anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.
The opioid dose for individual with cancer pain to provide adequate relief of pain with an acceptable degree of side effects is variable. Opioid titration is a process to obtain the tailored dose. Conventional titration is administered by a clinician or nurse. PCA is that patients control cancer pain by self-administration of intravenous opioids using programmable pump. The aim of our study is to evaluate the efficacy of PCA titration versus conventional titration intravenously for severe cancer pain (10-point numerical rating scale, NRS ≥ 7). Injectable Hydromorphone was selected as pharmaceutical analgesics, which works as well as morphine and oxycodone and had similar side effects.
The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1-3, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programmes at single-cell transcriptomic resolution. We uncover a tumour necrosis factor (TNF) signalling module, which is dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF signalling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF gene programme associated with epithelial-mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF gene programme is sufficient to mediate invasive properties and show that the TNF signature correlates with shorter overall survival of patients with squamous cell carcinoma. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF programmes in tumour evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.
The present invention relates to methods to elicit immature antigen-presenting cells loaded with apoptotic cells or apoptotic bodies. The present invention also relates to methods of obtaining antigen-specific regulatory T cells in vitro or in vivo. Cells loaded with apoptotic bodies/cells and regulatory T cells are obtainable by inducing apoptosis of antigen-presenting cells by cytolytic CD4+ T cells. The cells are used for suppressing or preventing diseases such as autoimmune diseases, graft rejection and allergic diseases, and medicaments related thereto. Further disclosed are the use of antigen-specific regulatory T cells for suppressing or preventing diseases such as autoimmune diseases, graft rejection and allergic diseases, and medicaments related thereto. Further disclosed are populations of antigen-specific regulatory T cells obtained by said method.
This research study is for people who have a brain hemorrhage, due to a ruptured aneurysm. Adding the drug cilostazol to the standard care may improve outcomes after surgery. The blood within the brain following aneurysmal hemorrhage can have harmful effects on the blood vessels causing them to narrow and thus decrease blood flow; this process is called vasospasm. Decreased blood flow in the brain can lead to more damage. Delayed cerebral ischemia is a complication which is believed to be a consequence of reduced blood flow to the brain following this type of hemorrhage. Cilostazol opens blood vessels and reduces the formation of blood clots. The standard treatment of these hemorrhages currently involves the use of nimodipine which also relaxes blood vessels and allows blood to flow more freely. The combination of these two drugs cilostazol and nimodipine may improve neurologic outcomes after surgery.
The primary objective of this study will be to evaluate the functional outcome of patients who present with a distal fibula fracture who were treated with either intermedullary nail (IMN) fixation or plate fixation. This objective will be accomplished using the Olerud-Molander score, a commonly accepted functional outcome score used to evaluate patients post-operatively who have undergone foot and ankle procedures. It is a survey that evaluates patient reported outcomes including pain, stiffness, swelling, stair climbing, running, jumping, squatting, use of supports, and work/activities of daily living (ADL) level. It does not involve physician-measured outcomes. The best possible score is a total of 100. Patients will be given a form to complete throughout follow-up and be utilized for data analysis. Functional outcome will be analyzed with regards to type of fracture, gender, cause of fracture, and affected side to determine if these factors are responsible for any difference.
Triglyceride-glucose (TyG) index is an emerging marker of adverse cardiometabolic conditions such as cardiovascular disease and type 2 diabetes. The long-term relevance of TyG index to chronic kidney disease (CKD) is uncertain. We aimed to assess the association of TyG index with CKD risk and its utility in risk prediction in a prospective study. The TyG index was calculated using fasting triglycerides and fasting plasma glucose (FPG) levels measured in 2362 men aged 42-61 years with normal kidney function using the formula: Ln (fasting triglycerides [mg/dL] × FPG [mg/dL]/2). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Correction for within-person variability was made using data from repeat measurements of triglycerides and FPG taken 11 years after baseline. Over a median follow-up duration of 17.5 years, 223 CKD cases were recorded. The age-adjusted regression dilution ratio for the TyG index was 0.54 (95% CI, 0.48-0.60). The risk of CKD increased continuously with increasing TyG index across the range 9.3 to 11.6 (p value for nonlinearity<.001). In analysis adjusted for established risk factors, a unit higher TyG index was associated with an increased risk of CKD (HR 1.59, 95% CI 1.24-2.05). Comparing extreme tertiles of the TyG index, the corresponding adjusted HR (95% CI) for CKD was 1.61 (1.15-2.27). Addition of the TyG index to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p value for difference in -2 log likelihood<.001; NRI=47.66%, p=.014; IDI=0.0164, p<.001). Higher TyG index is associated with an increased risk of CKD and improves the prediction and classification of CKD beyond established risk factors. Using single baseline estimations of the TyG index to investigate its association with CKD risk could considerably under-estimate the true association.
