Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Photolyases Repair Distinct DNA Lesions and Reactivate UVB-Inactivated Conidia of an Insect Mycopathogen under Visible Light

Protecting fungal cells from damage from solar UVB irradiation is critical for development and application of fungal insecticides but is mechanistically not understood in Beauveria bassiana, a classic insect pathogen. We unveil that two intranuclear photolyases, Phr1 and Phr2, play essential roles in repairing UVB-induced dsDNA lesions through respective decomposition of cytotoxic cyclobutane pyrimidine dimers and (6-4)-pyrimidine-pyrimidine photoproducts, hence reactivating UVB-inactivated cells effectively under visible light. Our findings shed light on the high potential of both photolyase genes for use in improving UVB resistance and application strategy of fungal insecticides. ABSTRACT Fungal conidia serve as active ingredients of fungal insecticides but are sensitive to solar UV irradiation, which impairs double-stranded DNA (dsDNA) by inducing the production of cytotoxic cyclobutane pyrimidine dimers (CPDs) and (6-4)-pyrimidine-pyrimidine photoproducts (6-4PPs). This study aims to elucidate how CPD photolyase (Phr1) and 6-4PP photolyase (Phr2) repair DNA damage and photoreactivate UVB-inactivated cells in Beauveria bassiana, a main source of fungal insecticides. Both Phr1 and Phr2 are proven to exclusively localize in the fungal nuclei. Despite little influence on growth, conidiation, and virulence, singular deletions of phr1 and phr2 resulted in respective reductions of 38% and 19% in conidial tolerance to UVB irradiation, a sunlight component most harmful to formulated conidia. CPDs and 6-4PPs accumulated significantly more in the cells of Δphr1 and Δphr2 mutants than in those of a wild-type strain under lethal UVB irradiation and were largely or completely repaired by Phr1 in the Δphr2 mutant and Phr2 in the Δphr1 mutant after optimal 5-h exposure to visible light. Consequently, UVB-inactivated conidia of the Δphr1 and Δphr2 mutants were much less efficiently photoreactivated than were the wild-type counterparts. In contrast, overexpression of either phr1 or phr2 in the wild-type strain resulted in marked increases in both conidial UVB resistance and photoreactivation efficiency. These findings indicate essential roles of Phr1 and Phr2 in photoprotection of B. bassiana from UVB damage and unveil exploitable values of both photolyase genes for improved UVB resistance and application strategy of fungal insecticides. IMPORTANCE Protecting fungal cells from damage from solar UVB irradiation is critical for development and application of fungal insecticides but is mechanistically not understood in Beauveria bassiana, a classic insect pathogen. We unveil that two intranuclear photolyases, Phr1 and Phr2, play essential roles in repairing UVB-induced dsDNA lesions through respective decomposition of cytotoxic cyclobutane pyrimidine dimers and (6-4)-pyrimidine-pyrimidine photoproducts, hence reactivating UVB-inactivated cells effectively under visible light. Our findings shed light on the high potential of both photolyase genes for use in improving UVB resistance and application strategy of fungal insecticides.
A Mini Review on Antidiabetic Properties of Fermented Foods

In general, fermented foods (FFs) are considered as functional foods. Since the awareness about the health benefits of FFs has increased, the consumption of FF also improved significantly in recent decades. Diabetes is one of the leading threats of the health span of an individual. The present manuscript details the general methods of the production of FFs, and the results of various studies (in vitro, in vivo, and clinical studies) on the antidiabetic properties of FFs. The fermentation method and the active microbes involved in the process play a crucial role in the functional properties of FFs. Several in vitro and in vivo studies have been reported on the health-promoting properties of FFs, such as anti-inflammation, anticancer, antioxidant properties, improved cognitive function and gastrointestinal health, and the reduced presence of metabolic disorders. The studies on the functional properties of FFs by randomized controlled clinical trials using human volunteers are very limited for several reasons, including ethical reasons, safety concerns, approval from the government, etc. Several scientific teams are working on the development of complementary and alternative medicines to improve the treatment strategies for hyperglycemia.
The puzzling construction of the conidial outer layer of Aspergillus fumigatus

