anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVES: I. Determine the maximum tolerated dose of oral BIBX 1382 in patients with solid tumors. II. Determine qualitative and quantitative toxicities of oral BIBX 1382 in these patients. III. Determine predictability, duration, intensity, onset, reversibility, and dose relationship of the toxicities of oral BIBX 1382 in these patients. IV. Determine safe and optimal doses of oral BIBX 1382 for a Phase II study. V. Assess the pharmacokinetics of oral BIBX 1382 in these patients. VI. Document any antitumor activity in these patients treated with oral BIBX 1382.

OUTLINE: This is a dose escalation study. Patients receive BIBX 1382 IV over 1 hour followed 7 days later by oral BIBX 1382. Beginning 3 days later, patients receive oral BIBX 1382 daily for 28 days. Courses of daily oral BIBX 1382 repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral BIBX 1382. The maximum tolerated dose (MTD) is defined as the dose at which dose limiting toxicity occurs in at least 2 of 6 patients. Patients are followed for up to 4 weeks.

PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study over 18 months.
BACKGROUND: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis.
METHODS: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice.
FINDINGS: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment.
INTERPRETATION: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC.
FUNDING: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the "European Union Next Generation EU/PRTR," the Regional Government of Castile and León (CSI144P20), European Union.
Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established. Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS. In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS. Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.
For the Phase 3 adjuvant breast carcinoma study, the following table shows the incidence of important severe adverse events for the 3121 patients (total population) who were evaluable for safety as well as for a group of 325 patients (early population) who, per the study protocol, were monitored more intensively than other patients.

The incidence of an adverse event for the total population likely represents an underestimation of the actual incidence given that safety data were collected differently based on enrollment cohort. However, since safety data were collected consistently across regimens, the safety of the sequential addition of paclitaxel following AC therapy may be compared with AC therapy alone. Compared to patients who received AC alone, patients who received AC followed by paclitaxel experienced more Grade III/IV neurosensory toxicity, more Grade III/IV myalgia/arthralgia, more Grade III/IV neurologic pain (5% vs 1%), more Grade III/IV flu-like symptoms (5% vs 3%), and more Grade III/IV hyperglycemia (3% vs 1%). During the additional 4 courses of treatment with paclitaxel, 2 deaths (0.1%) were attributed to treatment. During paclitaxel treatment, Grade IV neutropenia was reported for 15% of patients, Grade II/III neurosensory toxicity for 15%, Grade II/III myalgias for 23%, and alopecia for 46%.

