Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Drift Association with Cancer Risk and Survival, and Modification by Sex

Simple Summary: Ageing is the strongest cancer risk factor, and men and women exhibit disparate risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift might contribute to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 3,215 matched case-control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis. Abstract: To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case-control studies of colorectal (N=835), gastric (N=170), kidney (N=143), lung (N=332), prostate (N=869) and urothelial (N=428) cancers, and mature B-cell lymphoma (N=438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls) - replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios [HR]), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates (GS summary data) for these CpGs were 94%, 86% and 91%, respectively. Significant signals for cancer risk and survival were identified at some individual age-related CpGs. There was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Two CpGs overlapping TMEM49 and ARX genes were associated with survival of overall (HR=0.91, P=7.7x10-4) and colorectal (HR=1.52, P=1.8x10-4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.
Modified cross-linked polyethylenimine for the removal of selenite from mining wastewaters

Cross-linked branched polyethylenimine (CPEI) was sulfonated by reaction with 3-chloropropanesulfonyl chloride. The functionalized polymer was used as an adsorbent for the removal of SeO32− from aqueous solutions, particularly mining wastewaters. The binding affinity of the synthesized polymer to abstract SeO32– from synthetic solutions and wastewater samples has been assessed as well as its ability to be regenerated for reuse. The process demonstrated that sulfonated cross-linked polyethylenimine (SCPEI) exhibited good affinity to SeO32– with removal efficiency up to 81%. The kinetic rates were modeled using pseudo first-order and pseudo second-order equations. The pseudo second-order equation was found to explain the adsorption kinetics most effectively implying chemisorption. The Langmuir and Freundlich isotherms were used to interpret the adsorption of SeO32– onto the modified polymer. The Freundlich isotherm was found to best fit and describe the experimental data. The thermodynamic study of the adsorption process revealed high activation energies >41 kJ mole−1 which confirm chemisorption as a mechanism of interaction between the adsorbate (SeO32−) and adsorbent (SCPEI).
The red blood cell as a novel regulator of human B‐cell activation

Non‐immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B cells. Separation of RBC from peripheral blood mononuclear cells increased B‐cell expression of HLA‐DR/DP/DQ, whilst reconstitution reduced the levels of B‐cell activation markers HLA‐DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B cells required contact with RBC and was abrogated by either removal of sialic acids from RBC or blocking the corresponding lectin receptor CD22 on B cells. Chronic lymphocytic leukaemia B cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B cells whilst circulating in the bloodstream.
Self-reported cognitive impairment and daily life functioning 7-12 years after seeking care for stress-related exhaustion.

The overall aim of this study was to investigate self-reported cognitive difficulties, daily life activities, and health/sleep factors in former patients with exhaustion disorder (ED) who still fulfill the clinical criteria for exhaustion 7-12 years after seeking care. The Sahlgrenska Self-reported Cognitive Impairment Questionnaire (SASCI-Q) was used to measure cognitive difficulties, daily life activities, and health/sleep factors. Three groups were compared: previous patients still judged to be clinically exhausted seven years or more after seeking care (n = 51); previous patients considered clinically recovered (n = 98); and healthy controls (n = 50). Patients who still fulfilled the diagnostic criteria for ED reported widespread problems related to cognition, fatigue, and daily life functioning compared to the clinically recovered group. Furthermore, despite no longer fulfilling the clinical criteria, the recovered patients still reported more problems related to cognitive functioning and fatigue compared to healthy controls. Thus, this group appeared intermediary between the non-recovered group and healthy controls regarding self-reported cognitive functioning. To conclude, ED may have considerable negative long-term effects, and it is possible that some of these residual symptoms, particularly the cognitive problems and persistent fatigue, are permanent in some patients. Preventive measures should be the primary focus for all stakeholders, since the consequences of stress-related mental health problems seem to be extensive and long-lasting.
Circulating Myonectin and Irisin Levels in Gestational Diabetes Mellitus – A Case-control Study

