Miracle-dz/UniFAR-FTUs huggingface dataset:
A Constitutive Stress Response is a Result of Low Temperature Growth in the Antarctic Green Alga Chlamydomonas sp. UWO241.

The Antarctic green alga Chlamydomonas sp. UWO241 is an obligate psychrophile that thrives in the cold (4-6°C) but is unable to survive at temperatures ≥18°C. Little is known how exposure to heat affects its physiology or whether it mounts a heat stress response in a manner comparable to mesophiles. Here, we dissect the responses of UWO241 to temperature stress by examining its growth, primary metabolome and transcriptome under steady-state low temperature and heat stress conditions. In comparison with Chlamydomonas reinhardtii, UWO241 constitutively accumulates metabolites and proteins commonly considered as stress markers, including soluble sugars, antioxidants, polyamines, and heat shock proteins to ensure efficient protein folding at low temperatures. We propose that this results from life at extreme conditions. A shift from 4°C to a non-permissive temperature of 24°C alters the UWO241 primary metabolome and transcriptome, but growth of UWO241 at higher permissive temperatures (10°C and 15°C) does not provide enhanced heat protection. UWO241 also fails to induce the accumulation of HSPs when exposed to heat, suggesting that it has lost the ability to fine-tune its heat stress response. Our work adds to the growing body of research on temperature stress in psychrophiles, many of which are threatened by climate change. This article is protected by copyright. All rights reserved.
Association Between Crowdsourced Health Care Facility Ratings and Mortality in US Counties

Key Points Question Are online ratings of essential health care facilities associated with mortality at the county level? Findings In this cross-sectional study of reviews and ratings of 95 120 essential health care facilities across 1301 US counties, counties with facilities with a 1-point higher mean rating on an online review platform had 18.1 fewer age-adjusted deaths per 100 000 people. Natural language processing analyses found significant differences in online review content between counties with high vs low mortality. Meaning This study’s findings suggest that online reviews of essential health care facilities may reveal local health inequities and provide insights to improve local health care satisfaction.
Potency of Omadacycline against Mycobacteroides abscessus Clinical Isolates In Vitro and in a Mouse Model of Pulmonary Infection

The incidence of nontuberculous mycobacterial diseases in the United States is rising and has surpassed that of tuberculosis. Most notable among the nontuberculous mycobacteria is Mycobacteroides abscessus, an emerging environmental opportunistic pathogen capable of causing chronic infections. M. abscessus disease is difficult to treat, and the current treatment recommendations include repurposed antibiotics, several of which are associated with undesirable side effects. ABSTRACT The incidence of nontuberculous mycobacterial diseases in the United States is rising and has surpassed that of tuberculosis. Most notable among the nontuberculous mycobacteria is Mycobacteroides abscessus, an emerging environmental opportunistic pathogen capable of causing chronic infections. M. abscessus disease is difficult to treat, and the current treatment recommendations include repurposed antibiotics, several of which are associated with undesirable side effects. In this study, we have evaluated the activity of omadacycline, a new tetracycline derivative, against M. abscessus using in vitro and in vivo approaches. Omadacycline exhibited an MIC90 of 0.5 µg/mL against a panel of 32 contemporary M. abscessus clinical isolates, several of which were resistant to antibiotics that are commonly used for treatment of M. abscessus disease. Omadacycline combined with clarithromycin, azithromycin, cefdinir, rifabutin, or linezolid also exhibited synergism against several M. abscessus strains and did not exhibit antagonism when combined with an additional nine antibiotics also commonly considered to treat M. abscessus disease. Concentration-dependent activity of omadacycline was observed in time-kill assessments. Efficacy of omadacycline was evaluated in a mouse model of lung infection against four M. abscessus strains. A dose equivalent to the 300-mg standard oral human dose was used. Compared to the untreated control group, within 4 weeks of treatment, 1 to 3 log10 fewer M. abscessus CFU were observed in the lungs of mice treated with omadacycline. Treatment outcome was biphasic, with bactericidal activity observed after the first 2 weeks of treatment against all four M. abscessus strains.
High-quality genome assembly of an important biodiesel plant, Euphorbia lathyris L

