Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic significance of miR-210 as a potential tumor biomarker of human cancer detection: an updated pooled analysis of 30 articles

A large number of studies have explored the diagnostic value of miR-210 as a potential diagnostic cancer biomarker to detect various cancers in patients. However, the results of its diagnostic accuracy and reliability in individual studies are still inconsistent. Therefore, we conducted this updated pooled analysis to derive a more reliable conclusion of the overall accuracy of miR-210 in cancer detection and diagnosis. A comprehensive literature search was performed using the PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang databases. The quality of all eligible studies was scored according to Quality Assessment of Diagnostic Accuracy Studies-2 guidelines. The bivariate mixed model was applied to pooled sensitivity, specificity, likelihood ratios, and diagnostic ORs. The summary receiver operator characteristic (SROC) curve and the hierarchical SROC models were used to check overall diagnostic performance. Thirty articles with 2,304 patients and 1,673 controls were included in this study. The pooled parameters calculated from all studies are as follows: sensitivity −0.74 (95% CI: 0.68–0.79), specificity −0.79 (95% CI: 0.74–0.83), positive likelihood ratio −3.57 (95% CI: 2.85–4.47), negative likelihood ratio −0.32 (95% CI: 0.26–0.40), diagnostic OR −10.98 (95% CI: 7.55–15.98), SROC −0.84 (95% CI: 0.80–0.87). All of these results revealed that miR-210 had relatively moderate accuracy in distinguishing patients with various cancers from all other individuals. However, well-designed prospective studies with large sample sizes using different groups of the population are urgently warranted to confirm our findings.
Perceptions of engagement in health care among patients with tuberculosis: a qualitative study

Purpose Adherence to treatment is cited as a key challenge in fighting tuberculosis (TB). Treatment of TB requires patients to actively engage in their care. The purpose of this study was to explore the perceptions of patients with TB regarding their engagement in health care. Patients and methods The study was conducted in three medical wards in one hospital. Purposive sampling was used to recruit participants. Semi-structured, audiotaped interviews were conducted and analyzed using thematic analysis. Results Twenty-three patients participated in the study. Four major themes emerged: 1) devaluing engagement; 2) interacting with health care providers (HCPs); 3) facing inability; and 4) seeking external support. Conclusion The patients’ perceptions of their engagement in health care were generally negative. Paying attention to the preferences and needs of patients and making decisions accordingly are effective strategies for promoting patient engagement. Moreover, HCPs should be aware of their crucial role in helping patients make sense of what engagement is and how to engage. In the process of engagement, providers should establish effective interactions with patients and cooperate with family and peers.
Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders

Key Points Question What are the associations between specific adolescent cognitive abilities and Alzheimer disease and related disorders in later life? Findings In this cohort study of 43 014 men and 42 749 women, lower adolescent memory for words, in women, and lower mechanical reasoning, in men, were associated with higher odds of Alzheimer disease and related disorders in later life. Meaning Low performance on certain specific measures of cognitive ability may indicate future risk of Alzheimer disease and related disorders as early as adolescence.
Constitutive IP3R1-mediated Ca2+ release reduces Ca2+ store content and stimulates mitochondrial metabolism in mouse GV oocytes

ABSTRACT In mammals, fertilization initiates Ca2+ oscillations in metaphase II oocytes, which are required for the activation of embryo development. Germinal vesicle (GV) oocytes also display Ca2+ oscillations, although these unfold spontaneously in the absence of any known agonist(s) and their function remains unclear. We found that the main intracellular store of Ca2+ in GV oocytes, the endoplasmic reticulum ([Ca2+]ER), constitutively ‘leaks’ Ca2+ through the type 1 inositol 1,4,5-trisphosphate receptor. The [Ca2+]ER leak ceases around the resumption of meiosis, the GV breakdown (GVBD) stage, which coincides with the first noticeable accumulation of Ca2+ in the stores. It also concurs with downregulation of the Ca2+ influx and termination of the oscillations, which seemed underpinned by the inactivation of the putative plasma membrane Ca2+ channels. Lastly, we demonstrate that mitochondria take up Ca2+ during the Ca2+ oscillations, mounting their own oscillations that stimulate the mitochondrial redox state and increase the ATP levels of GV oocytes. These distinct features of Ca2+ homeostasis in GV oocytes are likely to underpin the acquisition of both maturation and developmental competence, as well as fulfill stage-specific cellular functions during oocyte maturation. Summary: Mouse GV oocytes display spontaneous Ca2+ oscillations that reduce intracellular Ca2+ stores and stimulate mitochondrial metabolic output, maintaining cellular homeostasis during prolonged meiotic arrest.
Neoadjuvant chemotherapy reduces the expression rates of ER, PR, HER2, Ki67, and P53 of invasive ductal carcinoma

