anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The precise mechanism of ferroptosis as a regulatory cell death in intestinal ischemia injury induced by vascular intestinal obstruction (Vio) remains to be elucidated. Here, we evaluated iron levels, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) changes after intestinal ischemia injury to validate ferroptosis. As an enzyme for Fe3+ reduction to Fe2+, Ferric Chelate Reductase 1 (FRRS1) is involved in the electron transport chain and the tricarboxylic acid (TCA) cycle in mitochondria. However, whether it is involved in ferroptosis and its role in intestinal ischemia injury need to be clarified. In the present study, FRRS1 was overexpressed in vivo and in vitro. The results showed that overexpression of FRRS1 prevented ischemia-induced iron levels, reactive oxygen species (ROS) production, lipid peroxidation, inflammatory responses, and cell death. Meanwhile, FRRS1 overexpression promoted GPX4 expression and suppressed ACSL4 levels. Further studies revealed that FRRS1 overexpression inhibited the activity of large tumor suppressor 1 (LATS1) / Yes-associated protein (YAP) / transcriptional co-activator with PDZ-binding motif (TAZ), a key component of Hippo signaling. In conclusion, this study demonstrates that FRRS1 is intimately involved in the inhibition of ferroptosis and thus protection of the intestine from intestinal ischemia injury, its downstream mechanism was related to Hippo signaling. These data provide new sight for the prevention and treatment of intestinal ischemia injury.
BACKGROUND: About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura.
METHODS: Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study - a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms.
RESULTS: Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache.
CONCLUSIONS: This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians' acumen in diagnosing migraine with aura in clinical settings.
PURPOSE:To provide a restorative dental material having improved adhesivity to tooth, preservability and handleability, by using a two-pack type adhesive containing a specific combination of a (meth)acrylic acid ester and a specific three-component hardener composed of a peroxide, an amine and a sulfinic acid salt. CONSTITUTION:The objective restorative dental material is composed of an adhesive for bonding tooth with a filler by applying to the surface of a dental cavity and a filler for filling the dental cavity. In the above material, the adhesive is a two-pack type adhesive consisting of (a) a (meth)acrylic acid ester and a hardener composed of (b) a peroxide, (c) a secondary or tertiary amine or its salt bonded to aryl group and (d) an alkali metal or alkaline earth metal sulfinate. The components (a) and (b) are packed in one package (A) and the components (c) and (d) are dissolved in a lower alcohol and packed in the other package (B). Both packages are opened and mixed together in use. A restorative dental material having excellent adhesivity to tooth surface, storage stability and handleability can be produced by the use of the adhesive.
Neuroimmunology is a rapidly expanding field since major advances have been made in basic immunology and numerous new clinical entities have been identified in the last 10 years. Even if these discoveries have led to major advances in patient's management and treatment, a lot of work needs to be done to improve the diagnosis and prognostic biomarkers. It is widely known that the immune system is implicated in a variety of neurological disorders such as infections, encephalitis or multiple sclerosis. Numerous neurological disorders affecting the central and peripheral nervous system can be attributed to the immune system and need to be recognized as some of them can be cured by appropriate immunotherapy. These neurological disorders include autoimmune encephalitis and paraneoplastic neurological syndromes but also myasthenia, chronic demyelinating inflammatory polyneuropathy and other neuromuscular pathologies.

These neurological disorders are characterized by the presence of autoantibodies in the patient's sera or cerebral spinal fluid (CSF). These autoantibodies are generally highly specific and necessary to make the diagnosis. However, in some cases, despite strong clinical arguments for a neuroimmunological disorder, we do not identify autoantibodies, leading to inappropriate treatment and a blind follow-up considering the risk of recurrence or of associated tumor. Furthermore, even if the specific role of some autoantibodies or of immune T cells in some of these pathologies are suspected or already documented, for most of them the exact mechanism is still unknown. We need to explore the sera and CSF of these patients to identify new diagnosis and prognosis biomarker. Moreover, the availability of immune cells isolated from these patients will help us to decipher the pathophysiological mechanisms to create new therapeutic strategies. For this, animal models are already available in Centre Physiopathology Toulouse and in the French reference center in Lyon. As genetic susceptibilities may underlie, at least in part, the variability of the clinical manifestations and of the response to treatment, DNA from patients will be collected and immune genes sequencing will be compared to other control groups, included international database.
