anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Just like the androgen receptor (AR), the estrogen receptor α (ERα) is expressed in the prostate and is thought to influence prostate cancer (PCa) biology. Yet the incomplete understanding of ERα functions in PCa hinders our ability to fully comprehend its clinical relevance and restricts the repurposing of estrogen-targeted therapies for the treatment of this disease. Using 2 human PCa tissue microarray cohorts, we first demonstrate that nuclear ERα expression was heterogeneous among patients, being detected in only half of the tumors. Positive nuclear ERα levels were correlated with disease recurrence, progression to metastatic PCa, and patient survival. Using in vitro and in vivo models of the normal prostate and PCa, bulk and single-cell RNA-Seq analyses revealed that estrogens partially mimicked the androgen transcriptional response and activated specific biological pathways linked to proliferation and metabolism. Bioenergetic flux assays and metabolomics confirmed the regulation of cancer metabolism by estrogens, supporting proliferation. Using cancer cell lines and patient-derived organoids, selective estrogen receptor modulators, a pure anti-estrogen, and genetic approaches impaired cancer cell proliferation and growth in an ERα-dependent manner. Overall, our study revealed that, when expressed, ERα functionally reprogrammed PCa metabolism, was associated with disease progression, and could be targeted for therapeutic purposes.
BACKGROUND: Observational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction.
METHODS: This study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results.
RESULTS: Based on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113∼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468∼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction.
CONCLUSIONS: This study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction.
The present invention relates to compounds and methods useful for the detection and treatment of disorders associated with frameshift mutations in coding microsatellite regions. The compounds and methods are applicable in cancers, especially of DNA mismatch repair deficient (MMR) sporadic tumors and HNPCC associated tumors. The compounds disclosed in the invention are useful for detection of disorders and in therapy such as e.g. immuno-therapy. The diagnostic methods relate to diagnosis and prognostic assessment of disorders associated with frameshift polypeptides originating from frameshift mutations in coding microsatellite regions of genes based on the detection of immunological entities directed against said frameshift polypeptides in body fluids. With respect to the treatment of cancer, especially of DNA mismatch repair deficient (MMR) sporadic tumors and HNPCC associated tumors, the invention pertains to methods which use immuno therapy with combinatorial mixtures of tumor specific frameshift peptides to elicit a cytotoxic T-cell response specifically directed against tumor cells for use in prevention as well as in curative treatment of cancers and precancers.
ALDURAZYME may cause infusion-associated reactions (IARs). Prior to ALDURAZYME administration, consider pre-medicating with antihistamines, with or without antipyretics, 60 minutes before the start of infusion to reduce the risk of IARs. However, IARs may still occur in patients after receiving pre-medication.

  * If a severe IAR occurs, discontinue ALDURAZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering ALDURAZYME following a severe IAR. Patients may be re-challenged using slower infusion rates. Once a patient tolerates the infusion, the infusion rate may be increased to reach the recommended infusion rate.
  * If a mild or moderate IAR occurs, consider temporarily holding the infusion or slowing the infusion rate [see Dosage and Administration (2.3), and Adverse Reactions (6.1, 6.2)].
The present invention relates to a composition for inducing a T cell mediated immune response for the treatment or prevention of prostate cancer, comprising a modified vaccinia virus ankara (MVA) vector expressing a 5T4 antigen polypeptide under the control of the poxvirus F11 promoter. Suitably, the poxvirus F11 promoter is an endogenous MVA F11 promoter. More suitably, the vector expresses a polypeptide having the amino acid sequence shown in SEQ ID NO. 1 or the vector expresses a polypeptide encoded by a polynucleotide having the nucleic acid sequence shown in SEQ ID NO. 2. The invention also relates to uses and methods.
This is an observational case-control study. One hundred school-age children who visited the Department of Ophthalmology at Guangzhou First People's Hospital in China from February 1, 2023 to March 31, 2023 were included in this study. Eighty children with COVID-19 infection were included in the case group. Controls without COVID-19 infection were matched to COVID-19 infection cases by a ratio of 1:4 using frequency matching on age and gender. The primary end point of this study is the retinal and choroidal microvascular changes in school-age children during the COVID-19 pandemic. Secondary endpoint is the
Voxelotor 1500 mg oral per day (GBT440) for 48 weeks, in case of discontinuation due to patient's wishes and/or adverse event above grade 2 : 1000mg during 14 days then complete discontinuation if no resolution. In case of sudden discontinuation a therapeutic phlebotomy will be authorized.