Abstract To analyze whether neoadjuvant chemotherapy (NAC) changes the expression rates of invasive ductal carcinoma (IDC) markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and P53. This was a retrospective study of 112 IDC patients who underwent NAC (docetaxel+epirubicin/pirarubicin+cyclophosphamide) but without pathological complete response (pCR) in 2012 to 2013 at the First Affiliated Hospital of Chongqing Medical University. The IDC subtypes and tumor protein markers were analyzed by immunohistochemistry (IHC). Specific changes in tumor protein markers before/after NAC were compared. The decrease in the positive rate of Ki-67 was the most significant, from 75.9% before NAC to 41.1% after NAC (P < .001). The positive rate of HER2 decreased from 42.0% before NAC to 32.1% after NAC (P = .04). The positive rate of ER decreased from 66.1% before NAC to 56.2% after NAC (P = .04). Increased number of metastatic lymph nodes (P = .006) and body mass index (BMI) (P = .028) seemed to be related to conversion of PR (positive to negative). There was statistical association between the Ki-67 (positive to negative) with the age greater or equal to 50 (P = .015). The BMI greater or equal to 24 (P = .021), age greater or equal to 50 (P = .047), and blood type A (P = .038) were independently associated with conversion of P53 (positive to negative). The BMI greater or equal to 24 (P = .004), number of metastatic lymph nodes greater or equal to 1 (P = .029) and TNM stages I–II (P = .008) were statistically associated with change of HER2 (positive to negative). In patients without pCR, NAC leads to changes in Ki-67, HER2, and hormone receptor (HR) expression. Age, BMI, number of metastatic lymph nodes, and TNM stage are associated with some changes of markers.
A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest

The Topo2a-dependent arrest is associated with faithful segregation of sister chromatids and has been identified as dysfunctional in numerous tumour cell lines. This genome-protecting pathway is poorly understood and its characterization is of significant interest, potentially offering interventional opportunities in relation to synthetic lethal behaviours in arrest-defective tumours. Using the catalytic Topo2a inhibitor ICRF193, we have performed a genome-wide siRNA screen in arrest-competent, non-transformed cells, to identify genes essential for this arrest mechanism. In addition, we have counter-screened several DNA-damaging agents and demonstrate that the Topo2a-dependent arrest is genetically distinct from DNA damage checkpoints. We identify the components of the SMC5/6 complex, including the activity of the E3 SUMO ligase NSE2, as non-redundant players that control the timing of the Topo2a-dependent arrest in G2. We have independently verified the NSE2 requirement in fibroblasts from patients with germline mutations that cause severely reduced levels of NSE2. Through imaging Topo2a-dependent G2 arrested cells, an increased interaction between Topo2a and NSE2 is observed at PML bodies, which are known SUMOylation hotspots. We demonstrate that Topo2a is SUMOylated in an ICRF193-dependent manner by NSE2 at a novel non-canonical site (K1520) and that K1520 sumoylation is required for chromosome segregation but not the G2 arrest.
Effect of Taekwondo Practice on Cognitive Function in Adolescents with Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neuro-developmental/behavioral disorders among adolescents. Sport and physical activity seem to play a major role in the development of cognition, memory, selective attention and motor reaction time, especially among adolescents with ADHD. In this context, the objective of this study was to investigate the effects of a one-and-a-half-year-long Taekwondo (TKD) intervention on cognitive function in adolescents with ADHD. Two cognitive instruments, namely the Stroop and the Ruff 2 and 7 tests, were administered to assess attentional inhibitory control and sustained and selective visual attention, respectively. Comparisons between the TKD and control groups at baseline did not reveal significant differences. For post-test scores, there were statistically significant differences on the Stroop color block test (large effect size or ES = 1.26 [95% confidence interval or CI 0.30–2.22]), the color-word interference test (large ES = 2.16 [95% CI 1.10–3.26]), the interference test (large ES = 1.63 [95% CI 0.62–2.64]) and error (large ES = −2.20 [95% CI −3.31 to −1.10]). Similar trends were reported for the Ruff 2 and 7 automated detection trials (large ES = 2.78 [95% CI 1.55–4.01]), controlled search trials (large ES = 2.56 [95% CI 1.38–3.75]) and total speed (large ES = −2.90 [95% CI −4.15 to −1.64]). In conclusion, TKD practice increased selective attention in adolescents with ADHD. Practitioners should implement martial art programs in their general plans to favorably influence attention and health in adolescents with ADHD.
Chemical Composition and Deposition Fluxes of Water-Soluble Inorganic Ions on Dry and Wet Deposition Samples in Wuhan, China

