Miracle-dz/UniFAR-FTUs huggingface dataset:
Programming filamentous network mechanics by compression

Fibrous networks are ideal functional materials since they provide mechanical rigidity at low weight. Such structures are omnipresent in natural biomaterials from cells to tissues, as well as in man-made materials from polymeric composites to paper and textiles. Here, we demonstrate that fibrous networks of the blood clotting protein fibrin undergo a strong and irreversible increase in their mechanical rigidity in response to compression. This rigidification can be precisely predetermined from the level of applied compressive strain, providing a means to program the network rigidity without having to change its composition. To identify the mechanism underlying this programmable rigidification, we measure single fiber-fiber interactions using optical tweezers. We further develop a minimal computational model of adhesive fiber networks that shows that load-induced bond formation can explain the adaptation of the fibrin networks to compressive loading. The model predicts that the network stiffness after compressive programming obeys a universal power-law dependence on the prestress built in by new bond formation, which we confirm experimentally. The generality of this functional stiffening mechanism together with our ability to quantitatively predict it provides a new powerful approach to program the stiffness of fibrous materials and dynamically adapt them to different loading conditions.
Selected E2F2 Polymorphisms in Oral and Oropharyngeal Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5′ nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.
A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates

Type 2 diabetes (T2D) plays a major role in the development of heart failure. Patients with T2D have an increased risk to develop HF than healthy subjects, and they always have very poor outcomes and survival rates. However, the underlying mechanisms for this are still unclear. To help develop new therapeutic interventions, well-characterized animal models for preclinical and translational investigations in T2D and HF are urgently needed. Although studies in rodents are more often used, the research findings in rodents have often failed to be translated into humans due to the significant metabolic differences between rodents and humans. Nonhuman primates (NHPs) serve as valuable translational models between basic studies in rodent models and clinical studies in humans. NHPs can recapitulate the natural progress of these diseases in humans and study the underlying mechanism due to their genetic similarity and comparable spontaneous T2D rates to humans. In this review, we discuss the importance of using NHPs models in understanding diabetic cardiomyopathy (DCM) in humans with aspects of correlations between hyperglycemia and cardiac dysfunction progression, glucose overload, and altered glucose metabolism promoting cardiac oxidative stress and mitochondria dysfunction, glucose, and its effect on cardiac resynchronization therapy with defibrillator (CRT-d), the currently available diabetic NHPs models and the limitations involved in the use of NHP models.
The Role of Quantification of Glucocorticoid-associated Toxicity in Severe Asthma

Until recently, oral glucocorticoid (GC) therapies were the mainstay of treatment for uncontrolled inflammatory disease across many body systems. The last 30 years, however, have witnessed a transformation in the management of many diseases due to the development of targeted biological agents leading to a reduction, albeit not a removal, of the dependence on oral GCs. The need for new glucocorticoid-sparing therapies was urgent given the ever increasing and robust literature on the multisystem adverse effects related to chronic or repeated oral GC exposures [1–6]. The importance of measuring the potential GC-toxicity reduction by “steroid-sparing” agents — and the absence of a validated tool with which to accomplish this goal — was recognised by a group of international investigators from a broad range of medical specialities. These investigators developed and validated such a tool, the Glucocorticoid Toxicity Index (GTI) [7].
Polymerized imidazolium ionic liquids crosslinking sulfonated poly(ether ether ketone) (SPEEK) for high-temperature proton exchange membrane

An ionic liquid (IL) monomer of (acryloyloxy)propanylimidazolium chloride with unsaturated carbon–carbon double bonds was synthesized. The IL monomer clung to sulfonated poly(ether ether ketone) (SPEEK) polymer owing to the electrostatic attraction between its cations and sulfonic groups. Polymerized ionic liquid (PIL) crosslinked with the SPEEK matrix after the in situ polymerization of the unsaturated carbon–carbon double bonds in the system of SPEEK/PIL. As a result, the SPEEK/PIL membrane displays a better performance in terms of tensile stress and chemical stability compared to those for the SPEEK/IL membrane. In order to improve the proton conductivity of the SPEEK/PIL membrane, phosphoric acid (PA) molecules were introduced through hydrogen bonds between imidazolium cations and phosphoric acid molecules. In the case of the SPEEK/PIL/PA membrane, a proton-conducting network was formed with more free and continuous phosphoric acid molecule chains owing to more phosphoric acid molecules being doped relative to the SPEEK/IL/PA membrane. The maximum proton conductivity of the SPEEK/PIL/PA membrane was 4.5 × 10−2 S cm−1 at 160 °C under anhydrous conditions and a value of 2.5 × 10−2 S cm−1 was even stable for more than 300 h at 140 °C. Moreover, the SPEEK/PIL/PA membrane possesses satisfactory mechanical properties, such as 2.64 MPa for tensile stress at 120 °C.
Predictive performance of machine and statistical learning methods: Impact of data-generating processes on external validity in the “large N, small p” setting

