anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Circular RNAs (circRNAs) have been implicated in tumorigenesis and progression of various cancers. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, a new oncogenic circRNA, hsa_circ_0070039 (circNUP54), was identified to be significantly upregulated in HCC through circRNA sequencing. As verified in 68 HCC samples, circNUP54 overexpression was correlated with aggressive cancerous behaviors and poor outcomes. Moreover, the function experiments showed that knockdown of circNUP54 inhibited the malignant progression of HCC in vitro and in vivo, whereas overexpression of circNUP54 had the opposite role. Mechanistic investigations carried out by RNA pull-down, RNA immunoprecipitation, and immunofluorescence revealed that circNUP54 interacted with the RNA-binding protein Hu-antigen R (HuR) and promoted its cytoplasmic export. The cytoplasmic accumulation of HuR stabilized the downstream BIRC3 mRNA through its binding to the 3' UTR region. Consequently, the encoded protein of BIRC3, cellular inhibitor of apoptosis 2 (cIAP2), proceeded to activate the NF-κB signal pathway and ultimately contributed to HCC progression. In addition, depletion of BIRC3 rescued the pro-tumorigenic effect of circNUP54 on HCC cells. Overall, this study demonstrated that circNUP54 facilitates HCC progression via regulating the HuR/BIRC3/NF-κB axis, which may serve as a promising therapeutic target for HCC treatment.
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m\^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Background Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction in patients with liver cirrhosis and recurrent symptoms of portal hypertension is primarily assessed with US and confirmed with invasive catheter venography, which can be used to measure the portosystemic pressure gradient (PSPG) to identify TIPS-refractory portal hypertension. To avoid the risks and costs of invasive catheter venography, noninvasive PSPG evaluation strategies are needed. Purpose To demonstrate the feasibility of the combination of four-dimensional (4D) flow MRI with computational fluid dynamics (CFD) for noninvasive PSPG assessment in participants with cirrhosis and TIPS. Materials and Methods Abdominal 4D flow MRI was performed prospectively in participants with cirrhosis and TIPS between January 2019 and September 2020. Flow rates were measured within the TIPS and inferior vena cava (IVC). The portal vein (PV), TIPS, right hepatic vein, and IVC were segmented on MRI scans to create a CFD mesh. The PV and infrahepatic IVC were defined as inflows for 4D flow MRI-derived flow rates. The suprahepatic IVC was defined as the outflow. CFD simulations were used to noninvasively estimate PSPG as the difference between the simulated pressures in the PV and suprahepatic IVC. Invasive venographic measurements of the PSPG served as the reference standard, and Pearson correlation analysis was conducted to evaluate the relationship between noninvasive estimates and invasive measurements. Results In all 20 participants with cirrhosis (mean age, 58 years ± 9 [SD]; 11 men), 4D flow MRI-based CFD simulations enabled visualization of flow velocities and pressure distributions within the segmented vasculature and TIPS. Noninvasive estimates and invasive measures of PSPG were strongly correlated (r = 0.77; P < .001). The 4D flow MRI-based CFD simulations correctly classified the presence or absence of a post-TIPS PSPG greater than 12 mm Hg in 16 of 20 participants (80%). Conclusion The combination of 4D flow MRI and CFD was feasible for noninvasive PSPG assessment in participants with cirrhosis, portal hypertension, and TIPS. © RSNA, 2024 See also the editorial by Motosugi and Watanabe in this issue.
Water-soluble, solid medicament carriers consist mainly of physicochemically modified PVA, water, suitable softening agents, and suitable additives for regulating isotonicity. Polyvinyl alcohols used are pref produced by solvolysis of PVAc and pref. have a mol wt 13000-150000 (esp. 30000-80000) and a degree of hydrolysis of 70-100% (esp. 80-90%) PVA and other components of the compsn (including the active ingredient) are pref dissolved in water or other suitable solvent (e.g. ethanol or isopropanol). Soln is adjusted to pH 4.0-8.0 with 1-N NCl/1-N NaOH, then used to produce a film of predetermined thickness. The initially good water-solubility of the film can be diminished by appropriate physicochemical methods (e.g. brief heating) in the order to control medicament release rate. Used in prolonged release formulations for application of medicaments such as antibiotics, chemotherapeutic agents, virustatics, moitics, mydriatics, vasoconstrictors anti-cataract agents etc in the eye, or other medicaments elsewhere in the body.
This is a pragmatic, prospective, multi-center trial with blinded outcome assessment of treatment candidates three months after stroke. Treatment candidates will be defined as patients with final discharge diagnosis of cerebral ischemia, and onset-to-alarm time ≤4 hours, symptoms not resolved at time of ambulance arrival, and able to walk without assistance prior to emergency. These patients will be included if their emergency call from a predefined catchment area in Berlin, Germany, caused a stroke alarm at the dispatch center during STEMO hours (7am-11pm, Monday-Sunday). About 45% of STEMO dispatches will be handled by regular ambulances since STEMO will be already in operation creating the quasi-randomized control group.

