anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Type T Large Granular Lymphocyte Leukemia (T-LGLL) is a chronic disorder characterized by the abnormal proliferation of clonal cytotoxic T cells. The intriguing association of T-LGLL with autoimmune and inflammatory diseases, the most prominent example being rheumatoid arthritis, raises questions about the underlying pathophysiologic relationships between these disorders which share several biological and clinical features, most notably neutropenia, which is considered as a clinical hallmark. Recent progress in molecular genetics has contributed to a better understanding of pathogenetic mechanisms, thus moving our knowledge in the field of LGL leukemias forward. Focusing on the constitutive activation of STAT3 pathway and the well-established role of STAT3 mutations in T-LGLL, we herein discuss whether the T cell clones occurring in comorbid conditions are the cause or the consequence of the immune-inflammatory associated events. Overall, this review sheds light on the intricate relationships between inflammation and cancer, emphasizing the importance of the STAT3 gene and its activation in the pathophysiology of these conditions. Gaining a deeper understanding of these underlying mechanisms seeks to pave the way for the development of novel targeted therapies for patients affected by inflammation-related cancers.
This study aimed to explore the intricate relationship between mitochondrial dysfunction, infection, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged PARK2-/- and C57BL/6J wild-type mice immunized with EBNA1386-405 or with active experimental autoimmune encephalomyelitis (EAE) induction by the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. The PARK2-/- mice developed more severe EAE than the wild-type mice. Following immunization with EBNA1386-405, only PARK2-/- exhibited symptoms resembling EAE. During the acute phase, PARK2-/- mice immunized with either MOG35-55 or EBNA1386-405 exhibited a similar infiltration of the T cells and macrophages in the spinal cord and decreased glial fibrillary acidic protein (GFAP) expression in the brain. However, the EBNA1386-405 -immunized PARK2-/- mice showed significantly increased frequencies of CD8a+ T cells and CD11c+ B cells, and distinct cytokine profiles in the periphery compared to the wild-type controls. These findings highlight the role of EBV in exacerbating inflammation, particularly in the context of mitochondrial deficiencies.
The invention discloses a new application of reserpine, and in particular discloses an application of reserpine in preparing antiviral drugs. The invention constructs a fluorescent report cell line capable of detecting the expression activation of I-type interferon IFN beta on the basis of HEK293 by utilizing CRISPR/Cas9 technology and through a homologous recombination mode. And high throughput screening of compounds was performed using this cell line. Reserpine was found to activate cells to produce type I interferon IFN beta from 8036 FDA approved drugs and natural products. Meanwhile, VSV and HSV cell infection models are utilized, and the reserpine has the effect of inhibiting virus infection cells. Therefore, reserpine has a great application prospect as a potential antiviral therapeutic drug.
Protein phosphatase 6 (PP6) is a Ser/Thr protein phosphatase with the catalytic subunit Ppp6c. Recent cell-level studies have revealed that Ppp6c knockdown suppresses neurite outgrowth, suggesting that Ppp6c is involved in the development of the nervous system. We found that the function of PP6 in neurons is essential for mouse survival after birth, as all neural-stem-cell-specific KO (Ppp6cNKO) and neuron-specific KO mice died within 2 days of birth. By contrast, approximately 40 % of oligodendrocyte-specific KO mice died within 2 days of birth, whereas others survived until weaning or later, suggesting that the lethality of PP6 loss differs between neurons and oligodendrocytes. Furthermore, the fetal brain of Ppp6cNKO mice exhibited decreased numbers of neurons in layers V-VI and interneurons in layer I of the neocortex. These results suggest for the first time that Ppp6c is essential for neonatal survival and proper development of neurons and interneurons in the neocortex.
Consecutive eligible patients presenting to the study institutions and associated clinics will be enrolled. Inclusion and exclusion criteria are detailed separately in the section on eligibility. The target enrollment population listed in the study design section provides a greater than 85% power to achieve the pre-specified goal for the sensitivity and specificity of the pre-specified model. Saliva will be collected in vials pre filled with mRNA stabilizer. Seven mRNA biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1) will be measured in a central laboratory by quantitative PCR with the laboratory personnel blinded to the patient diagnosis. The primary outcome is the validation of a pre-specified multi-marker model. This pre-specified model incorporates 3 of the cancer genes and the housekeeping gene. The model will be validated based on the sum of sensitivity and specificity exceeding 1.3 with the lower limit of the 95% confidence interval exceeding 1.0. A secondary endpoint is the development of new multi-maker models with potential improved performance. These new models will be developed by logistic regression and compared with the pre-specified model based on the area under the receiver operating characteristic curve and the maximum sum of sensitivity and specificity. Individual candidate biomarkers will also be validated based on a statistically significant up-regulation in cancer patients compared with controls. Potential new housekeeping genes will be evaluated based on their equivalence in cancer and control as well as their performance in multi-marker models in comparison with the pre-specified housekeeping gene which is GADPH..
