anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.
Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1-/- mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.
Molecular abnormalities that shape human neoplasms dissociate their phenotypic landscape from that of the healthy counterpart. Through the lens of a microscope, tumour pathology optically captures such aberrations projected onto a tissue slide and has categorized human epithelial neoplasms into distinct histological subtypes based on the diverse morphogenetic and molecular programmes that they manifest. Tumour histology often reflects tumour aggressiveness, patient prognosis and therapeutic vulnerability, and thus has been used as a de facto diagnostic tool and for making clinical decisions. However, it remains elusive how the diverse histological subtypes arise and translate into pleiotropic biological phenotypes. Molecular analysis of clinical tumour tissues and their culture, including patient-derived organoids, and add-back genetic reconstruction of tumorigenic pathways using gene engineering in culture models and rodents further elucidated molecular mechanisms that underlie morphological variations. Such mechanisms include genetic mutations and epigenetic alterations in cellular identity codes that erode hard-wired morphological programmes and histologically digress tumours from the native tissues. Interestingly, tumours acquire the ability to grow independently of the niche-driven stem cell ecosystem along with these morphological alterations, providing a biological rationale for histological diversification during tumorigenesis. This Review comprehensively summarizes our current understanding of such plasticity in the histological and lineage commitment fostered cooperatively by molecular alterations and the tumour environment, and describes basic and clinical implications for future cancer therapy.
OBJECTIVE: To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR).
MATERIALS AND METHODS: This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early- and late-onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro-placental-uterine ratio (CPUR), and amniotic-umbilical-to-cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission.
RESULTS: The study included 132 participants, divided into early- (n = 32) and late-onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late-onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early-onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late-onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early- and late-onset FGR on multivariate analysis.
CONCLUSIONS: AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late-onset FGR.
This is a prospective multi-site study to evaluate the PK/PD of extended duration AL in HIV-infected children on EFV-based ART and HIV-uninfected children not on ART. AL is the first-line treatment for malaria in Uganda. No change in standard of care treatment will be made for the purposes of this study except for the extension of AL to 5-day dosing. This study will enroll a) HIV-infected children, and b) HIV-uninfected children. All participants may be enrolled through Tororo District Hospital (TDH) or Masafu General Hospital (MGH) in Busia, or other referral centers the area. we will use a design where children will be randomized to either 3-day or 5-day AL and then for subsequent episodes of malaria, should they occur. Conservatively, assuming each enrolled child participates for only a single episode of malaria, up to 60 (30 HIV-infected on 3-day and 30 HIV-infected on 5-day) and 100 (50 HIV-uninfected on 3-day and 50 HIV-uninfected on 5-day) subjects will be enrolled for each of the intensive study groups. Up to 100 (50 HIV-infected on 3-day and 50 HIV-infected on 5-day) and 120 (60 HIV-uninfected on 3-day and 60 HIV-uninfected on 5-day) subjects will be enrolled for each of the population study groups. Comparisons of AL PK exposure will be made among and between a) HIV-infected children with malaria receiving EFV-based ART and b) HIV-uninfected children who are not on ART. Comparisons will be based on an intensive PK design for AL area under the concentration-time curve (AUC) estimations. Population PK study will be combined with intensive PK studies to allow for optimal PK-outcomes assessments.
BACKGROUND: May-Thurner syndrome (MTS) is iliac vein compression syndrome associated with postoperative deep vein thrombosis (DVT) resulting from chronic compression of the left iliac vein against lumbar vertebrae by the overlying right or left common iliac artery. MTS is not well known as a risk factor for DVT after total hip arthroplasty (THA). We evaluated the incidence of DVT after THA and analyzed if the MTS is a risk factor for DVT after THA. We hypothesized that MTS would be associated with an increased risk of developing DVT after THA.
METHODS: All patients > 65 years of age who underwent THA between January 1, 2009, and January 12, 2017, were identified. Among them, the patients who presented for postoperative DVT of the lower extremity were reviewed with medical record data. MTS was diagnosed with computed tomography (CT) angiography of the lower extremity. We analyzed the demographic data, symptoms, diagnoses, and treatment of MTS patients.