If the mycelium of Aspergillus fumigatus is very short‐lived in the laboratory, conidia can survive for years. This survival capacity and extreme resistance to environmental insults is a major biological characteristic of this fungal species. Moreover, conidia, which easily reach the host alveola, are the infective propagules. Earlier studies have shown the role of some molecules of the outer conidial layer in protecting the fungus against the host defense. The outer layer of the conidial cell wall, directly in contact with the host cells, consists of α‐(1,3)‐glucan, melanin, and proteinaceous rodlets. This study is focused on the global importance of this outer layer. Single and multiple mutants without one to three major components of the outer layer were constructed and studied. The results showed that the absence of the target molecules resulting from multiple gene deletions led to unexpected phenotypes without any logical additivity. Unexpected compensatory cell wall surface modifications were indeed observed, such as the synthesis of the mycelial virulence factor galactosaminogalactan, the increase in chitin and glycoprotein concentration or particular changes in permeability. However, sensitivity of the multiple mutants to killing by phagocytic host cells confirmed the major importance of melanin in protecting conidia.
Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas.

BACKGROUND International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported. SUBJECTS, MATERIALS, AND METHODS We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like). RESULTS Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%). CONCLUSION Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity. IMPLICATIONS FOR PRACTICE Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.
Efficacy of a Parent-Based, Indicated Prevention for Anorexia Nervosa: Randomized Controlled Trial

Background Web-based preventive interventions can reduce risk and incidence of bulimia and binge eating disorders among young high-risk women. However, their specific effects on core symptoms of anorexia nervosa (AN) are rather weak. Objective The primary objective of this study was to evaluate the efficacy of an indicated, parent-based, Web-based preventive program Eltern als Therapeuten (E@T) in reducing risk factors and symptoms of AN. Methods Girls aged between 11 and 17 years were screened by selected risk factors and early symptoms of AN. At-risk families were then randomized to E@T or an assessment-only control condition. Assessments took place at pre- and postintervention (6 weeks later) and at 6- and 12-month follow-up (FU). Results A total of 12,377 screening questionnaires were handed out in 86 German schools, and 3941 including consent returned. Overall, 477 (447/3941, 12.10%) girls were identified as at risk for AN and 256 of those could be contacted. In all, 66 families (66/256, 25.8% of those contacted) were randomized to the E@T or a wait-list control condition, 43 (43/66, 65%) participated in postassessments, and 27 (27/66, 41%) in 12-month FUs. Due to low participation and high dropout rates of parents, recruitment was terminated prematurely. At 12-month FU, girls’ expected body weight (EBW) percentage was significantly greater for intervention participants compared with control participants (group by time interaction beta=21.0 [CI 5.81 to 36.13], P=.007; group by time squared interaction beta=−15.5 [CI −26.6 to −4.49], P=.007; estimated Cohen d=0.42]. No other significant effects were found on risk factors and attitudes of disturbed eating. Conclusions Despite a significant increase in girls’ EBW percentage, parental participation and adherence to the intervention were low. Overall, parent-based, indicated prevention for children at risk for AN does not seem very promising, although it might be useful for parents who engage in the intervention. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 18614564; http://www.isrctn. com/ISRCTN18614564 (Archived by WebCite at http://www.webcitation.org/74FTV1EpF).
Targeting Cancer Stem Cells to Overcome Chemoresistance

Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness pathways or cancer stem cell surface markers. Gold nanoparticles have emerged as innovative tools, particularly for photo-thermal therapy since they can be excited by laser to induce hyperthermia. Gold nanoparticles can be functionalized with antibodies to specifically target cancer stem cells. Preclinical studies using photo-thermal therapy have demonstrated the feasibility of targeting chemo-resistant cancer cells to reverse clinical chemoresistance. Here, we review the data linking cancer stem cells and chemoresistance and discuss the way to target them to reverse resistance. We particularly focus on the use of functionalized gold nanoparticles in the treatment of chemo-resistant metastatic cancers.
Hepatitis A virus vaccination in childhood-onset systemic lupus erythematosus