Abstract Objective The objective of this study was to assess the levels of serum myonectin and irisin in pregnant women with and without gestational diabetes mellitus (GDM). Method A total of 80 pregnant women participated in our study (which consisted of 40 patients with GDM, 40 participants as the control group). Myonectin and irisin levels were analyzed through the ELISA technique, in addition to metabolic parameters in the serum samples of the participants. Results It was found that the levels of irisin and myonectin were lower in the GDM group compared to the control group. Moreover, it was determined that the values of age (p<0.001), body mass index (p=0.001), gravida (p=0.001), parity (p = 0.016), fasting serum glucose (p=0.001), fasting serum insulin (p=0.007), postprandial serum glucose (p=0.006), HbA1c (p<0.001), HOMA-IR (p<0.001) were higher; HDL cholesterol (p<0.001) was lower. Insulin resistance was significantly higher in the GDM group. Conclusions Levels of myonectin and irisin were determined to be low in the GDM group. Our results have demonstrated that myonectin and irisin could play a role in the development of GDM and that irisin as well as myonectin could be a novel biomarker for GDM.
Acoustics versus linguistics? Context is Part and Parcel to lateralized processing of the parts and parcels of speech

ABSTRACT The purpose of this review is to provide an accessible exploration of key considerations of lateralization in speech and non-speech perception using clear and defined language. From these considerations, the primary arguments for each side of the linguistics versus acoustics debate are outlined and explored in context of emerging integrative theories. This theoretical approach entails a perspective that linguistic and acoustic features differentially contribute to leftward bias, depending on the given context. Such contextual factors include stimulus parameters and variables of stimulus presentation (e.g., noise/silence and monaural/binaural) and variances in individuals (sex, handedness, age, and behavioural ability). Discussion of these factors and their interaction is also aimed towards providing an outline of variables that require consideration when developing and reviewing methodology of acoustic and linguistic processing laterality studies. Thus, there are three primary aims in the present paper: (1) to provide the reader with key theoretical perspectives from the acoustics/linguistics debate and a synthesis of the two viewpoints, (2) to highlight key caveats for generalizing findings regarding predominant models of speech laterality, and (3) to provide a practical guide for methodological control using predominant behavioural measures (i.e., gap detection and dichotic listening tasks) and/or neurophysiological measures (i.e., mismatch negativity) of speech laterality.
A second independent audit of electroconvulsive therapy in England, 2019: Usage, demographics, consent, and adherence to guidelines and legislation.

OBJECTIVES To assess progress towards improving the administering of electroconvulsive therapy (ECT) in England since an audit covering 2011, 2013, and 2015. The same information was gathered, for 2019, on usage, demographics, consent, and adherence to national guidelines and the Mental Health Act. DESIGN AND METHODS Freedom of Information Act requests were sent to 56 National Health Service Trusts. RESULTS Thirty-seven trusts (66%) provided data. The gradual decline in the use of ECT in England has levelled off at about 2,500 people per year. There was a 47-fold difference between the Trusts with the highest and lowest rates per capita. Most recipients are still women (67%) and over 60 (58%). Only one Trust could report how many people received psychological therapy prior to ECT, as required by government (NICE) guidelines. More than a third of ECT (37%) is still given without consent, with 18% of Trusts non-compliant with legislation concerning second opinions. There were slight declines, compared to a previous audit, in the use of standardized depression scales, down to 30%, and standardized measures of cognitive dysfunction, down to 24%. Only six Trusts provided any data for positive outcomes and seven for adverse effects. None provided data on efficacy or adverse effects beyond the end of treatment. Twelve Trusts used identical sentences to each other, verbatim, in response to one or more questions. CONCLUSIONS Given the apparent failure of current monitoring and accrediting of ECT clinics in England, by the Royal College of Psychiatrists' ECT Accreditation Service (ECTAS), an independent government sponsored review is urgently needed. PRACTITIONER POINTS Psychologists and other mental health staff should ensure that people are offered evidence-based psychological treatments before being offered E.C. T. All staff should ensure that patients are fully informed of the high risk of memory loss and the smaller risk of cardiovascular failure and mortality. Individuals receiving ECT should be closely monitored for adverse cognitive effects, and treatment immediately terminated if these become apparent. Because of increased risk of memory loss for women and older people, the use of ECT should be kept to a minimum and avoided where possible, with these two groups.
Factors Associated with Substance Use Disorder Treatment Completion, Rhode Island, USA, 2018

