Miracle-dz/UniFAR-FTUs huggingface dataset:
Hazard characterization of carcinogenicity, mutagenicity, and reproductive toxicity for short chain primary nitroalkanes

Nitroalkanes are organic aliphatic hydrocarbon compounds with a nitro moiety that are commonly used as solvents or intermediates to synthesize a variety of organic compounds due to their inherent reactivity. In June 2020, a harmonized classification and labeling (CLH) proposal was submitted to the European Chemicals Agency (ECHA) for the following harmonized carcinogenicity, mutagenicity, and reproductive toxicity (“CMR”) classifications for nitromethane (NM), nitroethane (NE), and 1‐nitropropane (1‐NP): NM Carc. 1B and Repr. 1B; NE Repr. 1B; and 1‐NP Repr. 2. In this assessment, a weight of evidence (WoE) evaluation of studies on animal carcinogenicity and reproductive and developmental toxicity, genotoxicity, and mode of action for these three nitroalkanes was performed to critically assess the relevance of the proposed CMR classifications. Overall, the WoE indicates that NM, NE, and 1‐NP are not carcinogenic, genotoxic, nor selective reproductive or developmental toxicants. Based on our analysis, classifying NM, NE, and 1‐NP as Category 2 reproductive toxicants is most appropriate. Furthermore, not classifying NE and 1‐NP with respect to their carcinogenicity is appropriate based on the available studies for this endpoint coupled with negative results in genotoxicity studies, metabolism data, and in silico predictions. We determined that the classification for NM of Carc. 1B is not appropriate, based on the fact that rat mammary and harderian tumors are likely not relevant to humans and lung and liver tumors reported in mice were equivocal in their dose–response and statistical significance.
Biological pathway expression complementation contributes to biomass heterosis in Arabidopsis

Significance Heterosis, referring to the better performance of an F1 hybrid compared with its parents, has been greatly exploited in agriculture to improve yield. Nevertheless, our understanding of its genetic and molecular mechanism has remained limited. We investigated the temporally dynamic phenotypes and transcriptomes during early seedling development in two Arabidopsis ecotypes together with their hybrid and unveiled differences in the transcriptional regulatory network between the hybrid and parents, orchestrating the hybrid growth vigor. Moreover, we found complementary high-parent expression in the hybrid between the network hub genes involved in photosynthesis and cell cycle. Our findings provide molecular-level evidence that dominant expression complementation between genes involved in two fundamental biological pathways contributes to heterosis. The mechanisms underlying heterosis have long remained a matter of debate, despite its agricultural importance. How changes in transcriptional networks during plant development are relevant to the continuous manifestation of growth vigor in hybrids is intriguing and unexplored. Here, we present an integrated high-resolution analysis of the daily dynamic growth phenotypes and transcriptome atlases of young Arabidopsis seedlings (parental ecotypes [Col-0 and Per-1] and their F1 hybrid). Weighted gene coexpression network analysis uncovered divergent expression patterns between parents of the network hub genes, in which genes related to the cell cycle were more highly expressed in one parent (Col-0), whereas those involved in photosynthesis were more highly expressed in the other parent (Per-1). Notably, the hybrid exhibited spatiotemporal high-parent–dominant expression complementation of network hub genes in the two pathways during seedling growth. This suggests that the integrated capacities of cell division and photosynthesis contribute to hybrid growth vigor, which could be enhanced by temporal advances in the progression of leaf development in the hybrid relative to its parents. Altogether, this study provides evidence of expression complementation between fundamental biological pathways in hybrids and highlights the contribution of expression dominance in heterosis.
Comparison of 2 shear wave elastography systems in reproducibility and accuracy using an elasticity phantom

