Miracle-dz/UniFAR-FTUs huggingface dataset:
Educational Attainment and Exercise Frequency in American Women; Blacks' Diminished Returns.

Background Minorities' Diminished Returns (MDRs) refer to smaller protects health effects of socioeconomic status (SES) indicators for Blacks and other minority groups than Whites. Objectives The current study aimed to explore Black- White differences in the association between educational attainment and exercise frequency among women in the US. Methods For the current study, we used the National Survey of American Life's (NSAL) data which included 3,175 women who were either White (n = 876) or Black (n = 2,299). The independent variable was educational attainment. The dependent variable was exercise frequency. Age, region, household income, financial distress, marital status, unemployment, and depression were the covariates. Race was the focal moderator. Linear regression was applied for data analysis. Results In the overall sample of women, high educational attainment was associated with higher exercise frequency (b = 0.07, 95% CI = 0.02-0.12). Race and educational attainment showed a significant interaction (b = -0.09, 95% CI = -0.19-0.00), suggestive of a smaller effect of education attainment on exercise frequency for Black women than White women. In race specific models, high educational attainment was associated with higher exercise frequency for White (b = 0.12, 95% CI =0.04-0.20) but not Black (b = 0.03, 95% CI = -0.03-0.08) women. Conclusion In line with the past research on MDRs, White women gain more health from their educational attainment than Black women. It is not race or class but race and class that shape the health behaviors of American women.
What is novel in the clinical management of pemphigus

ABSTRACT Introduction: Pemphigus, an autoimmune disease group characterized by blisters and erosions of the skin and/or mucosal membranes has been treated with systemic corticosteroids (CS) and immunosuppressive therapies for the past few decades. Areas Covered: However, common adverse effects and complications of long-term CS and immunosuppressive drugs are limiting their long-term use. The disease results in death if not treated. Thus, currently, researchers are trying to develop new and safer therapeutic approaches. Specifically, targeted therapies to pathogenic immune pathways are under investigation. The B cell inhibitors which block CD20 and CD19 are the main new drugs investigated in clinical trials as alternatives to systemic steroids. Expert Opinion: Randomized controlled trial (RCT) Level evidence shows that rituximab and short course CSs are more effective and safer than standard CS treatment. Specific BTK inhibitors have shown promise in data from a phase II international open-label study. Further studies are ongoing.
CDK and Mec1/Tel1-catalyzed phosphorylation of Sae2 regulate different responses to DNA damage

Abstract Sae2 functions in the DNA damage response by controlling Mre11-Rad50-Xrs2 (MRX)-catalyzed end resection, an essential step for homology-dependent repair of double-strand breaks (DSBs), and by attenuating DNA damage checkpoint signaling. Phosphorylation of Sae2 by cyclin-dependent kinase (CDK1/Cdc28) activates the Mre11 endonuclease, while the physiological role of Sae2 phosphorylation by Mec1 and Tel1 checkpoint kinases is not fully understood. Here, we compare the phenotype of sae2 mutants lacking the main CDK (sae2-S267A) or Mec1 and Tel1 phosphorylation sites (sae2-5A) with sae2Δ and Mre11 nuclease defective (mre11-nd) mutants. The phosphorylation-site mutations confer DNA damage sensitivity, but not to the same extent as sae2Δ. The sae2-S267A mutation is epistatic to mre11-nd for camptothecin (CPT) sensitivity and synergizes with sgs1Δ, whereas sae2-5A synergizes with mre11-nd and exhibits epistasis with sgs1Δ. We find that attenuation of checkpoint signaling by Sae2 is mostly independent of Mre11 endonuclease activation but requires Mec1 and Tel1-dependent phosphorylation of Sae2. These results support a model whereby CDK-catalyzed phosphorylation of Sae2 activates resection via Mre11 endonuclease, whereas Sae2 phosphorylation by Mec1 and Tel1 promotes resection by the Dna2-Sgs1 and Exo1 pathways indirectly by dampening the DNA damage response.
Mechanistic Studies on Trichoacorenol Synthase from Amycolatopsis benzoatilytica

Isotopic labeling experiments performed with a newly identified bacterial trichoacorenol synthase established a 1,5‐hydride shift occurring in the cyclization mechanism. During EI‐MS analysis, major fragments of the sesquiterpenoid were shown to arise via cryptic hydrogen movements. Therefore, the interpretation of earlier results regarding the cyclization mechanism obtained by feeding experiments in Trichoderma is revised.
Savoring Moderates the Link between Marijuana Use and Marijuana Problems

Abstract Background: The changing legal landscape for marijuana requires concerted efforts toward minimizing the potential harms related to use of the plant. Purpose/Objectives: Identifying buffers against negative consequences in regular users could help researchers fashion prevention efforts that could appeal to those who are uninterested in messages related to abstinence. Savoring, a positively-focused, mindful approach to making the most of positive experiences, appears to overlap with facets of treatment that have proven successful with problem users. The present study examined the role of savoring in the development of marijuana-related problems. Methods: We examined the potential role of savoring as a buffer against marijuana problems in 195 participants (27.3% female). Results: Participants in this sample used cannabis 3.06 days per week on average. Correlations revealed that problems decreased as savoring increased. In addition, a significant interaction revealed that savoring moderated the impact of frequent use on problems. As savoring increased, the positive association between frequency of use and negative consequences decreased, suggesting that those who are high on savoring experience fewer negative consequences than those who are low on savoring even when they use marijuana as frequently. Conclusions: These data support the idea of incorporating savoring into the prevention of marijuana problems.
Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients

ABSTRACT Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure–response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy. Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies. Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure–response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.
Endothelial function following interval exercise plus low‐calorie diet treatment in obese females