Abstract Introduction The successful retention of individuals with substance use disorders in treatment remains a challenge but is an important indicator of positive post-treatment outcomes. The aim of this study is to advance understanding of pre-admission factors associated with substance use treatment completion in Rhode Island. Methods Data for this longitudinal analysis are from the RI Behavioral Health On-Line Database (RI-BHOLD). The primary outcome of interest was substance use treatment completion defined as any planned discharge from treatment, including transfers to other facilities. Associations were assessed using generalized estimating equations (GEE) to account for the potential of repeated measures for the same individuals. Results Among the 7,351 clients discharged from a substance use treatment program in RI in 2018, the treatment completion rate was 58.1%. There was a positive relationship between the frequency of attendance of voluntary self-help groups and odds of treatment completion. Treatment completion rates were lower among those who reported use of opioids (AOR: 0.59; 95% CI: 0.52-0.66) and other drugs (AOR: 0.52; 95% CI: 0.44-0.62), compared to alcohol and for those with co-occurring mental health conditions (AOR: 0.85; 95% CI: 0.76-0.94). Conclusions This study highlights the importance of social connectedness in substance use disorder treatment completion. Future research is needed to identify the characteristics of persons who are most likely to benefit from self-help groups and the optimal combination of treatment participation and attendance of self-help groups across a spectrum of disorder severity and community resources.
Investigating the impact of different strategies for endometrial preparation in frozen cycles considering normal responders undergoing IVF/ICSI cycles: a multicenter retrospective cohort study

ABSTRACT Uncertainty exists concerning the type, adjunct, or dose of regimen to offer in frozen cycles in infertile women undergoing IVF/ICSI. Current systematic reviews have failed to identify one method of endometrial preparation as being more effective than another, whereas many IVF Units use variable and mixed protocols mainly based on their experience and convenience of use. Thus, we performed a four-center two-arm retrospective cohort study, encompassing 439 cycles in 311 women. The modalities analyzed were: Modified natural cycle without and with luteal support (Groups 1,2) and Hormone Replacement cycle (HRC) with and without GnRHa suppression (Groups 3,4). Various schemes of progesterone and estradiol were used and compared. χ2 tests for categorical data and t-tests for continuous data were employed, stratifying by exposure, along with univariate and multivariable Logistic Regression models and subgroup analyses, according to the number of embryos transferred (1 vs. ≥2) and day of transfer (d2 vs. d5). Group 3 presented with statistically significant higher live birth and miscarriage rates in comparison to Group 4 (RR = 5.87, 95%CI: 2.44–14.14 and RR = 0.19, 95%CI: 0.06–0.60, respectively), findings that persisted in subgroup analyses according to the day of transfer and the number of embryos transferred. Progesterone administration through the combination of vaginal tabs and gel was associated with lower clinical pregnancy rates when compared to tabs (RR = 0.19, 95%CI: 0.05–0.71). The stable estrogen protocol compared to increasing estrogen at day 5 was associated with a higher positive hCG test and clinical pregnancy rate, while the progesterone through vaginal tabs was linked with lower miscarriages compared either with gel or combinations. In conclusion, HRC with GnRHa appears to be superior to HRC without GnRHa, concerning live birth and miscarriage, especially when the number of embryos transferred are ≥2 and irrespective of day of transfer. The use of progesterone vaginal tabs compared to gel or combinations is associated with better outcomes. Age is a significant predictor of a negative hCG test and clinical pregnancy rates. A properly conducted RCT is needed to evaluate the optimal frozen embryo transfer preparation strategy. Abbreviations: SD: standard deviation; BMI: body mass index; PCOS: polycystic ovarian syndrome; IQR: interquartile range; FSH: follicle-stimulating hormone; LH: luteinizing hormone; TSH: thyroid-stimulating hormone.
High diffraction efficiency in crystals curved by surface damage

