Miracle-dz/UniFAR-FTUs huggingface dataset:
Three YXXL Sequences of a Bovine Leukemia Virus Transmembrane Protein are Independently Required for Fusion Activity by Controlling Expression on the Cell Membrane

Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia viruses, is the causative agent of enzootic bovine leukosis, the most common neoplastic disease of cattle. The transmembrane subunit of the BLV envelope glycoprotein, gp30, contains three completely conserved YXXL sequences that fit an endocytic sorting motif. The two N-terminal YXXL sequences are reportedly critical for viral infection. However, their actual function in the viral life cycle remains undetermined. Here, we identified the novel roles of each YXXL sequence. Syncytia formation ability was upregulated by a single mutation of the tyrosine (Tyr) residue in any of the three YXXL sequences, indicating that each YXXL sequence is independently able to regulate the fusion event. The alteration resulted from significantly high expression of gp51 on the cell surface, thereby decreasing the amount of gp51 in early endosomes and further revealing that the three YXXL sequences are independently required for internalization of the envelope (Env) protein, following transport to the cell surface. Moreover, the 2nd and 3rd YXXL sequences contributed to Env protein incorporation into the virion by functionally distinct mechanisms. Our findings provide new insights regarding the three YXXL sequences toward the BLV viral life cycle and for developing new anti-BLV drugs.
Photoelectrocatalytic Hydrogen Generation Enabled by CdS Passivated ZnCuInSe Quantum Dot-Sensitized TiO2 Decorated with Ag Nanoparticles

Here we present the photoelectrocatalytic hydrogen generation properties of CdS passivated ZnCuInSe (ZCISe) quantum dots (QDs) supported by TiO2 nanowires decorated with Ag nanoparticles. In this configuration, Ag nanoparticles were sandwiched between the photo-electrons collector (TiO2) and photo-sensitizers (ZCISe), and acted as an electron relay speeding up the charge carrier transport. ZCISe and CdS enabled the optical absorption of the photoelectrode ranging from ultraviolet to near infrared region, which significantly enhanced the solar-to-chemical energy conversion efficiency. A photocurrent of 10.5 mA/cm2 and a hydrogen production rate of about 52.9 μmol/h were achieved under simulated sunlight (1.5 AG).
Dual-functionalized liposome by co-delivery of paclitaxel with sorafenib for synergistic antitumor efficacy and reversion of multidrug resistance

Abstract Multidrug resistance (MDR) remains one of the major reasons for inefficiency of many chemotherapeutic agents in cancer therapy. In this study, a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and polylysine-deoxycholic acid copolymer (PLL-DA) co-modified cationic liposome coating with hyaluronic acid (HA) was constructed for co-delivery of paclitaxel (PTX) and chemosensitizing agent, sorafenib (SOR) to treat the MDR cancer. The multifunctional liposome (HA-TPD-CL-PTX/SOR) presented good stability against rat plasma and was capable of reversing surface zeta potential under acidic conditions in the presence of HAase. Additionally, experimental result confirmed that the PLL-DA copolymer would facilitate the endo-lysosomal escape of the liposome. In vitro study demonstrated that HA-TPD-CL-PTX/SOR could significantly enhance drug accumulation in resistant MCF-7/MDR cells by inhibiting the P-gp efflux, and effectively inhibited growth of tumor cells. Furthermore, the liposome showed an enhanced anticancer activity in vivo, with a tumor growth inhibition rate of 78.52%. In summary, HA-TPD-CL-PTX/SOR exhibited a great potential for effective therapy of resistant cancers by combining with chemotherapeutic agents and could be a promising nano-carrier for reversing MDR and improving the effectiveness of chemotherapy.
Transcriptional Analysis Shows a Robust Host Response to Toxoplasma gondii during Early and Late Chronic Infection in Both Male and Female Mice

The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. ABSTRACT The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased at 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females had far fewer genes that were significantly less abundant, which may have led to the slightly increased cyst burden in males. Transcripts for C-X-C motif chemokine ligand 13 and a C-C motif chemokine receptor 2 (CCR2) were significantly higher in females than in males during infection. As T. gondii chronic infection and profilin (PRF) confer resistance to Listeria monocytogenes infection in a CCR2-dependent manner, the differences in CCR2 expression led us to retest the protection of PRF in both sexes. Male mice were nearly as effective as female mice at reducing the bacterial burden either with a chronic infection or when treated with PRF. These data show that most of the host genes differentially expressed in response to T. gondii infection are similar between males and females. While differences in transcript abundance exist between the sexes, the infection phenotypes tested here did not show significant differences.
Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.
Diabetes and elevated preoperative HbA1c level as risk factors for postoperative delirium after cardiac surgery: an observational cohort study