B_PROUD uses data from the B-SPATIAL registry. The B-SPATIAL registry has started recruitment in January 2016. However, B_PROUD recruits patients with symptom onset October 1st, 2016 or later (because data access at the dispatch center had to be established first).
Recently, we showed that three months of resistance exercise significantly alters 18 canonical pathways related to chronic inflammation in PBMCs of older adults. In this exploratory sub-study, the aim is to explore whether resistance exercise enhances the PBMCs stress response by mimicking an acute infection through in vitro LPS stimulation. Women (≥65 years) were randomly divided into intensive strength training (IST), strength endurance training (SET), or flexibility training (as control group, CON) groups. PBMCs were isolated and cultured with and without LPS for 24 h. Their RNA was analyzed via targeted RNA sequencing of 407 inflammation-related genes, with relevant fold-changes defined as ≤0.67 or ≥1.5 (3 months vs. baseline). A pathway analysis using ingenuity pathway analyses identified significant pathways among 407 genes with p < 0.05 and z-scores of ≤-2 or ≥2. Fourteen women were included in the analyses. A total of 151 genes with a significant fold-change were identified. In the CON group, a less-pronounced effect was observed. Strength training altered 23 pathways in the LPS-stimulated PBMCs, none of which overlapped between the IST and SET groups. A balanced exercise program that includes both IST and SET could beneficially adapt the immune responses in older adults by inducing alterations in the inflammatory stress response of PBMCs through different genes and pathways.
The primary aim of this study is to assess objective adherence to treatment, for PAP and MAS, and to evaluate if there will be similar effectiveness (efficacy+adherence) between PAP and MAS treatment for patients with mild to severe OSA. The secondary aim is to assess if patient preference does correlate to the final treatment adherence. An exploratory aim is to assess if the strategy of patients having both treatments available to use interchangeably could further improve treatment adherence, sleepiness, quality of life and fatigue. Having a better insight into patient adherence will improve the cost-effectiveness of treatment and will improve the health and quality of life for many Canadians who suffer from sleep apnea.

The proposed trial is a randomized open-label, two-treatment, two-period cross-over trial followed by an observational trial. Sixty OSA patients (10≤AHI≤50) will receive both PAP and MAS. As a recent innovation, we have adherence monitors for MAS that can give a new and comprehensive comparative analysis of the effectiveness between MAS and PAP. In the randomized trial phase the two treatments will be used separately for 1 month each (after treatment adaptation/titration of 1-2 months for each device). Treatment efficacy and daily treatment use data will be assessed together with changes in symptoms (quality of life, sleepiness and fatigue). Patient initial preference will be determined by using a patient decision aid. This will be followed by the observational trial phase, where all patients will have access to both interventions at home for 6 months and be allowed to choose on a daily basis the intervention to use. The intervention duration of 6 months is to allow for a sustained response in long-term adherence and to observe changes in quality of life.
BACKGROUND: Psychological anxiety and depression, as well as memory impairment, are frequently linked to inflammation. Clove essential oil (CEO) administration and hydrogen (H2) inhalation have been proven to have anti-inflammatory and alleviating effects on related psychological disorders in the past. The current study investigated the potential to improve anxiety-like behaviors and cognitive function by a combination of CEO and H2 treatment.
METHODS: The mice were administered lipopolysaccharide (LPS) to induce inflammation and oxidative stress response and cause psychological disorders. Using this animal model, we conducted experiments to test whether essential oil and H2 inhalation could improve the psychological damage in behavior caused by LPS. Subsequently, elevated plus maze (EPM), forced swimming test (FST), and passive avoidance (PA) test were performed for evaluation of mice anxiety, depression, and response to electric shock, respectively. Furthermore, the biochemical analysis was used to examine the expression levels of inflammatory and oxidative stress markers.
RESULTS: Our results showed that CEO administration and H2 inhalation alone or in combination positively improved inflammation-induced anxiety, depression, and cognitive memory deficits in the mice. In the single treatment groups, CEO demonstrated better results than H2 inhalation in the elevated plus maze, forced swimming, and passive avoidance tests, while combined treatment with both provided a further improved enhancement effect. Biochemical analysis of the cerebral cortex revealed that CEO and H2 therapy reversed the LPS-induced inflammation and oxidative stress response.
CONCLUSIONS: Our results suggest that a combination of CEO and H2 has the potential to treat psychological disorders or neuropsychiatric disorders.