RESULTS: A total of 492 consecutive patients aged > 65 years who underwent operation for THA were enrolled. Among them, 5 patients (1.0%) presented for postoperative DVT of the lower extremity. After reviewing the CT angiography of the lower extremity, 4 out of 5 DVT patients (80%) were identified as having MTS. All MTS patients were female and presented with pain and swelling of the left leg. All MTS patients were treated with systemic anticoagulation, aspiration thrombectomy, and percutaneous transluminal angioplasty. Complete resolution of thrombus was observed in all patients.
CONCLUSIONS: If the diagnosis of MTS is delayed, the morbidity and mortality rates are significantly increased. Orthopedic surgeons should be aware of MTS as a risk factor for DVT after THA. Moreover, preoperative evaluation with duplex sonography or CT angiography to confirm MTS should be considered. In this regard, this study is considered to have sufficient clinical value for early diagnosis and appropriate treatment of MTS after THA.
A group of participants will undergo 1x1 transcranial direct current stimulation of the parietal lobes at 1 mA vs. 2 mA vs. sham stimulation. A second group of participants will undergo 1mA or 2mA stimulation, and sham, in right vs. left parietal lobes using 4x1 stimulation (e.g., 1mA left parietal lobes, 1mA right parietal lobes, sham; 2mA parietal lobes, 2mA right parietal lobes, sham).
The study was planned in a parallel randomized controlled trial design. The population of the research will be preterm infants followed in the Newborn Intensive Care Unit of Atatürk University Health Research and Application Center between May 2022 and September 2022. Randomization in the sample of the study will be done in the computer environment. Sample size was determined by power analysis. In the collection of data; Preterm Baby Information Form, Preterm Baby Follow-up Form, Neonatal Stress Scale and ALPS-NEO pain and stress assessment scale will be used. In the control group, the PIC intervention will be performed by the investigator in accordance with clinical procedures. In the experimental group, the baby's grasping reflex stimulation will be provided during the PIC attempt.
Post-transcriptional regulation and RNA-binding proteins (RBPs) play vital roles in the occurrence of secondary injury after intracerebral hemorrhage (ICH). Therefore, we identified RBPs distinctively expressed after ICH by screening and determined thioredoxin1 (Txn1) as one of the most distinctive RBPs. We employed an ICH model and in vitro experiments to investigate the role of Txn1 in ICH. Firstly, we found that Txn1 was mainly expressed in microglia and neurons in the central nervous system, and its expression was significantly reduced in perihematomal tissue. Additionally, adeno-associated virus (AAV) carrying Txn1 was injected into the ICH rat model. Our results showed that overexpression of Txn1 reduced secondary injury and improved outcome in the ICH rat model. Moreover, to understand the therapeutic mechanism of Txn1 after ICH, we performed RNA immunoprecipitation combined with high-throughput sequencing. The results showed that Txn1 binds to inflammation- and apoptosis-related mRNAs and affects gene expression through RNA splicing and translation. Finally, RNA pull-down assays and in vitro experiments confirmed that Txn1 binds to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), leading to reduced inflammation and apoptosis. Our study suggests that Txn1 is a potential therapeutic target for alleviating ICH-induced brain injury.
Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.
Smartphone-based technology for ECG recording has recently spread as a complementary tool for electrocardiographic screening and monitoring in adult horses and in other animal species. The present study aimed to assess the feasibility and accuracy of a smartphone-based ECG in healthy foals. This was a prospective observational study (authorization n. 45,865/2016) including 22 foals aged less than 21 days. A reference standard base-apex ECG (rECG) was acquired, and a smartphone ECG (sECG) was recorded immediately after by using a smartphone-based single lead electrocardiograph. All ECG tracings were evaluated in a blind fashion by a single board-certified cardiologist, who judged whether the tracings were acceptable for interpretation and performed ECG measurements and diagnosis. The Spearman correlation coefficient, the Cohen's k test and the Bland-Altman test were used to assess the agreement between sECG and rECG. All sECG tracings were acceptable for interpretation. All foals showed sinus rhythm on both rRCG and sECG tracings, with perfect agreement in heart rate classification (κ = 0.87; p < 0.001). No clinically relevant differences were found in the assessment of waves and intervals duration. Concerning P wave and QRS complex polarity, the percentage of agreement between rECG and sECG was 78% and 83%, respectively. About ECG tracing quality, rECG and sECG showed a substantial agreement (κ = 0.624; p < 0.001). In conclusion, the smartphone-based ECG device tested in the present study recorded good quality single-lead ECG tracings in foals, reliable for heart rate and ECG measurements, but different polarity of P waves and QRS complexes was found in some foals in comparison to rECG.