Self-supervised learning (SSL) has emerged as a powerful technique for improving the efficiency and effectiveness of deep learning models. Contrastive methods are a prominent family of SSL that extract similar representations of two augmented views of an image while pushing away others in the representation space as negatives. However, the state-of-the-art contrastive methods require large batch sizes and augmentations designed for natural images that are impractical for 3D medical images. To address these limitations, we propose a new longitudinal SSL method, 3DTINC, based on non-contrastive learning. It is designed to learn perturbation-invariant features for 3D optical coherence tomography (OCT) volumes, using augmentations specifically designed for OCT. We introduce a new non-contrastive similarity loss term that learns temporal information implicitly from intra-patient scans acquired at different times. Our experiments show that this temporal information is crucial for predicting progression of retinal diseases, such as age-related macular degeneration (AMD). After pretraining with 3DTINC, we evaluated the learned representations and the prognostic models on two large-scale longitudinal datasets of retinal OCTs where we predict the conversion to wet-AMD within a six-month interval. Our results demonstrate that each component of our contributions is crucial for learning meaningful representations useful in predicting disease progression from longitudinal volumetric scans.
YSPSL-0003 is an extension into 36 patients of the previous 12 patient pilot study YSPSL-0002 under an almost identical study protocol with extended inclusion criteria. Like YSPSL-0002, YSPSL-0003 is a single-center (UCLA), randomized, placebo-controlled, double-blind study. Patients are randomly assigned to either active study drug (Active group) or placebo (Control group) prior to transplantation. The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg \[approximately 0.27 mg/kg\] as an ex vivo flush. The doses are administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Placebo of a volume equivalent to active study drug is prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of \>10 units, receive an additional 1 mg/kg IV infusion of study agent (or placebo equivalent) at the end of the transplant surgery. The Investigator/Sponsor is blinded to the treatment assignment for each patient. Randomization assignment is maintained by UCLA's clinical pharmacist.
The primary and secondary endpoints of this study are to determine the kinetics of Circulating tumor DNA (ctDNA) as defined by a set of patient-specific tumor mutations. The analysis will be undertaken using the Signatera Assay from Natera. Circulating tumor DNA in plasma samples obtained over the course of pembrolizumab treatment will be assessed by high-intensity, next-generation genetic sequencing to identify genomic alterations in genes. The assay will target 16 defined patient specific mutations. Data acquired will be analyzed to characterize the association between these genetic elements, clinical response, and durability of responses. There will be prospective and retrospective groups for the study. Samples will be collected from patients in the prospective cohort who have been treated with pembrolizumab monotherapy at Columbia University Irving Medical Center under standard of care treatment. Subjects in the retrospective cohort will provide genetic data.
Mixed chimerism induces donor-specific transplantation tolerance to organ allografts. Strategies to establish mixed chimerism using partial conditioning having significantly reduced the morbidity associated with conditioning. The donor hematopoietic cell lineage(s) responsible for the induction and subsequent maintenance of tolerance in partially conditioned recipients are not defined at present. As one approaches the threshold for nonmyeloablative conditioning, donor factors that influence the induction of tolerance have become apparent. In this invention, recipient B10 (H2 b ) mice were pretreated in vivo with anti-αβ-TCR and anti-CD8 mAbs 3 days before TBI (day 0) and transplanted with 15×10 6  allogeneic (B10.BR;H2 k ) marrow cells. Engraftment occurred in 20%, 75% and 94% of animals conditioned with 100, 200 or 300 cGy TBI once month post BMT, respectively. In those animals that engrafted some exhibited multilineage production, including donor T cells, while others had only donor B cell, NK cell, macrophage, granulocyte and dendritic cell production. Animals without donor T cells lost their chimerism gradually within 6 months and rejected both donor and third-party skin grafts, even when they had significant (up to 70%) levels of donor chimerism. In animals with donor T cell production, chimerism remained stable for >_6 months and donor skin grafts were accepted. In the animals without donor T cell production, none of the expected stages of T cell development were present in the thymus, while in those with donor T cell production they were. Moreover, clonal deletion of Vβ 5.1/2 +  and Vβ 11 +  CD8 and CD4 T cells occurred only in chimeras with donor T cell production. These results show for the first time that donor T cell production plays a critical role in the maintenance of durable chimerism and induction of transplantation tolerance, and is directly correlated with deletion of potentially autoreactive cells.