Abstract This study aimed to compare the accuracy and inter- and intra-observer reproducibility of the measured elasticity between 2 shear wave elastography systems. Three breast radiologists examined 8 targets of 4 different levels of stiffness (size: 11 mm, 4 mm) in an elasticity phantom (Customized 049A Elasticity QA Phantom, CIRS, Norfolk, VA, USA) using 2 different shear wave ultrasound elastography systems: SuperSonic Imagine (SSI) (SSI, Aix en Provence, France) and ShearScan (RS-80A, Samsung Medison, Seoul, Korea). Three radiologists performed ultrasound (US) elastography examinations for the phantom lesions using 2 equipment over a 1-week interval. Intra- and inter-observer reproducibility and the accuracy of the measured elasticity were analyzed and compared between the 2 systems. The accuracy of shape was also analyzed by shape-matching between B-mode and elastography color image. Intra-class correlation coefficients (ICC) were used in statistical analysis. For measured elasticity, the intra-observer and inter-observer reproducibility were excellent in both SSI and ShearScan (0.994 and 0.998). The overall accuracy was excellent in both systems, but the accuracy in small lesions (4 mm target) was lower in SSI than ShearScan (0.780 vs 0.967). The accuracy of shape-matching on the elastography image was 59.0% and 81.4% in the SSI and ShearScan, respectively. In conclusion, the SSI and ShearScan showed excellent intra- and inter-observer reproducibility. The accuracy of the Young's modulus was high in both the SSI and ShearScan, but the SSI showed decreased accuracy in measurement of elasticity in small targets and poor shape-matching between the B-mode image and color-coded elastography image.
Lack of efficacy of cannabidiol for relieving back pain: time to re‐set expectations?

Decades of opioid overuse can teach us valuable lessons about how we should handle medicinal cannabinoids, including cannabidiol (CBD). One major lesson is that access to medicines should not move ahead of scientific evidence. Over time, evidence that context is critical has accumulated: using opioids to treat acute pain and cancer pain, in the management of opioid dependency, and in palliative care can be justified. However, the indication creep from acute to chronic noncancer pain was unwarranted. Consequently, clinicians are sensitive to new pain medicines being made available without evidence of benefit, and the motivations for accelerated access have been questioned.1
Managing shoulder pain: a meta-ethnography exploring healthcare providers’ experiences

Abstract Objective To review and synthesize qualitative research studies exploring the experiences of Healthcare Providers (HCPs) of managing shoulder pain. Methods A meta-ethnographic approach was adopted to review and synthesize eligible studies. The findings from each included study were translated into one another using Noblit and Hares’ seven-stage process. A systematic search of eleven electronic databases was conducted in February 2021. Methodological quality was assessed using the CASP Appraisal Tool. Results Ten studies were included in the meta-synthesis, all deemed of high methodological quality. Three themes were identified; (1) Lack of consensus: “we all have different approaches. ” (2) Challenges to Changing Practice: It’s “really hard to change and switch to a different approach,” (3) Getting “Buy in” to Treatment: “…so you have to really sell it early”. Conclusion Healthcare providers working with people with shoulder pain struggle to reconcile, often conflicting, research recommendations with their own clinical experience, beliefs and patient expectations. These findings help explain the continued lack of consensus on how best to manage shoulder pain in clinical practice. IMPLICATIONS FOR REHABILITATION Healthcare providers (HCPs) working with people with shoulder pain struggle to resolve conflicts between evidence-based recommendations, clinical experience, their own shoulder pain beliefs and patient expectations and preferences. Stronger collaboration across professional disciplines is needed to address the current lack of consensus on the management of shoulder pain. Many HCP’s find it difficult to engage patients with shoulder pain in exercise and they work hard to “sell” this approach to patients using strategies such as education, shared decision making and therapeutic alliance.
Is there any association between a delay in surgery and nodal positivity in the ER‐negative Her2 negative breast cancer subgroups?

To the Editor, I wish to congratulate Khader et al. for their article in which they investigated the association between delay in surgery and axillary upstaging of clinically node‐negative breast cancer patients. Patients diagnosed with cN0 BC undergoing surgery with sentinel lymph node biopsy were divided into four groups based on time intervals between diagnosis and surgery (<4, 4–8, 8–12, and >12 weeks). They reported that delay in BC surgery in cN0 patients was associated with an increased likelihood of axillary upstaging and decreased survival. In the subgroups of patients by hormone receptor status, the correlation between axillary upstaging and delay in surgery was only observed in the ER‐positive subgroup. There was no observed association between a delay in surgery and nodal positivity in the ER‐negative Her2 negative subgroups‐triple negative breast cancer (TNBC). Luminal types tend to have more frequent lymph node metastasis than HER2 or TNBC. The reason for this difference in the extent of nodal metastasis according to subtype is not clear. The expression of molecules that drive tumor growth and lymphatic metastasis may play a role. As estrogen was reported to downregulate the expression of VEGF, its level of expression in luminal types was relatively low, while HER2 and TNBC had higher expression of VEGF. TNBC has higher microvascular density and higher expression of VEGF. We studied capillary and lymphatic invasion in tumors of patients with TNBC. To differentiate the capillary invasion and lymphovascular invasion, the anti‐ human CD34 and anti‐human D2‐40 antibodies were used. Anti‐human CD34 antibodies stain the blood vessels and lymphatics. However, anti‐ human D2‐40 antibodies stain lymphatics specifically. Capillary invasion is more commonly observed than lymphatic invasion in patients with TNBC. This finding supports the fact that why there was no observed association between a delay in surgery and nodal positivity in the ER‐negative Her2 negative subgroups in the current study.
Molecular basis of F-actin regulation and sarcomere assembly via myotilin

