Miracle-dz/UniFAR-FTUs huggingface dataset:
Biotic and abiotic factors shape arbuscular mycorrhizal fungal communities associated with the roots of the widespread fern Botrychium lunaria (Ophioglossaceae).

Arbuscular mycorrhizal fungi (AMF) play central roles in terrestrial ecosystems by interacting with both above and belowground communities as well as by influencing edaphic properties. The AMF communities associated with the roots of the fern Botrychium lunaria (Ophioglossaceae) were sampled in four transects at 2400 m a.s. l. in the Swiss Alps and analyzed using metabarcoding. Members of four Glomeromycota genera were identified across the 71 samples. Our analyses revealed the existence of a core microbiome composed of four abundant Glomus OTUs, as well as a low OTU turnover between samples. The AMF communities were not spatially structured, which contrasts with most studies on AMF associated with angiosperms. pH, microbial connectivity and humus cover significantly shaped AMF beta diversity but only explained a minor fraction of variation in beta diversity. AMF OTUs associations were found to be significant by both cohesion and co-occurrence analyses, suggesting a role for fungus-fungus interactions in AMF community assembly. In particular, OTU co-occurrences were more frequent between different genera than among the same genus, rising the hypothesis of functional complementarity among the AMF associated to B. lunaria. Altogether, our results provide new insights into the ecology of fern symbionts in alpine grasslands. ORIGINALITY-SIGNIFICANCE STATEMENT: This study explores for the first time and at a regional scale, the diversity and community structure of arbuscular mycorrhizal fungi (AMF) associated with the widespread fern Botrychium lunaria (Ophioglossaceae). Most community ecology studies on AMF have focused on angiosperm hosts, leaving early divergent terrestrial plants largely understudied. In addition, AMF from alpine grasslands have received less attention than those from low altitude grasslands and arable soils. Metabarcoding of AMF from four transects located at an altitude of 2400 m a.s. l. in the Swiss Alps allowed us to comprehensively assess the AMF diversity associated to B. lunaria and also to identify a core microbiome composed of Glomus OTUs. This article is protected by copyright. All rights reserved.
Analysis and prediction of the effects of single amino acid variants in human disease

Over the past fifty years, the genetic bases for many human diseases have been discovered. Genome-wide association studies (GWAS) have pinpointed genetic loci containing disease-associated variants, which can be probed in more detail using targeted DNA sequencing and imputation. The falling cost of DNA sequencing has led to the adoption of whole-genome and whole-exome sequencing, enabling more of the genome to be investigated. However, with the masses of data being produced, it is vital to have tools to identify truly interesting disease-associated variation. This thesis describes the development of three tools to help researchers identify and characterise disease-associated genetic variants. Whole-genome sequencing data contain many reported variants that may be due to errors in sequencing, read-mapping or variant calling. It is therefore vital to filter out these incorrect variants and Chapter 6 describes the development of an ensemble machine learning method for filtering these variants, which is able to remove over 80% of incorrect variants at the expense of under 4% of true variation. Single amino acid variants (SAVs) are one of the best-studied groups of variants in human disease, and there are a number of tools available to predict whether SAV will be deleterious. SuSPect (disease-susceptibility–based SAV phenotype predictor) out-performs other tested methods, thanks to its incorporation of information from protein-protein interaction networks. Finally, knowing a variant is potentially damaging to a protein’s function does not tell a researcher whether or not it will cause the disease of interest,
Prognosis in young women less than 40 years of age with brain metastasis from breast cancer.