MA09-hRPE cells for transplantation will be provided by Ocata Therapeutics as a suspension frozen to the temperature of liquid nitrogen (approximately -196 °C). They will be processed at UCLA under GMPs according to protocol. Following vitrectomy performed under general anesthesia or waking sedation at the surgeon's discretion, hRPE cells will be introduced into a subretinal bleb formed by the injection of balanced salt solution (BSS). Direct viewing will guide the implantation of thawed and washed MA09-hRPE cells, resuspended in BSS, into the created bleb over a period of one minute. To avoid cell reflux, the cannula used to introduce the cells will be held in position for an additional minute. A suspension of either 50,000 MA09-hRPE cells (first cohort), 100,000 MA09-hRPE cells (second cohort), 150,000 MA09-hRPE cells (third cohort) or 200,000 MA09-hRPE cells (fourth cohort) in 150 uL of BSS plus will be implanted over 1 minute in the space created.
Metastatic (as well as tumor) microenvironments contain both cancer-promoting and cancer-restraining factors. The balance between these opposing forces determines the fate of cancer cells that disseminate to secondary organ sites. In search for microenvironmental drivers or inhibitors of metastasis, we identified, in a previous study, the beta subunit of hemoglobin (HBB) as a lung-derived antimetastatic factor. In the present study, exploring mechanisms regulating melanoma brain metastasis, we discovered that brain-derived factors restrain proliferation and induce apoptosis and necrosis of brain-metastasizing melanoma cells. Employing various purification procedures, we identified a heterodimer composed of hemoglobin alpha and beta chains that perform these antimetastatic functions. Neither the alpha nor the beta subunit alone was inhibitory. An alpha/beta chain dimer chemically purified from human hemoglobin inhibited the cell viability of primary melanomas, melanoma brain metastasis (MBM), and breast cancer cell lines. The dimer-induced DNA damage, cell cycle arrest at the SubG1 phase, apoptosis, and significant necrosis in four MBM cell lines. Proteomic analysis of dimer-treated MBM cells revealed that the dimer downregulates the expression of BRD4, GAB2, and IRS2 proteins, playing crucial roles in cancer cell sustainability and progression. Thus, we hypothesize that the hemoglobin dimer functions as a resistance factor against brain-metastasizing cancer cells.
Chronic pain is prevalent among individuals with higher body weight and associated with greater impairment. As a result, weight loss is a common recommendation for pain management among those with higher body weight. Body weight is an appealing target because it is modifiable and evidence-based treatments to produce weight loss are well-established. In the last 2 decades, there has been a growing line of scientific work investigating the application of weight loss to individuals with chronic pain. This represents an important step to integrate the conceptualization of pain and body weight and there is preliminary work suggesting treatment effects are enhanced when weight loss treatment is combined with pain coping skills. However, weight loss outcomes are variable and difficult to sustain, and access to evidence-based treatment is limited. These concerns are set against the backdrop of growing public and academic concern about the weight-centric approach to health care that dominates western medicine. This is a timely moment to reconsider the conceptualization of weight and pain, and the role of weight loss in chronic pain treatment. Using osteoarthritis as an exemplar, we review the evidence for and clinical uptake of weight loss as a chronic pain management strategy and conclude with key areas for consideration to advance the scientific understanding of these comorbid conditions and how to optimize pain management for individuals of higher body weight. PERSPECTIVE: This focus article critically considers the role of weight loss in management of chronic pain among individuals of higher body. Using knee osteoarthritis as an exemplar, the evidence and clinical uptake of weight loss for pain management is reviewed. Limitations are considered to guide future research and clinical care.
One capsule will be taken of placebo to match daily for seven days. On the eight day and for the remainder of the study 2 capsule will be taken twice a day. Medication will be taking daily for a total of 3 months.
IGMV will consist of a 12-week program that provides education on the biopsychosocial model of pain and multimodal treatments; physical movement; mindfulness training; and peer support. Non-pharmacologic approaches are based on guidelines on chronic pain management; feedback of experts, staff, and patients; and feasibility with the greatest potential to benefit participants. Participants will receive a binder with educational materials.
BACKGROUND: Overweight and obesity epidemic is still expanding, and it is affecting women of childbearing age. Multiple studies have shown unmatched results concerning the effect of body mass index (BMI) besides gestational weight gain (GWG) on pregnancy and neonatal outcomes. This study aims to determine the effect of each of the two anthropometric indicators: pre-gestational BMI and gestational weight gain on the course of pregnancy, and neonatal outcomes.
METHODS: A retrospective study was conducted at Notre Dame de Secours University Hospital (CHU-NDS) Jbeil-Lebanon. The data was collected from the hospital archive. Out of 804 deliveries during 2020, 583 women were included after randomly choosing their files and eliminating those with exclusion criteria or incomplete data.