AIM: To explore the relationship between the retroperitoneal vasculature and anterior surface of the lower spine, and to establish values for aiding in prediction of the pertinence of anterior approach at the L4-L5 and L5-S1 intervertebral discs.
MATERIAL AND METHODS: The study included 13 fresh human cadavers. After exploration of the abdominal cavity and removal of the visceral organs, the vasculature, and anterior spinal surface were revealed beneath the lower extension of the perirenal fascia. Morphometric measurements of the great vessels and the intervertebral discs were obtained. All measurements were analyzed and presented as mean and standard deviation. Differences in the values between sexes were assessed.
RESULTS: The anterior height of the L4-L5 and L5-S1 intervertebral disc was 6.8 ± 0.81 mm and 6.7 ± 0.99 mm, respectively. The widths of the aorta, inferior vena cava, right and left common iliac arteries, and right, and left common iliac veins were 16.4 ± 3.58, 20.6 ± 3.36, 11.5 ± 2.32, 11.5 ± 2.43, 14.7 ± 3.13, and 15.5 ± 3.27 mm, respectively. The mean aortic bifurcation angle was 45.5°. The aortic bifurcation was located above the lower endplate of the L4 vertebrae in 53.8% of the cadavers. The area of the interarterial and interiliac trigones was 14.6 ± 5.33 cm < sup > 2 < /sup > and 7.1 ± 4.35 cm2, respectively. No statistically significant differences were noted between the sexes.
CONCLUSION: An elaborate radiological examination of the vasculature should be performed prior to surgery to avoid unwanted vascular complications during the anterior approach. Knowing the area of the interarterial and interiliac triangles and the aortic bifurcation location could be aid in assessing the safe working zone.
BACKGROUND: By this survey, we aim to gain national-based information regarding trends in endovascular repair (ER) for the treatment of aortic disease in patients with genetically-triggered aortic disease (GTAD) and connective tissue disorder (CTD) over the last two decades.
METHODS: All Italian vascular surgery centers (N.=80) were invited to participate in an anonymous electronic cross-sectional survey on ER for GTAD/CTD.
RESULTS: Overall, 29 institutions completed the survey, thereby yielding a 36% response rate. The percentage of responding institutions rises to 64% if only regional hubs were considered (23/36). The median number of index procedures per center was 6.2, and a steady increase in the overall number of interventions over time was also noted. Most patients were males (73%) with a median age of 48 years. The most common endovascular procedure was TEVAR (N.=101), followed by F/BEVAR (N.=43) and EVAR (N.=37). The overall technical success rate was 83.4% while major adverse events and mortality at thirty days were reported at 18.2% and 9.9%, respectively. An additional 5.0% mortality rate was noted for an overall one-year mortality of 14.9%, while 3.7% of all treated patients were diagnosed with a type 1 endoleak.
CONCLUSIONS: This national cross-sectional survey, investigating trends in ER of GTADs and CTDs over two decades, highlights a consistent increase in the use of endovascular techniques for their treatment. Early mortality was acceptably low, yet influenced by the urgency of presentation. At one-year follow-up, a 5% additional death rate was noted, and the reintervention rate remained below one in ten.
The present invention relates to mixed metal compounds having pharmaceutical activity, especially as phosphate binders. It also extends to methods of manufacture of those compounds, as well as to pharmaceutical compositions containing such compounds. It further relates to their pharmaceutical use. In particular, the present invention relates to use of compounds of Formula (I): MMwherein Mis at least one bivalent metal (i.e. with two positive charges); M1is at least one trivalent metal (i.e. with three positive charges); and 1 > a > 0.4.