Introduction Postoperative delirium (POD) is a common complication of cardiac surgery associated with increased mortality, morbidity, and long-term cognitive dysfunction. Diabetic patients, especially those with poor diabetes control and long-standing hyperglycemia, may be at risk of developing delirium. The aim of this study was to analyze whether the occurrence of POD in cardiac surgery is associated with diabetes or elevated preoperative glycated hemoglobin (HbA1c) level. Materials and methods We performed a cohort analysis of prospectively collected data from a register of cardiac surgery department of a university hospital. Delirium assessment was performed twice a day during the first 5 days after the operation based on Diagnostic Statistical Manual of Mental Disorders, fifth edition criteria. Results We analyzed a cohort of 3,178 consecutive patients, out of which 1,010 (31.8%) were diabetic and 502 (15.8%) were diagnosed with POD. Patients with delirium were more often diabetic (42.03% vs 29.86%, P<0.001) and on oral diabetic medications (34.66% vs 24.07%, P<0.001), no difference was found in patients with insulin treatment. Preoperative HbA1c was elevated above normal (≥6%) in more delirious than nondelirious patients (44.54% vs 33.04%, P<0.001), but significance was reached only in nondiabetic patients (20.44% vs 14.86%, P=0.018). In univariate analysis, the diagnosis of diabetes was associated with an increased risk of developing POD (OR: 1.703, 95% CI: 1.401–2.071, P<0.001), but only for patients on oral diabetic medications (OR: 1.617, 95% CI: 1.319–1.983, P<0.001) and an association was noted between HbA1c and POD (OR: 1.269, 95% CI: 1.161–1.387, P<0.001). Multivariate analysis controlled for diabetes showed that POD was associated with age, heart failure, preoperative creatinine, extracardiac arteriopathy, and preoperative HbA1c level. Conclusion More diabetic patients develop POD after cardiac surgery than nondiabetic patients. Elevated preoperative HbA1c level is a risk factor for postcardiac surgery delirium regardless of the diagnosis of diabetes.
Estimating the Parameters of Fitzhugh–Nagumo Neurons from Neural Spiking Data

A theoretical and computational study on the estimation of the parameters of a single Fitzhugh–Nagumo model is presented. The difference of this work from a conventional system identification is that the measured data only consist of discrete and noisy neural spiking (spike times) data, which contain no amplitude information. The goal can be achieved by applying a maximum likelihood estimation approach where the likelihood function is derived from point process statistics. The firing rate of the neuron was assumed as a nonlinear map (logistic sigmoid) relating it to the membrane potential variable. The stimulus data were generated by a phased cosine Fourier series having fixed amplitude and frequency but a randomly shot phase (shot at each repeated trial). Various values of amplitude, stimulus component size, and sample size were applied to examine the effect of stimulus to the identification process. Results are presented in tabular and graphical forms, which also include statistical analysis (mean and standard deviation of the estimates). We also tested our model using realistic data from a previous research (H1 neurons of blowflies) and found that the estimates have a tendency to converge.
Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine

Fast diagnosis and more efficient therapies for cancer surely represent one of the huge tasks for the worldwide researchers’ and clinicians’ community. In the last two decades, our understanding of the biology and molecular pathology of cancer mechanisms, coupled with the continuous development of the material science and technological compounds, have successfully improved nanomedicine applications in oncology. This review argues on nanomedicine application of engineered extracellular vesicles (EVs) in oncology. All the most innovative processes of EVs engineering are discussed together with the related degree of applicability for each one of them in cancer nanomedicines.
Offline Authentication Scheme based on Blockchain Technology for Smart Lock

