Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanocarrier-based co-delivery approaches of chemotherapeutics with natural P-glycoprotein inhibitors in the improvement of multidrug resistance cancer therapy

Abstract Chemotherapy is the mainstay in cancer treatment; however, its application is clinically limited to patients with multidrug resistance (MDR). MDR reverses the role of chemotherapy through significant attribution to pharmacokinetic characteristics, where ATP-binding cassette transporter proteins, P-glycoprotein (P-gp), pump out the intracellularly transported chemotherapeutics from the cancer cells. Therefore, overexpression of such receptors on MDR cancer cell surfaces tends to decrease the efficacy of a large number of existing chemotherapeutics. P-gp inhibitors, especially of natural origin, play a vital role in enhancing the cellular concentration of clinically applicable chemotherapeutics. Therefore, co-administration of these natural P-gp inhibitors with chemotherapeutics could improve chemotherapeutic efficacy against MDR cancer, which has been evidenced in the literature. Co-delivery of these therapeutic components can effectively be made using the emerging nanotechnology platform, which could facilitate controlled delivery of the incorporated components to the cancerous microenvironment, through passive and active targeting. Thereby, cellular retention of chemotherapeutic agents by the P-gp mediated inhibitory effect on the efflux pump using the nanocarrier co-delivery platform could improve the anticancer potential of the chemotherapeutics. This review has presented the advancement of naturally occurring P-gp inhibitors as a promising adjuvant in chemotherapy to modulate the pharmacokinetic properties of chemotherapeutic agents using the nanotechnology platform.
Neuromolecular Etiology of Bipolar Disorder: Possible Therapeutic Targets of Mood Stabilizers

Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.
Anterior cruciate ligament reconstruction with lateral extra-articular tenodesis reduces knee rotation laxity and graft failure rate: A systematic review and meta-analysis

Purpose To determine whether the addition of lateral extra-articular tenodesis (LET) to anterior cruciate ligament reconstruction (ACLR) reduces rotational laxity of the knee, and to compare the clinical results of this treatment with those of ACLR alone. Methods PubMed, Embase, and Cochrane Library were searched by two researchers for clinical studies comparing ACLR with and without LET. Studies with only evidence levels I and II and studies in which anterior lateral ligament reconstruction was performed with grafts were excluded. The risk of bias of the studies was assessed using the Cochrane risk-of-bias and modified Downs & Black tools. The outcomes included (1) functional outcomes; (2) knee laxity measures; (3) knee injury osteoarthritis and outcome score; and (4) complications. The outcomes of the two groups were extracted, summarized and compared. Results A total of 234 studies were retrieved and 223 were excluded. Eleven clinical studies with 1745 patients were included in our meta-analysis. Compared to the patients who underwent ACLR alone, the patients who underwent ACLR with LET had reduced pivot-shift (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.31 to 0.74, p = 0.0009), and lower graft failure rate (OR 0.34, 95% CI 0.20 to 0.55, p < 0.0001). Conclusion Compared with ACLR only, ACLR combined with LET can effectively reduce rotation laxity of the knee joint, and reduce the graft failure rate in high-risk patients. However, the effects on the function and activity level of patients cannot be confirmed.
PEMBERIAN INTERVENSI MULLIGAN BENT LEG RAISE LEBIH BAIK DALAM MENURUNKAN NYERI FUNGSIONAL LOW BACK PAIN (LBP) NON-SPESIFIK DARI PADA PEMBERIAN INTERVENSI McKENZIE EXERCISE PADA BURUH ANGKUT BERAS DI DESA MENGESTA, TABANAN

Nyeri punggung bawah non-spesifik adalah nyeri punggung yang paling sering terjadi. Penelitian ini dilakukan untuk mengetahui apakah pemberian Mulligan Bent Leg Raise lebih baik dalam menurunkan nyeri fungsional punggung bawah non-spesifik dari pada McKenzie exercise pada buruh angkut beras di Desa Mengesta, Tabanan. Penelitian eksperimental dengan rancangan Pre and Post Test Control Group Design. Teknik pengambilan sampel adalah purposive sampling. Sampel merupakan 28 orang buruh angkut beras di Desa Mengesta dengan nyeri punggung bawah yang dipilih berdasarkan skor Modified Oswestry Low Back Pain Disability Questionnaire dengan nilai >20%. Rerata selisih penurunan skor nyeri fungsional LBP non-spesifik pada kelompok Mulligan Bent Leg Raise dan kelompok McKenzie Exercise diuji dengan Independent t-test dengan hasil yang bermakna p = 0,000 (p<0,05). Dengan demikian dapat disimpulkan bahwa pemberian intervensi Mulligan Bent Leg Raise lebih baik dalam menurunkan nyeri fungsional punggung bawah non-spesifik dari pada Pemberian McKenzie Exercise pada Buruh Angkut Beras di Desa Mengesta, Tabanan
Acetylation of CspC Controls the Las Quorum-Sensing System through Translational Regulation of rsaL in Pseudomonas aeruginosa

Bacterial infectious diseases impose a severe threat to human health. The ability to orchestrate virulence determinant in response to the host environment is critical for the pathogenesis of bacterial pathogens. Pseudomonas aeruginosa is a leading pathogen that causes various infections in humans. ABSTRACT Pseudomonas aeruginosa is a ubiquitous pathogenic bacterium that can adapt to a variety environments. The ability to effectively sense and respond to host local nutrients is critical for the infection of P. aeruginosa. However, the mechanisms employed by the bacterium to respond to nutrients remain to be explored. CspA family proteins are RNA binding proteins that are involved in gene regulation. We previously demonstrated that the P. aeruginosa CspA family protein CspC regulates the type III secretion system in response to temperature shift. In this study, we found that CspC regulates the quorum-sensing (QS) systems by repressing the translation of a QS negative regulatory gene, rsaL. Through RNA immunoprecipitation coupled with real-time quantitative reverse transcription-PCR (RIP-qRT-PCR) and electrophoretic mobility shift assays (EMSAs), we found that CspC binds to the 5′ untranslated region of the rsaL mRNA. Unlike glucose, itaconate (a metabolite generated by macrophages during infection) reduces the acetylation of CspC, which increases the affinity between CspC and the rsaL mRNA, leading to upregulation of the QS systems. Our results revealed a novel regulatory mechanism of the QS systems in response to a host-generated metabolite. IMPORTANCE Bacterial infectious diseases impose a severe threat to human health. The ability to orchestrate virulence determinant in response to the host environment is critical for the pathogenesis of bacterial pathogens. Pseudomonas aeruginosa is a leading pathogen that causes various infections in humans. In P. aeruginosa, the quorum-sensing (QS) systems play an important role in regulating the production of virulence factors. In this study, we find that a small RNA binding protein, CspC, regulates the QS systems by repressing the expression of a QS negative regulator. We further demonstrate that CspC is acetylated in response to a host-derived metabolite, itaconate, which alters the function of CspC in regulating the QS system. The importance of this work is in elucidation of a novel regulatory pathway that regulates virulence determinants in P. aeruginosa in response to a host signal.
Integration of Patient-reported Outcome Measures in Pediatric Hematology: A Qualitative Methods Study

Patient-reported outcome measures (PROMs) are self-reported questionnaires that allow patients and families to evaluate health-related experiences without influence or oversight from health care professionals. This study aimed to rate the relevance of existing PROMs for pediatric hematology patients, as identified by a recent systematic review, as well as to evaluate the receptivity of electronic PROM integration into clinical practice. Focus groups and interviews were conducted with children (10) and parents (19) impacted by nonmalignant hematological disorders, as well as with health care professionals (6). We observed strong support for the TranQol in thalassemia (100% for both parents [P] and children [C]); the Canadian Haemophilia Outcomes—Kids’ Life Assessment Tool (CHO-KLAT) (100% P, 75% C) and Haemophilia Quality of Life questionnaire (Haemo-QoL) (100% P and C) in hemophilia; the Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Module (75% P, 100% C); and the Kids ITP Tool in immune thrombocytopenia (100% P, 66.7% C). Generic tools such as the PedsQL Generic were met with mixed support. Electronic PROM integration received universal support. We obtained strong support for the integration of a web-based platform into clinical practice and a preference for disease-specific PROMs over generic PROMs. Future projects may explore the development of a child-friendly Canadian web-based platform to standardize quality-of-life evaluation within the clinical encounter.
Combination Therapy of an Antibody Specific for Transferrin Receptor 1 (ch128.1/IgG1) With Bortezomib or Lenalidomide Results in Increased Survival in an In Vivo Model of Human Multiple Myeloma: A Brief Communication

Transferrin receptor 1 (TfR1) is a universal cancer marker and a meaningful target for antibody-based immunotherapy. We previously developed a mouse/human chimeric antibody (ch128.1/IgG1) specific for the human TfR1 and reported that treatment of SCID-Beige mice bearing disseminated human multiple myeloma (MM) cells with ch128.1/IgG1 results in significant antitumor activity in early-stage and late-stage disease. Both bortezomib and lenalidomide are Food and Drug Administration (FDA) approved therapeutics used to treat MM in combination with other agents. Since combining treatments with different mechanisms of action is an effective antitumor strategy and given the relevance of bortezomib and lenalidomide in MM therapy, we decided to explore, for the first time, the combination of bortezomib or lenalidomide treatment with ch128.1/IgG1 within the context of late-stage MM disease. We found that treatment with a single dose of ch128.1/IgG1, or multiple doses of bortezomib or lenalidomide, used as single agents, results in significant antitumor activity in SCID-Beige mice bearing late-stage disseminated human MM.1S tumors. However, this antitumor activity is superior when ch128.1/IgG1 is combined with either bortezomib or lenalidomide, showing significantly longer survival compared with any therapy used alone. These novel results suggest that the combinations of ch128.1/IgG1 and bortezomib or lenalidomide are promising strategies against MM.
A commentary on soccer match-play simulations for applied research and practice

ABSTRACT Soccer is a fast-growing area of research, demonstrated by a 10-fold increase in the number of PubMed articles derived from the search term ‘soccer’ between 2001 and 2021. The scope of contemporary soccer-related articles ranges from match-play observations to laboratory evaluations of performance. The activity profile of soccer match-play is variable and techniques to collect data within matches are limited. Soccer-specific simulations have been developed to simulate the evolving demands of match-play. The evolutionary designs of novel simulations provide a reproducible exercise stimulus for varying researcher and practitioner objectives. The applied researcher can utilise simulations to investigate the efficacy of nutritional interventions and environmental stress on performance, while assessing the physiological and biomechanical responses to representations of match-play. Practitioners can adopt simulations for rehabilitation to progressively facilitate return-to-play processes, while implementing extra top-up conditioning sessions for unused and partial-match players. However, there are complexities involved with the selection of varying simulations which are dependent on the research question or practical application. There also remains a paucity of published information to support researchers and practitioners in selecting from differing simulation models. To assist with researcher and practitioner interpretations, we present a commentary of the current simulations to inform decision-making processes for research and training purposes and enhance the application of future research. An objective scoring system was adopted for rating the research and practical applications of each simulation design. Overall scores of 22, 16 and 18 out of 36 were revealed for free-running (n = 7), non-motorised- (n = 4) and motorised-treadmill-based simulations (n = 4), respectively.
Assessing Electronic Government Readiness of Public Organizations

Electronic Government (eGovernment) has rapidly become a political imperative at local, national and international level. Based on the perceived success realized by the private sector through information and communication technology (ICT) introduction, diffusion and adoption, governments around the world are becoming more and more interested in embracing ICT, and respectively have made a remarkable progress over the last few years. Once only regarded as a means for modernizing the public sector and increasing government productivity and efficiency, eGovernment is presently recognized as a driver and a key enabler of citizen-centric, cooperative, and seamless modern governance. This implies not only a profound transformation in the way government interacts with the governed but also the reinvention of its internal processes and how organizations carry their business both internally as well as externally with other segments of the community. Based on the literature, it is frequently claimed that the availability of an effective eGovernment assessment framework is a necessary condition for advancing eGovernment proper implementation. This paper aims to review some of the existing electronic readiness (eReadiness) and eGovernment readiness (EGR) frameworks, to identify the different aspects covered by both types, and to discuss to what extent they can really fulfill their intention in acting as guiding tools in the successful introduction and implementation of eGovernment. Based on this discussion, the paper concludes that such assessment tools are not suitable in assessing EGR over a micro level (i.e., a public organization). At the end, the paper presents the building blocks of an EGR assessment framework. These building blocks - categorized into four main dimensions: strategy, processes, technology, and people - cover all internal factors that should be addressed when setting an appraisal framework of eGovernment success on a public organization scale.
Blood serum levels of selected biomarkers of oxidative stress among printing workers occupationally exposed to low-levels of toluene and xylene

Printing workers (PWs) are exposed to a mixture of solvents, yet the health risks associated with such exposuer are unknown. This study aimed to compare the serum levels of selected biomarkers of oxidative stress among occupationally exposed PWs to low-level of toluene and xylenes and unexposed controls. Associations between levels of such biomarkers and occupational exposures to toluene and xylene were also investigated. Urinary levels of hippuric acid (HA) and methyl hippuric acids (MHAs) as exposure biomarkers of toluene and xylenes, respectively, and serum levels of oxidative stress biomarkers, including total antioxidant capacity (TAC), malondialdehyde (MDA), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were measured among the 84 subjects, comprising 44 PWs and 40 unexposed subjects. Mean concentrations of urinary HA and MHAs of PWs showed a significant increase compared with the unexposed controls. Although levels of urinary biomarkers of exposure to toluene (HA) and xylenes (MHAs) were well below the biological exposure indices (BEIs; ACGHI), PWs presented significantly increased serum levels of MDA, and significantly decreased serum activities of SOD and GPx compared to the unexposed controls. However, for serum TAC and CAT activity, no significant difference was observed between the two groups. Correlation analyses indicated that urinary levels of HA and MHAs were positively correlated with MDA levels and negatively correlated with GPx and SOD. Our study suggested that the alterations evidenced in serum levels of MDA, SOD, and GPx could be involved in the oxidative stress caused by co-exposure to low levels of toluene and xylene. Further investigation is needed to clarify the effect of low-level occupational exposure to solvents among PWs.
Recruitment Strategies to Engage Newcomer Mothers of African Descent in Maternal Mental Health Research in Canada

Introduction: Newcomer mothers of African descent are at risk for maternal mental stress because of inadequate social support, newcomer status, and stress of motherhood. Limited participation of newcomer African mothers in mental health research contributes to a knowledge gap in this area further impacting culturally competent health services. This article reports recruitment strategies to better engage African newcomer women in maternal mental health research. Methods: In-depth discussion of recruitment strategies, used in a qualitative descriptive study conducted with Black African newcomer mothers in Canada. Results: Ten African newcomer mothers were successfully recruited using recruitment strategies such as engagement with religious organizations, snowballing, and the use of social media. Discussion: Cultural beliefs on motherhood, resilience, and mental illness may account for hesitancy to engage in maternal mental health research. Recruitment strategies could help overcome the challenges and potentially diversify maternal mental health research in Canada through the engagement of African newcomer mothers.
Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes

The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. ABSTRACT The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS. Studies of borrelial tolerance/persistence in vitro in response to antimicrobials and experimental studies in mice and nonhuman primates, taken together with clinical reports, have revealed that B. burgdorferi becomes tolerant to antimicrobials and may sometimes persist in animals and humans after the currently recommended antimicrobial treatment. Moreover, B. burgdorferi is pleomorphic and can generate viable-but-nonculturable bacteria, states also involved in antimicrobial tolerance. The multiple regulatory pathways and structural genes involved in mediating this tolerance to antimicrobials and environmental stressors by persistence might include the stringent (rel and dksA) and host adaptation (rpoS) responses, sugar metabolism (glpD), and polypeptide transporters (opp). Application of this recently reported knowledge to clinical studies can be expected to clarify the potential role of bacterial antibacterial tolerance/persistence in Lyme disease and PTLDS.
A human coronavirus OC43‐derived polypeptide causes neuropathic pain

Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV‐OC43 p65‐like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP‐derived peptide exposure in the sciatic nerve produces pronociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV‐OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception‐, immune‐, and cellular energy‐related activities. Affinity capture shows the association of OC43p with an Na+/K+‐transporting ATPase, providing a potential direct target and mechanistic insight into virus‐induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV‐OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus‐induced neuropathic pain.
MOSFET'S 1/f Noise's Equivalent Capacity Model and the Switching Time Analysis

Aimed at the influence of the 1/f noise on the switching time of N-MOSFET, this article puts forward an equivalent capacity model of the 1/f noise. Based on this model, the paper tries to present a qualitative analysis of the effect exerted by 1/f noise to the switching time of MOSFET. Furthermore, the relationship between this capacitance and frequency exponent of 1/f noise was analysed. Finally, CoolMOS TM Power Transistor IPW60R045CP produced by Infineon is used to verify the analysis results and prove that the driving pulse frequency higher, the influence of 1/f noise on the switching time is weaker.
Taking Care of Intellectual Disabilities in the Era of COVID-19: Biological Substrates, Personalized Medicine and Counseling.

Giuseppe Marano1,2, Gianandrea Traversi3, Eleonora Gaetani4, Riccardo Daniele Pecora5,6, Alessandro Paris7, Salvatore Mazza1 & Marianna Mazza1* 1Institute of Psychiatry and Psychology, Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy, mariannamazza@hotmail.com, marianna.mazza@policlinicogemelli.it 2U.P. ASPIC Università Popolare del Counselling, Rome, Italy 3Department of Science, University of Rome “Roma Tre”, Rome, Italy 4Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy 5Associazione Italiana Psicologia Analitica, Rome, Italy 6International Association for Analytical Psychology 7Assistenza disabili Adulti e Anziani, ASL 1, Rome, Italy * correspondence author