Miracle-dz/UniFAR-FTUs huggingface dataset:
The ultrastructure of muscle fibers and satellite cells in experimental autoimmune encephalomyelitis after treatment with transcranial magnetic stimulation

ABSTRACT In this study, we investigated the effect of transcranial magnetic stimulation (TMS) on the ultrastructure of muscle fibers and satellite cells in rats with experimental autoimmune encephalomyelitis (EAE). EAE-induced animals were treated with TMS (60 Hz at 0.7 mT) for 2 hours in the morning, once a day, 5 days a week, for 3 weeks, starting on day 15 post-immunization. The rats were sacrificed on day 36 post-immunization, and the soleus muscles were evaluated by light microscopy and transmission electron microscopy. Findings were compared with a non-treated EAE group. Electron microscopy analysis showed the presence of degenerated mitochondria, autophagic vacuoles, and altered myofibrils in non-treated EAE group. This correlates with the presence of acid phosphatase activity in muscle fibers and core-targetoid lesions with desmin immunohistochemistry. Most myonuclei in the EAE group showed apoptotic features. In contrast, EAE induced-TMS treated animals had less ultrastructural changes in the mitochondria and the myofibrils, together with less frequent apoptotic nuclear features. Peripheral desmin+ protrusions, as a marker of active satellite cells, were significantly increased in TMS-treated group. This correlates ultrastructurally with the presence of active features in satellite cells in the TMS group. In conclusion, the attenuation of ultrastructural alterations in muscle fibers and activation response of satellite cells caused by EAE indicated that skeletal muscle had a regenerative response to TMS.
Inactivation of Hippo pathway characterizes a poor-prognosis subtype of esophageal cancer

Identification of molecular subtypes that reflect different prognoses and treatment responses, especially immune checkpoint inhibitors (ICIs) in esophageal squamous cell carcinoma (ESCC), is essential for treatment decisions. We performed targeted sequencing in 201 patients with ESCC to discover genetic subtypes and validate our findings via multiple data sets. We identified 3 driver genes (FCGBP, GRIN2B, and FRY), and recurrent truncating mutations in FRY impaired its tumor-suppressive function and promoted tumor proliferation. A 3-gene mutation signature (FAT1, FAT3, and FRY) recognized a molecular subtype named “FAT/FRY” with frequent Hippo pathway–related mutations. In multiple ESCC cohorts, the patients with the FAT/FRY subtype had poorer prognosis than did patients in the WT group. Transcriptome analysis indicated that the FAT/FRY subtype was characterized by inactivation of the Hippo pathway, hypoxia, chemoresistance, higher infiltration of CD8+ T cells and activated DCs, and a transcriptome similar to that of cancer responders. Furthermore, the 3-gene signature predicted better survival for patients treated with ICIs, partially explained by its positive correlation with the tumor mutation burden and neoantigen burden. The 3-gene signature is a biomarker to recognize the FAT/FRY molecular subtype, evaluate prognosis, and select potential beneficiaries of ICIs in ESCC.
Thymoquinone alleviates doxorubicin induced acute kidney injury by decreasing endoplasmic reticulum stress, inflammation and apoptosis

ABSTRACT Doxorubicin (DOX) is used as an anticancer drug despite its many side effects. Thymoquinone (THQ) is a plant-derived substance that exhibits antioxidant and anti-inflammatory properties. We investigated the protective effects of THQ on DOX induced nephrotoxicity in rats. Rats were divided into five groups of eight: group 1, untreated control; group 2, olive oil group given olive oil intraperitoneally (i.p.) for 14 days; group 3, THQ group given 10 mg/kg THQ i.p. for 14 days; group 4, DOX group given a single dose of 15 mg/kg DOX i.p. on day 7 of experiment; group 5, DOX + THQ given 10 mg/kg THQ i.p. for 14 days and 15 mg/kg DOX i.p. on day 7. Kidney tissues were evaluated for histopathology. Caspase-3, IL-17, GRP78 and TNF-α immunostaining was used to determine the expression levels of these proteins among the groups. The TUNEL method was used to determine the apoptotic index. Total antioxidant status (TAS), total oxidant status (TOS), and TNF-α and TGF-β1 levels in kidney tissue were measured using ELISA assay. Histopathologic damage, caspase-3, IL-17, GRP78 and TNF-α immunoreactivity, TUNEL positive cells, TOS, TNF-α and TGF-β1 levels were increased in group 4 compared to group 1. The TAS of group 4 decreased compared to group 1. We found decreased caspase-3, IL-17, GRP78 and TNF-α expressions and TUNEL positive cells in group 5 compared to group 4. In rats given DOX, THQ reduced kidney damage by suppressing endoplasmic reticulum stress, inflammation and apoptosis pathways.
‘Many Minds’ Interpretations of Quantum Mechanics: Replies to Replies