RESULTS: Underweight/healthy BMI mothers had a higher chance of having low GWG (45.5%), vaginal delivery (51.3%), and a baby of appropriate size (78.6%) or small size for gestational age (10.4%). Obese women had a higher risk of excessive GWG (49.3%), delivery via C-section. (69.3%), and large for gestational age babies (26.7%). Mothers who had low GWG were at a higher risk of having babies of appropriate size (80.1%) or small size for gestational age (13.1%). Mothers who had high GWG had a higher risk of having baby boys (58.9%), large for their gestational age (26.1%), with hypoglycemia at birth (20.6%).
CONCLUSION: Both extremes of BMI and GWG are linked to adverse neonatal outcomes. This highlights the importance of weight monitoring even during pregnancy to prevent its negative impact on neonates.
L-citrulline with a dose of 15 g/day will be administered in powder form that is mixed with water and taken orally, continuously and daily for at least 7 weeks. Dispensed at Visits 1 and 1a (if needed). Washout period of at least 5 weeks and then enter crossover phase of an additional 7 weeks. Drug will be dispensed at Visit 4.
Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.
Patients choose ingredients for cooking and consumption under the guidance of researchers, ensuring that the nutritional composition is about 90% fat, 10% protein, and can contain a small amount of carbohydrates (10%). The daily calorie intake is around 1600\~2400 kcal.
Fine-needle aspiration (FNA) cytology or biopsy of hepatic tumor is frequently applied in the collection of specimens because it is considered safe, efficacious, accurate and cost effective. Our previous study from small number of patients showed that specimens obtained from FNA had potential to be applied for primary culture of cancer cells. This study was to modified our method for primary culture of both hepatocellular carcinoma cells and cancer-associated fibroblasts in patients with tumor measuring larger than or equal to 3cm. All patients received one session of aspiration for the diagnosis of hepatic tumor. The aspirated specimens were applied for both cytologic and pathologic examinations at first. After then, 10 mL 0.9% NaCl was aspirated by the same needle connected with the same syringe and injected into 15 mL sterilized centrifugation tube. If the tube contained visible specimens, these specimens were sent for primary culture.
PURPOSE: The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse.
METHODS: The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated.
RESULTS: There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse.
CONCLUSIONS: Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.
Cancer-induced bone pain (CIBP) is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis. CIBP constitutes a specific pain state with distinct characteristics; however, it shares similarities with inflammatory and neuropathic pain. At present, although various therapies have been developed for this condition, complete relief from CIBP in patients with cancer is yet to be achieved. Hence, it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs. Herein, we focused on the peripheral mechanism associated with the initiation of CIBP, which involves tissue injury in the bone and changes in the tumor microenvironment (TME) and dorsal root ganglion. The nerve-cancer and cancer-immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis, ultimately leading to CIBP. The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.
After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.
PURPOSE:To prepare an agent for skin application, capable of preventing the increase of skin pigment and the piementation, giving a moist and pleasant felling to the skin, and making the skin smooth, beautiful and resilient, by using extract of crude bitter principles obtained from a cucurbitaceous plant. CONSTITUTION:The whole grass or esp. the fruit of a cucurbitaceous plant, e.g. squirting cucumber, cucumber, snake gourd, melon, etc., is sliced to small pieces, and extracted with water or a hydrophilic organic solvent such as ethanol, methanol, etc. The extracting solvent is distilled out from the extract liquid, and the resultant extract of crude bittern principles of cucurbitaceous plant is added as an active component to the base for skin agent. The amount to be added is 0.01-20 wt%, pref. 0.1-10wt%. The active components of the extract are cucurbitacins such as cucurbitacin A, cucurbitacin B, cucurbitacin C, etc.
A total of 100 healthy adults, pre-screened to be negative for anti-dengue antibodies will be enrolled upon written informed consent. 25 subjects in the control arm will not receive Japanese Encephalitis vaccine but will receive 1 dose of Yellow Fever vaccine.
Urethral diverticulum is a pathological lesion characterized by a sac-shaped protrusion of the urethra. Diverticulum is a rare condition in the urological practice. Clinical case. The diagnosis, conservative management of diverticulum during pregnancy and surgical treatment on the 7th day after natural childbirth is presented in the article. A review of similar cases showed that urethral diverticulum in pregnant women should be managed conservatively, using antibiotic therapy, anesthesia, puncture aspiration, and cystoscopic drainage. Diverticulectomy during pregnancy is not recommended, as it is associated with increased anesthetic and surgical risks. It is necessary to carry out additional training of urologists, obstetricians, gynecologists to improve knowledge about this rare disease.