anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Calmodulin, a protein critically important for the regulation of all major cardiac ion channels, is the quintessential cellular calcium sensor and plays a key role in preserving cardiac electrical stability. Its unique importance is highlighted by the presence of 3 genes in 3 different chromosomes encoding for the same protein and by their extreme conservation. Indeed, all 3 calmodulin (CALM) genes are among the most constrained genes in the human genome, that is, the observed variants are much less than expected by chance. Not surprisingly, CALM variants are poorly tolerated and accompany significant clinical phenotypes, of which the most important are those associated with increased risk for life-threatening arrhythmias. Here, we review the current knowledge about calmodulin, its specific physiological, structural, and functional characteristics, and its importance for cardiovascular disease. Given our role in the development of this knowledge, we also share some of our views about currently unanswered questions, including the rational approaches to the clinical management of the affected patients. Specifically, we present some of the most critical information emerging from the International Calmodulinopathy Registry, which we established 10 years ago. Further progress clearly requires deep phenotypic information on as many carriers as possible through international contributions to the registry, in order to expand our knowledge about Calmodulinopathies and guide clinical management.
BACKGROUND: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus.
METHODS: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences.
RESULTS: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively).
CONCLUSIONS: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.
FIELD: medicine. SUBSTANCE: the present innovation deals with treating and preventing male erectile disorders during sexual life and, also, in periods when sexual partner is not available. The method includes a course-type injection of erectogenic medicinal preparations to induce adequate, nocturnal spontaneous and/or artificial erections, the frequency and duration of which are sufficient to provide the level of oxygenation of penile cavernous bodies that is necessary to maintain their normal structure and functioning. The method enables to create necessary level of oxygenation of cavernous bodies for prophylaxis of penile fibrosis and maintain normal structure and functioning in cavernous tissue. EFFECT: higher efficiency of treatment and prophylaxis. 3 cl
Ischemia-reperfusion injury (IRI) is a critical pathological condition in which cell death plays a major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs cellular metabolism and decreases cellular bioenergetics through dysfunction of mitochondrial electron transport chain, causing a switch from cellular respiration to anaerobic metabolism, and subsequent cascades of events that lead to increased intracellular concentrations of Na+, H+ and Ca2+ and consequently cellular edema. Restoration of blood supply after ischemia provides oxygen to the ischemic tissue in excess of its requirement, resulting in over-production of reactive oxygen species (ROS), which overwhelms the cells' antioxidant defence system, and thereby causing oxidative damage in addition to activating pro-inflammatory pathways to cause cell death. Moderate ischemia and reperfusion may result in cell dysfunction, which may not lead to cell death due to activation of recovery systems to control ROS production and to ensure cell survival. However, prolonged and severe ischemia and reperfusion induce cell death by apoptosis, mitoptosis, necrosis, necroptosis, autophagy, mitophagy, mitochondrial permeability transition (MPT)-driven necrosis, ferroptosis, pyroptosis, cuproptosis and parthanoptosis. This review discusses cellular and molecular mechanisms of these various forms of cell death in the context of organ transplantation, and their inhibition, which holds clinical promise in the quest to prevent IRI and improve allograft quality and function for a long-term success of organ transplantation.
The present invention is directed toward identification of cardioprotective gene programs in the neonatal heart. Specifically, the newborn (immature) heart or alternatively fetal heart has been recognized as having an increased resistance to pathophysiological forms of stress, e.g. hypoxic stress. The pattern of gene expression in immature heart subject to naturally occurring hemodynamic and hypoxic stress, e.g. that associated with obstructive congenital heart disease, is herein revealed by differential gene profiling; and the induction of a cardioprotective gene pattern, and particularly useful subsets thereof, in the heart chronically adapted to stress is confirmed. Thus, the chronically stressed immature heart provides a novel biosynthetic platform for cardioprotective gene expression, useful as a basis for the development of diagnostic and therapeutic modalities.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life-threatening. Orally and parenterally administered clindamycin has been associated with severe colitis which may end fatally. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of orally and parenterally administered clindamycin, as well as with topical (dermal and vaginal) formulations of clindamycin. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of clindamycin, even when administered by the vaginal route, because approximately 5% of the clindamycin dose is systemically absorbed from the vagina.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia.Studies indicate that a toxin produced by Clostridioides difficile is a primary cause of "antibiotic-associated" colitis.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridioides difficile colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.
BACKGROUND: A substantial number of patients with bladder cancer fail to benefit from immune checkpoint inhibitors (ICIs). We aim to investigate whether the addition of other therapeutic modalities into immunotherapy may augment the immune reactivity, thereby improving the overall response rate.
METHODS: We conducted a comprehensive assessment of the immunological changes following immunotherapy and chemotherapy, employing both single-cell RNA sequencing and bulk RNA sequencing analyses.
RESULTS: The bladder cancer patient treated with ICIs exhibited a higher abundance of B cells and T follicular helper cells compared to the treatment-naïve patient. Analysis of public datasets and the in-house RJBLC-I2N003 cohort revealed the induction of tertiary lymphoid structure (TLS) neogenesis and maturation by immunotherapy. The IMvigor 210 study suggested that TLS could serve as a predictor of immunotherapy response and patient prognosis. In addition, genome-wide transcriptome data unveiled a shift towards the immune-enriched subtype over the desert subtype in patients receiving neoadjuvant chemotherapy. Notably, the proportions of CD20 + B cells, T follicular helper cells, and TLSs were significantly increased. In patients treated with a combination of neoadjuvant chemotherapy and ICIs, TLS positivity and maturity were improved compared to the baseline. Furthermore, neoadjuvant chemoimmunotherapy resulted in a higher rate of pathological complete response compared to monotherapies.
CONCLUSIONS: This work pinpointed the individual effect of immunotherapy and chemotherapy in fostering TLS development, and underscored the superior effectiveness of combined modalities in enhancing TLS maturation and response rates.
* 5-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model.



