anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Lipopolysaccharide binding proteins (LBPs) and bactericidal permeability increasing proteins (BPIs) play significant roles in the immune response of vertebrates against bacterial pathogens. These soluble proteins produced by immune cells, specifically interact with and bind to bacterial lipopolysaccharides (LPS), with BPIs also displaying antibacterial activity. In Argopecten purpuratus scallop larvae resistant to Vibrio bivalvicida VPAP30, we identified a significant overexpression of a transcript displaying molecular features of an LBP/BPI protein, both before and after infection. Therefore, in the present work we aimed to understand the role of this novel LBP/BPI, named ApLBP/BPI3, in the scallop resistance to this Vibrio. The ApLBP/BPI3 open reading frame encodes a putative protein of 506 amino acids, with a molecular weight 56.78 kDa. The protein contains a C-terminal domain of 403-amino acid that, after theorical cleavage, displays a soluble form of 44.99 kDa, featuring two BPI/LBP/CETP domains, an apolar binding pocket, a single disulfide bond and a BPI dimerization interface. Phylogenetic analysis reveals high similarity between ApLBP/BPI3 and other mollusk LBP/BPI proteins. Aplbp/bpi3 transcripts were constitutively and highly expressed in hemocytes, gills, mantle, and digestive gland tissues, and were induced following VPAP30 infection in scallop larvae and adult hemocytes. We characterized ApLBP/BPI3 protein using a polyclonal antibody against a synthetic peptide. ApLBP/BPI3 was secreted to the media by infected cultured hemocytes, detected by ELISA. ApLBP/BPI3 was spotted inside non-infected hemocytes, bound to the cell wall of V. bivalvicida after in vitro hemocyte infection, and coating the gills and mantle epithelial barriers before and after an in vivo immune challenge, with stronger detection after VPAP30 injection, detected by immunofluorescence. Infected scallop larvae showed increased ApLBP/BPI3 levels, with slightly higher production in resistant larvae, determined by Western blot. Finally, silencing the Aplbp/bpi3 transcript through RNA interference and and subsequently infecting scallop juveniles with an LD50 of V. bivalvicida resulted in 100 % mortality. Altogether, results demonstrate the essential role of this immune effector in the resistance of A. purpuratus.
A male baby born out of consanguineous marriage (third degree) to a primigravida mother presented to our hospital on day 21 of life as his third hospitalisation with jerky movements, respiratory distress and refusal to feed. The baby had blood culture-positive sepsis, which was treated adequately. He was given antiseizure therapy for jerky movements, but there was no response to multiple antiseizure therapy, and then pyridoxine was added. A significant response was noted with the addition of clonazepam. Neuroimaging and electroencephalogram were normal. The whole exome sequencing suggested a homozygous mutation (frameshift variant c.97delA in exon 2 of the GLRB gene) associated with hyperekplexia 2, resulting in the amino acid substitution p.Lys34fs*27.
The present disclosure provides materials and methods for treating a patient with one or more conditions or disorders associated with COL7A1 whether ex vivo or in vivo. For example, the present disclosure provides materials and methods for treating a patient with Dystrophic Epidermolysis Bullosa (DEB). Also provided are materials and methods for editing a COL7A1 gene in a cell by genome editing. The present disclosure also provides materials and methods for altering the contiguous genomic sequence of a COL7A1 gene in a cell. In addition, the present disclosure provides one or more gRNAs for editing a COL7A1 gene. Also provided are therapeutics comprising at least one or more gRNAs for editing a COL7A1 gene. In addition, the present disclosure provides therapeutics for treating patients with a COL7A1 related condition or disorder.
The labial surface of anterior teeth will be brushed by the circular brushing technique twice daily (morning and after 6hours) for at least 1 minute using (calcium carbonate /perlite) containing toothpaste. Soft bristles toothbrushes will provided to all patients. After 1 month, re-evaluation of the stains will be performed and the data will be recorded.
SCF (PromotorTM Soluble Corn Fiber 85, provided by manufacturer Tate \& Lyle) will be dispensed to participants as a dry powder in sachets of 12 g SCF85 product (which is approximately 10 g fiber). Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be asked to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.
Subjects received 4 Synera® patches for 2 hours in Session 1 and 4 patches for 12 hours in Session 4. During Study Session 2, subjects were randomly assigned to 4-hour applications of either 4 Synera® patches or 4 lidocaine/tetracaine patches without heat ("no heat patches") and were crossed over during Study Session 3.
