anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The aggregation of the protein α-synuclein is closely associated with several neurodegenerative disorders and as such the structures of the amyloid fibril aggregates have high scientific and medical significance. However, there are dozens of unique atomic-resolution structures of these aggregates, and such a highly polymorphic nature of the α-synuclein fibrils hampers efforts in disease-relevant in vitro studies on α-synuclein amyloid aggregation. In order to better understand the factors that affect polymorph selection, we studied the structures of α-synuclein fibrils in vitro as a function of pH and buffer using cryo-EM helical reconstruction. We find that in the physiological range of pH 5.8-7.4, a pH-dependent selection between Type 1, 2, and 3 polymorphs occurs. Our results indicate that even in the presence of seeds, the polymorph selection during aggregation is highly dependent on the buffer conditions, attributed to the non-polymorph-specific nature of secondary nucleation. We also uncovered two new polymorphs that occur at pH 7.0 in phosphate-buffered saline. The first is a monofilament Type 1 fibril that highly resembles the structure of the juvenile-onset synucleinopathy polymorph found in patient-derived material. The second is a new Type 5 polymorph that resembles a polymorph that has been recently reported in a study that used diseased tissues to seed aggregation. Taken together, our results highlight the shallow amyloid energy hypersurface that can be altered by subtle changes in the environment, including the pH which is shown to play a major role in polymorph selection and in many cases appears to be the determining factor in seeded aggregation. The results also suggest the possibility of producing disease-relevant structure in vitro.
All anesthetics were administered by a single experienced anesthesiologist. Anesthetic induction was performed progressively with inhaled 1-8% sevoflurane, if the patient was cooperative, otherwise directly to the 8%, and subsequent maintenance 2% in oxygen at 5 L /min. A face mask was connected to a Mapleson C circuit for it. Patients breathed spontaneously, unaided, via a pediatric face mask. A failure was defined as the patient continued to move after following the study protocol for sevoflurane inhalation. Insufficient sedation was treated with increments of 0.5% concentration to achieve the desired effect, ie, maintenance of immobility during botulinum toxin injection. The sevoflurane concentration in the next patient would be adjusted depending on the success or failure for immobility at given sevoflurane concentration ( if successful, 0.5% lower concentration, if failed, 0.5% higher concentration).

The child was recovered from sevoflurane sedation at the end of botulinum toxin injection and transferred to post-anesthetic care unit.
PURPOSE:A cosmetic, containing soluble elastin and/or the soluble elastin and a humectant comonent and/or a physiologically active compnent, capable of activiting the metabolism of the skin, increasing resilience of the skin, and having improved effect on the protection of the skin and retention of water. CONSTITUTION:A cosmetic containing (A) soluble elastin and/or the soluble elastin and (B) a humectant component, e.g. an amino acid, NMF component, peptide or polysaccharide, and/or a physiologically active component, e.g. a vitamin, enzyme, crude drug extract or nucleic acid related substance. The component (A) is supplied in the form of an aqueous solution containing 5-30wt% solid component, and the amount thereof to be incorporated is 0.0001wt% or more as the solid component. The amounts of the humectant and the physiologically active component are respectively 0.01wt% or more and 0.0001wt% or more. The above-mentioned cosmetic is used in the form of toilet water, various creams, milky lotion, pack or cleaning cosmetic, etc.
Mobility is crucial for independent living in old age. Older people with reduced physical ability (frailty) begin to limit their personal range of activities to their immediate living environment and ultimately to their immediate home. Diseases of the musculoskeletal system as well as neurological, psychological, cognitive, sensory, and circulatory disorders can limit functional competence (ability to live independently).In the Longitudinal Urban Cohort Ageing Study (LUCAS), from which selected results are reported in this article, participants were categorized into different functional classes (Robust, postRobust, preFrail, Frail) using the LUCAS functional index. The results show that losses in functional competence were associated with impaired mobility and reduced car driving. Impaired mobility led to restricted radius of action.The aim of healthcare in old age is to preserve independence and quality of life as long as possible. Car driving is an important part of older peoples' activities of daily living. Therefore, primary care physicians should address car driving regularly because preventive measures to strengthen functional health also strengthen car driving ability in older persons.
MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule.