Reponse aux differents commentateurs (dont D. Papineau) qui ont critique l'article de l'A. consacre a l'interpretation multispirituelle de la mecanique quantique (in «British journal for the philosophy of science», n°47, pp. 159-88). Rejetant toute description du monde dans le cadre elementaire de la mecanique quantique, l'A. defend la pertinence de la structure relativiste de la theorie du champ quantique
Predictors of non-stepping time in people with chronic stroke

ABSTRACT Background Sedentary time is an independent construct from active time. Previous studies have examined variables associated with sedentary time to inform behavior change programs; however, these studies have lacked data sets that encompass potentially important domains. Objectives The purpose of this study was to build a more comprehensive model containing previously theorized important predictors of sedentary time and new predictors that have not been explored. We hypothesized that variables representing the domains of physical capacity, psychosocial, physical health, cognition, and environmental would be significantly related to sedentary time in individuals post-stroke. Methods This was a cross-sectional analysis of 280 individuals with chronic stroke. An activity monitor was used to measure sedentary (i.e. non-stepping) time. Five domains (8 predictors) were entered into a sequential linear regression model: physical capacity (6-Minute Walk Test, assistive device use), psychosocial (Activities Specific Balance Confidence Scale and Patient Health Questionnaire-9), physical health (Charlson Comorbidity Index and body mass index), cognition (Montreal Cognitive Assessment), and environmental (Area Deprivation Index). Results The 6-Minute Walk Test (β = −0.39, p < .001), assistive device use (β = 0.15, p = .03), Patient Health Questionnaire-9 (β = 0.16, p = .01), and body mass index (β = 0.11, p = .04) were significantly related to non-stepping time in individuals with chronic stroke. The model explained 28.5% of the variability in non-stepping time. Conclusions This work provides new perspective on which variables may need to be addressed in programs targeting sedentary time in stroke. Such programs should consider physical capacity, depressive symptoms, and physical health.
COVID-19 disease induced alteration of oxidative stress and clinical laboratory parameters in moderate and severe patients.

OBJECTIVE The aim of our study was to present the clinical alterations of CRP, LDH, neutrophil to lymphocyte ratio, platelets to lymphocyte ratio, D-dimer, blood gas analyses, vitamin D, VEGF, IL-6, IFN-γ, CD4+, CD8+) and their correlation with oxidative stress index (OSI) in hospitalized COVID-19 patients. PATIENTS AND METHODS Oxidative stress index and clinical parameters were determined at admission and/or 7 days after hospitalization in 50 patients divided in moderate and severe group. RESULTS In the moderate group of patients, a good correlation (R2 = 0.7400, p<0.05) was found between OSI and PLR, D-dimers and LDH at admission and after 7 days. The OSI correlated well with vitamin D, INF-γ, IL-6, CD4+, CD8+ and the absolute CD8 cell number on admission (R2=0.7635, p<0.05). Vitamin D deficiency (15.37 ng/mL ± 2.81) was observed at admission in the severe group, accompanied by increased levels of IL-6 (295.3 pg/mL ± 40.06), INF-γ (1.603 pg/mL ± 0.134), VEGF (546.8 pg/mL ± 124.2) compared to non-infected individuals. All patients had low partial pressure of oxygen, although it did not show statistically significant difference between the two groups. CONCLUSIONS All investigated parameters were altered in both groups of patients and a good correlation between them was demonstrated.
The association between serum sex hormone-binding globulin changes during progestin-primed ovarian stimulation and embryo outcomes: a retrospective cohort study

