Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects

Variants of tubulin beta 8 class VIII (TUBB8) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi‐pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.
Effectiveness and Safety of Oral Anticoagulants Among Non-Valvular Atrial FibrillationPatients with Polypharmacy.

AIMS Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). METHODS AND RESULTS A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01JAN2013-30SEP2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥ 6 concomitant medications on the index date. Propensity score matching was conducted to compare non-Vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188,893 patients with polypharmacy were included, with an average of 8 concomitant medications (IQR 6-9). Compared to warfarin, apixaban (HR: 0.59, 95% CI: 0.52-0.68) and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban. CONCLUSIONS In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favorable for NOACs vs warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.
Membrane Interaction of Ibuprofen with Cholesterol-Containing Lipid Membranes

Deciphering the membrane interaction of drug molecules is important for improving drug delivery, cellular uptake, and the understanding of side effects of a given drug molecule. For the anti-inflammatory drug ibuprofen, several studies reported contradictory results regarding the impact of ibuprofen on cholesterol-containing lipid membranes. Here, we investigated membrane localization and orientation as well as the influence of ibuprofen on membrane properties in POPC/cholesterol bilayers using solid-state NMR spectroscopy and other biophysical assays. The presence of ibuprofen disturbs the molecular order of phospholipids as shown by alterations of the 2H and 31P-NMR spectra of the lipids, but does not lead to an increased membrane permeability or changes of the phase state of the bilayer. 1H MAS NOESY NMR results demonstrate that ibuprofen adopts a mean position in the upper chain/glycerol region of the POPC membrane, oriented with its polar carbonyl group towards the aqueous phase. This membrane position is only marginally altered in the presence of cholesterol. A previously reported result that ibuprofen is expelled from the membrane interface in cholesterol-containing DMPC bilayers could not be confirmed.
Acute Toxicity Assessment of Tribenuron-Methyl Herbicide in Silver Carp (Hypophthalmicthys molitrix), Common Carp (Cyprinus carpio) and Caspian Roach (Rutilus rutilus caspicus)

3 Abstract: A short term definitive tests by the static non-renewal bioassay method was made inthe laboratory to determine the acutetoxicity (LC ) of technical grade of tribenuron-methyl herbicide (95%) in three non-target 50 freshwater fish. Groups of ten silver carp (Hypophthalmicthys molitrix), common carp (Cyprinus carpio) and caspian roach (Rutilusrutiluscaspicus) were exposed to the tribenuron-methyl (0, 50, 100, 200, 300 and 500 ppm). Data obtained from the tribenuron-methyl acute toxicity tests were evaluated using the probitanalysis statistical method. The estimated 96 hrs LC values (95% confidence limits) of tribenuron-methyl for caspian 50 roach, common carp and silver carpwere152.74 (112.10-197.98), 289.08 (240.93 - 357.29) and 139.45 (105.32- 176.69) ppm, respectively.At various concentrations of tribenuron-methyl (100-500 ppm), fish showed abnormal behavioral responses (rapid gill movement, gulping air at the surface, erraticswimming, loss of equilibrium, reduction of body pigment and increased mucus secretion). Results of the present study indicate that technical grade of tribenuron-methyl is toxic to studied fish.
Masters of asymmetry – lessons and perspectives from 50 years of septins

Septins are a unique family of GTPases, which were discovered 50 years ago as essential genes for the asymmetric cell shape and division of budding yeast. Septins assemble into filamentous nonpolar polymers, which associate with distinct membrane macrodomains and subpopulations of actin filaments and microtubules. While structurally a cytoskeleton-like element, septins function predominantly as spatial regulators of protein localization and interactions. Septin scaffolds and barriers have provided a long-standing paradigm for the generation and maintenance of asymmetry in cell membranes. Septins also promote asymmetry by regulating the spatial organization of the actin and microtubule cytoskeleton, and biasing the directionality of membrane traffic. In this 50th anniversary perspective, we highlight how septins have conserved and adapted their roles as effectors of membrane and cytoplasmic asymmetry across fungi and animals. We conclude by outlining principles of septin function as a module of symmetry breaking, which alongside the monomeric small GTPases provides a core mechanism for the biogenesis of molecular asymmetry and cell polarity.
House Cricket Acetylcholinesterase: Histochemical Localization and in Situ Inhibition by O,O-Dimethyl S-Aryl Phosphorothioates,