PURPOSE: The aim of the present meta-analysis was to systematically determine the overall complication rate and incidence of cryoshock in patients undergoing cryoablation of the liver.
METHODS: A systematic review and meta-analysis adhering to the PRISMA guidelines and focusing on studies of cryotherapy for liver malignancies published after 2000 were conducted. PubMed, Web of Science, Embase, and Scopus were systematically searched for articles reporting incidences of adverse events associated with percutaneous cryoablation in patients with liver malignancies. Data extraction and screening were independently conducted by two reviewers, who resolved discrepancies through consensus. Statistical analysis was performed to assess heterogeneity and pooled complication rates and included a moderator analysis to explore factors influencing the occurrence of complications.
RESULTS: The initial search yielded 4,145 articles, of which 26 met our inclusion criteria. From these 26 articles, pooled data on 4,029 patients were extracted. Variance between studies reporting cryoshock was low (I2 = 13.15%), while variance among studies reporting major complications was high (I2 = 82.52%). The pooled weighted proportion of major complications was 4.71% while that of cryoshock was as low as 0.265%. Moderator analysis identified publication year as the only moderator for major complications and no moderator for the occurrence of cryoshock.
CONCLUSION: Analysis of currently available evidence indicates that cryoablation has a relative safe profile with a pooled incidence of major complications below 5%. Cryoshock occurred in less than 0.3% of procedures and was not reported for liver lesions smaller than 3 cm.
Rationale: Pulmonary fibrosis is a chronic progressive lung disease with limited therapeutic options. We previously revealed that there is iron deposition in alveolar epithelial type II cell (AECII) in pulmonary fibrosis, which can be prevented by the iron chelator deferoxamine. However, iron in the cytoplasm and the mitochondria has two relatively independent roles and regulatory systems. In this study, we aimed to investigate the role of mitochondrial iron deposition in AECII injury and pulmonary fibrosis, and to find potential therapeutic strategies. Methods: BLM-treated mice, MLE-12 cells, and primary AECII were employed to establish the mouse pulmonary fibrosis model and epithelial cells injury model, respectively. Mitochondrial transplantation, siRNA and plasmid transfection, western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), polymerase chain reaction (PCR), immunofluorescence, immunoprecipitation (IP), MitoSOX staining, JC-1 staining, oxygen consumption rate (OCR) measurement, and Cell Counting Kit-8 (CCK8) assay were utilized to elucidate the role of mitochondrial iron deposition in cell and lung fibrosis and determine its mechanism. Results: This study showed that prominent mitochondrial iron deposition occurs within AECII in bleomycin (BLM)-induced pulmonary fibrosis mouse model and in BLM-treated MLE-12 epithelial cells. Further, the study revealed that healthy mitochondria rescue BLM-damaged AECII mitochondrial iron deposition and cell damage loss. Mitoferrin-2 (MFRN2) is the main transporter that regulates mitochondrial iron metabolism by transferring cytosolic iron into mitochondria, which is upregulated in BLM-treated MLE-12 epithelial cells. Direct overexpression of MFRN2 causes mitochondrial iron deposition and cell damage. In this study, decreased ubiquitination of the ubiquitin ligase F-box/LRR-repeat protein 5 (FBXL5) degraded iron-reactive element-binding protein 2 (IREB2) and promoted MFRN2 expression as well as mitochondrial iron deposition in damaged AECII. Activation of the prostaglandin E2 receptor EP4 subtype (EP4) receptor signaling pathway counteracted mitochondrial iron deposition by downregulating IREB2-MFRN2 signaling through upregulation of FBXL5. This intervention not only reduced mitochondrial iron content but also preserved mitochondrial function and protected against AECII damage after BLM treatment. Conclusion: Our findings highlight the unexplored roles, mechanisms, and regulatory approaches of abnormal mitochondrial iron metabolism of AECII in pulmonary fibrosis. Therefore, this study deepens the understanding of the mechanisms underlying pulmonary fibrosis and offers a promising strategy for developing effective therapeutic interventions using the EP4 receptor activator.
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive.
METHODS: By leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays.
RESULTS: Our investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth.
CONCLUSION: Our findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.