The COVID-19 pandemic has brought significant changes in daily life for humanity and has had a profound impact on mental health. As widely acknowledged, the pandemic has led to notable increases in rates of anxiety, depression, distress, and other mental health-related issues, affecting both infected patients and non-infected individuals. COVID-19 patients and survivors face heightened risks for various neurological and psychiatric disorders and complications. Vulnerable populations, including those with pre-existing mental health conditions and individuals living in poverty or frailty, may encounter additional challenges. Tragically, suicide rates have also risen, particularly among young people, due to factors such as unemployment, financial crises, domestic violence, substance abuse, and social isolation. Efforts are underway to address these mental health issues, with healthcare professionals urged to regularly screen both COVID-19 and post-COVID-19 patients and survivors for psychological distress, ensuring rapid and appropriate interventions. Ongoing periodic follow-up and multidimensional, interdisciplinary approaches are essential for individuals experiencing long-term psychiatric sequelae. Preventive strategies must be developed to mitigate mental health problems during both the acute and recovery phases of COVID-19 infection. Vaccination efforts continue to prioritize vulnerable populations, including those with mental health conditions, to prevent future complications. Given the profound implications of mental health problems, including shorter life expectancy, diminished quality of life, heightened distress among caregivers, and substantial economic burden, it is imperative that political and health authorities prioritize the mental well-being of all individuals affected by COVID-19, including infected individuals, non-infected individuals, survivors, and caregivers.
Premature ejaculation (PE) has been known as one of the most common male sexual dysfunction. PE can deteriorate sexual satisfaction and quality of life of the patients and their partners. Recently, the International Society for Sexual Medicine (ISSM) gave a definition that PE is a 'male sexual dysfunction characterized by ejaculation that always or nearly always occurs prior to or within 1 min of vaginal penetration from the first sexual experience (lifelong PE), or a clinically significant reduction in latency time, often to about 3 min or less (acquired PE)' . Until now, several treatment modalities for PE have been introduced. Psychological/behavioral; pharmacologic therapies, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, tramadol, phosphodiesterase 5 inhibitor, alpha 1-andreoreceptor antagonists; topical anaesthetics, and even surgical treatments have been used for PE in practice. Dapoxetine is the first oral pharmacological agent developed for the treatment of PE and the only SSRI approved in more than 60 countries for PE. The introduction of dapoxetine was accompanied with high expectation because of the optimal efficacy/ safety profile showed in the phase 3 trials. However, several clinical studies using depoxetine confirmed the efficacy in increasing IELT, it reveals significant dropout rate likely which was shown in the treatment using off-label SSRIs. Despite high efficacy and safety, discontinuation rate of dapoxetine is high compared to PDE5 inhibitors in patients with erectile dysfunction (ED).

Until now dapoxetine is the only approved medical treatment option and there is no second line therapy in case of no-response or refuse to dapoxetine, a comprehensive evaluation of the factors that lead to dropout is needed especially in a real-practice setting. With this background, investigators will assesse the discontinuation rate of dapoxetine treatment in patients with PE and the reasons for discontinuation in a clinical setting throughout a follow-up period of 2 years.
INTRODUCTION: This consensus paper provides recommendations for oral health professionals on why and how to assess caries activity and progression with special respect to the site of a lesion.
METHODS: An expert panel was nominated by the executive councils of the European Organization for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD). The steering committee built three working groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity and progression assessment, and (3) obtain individualized caries diagnoses. The experts of work group 2 phrased and agreed on provisional general and specific recommendations on caries lesion activity and progression, based on a review of the current literature. These recommendations were then discussed and refined in a consensus workshop followed by an anonymous Delphi survey to determine the agreement on each recommendation.
RESULTS: The expert panel agreed on general (n = 7) and specific recommendations (n = 6). The specific recommendations cover coronal caries on pits and fissures, smooth surfaces, proximal surfaces, as well as root caries and secondary caries/caries adjacent to restorations and sealants. 3/13 recommendations yielded perfect agreement.
CONCLUSION: The most suitable method for lesion activity assessment is the visual-tactile method. No single clinical characteristic is indicative of lesion activity; instead, lesion activity assessment is based on assessing and weighing several clinical signs. The recall intervals for visual and radiographic examination need to be adjusted to the presence of active caries lesions and recent caries progression rates. Modifications should be based on individual patient characteristics.