Driven by the technology of mobile Internet of things and the wide demand of sharing economy, the development of smart locks is changing with each passing day. Current schemes rely on the open network architecture which has security vulnerabilities, privacy leaks, vulnerability to various attacks and other security risks. We propose an end-to-end succinct non-interactive offline authentication scheme based on blockchain technology(BC-SNOA). Using blockchain techniques such as anonymity, ellipticcurve cryptography, workload consensus, and privacy-preserving zero-knowledge proof, the BC-SNOA implements one-time pad to improve confidentiality, offline authentication to avoid network remote intrusions and the risk of network services interruptions. It is difficult to replicate and crack because of the in chip calculation of workloads and mathematical problems. Compared with current smart locks which extract biometric verification information and control by network services, the BC-SNOA scheme is likely to accomplish beneficial properties such as high verification performance and more secure, and also makes simple hardware implementations possible.
Gaussian Mixture PHD Filter with Measurement-labelled Adaptive Target Birth Intensity

The Gaussian mixture probability hypothesis density (GMPHD) filter is an efficient and real-time method for estimating multiple target states with varying target number in clutter. However, the main drawback of this method is that the target birth intensity is known as a priori. In other words, the GMPHD filter is inapplicable to the tracking scenario with no priori spatial information on where targets can appear. To address this limitation, a measurement-labelled adaptive target birth intensity for GMPHD filter is proposed in this paper. All key equations of this proposed method are derived, and a multi-target tracking scenario is designed to demonstrate the performance of the proposed method. Simulation results suggest that the measurement-labelled method is an effective and efficient solution to target birth intensity adaptive problem.
Complexity, cost, and content – three important factors for translation of clinical protein mass spectrometry tests, and the case for apolipoprotein C-III proteoform testing

Abstract Complexity, cost, and content are three important factors that can impede translation of clinical protein mass spectrometry (MS) tests at a larger scale. Complexity stems from the many components/steps involved in bottom-up protein MS workflows, making them significantly more complicated than enzymatic immunoassays (EIA) that currently dominate clinical testing. This complexity inevitably leads to increased costs, which is detrimental in the price-competitive clinical marketplace. To successfully compete, new clinical protein MS tests need to offer something new and unique that EIAs cannot – a new content of proteoform detection. The preferred method for proteoform profiling is intact protein MS analysis, in which all proteins are measured as intact species thus allowing discovery of new proteoforms. To illustrate the importance of intact proteoform testing with MS and its potential clinical implications, we discuss here recent findings from multiple studies on the distribution of apolipoprotein C-III proteoforms and their correlations with key clinical measures of dyslipidemia. Such studies are only made possible with assays that are low in cost, avoid unnecessary complexity, and are unique in providing the content of proteoforms.
Validation of the GenoType® MTBDRplus Ver 2.0 assay for detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis complex isolates at UZCHS-CTRC TB research laboratory

Background: Multidrug-resistant tuberculosis (MDR-TB) is a public health concern globally. MDR-TB is defined as resistance to rifampicin (RIF) and isoniazid (INH), the two-major anti-TB first-line TB treatment drugs. Rapid identification of MDR-TB can contribute significantly to the control of TB. The GenoType® MTBDRplus Ver 2.0 assay is a molecular assay used to detect genetic mutations that result in RIF and INH resistance. The aim of this study was to validate the performance of the GenoType® MTBDRplus Ver 2.0 assay for the detection of INH and RIF resistance. Methods: Fifty-five stored Mycobacterium tuberculosis isolates were tested using both the mycobacterial growth indicator tube (MGIT), antimicrobial susceptibility testing (AST), and the GenoType® MTBDRplus Ver 2.0 assay. The MGIT AST was done according to the BBL MGIT AST SIRE system with RIF and INH final critical concentrations of 1.0 μg/ml and 0.1 μg/ml, respectively. The GenoType® MTBDRplus assay (Hain Lifescience, Germany) was performed following the manufacturer's instructions. Results: The GenoType® MTBDRplus Ver 2.0 assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 100% for INH and RIF resistance. The intra-assay precision for the assay was 100%. Conclusion: The GenoType® MTBDRplus Ver 2.0 assay's sensitivity and specificity show that the assay is highly accurate for the detection of RIF and INH resistance and thus can be used as an alternate platform due to its shorter results turnaround time.
Implicit Attitudes About Agricultural and Aquatic Products From Fukushima Depend on Where Consumers Reside

