Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression, Purification and Characterization of the Hepatitis E Virus Like-Particles in the Pichia pastoris

Hepatitis E virus (HEV) is associated with acute hepatitis disease, which may lead to chronic disease in immunocompromised individuals. The disease is particularly severe among pregnant women (20–30% mortality). The only licensed vaccine against HEV, which is available in China, is the Escherichia coli purified recombinant virus-like particles (VLPs) encompassing the 368–660 amino acids (aa) of the viral ORF2 protein. The viral capsid is formed by the ORF2 protein, which harbors three glycosylation sites. Baculo virus expression system has been employed to generate a glycosylated VLP, which encompasses 112–608aa of the ORF2 protein. Here, we sought to produce a recombinant VLP containing 112–608aa of the ORF2 protein in Pichia pastoris (P. pastoris) expression system. The cDNA sequence encoding 112–608aa of the ORF2 protein was fused with the α-mating factor secretion signal coding sequence (for release of the fusion protein to the culture medium) and cloned into the yeast vector pPICZα. Optimum expression of recombinant protein was obtained at 72 h induction in 1.5% methanol using inoculum density (A600) of 80 and at pH-3.0 of the culture medium. Identity of the purified protein was confirmed by mass spectrometry analysis. Further studies revealed the glycosylation pattern and VLP nature of the purified protein. Immunization of BALB/c mice with these VLPs induced potent immune response as evidenced by the high ORF2 specific IgG titer and augmented splenocyte proliferation in a dose dependent manner. 112–608aa ORF2 VLPs produced in P. pastoris appears to be a suitable candidate for development of diagnostic and prophylactic reagents against the hepatitis E.
Performance of and Factors Associated With Tuberculosis Screening and Diagnosis Among People Living With HIV: Analysis of 2012–2016 Routine HIV Data in Tanzania

People Living with HIV (PLHIV) should be screened for tuberculosis (TB) at every visit to the HIV care and treatment clinic (CTC), and those with positive results on screening should undergo further diagnostic investigations. We evaluated the performance of the TB diagnosis cascade among PLHIV attending CTC between January 2012 and December 2016 in three regions of Tanzania: Dar es Salaam, Iringa, and Njombe. We used descriptive epidemiology to evaluate performance and logistic regression to determine odds ratios (OR) for factors associated with TB screening and further TB diagnosis after positive TB screening. We analyzed 169,741 PLHIV who made 2,638,876 visits to CTC between January 2012 and December 2016. We excluded 2,074 (0.80%) visits as these involved PLHIV enrolled in CTC with a prior TB disease diagnosis. Of the 2,636,802 visits, 2,524,494 (95.67%) had TB screening according to national guidelines, of which 88,028 (3.49%) had TB screening positive results. Of the 88,028 visits with a positive TB screening, 27,810 (31.59%) had no records for further TB diagnosis following positive TB screening. Of all visits with positive TB screening, 32,986 (37.50%) had a TB disease diagnosis. On multivariate logistic regression, those who visited with World Health Organization (WHO) clinical stage four (aOR = 3.61, 95% CI 3.48–3.75, P < 0.001), enrolled in health center (aOR = 1.26, 95% CI 1.24–1.29, P < 0.001), enrolled in Iringa region (aOR = 1.54, 95% CI 1.50–1.57, P < 0.001), and enrolled in 2015 (aOR = 1.20, 95% CI 1.18–1.24, P < 0.001) were more likely to have no TB screening. Visits involving those who were of the female sex (aOR = 1.14, 95% CI 1.11–1.18, P < 0.001), enrolled in Njombe region (aOR = 4.36, 95% CI 4.09–4.65, P < 0.001), and enrolled in 2016 (aOR = 2.62, 95% CI 2.49–2.77, P < 0.001) were more likely to have no further TB diagnosis after positive TB screening. The study documented high performance of TB screening for PLHIV in HIV CTCs but a low transition of presumptive TB case undergoing further investigations. Better systems are needed for ensuring presumptive TB cases are diagnosed including using more efficient diagnostic methods like Gene pert.
Relationships Between Forced Oscillatory Impedance and 6-minute Walk Distance After Pulmonary Rehabilitation in COPD

