anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INTRODUCTION: The revision of International Federation of Gynaecology and Obstetrics staging in 2018 with recommendations to include cross-sectional imaging and a separate stage for node positive disease have opened a lot of uncertainties in implementing the correct treatment approach in these patients. While studies have suggested higher chances of occult para-aortic lymph node (PALN) even with advanced imaging, especially in pelvic node positive disease which tend to recur after pelvic radiation therapy. This study intends to study these patients and isolate the subset who will benefit most from elective PALN irradiation.
METHODS AND ANALYSIS: This is an ongoing multicentric phase III randomised controlled trial with a sample size of 274 subjects in two arms (137 in each arm) to determine the superiority of limited elective para-aortic irradiation compared with no irradiation. Arm one includes radiation to the lower PALN and pelvis; Arm two includes radiation to the pelvis. Concurrent chemotherapy followed by brachytherapy is standard in both arms. Patients with cervical cancer and radiologically positive pelvic LNs aged>18 years and<70 years are screened for the study. The primary endpoint of this study is 3-year disease-free survival. The secondary endpoints include 3-year para-aortic recurrence-free survival, 3-year distant metastasis-free survival, 3-year overall survival, acute and late toxicity, quality of life. Translational study to evaluate systemic immune response by FAPI-PETCT (fibroblast activator protein inhibitor positron emission tomography) and assessment of p16, L1 cell adhesion molecule (L1CAM) and protein death ligand-1 (PDL-1) expression by immunohistochemistry.
ETHICS AND DISSEMINATION: The study has been approved by the institutional ethics committee and will be routinely monitored according to standard guidelines. The results of the study will be published in peer-reviewed scientific journals, presented at conferences and submitted to regulatory authorities.
TRIAL REGISTRATION NUMBER: The study was registered on 17 January 2022 under CTRI/2022/01/039495 (http://ctri.nic.in).
This is a randomized double-blind, controlled feeding experiment examining the effect of CMC on the stool microbiota composition, gene expression, and microbiota localization with respect to the epithelium. In addition, the investigators will assess the impact of CMC exposure in the diet on markers of metabolic syndrome including response to oral glucose tolerance testing and other plasma metabolite measurements.

Sixteen healthy volunteers were be recruited. 3 were admitted for 17 days and 13 participants were admitted for an 11-day in-patient study. All participants received 3 full days of freshly prepared emulsifier-free food to begin the study. This will be called the "washout period". Those will a 17 day stay received the wash out diet while inpatient and those with an 11 day stay received the wash out dies while out patient. Participants will then be randomized into an "emulsifier-free" arm and a "CMC" arm in a 1:1 ratio. Both arms will continue the same diet except that the "CMC" arm's brownie and sorbet will have CMC added to achieve a level of 15 gm per person per day consumption. Serial collection of fecal, plasma, urine and mucosal biopsy samples will be performed to investigate the extent to which CMC consumption by humans impacts the gut microbiota and its interaction with the host parameters related to inflammation and metabolism. Participants will have daily urine and stool collections. Sigmoidoscopies and glucose tolerance testing will be completed on the day prior to the start of the intervention and the last day of the inpatient stay (Days 4 and 17 for the 3 participants with a 17 day stay and days 1 and 11 for participants with an 11 day stay. Blood samples were collected on days 1-4, 5, 8, 10, 12, 15, and 17 for those with a 17 day inpatient stay and 1-4, 8, 10, and 11 for those with an 11 day stay.