Background Brain metastasis from breast cancer (bca) in young women is doubly devastating because both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged, survival is expected to increase for these young women. Methods Using the oacis and sardo patient databases, we identified 121 patients diagnosed with bca and brain metastasis between 2006 and 2016 at the University of Montreal Hospital Centre. Those patients were divided into Group A, patients who developed brain metastasis during the evolution of metastatic bca, and Group B, patients whose first metastasis was to the brain. For each group, we compared young patients (<40 years of age) with older patients (≥40 years of age). Results Among the 121 patients with brain metastasis, median overall survival (mos) was significantly longer for those less than 40 years of age than for those 40 or more years of age (18 months vs. 4 months, p < 0.001). With respect to the timing of brain metastasis, survival was significantly longer in Group B than in Group A (7 months vs. 4 months, p = 0.032). In Group A, mos was significantly longer for patients less than 40 years of age than for patients 40 or more years of age (18 months vs. 3 months, p = 0.0089). In Group B, the 2-year overall survival rate was 57% for patients less than 40 years of age and 12% for those 40 or more years of age (mos: not reached vs. 7 months; p = 0.259). Conclusions In our single-centre retrospective cohort of women with brain metastasis from bca, prognosis was better for young women (<40 years) than for older women (≥40 years). Survival was also longer for patients whose initial metastasis was to the brain than for patients whose brain metastasis developed later in the disease course. In patients who received systemic treatment, median survival remained significantly higher in women less than 40 years of age. Further studies are needed to validate those results.
The Association of Occupational Noises and the Prevalence of Metabolic Syndrome.

OBJECTIVES Previous studies have shown the association of exposure to noise with cardiovascular diseases such as hypertension, however, it is not well known whether the exposure has any effect on metabolic syndrome (MetS). This study aimed to quantify and clarify the association between noise exposure and the prevalence of MetS. METHODS This cross-sectional study was conducted in 2017 among 518 workers in a thermal power plant industry. According to types of work and 8-h equivalent A-weighted sound pressure level (8-h LAeq), the participants were divided into the following groups: office workers and line-production workers exposed to < 85, 90 to <95, 95 to <100, and ≥100 dBA. We used the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria to identify subjects with MetS. The logistic regression was used to determine the odds of MetS among study groups. RESULTS We observed the significant differences in the number (%) of subjects with high blood pressure in line-production workers who exposed to noise ≥100 (12 [19.7%]) versus <85 dBA (7 [7.1%]) and office (10 [4.7%]) groups. For the waist circumference (>102 cm), there was a significant difference in the ≥100 dBA group (12 [19.7%]) compared with office group (21 [9.8%]). Obtained results indicated only the significant difference in the prevalence of MetS in ≥100 versus <85 dBA groups (10 [16.4%] versus 6 [6.1%]). The unadjusted and adjusted odds ratios and 95% confidence intervals of MetS in ≥100 versus <85 dBA groups were estimated 3.01 (1.03, 8.75) and 3.24 (1.01, 10.42), respectively. CONCLUSIONS This study indicated the significant association between noise exposure and MetS in line-production workers. However, more studies are needed to confirm our results.
Initial experience with high dose rate brachytherapy of periorbital sarcoids in the horse

Summary Periorbital sarcoids are a common condition in the horse and are difficult to treat due to their location and invasive nature. Radiotherapy is considered the gold standard treatment, and high dose rate brachytherapy (HDRB) may represent a safer and more effective method of delivering radiotherapy in the standing sedated horse. The objective of this retrospective clinical case series study was to describe the response rate and safety of HDRB for the treatment of periorbital sarcoids in the horse. Horses and ponies referred for HDRB treatment of confirmed periorbital sarcoids were eligible for inclusion in the study. Sarcoids were confirmed via clinical diagnosis and biopsy. Horses were given 2 fractions of 12.5 Gy per fraction, delivered a week apart, under standing sedation via a novel HDRB technique. Eight horses with periorbital sarcoids were treated with HDRB under standing sedation. A complete response occurred in all cases. No significant acute adverse effects were noted after treatment and the cosmetic result was excellent, with permanent epilation and leucotrichia the only long-term sequelae. Follow-up was available for between 10 and 12 months after treatment. The major limitation of this study is the lack of long-term follow-up and the small case numbers. It was concluded that HDRB appears to be an effective and safe method of treating periorbital sarcoids in the horse. Long-term follow-up is required to determine the risk of recurrence of treated lesions.
Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing

Macrophages, renowned for clearance of debris and bacteria in the wound, can also uptake signaling inhibitors to promote fibrosis. Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.
Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens

Objective To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the re-myelination.
Epithelial-Myoepithelial Carcinoma of the Palate: Report of a Case and Review of the Literatures