Breast-feeding is of such critical importance to the general health of the infant, as well as the mother-infant relationship, that special efforts should be made to retain this practice even during the HIV pandemic. Breast-feeding is associated with lower rates of infant gastrointestinal infections and protects against high infant mortality from respiratory and gastrointestinal diseases. These protective effects are greatest in the first 6 months of life. However, HIV is transmitted through breast-feeding. HIV-infected women whose circumstances permit them a choice between breast- and formula-feeding have been encouraged to formula-feed. But in developing countries there are HIV-infected women who cannot afford to formula-feed or who, knowing the risks, choose to breast-feed. In these societies, HIV-infected women who deviate from the cultural norm of breast-feeding risk exposing their HIV status and becoming prey to negative social implications. For this group of women, defining strategies that can reduce their risk of transmitting HIV to their infants is essential. Based on data from previous studies, this study proposes to test the hypothesis that NVP will reduce breast-feeding transmission of HIV.

Pregnant HIV-positive women take an oral dose of NVP at the onset of labor. A second dose of NVP will be given 48 hours after the first dose if the woman remains in labor. Infants who initiate breast-feeding are randomized to 1 of the 3 study arms below and receive their first dose of NVP within 48 hours of birth.

Arm 1 receives NVP once a week, Arm 2 receives NVP twice a week, and Arm 3 receives NVP daily. There is no placebo control group. The first 18 infants enrolled in each arm will contribute pre- and post- NVP dose blood samples for pharmacokinetics. The remaining infants will contribute data on safety and pre-dose NVP levels only. Infants return to the clinic weekly for visual assessment of NVP toxicity. Women are counseled to stop breast-feeding their infants by the end of 6 months. Infants receive their last dose of NVP at either 24 weeks of age or 1 week after breast-feeding cessation, whichever occurs first, and have follow-up visits until the infant is 32 weeks old.
PURPOSE:To obtain a new peptide useful for treating diseases related by neuropeptide Y such as overeating neuropathy, apastia neuropathy, depression, epilepsy, hypertension, cardiac incompetence and hormone aberration, having affinity to neuropeptide Y receptor. CONSTITUTION:A peptide of formula I (X1 and X2 are Gly, Ala, Val, etc.; (m) and (n) are 0 or 1; Y is Ala, Ser, Thr, etc.; one of Z1 and Z2 is L-Arg and the other is L-Arg, L-Lys, L-Leu. etc.) or its salt such as a peptide of formula II. This peptide is preferably obtained by condensing a solid-phase resin with a alpha-amino-protected terminal C amino acid by using a peptide autosynthesiger, bonding the alpha-amino-protecting amino acids constituting the objective polypeptide in order, then acetylating the terminal N amino group of the formed polypeptide, eliminating the objective polypeptide from the solid-phase resin, further eliminating the protecting group and subjecting two thiols in the prepared peptide to ring formation reaction through oxidation.
Monocentric trial to evaluate differences in musculoskeletal and cognitive demands of robot-assisted laparoscopic surgery (RALS) vs. conventional laparoscopic surgery (CLS). Demographic and personal data are collected and pseudonymized. During surgery surface electromyography (EMG), electrocardiography (ECG), motion tracking data are collected and the surgery is documented by photos (1 photo/per second). Additionally, perceived physical discomfort (frequency and intensity) and mental load will be assessed within certain time intervals and at the very end of the surgery. The surgeon will not be disturbed in his actions and movement by the measurement equipment or applied procedures. Previous studies with similar designs can be seen as references in this context (549/2012BO1, 409/2013BO1, 262/2018BO1). After completing the surgery, the surgeon will rate difficulty of the surgery, work precision, eye strain and ergonomics during the surgery. Routine interventions like hysterectomies and other selected indications will be analyzed.
Currently, a significant percentage of patients with DLBCL are refractory or relapse after a first line of immunochemotherapy. Second relapses after autologous stem cell transplantation or chimeric antigen receptor T-cell therapies present few treatment options and do not yield good results. New molecules have entered the immunotherapy arsenal. Loncastuximab tesirine comprises a humanized anti-CD19 monoclonal conjugated antibody, which consists of an anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Several studies have proven its efficacy in the treatment of refractory cases of DLBCL with a good safety profile, with the main adverse effects being neutropenia, thrombopenia, and liver enzyme involvement. In this review, we explain the mechanism of action of this molecule, the clinical data that have led to its acceptance by the FDA, and the new therapeutic options that are proposed in association with this drug.
Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to the accelerated pace of modern life. The accumulation of AGEs is primarily attributed to their inherent difficulty in metabolism, which makes them promising biomarkers for chronic disease detection. This review aims to provide a comprehensive overview of the recent advancements and findings in AGE research. The discussion is divided into two main sections: endogenous AGEs (formed within the body) and exogenous AGEs (derived from external sources). Various aspects of AGEs are subsequently summarized, including their production pathways, pathogenic mechanisms, and detection methods. Moreover, this review delves into the future research prospects concerning AGEs. Overall, this comprehensive review underscores the importance of AGEs in the detection of chronic diseases and provides a thorough understanding of their significance. It emphasizes the necessity for further research endeavors to deepen our comprehension of AGEs and their implications for human health.
A locating system includes a tag with body that has a first button and a second button, a driver configured to determine a type of button press of at least one of the first button and the second button, and a control unit in communication with the driver. The control unit is configured to communicate the type of button press determined by the driver. The tag also includes a transmitter in communication with the control unit. At least one receiver is configured to selectively communicate with the transmitter. A controller is in communication with the at least one receiver. The controller is configured to determine a location of the tag within a predefined area based on information from the at least one receiver, correlate the type of button press from the tag with a message, and generate a notification to communicate the message.
The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants. Fifteen participants will be conditioned with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (ATG), and given an infusion of donor "mobilized" blood mononuclear cells prior to transplantation.

This is a single-center, open-label study in adult renal transplant patients. Fifteen patients will receive TLI, ATG, and an infusion of CD34+ selected G-CSF mobilized blood cells combined with a fixed number (1x10\^6) of CD3+ T cells from the same mobilized blood cell source. Patients will receive a one-month course of mycophenolate mofetil and a six to 12 month tapering course of cyclosporine that will be discontinued at six months. At serial timepoints (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, (3) mixed lymphocyte response (MLR) assays of peripheral blood mononuclear cells against donor and third party cells will be performed, and (4) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue cyclosporine at six months if (1) chimerism is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) there is stable graft function without clinical rejection episodes, and (3) there is lack of histologic rejection on protocol biopsies. In the proposed study, patients will be given a target dose of 8-10x10\^6 CD34+ cells/kg and 1x10\^6 CD3+ cells/kg because sustained chimerism may be necessary for sustained tolerance to the graft.
This research study is a randomized, controlled trial that will evaluate whether diet and nutrition education on, and short-term partial feeding of, specific plant foods high in the antioxidant glutathione will impact total glutathione status, gamma-glutamyltransferase (GGT) activity, glucose control or insulin sensitivity in people with type 2 diabetes. Dietary education will include information on plant sources of glutathione, as well as, cooking methods to reduce glycation and lipid peroxidation during cooking, which may indirectly alter glutathione status by reduce demand for elimination of these compounds. Participants will be randomized to one of two groups: the educational intervention plus partial feeding of two small meals per day vs. a wait list control group that will receive standard advice on nutrition for diabetes. After 12 weeks, the intervention group will no longer receive foods, but will be followed for 12 additional weeks to determine if lasting effects are achieved. After 12 weeks, the control group will receive access to the educational materials, but will not receive study foods, to see if the educational intervention alone impacts food/nutrition choices. Both groups will have lab measures (as described above) again after this additional 12 weeks, for a total duration of 24 weeks in the trial.
An example of a system for managing pain may include a pain monitoring circuit, a pain relief device, and a control circuit. The pain monitoring circuit may include a parameter analyzer and a pain score generator. The parameter analyzer may be configured to receive and analyze at least two parameters selected from a physiological parameter indicative of a physiological function or state of a patient, a functional parameter indicative of a physical activity or state of the patient, or a patient parameter including subjective information provided by the patient. The pain score generator may be configured to compute a composite pain score using an outcome of the analysis. The composite pain score may indicate a degree of the pain. The pain relief device may be configured to deliver a pain-relief therapy. The control circuit may be configured to control the delivery of the pain-relief therapy using the composite pain score.