OBJECTIVE: Chronic low back pain, affecting up to 58% of the population, often stems from intervertebral disc degeneration. Although magnetic resonance imaging (MRI) is commonly used for diagnostics, challenges arise in pinpointing pain sources due to frequent asymptomatic findings. Single-photon emission tomography (SPECT) integrated with computed tomography (CT) offers a promising approach, enhancing sensitivity and specificity.
METHODS: In this retrospective study, spanning 2016 to 2022, SPECT/CT imaging was performed on 193 patients meeting specific criteria. We correlated SPECT/CT findings with lumbar MRI results, utilizing Pfirrmann and Rajasekaran classifications for disc degeneration and endplate damage assessment. Logistic regression analysis adjusted for age and sex evaluated associations.
RESULTS: Of 965 spinal levels assessed, SPECT/CT positivity strongly correlated with higher Pfirrmann grades and Rajasekaran endplate classifications. Notably, Modic changes (MCs) on MRI displayed a nonsignificant relationship with SPECT/CT positivity. Significant associations were observed in older patients with positive MCs, Pfirrmann grades, and Rajasekaran classifications.
CONCLUSIONS: This comprehensive study, the largest of its kind, establishes a significant link between SPECT/CT positivity and advanced lumbar degenerative changes. Higher Pfirrmann grades and increased Rajasekaran endplate damage demonstrated substantial correlations with SPECT/CT positivity. Notably, MCs did not exhibit such association. Our findings underscore the potential of SPECT/CT in identifying pain generators in degenerative spinal conditions, offering valuable insights for future interventions.
Lateral ankle sprain (LAS) is a common injury in athletic and regular activities; with an incidence of 7 per 1000 exposure. After LAS, residual symptoms may persist leading to chronic ankle instability (CAI). This instability is believed to arise from dysfunctional postural control, defective proprioception, weak muscles, or reduced ankle range of motion (ROM).Thus, assessment of postural control is essential for proper clinical decision-making and treatment selection.

With advances in technology, smartphone has been introduced as an assessment tool for the musculoskeletal system. For example, it was used in assessment of ROM and mobility in stroke patients and frail elderly conditions. Further, it was used to assess balance and falling risk in those population. In addition, it was used to assess balance in healthy and participants with chronic ankle sprain. These studies proved that smartphone is a valid and reliable tool that is light in weight and inexpensive. Yet, these studies have some methodological concerns. For example, the application was not validated against gold standard or was validated only in healthy volunteers rather than in patients with musculoskeletal dysfunction. Further, a few of these studies did not establish the application discriminative validity between patients and healthy controls. Thus, this study will try to answer the following question: "Is smartphone application a valid and reliable tool to assess balance in patients with CAI compared to gold standards?
Atezolizumab will be administered at a flat dose of 1200 mg by intravenous route. Atezolizumab will be delivered in 250-mL 0.9% NaCl (sodium chloride) intravenous (IV) infusion bags. The administration will be repeated every 3 weeks (21 \[± 3\] days). The initial dose will be delivered over 60 (± 15) minutes. In case the first infusion is tolerated without any infusion-associated AEs the second infusion may be delivered over 30 (± 10) minutes. If the second 30 minutes infusion is well tolerated all the subsequent infusions may be administered over 30 (± 10) minutes. The treatment will be continued until disease progression, intolerable toxicity, patient refusal or Investigator's decision or any criterion for withdrawal from the trial or trial drug is fulfilled.
Most studies on CTCs have focused on isolating cells that express EpCAM. In this study, we emphasize the presence of EpCAM-negative and EpCAMlow CTCs, in addition to EpCAMhigh CTCs, in early BC. We evaluated stem cell markers (CD44/CD24 and CD133) and EMT markers (N-cadherin) in each subpopulation. Our findings indicate that all stemness variants were present in both EpCAMhigh and EpCAM-negative CTCs, whereas only one variant of stemness (nonCD44+CD24-/CD133+) was observed among EpCAMlow CTCs. Nearly all EpCAMhigh CTCs were represented by CD133+ stem cells. Notably, the hybrid EMT phenotype was more prevalent among EpCAM-negative CTCs. scRNA-seq of isolated CTCs and primary tumor partially confirmed this pattern. Therefore, further investigation is imperative to elucidate the prognostic significance of EpCAM-negative and EpCAMlow CTCs.
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is the standard care of treatment for locally advanced rectal cancer (LARC), which could effectively reduce the risk of local recurrence, increase the chance of sphincter preservation, and effectively improve the quality of life of patients. However, only about 8% of patients can benefit from nCRT. Therefore, to improve the therapeutic effect of nCRT and retain the organ function of patients so as to improve their quality of life is the focus of the current investigation.