Control participants will not get an exercise prescription. They will be asked to refrain from lifestyle changes for 6 mos. After the 6-month waitlist period, Controls will receive the same resources as Exercisers.
This study is designed to evaluate the diaphragm kinetics with ultrasonography parameters in patients who underwent pulmonary vein isolation (PVI) for atrial fibrillation (AF) by Cryoballoon. Due to the proximity of the pulmonary veins to the phrenic nerve, phrenic nerve paralysis can be seen rarely during the procedure. In contemporary practice, phrenic nerve damage is detected by visual monitoring of diaphragm movement as a result of pacing with high output by placing the intracardiac stimulation catheter at the level of the superior vena cava. However, subclinical nerve damage may be critical regarding respiratory functions, especially in patients with comorbidities. It has been shown in the literature that the evaluation of diaphragm kinetics with Tissue Doppler Imaging (TDI) can be used in effective ventilation monitoring and weaning. However, this technique has not been used in patients who have previously undergone cryoballoon therapy. It is aimed to investigate the positive or negative effects on diaphragm kinetics, as a very cost-effective and rapidly accessible technique, with the help of this technique.
OBJECTIVE: Inframalleolar disease is present in most diabetic patients presenting with tissue loss. Inframalleolar (pedal) artery disease and pedal medial arterial calcification (pMAC) are associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). This study aimed to examine the impact of pMAC on the outcomes after isolated inframalleolar (pedal artery) interventions.
METHODS: A database of lower extremity endovascular intervention for patients with tissue loss between 2007 and 2022 was retrospectively queried. Patients with CLTI were selected, and those undergoing isolated inframalleolar intervention on the dorsalis pedis and medial and lateral tarsal arteries and who had foot x-rays were identified. X-rays were assessed blindly for pMAC and scored on a scale of 0 to 5. Patients with concomitant superficial femoral artery and tibial interventions were excluded. Intention to treat analysis by the patient was performed. Amputation-free survival (survival without major amputation) was evaluated.
RESULTS: A total of 223 patients (51% female; 87% Hispanic; average age, 66 years; 323 vessels) underwent isolated infra-malleolar intervention for tissue loss. All patients had diabetes, 96% had hypertension, 79% had hyperlipidemia, and 63% had chronic renal insufficiency (55% of these were on hemodialysis). Most of the patients had Wound, Ischemia, and foot Infection (WIfI) stage 3 disease and had various stages of pMAC: severe (score = 5) in 48%, moderate (score = 2-4) in 31%, and mild (score = 0-1) in 21% of the patients. Technical success was 94%, with a median of one vessel treated per patient. All failures were in severe pMAC. Overall, major adverse cardiovascular events was 0.9% at 90 days after the procedure. Following the intervention, most patients underwent a planned forefoot amputation (single digit, multiple digits, ray amputation, or trans-metatarsal amputation). WIfI ischemic grade was improved by 51%. Wound healing at 3 months was 69%. Those not healing underwent below-knee amputations. The overall 5-year amputation-free survival rate was 35% ± 9%. The severity of pMAC was associated with decreased AFS.
CONCLUSIONS: Increasing severity of pMAC influences the technical and long-term outcomes of infra-malleolar intervention in diabetes. Severe pMAC is associated with amputation and should be considered as a variable in the shared decision-making of diabetic patients with CLTI.
Tonsillectomy is a common operation performed in children that is associated with marked pain and a high incidence of nausea and vomiting. Therefore, national and international guidelines have recommended the use of a setron as a prevention to nausea and vomiting and also the systematic administration of paracetamol to help in the control of postoperative pain. However, a potential interaction between setrons and paracetamol has been reported in different animal studies and in human volunteers although its existence has never been found in the clinic. Indeed, several hypotheses are proposed to explain the mechanism of action of paracetamol in the treatment of pain. However, a recent one involves the endocannabinoid system and spinal serotonin receptors. Serotonin receptors are also involved in the mechanism of action of antiemetics such as setrons. Indeed, these drugs are serotonin antagonists. Therefore, the investigators hypothesized that the concomitant administration of paracetamol and ondansetron leads to an interaction that will decrease the analgesic effect of paracetamol.