Machine learning approaches are increasingly suggested as tools to improve prediction of clinical outcomes. We aimed to identify when machine learning methods perform better than a classical learning method. We hereto examined the impact of the data-generating process on the relative predictive accuracy of six machine and statistical learning methods: bagged classification trees, stochastic gradient boosting machines using trees as the base learners, random forests, the lasso, ridge regression, and unpenalized logistic regression. We performed simulations in two large cardiovascular datasets which each comprised an independent derivation and validation sample collected from temporally distinct periods: patients hospitalized with acute myocardial infarction (AMI, n = 9484 vs. n = 7000) and patients hospitalized with congestive heart failure (CHF, n = 8240 vs. n = 7608). We used six data-generating processes based on each of the six learning methods to simulate outcomes in the derivation and validation samples based on 33 and 28 predictors in the AMI and CHF data sets, respectively. We applied six prediction methods in each of the simulated derivation samples and evaluated performance in the simulated validation samples according to c-statistic, generalized R2, Brier score, and calibration. While no method had uniformly superior performance across all six data-generating process and eight performance metrics, (un)penalized logistic regression and boosted trees tended to have superior performance to the other methods across a range of data-generating processes and performance metrics. This study confirms that classical statistical learning methods perform well in low-dimensional settings with large data sets.
Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19

Throughout the world, including the United States, men have worse outcomes from COVID-19 than women. SARS-CoV-2, the causative virus of the COVID-19 pandemic, uses angiotensin-converting enzyme 2 (ACE2) to gain cellular entry. ACE2 is a member of the renin-angiotensin system (RAS) and plays an important role in counteracting the harmful effects mediated by the angiotensin type 1 receptor. Therefore, we conducted Ovid MEDLINE and Embase database searches of basic science studies investigating the impact of the biological variable of sex on ACE2 expression and regulation from 2000, the year ACE2 was discovered, through December 31, 2020. Out of 2,131 publications, we identified 853 original research articles on ACE2 conducted in primary cells, tissues, and/or whole mammals excluding humans. The majority (68.7%) of these studies that cited the sex of the animal were conducted in males, while 11.2% were conducted solely in females; 9.26% compared ACE2 between the sexes, while 10.8% did not report the sex of the animals used. General findings are that sex differences are tissue-specific and when present, are dependent upon gonadal state. Renal, cardiac, and adipose ACE2 is increased in both sexes under experimental conditions that model co-morbidities associated with worse COVID-19 outcomes including hypertension, obesity, and renal and cardiovascular diseases; however, ACE2 protein was generally higher in the males. Studies in Ace2 knockout mice indicate ACE2 plays a greater role in protecting the female from developing hypertension than the male. Studying the biological variable of sex in ACE2 research provides an opportunity for discovery in conditions involving RAS dysfunction and will shed light on sex differences in COVID-19 severity.
Discontinuation of biologic DMARDs in a real-world population of patients with rheumatoid arthritis in remission: outcome and risk factors.

OBJECTIVES Data from randomized controlled trials have shown the feasibility of discontinuation of bDMARD therapy in patients with RA that have reached remission. Criteria for selecting patients that are likely to remain in remission are still incompletely defined.We aimed to identify predictors of successful discontinuation of bDMARD therapy in the Swiss Clinical Quality Management (SCQM) registry, a real-world cohort of RA patients. METHODS RA patients in DAS28-ESR remission who stopped bDMARD/tsDMARD treatment were included. Loss of remission was defined as a DAS28-ESR > 2.6 or restart of a bDMARD/tsDMARD. Time to loss of remission was the main outcome. Kaplan-Meier methods were applied and cox regression was used for multivariable analyses adjusting for confounding factors. Missing data were imputed using multiple imputation. RESULTS 318 patients in a bDMARD/tsDMARD-free remission were followed between 1997 and 2017. 241 patients (76%) lost remission after a median time of 0.9 years (95%CI 0.7-1.0). The time to loss of remission was shorter in women, in patients with a longer disease duration >4yrs and in patients who did not meet CDAI remission criteria at baseline. Remission was longer in patients with csDMARD therapy during b/tsDMARD free remission (HR 0.8, p= 0.05, 95%CI 0.6-1.0). CONCLUSION In a real-world patient population the majority of patients who discontinued b/tsDMARD treatment lost remission within <1 year. Our study confirms that fulfilment of more rigorous remission criteria and csDMARD treatment increases the chance of maintaining b/tsDMARD free remission.
Motivation to recover for adolescent and adult eating disorder patients in residential treatment.