Engineered antibodies that are stable and can be conjugated to a ligand or drug at a ligand/drug to antibody ratio of above 3, making these conjugates suitable for treatment of a variety of indications, are provided. Methods of producing these engineered antibodies are also provided. In a first embodiment, the antibody comprises a first engineered reactive amino acid residue at position 274 according to the numbering of the EU index of Kabat and a second engineered reactive amino acid residue at position 339, 360, 384, 385, 422 and/ or 440. In a second embodiment, the antibody comprises a first engineered reactive amino acid residue at position 339 according to the numbering of the EU index of Kabat and a second engineered reactive amino acid residue at position 290, 360, 384, 385, 422 and/or 440. In a third embodiment, the antibody comprises a first engineered reactive amino acid residue at position 118 according to the numbering of the EU index of Kabat and a second engineered reactive amino acid residue at position 274, 339, 384, 385, 422 and/or 440. In a fourth embodiment, the antibody comprises a first engineered reactive amino acid residue at position 384 according to the numbering of the EU index of Kabat and a second engineered reactive amino acid residue at position 118, 274, 290 and/or 339. In a preferred embodiment, the engineered reactive amino acid residue is cysteine.
Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).
PROBLEM TO BE SOLVED: To prepare the subject suppressant, having suppressing actions on delayed type allergic reactions and useful for a therapeutic agent for anaphylaxia, etc., by including bucillamine (salt) as an active in gredient therein. SOLUTION: This suppressant for delayed type allergy is prepared by including bucillamine represented by the formula or its salt as an active ingredient therein. The method for administration may be either one of oral and parenteral ones and the daily dose thereof is preferably 10-1,000mg administered in one to several divided portions. The suppression of the delayed type allergic reaction induced by a chicken albumen lysozyme is recognized in the suppressant. The bucillamine (salt) is useful as a therapeutic agent for contact dermatitis caused by the delayed type allergic reaction. It has already been reported that the bucillamine is useful as an antirheumatic agent, a sputum dissolving agent, a hepatopathy suppressant, a therapeutic agent for cataract and diabetes, an antiosteoporotic agent and a therapeutic agent for renopathy and cystinuria.
BACKGROUND: Antimicrobial resistance (AMR) has become one of the major public health threats worldwide, emphasizing the necessity of preventing the development and transmission of drug resistant microorganisms. This is particularly important for people with vulnerable health conditions, such as people with intellectual disabilities (ID) and long-term care residents. This study aimed to assess the current status of AMR, antimicrobial stewardship (AMS) and infection prevention and control (IPC) in Dutch long-term care facilities for people with intellectual disabilities (ID-LTCFs).
METHODS: A web-based cross-sectional survey distributed between July and November 2023, targeting (both nonmedically and medically trained) healthcare professionals working in ID-LTCFs in The Netherlands, to study knowledge, attitudes and perceptions regarding AMR, AMS and IPC.
RESULTS: In total, 109 participants working in 37 long-term care organizations for people with intellectual disabilities throughout the Netherlands completed the questionnaire. The knowledge levels of AMR and IPC among nonmedically trained professionals (e.g., social care professionals) were lower than those among medically trained professionals (p = 0.026). In particular regarding the perceived protective value of glove use, insufficient knowledge levels were found. Furthermore, there was a lack of easy-read resources and useful information regarding IPC and AMR, for both healthcare professionals as well as people with disabilities. The majority of the participants (> 90%) reported that AMR and IPC need more attention within the disability care sector, but paradoxically, only 38.5% mentioned that they would like to receive additional information and training about IPC, and 72.5% would like to receive additional information and training about AMR.
CONCLUSION: Although the importance of AMR and IPC is acknowledged by professionals working in ID-LTCFs, there is room for improvement in regards to appropriate glove use and setting-specific IPC and hygiene policies. As nonmedically trained professionals comprise most of the workforce within ID-LTCFs, it is also important to evaluate their needs. This can have a substantial impact on developing and implementing AMR, AMS and/or IPC guidelines and policies in ID-LTCFs.