Objectives: Vaccination of systemic lupus erythematosus patients with non-live vaccines may decrease vaccine-preventable infections and mortalities. In the present study, we aimed to compare the immunogenicity and safety of inactivated hepatitis A vaccination in childhood-onset systemic lupus erythematosus and healthy subjects. Methods: A total of 30 childhood-onset systemic lupus erythematosus and 39 healthy participants who were seronegative for hepatitis A received two doses of the hepatitis A vaccine in a 0- and 6-month schedule. Hepatitis A virus (HAV) IgG antibodies were measured before vaccination and 7 months after the vaccination. Results: Although anti-HAV IgG antibody titers after vaccination were found to be somewhat lower in children with systemic lupus erythematosus than that of the healthy subjects (p < 0.05), the difference in seroconversion rate was insignificant between childhood-onset systemic lupus erythematosus patients (n = 24/30, 80%) and healthy controls (n = 33/39, 84.6%). There was no increase in median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores and anti-ds DNA levels after the vaccination procedure. Seroconversion rates in childhood-onset systemic lupus erythematosus patients were not affected by medication, high disease activity (SLEDAI-2K >6) and anti-ds DNA positivity. None of the patients experienced any flare or adverse reaction throughout the study. Conclusions: According to these results, we conclude that inactivated hepatitis A vaccine is safe and well tolerated in childhood-onset systemic lupus erythematosus patients, with no adverse events or increase in activity. Immunogenicity to the hepatitis A vaccine was adequate, with a seropositivity rate of 80%.
Using Machine Learning To Predict Suitable Conditions for Organic Reactions

Reaction condition recommendation is an essential element for the realization of computer-assisted synthetic planning. Accurate suggestions of reaction conditions are required for experimental validation and can have a significant effect on the success or failure of an attempted transformation. However, de novo condition recommendation remains a challenging and under-explored problem and relies heavily on chemists’ knowledge and experience. In this work, we develop a neural-network model to predict the chemical context (catalyst(s), solvent(s), reagent(s)), as well as the temperature most suitable for any particular organic reaction. Trained on ∼10 million examples from Reaxys, the model is able to propose conditions where a close match to the recorded catalyst, solvent, and reagent is found within the top-10 predictions 69.6% of the time, with top-10 accuracies for individual species reaching 80–90%. Temperature is accurately predicted within ±20 °C from the recorded temperature in 60–70% of test cases, with higher accuracy for cases with correct chemical context predictions. The utility of the model is illustrated through several examples spanning a range of common reaction classes. We also demonstrate that the model implicitly learns a continuous numerical embedding of solvent and reagent species that captures their functional similarity.
Healthcare staff's evaluation of a walk-in centre at a healthcare centre in an immigrant-dense area.

AIMS AND OBJECTIVES To evaluate a walk-in centre at a healthcare centre in an immigrant-dense area where a high proportion of the patients have limited language ability in Swedish, from the perspective of healthcare personnel. BACKGROUND Increased global migration results in higher vulnerability in migrants, with the risk of increased morbidity and mortality. Migrants' health often deteriorates, which can be attributed to an increased level of stress and adaptation to a new lifestyle. Therefore, immigrants are at higher risk of being affected by, for example, cardiovascular diseases and diabetes. This requires access to good health care. DESIGN A qualitative exploratory study was conducted, using semi-structured interviews. Content analysis was used in the analysis process. METHODS Semi-structured interviews were held with 15 purposively sampled doctors and nurses, working at a healthcare centre in Sweden. Data were collected during autumn 2017. The study was performed in accordance with COREQ. RESULTS Working at the walk-in centre involved caring for everything from basic to advanced health problems and meant a high pace that required stress-resistant personnel. The walk-in centre was described as both promoting and threatening patient safety. The personnel had several ideas on how to develop the walk-in centre. CONCLUSIONS A walk-in centre can be seen as a necessity related to issues of ensuring patient safety and delivering care for everyone in an immigrant-dense area. However, it cannot be the only form of care offered, as it seems not be adapted to certain groups, such as people with disabilities and the elderly. RELEVANCE TO CLINICAL PRACTICE The findings emphasise that a walk-in centre is a way to increase accessibility for the entire population and offer equal care for all, even if it involves challenges that need to be addressed.
In Vivo Photovoltaic Performance of a Silicon Nanowire Photodiode–Based Retinal Prosthesis