OBJECTIVE This study aimed to assess how baseline motivation to recover impacts eating disorder (ED) and comorbid symptoms at end-of-treatment (EOT) for adolescents and adults in inpatient/residential treatment. METHOD Two hundred and three adolescent (M = 15.90) and 395 adult (M = 25.45) patients with a Diagnostic Statistical Manual, 5th edition ED diagnosis completed the Decisional Balance Scale (DBS) at baseline, and psychosocial measures (ED symptoms, anxiety, depression, obsessive-compulsive disorder symptoms), and %body mass index (kg/m2 ; BMI) or median %BMI (for adolescents) at baseline and EOT. RESULTS The DBS Avoidance Coping and Burdens subscales at baseline were significantly lower for adolescents than adults (p < 0.001), whereas the DBS Benefits subscale at baseline did not significantly differ between subsamples (p = 0.06). Motivation to recover via DBS subscales was a more reliable predictor of EOT outcomes for both ED and comorbid psychopathology in adults (significant predictor in 19 of 54 total analyses, and 4 significant associations post-Bonferroni correction) than adolescents (significant predictor in 5 of 54 total analyses, and 1 significant association post-Bonferroni correction). CONCLUSIONS Baseline motivation to recover may be an important predictor of outcome for adult patients in inpatient/residential treatment but does not appear associated with outcomes for adolescent patients.
Is executive dysfunction a potential contributor to the comorbidity between basic reading disability and attention-deficit/hyperactivity disorder?

ABSTRACT Our study is one of the few to analyze executive functioning (EF) in a comprehensive, multi-modal fashion as a potential contributor to the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and basic reading disability (RD). We included multiple, traditional, neuropsychological measures of EF, along with the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire, to assess inhibit, shift, working memory (WM), planning, generation fluency, and problem-solving. Participants included 263 children, ages 8–12 years, with RD, ADHD, RD/ADHD, and typically developing controls. When using the traditional measures in a 2 × 2 MANCOVA, we found both RD and ADHD had poor cognitive EF in most areas at the group level, with phonological loop deficits being more specific to RD and behavioral regulation deficits being more specific to ADHD. Children with RD/ADHD performed comparably to those with RD and ADHD alone. Results were similar on the BRIEF. In contrast, only WM predicted both basic reading and inattention when the data were assessed in a continuous fashion. It also explained the correlations between basic reading and inattention, being worthy of longitudinal research to determine if it is a shared contributor to RD/ADHD. When comparing hypotheses as to the nature of RD/ADHD, we found the multiple deficit hypothesis was better supported by our EF data than the phenocopy hypothesis or the cognitive subtype hypothesis.
Possible role of microbiome in the pathogenesis of endometriosis.

INTRODUCTION There is an urgent necessity to explore the complex pathophysiological nature of endometriosis, which may enable the rationale for new diagnostic and therapeutic strategies to be discovered. This systematic review aimed to clarify the bidirectional relationship between endometriosis and the microbiome and evaluate if the microbiome may be involved in endometriosis's pathogenesis, establishing a potential connection between the different studies. EVIDENCE ACQUISITION Studies were identified through a systematic literature search of papers that evaluated the microbiomes of human or other animal species with endometriosis and of those without in the electronic database PubMed/Medline, and Embase without a date restriction. We included all cohort studies focusing on the interaction between endometriosis and the microbiomes of humans or other mammals, evaluating if the microbiome may be involved in endometriosis's pathogenesis. EVIDENCE SYNTHESIS Endometriosis appears to be associated with elevated levels of different microorganisms across various microbiome sites. An ineffective immune response seems to play a key role in endometriosis pathogenesis, and there is some scientific proof to state that the immune response may be modulated by the microbiome. Interestingly, nine studies of our review detected species belonging to the phyla Proteobacteria, Bacteroidetes, and Negativicutes characterized by Gram-negative staining, that were significantly increased in endometriosis cohorts. CONCLUSIONS Laboratory and clinical investigations indicate that hosts' microbiome profiles with and without endometriosis can be significantly different. To further our understanding of the relationships between endometriosis and the host microbiome, more studies are necessary.
Einfluss von doppelsträngiger RNA auf die Thrombusbildung in der Mikrozirkulation der Maus