Barrier resection was defined as "en bloc" removal of tumor with surrounding barriers. The barriers include muscular fascia, vascular adventitia, epineurium and periosteum, in some cases where there is no barrier, 3-5cm of healthy tissue is considered equivalent. Barrier resection was developed according to the above characteristics of STSs, which featured with the fact that sarcomas take the path of least resistance and initially grow within the anatomical compartment in which they arose, and the phenomenon that skip metastases are limited within the same anatomic compartment in which the primary lesion is located.Further surgery would be 1cm resection if a recurrence occurs.
Clinical studies of lorazepam generally were not adequate to determine whether subjects aged 65 and over respond differently than younger subjects; however, the incidence of sedation and unsteadiness was observed to increase with age (see ). ADVERSE REACTIONS

Age does not appear to have a significant effect on lorazepam kinetics (see ). CLINICAL PHARMACOLOGY

Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered. Greater sensitivity (e.g., sedation) of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, and lower doses may be sufficient in these patients (see ). DOSAGE AND ADMINISTRATION
Extraesophageal reflux (EER) has recently been found to be a risk factor for many head and neck pathologies. Many studies have shown that contact between the refluxed content and mucous tissue can cause local inflammation and edema and thus facilitate the development of inflammation. Although important, the diagnostics of EER is not easy. The simplest means of collecting information about reflux problems is questioning potential sufferers. However, although many questionnaires have been developed over the last few years, questioning is still not a suitable technique for the evaluation of EER, the reason being that symptoms of EER are heterogeneous and very common. Currently, 24-h dual-probe esophageal pH monitoring or impedance is considered the best diagnostic method for EER. The 24-h oropharyngeal pH monitoring is a newer method aimed at detecting episodes of reflux to the oropharynx and seems to generate similar results. However, these methods may not be tolerated well. Moreover, the position of the sensor, which is placed in the hypopharynx or oropharynx, does not precisely reflect the amount of reflux content that reaches larynx, nasopharynx, nasal cavity or middle ear. Another disadvantage of pH monitoring is that it enables only a short-term analysis over a timespan of just 24-48 h. Detection of pepsin in fluids and tissues is considered by some authors to be perhaps more appropriate than pH monitoring because it reflects the long-term effects of EER and proves that EER is truly affecting the examined region. This is particularly true for more distant regions like the middle ear. Pepsin detection in saliva would be very well tolerated and fast diagnostic method. However, data of its reliability are lacking. The aim of the study is to compare results of oropharyngeal pH monitoring and esophageal impedance monitoring, compared to a quantified pepsin presence in the saliva obtained immediately prior to 24-hour monitoring and to evaluate the feasibility of this diagnostic option as a routine method.
Multiple sclerosis (MS) is an autoimmune disease characterized by the infiltration of immune cells and demyelination in the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic animal model for studying MS. In this study, we aimed to investigate the role of CD4 T cells in the initiation and relapse of EAE, focusing on the activation phase and immune response. To create the EAE mice model, female mice were immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 emulsified with complete Freund's adjuvant (CFA). Clinical scores were assessed daily, and results demonstrated that mice in the EAE group exhibited a classic relapsing-remitting pattern. Hematoxylin-eosin (H&E) and luxol fast blue (LFB) staining analysis revealed significant infiltration of inflammatory cells in the CNS and demyelination in EAE mice. Regarding the activation phase, both CD4+CD69+ effector T (Teff) cells and CD4+CD44+CD62L- effector memory T (Tem) cells may contribute to the initiation of EAE, however, the relapse stage was probably dominated by CD4+CD44+CD62L- Tem cells. Additionally, in terms of immune function, helper T (Th)1 cells are primarily involved in initiating the EAE. However, both Th1 and Th17 cells contribute to the relapse stage, and the immunosuppressive function of regulatory T (Treg) cells was inhibited during the EAE pathological process.