The distribution of acetylcholinesterase (AChE) in the central nervous system of the house cricket, Acheta domesticus L. , was investigated by histochemical localization. Abundant enzyme activity was evident in the head in the frontal ganglion, cerebrum, subesophageal ganglion, and optical lobes; and in the thorax in the ganglia and interganglionic connectives. AChE was concentrated in areas of complex synapses but was also present in the cell body region and in interganglionic connectives. The patterns of in situ inhibition of AChE by O,O -dimethyl S -aryl phosphorothioates were investigated. At the hyperactive state of poisoning AChE was reduced throughout the brain and in the peripheral areas of the thoracic ganglia and interganglionic connectives. In the paralytic stage, enzyme activity was still further decreased, and a few hours after knockdown, the enzyme activity had virtually disappeared. However, some spontaneous reactivation of AChE in dead animals was observed after 48 hours.
Mood symptoms and impairment due to substance use: A network perspective on comorbidity.

BACKGROUND Mood disorders and problematic substance use co-occur and confer reciprocal risk for each other. Few studies use analytic approaches appropriate for testing whether specific features of one disorder confer risk for the other. METHODS 445 participants (59.8% female, Mean age = 20.3 years) completed measures of depression and hypo/mania symptoms and substance use-related impairment; 330 had complete data at follow-up. Of these, 28% reported a history of depression, 4% of bipolar spectrum disorder, 11% of substance use disorder, and 55% reported substance-related impairment. Symptoms and domains of substance-related impairment were modeled in cross-sectional and cross-lagged panel network models. RESULTS Impulsive and interpersonal impairment were most highly comorbid with mood symptoms. Suicidal ideation, sadness, decreased need for sleep, and guilt were the symptoms most highly comorbid with impairment. Interpersonal impairment due to substance use was the strongest cross-construct predictor of mood symptoms and suicidal ideation was most predictive of impairment. Social, intrapersonal, and physical impairment due to substance use were most predicted by previous mood symptoms and decreased need for sleep, guilt, and euphoria were most strongly predicted by past impairment. LIMITATIONS Measures do not assess all mood symptoms, participants with low reward sensitivity were excluded, only self-report measures were used, and some variables were single-items. CONCLUSIONS Components of these syndromes that confer cross-construct risk might not be the same components that are predicted by the other construct. The bidirectional relationship between mood symptoms and problematic substance use might be better conceptualized at the element, rather than diagnostic, level.
Topological Hall Signatures of Two Chiral Spin Textures Hosted in a Single Tetragonal Inverse Heusler Thin Film

Magnetic skyrmions and antiskyrmions are observed in material classes with different crystal symmetries, where the Dzyaloshinskii–Moriya interaction stabilizes either skyrmions or antiskyrmions. Here, we report the observation of two distinct peaks in the topological Hall effect in a thin film of Mn2RhSn. Utilizing a phenomenological approach and electronic transport simulations, these topological Hall effect features are attributed to be direct signatures of two topologically distinct chiral spin objects, namely, skyrmions and antiskyrmions. Topological Hall effect studies allow us to determine the existence of these two topological objects over a wide range of temperature and magnetic fields. In particular, we find skyrmions to be stable at low temperatures, suggesting the increased importance of dipolar interactions.
Twenty-year follow-up of a pilot/phase II trial on the Bonn protocol for primary CNS lymphoma

Objective To determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a very long-term follow-up of nearly 20 years. Methods Sixty-five patients (median age 62 years, range 27–75; median Karnofsky performance score 70, range 20–90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation. Results Median follow-up for surviving patients was 19.6 years (17.5–23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval [CI] 2.9–5.9); for patients ≤60 years, 11.0 years (95% CI 4.8–17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years. Conclusion At a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL. Classification of evidence This work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.
The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1