In the past century, there have been great achievements in identifying resistance (R) genes and quantitative trait loci (QTLs) as well as revealing the corresponding molecular mechanisms for resistance in rice to major diseases and insect pests. The introgression of R genes to develop resistant rice cultivars has become the most effective and eco-friendly method to control pathogens/insects at present. However, little attention has been paid to durable and broad-spectrum resistance, which determines the real applicability of R genes. Here, we summarize all the R genes and QTLs conferring durable and broad-spectrum resistance in rice to fungal blast, bacterial leaf blight (BLB), and the brown planthopper (BPH) in molecular breeding. We discuss the molecular mechanisms and feasible methods of improving durable and broad-spectrum resistance to blast, BLB, and BPH. We will particularly focus on pyramiding multiple R genes or QTLs as the most useful method to improve durability and broaden the disease/insect spectrum in practical breeding regardless of its uncertainty. We believe that this review provides useful information for scientists and breeders in rice breeding for multiple stress resistance in the future.
Reactive sulfur species including sulfides, polysulfides and cysteine hydropersulfide play extensive roles in health and disease, which involve modification of protein functions through the interaction with metals bound to the proteins, cleavage of cysteine disulfide (S-S) bonds and S-persulfidation of cysteine residues. Sulfides over a wide micromolar concentration range enhance the activity of Cav3.2 T-type Ca2+ channels by eliminating Zn2+ bound to the channels, thereby promoting somatic and visceral pain. Cav3.2 is under inhibition by Zn2+ in physiological conditions, so that sulfides function to reboot Cav3.2 from Zn2+ inhibition and increase the excitability of nociceptors. On the other hand, polysulfides generated from sulfides activate TRPA1 channels via cysteine S-persulfidation, thereby facilitating somatic, but not visceral, pain. Thus, Cav3.2 function enhancement by sulfides and TRPA1 activation by polysulfides, synergistically accelerate somatic pain signals. The increased activity of the sulfide/Cav3.2 system, in particular, appears to have a great impact on pathological pain, and may thus serve as a therapeutic target for treatment of neuropathic and inflammatory pain including visceral pain.
A phenolic cpd. (phenol, e.g. resorcinol or phenolic resin) is added during prepn. of oil filled microcapsules by coacervation of a hydrophilic colloid (gelatin). The phenolic cpd. is pref. added above 8 degrees C after dilution of the emulsion with water. The colloid is coacervated by pH adjustment with a salt, the product cooled and a hardner added (formaldehyde) with a viscosity regulator (carboxymethyl cellulose) The addition of phenolic cpd. gives increased wall thickness and walls which are less porus and more heat resistant. Suitable liquids for encapsulation are chemicals, medicines, perfumes, dyes and catalysts.
Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
Human gallstones are the most common disorder in the biliary system, affecting up to 20 % of the adult population. The formation of gallstones is primarily due to the supersaturating of cholesterol in bile. In order to comprehend gallstone disease in detail, it is necessary to have accurate information about phase identification and molecular structure. Different types of gallstone samples were collected from the Middle East area after surgical operations including; cholesterol, pigment, and mixed gallstones. To estimate the basic information about the stone formation and the pathophysiology of cholelithiasis as well as to classify the collected human gallstones, attenuated total reflection Fourier transform Infrared spectrometry (ATR-FTIR) was used to analyze the different gallstone structures in the wavenumber range from 400 to 4000 cm-1. Calcium bilirubinate was specified by the bands at 1662 cm-1, 1626 cm-1, and 1572 cm-1, while cholesterol rings were designated by the bands at 1464, 1438, 1055, and 1022 cm-1. It can be assumed that all samples consist of mixed gallstones based on the doublets at 1375 cm-1 and 1365 cm-1. The levels of calcium bilirubin and various minerals varied among the analyzed samples, indicating the heterogeneity in their composition and suggesting potential implications for gallstone formation. Based on the quantitative phase analysis using synchrotron radiation X-ray diffraction (SR-XRD), two phases of anhydrous cholesterol as a major content and one phase of monohydrate cholesterols as trace content represent the main components of most of the gallstones. Additional phases of calcium carbonate in the form of calcite, vaterite, aragonite, and bilirubinate were also quantified. According to the outcomes of the FTIR and the SR-XRD measurements, there exists a statistical correlation between the different types of chemical constituents of the gallstones.