Rationale Pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) reduces dyspnoea and improves exercise capacity and quality of life. The improvement in exercise capacity is variable and unpredictable, however. Respiratory system impedance obtained by forced oscillation technique (FOT) as a measure of ventilatory impairment in COPD may relate to improvement in exercise capacity with pulmonary rehabilitation. We aimed to determine if baseline FOT parameters relate to changes in exercise capacity following pulmonary rehabilitation. Methods At the start of rehabilitation, 15 COPD subjects (mean(SD) 75.2(6.1) years, FEV1 z-score −2.61(0.84)) had measurements by FOT, spirometry, plethysmographic lung volumes and 6-minute walk distance (6MWD). Respiratory system resistance (Rrs) and reactance (Xrs) parameters as the mean over all breaths (Rmean, Xmean), during inspiration only (Rinsp, Xinsp), and expiratory flow limitation (DeltaXrs = Xinsp−Xexp), were calculated. FOT and 6MWD measurements were repeated at completion of rehabilitation and 3 months after completion. Results At baseline, Xrs measures were unrelated to 6MWD. Xinsp improved significantly with rehabilitation (from mean(SD) −2.35(1.02) to −2.04(0.85) cmH2O.s. L−1, p=0.008), while other FOT parameters did not. No FOT parameters related to the change in 6MWD at program completion. Baseline Xmean, DeltaXrs, and FVC z-score correlated with the change in 6MWD between completion and 3 months after completion of rehabilitation (rs=0.62, p=0.03; rs=−0.65, p=0.02; and rs=0.62, p=0.03, respectively); with worse ventilatory impairment predicting loss of 6MWD. There were no relationships between Rrs parameters, FEV1 or FEV1/FVC z-scores and changes in 6MWD. Conclusion Baseline reactance parameters may be helpful in predicting those patients with COPD at most risk of loss of exercise capacity following completion of pulmonary rehabilitation.
Long Noncoding MAGI2-AS3 Suppresses Several Cellular Processes of Lung Squamous Cell Carcinoma Cells by Regulating miR-374a/b-5p/CADM2 Axis

Background Lung squamous cell carcinoma (LUSC) accounts for approximately 30% of all lung cancers that possesses the highest occurrence and mortality in all cancer types. Long noncoding RNAs have been reported to modulate tumor development for several decades. Aim of the Study This research aims to investigate the role of MAGI2-AS3 in LUSC. Methods RT-qPCR tested genes (including MAGI2-AS3, miR-374a/b-5p and CADM2) expression. Cell proliferation was detected by colony formation and EdU assays. Cell migration and invasion were evaluated by transwell assay. Flow cytometry analysis of apoptotic cells and Western blot analysis on apoptosis-related genes were applied to measure cell apoptosis. Nuclear-cytoplasmic fractionation and FISH assay positioned MAGI2-AS3. The combination between miR-374a/b-5p and MAGI2-AS3 (or CADM2) was determined by luciferase reporter assay and RIP assay. Results MAGI2-AS3 inhibited the proliferative, migratory and invasive capability of LUSC cells with upregulated expression. Additionally, MAGI2-AS3 overexpression promoted cell apoptosis. We discovered that MAGI2-AS3 was located in the cytoplasm. Hereafter, we found out that MAGI2-AS3 targeted miR-374a/b-5p. CADM2 was targeted by miR-374a/b-5p. Finally, rescue assays indicated that the promoting effects of miR-374a/b-5p amplification on biological activities were restored by CADM2 addition. Conclusion In conclusion, lncRNA MAGI2-AS3 suppressed LUSC by regulating miR-374a/b-5p/CADM2 axis, which might potentially serve as a therapeutic marker for LUSC patients.
pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy

Background Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT. Materials and Methods The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 μg/mL), (2) NDs (30 μg/mL), (3) PTX-loaded NDs (34 μg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT. Results The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (<300 nm with PDI<0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT. Conclusion The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.
Prevalence of Myopia in Newly Enlisted Airmen at Joint Base San Antonio