The incidences of severe hematologic toxicities, infections, mucositis, and cardiovascular events increased with higher doses of doxorubicin.
Sporadic hemophilia A (HA) enables the persistence of HA in the population. F8 gene inversion originates mainly in male germ cells during meiosis. To date, no studies have shown the origin and timing of HA sporadic noninversion variants (NIVs); herein, we assume that HA-sporadic NIVs are generated as a de novo variant. Of the 125 registered families with HA, 22 were eligible for inclusion. We conducted a linkage analysis using F8 gene markers and amplification refractory mutation system-quantitative polymerase chain reaction to confirm the origin of the sporadic NIVs (~0% mutant cells) or the presence of a mosaic variant, which requires further confirmation of the origin in the parent. Nine mothers, four maternal grandmothers, and six maternal grandfathers were confirmed to be the origin of sporadic NIVs, which most likely occurred in the zygote within the first few cell divisions and in single sperm cells, respectively. Three mothers had mosaic variants, which most likely occurred early in postzygotic embryogenesis. All maternal grandparents were free from sporadic NIV. In conclusion, F8 NIVs in sporadic HA were found to be caused primarily by de novo variants. Our studies are essential for understanding the genetic pathogenesis of HA and improving current genetic counseling.
PROBLEM TO BE SOLVED: To safely perform the antiseptic treatment of foods and cosmetics in high practicality by using a specific component originated from natural material or its extract as an active component. SOLUTION: A food or cosmetic is incorporated with squeezed juice of persimmon fruit or astringent juice of persimmon or their extract as an active component. The active component may be a tannin and/or polyphenol produced from the squeezed juice of persimmon fruit or the astringent juice of persimmon. The persimmon fruit is preferably unripe fruit or astringent persimmon. The concentration of the active component in the food or cosmetic is preferably 0.001-20wt.%. The active component has excellent safety compared with synthetic products, exhibits wide antibacterial spectrum and exerts strong effect.
In order to avoid bias in the intervention applied in our study, the experimental group was started after the control group was finished. The participants were informed about the purpose of working face-to-face in a quiet room so that EFT, which will be applied online for 7 (seven) days by the researcher, can be applied effectively and accurately. STAI-D, STAI-S, SUD, P19-S scales were completed after their consent was obtained. The researcher, who has the EFT certificate, first showed the application steps on himself with the guidance of the EFT guideline, and ensured that the application steps were applied again simultaneously on both himself and the participant. After this application, it was provided to make EFT online for 7 (seven) days. STAI-D, STAI-S, SUD, P19-S scales were filled in after the last EFT application.
BACKGROUND: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour.
METHODS: We searched MEDLINE, Embase, and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews; and Epistemonikos. We included systematic reviews that evaluate any type of intervention aimed at impacting opioid prescriber behaviour for adult CNCP in an outpatient setting.
RESULTS: We identified three full texts for our review that contained 68 unique primary studies. The main interventions we evaluated were structured prescriber education (one review) and prescription drug monitoring programmes (PDMPs) (two reviews). Due to the paucity of data available, we could not determine with certainty that education interventions improved outcomes in deprescribing. There is some evidence that PDMPs decrease the number of adverse opioid-related events, increase communication among healthcare workers and patients, modify healthcare practitioners' approach towards their opioid prescribed patients, and offer more chances for education and counselling.
CONCLUSIONS: Our overview explores the possibility of PDMPs as an opioid deprescribing intervention and highlights the need for more high-quality primary research on this topic.
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Methods and compositions are provided for the analysis of skin surfaces to determine the presence of neoplastic tissue. In the methods of the invention, a composition comprising a florescent probe that binds to a specific neoplasia associated marker is applied topically to the area of interest. After topical administration, the probe preferentially binds to markers associated in neoplastic lesions in situ, which binding is detected with a compact illumination unit that provides illumination at a wavelength appropriate for image acquisition. The illumination unit comprises a light source and fiber optic bundle to direct the light towards the area of examination. A detection unit is used to capture and record an image of the area of investigation. The detection unit may be a digital camera, film camera, etc. A mapping module may also be provided to catalogue the site of examination.
PURPOSE: Lateral unicompartmental knee arthroplasty (UKA) is an accepted treatment option in cases of end-stage lateral osteoarthritis. While lateral UKA has many proposed advantages compared to total knee arthroplasty, its technical challenges and relatively small number of cases make this an uncommon procedure. The aim of this study was to report the survivorship and functional outcomes beyond 20 years of follow-up of isolated UKA.
METHODS: Between January 1988 and October 2003, 54 lateral UKAs were performed in a single center. The fitted prosthesis was a fixed plate and cemented polyethylene (PE). All patients had isolated lateral tibiofemoral osteoarthritis, including five open meniscectomies, three arthroscopies, and three open reductions of lateral tibial plateau fractures. Patients with a minimum of 20 years of follow-up were included in the final analysis.
RESULTS: Of the 54 UKA, 22 died before reaching the minimum follow-up period and four were lost to follow-up. Twenty-eight were included in the final analysis. Among them, 21 patients remained alive and an additional seven were deceased after 20 years. The mean age at the last follow-up was 84.8 ± 11.9 years with a mean follow-up duration of 22.5 ± 2.1 years. Of the 28 knees, eight underwent revision surgery (5 for the progression of osteoarthritis; 2 for aseptic loosening; 1 for PE wear). Kaplan-Meier survival analysis revealed a survival rate at 20 and 25 years of 72.3% (CI 59.1; 88.6). The average time to revision was 14.9 ± 4.9 years. At the last follow-up, the mean function Knee Society Score (KSS) was 41.5 ± 32.9 and the mean objective KSS score was 79.4 ± 9.7. In the unrevised population, 94.7% of patients (n = 18) reported being satisfied or very satisfied with the surgery.
CONCLUSION: Lateral UKA remains a viable treatment option for patients with isolated lateral tibiofemoral osteoarthritis, providing satisfactory 20-year implant survivorship and high patient satisfaction.
A growing body of research has indicated that placebos contribute substantially to clinical outcomes. Yet, the implementation of deceptive placebos in clinical practice is incompatible with key principles of openness and patient autonomy. However, recent research suggests that placebos remain effective even if they openly described as placebos (so-called Open-Label Placebos (OLP)), hence questioning the necessity of deception in clinical trials.