Purpose For more than 20 years, there has been an international, multidisciplinary effort to develop retinal prostheses to restore functional vision to patients blinded by retinal degeneration. We developed a novel subretinal prosthesis with 1512 optically addressed silicon nanowire photodiodes, which transduce incident light into an electrical stimulation of the remaining retinal circuitry. This study was conducted to evaluate the efficacy of optically driving the subretinal prosthesis to produce visual cortex activation via electrical stimulation of the retina. Methods We measured electrically evoked potential responses (EEPs) in rabbit visual cortex in response to illumination of the subretinal nanowire prosthesis with pulsed 852-nm infrared (IR) light. We compared the EEP responses to visually evoked potential responses (VEPs) to pulsed 532-nm visible light (positive control) and pulsed 852-nm IR light (negative control). Results Activating the devices with IR light produced EEP responses with a significantly higher trough-to-peak amplitude (54.17 ± 33.4 μV) than IR light alone (24.07 ± 22.1 μV) or background cortical activity (23.22 ± 17.2 μV). EEP latencies were significantly faster than focal VEP latencies. Focal VEPs produced significantly higher amplitudes (94.88 ± 43.3 μV) than EEPs. We also demonstrated how an electrode placed on the cornea can be used as a noninvasive method to monitor the function of the implant. Conclusions These results show that subretinal electrical stimulation with nanowire electrodes can elicit EEPs in the visual cortex, providing evidence for the viability of a subretinal nanowire prosthetic approach for vision restoration.
Influence of Implant Material and Surface on Differentiation and Proliferation of Human Adipose-Derived Stromal Cells

For the guided regeneration of periimplant hard and soft tissues, human adipose-derived stromal cells (hADSC) seem to be a promising source for mesenchymal stromal cells. For this, the proliferation and differentiation of hADSC were evaluated on titanium and zirconia dental implants with different surface treatments. Results were compared to edaphic cells as human osteoblasts (hOB) and human gingival fibroblasts (HGF). Primary cells were cultured on (1) titanium implants with a polished surface (Ti-PT), (2) sandblasted and acid-etched titanium (Ti-SLA), (3) sandblasted and alkaline etched zirconia (ZrO2-ZLA) and (4) machined zirconia (ZrO2-M). The cell proliferation and differentiation on osteogenic lineage were assessed after 1, 7 and 14 days. Statistical analysis was performed by one-way ANOVA and a modified Levene test with a statistical significance at p = 0.05. PostHoc tests were performed by Bonferroni-Holm. Zirconia dental implants with rough surface (ZrO2-ZLA) showed the highest proliferation rates (p = 0.048). The osteogenic differentiation occurred early for zirconia and later for titanium implants, and it was enhanced for rough surfaces in comparison to polished/machined surfaces. Zirconia was more effective to promote the proliferation and differentiation of hADSCs in comparison to titanium. Rough surfaces were able to improve the biological response for both zirconia and titanium.
Enhancer Trapping and Annotation in Zebrafish Mediated with Sleeping Beauty, piggyBac and Tol2 Transposons

Although transposon-mediated enhancer trapping (ET) is successfully applied in diverse models, the efficiency of various transposon systems varies significantly, and little information is available regarding efficiency of enhancer trapping by various transposons in zebrafish. Most potential enhancers (Ens) still lack evidence of actual En activity. Here, we compared the differences in ET efficiency between sleeping beauty (SB), piggyBac (PB) and Tol2 transposons. Tol2 represented the highest germline transfer efficiencies at 55.56% (NF0 = 165), followed by SB (38.36%, NF0 = 151) and PB (32.65%, NF0 = 149). ET lines generated by the Tol2 transposon tended to produce offspring with a single expression pattern per line, while PB and SB tended to generate embryos with multiple expression patterns. In our tests, 10 putative Ens (En1–10) were identified by splinkerette PCR and comparative genomic analysis. Combining the GFP expression profiles and mRNA expression patterns revealed that En1 and En2 may be involved in regulation of the expression of dlx1a and dlx2a, while En6 may be involved in regulation of the expression of line TK4 transgene and rps26, and En7 may be involved in the regulation of the expression of wnt1 and wnt10b. Most identified Ens were found to be transcribed in zebrafish embryos, and their regulatory function may involve eRNAs.