Japanese consumers are still hesitant to purchase products from Fukushima, although 7 years have passed since the Fukushima nuclear disaster, and these products are officially considered safe. In this study, we examined whether Japanese consumers have negative implicit attitudes toward agricultural and aquatic products from the Fukushima region and whether these attitudes are independent of their explicit attitudes. Japanese students completed an implicit association test and a questionnaire to assess their implicit and explicit attitudes toward products from Fukushima relative to another region. The results of two experiments reliably demonstrated that the public has negative implicit attitudes toward Fukushima products, whereas their explicit attitudes are consistently positive. These observations predominantly held for participants living close to Fukushima (Tokyo) as opposed to participants living far away (Hiroshima): Experiment 1 (n = 40). Furthermore, individual differences in aversion to germs contributed to the implicit attitudes; the implicit negative attitudes were attenuated among the participants with a relatively low aversion to germs: Experiment 2 (n = 60). These results suggest that the implicit attitudes associated with the behavioral immune system, which is conceptualized as a suite of psychological mechanisms designed to proactively resist pathogenic threats, may underlie the hesitation to purchase products from Fukushima.
The effectiveness of physiotherapy interventions on pain and quality of life in adults with persistent post-surgical pain compared to usual care: A systematic review

Background Persistent post-surgical pain (PPSP) is a common condition following surgery, resulting in persistent pain and reduced quality of life (QoL). While pharmacological management is common, its effectiveness remains equivocal. This systematic review investigated the effectiveness of physiotherapy management in adults with PPSP in comparison to usual care. Methods A systematic search of six electronic databases was conducted. Studies of human adults (>18 years) with PPSP localised or directly referred from the surgical site, pain persisting for at least two months post-surgery and with physiotherapy as the intervention were included. This review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The McMaster critical review form for quantitative studies was utilised to assess the methodological quality. A descriptive synthesis was undertaken due to the heterogeneity of the included studies. Results Of the 1395 articles that were screened, eight studies met the inclusion criteria. A diverse range of physiotherapy interventions were utilised, and effectiveness was measured through diverse outcomes and measures. Summarised findings from the heterogenous evidence base indicated that physiotherapy interventions for PPSP has a positive impact across a range of outcomes, including pain, quality of life (QoL), physical function and depression. While these are encouraging findings, the current evidence base lacks uniformity with regards to participant characteristics, time periods since diagnosis, interventions delivered, and its parameters, and outcomes measured. Conclusion Due to ongoing challenges in the management of PPSP, alternate treatment strategies such as physiotherapy are being trialled. Despite a number of methodological constraints, current evidence indicates that physiotherapy could play a role in the management of PPSP. PROSPERO registration CRD42019129580
Overexpression of SH2-Containing Inositol Phosphatase Contributes to Chronic Lymphocytic Leukemia Survival

Key Points B cell–specific deletion of Ship2 phosphatase reduces CLL formation in a mouse model. Ship2 inhibition reduces Akt/mTORC1/S6 signaling in murine and human CLL cells. Ship2 supports survival of CLL cells via the key antiapoptotic protein Mcl-1. Balanced activity of kinases and phosphatases downstream of the BCR is essential for B cell differentiation and function and is disturbed in chronic lymphocytic leukemia (CLL). In this study, we employed IgH. TEμ mice, which spontaneously develop CLL, and stable EMC CLL cell lines derived from these mice to explore the role of phosphatases in CLL. Genome-wide expression profiling comparing IgH. TEμ CLL cells with wild-type splenic B cells identified 96 differentially expressed phosphatase genes, including SH2-containing inositol phosphatase (Ship2). We found that B cell–specific deletion of Ship2, but not of its close homolog Ship1, significantly reduced CLL formation in IgH. TEμ mice. Treatment of EMC cell lines with Ship1/2 small molecule inhibitors resulted in the induction of caspase-dependent apoptosis. Using flow cytometry and Western blot analysis, we observed that blocking Ship1/2 abrogated EMC cell survival by exerting dual effects on the BCR signaling cascade. On one hand, specific Ship1 inhibition enhanced calcium signaling and thereby abrogated an anergic response to BCR stimulation in CLL cells. On the other hand, concomitant Ship1/Ship2 inhibition or specific Ship2 inhibition reduced constitutive activation of the mTORC1/ribosomal protein S6 pathway and downregulated constitutive expression of the antiapoptotic protein Mcl-1, in both EMC cell lines and primary IgH. TEμ CLL cells. Importantly, also in human CLL, we found overexpression of many phosphatases including SHIP2. Inhibition of SHIP1/SHIP2 reduced cellular survival and S6 phosphorylation and enhanced basal calcium levels in human CLL cells. Taken together, we provide evidence that SHIP2 contributes to CLL pathogenesis in mouse and human CLL.