Epithelial-myoepithelial carcinoma (EMC) is considered as a rare malignant salivary gland neoplasm with good prognosis, low recurrence rate and rare metastasis. Here we present a case of epithelial-myoepithelial carcinoma in a 42-year-old female with a swelling of 3-year duration in her palate. Histopathologic evaluation of the lesion demonstrated a well-circumscribed, biphasic salivary gland tumor composed of double-layered ductal/glandular structures, composed of small luminal eosinophilic cells and abluminal larger clear myoepithelial cells, and luminal cells were positive for pan-cytokeratin, while the abluminal cells exhibited strong immunoreactivity for p63. Ki-67 proliferative index was 1% in abluminal cells. In this article, histopathologic and immunohistochemical features of EMC and its mimics are discussed and the previously reported cases of EMC in the literature are summarized.
Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma

Objective Hepatocellular carcinoma (HCC) is the fastest-growing cause of cancer-related mortality with chronic viral hepatitis and non-alcoholic steatohepatitis (NASH) as major aetiologies. Treatment options for HCC are unsatisfactory and chemopreventive approaches are absent. Chronic hepatitis C (CHC) results in epigenetic alterations driving HCC risk and persisting following cure. Here, we aimed to investigate epigenetic modifications as targets for liver cancer chemoprevention. Design Liver tissues from patients with NASH and CHC were analysed by ChIP-Seq (H3K27ac) and RNA-Seq. The liver disease-specific epigenetic and transcriptional reprogramming in patients was modelled in a liver cell culture system. Perturbation studies combined with a targeted small molecule screen followed by in vivo and ex vivo validation were used to identify chromatin modifiers and readers for HCC chemoprevention. Results In patients, CHC and NASH share similar epigenetic and transcriptomic modifications driving cancer risk. Using a cell-based system modelling epigenetic modifications in patients, we identified chromatin readers as targets to revert liver gene transcription driving clinical HCC risk. Proof-of-concept studies in a NASH-HCC mouse model showed that the pharmacological inhibition of chromatin reader bromodomain 4 inhibited liver disease progression and hepatocarcinogenesis by restoring transcriptional reprogramming of the genes that were epigenetically altered in patients. Conclusion Our results unravel the functional relevance of metabolic and virus-induced epigenetic alterations for pathogenesis of HCC development and identify chromatin readers as targets for chemoprevention in patients with chronic liver diseases.
Acceptability of anal cancer screening tests for women living with HIV in the EVVA study.

Background Anal cancer is potentially preventable through screening. For screening to be implemented, the screening procedures must be acceptable to the affected population. The objective of the present study was to measure the acceptability of currently available anal cancer screening tests in a population of women living with hiv who had experienced the tests. Methods The evva study ("Evaluation of Human Immunodeficiency Virus, Human Papillomavirus, and Anal Intraepithelial Neoplasia in Women") is a prospective cohort study of adult women living with hiv in Montreal, Quebec. Participants were screened with cervical or anal hpv testing and cervical or anal cytology every 6 months for 2 years. High-resolution anoscopy (hra) and digital anal rectal examination (dare) were also performed systematically, with biopsies, at baseline and at 2 years. An acceptability questionnaire was administered at the final visit or at study withdrawal. Results Of 124 women who completed the acceptability questionnaire, most considered screening "an absolute necessity" in routine care for all women living with hiv [77%; 95% confidence interval (ci): 69% to 84%]. Yearly anal cytology or anal hpv testing was considered very acceptable by 81% (95% ci: 73% to 88%); hra every 2 years was considered very acceptable by 84% (95% ci: 77% to 90%); and yearly dare was considered very acceptable by 87% (95% ci: 79% to 92%). Acceptability increased to more than 95% with a longer proposed time interval. Pain was the main reason for lower acceptability. Conclusions Most participating women considered anal cancer screening necessary and very acceptable. Longer screening intervals and adequate pain management could further increase the acceptability of repeated screening.
Development and validation of a QuEChERS-based liquid chromatography tandem mass spectrometry multi-method for the determination of 38 native and modified mycotoxins in cereals.