Low back pain (LBP) is a pervasive global health issue. Roughly 40% of LBP cases are attributed to intervertebral disc degeneration (IVDD). While the underlying mechanisms of IVDD remain incompletely understood, it has been confirmed that apoptosis and extracellular matrix (ECM) degradation caused by many factors such as inflammation, oxidative stress, calcium (Ca2+) homeostasis imbalance leads to IVDD. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are involved in these processes. The initiation of ER stress precipitates cell apoptosis, and is also related to inflammation, levels of oxidative stress, and Ca2+ homeostasis. Additionally, mitochondrial dynamics, antioxidative systems, disruption of Ca2+ homeostasis are closely associated with Reactive Oxygen Species (ROS) and inflammation, promoting cell apoptosis. However, numerous crosstalk exists between the ER and mitochondria, where they interact through inflammatory cytokines, signaling pathways, ROS, or key molecules such as CHOP, forming positive and negative feedback loops. Furthermore, the contact sites between the ER and mitochondria, known as mitochondria-associated membranes (MAM), facilitate direct signal transduction such as Ca2+ transfer. However, the current attention towards this issue is insufficient. Therefore, this review summarizes the impacts of ER stress and mitochondrial dysfunction on IVDD, along with the possibly potential crosstalk between them, aiming to unveil novel avenues for IVDD intervention.
The human oral mucosa contains one of the most complex cellular systems that are essential for normal physiology and defense against a wide variety of local pathogens. Evolving techniques and experimental systems have helped refine our understanding of this complex cellular network. Current single-cell RNA sequencing methods can resolve subtle differences between cell types and states, thus providing a great tool for studying the molecular and cellular repertoire of the oral mucosa in health and disease. However, it requires the dissociation of tissue samples, which means that the interrelationships between cells are lost. Spatial transcriptomic methods bypass tissue dissociation and retain this spatial information, thereby allowing gene expression to be assessed across thousands of cells within the context of tissue structural organization. Here, we discuss the contribution of spatial technologies in shaping our understanding of this complex system. We consider the impact on identifying disease cellular neighborhoods and how space defines cell state. We also discuss the limitations and future directions of spatial sequencing technologies with recent advances in machine learning. Finally, we offer a perspective on open questions about mucosal homeostasis that these technologies are well placed to address.
Patients will receive placebo solution oral gargle twice per day (5ml for each dose, garble for 3 minutes) and continue for 3 weeks. A standard dose of glucocorticoids (mucosal-dominant PV: prednisone 0.5 mg/kg/d, moderate mucocutaneous PV: prednisone 0.75 mg/kg/d) will be applied at the same time.
Aatients receive CBX-12 IV, over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and CT scans on study and undergo blood sample collection throughout the trial.
BACKGROUND: Renal denervation (RDN) has been proved to relieve cardiac hypertrophy; however, its detailed mechanisms remain obscure. This study investigated the detailed protective mechanisms of RDN against cardiac hypertrophy during hypertensive heart failure (HF).
METHODS: Male 5-month-old spontaneously hypertension (SHR) rats were used in a HF rat model, and male Wistar-Kyoto (WKY) rats of the same age were used as the baseline control. Myocardial hypertrophy and fibrosis were evaluated by hematoxylin-eosin (HE) staining and Masson staining. The expression of target molecule was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, immunohistochemical and immunofluorescence, respectively. Cardiomyocyte hypertrophy was induced by norepinephrine (NE) in H9c2 cells in vitro and evaluated by brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), β-myosin heavy chain (β-MHC), and α-myosin heavy chain (α-MHC) levels. Oxidative stress was determined by malondialdehyde (MDA) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzyme activities. Mitochondrial function was measured by mitochondrial membrane potential, adenosine triphosphate (ATP) production, mitochondrial DNA (mtDNA) number, and mitochondrial complex I-IV activities. Molecular mechanism was assessed by dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays.
RESULTS: RDN decreased sympathetic nerve activity, attenuated myocardial hypertrophy and fibrosis, and improved cardiac function in the rat model of HF. In addition, RDN ameliorated mitochondrial oxidative stress in myocardial tissues as evidenced by reducing MDA and mitochondrial reactive oxygen species (ROS) levels, and enhancing SOD and GSH-Px activities. Moreover, phosphofurin acid cluster sorting protein 2 (PACS-2) and broad-complex, tramtrak and bric à brac (BTB) domain and cap'n'collar (CNC) homolog 1 (BACH1) were down-regulated by RDN. In NE-stimulated H9c2 cells, PACS-2 and BACH1 levels were markedly elevated, and knockdown of them could suppress NE-induced oxidative stress, cardiomyocyte hypertrophy, fibrosis, as well as mitochondrial dysfunction. Transforming growth factor beta1(TGFβ1)/SMADs signaling pathway was inactivated by RDN in the HF rats, which sequentially inhibited specificity protein 1 (SP1)-mediated transcription of PACS2 and BACH1.
