Miracle-dz/UniFAR-FTUs huggingface dataset:
Ovarian cancer: Current status and strategies for improving therapeutic outcomes

Of all the gynecologic tumors, ovarian cancer (OC) is known to be the deadliest. Advanced‐stages of OC are linked with high morbidity and low survival rates despite the immense amount of research in the field. Shortage of promising screening tools for early‐stage detection is one of the major challenges linked with the poor survival rate for patients with OC. In OC, therapeutic management is used with multidisciplinary approaches that includes debulking surgery, chemotherapy, and (rarely) radiotherapy. Recently, there is an increasing interest in using immunomodulation for treating OC. Relapse rates are high in this malignancy and averages around every 2‐years. Further treatments after the relapse are more intense, increasing the toxicity, resistance to chemotherapy drugs, and financial burden to patients with poor quality‐of‐life. A procedure that has been studied to help reduce the morbidity rate involves pre‐sensitizing cancer cells with standard therapy in order to produce optimal results with minimum dosage. Utilizing such an approach, platinum‐based agents are effective due to their increased response to platinum‐based chemotherapy in relapsed cases. These chemo‐drugs also help address the issue of drug resistance. After conducting an extensive search with available literature and the resources for clinical trials, information is precisely documented on current research, biomarkers, options for treatment and clinical trials. Several schemes for enhancing the therapeutic responses for OC are discussed systematically in this review with an attempt in summarizing the recent developments in this exciting field of translational/clinical research.
Two-Point Dynamic Observation of Alzheimer’s Disease Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Background: Extensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one-point observation. Objective: To investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients. Methods: We analyzed CSF concentrations of tau, amyloid-β (Aβ) 42 and 40, and leucine rich α-2-glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two-point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo-peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF). Results: Tau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aβ42 (LD/FD = 0.80, p < 0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p < 0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with LD concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively. Conclusions: Dynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH and could be used to predict shunt effectiveness.
Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2′-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.
Skin-associated lactic acid bacteria from North American bullfrogs as potential control agents of Batrachochytrium dendrobatidis

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis and has been a key driver in the catastrophic decline of amphibians globally. While many strategies have been proposed to mitigate Bd outbreaks, few have been successful. In recent years, the use of probiotic formulations that protect an amphibian host by killing or inhibiting Bd have shown promise as an effective chytridiomycosis control strategy. The North American bullfrog (Lithobates catesbeianus) is a common carrier of Bd and harbours a diverse skin microbiota that includes lactic acid bacteria (LAB), a microbial group containing species classified as safe and conferring host benefits. We investigated beneficial/probiotic properties: anti-Bd activity, and adhesion and colonisation characteristics (hydrophobicity, biofilm formation and exopolysaccharide-EPS production) in two confirmed LAB (cLAB-Enterococcus gallinarum CRL 1826, Lactococcus garvieae CRL 1828) and 60 presumptive LAB (pLAB) [together named as LABs] isolated from bullfrog skin.We challenged LABs against eight genetically diverse Bd isolates and found that 32% of the LABs inhibited at least one Bd isolate with varying rates of inhibition. Thus, we established a score of sensitivity from highest (BdGPL AVS7) to lowest (BdGPL C2A) for the studied Bd isolates. We further reveal key factors underlying host adhesion and colonisation of LABs. Specifically, 90.3% of LABs exhibited hydrophilic properties that may promote adhesion to the cutaneous mucus, with the remaining isolates (9.7%) being hydrophobic in nature with a surface polarity compatible with colonisation of acidic, basic or both substrate types. We also found that 59.7% of LABs showed EPS synthesis and 66.1% produced biofilm at different levels: 21% weak, 29% moderate, and 16.1% strong. Together all these properties enhance colonisation of the host surface (mucus or epithelial cells) and may confer protective benefits against Bd through competitive exclusion. Correspondence analysis indicated that biofilm synthesis was LABs specific with high aggregating bacteria correlating with strong biofilm producers, and EPS producers being correlated to negative biofilm producing LABs. We performed Random Amplified Polymorphic DNA (RAPD)-PCR analysis and demonstrated a higher degree of genetic diversity among rod-shaped pLAB than cocci. Based on the LAB genetic analysis and specific probiotic selection criteria that involve beneficial properties, we sequenced 16 pLAB which were identified as Pediococcus pentosaceus, Enterococcus thailandicus, Lactobacillus pentosus/L. plantarum, L. brevis, and L. curvatus. Compatibility assays performed with cLAB and the 16 species described above indicate that all tested LAB can be included in a mixed probiotic formula. Based on our analyses, we suggest that E. gallinarum CRL 1826, L. garvieae CRL 1828, and P. pentosaceus 15 and 18B represent optimal probiotic candidates for Bd control and mitigation.
Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Engevik et al. show that loss of myosin Vb results in the formation of large subapical vesicles, termed inclusions, lined by microvilli in small-intestinal enterocytes. Inclusions arise through apical bulk endocytosis of the brush border through a dynamin- and pacsin 2–dependent mechanism.
25-Hydroxyvitamin D and Total Cancer Incidence and Mortality: A Meta-Analysis of Prospective Cohort Studies

Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D and total cancer incidence and mortality. The aim of this study was to quantitatively assess these associations by combining results from prospective cohort studies. A systematic literature search was implemented in PubMed and Scopus databases in April 2019. Comparing the highest with the lowest categories, the multivariate-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. A trend estimation was performed using a two-stage, dose-response, meta-analysis method. Twenty-three independent prospective studies were included for data synthesis. Eight studies investigated the association between 25-hydroxyvitamin D and the risk of cancer incidence (7511 events and 70,018 participants), and the summary estimate showed that 25-hydroxyvitamin D is marginally associated with cancer risk (Summary RR = 0.86; 95% CI: 0.73, 1.02; I2 = 70.8%; p = 0.001). Sixteen studies investigated the association between 25-hydroxyvitamin D and the risk of cancer mortality (8729 events and 101,794 participants), and a higher 25-hydroxyvitamin D concentration was inversely associated with the risk of cancer mortality (Summary RR = 0.81; 95% CI: 0.71, 0.93; I2 = 48.8%, p = 0.012). Dose-response analysis indicated that the risk of cancer incidence was reduced by 7% (RRs = 0.93; 95% CI: 0.91, 0.96), and the risk of cancer mortality was reduced by 2% (RRs = 0.98; 95% CI: 0.97, 0.99), with each 20 nmol/L increment of 25-hydroxyvitamin D concentration. This meta-analysis provides evidence that a higher 25-hydroxyvitamin D concentration is associated with a lower cancer incidence and cancer mortality.
Depression Trends in Patients with Chronic Pain: An Analysis of the Nationwide Inpatient Sample.

BACKGROUND Chronic pain remains a major public health issue that affects the lives of many worldwide, including patients with chronic pain. Comorbidities like depression have been associated with decreased quality of sleep, decreased enjoyment of life activities, increased anxiety, and decreased efficacy in treatments among patients with chronic pain. Despite these associations, the trends and demographic characteristics of patients with chronic pain with depression is yet to be investigated. OBJECTIVES To investigate the trends and demographic characteristics of hospitalized patients with chronic pain with comorbid depression from years 2011 to 2015 in the United States. STUDY DESIGN This was an observational study. SETTING Patients were identified from a Healthcare Cost and Utilization Project database called National Inpatient Sample (NIS) documentation. METHODS Patients were identified from the NIS database using International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and ICD-10) diagnosis codes for chronic pain and comorbid depression from years 2011 to 2015. RESULTS Between 2011 and 2015, an estimated 9.3 million patients with chronic pain were identified. Of this cohort, 2.2 million patients (22.9%) were diagnosed with comorbid depression. The estimated number of patients with depression varied from 399,865 (22.6%) in 2011 to 421,490 (23.1%) in 2015 (P = 0.13). From 2011 to 2015, there was a significant upward trend of depression among blacks (8.1 ± 0.42% to 9.7 ± 0.27%), patients aged 65 to 84 years (29.0 ± 0.39% to 32.4 ± 0.23%), Medicare insured patients (56.1 ± 0.54% to 58.5 ± 0.29%), Medicaid insured patients (14.7 0.4% to 17.1 ± 0.24%), and patients from zip code areas with lowest annual household income (29.2 ± 1.3% to 32.0 ± 0.59%). Among patients with depression, the adjusted total hospitalization cost increased from $43,584 in 2011 to $49,923 in 2015 (P < 0.001), with average length of hospital stay stable around 5.05 ± 0.02 days. Most patients were discharged home or with self-care compared with short-term facility (57.9 ± 0.14% vs. 2.0 ± 0.03%). LIMITATIONS Large database research comes with several limitations. The NIS database does not contain variables that can evaluate disease severity such as depression. In addition, the NIS database is highly dependent on the selection and report accuracy of the appropriate diagnostic ICD codes. These estimates could be imprecise from over or underestimation of the number of patients with chronic pain with comorbid depression. CONCLUSIONS These findings from the present investigation suggest that depression in patients with chronic pain remained stable from 2011 to 2015, with the majority of patients identified as women, white, and ages 45 to 65 years. KEY WORDS Chronic pain, depression, National Inpatient Sample.
Eye-Tracking Metrics Predict Perceived Workload in Robotic Surgical Skills Training