Sarcomeres, the basic contractile units of striated muscle cells, contain arrays of thin (actin) and thick (myosin) filaments that slide past each other during contraction. The Ig-like domain-containing protein myotilin provides structural integrity to Z-discs—the boundaries between adjacent sarcomeres. Myotilin binds to Z-disc components, including F-actin and α-actinin-2, but the molecular mechanism of binding and implications of these interactions on Z-disc integrity are still elusive. To illuminate them, we used a combination of small-angle X-ray scattering, cross-linking mass spectrometry, and biochemical and molecular biophysics approaches. We discovered that myotilin displays conformational ensembles in solution. We generated a structural model of the F-actin:myotilin complex that revealed how myotilin interacts with and stabilizes F-actin via its Ig-like domains and flanking regions. Mutant myotilin designed with impaired F-actin binding showed increased dynamics in cells. Structural analyses and competition assays uncovered that myotilin displaces tropomyosin from F-actin. Our findings suggest a novel role of myotilin as a co-organizer of Z-disc assembly and advance our mechanistic understanding of myotilin’s structural role in Z-discs.
Challenges and perspectives for immunotherapy in oesophageal cancer: A look to the future (Review)

Oesophageal cancer is one of the most aggressive malignancies with limited treatment options, thus resulting in a high morbidity and mortality. With 5-year survival rates of only 5-10%, oesophageal cancer holds a dismal prognosis for patients. In order to improve overall survival, the early diagnosis and tools for patient stratification for personalized treatment are urgent needs. A minority of oesophageal cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). Microsatellite instability is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumours, such as colorectal and gastric cancer. In the latter, high levels of MSI are associated with a better prognosis and with an increased benefit to immune-based therapies. Therefore, similar therapeutic approaches could offer an opportunity of treatment for oesophageal cancer patients with MSI. Apart from immune checkpoint inhibitors, other immunotherapies such as adoptive T-cell transfer, peptide vaccine and oncolytic viruses are under investigation in oesophageal cancer patients. In the present review, the rationale and current knowledge about immunotherapies in oesophageal cancer are summarised.
A comparison of oncologic and functional outcomes in patients with pt3a renal cell carcinoma treated with partial and radical nephrectomy

ABSTRACT Hypothesis: Partial Nephrectomy is oncological safe in patients with pT3a RCC. Purpose: To compare the oncological and functional outcomes of patients with pT3a RCC scheduled for PN and RN. Materials and Methods: We retrospectively reviewed patients with pT3a N0 M0 RCC who underwent partial or radical nephrectomy from 2005 to 2016. Perioperative characteristics, including estimated glomerular filtration rate, tumor size, pathological histology, and RENAL nephrometry score, were compared between patients scheduled for partial or radical nephrectomy. We used multivariable Cox proportional hazards regression models to compare overall survival, cancer-specific survival, and recurrence-free survival between planned procedure type. Results: Of the 589 patients, 369 (63%) and 220 (37%) were scheduled for radical and partial nephrectomy, respectively; 26 (12%) of the scheduled partial nephrectomy cases were intraoperatively converted to radical nephrectomy. After adjusting for tumor size and histology, there were no statistically significant differences in overall survival (hazard ratio 0.66; 95% CI, 0.38–1.13), cancer-specific survival (hazard ratio 0.53; 95% CI, 0.16–1.75), or recurrence-free survival (hazard ratio 0.66; 95% CI, 0.34–1.28) between patients scheduled for partial or radical nephrectomy. Fewer patients scheduled for partial nephrectomy had estimated glomerular filtration rate reductions 3 to 9 months after surgery than patients scheduled for radical nephrectomy. Conclusion: We found no evidence that patients scheduled to undergo partial nephrectomy had poorer oncologic outcomes than patients scheduled to undergo radical nephrectomy. In select patients with pT3a renal cell carcinoma in whom partial nephrectomy is deemed feasible by the surgeon, partial nephrectomy should not be discouraged.
Clinical and Demographic Factors Associated with Distress in Adolescent and Young Adults with Cancer.