CONCLUSION: Collectively, these data demonstrated that RDN improved cardiac hypertrophy and sympathetic nerve activity of HF rats via repressing BACH1 and PACS-2-mediated mitochondrial oxidative stress by inactivating TGF-β1/SMADs/SP1 pathway, which shed lights on the cardioprotective mechanism of RDN in HF.
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Participants will receive a loading dose of SC dupilumab Dose 1 at Week 0, SC placebo every two week (q2w) from Week 1 through Week 15 and then dupilumab Dose 2 q2w from Week 2 through Week 14. At Week 16, participants who achieve EASI-75 response (dupilumab responders) will continue on dupilumab Dose 2 q2w through Week 30 and placebo q2w from Week 17 through Week 31. Participants who do not achieve an EASI-75 response (dupilumab non-responders) will receive placebo qw from Week 16 through Week 18 (washout period) and bermekimab Dose 2 qw from Week 19 through Week 31.
The treatment of proximal deep vein thrombosis (DVT) of the lower limbs includes an initial management phase, covering the first 1 to 3 weeks, a primary treatment phase, lasting a minimum of 3 months, and a secondary treatment phase for those patients requiring continuing anticoagulation beyond the first 3 to 6 months. During the initial phase most patients with DVT can be managed as outpatients. Exclusion criteria for home treatment include high risk of bleeding, limb threatening DVT or other conditions requiring hospitalisation. Anticoagulant drugs represent the mainstay of treatment and include parenteral drugs such as unfractionated heparin or low molecular weight heparin, and oral drugs such as the vitamin K antagonists and the direct oral anticoagulants (DOACs). DOACs are currently recommended as the first line of treatment for proximal DVT of the lower limbs, with no preference for one DOAC over another. Factors to consider when choosing the anticoagulant strategy include, among others, renal and liver function, underlying diseases such as cancer or the antiphospholipid syndrome, and patient preferences. Indefinite duration of anticoagulation beyond the first 3 to 6 months is recommended for patients with unprovoked DVT and patients with permanent, chronic risk factors. Two DOACs, namely apixaban and rivaroxaban, can be administered at low doses for the secondary prevention of DVT. Elastic compression stockings (ECS) have been used for decades in patients with proximal DVT with the aim of counteracting the venous hypertension generated by the vascular disorder and reducing leg edema and to prevent the post-thrombotic syndrome.
The current study was planned to explore the potential synergistic role of the co-administration of sarilumab and dexamethasone in reducing blood biomarkers associated with cytokine release syndrome in hospitalised patients of coronavirus disease-2019. The sample comprised 22 patients hospitalised with severe and critical severity levels and who were treated with sarilumab and dexamethasone. Positive responses were seen in blood biomarkers, including decreased interleukin-6 alpha levels and improved oxygen saturation. Tumour necrosis factor, Ddimer, C-reactive protein, ferritin and lymphocyte count also showed positive responses in patients who survived than those who died. Lactate dehydrogenase levels fluctuated with improvement among the survivors, but had limited effectiveness in those who died. The findings suggested promising avenues for future treatment strategies in patients with severe coronavirus disease-2019 and cytokine release syndrome.
Multiple dose (18) subjects with binge drinking/AUD: Once Part B and Part C has been completed, the data analyzed and approved by the DSMB, Part D will be initiated. This part will consist of a repeated-dose cohort, based on the higher tolerable dose found in Part C and considering the dose effects found in Part B. Subjects will be randomized into either the treatment or the placebo arm at a ratio of 2:1 (12 subjects treated with the investigation product and 6 subjects receiving placebo) and will receive the drug/placebo at a daily basis for a total of 10 consecutive days. Each subject will be sampled for PK for 24 hours after first and last dosing and will be daily monitored for drug effects and safety throughout the study period and until 1 week after the last dosing. The PK and safety information gathered from in this part of the study will be evaluated by the DSMB.