As America ages, cost-effective care for chronic diseases, such as low back pain, becomes more important. Although estimates vary, 70-85% of Americans will suffer from back pain at some point in their lives. Back pain is well established as one of the most common reasons for seeking care from a medical doctor. The American public also turns to alternative medicine providers, such as doctors of chiropractic, for back pain care. However, few clinical examples and little scientific evidence exist of care coordination between these two provider groups in general, and none that specifically target older adults above the age of 65. The purpose of the Collaborative Care for Older Adults with Back Pain (COCOA) Clinical Trial is to evaluate the clinical effectiveness and feasibility of a collaborative care model (medical and chiropractic care) through a pragmatic, prospective pilot trial conducted with 120 older adults over the age of 65 with low back pain of at least 1 month duration. Participants will be randomized to 3-parallel treatment arms: a) conventional medical care (MED CARE), b) unlinked conventional medical and chiropractic care (DUAL CARE), and c) a co-management model including conventional medical and chiropractic care (SHARED CARE). Participants in all three groups will receive up to 12 weeks of usual back pain treatment from medical doctors or doctors of osteopathy (MD/DO) at Genesis Family Medical Center. Participants in two treatment groups additionally will receive up to 12 weeks of usual chiropractic care for back pain from doctors of chiropractic at the Palmer Research Clinic. Outcomes including pain, disability and secondary outcomes will be measured at 1, 2, and 3 months (primary endpoint) with follow-up assessments completed by telephone at 6, 9, and 12 months.
Epidural Analgesia (EDA) An epidural catheter was inserted at thoracic level (Th8-Th10) before induction of anesthesia. A bolus of 5 mL of bupivacaine 0.5% was started as soon as the epidural catheter was in place, and a continuous perfusion of bupivacaine 0.5% at 5 mL/hr was initiated until the end of surgical procedure.
Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.
Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. For Arm A, one cycle constitutes two durvalumab treatments on Day 1 and Day 15, respectively, repeated every 28 days.
This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution(TM)). A particular advantage of exonuclease-mediated reassembly methods is the ability to reassemble nucleic acid strands that would otherwise be problematic to chimerize. Exonuclease-mediated reassembly methods can be used in combination with other mutagenesis methods provided herein. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis(TM)) and non-stochastic polynucleotide reassembly (GeneReassembly(TM)). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines. Vectors obtained by using the methods can have, for example, enhanced antigen expression, increased uptake into a cell, increased stability in a cell, ability to tailor an immune response, and the like. Furthermore, this invention provides methods of obtaining a variety of novel biologically active molecules, in the fields of antibiotics, pharmacotherapeutics, and transgenic traits.
OBJECTIVE: To investigate the regulatory mechanisms of radiation-induced rectal fibrosis (RIRF) and assess the therapeutic potential of S3I-201.
METHODS: Sprague-Dawley rats were divided into control and radiation groups, with the latter exposed to 20 Gray pelvic X-rays. After 10 weeks, rectal tissues were analyzed using tandem mass tag (TMT) proteomics and phosphoproteomics. Pathway enrichment was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, with secondary annotation using Cluego. Representative proteins and their phosphorylated counterparts were validated through immunoblotting in another cohort. STAT3 levels in rectal tissues from irradiated and non-irradiated colorectal cancer patients were examined, and the effects of S3I-201 on human rectal fibroblasts were evaluated.
RESULTS: The radiation group showed significant inflammatory responses and collagen deposition in the rat rectal walls. Enrichment analysis revealed that radiation-induced proteins and phosphoproteins were primarily involved in extracellular matrix-receptor interaction and the MAPK signaling pathway. Immunoblotting indicated increased expression of p-CAMKII, p-MRACKS, p-Cfl1, p-Myl9, and p-STAT3 in the radiation group compared to the control, while p-AKT1 expression decreased. Elevated phosphorylation of STAT3 was observed in submucosal fibroblasts of the post-radiation human rectum. S3I-201 specifically inhibited STAT3 phosphorylation and suppressed activation of human rectal fibroblasts, also inhibiting the pro-fibrotic effects of the classical TGF-β/Smad/CTGF pathway.
CONCLUSION: By integrating phosphoproteomics and proteomics, this study elucidated the protein regulatory network of RIRF and identified the potential therapeutic targets, including phosphoproteins such as STAT3 in managing RIRF.