Abstract Objective: This study is aimed to examine the associations between embryo outcomes and serum sex hormone-binding globulin (SHBG) changes during progestin-primed ovarian stimulation (PPOS) protocols in IVF/ICSI cycles. Research methods: This study included 2790 eligible consecutive cycles of patients aged 21–53 years undergoing PPOS treatment. Multivariable linear regression analysis was performed to explore the association between SHBG changes and embryo outcomes. Results of the study: Our results showed that the SHBG-increase rate on the HCG day and in the late follicular phase were positively and linearly correlated with available embryos in day3, with adjusted regression coefficients (β) for the SHBG-increase rate on the HCG day, in the late follicular phase were 0.6 (0.4, 0.9), 0.4 (0.2, 0.6), but in the middle follicular phase and in the early follicular phase, this correlation was not significant (p > 0.05). Conclusion: Our results indicate that serum SHBG increment may serve as a biomarker of the developmental potential of the oocytes from patients undergoing the PPOS protocol.
Extra-pair paternity drives plumage colour elaboration in male passerines

The elaborate ornamental plumage displayed by birds has largely been attributed to sexual selection, whereby the greater success of ornamented males in attaining mates drives a rapid elaboration of those ornaments. Indeed, plumage elaboration tends to be greatest in species with a high variance in reproductive success such as polygynous mating systems. Even among socially monogamous species, many males are extremely colourful. In their now-classic study, Møller and Birkhead (1994) suggested that increased variance in reproductive success afforded by extra-pair paternity should intensify sexual selection pressure and thus an elaboration of male plumage and sexual dichromatism, but the relatively few measures of extra-pair paternity at the time prevented a rigorous test of this hypothesis. In the nearly three decades since that paper’s publication, hundreds of studies have been published on rates of extra-pair paternity and more objective measures of plumage colouration have been developed, allowing for a large-scale comparative test of Møller and Birkhead’s (1994) hypothesis. Using an analysis of 186 socially monogamous passerine species with estimates of extra-pair paternity, our phylogenetically controlled analysis confirms Møller and Birkhead’s (1994) early work, demonstrating that rates of extra-pair paternity are positively associated with male, but not female, colouration and with the extent of sexual dichromatism. Plumage evolution is complex and multifaceted, driven by phylogenetic, ecological, and social factors, but our analysis confirms a key role of extra-pair mate choice in driving the evolution of ornamental traits.
FAM13A Controls TGFb2 Secretion by Modulating AP-3 Transport

Chronic obstructive pulmonary disease (COPD) is a common, complex disease andamajor causeofmorbidity andmortality.Althoughmultiple genetic determinants of COPD have been implicated by genome-wide association studies (GWASs), the pathophysiological significance of these associations remains largely unknown. From a COPD protein–protein interactionnetworkmodule,we selectedanetworkpath between two COPD GWAS genes for validation studies: FAM13A (family with sequence similarity 13 member A)–AP3D1–CTGF– TGFb2. We find that TGFb2, FAM13A, and AP3D1 (but not CTGF) form a cellular protein complex. Functional characterization suggests that this complex mediates the secretion of TGFb2 through an AP-3 (adaptor protein 3)–dependent pathway, with FAM13A acting as a negative regulator by targeting a late stage of this transport that involves thedissociationof coat–cargo interaction.Moreover,we find thatTGFb2 is a transmembraneprotein that engages theAP-3complex fordelivery to the late endosomal compartments for subsequent secretion through exosomes. These results identify a pathophysiological context that unifies the biological network role of two COPDGWAS proteins and reveal novel mechanisms of cargo transport through an intracellular pathway.
Least Squares and Robust Rank-Based Double Bootstrap Analyses for Time-Series Intervention Designs