Objective The aim of this study is to assess the relationship between eye-tracking measures and perceived workload in robotic surgical tasks. Background Robotic techniques provide improved dexterity, stereoscopic vision, and ergonomic control system over laparoscopic surgery, but the complexity of the interfaces and operations may pose new challenges to surgeons and compromise patient safety. Limited studies have objectively quantified workload and its impact on performance in robotic surgery. Although not yet implemented in robotic surgery, minimally intrusive and continuous eye-tracking metrics have been shown to be sensitive to changes in workload in other domains. Methods Eight surgical trainees participated in 15 robotic skills simulation sessions. In each session, participants performed up to 12 simulated exercises. Correlation and mixed-effects analyses were conducted to explore the relationships between eye-tracking metrics and perceived workload. Machine learning classifiers were used to determine the sensitivity of differentiating between low and high workload with eye-tracking features. Results Gaze entropy increased as perceived workload increased, with a correlation of . 51. Pupil diameter and gaze entropy distinguished differences in workload between task difficulty levels, and both metrics increased as task level difficulty increased. The classification model using eye-tracking features achieved an accuracy of 84.7% in predicting workload levels. Conclusion Eye-tracking measures can detect perceived workload during robotic tasks. They can potentially be used to identify task contributors to high workload and provide measures for robotic surgery training. Application Workload assessment can be used for real-time monitoring of workload in robotic surgical training and provide assessments for performance and learning.
Targeting the metabolic response to statin-mediated oxidative stress produces a synergistic anti-tumor response.

Statins are widely prescribed inhibitors of the mevalonate pathway, acting to lower systemic cholesterol levels. The mevalonate pathway is critical for tumorigenesis and is frequently upregulated in cancer. Nonetheless, reported effects of statins on tumor progression are ambiguous, making it unclear if statins, alone or in combination, can be used for chemotherapy. Here, using advanced mass spectrometry and isotope tracing, we showed that statins only modestly affected cancer cholesterol homeostasis. Instead, they significantly reduced synthesis and levels of another downstream product, the mitochondrial electron carrier coenzyme Q, both in cultured cancer cells and tumors. This compromised oxidative phosphorylation, causing severe oxidative stress. To compensate, cancer cells upregulated antioxidant metabolic pathways, including reductive carboxylation, proline synthesis, and cystine import. Targeting cystine import with an xCT transporter-lowering MEK inhibitor, in combination with statins, caused profound tumor cell death. Thus, statin-induced ROS production in cancer cells can be exploited in a combinatorial regimen.
Prevalence and Associations of Fundus Tessellation Among Junior Students From Greater Beijing.

Purpose To determine the prevalence of fundus tessellation and associations with ocular and systemic parameters among junior students from Greater Beijing. Methods The school-based study included 1443 individuals with a mean age of 12.4 ± 0.5 years (range: 9-16 years). All participants underwent a comprehensive ophthalmic examination and an interview. Fundus tessellation, defined as variation in the visibility of large choroidal vessels, was differentiated into three grades. Results The prevalence and degree of fundus tessellation were 688/1430 (48.1%; 95% confidence intervals [CI]: 45.5%, 50.7%) and 0.54 ± 0.61 (median, 0.00; range, 0-3), respectively. In multivariable regression analysis, a higher degree of fundus tessellation was associated with reduced subfoveal choroidal thickness (P < 0.001; beta, -0.02; odds ratio [OR], 0.98; 95% CI: 0.98, 0.99) and longer axial length (P < 0.001; beta, 0.23; OR, 1.25; 95% CI: 1.10, 1.43). Subfoveal choroidal thickness decreased from 299 ± 61 μm (95% CI: 293, 304) in eyes without fundus tessellation to 246 ± 57 μm (95% CI: 241, 251), 197 ± 43 μm (95% CI: 187, 207), and 131 ± 30 μm (95% CI: 93, 168) in eyes with grade 1, 2, and 3 fundus tessellation, respectively. A higher degree of peripapillary fundus tessellation was associated with reduced subfoveal choroidal thickness (P < 0.001; beta, -0.02; OR, 0.98; 95% CI: 0.98, 0.99) and younger age at myopia onset (P = 0.008; beta, 0.41; OR, 1.51; 95% CI: 1.11, 2.04). Conclusions The prevalence of fundus tessellation is relatively high in Chinese teenagers. As in adults, the degree of fundus tessellation is a surrogate for choroidal thickness in teenagers. Marked fundus tessellation indicates a leptochoroid and is associated with earlier myopia onset.
A Staged Treatment of Symptomatic Lumbar Intraspinal Synovial Cysts.