For women whose risk factors are not described in the above examples, the Gail Model is necessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-866-292-6719.

There are no data available regarding the effect of tamoxifen on breast cancer incidence in women with inherited mutations (BRCA1, BRCA2).

After an assessment of the risk of developing breast cancer, the decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. In the NSABP P-1 trial, tamoxifen treatment lowered the risk of developing breast cancer during the follow-up period of the trial, but did not eliminate breast cancer risk (See Table 3 in CLINICAL PHARMACOLOGY).
Patients with peripheral artery disease (PAD) have a higher risk of cardiovascular events. We examined the histology of atheromatous plaques in the femoral artery and investigated their association with subsequent cardiovascular events in patients with PAD. Patients who underwent femoral artery endarterectomy between March 2010 and January 2021 were included. We analyzed the expression of myeloperoxidase (MPO), citrullinated histone, and programmed cell death ligand 1 (PD-L1) in femoral artery plaques by immunohistochemistry. Data on the subsequent occurrence of major adverse cardiovascular events (MACEs), major adverse limb events (MALEs), and all-cause mortality were retrospectively collected. A total of 37 patients were included. The median age was 71 (range, 42-90) years, and 25 patients (67.6%) were male. During the median follow-up of 24 months, 10 patients experienced MACEs and 16 patients had MALEs. Patients with MACEs had a higher number of MPO-stained cells (p = 0.044) and lower PD-L1 staining intensity (p = 0.021) in atheromatous plaques compared with those of patients with a stable prognosis. When the patients were grouped according to the immunologic score based on the MPO-stained cell number and PD-L1 staining intensity, those with a higher score had a significantly higher cumulative risk of MACEs (p = 0.014). The immunologic profile of excised peripheral artery plaques may be associated with future cardiovascular events in patients with PAD.
The training workshop is designed as a 3-hour session for care providers. The training will be delivered by trans women. During this training, we plan to have providers: 1) discuss human rights for trans women; 2) teach providers about common words with which to discuss gender identity and expression, and develop a basic understanding of trans healthcare, HIV prevention, and HIV treatment, and how these types of healthcare affect trans women living with and affected by HIV; 3) discuss what it means to be trans-affirming in their work and how they can make their organizations more trans- affirming; and 4) have participants complete a case study to apply what they have learned to practice. These case studies will address issues affecting trans women who are immigrants/newcomers, trans women who are living with HIV, and trans women who experience other vulnerabilities.
The invention discloses a preparation for preventing and treating liver enterocytozoosis of prawns and shrimps, a preparation method and application thereof, wherein the preparation comprises the following raw materials: rosemary oil, anise oil, talcum powder and auxiliary materials. The preparation comprises the following components in percentage by mass: 3.0 to 3.5 percent of rosemary oil, 1.0 to 2.0 percent of fennel oil, 15.0 to 18.0 percent of talcum powder and 78.0 to 80.0 percent of auxiliary material. The talcum powder is feed grade talcum powder, and the auxiliary material is corn starch. The invention also provides a preparation method and application of the preparation. The preparation is added into prawn feed, and is mixed with 2-3g per kilogram of prawn feed for oral administration for 5-7 days. The compound preparation prepared by the invention is safe for target animals, can effectively inhibit the growth of the shrimp liver enterocytozoon and kill the shrimp liver enterocytozoon, and has the advantages of simple preparation process, convenient use, no toxicity and no risk of drug residue.
Starts in year 1; intervention package with 11-13 year old girls for 10 months; standard parental and community engagement. All programming ends after 10 months.
Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.
Systems and methods for treating gingival tissue or oral biofilm includes applying to the gingival tissue (sulcus or periodontal pocket) a biofilm penetrating antimicrobial agent; removing the imbedded anaerobic bacteria from the gingival tissue following at least one applying of the antimicrobial agent to the gingival tissue; administering colloidal hydrogen peroxide gel to the gingival tissue following the removing of imbedded anaerobic bacteria; and cleaning the gingival tissue with a cleaning agent directly following the administering of the colloidal hydrogen peroxide gel for modifying the environment from anaerobic (dis-eased) to aerobic (healthy). Methods and systems for treating and controlling oral periopathogens that have been found to be asso-ciated with systemic inflammation and/or disease in a periodontal pocket, inhibiting their entry into the host circulatory system, and decreasing the systemic effects. A bacterial community present in one or more oral treatment regions is determined. A  peri-odontal medicament delivery tray is prepared for the patient with the delivery tray being configured with one or more application regions, each configured for applying a medicament to a different one of the oral treatment regions. The medicaments are applied to each oral treatment region, including placing each medicament into a different application region of the delivery tray. Each of the applied medicaments is applied as a function of a determined efficacy of the medicament against the bacterial community de-termined to be in the oral treatment region associated with the application region in which each medicament is applied.