Subjects will be on existing ART for one week followed by PRO 140 700mg weekly SC Inj. + existing ART for the next week. Subsequently, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Nanoparticle albumin-bound paclitaxel is given at 120mg/m2 intravenously over 30 minutes on day 1 and 8, in combination with S-1 which is orally administered (40-60 mg according to the body surface, Bid) on day 1-14 of each 21-days cycle. Number of cycle: 6 cycles.
Neonatal sepsis leads to severe morbidity and occasionally death among neonates within the first week following birth, particularly in low- and middle-income countries. Empirical therapy includes antibiotics recommended by WHO. However, these have been ineffective against antimicrobial multidrug-resistant bacterial strains such as Klebsiella spp, Escherichia coli, and Staphylococcus aureus species. To counter this problem, new molecules and alternative sources of compounds with antibacterial activity are sought as options. Actinobacteria, particularly pathogenic strains, have revealed a biotechnological potential still underexplored. This study aimed to determine the presence of biosynthetic gene clusters and the antimicrobial activity of actinobacterial strains isolated from clinical cases against multidrug-resistant bacteria implicated in neonatal sepsis. In total, 15 strains isolated from clinical cases of actinomycetoma were used. PCR screening for the PKS-I, PKS-II, NRPS-I, and NRPS-II biosynthetic systems determined their secondary metabolite-producing potential. The strains were subsequently assayed for antimicrobial activity by the perpendicular cross streak method against Escherichia fergusonii Sec 23, Klebsiella pneumoniae subsp. pneumoniae H1064, Klebsiella variicola H776, Klebsiella oxytoca H793, and Klebsiella pneumoniae subsp. ozaenae H7595, previously classified as multidrug-resistant. Finally, the strains were identified by 16S rRNA gene sequence analysis. It was found that 100% of the actinobacteria had biosynthetic systems. The most frequent biosynthetic system was NRPS-I (100%), and the most frequent combination was NRPS-I and PKS-II (27%). All 15 strains showed antimicrobial activity. The strain with the highest antimicrobial activity was Streptomyces albus 94.1572, as it inhibited the growth of the five multidrug-resistant bacteria evaluated.
PURPOSE: A single phase silicon acrylate mold is provided to minimize phase separation by including a silicon functional group, an acrylate functional group, and a silicon acrylate hybrid compatibilizing agent. CONSTITUTION: A single phase silicon acrylate mold is a silicon acrylate hybrid compatibilizer which includes at least one of silicon, acrylate, and a combination thereof, a silicon functional group, and an (meth)acrylate functional group. The single phase silicon acrylate mod comprises a silicon-containing pressure-sensitive composition and the silicon acrylate hybrid compatibilizer which is a reaction product of a (meth)acrylate monomer. The acrylate is randomly a combination of 2-ethylhexyl acrylate and methacrylate. A silicon resin and a silicon resin are reacted and form a pressure-sensitive adhesive. The silicon-containing capping agent is introduced before, during, or after the reaction of the silicon resin and the silicon polymer. The single phase silicon acrylate mold is resistant against phase separation.
Compact air-tight medicinal tablets or confectionery are prepared by compressing a granulate or powder containing the active substances e.g. medicines, colouring or flavouring substances, which is solid at room temperature but sinters or melts at a temperature above 40 DEG C., to form tablets which are sintered or melted to become compact without losing their external shape.  The tablets may be coated in known manner, e.g. with sugar, before and/or after being sintered which may then take place at a temperature such that the mass is more or less melted within the coating.  The granulate or powder may be prepared by mixing the normal components of a tablet base e.g. mono-, di- or polysaccharides, sorbitol, mannitol, talcum, starch, gelatin or gum arabic, heating the mixture to remove water if desired, adding the active substances e.g. etheric oils, citric acid and citric oil, to the cooled plastic mass and grinding the mass when hardened.
The effectiveness of LUMRYZ for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy has been established based on a double-blind, randomized, placebo-controlled, two-arm multi-center study to assess the efficacy and safety of a once nightly administration of LUMRYZ in patients with narcolepsy (Study 1; NCT02720744).