BACKGROUND Lumbar intraspinal synovial cyst (LISC) refers to a cyst that arises from the zygapophyseal joint capsule of the lumbar spine and contains serous or gelatinous fluid. In cases of LISCs resistant to conservative treatments, various minimally invasive percutaneous spinal techniques (MIPSTs) may be applied prior to open surgery. OBJECTIVES The outcomes of 3-staged MIPSTs for the treatment of symptomatic LISCs resistant to conservative treatments were evaluated. STUDY DESIGN An institutional review board approved retrospective chart review. SETTING University hospital inpatients referred to our pain clinic. METHODS Review of charts of all patients who underwent MIPSTs for symptomatic LISCs resistant to conservative treatments during a time period of 13 years at a university hospital pain clinic. Patients with symptomatic LISCs resistant to conservative treatments were treated with 3-staged MIPSTs, including image-guided intraarticular aspiration, cyst distention and rupture, and injection of corticosteroids (ARI), endoscopic cyst enucleation (ECE), and endoscopic superior facetectomy (ESF) by a single pain specialist. A symptom-free period after each intervention was evaluated. Recurrence was defined as the same recurrent symptomatic radicular pain with confirmation of the LISC on magnetic resonance imaging. All patients with a minimum follow-up time of 3 years were included. RESULTS Of the 40 patients who underwent ARI, 3 patients failed to complete a follow-up and 19 patients (51.4%) who had recurring symptoms received ECE. Ten patients (52.6%) who had re-recurring symptoms after ECE received ESF. There was no recurrence after ESF. LIMITATIONS This retrospective and observational study with a limited number of patients does not represent a high level of evidence. CONCLUSIONS This information provided the recurrence rate after each intervention. Half of the patients who went on to receive ARI experienced recurrence, whereas half of the patients with recurrence who received ECE experienced re-recurrence. ESF treatment resulted in no recurrence within the 3-year study period. KEY WORDS Conservative treatment, endoscopic surgical procedures, facet joint, intraarticular injection, minimally invasive surgical procedures, needle biopsy, nerve root compression, radiculopathy, synovial cysts.
Self-determination in young adults with autism spectrum disorder

This study examined rates of and contributing factors to self-determination among young adults with autism spectrum disorder. Caregivers of young adults with autism spectrum disorder, 16–25 years, from five Autism Treatment Network sites completed surveys about their young adults’ transition experiences including the American Institutes for Research Self-Determination measure. Data were analyzed using univariate and multivariate analysis. Caregivers (n = 479) reported their young adults with autism spectrum disorder as having moderate overall self-determination (x = 38; standard deviation = 9.04) with low capacity (x = 15.3; standard deviation = 5.67) and high opportunities at home (x = 23.1; standard deviation = 4.59). Young adults with autism spectrum disorder with intellectual disability or severe autism spectrum disorder symptomology experience significant disparities in overall self-determination compared to those without intellectual disability and less frequent symptom expression and severity. Barring severity indicators, there were few significant predictors of self-determination. Findings show a breakdown in self-determination skill-building. Young adults with autism spectrum disorder with intellectual disability or severe symptomology experienced significant disparities in self-determination. These findings show that current promotion of self-determination is not meeting the needs of young adults with autism spectrum disorder. Future interventions must identify what supports young adults with autism spectrum disorder need to capitalize on these opportunities to be independent and exert autonomy in their daily lives.
Application of ZnO-Based Nanocomposites for Vaccines and Cancer Immunotherapy

Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform.