Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of an active break and postural shift intervention on preventing neck and low-back pain among high-risk office workers: a 3-arm cluster-randomized controlled trial

Objective: This study evaluated the effects of the promotion of active breaks and postural shifts on new onset of neck and low-back pain during a 6-month follow-up among high-risk office workers. Methods: A 3-arm cluster-randomized controlled trial with 6-month follow-up was conducted among healthy but high-risk office workers. Participants were recruited from six organizations in Bangkok, Thailand (N=193) and randomly assigned at cluster level into active break intervention (N=47), postural shift intervention (N=46), and control (N=100) groups. Participants in the intervention groups received a custom-designed apparatus to facilitate designated active breaks and postural shifts during work. Participants in the control group received a placebo seat pad. The primary outcome measure was new onset of neck and low-back pain during 6-month follow-up. Analyses were performed using Cox proportional hazard models. Results: One-hundred and eighty-six (96%) predominantly female participants were successfully followed up over six months. New onset of neck pain during the 6-month follow-up occurred in 17%, 17%, and 44% of the participants in the active break, postural shift, and control groups, respectively. For new onset of low-back pain, these percentages were 9%, 7%, and 33%, respectively. Hazard rate (HR) ratios after adjusting for biopsychosocial factors indicated a protective effect of the active break and postural shift interventions for neck pain [HRadj 0.45, 95% confidence interval (CI) 0.20–0.98 for active break and HRadj 0.41, 95% CI 0.18–0.94 for postural shift] and low-back pain (HRadj 0.34, 95% CI 0.12–0.98 for active break and HRadj 0.19, 95% CI 0.06–0.66 for postural shift). Conclusion: Interventions to increase either active breaks or postural shifts reduced new onset of neck and low-back pain among high-risk office workers.
Cellular Uptake of the ATSM−Cu(II) Complex under Hypoxic Conditions

Abstract The Cu(II)‐diacetyl‐bis (N4‐methylthiosemicarbazone) complex (ATSM−Cu(II)) has been suggested as a promising positron emission tomography (PET) agent for hypoxia imaging. Several in‐vivo studies have shown its potential to detect hypoxic tumors. However, its uptake mechanism and its specificity to various cancer cell lines have been less studied. Herein, we tested ATSM−Cu(II) toxicity, uptake, and reduction, using four different cell types: (1) mouse breast cancer cells (DA‐3), (2) human embryonic kidney cells (HEK‐293), (3) breast cancer cells (MCF‐7), and (4) cervical cancer cells (Hela) under normoxic and hypoxic conditions. We showed that ATSM−Cu(II) is toxic to breast cancer cells under normoxic and hypoxic conditions; however, it is not toxic to normal HEK‐293 non‐cancer cells. We showed that the Cu(I) content in breast cancer cell after treatment with ATSM−Cu(II) under hypoxic conditions is higher than in normal cells, despite that the uptake of ATSM−Cu(II) is a bit higher in normal cells than in breast cancer cells. This study suggests that the redox potential of ATSM−Cu(II) is higher in breast cancer cells than in normal cells; thus, its toxicity to cancer cells is increased.
Insights into oral bioavailability enhancement of therapeutic herbal constituents by cytochrome P450 3A inhibition

Abstract Herbal plants typically have complex compositions and diverse mechanisms. Among them, bioactive constituents with relatively high exposure in vivo are likely to exhibit therapeutic efficacy. On the other hand, their bioavailability may be influenced by the synergistic effects of different bioactive components. Cytochrome P450 3A (CYP3A) is one of the most abundant CYP enzymes, responsible for the metabolism of 50% of approved drugs. In recent years, many therapeutic herbal constituents have been identified as CYP3A substrates. It is more evident that CYP3A inhibition derived from the herbal formula plays a critical role in improving the oral bioavailability of therapeutic constituents. CYP3A inhibition may be the mechanism of the synergism of herbal formula. In this review, we explored the multiplicity of CYP3A, summarized herbal monomers with CYP3A inhibitory effects, and evaluated herb-mediated CYP3A inhibition, thereby providing new insights into the mechanisms of CYP3A inhibition-mediated oral herb bioavailability.
LOXL1-AS1 promotes thymoma and thymic carcinoma progression by regulating miR-525-5p-HSPA9

Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the present study was to explore the mechanism by which the long noncoding RNA (lncRNA) LOXL1-AS1 affects thymoma and thymic carcinoma progression by targeting the miR-525-5p-HSPA9 axis. Bioinformatics was used to analyse the process of LOXL1-AS1 targeting miR-525-5p-HSPA9 and its expression characteristics in TET. The relationships between LOXL1-AS1, miR-525-5p, HSPA9 and prognosis were analysed. The dual luciferase reporter assay was applied to verify targeting. The gene was knocked down or overexpressed by plasmid transfection. Cell counting kit 8 (CCK-8) assay, flow cytometry and Transwell assay were used to detect cell viability, apoptosis and invasion ability, respectively. Proteins and RNAs were examined by western blot analysis and qPCR, respectively. A tumour-burdened assay was used to perform in vivo verification. LOXL1-AS1 and HSPA9 were overexpressed in thymoma and thymic carcinoma; high levels of LOXL1-AS1 and HSPA9 were associated with poor prognosis, and there was a significant positive correlation between their levels. Downregulation of miR-525-5p expression was also associated with poor prognosis of patients. Clinical trials also demonstrated the same trends. miR-525-5p inhibited the expression of HSPA9 protein by targeting the 3′-untranslated region (UTR) of HSPA9 mRNA. LOXL1-AS1 promoted the expression of HSPA9 as a sponge targeting miR-525-5p. Animal experiment results also showed that knockdown of miR-525-5p promoted cancer by promoting the expression of HSPA9. In conclusion, LOXL1-AS1 and HSPA9 are highly expressed in thymoma and thymic carcinoma; miR-525-5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR-525-5p is associated with poor prognosis. In summary, this study demonstrates that LOXL1-AS1 acts as a sponge that targets miR-525-5p to promote HSPA9 expression, thereby promoting the growth and invasion and inhibiting apoptosis of thymoma and thymic carcinoma cells.
Current smoking predicts inadequate response to methotrexate monotherapy in rheumatoid arthritis patients naïve to DMARDs

Abstract Identifying predictors of inadequate response to methotrexate (MTX) in rheumatoid arthritis (RA) is key to move from a “trial and error” to a “personalized medicine” treatment approach where patients less likely to adequately respond to MTX monotherapy could start combination therapy at an earlier stage. This study aimed to identify potential predictors of inadequate response to MTX in RA patients naïve to disease modifying anti-rheumatic drugs. Data from a real-life cohort of newly diagnosed RA patients starting MTX (baseline, T0) as first-line therapy were analyzed. Outcomes, assessed after 6 months (T1), were defined as failure to achieve a disease activity score 28 (DAS28) low disease activity (LDA) or a good/moderate response to MTX, according to the European League Against Rheumatism (EULAR) response criteria. Logistic regression was used to assess the associations between baseline variables and the study outcomes. Overall, 294 patients (60.5% females, median age 54.5 years) with a median disease duration of 7.9 months were recruited. At T1, 47.3% of subjects failed to achieve LDA, and 29.3% did not have any EULAR-response. In multivariate analysis, significant associations were observed between no LDA and current smoking (adjusted odds ratio [adjOR] 1.79, P = .037), female gender (adjOR 1.68, P = .048), and higher DAS28 (adjOR 1.31, P = .013); and between no EULAR-response and current smoking (adjOR: 2.04, P = .019), age (adjOR: 0.72 per 10-years increases, P = .001), and higher erythrocyte sedimentation rate (adjOR: 0.49; P = .020). By contrast, there were no associations between past smoker status and study outcomes. In summary, in our real-life cohort of disease modifying anti-rheumatic drug naïve RA patients, current smoking habit independently predicts inadequate response to MTX. This, together with other independent predictors of response to treatment identified in our study, might assist with personalized monitoring in RA patients. Further studies are required to investigate whether smoking quitting strategies enhance the therapeutic response to MTX.
Emerging technologies for the management of type 2 diabetes mellitus

Diabetes mellitus is a global health problem affecting 422 million people worldwide, of which 34.2 million live in the United States alone. Complications due to diabetes can lead to considerable morbidity and mortality related to both microvascular and macrovascular disease. While glycosylated hemoglobin testing is the standard test utilized to evaluate glycemic control, emerging targets like “time in range” and “glycemic variability” often provide more accurate assessments of glycemic fluctuations and have implications for diabetes complications and quality of life. Patients with diabetes face considerable burdens of self‐care including frequent glucose monitoring, multiple insulin injections, dietary management, and the need to track daily activities, all of which lead to reduced adherence and psychological burnout. From the provider perspective, limited patient data and access to self‐management tools lead to treatment inertia and a reduced ability to help patients achieve and maintain their glycemic goals. In the past few decades, there have been considerable advances in treatment‐based technology and technological applications designed to help reduce patient burden and provide tools for better self‐management. These advances make real‐time clinical data available for clinicians to make necessary changes in treatment regimens. In this review, we discuss the latest emerging technologies available for the management of people with type 2 diabetes mellitus.
Changes in the Psychological State of Medical Personnel in the Department of Radiotherapy at a Tertiary Care Teaching Hospital in China during the Epidemic

Abstract Objectives The aim of the present study was to investigate changes in the psychological state of medical personnel in the Department of Radiotherapy during the COVID-19 epidemic. Methods Psychological state was evaluated using the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). All three questionnaires were first completed by medical personnel on 17–18 February 2020 and were repeated every 3 months thereafter until 17–18 August. The number and intentions of patients receiving radiotherapy (RT) in our department were also collected. Results Twenty medical personnel participated in the present study. The global PSQI score recorded in August was significantly lower than that recorded in February (P = 0.045). Among the seven components of the PSQI, sleep quality (P = 0.048) and daytime dysfunction (P = 0.006) in August were significantly improved compared with February, whereas SDS and SAS did not significantly differ among the three different time points. The proportion of patients who received palliative radiotherapy was significantly higher on 18 May than on 17 February (P = 0.005). Conclusions Medical personnel in the Department of Radiotherapy experienced a significantly elevated incidence of sleeping problems during the early COVID-19 outbreak period. Multiple combinations of protective measures to avoid infection could improve sleep quality and ensure the safe delivery of RT to cancer patients.
Extracellular sulfatases as potential blood-based biomarkers for early detection of lung cancer

Abstract Purpose Non-small lung (NSCLC) is the deadliest cancer, with survival measured in months. Earlier diagnosis using a robust biomarker would likely improve survival. This study aims to determine whether blood levels of the extracellular sulfatases (SULF1 and SULF2) and their bio-activity can serve as novel biomarkers for NSCLC early detection. Materials and Methods Using human plasma specimens from NSCLC patients, nonmalignant COPD patients, and healthy individuals, we determined the association between plasma SULF levels and the presence of NSCLC. We assessed the plasma SULF levels as a function of sex and age. We also evaluated the plasma levels of heparin-binding factors potentially mobilized by the SULFs. To increase test specificity of blood SULF2 as a biomarker for the early diagnosis of NSCLC, we investigated the presence of a tumor-specific SULF2 isoform released in the blood, which could be used as a biomarker alone or in multiplex assays. Results The median level of plasma SULF2 was significantly elevated in NSCLC patients than in healthy controls (∼2 fold). However, these data were confounded by age. Surprisingly, COPD patients also showed a dramatically increased SULF2 plasma level. We showed a significant increase in the median plasma levels of several HSPG-binding factors in early-stage NSCLC patients compared to controls. Furthermore, we revealed a significant positive correlation of the SULF2 protein level with the plasma levels of two HSPG-binding factors IL6 and IL8. We demonstrated that NSCLC cancer cells and tissues overexpress a SULF2 splice variant. We determined the presence of a SULF2 splice variant form in NSCLC plasma, which was not detectable in COPD and control plasmas. Conclusion Our findings highlight the potential for the plasma levels of SULF2 protein and its bio-activity as novel blood biomarkers for early diagnosis of NSCLC.
Green synthesis of metallic nanoparticles using pectin as a reducing agent: a systematic review of the biological activities

Abstract Context Pectin is a plant heteropolysaccharide that is biocompatible and biodegradable, enabling it to be an excellent reducing agent (green synthesis) for metallic nanoparticles (MNPs). Nevertheless, in the biological industry, pectin has been left behind in synthesising MNPs, for no known reason. Objective To systematically review the biological activities of pectin synthesised MNPs (Pe-MNPs). Methods The databases Springer Link, Scopus, ScienceDirect, Google Scholar, PubMed, Mendeley, and ResearchGate were systematically searched from the date of their inception until 10th February 2020. Pectin, green synthesis, metallic nanoparticles, reducing agent and biological activities were among the key terms searched. The data extraction was focussed on the biological activities of Pe-MNPs and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations for systematic reviews. Results A total of 15 studies outlined 7 biological activities of Pe-MNPs in the only three metals that have been explored, namely silver (Ag), gold (Au) and cerium oxide (CeO2). The activities reported from the in vitro and in vivo studies were antimicrobial (9 studies), anticancer (2 studies), drug carrier (3 studies), non-toxic (4 studies), antioxidant (2 studies), wound healing (1 study) and anti-inflammation (1 study). Conclusions This systematic review demonstrates the current state of the art of Pe-MNPs biological activities, suggesting that Ag and Au have potent antibacterial and anticancer/chemotherapeutic drug carrier activity, respectively. Further in vitro, in vivo, and clinical research is crucial for a better understanding of the pharmacological potential of pectin synthesised MNPs.
Spike in Diabetic Ketoacidosis Rates in Pediatric Type 2 Diabetes During the COVID-19 Pandemic

OBJECTIVE The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on the incidence of new-onset type 2 diabetes and diabetic ketoacidosis (DKA) is unclear. It is unknown whether the coincidence of DKA noted in adult patients with type 2 diabetes is an issue for youth during the coronavirus disease 2019 pandemic. RESEARCH DESIGN AND METHODS A retrospective single-center medical record review was conducted in a large, urban children’s hospital of pediatric subjects presenting with new-onset type 2 diabetes between March and August of 2018 to 2020. RESULTS The proportion of subjects presenting with new-onset type 2 diabetes in DKA dramatically increased in 2020 (9% in 2018, 3% in 2019, and 20% in 2020, P = 0.029). CONCLUSIONS In 2020, youth with new-onset type 2 diabetes had a greater incidence of DKA at presentation than previously observed. Future studies should examine the impact of SARS-CoV2 exposure on the presentation of type 2 diabetes in all age-groups to inform better patient care.
Singing to infants matters: Early singing interactions affect musical preferences and facilitate vocabulary building

Abstract This research revealed that the frequency of reported parent-infant singing interactions predicted 6-month-old infants’ performance in laboratory music experiments and mediated their language development in the second year. At 6 months, infants (n = 36) were tested using a preferential listening procedure assessing their sustained attention to instrumental and sung versions of the same novel tunes whilst the parents completed an ad-hoc questionnaire assessing home musical interactions with their infants. Language development was assessed with a follow-up when the infants were 14-month-old (n = 26). The main results showed that 6-month-olds preferred listening to sung rather than instrumental melodies, and that self-reported high levels of parental singing with their infants [i] were associated with less pronounced preference for the sung over the instrumental version of the tunes at 6 months, and [ii] predicted significant advantages on the language outcomes in the second year. The results are interpreted in relation to conceptions of developmental plasticity.
Pathways to exotic metastable silicon allotropes