Time-series intervention designs that include two or more phases have been widely discussed in the healthcare literature for many years. A convenient model for the analysis of these designs has a linear model part (to measure changes in level and trend) plus a second part that measures the random error structure; the error structure is assumed to follow an autoregressive time-series process. Traditional generalized linear model approaches widely used to estimate this model are less than satisfactory because they tend to provide substantially biased intervention tests and confidence intervals. We describe an updated version of the original double bootstrap approach that was developed by McKnight et al. (2000) to correct for this problem. This updated analysis and a new robust version were recently implemented in an R package (McKean & Zhang, 2018). The robust method is insensitive to outliers and problems associated with common departures from normality in the error distribution. Monte Carlo studies as well as published data are used to demonstrate the properties of both versions. The R code required to perform the analyses is provided and illustrated.
Endoscopic ultrasound‑guided biliary drainage in patients with surgically altered anatomy: a systematic review and Meta‑analysis

Abstract Background and aims Endoscopic retrograde cholangiopancreatography is technically challenging to perform in patients with surgically altered anatomy (SAA). For these patients, endoscopic ultrasound-guided biliary drainage (EUS-BD) is one of the good indications. The aim of our systematic review and meta-analysis was to identify and evaluate evidence of the efficacy and safety of EUS-BD in patients with SAA. Methods A systematic review of the PubMed was conducted through to December 2021 to identify studies performing EUS-BD in patients with SAA. The primary outcome was the pooled technical success proportion in patients with SAA. The pooled clinical success and adverse event proportions in patients with SAA were also analyzed. Results The search identified 1195 possible records, with 18 studies meeting our criteria for analysis, reporting data for 409 patients with SAA who underwent EUS-BD. The pooled technical success, clinical success and adverse event proportions in patients with SAA were 97.8% (95% confidence interval [CI], 95.8–99.7%), 94.9% (95% CI, 91.8–98.1%), and 12.8% (95% CI, 7.4–18.1%), respectively. Conclusions EUS-BD is effective for patients with SAA. However, adverse events should be considered when performing EUS-BD in these patients.
“I feel like I’m in a revolving door, and COVID has made it spin a lot faster”: The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, Canada

Purpose Research has shown that youth experiencing homelessness (YEH) face barriers to social inclusion and are at risk for poor mental health. With the COVID-19 pandemic threatening the health, wellbeing, and economic circumstances of people around the world, this study aims to assess the impacts of the pandemic on YEH in Toronto, Ontario, as well as to identify recommendations for future waves of COVID-19. Methods Semi-structured interviews were conducted with YEH (ages 16–24, n = 45) and staff who work in one of four downtown emergency shelters for youth (n = 31) in Toronto, Ontario. Results YEH experienced both structural changes and psychosocial impacts resulting from the pandemic. Structural changes included a reduction in services, barriers to employment and housing, and changes to routines. Psychosocial outcomes included isolation, worsened mental health, and increased substance use. Impacts were magnified and distinct for subpopulations of youth, including for youth that identified as Black, 2SLGBTQ+, or those new to Canada. Conclusions The COVID-19 pandemic increased distress among YEH while also limiting access to services. There is therefore a need to balance health and safety with continued access to in-person services, and to shift the response to youth homelessness to focus on prevention, housing, and equitable supports for subpopulations of youth.
The Two-Track Model of Dementia Grief and spousal response to illness and death

Abstract This cross-sectional study examined the experiences of healthy spouses caring for their partners via the Two-Track Model of Dementia Grief thereby broadening our understanding of the functional and relational aspects of this process. The 122 participating older adults had spouses drawn from four groups: mild to moderate cognitive-impairment; advanced cognitive-impairment; deceased following dementia; and, healthy controls. They completed a battery of self-report measures. Results showed elevated scores on both tracks of the model for all affected groups. Assisting spouses of those living with cognitive-impairment begins with the earliest symptoms of decline and continues after the death of the loved one.
Effects of the Collective Gratitude on Work Engagement