Purpose Myopia is the most common type of refractive error and can lead to significant visual impairment. The frequency of myopia has risen considerably, and its worldwide prevalence is expected to continue to increase. Myopia is present in an increasing number of Basic Military Trainees upon entry into the United States Air Force. This study aims to demonstrate the prevalence of myopia in newly enlisted members of the United States Air Force. Methods This study is an institutional retrospective analysis of data collected from the United States Air Force candidates entering Basic Military Training from 1 January 2017 to 31 March 2017. A random selection of 767 Air Force Basic Military Trainees were included in the analysis, yielding 1534 total eyes. The primary outcome measure studied is the mean spherical equivalent (MSE) of participants at initial evaluation. A linear regression analysis was performed to identify any associations related to participant demographics. Results Of participants analyzed, 45% had myopia (<−0.5 D) and 2% high myopia (<−6.0 D) upon entry into the United States Air Force. Myopia was found to be associated with male gender (p = <0.001). Conclusion Myopia is present in a significant proportion of Basic Military Trainees upon entry into the United States Air Force, regardless of age, gender, race, or ethnicity. The prevalence of myopia presented is higher than previous studies, reflecting a continued trend towards increased myopia prevalence worldwide.
Specific Measures of Quality of Life in Patients with Multimorbidity in Primary Healthcare: A Systematic Review on Patient-Reported Outcome Measures’ Adequacy of Measurement

Purpose The aim of this study is to search systematically for Patient Reported Outcome Measures (PROMs) used among patients with multimorbidity. Furthermore, the aim is to evaluate the adequacy and validity of the PROMs identified. Design and setting This systematic review follows the PRISMA guidelines. To assess the adequacy and validity of the identified PROMs the COSMIN Risk of Bias Checklist is used, more specifically a validation of the development, content validity, structural validity, and internal consistency of the PROMs. Results Four PROMs were identified in the primary search, and one was found from references. The sixth PROM was published after the primary search. None of the identified PROMs were aimed specifically at measuring the quality of life in patients with multimorbidity. According to the checklist, the development process and content validity were rated “adequate” in only one measure and “invalid”/“doubtful”/“inadequate” in the rest of the measures. The structural validity of the measures was rated “adequate” in four measures and “very good” in one. Regarding the internal consistency, two measures were rated doubtful and three “very good”. None of the six PROMs reported analyses about invariant measurement. The COSMIN Risk of Bias Checklist proved easy to use; however, there are some concerns in the rating of bias, that are discussed further. Conclusion All six PROMs developed for patients with multimorbidity identified possessed inadequacy in their measurement properties. Therefore, the aim for the future is to develop a valid and adequate measure of the quality of life among patients with multimorbidity.
TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells

Background and aim Ewing sarcoma (ES) is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. In the current study, we were aiming to investigate the function of TRIM3 in autophagy in ES cells. Methods The expression of TRIM3 in Ewing sarcoma tissues and normal tissues was examined by quantitative PCR and western blot. The effect of TRIM3 on autophagy was detected by western blot and immunoﬂuorescence assay. Target of TRIM3 was examined by western blot, immunoprecipitation and ubiquitination assay. Results We found the expression of TRIM3 was significantly up-regulated in Ewing sarcoma tissues compared with normal tissues, and this phenomenon was regulated by EWS-FLI1 expression. Furthermore, we observed that overexpression of TRIM3 markedly and consistently inhibited autophagy in ES cells, and autophagy was enhanced in TRIM3-silenced ES cells. Finally, we found in ES cells, TRIM3 could directly interact with Beclin1, and improved its K48-linked polyubiquitinaion, leading to the degradation of Beclin1 and then regulated autophagy. Conclusion In the present research, for the first time we revealed that TRIM3 negatively regulates autophagy through promoting degradation of Beclin1 in Ewing sarcoma cells, and these findings may provide ideas for ES research.
Dioscin Inhibited Glycolysis and Induced Cell Apoptosis in Colorectal Cancer via Promoting c-myc Ubiquitination and Subsequent Hexokinase-2 Suppression