However, comparisons between OLP and deceptive placebos (DP) with regard to their particular mechanisms are lacking. Therefore, the current study aims to identify components of OLP and DP. For this purpose, experimentally induced sadness is examined using a standardized paradigm which has previously been developed by our working group. In particular, healthy volunteers are informed that a new application method for a well-known antidepressant would be tested. Sadness is assessed before and after receiving a nasal spray. Two experimental groups (DP groups) are informed that they would receive an antidepressant nasal spray, another two experimental groups (OLP groups) are informed that they would receive a placebo. In fact, all nasal sprays are active placebos inducing prickling nasal sensations (sesame oil with 0.014% capsaicin). In addition to the factor "Transparency" (DP vs. OLP), the instruction is experimentally varied, with which the substance is administered (scientifically-objective vs. personally-affective), resulting in a 2x2 design. Further, there is an additional fifth group receiving no intervention. The primary outcome is self-rated sadness after taking the nasal spray.
The invention belongs to the field of immunology, and relates to an anti-IL-17A single domain antibody and application thereof. The single domain antibody is composed of a heavy chain, wherein the heavy chain comprises a heavy chain CDR1 shown by any one of SEQ ID NO. 19-25, a heavy chain CDR2 shown by any one of SEQ ID NO. 26-32 and a heavy chain CDR3 shown by any one of SEQ ID NO. 33-41. Compared with the prior art, the invention has the beneficial effects that: the invention screens out the single-domain antibody specific to the IL-17A by using a biological gene engineering technology, has better antibody affinity, can block specific cells from releasing cytokines, has good binding activity through prokaryotic expression and eukaryotic expression, and has certain druggability.
1. Written informed consent must be obtained before any study specific procedures are undertaken.
2. All patients were received epidural anesthesia with 2% Lidocaine and patient-controlled epidural analgesia (PCEA) for post- operative pain control. PCEA randomly allocated into three groups. Group A patients received 0.08% ropivacaine plus 4 mcg /mL fentanyl, Group B patients received 0.08% ropivacaine plus 2mcg /mL fentanyl, and Group C patients received 0.16 % ropivacaine plus 2 mcg /mL fentanyl. Dermographic data, dosage of PCEA during first 48 hours post-operation，NRS scores, patient satisfaction and the intensity of motor block will be recorded and analyzed.
Intensification of care. Besides routine medical care that include free demand consultation and free medicines, subjects were invited to have 6 structured medical encounters based on a social-psychological approach. Doctors must follow a protocol to conduct the encounter that have around 30 minutes each.
BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.
METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.
RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.
CONCLUSION: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.
The invention discloses a human metapneumovirus virus-like particle, a preparation method, application and a vaccine. The human metapneumovirus virus-like particle is formed by assembling M1 protein of influenza virus H2N2 and F protein of human metapneumovirus, wherein the nucleic acid sequence for encoding the M1 protein is shown as SEQ ID NO. 1, and the nucleic acid sequence for encoding the F protein is shown as SEQ ID NO. 2. The preparation method comprises (1) constructing recombinant plasmid: cloning M1 gene of influenza virus H2N2 and F gene sequence of human metapneumovirus into pFastBacDual vector to obtain recombinant plasmid pFastBacDual-M1-F; (2) transfection: transfecting the recombinant plasmid pFastbacdusal-M1-F into sf9 insect cells to obtain recombinant sf9 cells; (3) separation and purification: culturing recombinant sf9 cells, and centrifugally purifying to obtain the VLP of the human metapneumovirus virus-like particles. The invention prepares virus-like particles based on HMPV F protein and influenza virus M1 protein by adopting a baculovirus insect cell expression system, has immunogenicity and excellent immunoprotection, and lays a foundation for the research and development of HMPV vaccines, in particular VLP vaccines.
Implantation of ICL (V4c with central hole) for treatment of myopia in adults using peribulbar anesthesia. Thirty minutes before surgery, cycloplegic and phenylephrine eye drops were applied. Five minutes before surgery, povidone-iodine 5% was applied. The anterior chamber was filled with sodium hyaluronate 1%, which was completely removed at the end of the surgery. The lens was inserted using the ICL injector. Tobramycin and dexamethasone 0.1% eye drops were used four times a day for 10 days, after which diclofenac sodium eye drops were started four times a day for 2 weeks.
Patients randomized to control study arm, receiving continued immunotherapy only. Patients in both study arms will continue with PD-1 inhibitor 12 months after randomization, and will then be treated according to their medical oncologist.
Refractory wounds present complex and serious clinical dilemmas in plastic and reconstructive surgeries. Currently, there are no standard guidelines for the treatment of refractory wounds. To observe the clinical effects of ultraviolet (UV) therapy combined with autologous platelet-rich plasma (PRP) on chronic refractory wounds. Between January 2021 and December 2022, 60 inpatients with chronic refractory wounds were enrolled. Twenty patients were assigned to each of control groups 1 and 2 and treatment group according to whether they received PRP or UV treatment. All the patients underwent thorough debridement. Control group 2 received UV radiation. The treatment group underwent UV radiation combined with PRP gel covering the wound. Control group 1 underwent routine dressing changes after surgery, followed by skin grafting or skin key transfer if needed. One month later, we observed the wound healing in the two groups. After 2-4 PRP gel treatments, the wounds of patients in the treatment group healed. The healing time was 25.25 ± 4.93 days, and the dressings were changed 4.15 ± 3.30 times, both of which were better outcomes than in both control groups. In the treatment group, epidermal growth factor (EGF), insulin-like growth factor (IGF), platelet-derived growth factor (PGF), and transforming growth factor β (TGF-β) were slightly higher, and the concentration of vascular endothelial growth factor (VEGF) was significantly higher than in the control group (p < 0.05). PRP combined with UV therapy significantly increased the concentration of wound growth factors, accelerated wound healing, shortened treatment time, reduced treatment costs, and alleviated pain in patients.