Four afatinib derivatives were designed and modeled. These derivatives were compared to the known tyrosine-kinase inhibitors in treating Chronic Myeloid Leukemia, i.e., imatinib and ponatinib. The molecules were evaluated through computational methods, including docking studies, the non-covalent interaction index, Electron Localization and Fukui Functions, in silico ADMET analysis, QTAIM, and Heat Map analysis. The AFA(IV) candidate significantly increases the score value compared to afatinib. Furthermore, AFA(IV) was shown to be relatively similar to the ponatinib profile when evaluating a range of molecular descriptors. The addition of a methylpiperazine ring seems to be well distributed in the structure of afatinib when targeting the BCR-ABL enzyme, providing an important hydrogen bond interaction with the Asp381 residue of the DFG-switch of BCR-ABL active site residue and the AFA(IV) new chemical entities. Finally, in silico toxicity predictions show a favorable index, with some molecules presenting the loss of the irritant properties associated with afatinib in theoretical predictions.
Participants will receive AMG 650 in 1 of 3 alternative schedules. The maximum tolerated dose (MTD) of each schedule will be estimated using isotonic regression (Ji et al, 2010). The Recommended Phase 2 Dose (RP2D) may be identified based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching an MTD.
The laser used in this group for surgical procedure ureteroscopic lithotripsy will be the Olympus SOLTIVETM Premium SuperPulsed laser system with a 365micron laser fibre. The laser pulse setting will be 1J x 10Hz, short pulse duration (adjusted up to 600microseconds).
Provided are a bispecific antibody and a use thereof. The bispecific antibody includes an IL-21 molecule and a CD16a antibody. The CD16a antibody includes a CD16a single-chain antibody and FC. The N-terminus of the FC is linked to the C-terminus of the single-chain antibody. The CD16a single-chain antibody includes a heavy chain variable region and a light chain variable region. The C-terminus of the FC is linked to the N-terminus of the IL21 molecule. The prepared bispecific antibody can simultaneously target CD16 and IL-21 receptors and can also activate NK cells. It has a long half-life period, exhibiting stronger anti-tumor and antiviral capabilities than single-target antibodies. It has the application potential of promoting NK cell proliferation and can be used for in-vitro culture and expansion of NK cells, and the expanded NK cells have good cytotoxicity.
KRYSTEXXA (pegloticase) is a uric acid specific enzyme which is a PEGylated product that consists of recombinant modified mammalian urate oxidase (uricase) produced by a genetically modified strain of Escherichia coli. Uricase is covalently conjugated to monomethoxypoly(ethylene glycol) [mPEG] (10 kDa molecular weight). The cDNA coding for uricase is based on mammalian sequences. Each uricase subunit has a molecular weight of approximately 34 kDa per subunit. The average molecular weight of pegloticase (tetrameric enzyme conjugated to mPEG) is approximately 540 kDa.

KRYSTEXXA is intended for intravenous infusion.

KRYSTEXXA is a sterile, clear, colorless solution containing 8 mg/mL pegloticase in phosphate-buffered saline.

KRYSTEXXA (pegloticase) concentrations are expressed as concentrations of uricase protein. Each mL of KRYSTEXXA contains 8 mg of uricase protein (conjugated to 24 mg of 10 kDa mPEG), 2.18 mg Disodium Hydrogen Phosphate Dihydrate (Na2HPO4•2H2O), 8.77 mg Sodium Chloride (NaCl), 0.43 mg Sodium Dihydrogen Phosphate Dihydrate (NaH2PO4•2H2O), and Water for Injection to deliver 8 mg of pegloticase (as uricase protein).
Participants received mirabegron 50 mg and solifenacin 5 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of solifenacin 10 mg, if the treatment was not effective.
BACKGROUND: Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both actions. The latter has been well documented in vitro but not in vivo. The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.
AIM: To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin (CTX) in mice.
METHODS: CTX was given orally to C57BL/6 mice to induce diarrhea. Calcium and calcimimetic R568 were used to activate CaSR. To maximize their local intestinal actions, calcium was administered luminally via oral rehydration solution (ORS), whereas R568 was applied serosally using an intraperitoneal route. To verify that their actions resulted from the intestine, effects were also examined on Cre-lox intestine-specific CaSR knockouts. Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl- or clinically by assessing stool consistency and weight loss.
RESULTS: CTX induced secretory diarrhea, as evidenced by increases in fecal Cl-, stool consistency, and weight loss following CTX exposure, but did not alter CaSR, neither in content nor in function. Accordingly, calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines. Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts (villinCre/Casrflox/flox) and neuronal CaSR knockouts (nestinCre/Casrflox/flox).