Patients aged 2-7 years old and scheduled for a tonsillectomy will be recruited. They will all receive intraoperatively intravenous paracetamol together with either ondansetron or droperidol. Pain scores using the CHEOPS scale will be recorded for 24 hours. Furthermore, patients will receive i.v. morphine during the operation and in the recovery room if necessary and a non-steroidal anti-inflammatory drug for postoperative pain; on the ward, oral codeine will be administered when needed. Pain scores will be recorded regularly for up to 24 hours together with opioid consumption and the incidence of nausea and vomiting in the same period. Any adverse event will also be recorded.
Patients will be given an individualized diet and exercise plan by a physical therapist and registered dietician. The diet and exercise plan will be carried out by the participant for 16 weeks. The exercise plan, an aerobic and strength training regimen, will be performed under the supervision of a personal trainer or certified exercise physiologist that is local to the participant. The participant will complete core-stabilizing exercises which can be performed at home or in an approved group class. The participant will wear an activity tracker at all times during this 16 week period, and will be asked to manually enter data into a phone app, such as daily food intake and weight.
Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Since these phagocytes reside in proximity in most tissues, whether cross-communication exists between them during cell clearance, and how this might impact inflammation are not known. Here, we show that macrophages, via the release of a soluble growth factor and microvesicles, redirect the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During apoptotic cell engulfment or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was dampened while engulfment of microvesicles was enhanced. Macrophages were refractory to this IGF-1 mediated engulfment modulation. Macrophages also released microvesicles, whose uptake by epithelial cells, enhanced by IGF-1, led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal a novel IGF-1 and microvesicle-dependent communication between macrophages and epithelial cells that can critically influence the magnitude of tissue inflammation in vivo.
A plant having at least 1 of the following genetic traits (A) to (E). (A) Homozygosity or heterozygosity for an allele having a base C at a position corresponding to position 40 of SEQ ID NO. 1. (B) Homozygosity or heterozygosity for an allele having a base T at a position corresponding to position 21 of SEQ ID NO. 2. (C) Homozygosity or heterozygosity for an allele having T as the base at a position corresponding to position 28 of SEQ ID NO. 3. (D) Homozygosity or heterozygosity for an allele having C as the base at the position corresponding to the 59 th position of SEQ ID NO. 4. (E) The allele having T as the base at the position corresponding to position 64 of SEQ ID NO. 5 exhibits homozygosity or heterozygosity.
This is an open-label study of ZYC300 in the treatment of advanced stage malignancy of the kidney in patients who have not had previous immune-based therapies or treatment of advanced stage malignancies (cancerous growths) of the ovary, breast, colon, or hormone-refractory prostate in patients who have failed at least one but no more than two prior regimens of chemotherapy. Patients who meet all entry criteria will be administered 600 mg/m\^2 cyclophosphamide intravenously 3 days before each dose of ZYC300. ZYC300 will be administered at 400 micrograms DNA/total dose every two weeks for a maximum of six doses (6 cycles).

ZYC300 is a plasmid DNA formulated within biodegradable microencapsulated particles. This is the first time that ZYC300 and Cyclophosphamide will be given together. Cyclophosphamide is a chemotherapy drug approved by the FDA that has been used for many years in many different kinds of cancer. In this trial the study drug will be used to boost the immune system. Sometimes the immune system cannot fight infected or abnormal cells because of other cells called T reg cells. The T reg cells limit the immune systems attack on infected or abnormal cells. In this study, the hope is that Cyclophosphamide will inhibit the T regs cells so that the ZYC300 can work better to attack the cancer cells.