The findings underline the importance of developing collective gratitude in the workplace. To cultivate collective gratitude, increasing the number of grateful employees and sharing them through social interaction is necessary. It would be useful for managers and occupational health staff to consider initiatives including reciprocal gratitude in the workplace. Objective Work engagement is a key concept because of its positive association with physical/mental health, job performance, and well-being. This study aims to examine the relationship between organizational-level gratitude (collective gratitude) as a work climate and work engagement. Methods Utrecht Work Engagement Scale measured work engagement. Gratitude at Work Scale measured individual-level gratitude, and collective gratitude was calculated by aggregating individual-level gratitude after confirming within-group agreement and the intraclass correlations. Multilevel analysis was conducted. Results A total of 1187 workers from 72 organizations were analyzed. The multilevel analysis showed a significant positive association between collective gratitude and work engagement while controlling for individual-level confounders. Conclusions The findings indicated developing collective gratitude would improve work engagement in the workplace. It would be useful for managers and occupational health staff to consider collective gratitude initiatives.
Origin and Evolution of Nitrogen Fixation in Prokaryotes

Abstract The origin of nitrogen fixation is an important issue in evolutionary biology. While nitrogen is required by all living organisms, only a small fraction of bacteria and archaea can fix nitrogen. The prevailing view is that nitrogen fixation first evolved in archaea and was later transferred to bacteria. However, nitrogen-fixing (Nif) bacteria are far larger in number and far more diverse in ecological niches than Nif archaea. We, therefore, propose the bacteria-first hypothesis, which postulates that nitrogen fixation first evolved in bacteria and was later transferred to archaea. As >30,000 prokaryotic genomes have been sequenced, we conduct an in-depth comparison of the two hypotheses. We first identify the six genes involved in nitrogen fixation in all sequenced prokaryotic genomes and then reconstruct phylogenetic trees using the six Nif proteins individually or in combination. In each of these trees, the earliest lineages are bacterial Nif protein sequences and in the oldest clade (group) the archaeal sequences are all nested inside bacterial sequences, suggesting that the Nif proteins first evolved in bacteria. The bacteria-first hypothesis is further supported by the observation that the majority of Nif archaea carry the major bacterial Mo (molybdenum) transporter (ModABC) rather than the archaeal Mo transporter (WtpABC). Moreover, in our phylogeny of all available ModA and WtpA protein sequences, the earliest lineages are bacterial sequences while archaeal sequences are nested inside bacterial sequences. Furthermore, the bacteria-first hypothesis is supported by available isotopic data. In conclusion, our study strongly supports the bacteria-first hypothesis.
A simplified cardiac damage staging predicts the outcome of patients undergoing TAVR—A multicenter analysis

A significant number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) suffer from extra‐aortic cardiac damage. Few studies have investigated strategies to quantify cardiac damage and stratify patients accordingly in different risk groups. The aim of this retrospective multicenter study was to provide a user‐friendly simplified staging system based on the proposed classification system of Généreux et al. as a tool to evaluate the prognosis of patients undergoing TAVR more easily. Moreover, we analyzed changes in cardiac damage after TAVR.
A Mouse Model of Celiac Disease

The design and use of mouse models that reproduce key features of human diseases are critical to advance our understanding of the pathogenesis of autoimmune diseases and to test new therapeutic strategies. Celiac disease is a unique organ‐specific autoimmune‐like disorder occurring in genetically susceptible individuals carrying HLA‐DQ2 or HLA‐DQ8 molecules who consume gluten. The key histological characteristic of the disease in humans is the destruction of the lining of the small intestine, a feature that has been difficult to reproduce in immunocompetent animal models. This unit describes the DQ8‐Dd‐villin‐IL‐15 transgenic mouse model of CeD, which was engineered based on the knowledge acquired from studying CeD patients’ intestinal samples, and which represents the first animal model that develops villous atrophy in an HLA‐ and gluten‐dependent manner without administration of any adjuvant. We provide detailed protocols for inducing and monitoring intestinal tissue damage, evaluating the cytotoxic properties of intraepithelial lymphocytes that mediate enterocyte lysis, and assessing the activation of the enzyme transglutaminase 2, which contributes to the generation of highly immunogenic gluten peptides. Detailed protocols to prepare pepsin‐trypsin digested gliadin (PT‐gliadin) or chymotrypsin‐digested gliadin (CT‐gliadin), which allow antibody detection against native or deamidated gluten peptides, are also provided in this unit. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.