CONCLUSION: Treatment of acute secretory diarrheas remains a global challenge. Despite advances in diarrhea research, few have been made in the realm of diarrhea therapeutics. ORS therapy has remained the standard of care, although it does not halt the losses of intestinal fluid and ions caused by pathogens. There is no cost-effective therapeutic for diarrhea. This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
Participants with HIV-1 infection who started a new antiretroviral drug as part of a combination antiretroviral therapy (cART) regimen on or after 1 January 2006 and before 21 December 2007. Participants had no previous exposure to the new drug and had at least 1 month prospective follow-up in the Historical Cohort.
Process for the obtaining of substitute 4-fluorophenil-piperidins in position 3 and of their physiologically compatible acid addition salts, of formula (I), where r is hydrogen or alcohil c <003>; and the atom of fluor can occupy any available position. It consists of the reaction of 3,4-methylendioxypenol with a derivative of formula (II) pyridine, where r is the same as in formula (I), and x is halogen, group ester or hydroxyl. When x is chlorine or ester group, the reaction is carried out in methanol, in the presence of sodium at a temperature between 0ºc and lade reflux. When x is hydroxyl the reaction is carried out through a coupling reagent at a temperature between 160ºc and 180ºc. These compounds have pharmacological applications as antidepressive and anti-perkinsonian agents. (Machine-translation by Google Translate, not legally binding)
A Vitamin B12 active substance is separated from contaminants associated therewith by treating a solution thereof with an anion exchange resin in the presence of cyanide ion.  The adsorbate is then eluted, e.g. with sulphuric, hydrochloric, phosphoric and acetic acids or salts such as monobasic sodium or potassium phosphate, sodium and potassium chloride, and sodium and potassium sulphate and bases such as sodium hydroxide, to recover a purified Vitamin B12 active substance.  The Vitamin B12 active substances may be derived from liver, fermentation products, mother liquors, wash waters or other by-products of Vitamin B12 recovery procedures.  Suitable anion-exchange resins are highly porous and strongly basic and derive their exchange capacity essentially from quaternary ammonium groups. The Vitamin B12 active substance and associated contaminants may be subjected to a preliminary treatment with an anion exchange resin in the absence of cyanide ions in order that a portion of the contaminants may be pre-removed.
This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN® Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2 months after placement. The WATCHMAN® Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus. Extensive workup revealed reduced left ventricular cardiac function and decreased renal function, both of which were felt to be potentially reversible with device removal. The patient then underwent retrieval of the device and all associated thrombus via an open retroperitoneal approach. This case demonstrates a potential consequence of implanting devices such as an atrial appendage occlusion device and describes a technique for removal.
PURPOSE: The purpose of this study is to describe the postoperative psychological state of patients following osteochondral allograft (OCA) transplantation in the knee and to determine whether patient-perceived kinesiophobia is associated with the rate of return to sport (RTS).
METHODS: A retrospective review of the electronic medical record at a single institution was conducted for all patients that underwent OCA transplantation from January 2010 to 2020. Patient-reported outcomes including the visual analog scale (VAS), knee injury and osteoarthritis outcome score (KOOS) and the Tampa scale of kinesiophobia-11 (TSK-11) were collected. Patients were surveyed regarding their postoperative RTS status.
RESULTS: A total of 38 patients (52.6% female) were included in our analysis. Overall, 24 patients (63.2%) returned to sport with 12 (50%) of these patients returning at a lower level of play. When comparing patients that return to sport to those that did not, patients that return had significantly superior KOOS pain (p = 0.019) and KOOS QOL (p = 0.011). Measures of kinesiophobia (TSK-11) were significantly higher among patients that did not return to sport (p = 0.014), while satisfaction (n.s.) and pain intensity (n.s.) were comparable between groups. Logistic regression models controlling for demographic factors, VAS pain scores and lesion size showed that for every one-point increase in TSK-11 kinesiophobia score, patients were 1.33 times more likely to return to sport at a lower level (p = 0.009). For every one-point increase in TSK-11 scores KOOS QOL decreased by 2.4 points (p < 0.001).
CONCLUSION: Fear of reinjury decreases the likelihood that patients will return to their preoperative level of sport after OCA transplantation. Patients that do not return to sport report significantly greater fear of reinjury and inferior clinical outcomes, despite similar levels of satisfaction and pain compared to those that return.
LEVEL OF EVIDENCE: Level III.