The Group 14 element silicon possesses a complex free-energy landscape with many (local) minima, allowing for the formation of a variety of unusual structures, some of which may be stabilized at ambient conditions. Such exotic silicon allotropes represent a significant opportunity to address the ever-increasing demand for novel materials with tailored functionality since these exotic forms are expected to exhibit superlative properties including optimized band gaps for solar power conversion. The application of pressure is a well-recognized and uniquely powerful method to access exotic states of silicon since it promotes large changes to atomic bonding. Conventional high-pressure syntheses, however, lack the capability to access many of these local minima and only four forms of exotic silicon allotropes have been recovered over the last 50 years. However, more recently, significant advances in high pressure methodologies and the use of novel precursor materials have yielded at least three more recoverable.
Characterizing Runoff from Roads: Particle Size Distributions, Nutrients, and Gross Solids

AbstractParticulate matter, nutrients, and gross solids from roads contribute nonpoint-source pollution to waterways. To inform road runoff management, a field monitoring study was undertaken at eight road sites across North Carolina. Particle size distributions (PSD) of edge-of-pavement runoff samples were analyzed to understand the granulometry of the particulate matter. Knowledge of PSDs is critical when attempting to understand sediment fate and transport through stormwater control measures (SCMs), especially when the primary removal mechanism is particle settling. For 43 road runoff events, median particle size varied from 31 to 144 μm. The median PSD from hot mix asphalt (HMA) was 2.6% clay, 44.8% silt, and 52.6% sand. PSD was not correlated to roadway classification or ecoregion; however, PSD was significantly correlated to the presence of a permeable friction course (PFC) overlay, which is a layer of porous asphalt placed over traditional HMA. The median d90 for PFC (131 μm) was significantly smal.
Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9

Cellular RNAs guide CRISPR-Cas9 The Cas9 nuclease widely used for genome editing is derived from natural bacterial defense systems that protect against invading viruses. Cas9 is directed by RNA guides to cut matching viral DNA. Jiao et al. discovered that RNA guides can also originate from cellular RNAs unassociated with viral defense (see the Perspective by Abudayyeh and Gootenberg). They rendered this process programmable, linking the presence of virtually any RNA to cutting of matching DNA by Cas9. This capability is the basis of a new CRISPR diagnostic method developed by the authors that can detect many biomarkers at once. Named LEOPARD, this method can detect, for example, RNAs from severe acute respiratory syndrome coronavirus 2 and other viruses, thereby translating a new CRISPR discovery into a powerful diagnostic tool. Science, abe7106, this issue p. 941; see also abi9335, p. 914 Cas9 guide RNAs can be derived from cellular RNAs, inspiring a multiplexable diagnostic platform. CRISPR-Cas systems recognize foreign genetic material using CRISPR RNAs (crRNAs). In type II systems, a trans-activating crRNA (tracrRNA) hybridizes to crRNAs to drive their processing and utilization by Cas9. While analyzing Cas9-RNA complexes from Campylobacter jejuni, we discovered tracrRNA hybridizing to cellular RNAs, leading to formation of “noncanonical” crRNAs capable of guiding DNA targeting by Cas9. Our discovery inspired the engineering of reprogrammed tracrRNAs that link the presence of any RNA of interest to DNA targeting with different Cas9 orthologs. This capability became the basis for a multiplexable diagnostic platform termed LEOPARD (leveraging engineered tracrRNAs and on-target DNAs for parallel RNA detection). LEOPARD allowed simultaneous detection of RNAs from different viruses in one test and distinguished severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its D614G (Asp614→Gly) variant with single-base resolution in patient samples.