Abstract Caper spurge, Euphorbia lathyris L. , is an important energy crop and medicinal crop. Here, we generated a high-quality, chromosome-level genome assembly of caper spurge using Oxford Nanopore sequencing, Illumina sequencing, and Hi-C technology. The final genome assembly was ∼988.9 Mb in size, 99.8% of which could be grouped into 10 pseudochromosomes, with contig and scaffold N50 values of 32.6 and 95.7 Mb, respectively. A total of 651.4 Mb repetitive sequences and 36,342 protein-coding genes were predicted in the genome assembly. Comparative genomic analysis showed that caper spurge and castor bean clustered together. We found that no independent whole-genome duplication event had occurred in caper spurge after its split from the castor bean, and recent substantial amplification of long terminal repeat retrotransposons has contributed significantly to its genome expansion. Furthermore, based on gene homology searching, we identified a number of candidate genes involved in the biosynthesis of fatty acids and triacylglycerols. The reference genome presented here will be highly useful for the further study of the genetics, genomics, and breeding of this high-value crop, as well as for evolutionary studies of spurge family and angiosperms.
A deep dive into CDK4/6 inhibitors: Evaluating real world toxicities and treatment paradigms in the elderly population

Background Cyclin-dependent kinase 4/6 inhibitors have become part of the standard of care in the treatment of hormone receptor positive, Her2Neu negative metastatic breast cancer. There is concern regarding the efficacy and potential increased cyclin-dependent kinase 4/6 inhibitors toxicity in the geriatric population in the community compared to the clinical trial population. Methods We evaluated patients treated with cyclin-dependent kinase 4/6 inhibitors from 2015 to 2019 and stratified according to age ≥70 and <70 years. Complete blood count from the first two cycles was recorded. Rates of hematologic toxicities, dose interruptions and reductions, progression-free survival, and overall survival were compared between both groups. We sought to assess the hematologic toxicities between the age groups and the relationship between previous chemotherapy exposure, bone metastasis and starting cyclin-dependent kinase 4/6 inhibitors dose with progression-free survival and overall survival. Results A total of 202 patients were included, 73 were ≥70 years and 129 were <70 years of age. There was no association between age group and grade of neutropenia or thrombocytopenia. There was a profound association between progression-free survival and overall survival and starting dose, where patients with recommended starting dose had higher progression-free survival and overall survival than those with a reduced dose (p = 0.0003 and p = 0.04). Conclusions Our study showed similar progression-free survival and overall survival between age groups without significant differences in neutropenia or thrombocytopenia toxicity. Nevertheless, we found an association between starting dose and progression-free survival and overall survival that has not been previously reported. Given the good tolerability across age groups and the improvement in progression-free survival and overall survival, patients should be treated at the cyclin-dependent kinase 4/6 inhibitors recommended dose and monitored appropriately.
Are remote clinical assessments a feasible and acceptable method of assessment? A systematic review

Abstract The COVID-19 pandemic presented an enormous and immediate challenge to assessing clinical skills in healthcare professionals. Many institutions were unable to deliver established face-to-face assessment methods such as Objective Structured Clinical Examinations (OSCEs). Assessors needed to rapidly institute alternative assessment methods to ensure that candidates met the clinical competences required for progression. Using a systematic review, we aimed to evaluate the feasibility, and acceptability of remote methods of clinical skills assessment, including remote structured clinical assessments and the submission of video recordings. We searched for studies reporting on Remote Clinical Assessments or its variants in MEDLINE, Embase and The Cochrane library from 2000 to March 2021. Twenty eight studies were included in the review; 20 studies related to remote structured clinical examinations or OSCEs and 8 reported the use of video submissions. The participants of the different studies included medical students, nursing students, dental students and doctors in training. A variety of different online platforms were utilised including Zoom, Skype, webcams, and Adobe Connect online. The studies found that delivery of remote clinical assessments is possible and provides an alternative method of assessing many clinical skills, but most also acknowledge limitations and challenges. They are acceptable to both candidates and examiners, and where measured, show moderate agreement with on-site clinical assessments. Current evidence is based on studies with low methodological quality and for the most part, small sample sizes.
Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects

Aims Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. Methods The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. Results The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. Conclusion Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677–689.
Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation.

