissue. However, it is not clear whether FOXP3-positive cells contribute to the development of critical colonization. Here, we examined whether inhibition of FOXP3-positive cell could induce critical colonization when the commensal microbiota was present in the wounds.
METHODS: Sprague-Dawley rats were administered FK506 or vehicle to inhibit differentiation into FOXP3-positive cells. Full-thickness wounds were made on the dorsal skin and inoculated with bacterial solution (dysbiosis group) or Luria-Bertani medium (commensal group). A bacterial solution was prepared by anaerobically culturing bacteria from the skin of donor rats on an artificial dermis in Luria-Bertani medium for 72 hours. Tissues were collected on day 4 postwounding for histological evaluation.
RESULTS: After microbiota transplantation, excessive inflammation occurred in the FK506 + commensal group. In contrast, wounds with transplanted dysbiotic microbiota showed the same level of neutrophil infiltration, regardless of FK506 administration. Furthermore, the wound area was larger in the FK506 + commensal group than in the vehicle + commensal group on day 4 postwounding ( P = 0.01). This area was also significantly larger in both the vehicle + dysbiosis ( P = 0.01) and FK506 + dysbiosis groups ( P = 0.03) than in the vehicle + commensal group.
CONCLUSIONS: This study has shown that dysbiosis may be at least related to developing critical colonization, and the results suggest that FOXP3-positive cells are involved in this process. Our study may contribute to establishing new interventions that prevent critical colonization by correcting wound microbiota.
Perioperative pain management has become an important component of Enhanced Recovery After Surgery (ERAS) protocols in patients undergoing cardiac surgery. Pain is most intense in the first two days after cardiac surgery. Inadequate pain control has been shown to cause an increase in pulmonary complications due to inadequate mobility and coughing, an increase in sympathetic activation, an increase in myocardial infarction and thromboembolic events, delayed wound healing, and prolonged hospital and intensive care unit stay. Non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioids, epidural anesthesia and ultrasound-guided fascial plane blocks are widely used for pain management after cardiac surgery. The pectointercostal fascial plane (PIFP) block is an ultrasound-guided, superficial fascial plane block that can be applied as part of multimodal postoperative analgesia, especially after cardiac surgery. PIFB block has been shown to reduce postoperative analgesic consumption and improve pain scores not only in patients undergoing cardiac surgery but also in non-cardiac surgeries and thoracic procedures. The aim of this study was to evaluate the effect of PIFP block on regional haemodynamic parameters in patients undergoing cardiac surgery.
Excessive drinking (ED) and alcohol use disorders (AUD) remain one of the nation's leading public health problems, yet this problem is largely under-recognized and undertreated. Although many people with ED/AUD see a primary care physician annually, there has been limited research and implementation of models to treat ED/AUD in primary care. Important changes in the healthcare system and advances in alcohol research offer new and potentially transformative opportunities to integrate ED/AUD treatment into primary care practices. In particular, these changes have led to the development of new patient-centered, integrated care models that facilitate the treatment behavioral health issues in primary care. Experts have repeatedly called for the development of a chronic care model to treat alcohol problems in primary care, similar to models now used to treat other chronic illnesses, including depression. Yet, research to develop and test such models has been surprisingly limited. The primary aim of this study is to develop and test a chronic care model to treat ED/AUD in the patient-centered model home (PCMH) using the NIH stage model of intervention development. Specifically, using a mixed methods approach, this study proposes to adapt and test the collaborative care (CC) model for depression to treat ED/AUD in a high volume PCMH. Importantly, we will build the CC model onto a Screening, Brief Intervention, and Referral to Treatment (SBIRT) program that is already in place in the PCMH. Notably, this SBIRT model currently refers those with ED/AUD out to specialty treatment providers. The proposed study will be conducted in two phases. Phase I will involve initial adaptation of the CC model for depression. During this phase, relevant depression CC protocols and measures will be adapted for ED/AUD and piloted tested on participants (n = 25) recruited in a PCMH. Phase II will involve model refinement based on iterative cycles of patient and PCMH staff feedback and examination of drinking outcome data. During this phase, participants (n = 60) will be assessed and followed for three months. Iterative development will focus on: 1) utilizing a stepped-care model of treatment which will include outpatient detoxification, behavioral interventions, and medication intervention and management, 2) maximizing patient engagement, and 3) balancing the resource and expertise constraints of treating ED/AUD in a PCMH. Participants in Phases 1 and 2 will be followed at 1 and 3 months and primary outcome data on drinking outcomes will be examined.