Measurement of PM2.5 concentration, dry and wet deposition of water-soluble inorganic ions (WSII) and their deposition flux was carried out. During sampling, a total number of 31 samples of PM2.5, five wet deposition samples and seven dry deposition samples were collected. The analyses results showed that the average concentration of PM2.5 was 122.95 µg/m3 whilst that of WSII was 51.63 µg/m3, equivalent to 42% of the total mass of PM2.5. The correlation coefficients between WSII in samples of PM2.5 was significant (r = 0.50 and p-value of 0.0019). Ions of SO42−, NO3−, Cl−, and NH4+ were dominant in the entire samples (PM2.5, dry and wet depositions), nevertheless, the average concentration of both SO42− and Cl− were below the China environmental quality standard for surface water. The ratio of dominant anions in wet deposition (SO42−/NO3−) was 1.59, whilst that for dry deposition (SO42−/Cl−) was 1.4, indicating that acidity was mainly derived from sulphate. In the case of dominant cations, the dry and wet deposition ratios (Ca2+/NH4+) were 1.36 and 1.37, respectively, suggesting the alkaline substances were mainly dominated by calcium salts. Days with higher recorded concentrations of PM2.5 were accompanied by dry and warm boundary layer structure, weak low-level wind and strong inversion layer.
Polysubstance addiction vulnerability in mental illness: Concurrent alcohol and nicotine self‐administration in the neurodevelopmental hippocampal lesion rat model of schizophrenia

Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain‐based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35‐60). Starting in adulthood (PD 63), rats acquired lever pressing for concurrent oral alcohol (10% with 2% sucrose) and iv nicotine (0.015 mg/kg/injection) across 15 sessions. Subsequently, 10 operant extinction sessions and 3 reinstatement sessions examined drug seeking upon withholding of nicotine, then both nicotine and alcohol, then reintroduction. Adolescent alcohol consumption did not differ between NVHLs and controls. However, in adulthood, NVHLs showed increased lever pressing at alcohol and nicotine levers that progressed more strongly at the nicotine lever, even as most pressing by both groups was at the alcohol lever. In extinction, both groups showed expected declines in effort as drugs were withheld, but NVHLs persisted with greater pressing at both alcohol and nicotine levers. In reinstatement, alcohol reaccess increased pressing, with NVHLs showing greater nicotine lever activity overall. Developmental temporal‐limbic abnormalities that produce mental illness can thus generate adult polydrug addiction vulnerability as a mechanism independent from putative cross‐sensitization effects between addictive drugs. Further preclinical modeling of third‐order (and higher) addiction‐mental illness comorbidities may advance our understanding and treatment of these complex, yet common brain illnesses.
Performance Characteristics of the Digital Biograph Vision PET/CT System