Participants received GLPG0634 25 mg capsules, orally, BID during Weeks 1 to 12. Participants who were responders (having at least 20% improvement on TJC68 and SJC66) remained on 25 mg BID while nonresponders were re-randomized to 50 mg BID during Weeks 13 to 24.
Crossing the vascular endothelium is a necessary stage for circulating cells aiming to reach distant organs. Leukocyte passage through the endothelium, known as transmigration, is a multistep process during which immune cells adhere to the vascular wall, migrate and crawl along the endothelium until they reach their exit site. Similarly, circulating tumor cells (CTCs), which originate from the primary tumor or reseed from early metastatic sites, disseminate using the blood circulation and also must cross the endothelial barrier to set new colonies in distant organs. CTCs are thought to mimic arrest and extravasation utilized by leukocytes; however, their extravasation also requires processes that, from an endothelial perspective, are specific to cancer cells. Although leukocyte extravasation relies on maintaining endothelial impermeability, it appears that cancer cells can indoctrinate endothelial cells into promoting their extravasation independently of their normal functions. In this Review, we summarize the common and divergent mechanisms of endothelial responses during extravasation of leukocytes (in inflammation) and CTCs (in metastasis), and highlight how these might be leveraged in the development of anti-metastatic treatments.
Psoriasis is a common chronic inflammatory skin disease, associated with significant morbidity and a considerable negative impact on the patients' quality of life. The complex pathogenesis of psoriasis is still incompletely understood. Genetic predisposition, environmental factors like smoking, alcohol consumption, psychological stress, consumption of certain drugs, and mechanical trauma, as well as specific immune dysfunctions, contribute to the onset of the disease. Mounting evidence indicate that skin dysbiosis plays a significant role in the development and exacerbation of psoriasis through loss of immune tolerance to commensal skin flora, an altered balance between Tregs and effector cells, and an excessive Th1 and Th17 polarization. While the implications of skin dysbiosis in psoriasis pathogenesis are only starting to be revealed, the progress in the characterization of the skin microbiome changes in psoriasis patients has opened a whole new avenue of research focusing on the modulation of the skin microbiome as an adjuvant treatment for psoriasis and as part of a long-term plan to prevent disease flares. The skin microbiome may also represent a valuable predictive marker of treatment response and may aid in the selection of the optimal personalized treatment. We present the current knowledge on the skin microbiome changes in psoriasis and the results of the studies that investigated the efficacy of the different skin microbiome modulation strategies in the management of psoriasis, and discuss the complex interaction between the host and skin commensal flora.
A method for screening compound libraries or portions thereof by one or more bioavailability properties including absorption is provided. Novel compound libraries selected for bioavailability as produced by the method also are provided. The methods involve screening of compounds by absorption properties, and optionally absorption and one or more additional properties. The methods are exemplified by screening of a plurality of compounds of a first compound library and generating an absorption profile for each test sample of interest.  Absorption profiles derived from screening the first library are compared and compounds having a desired absorption profile are selected to generate a second library. The absorption profiles are capable of being generated by supplying in vitro bioavailability data to a computer-implemented physiologic-based pharmacokinetic tool of the invention to generate as output a simulated absorption profile for each test sample. The process can be repeated one or more times so as to obtain a convergent library of compounds increasingly optimized for a bioavailability parameter including absorption.
###  Risk Summary

There are no available data on Lymphoseek use in pregnant women. Additionally, animal reproduction studies have not been conducted with technetium Tc 99m tilmanocept. However, all radiopharmaceuticals, including Lymphoseek, have a potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering Lymphoseek administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from the drug and the gestational timing of exposure. 

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively, regardless of drug exposure.