SIGNIFICANCE: In our research, we employed TMT labeling alongside LC-MS/MS techniques to comprehensively explore the proteomic and phosphoproteomic landscapes in rat models of radiation-induced intestinal fibrosis (RIRF). Our analysis revealed the function and pathways of proteins and phosphorylated proteins triggered by radiation, as well as those with protective roles. We mapped a network of interactions among these proteins and validated key protein expression levels using quantitative methods. Furthermore, we investigated STAT3 as a potential therapeutic target, assessing the efficacy of the inhibitor S3I-201 in laboratory settings, and highlighting its potential for RIRF treatment. Overall, our findings provide groundbreaking insights into the mechanisms underlying RIRF, paving the way for the development of future antifibrotic therapies.
The incidence of young-onset colorectal cancer (CRC) - defined as a diagnosis of CRC prior to age 50 - has increased at alarming rates in recent years. Over 75% of cases occur in patients diagnosed between 40-49 years old, a group that is not traditionally included in young adult cancer initiatives tailored only to patients up to 39 years of age. Young age of CRC onset is a defining feature of hereditary CRC syndromes; as such, the National Comprehensive Cancer Network and American College of Medical Genetics and Genomics recommend germline genetics evaluations for all patients diagnosed with CRC under the age of 50. However, multiple studies have shown suboptimal rates and racial and socioeconomic disparities in guideline-recommended genetics evaluations.

In this pilot implementation study, the investigators aim to develop, implement, and evaluate the effects of a default genetics referral process among patients with young-onset CRC diagnosed between 40-49 years old. The investigators hypothesize that by applying defaults, or pre-selected choices, to minimize the cognitive effort that patients and clinicians use to make decisions, default referrals will improve rates of genetics referrals while reducing existing racial and socioeconomic disparities. The investigators will implement this intervention at five academic and community hospitals within Penn Medicine that serve a racially, socioeconomically, and geographically diverse patient population. The investigators will use an automated electronic health record-based algorithm to identify eligible patients, after which default referrals for genetic risk evaluation will be made unless patients or their oncology clinicians opt out. The investigators will rigorously evaluate the impact of this default genetics referral process using mixed methods leveraging models and frameworks from the field of implementation science.
Mitral regurgitation (MR) is the most common heart valve condition in the world. MR occurs when the mitral valve does not close properly, allowing blood to leak back into the upper chamber of the heart. As a result, the heart may try to pump harder in order to compensate for the decrease in blood flow to the rest of the body. Patients with severe MR suffer from debilitating symptoms such as shortness of breath, heart palpitations, lightheadedness, and fatigue. These patients are at risk of poor quality of life, marked limitation in activity, repeated heart failure hospitalizations, and increased mortality. Chronic severe MR is often associated with heart failure and can lead to death if left untreated.

While mitral valve repair or replacement surgery is currently regarded as standard of care, many patients with clinically significant MR are at an unacceptable risk of morbidity and mortality and are therefore not appropriate surgical candidates. To optimize afterload reduction and treatment of fluid load, these patients are often treated with medical management (i.e., beta blockers, ACE inhibitors, angiotensin II receptor blockers) which may relieve MR symptoms, but does not address the underlying cause of the condition. As a result, a significant portion of patients treated medically continue to progress to heart failure and experience an increasingly debilitating quality of life. A significant unmet clinical need thus exists for the treatment of moderate-to-severe and severe MR in high surgical risk patients.

The MitraClip System has been in clinical use for treatment of significant MR since 2003. The device received CE (Conformité Européenne) Mark for both DMR and FMR indications in March 2008 and was approved by FDA for DMR indication in October 2013 and for FMR indication in March 2019. The system is approved for use in more than 80 countries or regions. More than 80,000 patients have undergone the MitraClip procedure worldwide, with the majority of experience in high surgical risk patients.
PURPOSE: An antioxidative composition containing Umbilibaria escuenta hydrolase extract is provided to suppress or treat aging and various diseases without toxicity and side effects. CONSTITUTION: An Umbilibaria escuenta hydrolase extract is prepared by treating protein or sugar hydrolase to Umbilibaria escuenta in pH 2.0-8.0 of buffer solution at 30-80°C for 6-10 hours. The proteinase is protamex, flavourzyme, neutrase, alcalase, alpha-chymotrypsin, pepsin, trypsin, or papain. The buffer is phosphate buffer, sodium acetate-acetic acid buffer or glycine-HCl. The pH of the buffer solution is 2.2-7.0. An antioxidative composition contains Umbilibaria escuenta proteinase extract or Umbilibaria escuenta sugar hydrolase extract as an active ingredient. The antioxidative composition is used in the form of medicine, health supplement, cosmetic product, food, and food additive.