A total of 212 patients were randomized to receive LUMRYZ or placebo in a 1:1 ratio and received at least one dose of study drug. The study was divided into four sequential study periods, and incorporated dose titration to stabilized dose administration of LUMRYZ (4.5 g, 6 g, 7.5 g, and 9 g). There was a three-week screening period, a 13-week treatment period including up-titration over a period of eight weeks, five weeks of stable dosing at 9 g/night, and a one-week follow-up period. Patients could be on concomitant stimulant as long as dosage was stable for 3 weeks prior to study start.

The three co-primary endpoints were the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I), and mean change in weekly cataplexy attacks. The MWT measures latency to sleep onset (in minutes), averaged over five sessions at 2-hour intervals following nocturnal polysomnography. For each test session, patients were instructed to remain awake for as long as possible during 30-minute test sessions, and sleep latency was determined as the number of minutes patients could remain awake. The overall score was the mean sleep latency for the 5 sessions. The CGI-I was evaluated on a 7-point scale, centered at No Change, and ranging from Very Much Worse to Very Much Improved. Patients were rated by evaluators who based their assessments on the severity of narcolepsy at Baseline.

Demographic and mean baseline characteristics were similar for the LUMRYZ and placebo groups. A total of 76% were narcolepsy type 1 (NT1; with both symptoms of EDS and cataplexy) patients, and 24% were narcolepsy type 2 (NT2; with symptoms of EDS and without cataplexy) patients. The mean age was 31 years, and 68% were female. Approximately 63% of patients were on concomitant stimulant use. The mean MWT at baseline was 5 minutes for the LUMRYZ group, and 4.7 minutes for the placebo group. The mean number of cataplexy attacks per week at baseline was 18.9 in the LUMRYZ group and 19.8 in the placebo group. A statistically significant improvement was seen on the MWT, CGI-I, and mean weekly cataplexy attacks, for the 6 g (Week 3), 7.5 g (Week 8), and 9 g (Week 13) dose of LUMRYZ, compared to the placebo group (see Table 3, Table 4, and Table 5).
All patients will undergo SRS with the planned target volume (PTV) defined as the resection cavity plus a 3-mm margin after surgical resection of a single brain metastasis. Dose will be prescribed to the maximum isodose line completely encompassing the PTV using the guidelines established in RTOG 9005. All patients will be evaluated for neurocognitive function via Mini-Mental State Examination (MMSE), Quality of Life (QOL) via FACT-Br, and for local recurrence via MRI every 3 months over the course of the study.
TGF-β is considered an important cytokine in the development of interstitial fibrosis in chronic kidney disease. The TGF-β co-receptor endoglin (ENG) tends to be upregulated in kidney fibrosis. ENG has two membrane bound isoforms generated via alternative splicing. Long-ENG was shown to enhance the extent of renal fibrosis in an unilateral ureteral obstruction mouse model, while short-ENG inhibited renal fibrosis. Here we aimed to achieve terminal intron retention of endoglin using antisense-oligo nucleotides (ASOs), thereby shifting the ratio towards short-ENG to inhibit the TGF-β1-mediated pro-fibrotic response. We isolated mRNA from kidney biopsies of patients with chronic allograft disease (CAD) (n = 12) and measured total ENG and short-ENG mRNA levels. ENG mRNA was upregulated 2.3 fold (p < 0.05) in kidneys of CAD patients compared to controls, while the percentage short-ENG of the total ENG mRNA was significantly lower (1.8 fold; p < 0.05). Transfection of ASOs that target splicing regulatory sites of ENG into TK173 fibroblasts led to higher levels of short-ENG (2 fold; p < 0.05). In addition, we stimulated these cells with TGF-β1 and measured a decrease in upregulation of ACTA2, COL1A1 and FN1 mRNA levels, and protein expression of αSMA, collagen type I, and fibronectin. These results show a potential for ENG ASOs as a therapy to reduce interstitial fibrosis in CKD.