AIMS We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry. METHODS AND RESULTS Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2 weeks) and in 240 patients at 1 year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR ≤ 0.80), and microvascular dysfunction (either IMR ≥ 25 or CFR ≤ 2.0 with FFR > 0.80). The primary outcome was the composite of death or re-transplantation at 10 years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P = 0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P = 0.73) were not predictors of death and re-transplantation at 10 years. At 1 year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P = 0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P = 0.015) were associated with significantly increased risk of death or re-transplantation at 10 years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (χ2 improvement: 7.41, P = 0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes. CONCLUSION Abnormal coronary physiology 1 year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10 years.
Association between apolipoprotein E gene polymorphism and nonalcoholic fatty liver disease in Southern China: A case‐control study

Apolipoprotein E (ApoE) polymorphisms have been reported to be associated with nonalcoholic fatty liver disease (NAFLD), but the conclusions of studies are inconsistent in different regions. The present study aims to investigate the role of ApoE genotypes on NAFLD in southern China.
Integrating network pharmacology and in vitro model to investigate hippocampal neurotoxicity induced by atrazine

Abstract Atrazine (ATR), a commonly applied herbicide in agriculture, has been found to cause hippocampal injury in rodents. However, the underlying toxicological targets and mechanisms are unclear. In this study, network pharmacology analysis and in vitro model were integrated to investigate the effect and mechanism of ATR-induced hippocampal neurotoxicity. In total, 71 targets of hippocampal neurotoxicity induced by ATR were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) enrichment analysis suggested that these targets were related to multiple GO terms and signaling pathways. To further investigate the underlying mechanisms, the top 10 hub targets were screened and included tumor protein p53 (Tp53), caspase 3 (Casp3), prostaglandin-endoperoxide synthase 2 (Ptgs2), cAMP-responsive element-binding protein 1 (Creb1), estrogen receptor 1 (Esr1), Jun proto-oncogene (Jun), brain-derived neurotrophic factor (Bdnf), catalase (Cat), sirtuin 1 (Sirt1) and Fos proto-oncogene (Fos). Moreover, the cell counting kit-8 (CCK8) and lactate dehydrogenase (LDH) assay showed that ATR had time and dose-dependent cytotoxicity on H19-7 cells. TUNEL staining revealed that ATR increased the apoptotic ratio. In addition, Real-time quantitative polymerase chain reaction (RT-qPCR) results indicated that the mRNA expression levels of all hub targets showed significant changes, except Esr1 and Jun. Our study demonstrated that ATR mainly acted on multiple targets and signaling pathways to exert its hippocampal neurotoxicity. These results provided initial evidence for the further exploration of the toxicological mechanism of ATR.
Bisphenol A induced apoptosis via oxidative stress generation involved Nrf2/HO‐1 pathway and mitochondrial dependent pathways in human retinal pigment epithelium (ARPE‐19) cells

Bisphenol A (BPA) is an estrogen‐like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE‐19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE‐19 cells. After BPA treatment, the expression of Bcl‐XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase‐9 to promote downstream caspase‐3 leading to cytotoxicity. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase 1 (HO‐1) pathway play a major role in age‐related macular degeneration. Our results showed that expression of HO‐1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP‐activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA‐induced ROS generation and cytotoxicity were reduced by N‐acetyl‐l‐cysteine. Taken together, these results suggest that BPA induced ARPE‐19 cells via oxidative stress, which was associated with down regulated Nrf2/HO‐1 pathway, and the mitochondria dependent apoptotic signaling pathway.
The Parkinson’s Disease-Cognitive Rating Scale: Greek Normative Data, Clinical Utility and Cultural Considerations

Background: The Parkinson’s Disease-Cognitive Rating Scale (PD-CRS) is a comprehensive screening procedure for the evaluation of cognitive impairment in patients with Parkinson’s disease (PD). Objectives: In the present study we adjusted the PD-CRS for the Greek population, developed normative data and examined its clinical utility for the assessment of cognitive functioning in Greek PD patients. In addition, the correlation of clinical characteristics with cognitive performance in PD patients was examined. Methods: Three hundred four community-dwelling healthy adults and 59 patients with PD, completed the adapted PD-CRS. Results: Healthy adults outperformed the PD patients on the total, the cortical and subcortical scores of the PD-CRS. Normative data indicated effects of both education and age on the PD-CRS. The optimal total PD-CRS cutoff score for the identification of cognitive impairment in a heterogeneous sample of PD patients, with regard to the severity of cognitive difficulties, was 79, yielding a modest sensitivity and specificity. Clinical characteristics of the patients (i.e., disease duration and functional disease burden) were related to poor performance on the PD-CRS. Conclusions: The Greek version of the PD-CRS is a useful instrument for the assessment of cognition in PD. Future prospective studies should examine its clinical utility to identify PD-cognitive subtypes (i.e., PD patients with mild cognitive impairment), to monitor cognitive changes, as well as its predictive accuracy for subsequent dementia.
Deficiencies in the DNA Binding Protein ARID3a Alter Chromatin Structures Important for Early Human Erythropoiesis

ARID3a is a DNA-binding protein important for normal hematopoiesis in mice and for in vitro lymphocyte development in human cultures. ARID3a knockout mice die in utero with defects in both early hematopoietic stem cell populations and erythropoiesis. Recent transcriptome analyses in human erythropoietic systems revealed increases in ARID3a transcripts implicating potential roles for ARID3a in human erythrocyte development. However, ARID3a transcript levels do not faithfully reflect protein levels in many cells, and the functions and requirements for ARID3a protein in those systems have not been explored. We used the erythroleukemic cell line K562 as a model to elucidate functions of ARID3a protein in early human erythropoiesis. ARID3a knockdown of hemin-stimulated K562 cells resulted in lack of fetal globin production and modifications in gene expression. Temporal RNA sequencing data link ARID3a expression with the important erythroid regulators Gata1, Gata2, and Klf1. Ablation of ARID3a using CRISPR-Cas9 further demonstrated it is required to maintain chromatin structures associated with erythropoietic differentiation potential. These data demonstrate that the ARID3a protein is required for early erythropoietic events and provide evidence for the requirement of ARID3a functions for proper maintenance of appropriate chromatin structures.
Resilience of adolescents, though weakened during pandemic-related lockdown, serves as a protection against depression and sleep problems

ABSTRACT Adolescents facing adversities are susceptible to depression and sleep problems. Resilience is an important protective mechanism for coping with adversity. During the COVID-19 pandemic, adolescents faced hardships including being pulled from their schools and being unable to socialize with friends during mandated lockdowns. We had three aims in this study. First, we sought to test whether Chinese adolescents’ resilience was strengthened, maintained, or weakened during the COVID-19 lockdown. Second, we sought to test whether adolescents’ resilience predicted depressive symptoms and in turn, sleep problems. Third, we sought to examine the role social support may play. In a partially-longitudinal survey study, we demonstrated via a within-subject t-test and its Bayesian equivalent that Chinese adolescents’ resilience weakened during the lockdown compared with before the pandemic. However, resilience remained an important predictor: A mediation model demonstrated that higher resilience was associated with fewer depressive symptoms, which in turn predicted fewer sleep problems. Moreover, we found that social support moderated this mediation: Strong social support reduced the negative effects of low resilience levels. These results help shed light on the fragility of resilience, its importance for adolescents’ mental health when facing adversity, and how we might support adolescents experiencing social distancing mandates or who are otherwise isolated from their peers.