Herpes simplex virus 1 (HSV-1) is very successful in establishing acute and latent infections in humans by counteracting host antiviral innate immune responses. HSV-1 has evolved various strategies to evade host antiviral innate immunity and some cellular survival-associated pathways. Since there is still no vaccine available for HSV-1, a continuous update of information regarding the interaction between HSV-1 infection and the host antiviral innate immunity will provide novel insights to develop new therapeutic strategies for HSV-1 infection and its associated diseases. SUMMARY Herpes simplex virus 1 (HSV-1) is very successful in establishing acute and latent infections in humans by counteracting host antiviral innate immune responses. HSV-1 has evolved various strategies to evade host antiviral innate immunity and some cellular survival-associated pathways. Since there is still no vaccine available for HSV-1, a continuous update of information regarding the interaction between HSV-1 infection and the host antiviral innate immunity will provide novel insights to develop new therapeutic strategies for HSV-1 infection and its associated diseases. Here, we update recent studies about how HSV-1 evades the host antiviral innate immunity, specifically how HSV-1 proteins directly or indirectly target the adaptors in the antiviral innate immunity signaling pathways to downregulate the signal transduction. Additionally, some classical intracellular stress responses, which also play important roles in defense of viral invasion, will be discussed here. With a comprehensive review of evasion mechanisms of antiviral innate immunity by HSV-1, we will be able to develop potential new targets for therapies and a possible vaccine against HSV-1 infections.
Fatty Acid Synthase Beta Dehydratase in the Lipid Biosynthesis Pathway Is Required for Conidiogenesis, Pigmentation and Appressorium Formation in Magnaporthe oryzae S6

Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty acid synthase beta subunit dehydratase (FAS1) gene in lipid biosynthesis. The FAS1 gene was silenced through homologous double crossover in Magnaporthe oryzae strain S6 to study the effect on lipid biosynthesis. The vegetative growth of Δfas1 mutants show the highest drop on oleic acid (between 10 and 50%), while the mycelial dry weight of mutants dropped significantly on all media. Conidiation of FAS1 mutants show a ~10- and ~5-fold reduction on oatmeal and Potato Dextrose Agar (PDA), respectively. Mutants formed mycelium that were mildly pigmented, indicating that the deletion of FAS1 may have affected melanin biosynthesis. Biochemical and gene expression studies concluded that the fatty acid degradation pathway might have been interrupted by FAS1 deletion. FAS1 mutants showed no enzyme activity on glucose or olive oil, suggesting that the mutants may lack functional peroxisomes and be defective in β-oxidation of fatty acids, hence explaining the reduced lipid deposits in the spores.
Valganciclovir as Add-On to Standard Therapy in Secondary Glioblastoma

Patients with glioblastoma have a very poor prognosis despite aggressive therapeutic strategies. Cytomegalovirus has been detected in >90% of glioblastoma tumors. This virus can affect tumor progression and may represent a novel glioblastoma therapy target. We report, here, a retrospective survival analysis of patients with secondary glioblastoma who were treated with the anti-viral drug valganciclovir at Karolinska University Hospital in Stockholm. We performed survival analyses of eight patients with secondary glioblastoma who were treated with a standard dose of valganciclovir as an add-on to second-line therapy after their disease progression to glioblastoma. Thirty-six patients with secondary glioblastoma admitted during the same time period who received similar treatment and care served as contemporary controls. The patients treated with valganciclovir showed an increased median overall survival after progression to glioblastoma compared with controls (19.1 versus 12.7 months, p = 0.0072). This result indicates a potential positive effect of valganciclovir in secondary glioblastoma, which is in agreement with our previous observation that valganciclovir treatment improves the outcomes of patients with newly diagnosed glioblastoma. Larger randomized studies are warranted to prove this hypothesis.
What Makes Hotel Chefs in Korea Interact with SNS Community at Work? Modeling the Interplay between Social Capital and Job Satisfaction by the Level of Customer Orientation