This study evaluated the performance of the Biograph Vision digital PET/CT system according to the NEMA NU 2-2012 standard (published by the National Electrical Manufacturers Association [NEMA]) to allow for a reliable, reproducible, and intersystem-comparable performance measurement. Methods: The new digital PET/CT system features silicon photomultiplier–based detectors with 3.2-mm lutetium oxyorthosilicate crystals and full coverage of the scintillator area. The PET components incorporate 8 rings of 38 detector blocks, and each block contains 4 × 2 mini blocks. Each mini block consists of a 5 × 5 lutetium oxyorthosilicate array of 3.2 × 3.2 × 20 mm crystals coupled to a silicon photomultiplier array of 16 × 16 mm, resulting in an axial field of view of 26.1 cm. In this study, PET/CT system performance was evaluated for conformation with the NEMA NU 2-2012 standard, with additional measurements described in the new NEMA NU 2-2018 standard. Spatial resolution, sensitivity, count-rate performance, accuracy of attenuation and scatter correction, image quality, coregistration accuracy, and time-of-flight performance were determined. Measurements were directly compared with results from its predecessor, the Biograph mCT Flow, using existing literature. Moreover, feasibility to comply with the European Association of Nuclear Medicine Research Ltd. (EARL) criteria was evaluated, and some illustrative patient PET images were obtained. Results: The Biograph Vision showed a transverse and axial spatial resolution of 3.6 and 3.5 mm, respectively, in full width at half maximum at a 1-cm offset from the center of the field of view (measured with a 22Na 0.25-mm point source), a NEMA sensitivity of 16.4 kcps/MBq, and a NEMA peak noise-equivalent count-rate of 306 kcps at 32 kBq/mL. Time-of-flight resolution varied from 210 to 215 as count-rate increased up to the peak noise-equivalent count-rate. The overall image contrast seen with the NEMA image quality phantom ranged from 77.2% to 89.8%. Furthermore, the system was able to comply with the current and future EARL performance criteria. Conclusion: The Biograph Vision outperforms the analog Biograph mCT Flow, and the system is able to meet European harmonizing performance standards.
The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential

OBJECTIVES To assess the ability of oxyclozanide to enhance tobramycin killing of Pseudomonas aeruginosa biofilms and elucidate its mechanism of action. METHODS Twenty-four hour biofilms formed by the P. aeruginosa strain PAO1 and cystic fibrosis (CF) isolates were tested for susceptibility to oxyclozanide and tobramycin killing using BacTiter-Glo™ and cfu. Biofilm dispersal was measured using crystal violet staining. Membrane potential and permeabilization were quantified using DiOC2(3) and TO-PRO-3, respectively. RESULTS Here we show that the ionophore anthelmintic oxyclozanide, combined with tobramycin, significantly increased killing of P. aeruginosa biofilms over each treatment alone. This combination also significantly accelerated the killing of cells within biofilms and stationary phase cultures and it was effective against 4/6 CF clinical isolates tested, including a tobramycin-resistant strain. Oxyclozanide enhanced the ability of additional aminoglycosides and tetracycline to kill P. aeruginosa biofilms. Finally, oxyclozanide permeabilized cells within the biofilm, reduced the membrane potential and increased tobramycin accumulation within cells of mature P. aeruginosa biofilms. CONCLUSIONS Oxyclozanide enhances aminoglycoside and tetracycline activity against P. aeruginosa biofilms by reducing membrane potential, permeabilizing cells and enhancing tobramycin accumulation within biofilms. We propose that oxyclozanide counteracts the adaptive resistance response of P. aeruginosa to aminoglycosides, increasing both their maximum activity and rate of killing. As oxyclozanide is widely used in veterinary medicine for the treatment of parasitic worm infections, this combination could offer a new approach for the treatment of biofilm-based P. aeruginosa infections, repurposing oxyclozanide as an anti-biofilm agent.
Might Oral Human Papillomavirus (HPV) Infection in Healthy Individuals Explain Differences in HPV-Attributable Fractions in Oropharyngeal Cancer? A Systematic Review and Meta-analysis