Background: Stillbirth is a devastating event for families as well as hospital staff. Hospital practices around internal and external staff communication, debriefing, and training are unknown. Methods: We systematically sampled U.S. hospitals that provide obstetrical care. Staff knowledgeable of bereavement care on labor and delivery were invited to participate in an anonymous survey linked to hospital descriptors. We evaluated stillbirth communication, debriefing, and training for staff. Results: We received 289 usable surveys from 429 eligible staff (67% response). Most (94%) noted hospitals' marked rooms housing bereaved families, but only a third (37%) reported a marker on the paper or electronic medical record. Half of the hospitals had no standard debriefings post-loss, and 38% reported no perinatal loss training for labor and delivery nurses. Conclusions: Hospitals have significant variations and gaps in staff communication, support, and training, which are key aspects of respectful stillbirth care.
The investigators also prospectively surveyed adult patients with functional gastroenterological symptoms according to the Rome III criteria, and a definitive diagnosis of NCWS. The patients were recruited between December 2014 and March 2016 at 3 centers: the two already mentioned and the Gastroenterology Unit of the ARNAS Civico Hospital of Palermo, Italy. Most of the patients had been referred due to gastrointestinal symptoms, the onset of which, they reported, could be related to wheat ingestion. Again, the characteristics of the NCWS patients suffering from nickel allergy were compared with those of the NCWS patients who did not suffer from nickel allergy.
Participants in this arm will receive the usual treatment for obesity at our hospital, based on lifestyle changes (encouraging a healthy diet and physical activity) for 3 months. Participants will receive a daily dose of postbiotic blend (ABB C3) for these 3 months, then given the option to receive a daily dose of probiotic ABB C3 for 3 more months.
Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease that compromises liver function, for which there is not a specifically approved medicine. Recent research has identified transcription factor NRF2 as a potential therapeutic target. However, current NRF2 activators, designed to inhibit its repressor KEAP1, exhibit unwanted side effects. Alternatively, we previously introduced PHAR, a protein-protein interaction inhibitor of NRF2/β-TrCP, which induces a mild NRF2 activation and selectively activates NRF2 in the liver, close to normal physiological levels. Herein, we assessed the effect of PHAR in protection against NASH and its progression to fibrosis. We conducted experiments to demonstrate that PHAR effectively activated NRF2 in hepatocytes, Kupffer cells, and stellate cells. Then, we used the STAM mouse model of NASH, based on partial damage of endocrine pancreas and insulin secretion impairment, followed by a high fat diet. Non-invasive analysis using MRI revealed that PHAR protects against liver fat accumulation. Moreover, PHAR attenuated key markers of NASH progression, including liver steatosis, hepatocellular ballooning, inflammation, and fibrosis. Notably, transcriptomic data indicate that PHAR led to upregulation of 3 anti-fibrotic genes (Plg, Serpina1a, and Bmp7) and downregulation of 6 pro-fibrotic (including Acta2 and Col3a1), 11 extracellular matrix remodeling, and 8 inflammatory genes. Overall, our study suggests that the mild activation of NRF2 via the protein-protein interaction inhibitor PHAR holds promise as a strategy for addressing NASH and its progression to liver fibrosis.
The present disclosure describes compositions and methods for treating solid tumors expressing mesothelin (MSLN) using chimeric antigen receptor (CAR) T cell therapy. The compositions comprise CARs with an extracellular domain that specifically binds MSLN. The extracellular domain comprises a single variable domain (VHH) antibody that targets MSLN. Polynucleotides encoding the anti-MSLN CAR constructs are provided. Pharmaceutical compositions comprising CAR T cells expressing the anti-MSLN CARs are also described. The CAR T cells demonstrate cytotoxicity against MSLN-expressing tumor cells in vitro and anti-tumor activity in vivo. Methods are provided for generating the CAR T cells by transfecting T cells with lentiviral or retroviral vectors carrying anti-MSLN CAR encoding sequences. The anti-MSLN CAR T cell therapy described herein provides an effective approach for treating solid tumors expressing MSLN, such as mesothelioma, ovarian cancer, pancreatic cancer, and lung cancer.