This study aimed to investigate the effect of social network services (SNS) on hotel chef job satisfaction, and to provide an effective strategy to reduce chef turnover and maintain sustainable economic development in hospitality. The intention was to empirically test and analyze the effect of SNS on hotel chef job satisfaction by applying the social capital theory. The social capital theory was explored and the effect of chefs’ social capital on their social presence and job satisfaction was demonstrated. Furthermore, this study aimed to determine the moderation effect of customer orientation. A total of 130 surveys were collected from chefs working at Michelin-starred restaurants in Seoul, Korea. SPSS and AMOS were used to conduct statistical analyses. The outputs included exploratory factor analysis, confirmatory factor analysis, convergent analysis, discriminant analysis, path analysis, mediation effect analysis, and moderation effect analysis. The results illustrated that bridging social capital significantly impacts chef social presence, while bonding social capital does not significantly influence their presence. In addition, both bonding and bridging social capital positively relate to chef job satisfaction. Significant mediation and moderation effects were demonstrated on the path taken by chefs. The results of this study offer theoretical and managerial implications for hotel human resources managers to enhance chef job satisfaction.
Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic

The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk for or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.
Solution structure and RNA-binding of a minimal ProQ-homolog from Legionella pneumophila (Lpp1663)

Small regulatory RNAs (sRNAs) play an important role for posttranscriptional gene regulation in bacteria. sRNAs recognize their target messenger RNAs (mRNAs) by base-pairing, which is often facilitated by interactions with the bacterial RNA-binding proteins Hfq or ProQ. The FinO/ProQ RNA-binding protein domain was first discovered in the bacterial repressor of conjugation, FinO. Since then, the functional role of FinO/ProQ-like proteins in posttranscriptional gene regulation was extensively studied in particular in the enterobacteria E. coli and Salmonella enterica and a wide range of sRNA-targets was identified for these proteins. In addition, enterobacterial ProQ homologs also recognize and protect the 3′-ends of a number of mRNAs from exonucleolytic degradation. However, the RNA-binding properties of FinO/ProQ proteins with regard to the recognition of different RNA targets are not yet fully understood. Here, we present the solution NMR structure of the so far functionally uncharacterized ProQ homolog Lpp1663 from Legionella pneumophila as a newly confirmed member and a minimal model system of the FinO/ProQ protein family. In addition, we characterize the RNA-binding preferences of Lpp1663 with high resolution NMR spectroscopy and isothermal titration calorimetry (ITC). Our results suggest a binding preference for single-stranded uridine-rich RNAs in the vicinity of stable stem–loop structures. According to chemical shift perturbation experiments, the single-stranded U-rich RNAs interact mainly with a conserved RNA-binding surface on the concave site of Lpp1663.
Fatty acid composition of meat from the hind leg cut of rabbits (Oryctolagus cunniculus) fed diets containing graded levels of processed tallow (Detarium microcarpum) seed meal.

Eighty one (81) weaned rabbits of mixed breeds and sexes (male and female) were randomly allotted to nine treatment groups with nine rabbits per treatment. Each treatment had three replicates with three rabbits per replicate. Processed tallow was included in the diets as a source of protein which was set at 16 % CP. The control diet had 100 % palm kernel cake (PKC) and 0 % tallow seed meal (TSM). Diets 1 - 4 contained cooked tallow seed meal (CTSM) included at 75 % PKC: 25 % CTSM, 50 % PKC: 50% CTSM, 25% PKC:75 % CTSM and 0 % PKC: 100 % CTSM, while groups 5 - 8 had fermented tallow seed meal diets (FTSM) and included at the same levels as in the cooked diets. Fifty four rabbits were randomly selected for slaughtering from the nine groups with six rabbits (male and females) per group. Fatty acid content of the hind leg of rabbits were determined. All the fatty acids measured were significantly (P<0.05) influenced by the processing methods except decosenoic acid methyl ester and pentadecanoic acid methyl esters. The levels of inclusion of tallow also significantly (P<0.05) affected all the fatty acids composition measured. It was therefore concluded that irrespective of the processing methods the use of tallow in the diets of rabbits has no negative effect on the fatty acid composition of rabbit meat.