Here a reliable and sensitive method for the determination of 38 (modified) mycotoxins was developed. Using a QuEChERS-based extraction method (acetonitrile/water/formic acid (75:20:5, v/v/v)), followed by two runs of high performance liquid chromatography tandem mass spectrometry with different conditions, relevant mycotoxins in cereals were analyzed. The method was validated according to the performance criteria defined by the European Commission (EC) in Commission Decision No. 657/2002. Limits of quantification ranged from 0.05 to 150 µg/kg. Good linearity (R2 > 0.99), recovery (61 to 120%), repeatability (RSDr < 15%), and reproducibility (RSDR < 20%) were obtained for most mycotoxins. However, validation results for Alternaria toxins and fumonisins were unsatisfying. Matrix effects (-69 to +59%) were compensated using standard addition. Application on reference materials gave correct results while analysis of samples from local retailers revealed contamination, especially with deoxynivalenol, deoxynivalenol-3-glucoside, fumonisins, and zearalenone in concentrations up to 369, 58, 1002, and 21 µg/kg.
Physicians’ Understanding and Practices of Pharmacovigilance: Qualitative Experience from a Lower Middle-Income Country

Developed countries have established pharmacovigilance systems to monitor the safety of medicines. However, in the developing world, drug monitoring and reporting are facing enormous challenges. The current study was designed to explore the challenges related to the understanding and practices of physicians in reporting adverse drug reactions in Lahore, Pakistan. Through the purposive sampling technique, 13 physicians were interviewed. All interviews were audio-recorded, transcribed verbatim, and analyzed for a thematic content analysis. The thematic content analysis yielded six major themes: (1) Familiarity with medication safety and adverse drug reaction (ADR) concept, (2) Knowledge about pharmacovigilance activities, (3) Practices related to ADR reporting, (4) Barriers impeding ADR reporting, (5) Acknowledgement of the pharmacist’s role, and (6) System change needs. The majority of the physicians were unaware of the ADR reporting system; however, they were ready to accept practice changes if provided with the required skills and training. A lack of knowledge, time, and interest, a fear of legal liability, poor training, inadequate physicians’ and other healthcare professionals’ communication, and most importantly lack of a proper reporting system were reported as barriers. The findings based on emerging themes can be used to establish an effective pharmacovigilance system in Pakistan. Overall, physicians reported a positive attitude towards practice changes, provided the concerned authorities support and take interest in this poorly acknowledged but most needed component of the healthcare system.
Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling

Abstract Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, which is monitored by the spindle assembly checkpoint (SAC) signaling. As an upstream factor of SAC, the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling. However, the underlying molecular mechanism remains elusive. Here, we demonstrated that the multisite interactions between Mps1 and Ndc80 complex (Ndc80C) govern Mps1 kinetochore targeting. Importantly, we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C. We further identified that Mps1 C-terminal fragment, which contains the protein kinase domain and C-tail, enhances Mps1 kinetochore localization. Mechanistically, Mps1 C-terminal fragment mediates its dimerization. Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1, leading to aberrant mitosis due to compromised SAC function. Taken together, our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.
Transcriptional Factors Regulate Plant Stress Responses Through Mediating Secondary Metabolism

Plants are adapted to sense numerous stress stimuli and mount efficient defense responses by directing intricate signaling pathways. They respond to undesirable circumstances to produce stress-inducible phytochemicals that play indispensable roles in plant immunity. Extensive studies have been made to elucidate the underpinnings of defensive molecular mechanisms in various plant species. Transcriptional factors (TFs) are involved in plant defense regulations through acting as mediators by perceiving stress signals and directing downstream defense gene expression. The cross interactions of TFs and stress signaling crosstalk are decisive in determining accumulation of defense metabolites. Here, we collected the major TFs that are efficient in stress responses through regulating secondary metabolism for the direct cessation of stress factors. We focused on six major TF families including AP2/ERF, WRKY, bHLH, bZIP, MYB, and NAC. This review is the compilation of studies where researches were conducted to explore the roles of TFs in stress responses and the contribution of secondary metabolites in combating stress influences. Modulation of these TFs at transcriptional and post-transcriptional levels can facilitate molecular breeding and genetic improvement of crop plants regarding stress sensitivity and response through production of defensive compounds.