Purpose: Distress in cancer is defined as multifactorial unpleasant experience of an emotional, psychological, social, or spiritual nature that interferes with ones' ability to cope with cancer and its symptoms and treatment. The aim of this study was to determine clinical and demographic factors associated with the presence of distress in adolescent and young adults (AYAs) with cancer. Methods: Data were collected as part of a field-test study conducted between August 2016 and November 2017 in Canada (Toronto, Edmonton, and Vancouver) to determine the reliability and validity of CDS-AYA (Cancer Distress Scales for Adolescent and Young Adults). The CDS-AYA consist of five independently functioning scales including impact of cancer, physical, emotional, cognitive, and cancer worry. Multivariate logistic regression analyses, using established CDS-AYA cut points, were performed to identify clinical and demographic factors associated with the presence of distress in AYAs of ages 15-39 years with cancer. Results: Across all scales, increased distress was associated with female gender (p < 0.05), on-treatment status (p < 0.05), and reported poor overall health (p < 0.001). For the emotional scale, distress was also associated with being of age 15-19 years (p = 0.01). The greatest effect size for all scales was associated with treatment status [exp(β) = 1.78-4.6], except for the cognitive scale where gender had a slightly greater effect size. Conclusion: Factors associated with distress in AYA patients with cancer were similar across five CDS-AYA scales. Although it is important to screen all patients for distress, our findings reveal that patients who are female, on treatment, or who report having poorer health may be at a greater risk.
Cellular immune responses in the pathophysiology of preeclampsia

Preeclampsia, defined as new‐onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi‐systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti‐angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal‐fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.
Epidemiologic characteristics associated with SARS-CoV-2 antigen-based test results, rRT-PCR cycle threshold values, subgenomic RNA, and viral culture results from university testing

Abstract Background Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for SARS-CoV-2. Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. Methods Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. Results Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (OR 4.6, CI:1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, CI:0.03-0.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, CI:0.4-0.8) were less likely, and specimens positive for sgRNA (OR 10.2, CI:1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values <29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). Conclusions SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.
Performance characteristics of five SARS-CoV-2 serological assays: Clinical utility in health-care workers

Study objective: SARS-CoV-2, which causes coronavirus disease (COVID-19), continues to cause significant morbidity and mortality. The diagnosis of acute infection relies on reverse transcription-polymerase chain reaction (RT-PCR)-based viral detection. The objective of this study was to evaluate the optimal serological testing strategy for anti-SARS-CoV-2 antibodies which provides an important indicator of prior infection and potential short-term immunity. Methods The sensitivity and specificity of four different ELISA assays (Euroimmun IgG, Euroimmun NCP-IgG, Fortress and DIAsource) and one CLIA assay (Roche ELECSYS) were evaluated in 423 samples; 137 patients with confirmed RT-PCR COVID-19 infection (true positives), and 100 pre-pandemic samples collected prior to October 2019 (true negatives). A further 186 samples were collected from health-care staff and analysed by all five assays. Results The Fortress ELISA assay demonstrated the highest sensitivity and specificity followed by the Roche ECLIA assay. The highest overall sensitivity came from the assays that measured total antibody (IgM–IgG combined) and the three assays that performed the best (Fortress, Roche, Euroimmun IgG) all have different antigens as their target proteins which suggests that antigen target does not affect assay performance. In mildly symptomatic participants with either a negative RT-PCR or no RT-PCR performed, 16.76% had detectable antibodies suggesting previous infection. Conclusions We recommend a combined testing strategy utilizing assays with different antigenic targets using the fully automated Roche ECLIA assay and confirming discordant samples with the Fortress Total Antibody ELISA assay. This study provides an important indicator of prior infection in symptomatic and asymptomatic individuals.