In the previous study, the investigator have completed a series of clinical researches of irinotecan guided by UGT1A1 gene for nCRT in rectal cancer. A dose climbing study was firstly conducted to explore the maximum tolerable dose of irinotecan for nCRT in rectal cancer. The results indicated that the weekly dose intensity of irinotecan could be increased from 50mg/m2 to 80mg/m2 when the genotype of UGT1A1\*28 locus was 6/6, and the weekly dose intensity of irinotecan could also reach 65mg/m2 when the genotype of irinotecan was 6/7 phenotype. Further analysis also demonstrated that there was a dose-effect relationship between the total dose of irinotecan and pathological complete remission (pCR). The recently published CinClare study is a 3-phase randomized controlled trial that doubles the pCR rate and the total CR rate in combination with irinotecan on the basis of capecitabine combined with radiotherapy. However, in the Aristotle study conducted in the United Kingdom at the same phase, it has not been proved that irinotecan could improve the pCR rate, and it is not known whether the difference between the two studies is completely attributed to the irinotecan dose. Therefore, the investigator designed this real-world study to explore whether irinotecan can indeed improve the treatment efficacy in the real world when using irinotecan under the guidance of UGT1A1 gene in nCRT for LARC. Any locally advanced rectal cancer patients treated with irinotecan-based neoadjuvant radiotherapy and chemotherapy can be enrolled in this study. It is expected that the results of this study could provide more basis for individualized treatment of LARC.
Treatment-related cataracts were detected in rodents in a dose- and time-dependent manner. At greater than or equal to 6 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 3 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day, cataracts were observed in mice after 6 weeks and in rats after 28 weeks of dosing. At greater than or equal to 4 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 2 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day, cataracts were observed in mice after 13 weeks and in rats after 39 weeks of dosing [see Warnings and Precautions (5.5)].

Renal tubular toxicity was observed in studies up to 14 days in duration in mice and rats at exposures that were generally associated with morbidity and mortality. Tubular toxicity was also observed in a 2-year oral carcinogenicity study in mice at doses of 25, 75, and 150 mg/kg/day. The exposure at the lowest dose was 1.2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.6 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day. No similar effects were observed in mice after 13 weeks at exposures greater than those associated with renal changes in the 2-year study, suggesting that this effect is both dose- and time-dependent.
Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.
BACKGROUND: The mechanism underlying maternal fever and prolonged labor progression associated with neuraxial analgesia (NA) remains elusive, raising concerns among certain pregnant women regarding the application of NA during vaginal delivery. This study aimed to investigate the impact of early and late NA on maternal and neonatal outcomes in multiparous women.
METHODS: This retrospective study collected data from 1119 multiparous women with singleton pregnancies, full term and live births at our labor and delivery center between August 1st, 2021 and July 31st, 2022. Based on the timing of NA initiation, participants were categorized into three groups: no-NA, early-NA and late-NA. The no-NA group comprised of 172 women who did not receive NA during vaginal delivery; the early-NA group included 603 women in which NA was initiated when cervical dilation was between 0.5 and 2.0 cm; and the late-NA group comprising 344 cases in which NA was initiated at the cervical dilation of ≥ 2 cm. Maternal and neonatal outcomes were observed, including durations of the first, second, third and total stage of labor, the rate of intrapartum cesarean delivery (CD), intrapartum fever, postpartum hemorrhage (PPH), transfer to intensive care unit (ICU), admission to the neonatal intensive care unit (NICU), meconium-stained amniotic fluid, and neonatal Apgar scores at 1 and 5 min.
RESULTS: No differences were noted in the maternal age, body mass index (BMI) on admission, gestations, parity, gestational weeks at delivery and neonatal birth weight, or the rate of gestational diabetes mellitus (GDM) and hypertension disorder did not significantly differ among the three groups (p > 0.05). The no-NA group had shorter durations of first stage, second stage of labor compared to the early-NA or late-NA group (median, 215.0 min and 10.0 min vs. 300.0 min and 12.0 min vs. 280.0 min and 13.0 min) (p < 0.05), but no differences were observed between the early-NA and late-NA group (p > 0.05). There were no differences in the rate of intrapartum CD, intrapartum fever, PPH, maternal transferred to ICU, neonatal transfer to NICU, meconium-stained amniotic fluid, and postpartum stay ≥ 7d, as well as the neonatal the Apgar scores at 1 and 5 min among the three groups (p > 0.05).
CONCLUSION: NA is associated with extended durations of the first, second and total stages of labor. However, the early initiation of NA in multiparous women (cervical dilation within 0.5-2.0 cm) does not increase the risk of intrapartum CD or intrapartum fever. These findings endorse the secure utilization of early NA for pain relief during labor in multiparous women.
Participants will receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 16, participants will receive a placebo infusion to maintain the blind.
Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0-36.0 Gy in 5-6 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/m\^2) and weekly nab-paclitaxel at escalating doses (33 mg/m\^2 per week).