Intrahepatic cholangiocarcinoma (iCCA) is classified among primary liver tumors and has demonstrated a consistently increasing incidence in recent years. Due to the poor long-term survival rates reported in older studies, liver transplantation continues to be a contraindication in the curative treatment of iCCA. The persistent shortage of organs also necessitates that each new indication for transplantation be carefully evaluated and critically scrutinized. Currently, partial resection remains the preferred treatment modality, although at diagnosis, only approximately 20% of cases are amenable to this approach. Post-partial resection, the five-year survival rate is observed to be between 20-34%. In cases of irresectability, palliative chemotherapy often remains the only option, typically associated with a poor prognosis. Numerous studies have demonstrated that long-term outcomes following liver transplantation for iCCA have evolved and improved over the years. In a meta-analysis by Ziogas et al., data from a total of 18 studies (involving 355 patients) and one registry study (385 patients) were analyzed. The pooled 1-, 3-, and 5-year survival rates were 75%, 56%, and 42%, respectively. Meanwhile, the pooled 1-, 3-, and 5-year recurrence-free survival rates were 70%, 49%, and 38%, with an overall recurrence rate of 43%. A potential reason for this marked improvement may be attributed to the introduction of neoadjuvant therapy. Studies by Hu et al. and Lunsford et al. have demonstrated that the utilization of neoadjuvant therapy is associated with significantly improved survival outcomes. The study aims to conduct a prospective, non-randomized study (LIVINCA) to further explore the effects of living-donor liver transplantation in the treatment of unresectable neoadjuvant treated (chemotherapy AND selective internal radiotherapy) intrahepatic cholangiocarcinoma.
Network models are increasingly invoked to characterize the neurobiological underpinnings of mental illnesses. Dysfunction within specific circuits promotes the formation of specific symptoms. This suggests an opportunity to treat specific symptoms by modulating specific circuits. Repetitive transcranial magnetic stimulation (rTMS) is capable of circuit-specific neuromodulation. It is also an established treatment for Major Depressive Disorder (MDD). Clinical experience suggests that rTMS treats different symptom constructs by stimulating different circuits. However, there remains a critical lack of mechanistic evidence to support putative network mechanisms of rTMS, limiting its ability to treat patients with more personalized and optimized approaches. This mechanistic proposal will first use resting-state functional connectivity (FC) MRI and customized analytic pipelines to characterize functional network topography in healthy and depressed individuals at high resolution.This data will be used to derive rTMS targets functionally situated in discrete prefrontal networks (e.g., control, default, salience, limbic/reward). Next, patients will take part in a within-subject design in which they undergo rTMS to each target on separate days. Each target will be stimulated four times on a given day, and after each stimulation changes will be measured with: (1) REST-BOLD MRI (to assess FC changes), (2) TASK-BOLD MRI (to assess changes in BOLD activation on paradigms validated to test RDoC constructs), (3) state-based questionnaires or (4) neuropsychological tests. This work will facilitate individualized neuromodulation approaches based on network topography. This will pollinate large-scale clinical trials assessing the effects of differential circuit modulation. It will also illuminate circuit-construct relationships across neuropsychiatric disorders.
Exposure to chronic and unpredictable stressors can precipitate mood-related disorders in humans, particularly in individuals with pre-existing mental health challenges. L-type calcium channels (LTCCs) have been implicated in numerous neuropsychiatric disorders, as LTCC encoding genes have been identified as candidate risk factors for neuropsychiatric illnesses. In these sets of experiments, we sought to examine the ability of LTCC blockade to alter depression, anxiety, and anhedonic-related behavioral responses to chronic unpredictable stress (CUS) exposure in female and male rats. Rats first underwent either 21 days of CUS or no exposure to chronic stressors, serving as home cage controls (HCC). Then rats were examined for anhedonia-related behavior, anxiety and depression-like behavioral responses as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). CUS exposed females and males showed anhedonic and anxiogenic-like behavioral responses on the SPT and EPM, respectively, when compared to HCCs. In female and male rats, systemic administration of the LTCC blocker isradipine (0.4 mg/kg and 1.2 mg/kg, I.P.) attenuated the CUS-induced decrease in sucrose preference and reversed the CUS-induced decrease in open arm time. In the FST, systemic isradipine decreased immobility time across all groups, consistent with an antidepressant-like response. However, there were no significant differences in forced swim test immobility time between HCC and CUS exposed animals. Taken together, these data point to a role of LTCCs in the regulation of mood disorder-related behavioral phenotype responses to chronic stress exposure.
A disinfectant or pharmaceutical composition for human or veterinary use comprises a mixture of oxytetracycline and carbomycin, preferably in a proportion of 5 to 95 parts by weight of oxytetracycline to 95 to 5 parts by weight of carbomycin.  The antibiotic may be in any biological form, either pure or impure. Specified are amphoteric oxytetracycline, the hydrochloride, sulphate and sodium salt of oxytetracycline; carbomycin base, and the hydrochloride and sulphate salts of carbomycin. Pharmaceutical preparations are (a) injections in e.g. saline solution; (b) oval preparations in the form of capsules, tablets, elizirs powders, solutions or suspensions; and (c) topical preparations such as ointments.  Specification 732,150, [Group IV (b)], is referred to.