Diffraction profiles of curved Si and GaAs crystals obtained by a controlled damage process on one side of planar crystals have been investigated at X-ray energies E = 17, 59 and 120 keV. At E = 17 and 59 keV in the condition of slight curvature, that is when the diffracting plane bending over the extinction length is lower than the Darwin width, the Laue diffraction profiles with lattice planes parallel or inclined with respect to the curvature radius R show an enhancement of integrated intensity proportional to 1/R, much larger than in the corresponding perfect bent crystals. At E = 120 keV, in the condition of strong curvature, the crystals behave as bent perfect crystals with integrated intensity corresponding to that of a mosaic crystal. These crystals are proposed as optical elements for focusing hard X-ray beams.
Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease.

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state-fMRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: First, we included 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls. Second, we included 156 amyloid-PET positive subjects across the spectrum of sporadic Alzheimer's disease as well as 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal-lobe tau-PET (i.e. composite across Braak stage I & III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher fMRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (p = 0.007). Similarly, for sporadic Alzheimer's disease patients, higher fMRI-assessed system segregation was associated with less decrement in global cognition (p = 0.001) and episodic memory (p = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.
Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease

Abstract Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-β (Aβ) protein by GO. Both in vivo and in vitro models were induced using Aβ1-42, and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels in vitro; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Aβ1-42-induced AD. This proved that GO loaded with Dau could protect against Aβ1-42-induced oxidative damage and apoptosis in both in vitro and in vivo AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD.
A sobering addition to the literature on COVID-19 and the brain.

Several COVID-19 studies have focused on neuropathology. In this issue of the JCI, Qin, Wu, and Chen, et al. focused specifically on people whose acute infection lacked obvious neurological involvement. Severely infected patients showed abnormal grey matter volumes, white matter diffusion, and cerebral blood flow compared with healthy controls and those with mild infection. The data remain associative rather than mechanistic, but correlations with systemic immune markers suggest effects of inflammation, hypercoagulation, or other aspects of disease severity. Mechanistic research is warranted. Given the lack of obvious neurological symptoms, neurocognitive assessments were not performed, but the findings suggest that such assessments may be warranted in severely affected patients, even without obvious symptoms. Further, studying CNS involvement of other disorders with overlapping pathophysiologies, such as inflammation, coagulation, hypoxia, or direct viral infection may reveal the causes for COVID-19 related neuropathology.
Effects of exercise training on autonomic modulation and mood symptoms in patients with obstructive sleep apnea

We evaluated the effects of exercise training (ET) on the profile of mood states (POMS), heart rate variability, spontaneous baroreflex sensitivity (BRS), and sleep disturbance severity in patients with obstructive sleep apnea (OSA). Forty-four patients were randomized into 2 groups, 18 patients completed the untrained period and 16 patients completed the exercise training (ET). Beat-to-beat heart rate and blood pressure were simultaneously collected for 5 min at rest. Heart rate variability (RR interval) was assessed in time domain and frequency domain (FFT spectral analysis). BRS was analyzed with the sequence method, and POMS was analyzed across the 6 categories (tension, depression, hostility, vigor, fatigue, and confusion). ET consisted of 3 weekly sessions of aerobic exercise, local strengthening, and stretching exercises (72 sessions, achieved in 40±3.9 weeks). Baseline parameters were similar between groups. The comparisons between groups showed that the changes in apnea-hypopnea index, arousal index, and O2 desaturation in the exercise group were significantly greater than in the untrained group (P<0.05). The heart rate variability and BRS were significantly higher in the exercise group compared with the untrained group (P<0.05). ET increased peak oxygen uptake (P<0.05) and reduced POMS fatigue (P<0.05). A positive correlation (r=0.60, P<0.02) occurred between changes in the fatigue item and OSA severity. ET improved heart rate variability, BRS, fatigue, and sleep parameters in patients with OSA. These effects were associated with improved sleep parameters, fatigue, and cardiac autonomic modulation, with ET being a possible protective factor against the deleterious effects of hypoxia on these components in patients with OSA.