Doppelstrangige RNA in Form des synthetischen Analogons poly(I:C) fuhrte in den Arteriolen der Mikrozirkulation der Maus nach Behandlung zu einer beschleunigten Thrombusbildung in vivo. Hierzu wurde die Zeit bis zum Beginn der Thrombusbildung und des kompletten Gefasverschlusses per photochemischer Schadigung bestimmt ("Light-dye-injury"). Auserdem konnte auf mRNA-Ebene in menschlichen Endothel- und Mesangialzellen eine Hochregulation prothrombotischer Faktoren (Tissue factor, PAI-1) in der quantitativen real time PCR gesehen werden. Zelllysatmaterial derartig behandelter Zellen, beschleunigte die Gerinnungszeit menschlichen Vollbluts in einem Funktionsassay (Clotting Assay). Es konnten in vitro keine direkten Effekte von poly(I:C) auf menschliche Thrombozyten gesehen werden. Ebenso zeigten sich keine signifikanten Effekte auf die Thrombusbildung in TLR-3-KO-Mausen. Aktiviertes Protein C konnte die durch poly(I:C) induzierten Effekte auf die mRNA-Expression prothrombotischer Faktoren reduzieren. Eine Behandlung von Mausen mit Protein C fuhrte zu einer verzogerten Thrombusbildung in vivo.
A Heterogeneous Ensemble Learning Method For Neuroblastoma Survival Prediction

Neuroblastoma is a pediatric cancer with high morbidity and mortality. Accurate survival prediction of patients with neuroblastoma plays an important role in the formulation of treatment plans. In this study, we proposed a heterogeneous ensemble learning method to predict the survival of neuroblastoma patients and extract decision rules from the proposed method to assist doctors in making decisions. After data preprocessing, five heterogeneous base learners were developed, which consisted of decision tree, random forest, support vector machine based on genetic algorithm, extreme gradient boosting and light gradient boosting machine. Subsequently, a heterogeneous feature selection method was devised to obtain the optimal feature subset of each base learner, and the optimal feature subset of each base learner guided the construction of the base learners as a priori knowledge. Furthermore, an area under curve-based ensemble mechanism was proposed to integrate the five heterogeneous base learners. Finally, the proposed method was compared with mainstream machine learning methods from different indicators, and valuable information was extracted by using the partial dependency plot analysis method and rule-extracted method from the proposed method. Experimental results show that the proposed method achieves an accuracy of 91.64%, recall of 91.14%, and AUC of 91.35% and is significantly better than the mainstream machine learning methods. In addition, interpretable rules with accuracy higher than 0.900 and predicted responses are extracted from the proposed method. Our study can effectively improve the performance of the clinical decision support system to improve the survival of neuroblastoma patients.
Circular RNA circZNF292 regulates H2O2‐induced injury in human lens epithelial HLE‐B3 cells depending on the regulation of the miR‐222‐3p/E2F3 axis

Circular RNAs (circRNAs) play important roles in the pathogenesis of age‐related cataract (ARC). CircRNA zinc finger protein 292 (circZNF292, hsa_circ_0004058) is downregulated in ARC lens capsules. Here, we focused on its precise roles in oxidative stress underlying the pathogenesis of ARC. CircZNF292, microRNA (miR)‐222‐3p, and E2F transcription factor 3 (E2F3) were quantified by quantitative real‐time polymerase chain reaction or western blot. Cell viability was assessed by the cell counting kit‐8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. The activities of superoxide dismutase, catalase, and malondialdehyde were measured using the corresponding assay kit. Targeted correlations among circZNF292, miR‐222‐3p, and E2F3 were verified by the dual‐luciferase reporter, RNA immunoprecipitation and RNA pull‐down assays. Our data showed that circZNF292 was downregulated in ARC tissues and H2O2‐treated human lens epithelial B3 (HLE‐B3) cells. Increased expression of circZNF292 alleviated H2O2‐induced cell viability suppression, apoptosis promotion, and oxidative stress enhancement. Mechanistically, circZNF292 directly targeted miR‐222‐3p, and circZNF292 regulated E2F3 expression through miR‐222‐3p. MiR‐222‐3p was a functional mediator of circZNF292 in modulating H2O2‐induced injury in HLE‐B3 cells. Furthermore, reduced level of miR‐222‐3p ameliorated H2O2‐induced HLE‐B3 cell damage by upregulating E2F3. Our present study demonstrated that increased expression of circZNF292 ameliorated H2O2‐induced injury in HLE‐B3 cells at least in part through the miR‐222‐3p/E2F3 axis, highlighting a novel insight into the involvement of circRNAs in the pathogenesis of ARC.