The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 120 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks. In the FU1 phase, all participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants who receive post-double progression ocrelizumab (PDP OCR) treatment, other immunomodulatory or immunosuppressive treatment(s) for MS, commercial ocrelizumab, or no treatment. The FU1 phase will run in parallel with the double-blind treatment phase until the primary analysis is performed. If the primary analysis is positive, an optional OLE phase is planned for eligible participants who either have remained in the double-blind treatment phase or are on PDP OCR treatment at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment. The follow-up 2 (FU2) phase will begin after the primary analysis is performed. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 and not on PDP OCR treatment at the time of primary analysis; participants who are ongoing in the double-blind treatment phase or receiving PDP OCR at the time of the primary analysis and do not enter the OLE phase; participants who complete or withdraw from the OLE phase. At the end of the FU2, all participants will move into B-cell monitoring (BCM) phase until the end of the study. This study will end when all participants who are not being treated with an alternative B-cell depleting therapy have repleted his or her B-cells.
An animal collagen or gelatin based crumble, and processes for the preparation of the particulate crumble, are useful in the preparation of collagen or gelatin based compositions. The crumble is prepared by extracting animal collagen from an animal tissue source and combining the collagen with sufficient water to form a composition comprising about 15-45 wt % animal collagen and about 0.01-5 wt % of a stabilizer or preservative. Such a combination of materials can be solidified and then processed into a large particulate format. The large particulate comprises a, regular or amorphous shaped, roughly crumbled or roughly divided, crumble product. The typical particle size of a majority of the crumble is about 0.2-5 cm. The crumble is easily manufactured, packaged, stored, handled and distributed. The crumble can be easily used as is. The material melts easily into a use locus. The crumble is also particularly adapted to a use in combination with an aqueous diluent to form an aqueous animal collagen or gelatin solution that have a variety of uses. The aqueous solution of the crumble can be made with minimal heating to dissolve the crumble in the aqueous liquid.
Patients will have the usual follow-up for this indication, i.e. a follow-up consultation 3 months after the 1st consultation with the rheumatologist to assess their clinical course.
FIELD: medicine, stomatology. SUBSTANCE: the composition in question contains two aqueous solutions. The first includes alkali, the second contains sodium hypochlorite. Moreover, the first solution additionally contains ethylenediaminetetraacetate disodium salt, aerosyl, glycerol and surface-active substance. The second one additionally contains carbopol and alkali. Components are taken at a certain quantitative ratio. Composition maintains activity for 20 min that enables to treat several cavities in one patient. Moreover, it has got an impact upon caries-affected dentin causing no damage of healthy tissue or slightly demineralized dentin. EFFECT: higher quality. 3 cl, 26 ex, 3 tbl
This is a multicenter, prospective, single arm, open label, interventional study. The goal of this study, is to evaluate feasibility and efficacy of pembrolizumab for the treatment of recurrent or progressive meningioma (WHO grades II-III) or hemangiopericytoma (HPC). All patients will receive IV pembrolizumab, at a dose of 200mg, every 3 weeks. Patients will be treated until disease progression or intolerable toxicity. Treatment can be stopped after one year of treatment in case of stable disease or completer response, with re-initiation of treatment upon progression. Expression of PD1 and PD-L1 will be tested, on tumor cells, using IHC staining on biopsy material obtained from previous surgeries.

All patients will have a baseline neurologic and clinical exam, MRI scan, a brain dedicated CT-PET scan, a baseline cognitive exam and QOL assessment with a dedicated questionnaire. Patients will have a clinical and neurological exam every treatment cycle. MRI scan will be repeated after 2 months from the beginning of the trial drug administration and then every 2-3 months. There are no designated and specific criteria for response assessment in the treatment of meningioma. Therefore, response evaluation will be made using the RECIST 1.1 criteria, as used for solid tumors. The trial will allow the continuation of pembrolizumab in case of stable or improved clinical response, when pseudo-progression is suspected in the MRI. In addition, response assessment will also be made according to the RANO criteria, as used for high grade glioma. This will be compared to the RECIST evaluation, but will not be used for treatment decision making.