BACKGROUND Differences in oral human papillomavirus (HPV) prevalence and contrasts in HPV-attributable fractions (AFs) in oropharyngeal cancer (OPC) have not been evaluated in depth. METHODS A systematic review was performed to identify studies in which at least 50 healthy individuals were tested for oral HPV infection. Information on sex, age, tobacco/alcohol consumption, sex practices, specimen collection, HPV detection, and population type was extracted. Prevalences were pooled using random-effects models for meta-analyses of binomial data. Correlations were assessed by the Spearman test. RESULTS Forty-eight reports comprising 28 544 individuals fulfilled inclusion criteria. Global oral HPV prevalence was 4.9%. Estimates were highest in Europe, although regional differences were not statistically significant. HPV16 prevalence was 1.0% globally, and regional differences became statistically significant. A lifetime history of >6 sex partners showed a higher risk of oral HPV infection. The age-specific HPV distribution revealed a prevalence of ≥5% over 40 years of age and a lower prevalence at younger ages. There was no association between oral HPV prevalence and HPV-AFs or age-standardized rates (ASRs) of OPC, genital HPV in healthy women, or tobacco use. CONCLUSIONS Differences in HPV-AFs or ASRs of OPC cannot be explained by differences in the prevalence of oral HPV infection across healthy populations. Consistent research on determinants of oral HPV prevalence, acquisition, clearance, and persistence is warranted.
Bioprospecting of Native Efflux Pumps To Enhance Furfural Tolerance in Ethanologenic Escherichia coli

Lignocellulosic biomass, especially agricultural residues, represents an important potential feedstock for microbial production of renewable fuels and chemicals. During the deconstruction of hemicellulose by thermochemical processes, side products that inhibit cell growth and production, such as furan aldehydes, are generated, limiting cost-effective lignocellulose conversion. Here, we developed a new approach to increase cellular tolerance by expressing multidrug resistance (MDR) pumps with putative efflux activities for furan aldehydes. The developed plasmid library and screening methods may facilitate new discoveries of MDR pumps for diverse toxic chemicals important for microbial conversion. ABSTRACT Efficient microbial conversion of lignocellulose into valuable products is often hindered by the presence of furfural, a dehydration product of pentoses in hemicellulose sugar syrups derived from woody biomass. For a cost-effective lignocellulose microbial conversion, robust biocatalysts are needed that can tolerate toxic inhibitors while maintaining optimal metabolic activities. A comprehensive plasmid-based library encoding native multidrug resistance (MDR) efflux pumps, porins, and select exporters from Escherichia coli was screened for furfural tolerance in an ethanologenic E. coli strain. Small multidrug resistance (SMR) pumps, such as SugE and MdtJI, as well as a lactate/glycolate:H+ symporter, LldP, conferred furfural tolerance in liquid culture tests. Expression of the SMR pump potentially increased furfural efflux and cellular viability upon furfural assault, suggesting novel activities for SMR pumps as furfural efflux proteins. Furthermore, induced expression of mdtJI enhanced ethanol fermentative production of LY180 in the presence of furfural or 5-hydroxymethylfurfural, further demonstrating the applications of SMR pumps. This work describes an effective approach to identify useful efflux systems with desired activities for nonnative toxic chemicals and provides a platform to further enhance furfural efflux by protein engineering and mutagenesis. IMPORTANCE Lignocellulosic biomass, especially agricultural residues, represents an important potential feedstock for microbial production of renewable fuels and chemicals. During the deconstruction of hemicellulose by thermochemical processes, side products that inhibit cell growth and production, such as furan aldehydes, are generated, limiting cost-effective lignocellulose conversion. Here, we developed a new approach to increase cellular tolerance by expressing multidrug resistance (MDR) pumps with putative efflux activities for furan aldehydes. The developed plasmid library and screening methods may facilitate new discoveries of MDR pumps for diverse toxic chemicals important for microbial conversion.