Purpose Dioscin is a natural product isolated from traditional Chinese medicines and is reported to have antitumor activities against several cancers. In the present study, we aimed to investigate its potency against colorectal cancers, especially the effects on tumor glycolysis, and to elaborate related molecular mechanisms. Methods The antitumor activities of dioscin were evaluated by cell proliferation assays and colony formation assays in vitro and the mouse xenograft models in vivo. The effects of dioscin on tumor glycolysis were determined by measuring glucose absorption and lactate generation. Cell apoptosis was detected by cleaved PARP and the activity of caspase-3. Protein overexpression or gene knockdown was conducted to illustrate molecular mechanisms. Immunoprecipitation experiments were applied to identify the interaction between different proteins. Results Dioscin substantially inhibited colorectal cancer cell proliferation in vitro and suppressed the xenograft growth in nude mice. After dioscin treatment, with the suppression of hexokinase-2, the tumor glycolysis was significantly decreased. Dioscin substantially impaired the interaction between hexokinase-2 and VDAC-1, and induced cell apoptosis. Exogenous overexpression of hexokinase-2 significantly antagonized the glycolysis suppression and apoptosis induction by dioscin. Through enhancing the binding of E3 ligase FBW7 to c-myc, dioscin promoted the ubiquitination of c-myc and gave rise to c-myc degradation, which contributed to the inhibition of hexokinase-2. Conclusion Our studies revealed a novel mechanism by which dioscin exerted its antitumor activity in colorectal cancer, and verified that dioscin or its analog might have potentials for colorectal cancer therapy.
Correlation Analysis Between Preoperative Serum Iron Level and Prognosis as Well as Recurrence of HCC After Radical Resection

Background The purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC). Methods A total of 253 HCC patients who underwent radical resection were involved in this study. Results According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p < 0.001). The recurrence rate of patients in the low iron group was higher than that in the high iron group (p = 0.011). Correlation analysis showed that preoperative serum iron level was correlated with tumor size >5 cm (χ2 = 11.590, p < 0.001), recurrence (χ2 = 5.714, p = 0.017) and microvascular invasion (χ2 = 5.087, p = 0.024). In addition, univariate analysis showed that OS and disease-free survival (DFS) of HCC patients with high iron level were better than those with low iron level. Furthermore, multivariate COX proportional hazards regression analysis showed that serum iron ≤94 μg/dL, tumor size >5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS. Conclusion Patients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.
Baerveldt Glaucoma Implant versus Ahmed Glaucoma Implant in a One-Year Follow Up, Comparative Study

Aim To compare clinical outcomes between Ahmed glaucoma implant (AGV-S2 and FP7 models) and Baerveldt–350 glaucoma implant (BGI). Design Prospective randomized study. Methods and subjects Eighty-one participants with glaucoma after ocular surgery or secondary glaucoma with persistent and uncontrolled IOP > 21 mmHg were randomized for placement of BGI or AGV models using a standardized surgical technique. The primary outcome was failure, which was defined as IOP >16 mmHg with glaucoma medication, on 2 consecutive study visits. Secondary outcomes were IOP, medication use, visual acuity, complications, and interventions. Results At one-year follow up, the mean IOP was 14.76±2.5 mmHg in BGI group and 16.57±3.35 mmHg in AGV group (P=0.015). The mean number of glaucoma medications in use was 1.6±0.81 in the BGI group and 3.91±0. 0.28 in the AGV group (P <0.001). There was 1.81 mmHg difference in the mean IOP between participants in both groups with 0.85 SD difference. At 12 months, the failure rate was 11/56 (19.67%) in AGV group and 3/25 (12%) in BGI group (P=0.352). The VA was stable in 77% in the BGI group (P=0.93) versus 80% of patients in AGV group (P=0.88). No significant change was observed in logMAR Snellen VA between both groups (P=0.254). None of the patients lost light perception. Conclusion Both the Ahmed valve implant and the Baerveldt implant are effective in reducing preoperative IOP and glaucoma medications in patients with refractory glaucoma. This trial cannot give clear clinical proof for valve superiority over the other. The Baerveldt-350 implant can be a good choice for refractory glaucoma cases. Capsular scarring around the plate is considered as the main factor for surgical failure and resistant IOP. Trial registration The trial was registered with the Research Ethical Committee, Ain Shams University, FWA 000017585 FMASU 21/2017, and registered at Clinical Trial. gov: NCT04215575.
Regeneration of Denervated Skeletal Muscles – Brunelli’s CNS-PNS Paradigm

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians’ understanding of Brunelli’s spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry. The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation. A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed. After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude. Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae. Brunelli’s concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin. Brunelli’s CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.
Do follicles matter? Testing the effect of follicles on hair cortisol levels

To determine the potential influence of hair follicles on cortisol levels, we conducted an experiment comparing cortisol concentrations in paired subsamples of brown bear hair with and without follicles. We found significantly greater cortisol values in subsamples that included follicles, suggesting that the presence of follicles may influence cortisol concentrations measured in hair. Our findings underscore the importance of standardizing hair collection and preparation methods to enable comparisons across studies.