We determined if interval exercise plus a low‐calorie diet (LCD + INT) increases endothelial function more than an energy‐matched LCD. Obese women (47.2 ± 2.6y, 37.5 ± 1.3kg/m2) were randomized to 13 days of a LCD (n = 12; mixed meals of ~ 1200kcal/d) or LCD + INT (n = 13; 12 supervised 60‐min INT bouts of 3 min at 90% and 50% HRpeak). LCD + INT subjects received 350kcal postexercise to equate energy availability with LCD. Fitness (VO2peak) and body composition (BodPod) were determined and a 120 min, 75 g oral glucose tolerance test was performed to examine fasting and postprandial flow‐mediated dilation (FMD, endothelial function), respiratory exchange ratio (RER) via indirect calorimetry as well as glucose and insulin incremental area under the curve (iAUC120min). LCD + INT increased VO2peak (P = 0.02) compared with LCD, and both treatments decreased fat mass (P < 0.001) and insulin iAUC120min (P = 0.03). There was no overall treatment effect on fasting or iAUC120min FMD. However, in participants who increased fasting endothelial function after each treatment (Δ > 50%; LCD n = 5, LCD + INT n = 7), LCD + INT increased fasted (P = 0.005) and decreased iAUC120min (P = 0.003) FMD compared with LCD. Enhanced fitness correlated with increased fasting FMD (r = 0.43, P = 0.03) and diminished FMD iAUC120min (r = −0.44, P = 0.03). Decreased FMD iAUC120min correlated with reduced glucose iAUC120min (r = 0.64, P = 0.001) as well as increased 60‐min RER (r = −0.42, P = 0.04). Low baseline fasting and iAUC120min FMD was also linked to enhanced fasting and iAUC120min FMD post‐treatment (r = −0.71, P < 0.001; r = −0.89, P < 0.001, respectively). In conclusion, increasing fitness via INT may increase the effect of LCD on lowering cardiovascular disease risk in obese women.
Dietary patterns are associated with depressive symptoms in older Australian women but not men

Abstract Studies have examined the association between depressive symptoms and dietary patterns; however, only few studies focused on older adults. The present study examines the association between current and past dietary patterns and depression in a community-dwelling adult population aged 55 years and over. Adults (n 4082) were recruited into the Wellbeing, Eating and Exercise for a Long Life study in Victoria, Australia. In 2010 and 2014, data were collected using self-administered questionnaires including a 111-item FFQ, the RAND thirty-six-item Short Form Health Survey of health-related quality of life and the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale in 2014. Current (2014) and past (2010) dietary patterns were determined using principal component analysis. Association between dietary patterns and depressive symptoms was assessed using a mixed model analysis with adjustment for covariates. Two similar dietary patterns were identified in men and women (n 2142). In women, a healthy dietary pattern (characterised by frequent intake of vegetables, fruits and fish) was associated with lower levels of depressive symptoms (current diet: β = −0·260, 95 % CI −0·451, −0·070; past diet: β = −0·201, 95 % CI −0·390, −0·013). A current unhealthy dietary pattern in women (characterised by frequent intake of red and processed meat, potatoes, hot chips, cakes, deserts and ice cream) was associated with higher levels of depressive symptoms (β = 1·367, 95 % CI 0·679, 2·056). No associations were identified in men. Further research is needed to confirm these findings and to understand the differences that may occur by sex.
How European primary care practitioners think the timeliness of cancer diagnosis can be improved: a thematic analysis

Background National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. Objectives This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. Design In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. Setting A primary care study, with participating centres in 20 European countries. Participants A total of 1352 PCPs answered the final survey question, with a median of 48 per country. Results The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. Conclusions To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.
Correlated factors of depression among male and female inmates.

INTRODUCTION The prevalence of depression is high in the prison system, and the differences between sex regarding associated risk factors are still not clear. We analyzed the correlated factors of depression among incarcerated men and women in the state of São Paulo, Brazil. METHODOLOGY A cross-sectional study with stratified and multi-stage probabilistic sample was performed. Composite International Diagnostic Interview (CIDI) was applied for psychiatric diagnostic classification, as well as a questionnaire on criminal history with 1,192 men and 617 women. Lifetime prevalence of mental disorder was calculated, and association analysis performed by multinomial logistic regression stratified by sex. A dependent variable was categorized into depression, any other mental disorder and no mental disorder (reference). RESULTS The prevalence of depression was of 33.3% -(30.3 - 36.5) in women and 12.9% (11.1 - 15.0) in men. Depression was associated with disciplinary penalty, being in a stable relationship, physical health problems and history of infringement in adolescence in men. Regarding other mental illnesses, the correlated factors were historical transgression during adolescence and re-offense. Among women, depression was associated with physical health problems, drug crimes, violent crimes and being imprisoned. DISCUSSION Results confirmed the differences between associated factors with depression regarding sex. CONCLUSION Differences in the profile between men and women require effective specialized programs, considering the need for coping strategies for incarcerated men and health-related rehabilitation for women with depression.
Designing new generation of potent inhibitors against membrane-type matrix metalloproteinase-2: a computational effort against multiple myeloma

Abstract Matrix metalloproteinases (MMPs) play important roles in cancer progression and, despite their inhibitors have failed in the clinical trials, they have always been considered as suitable targets for the treatment of tumor. We have recently shown that membrane type (MT) 2-MMPs, is selectively expressed in multiple myeloma (MM) cells and mediates the metastatic characteristics of these cells. In this study, we designed efficient inhibitors against MT2-MMP using state-of-art molecular modeling methods. First, the 3D structure of MT2-MMP was predicted. Then, the proposed potent inhibitors against two regions of the catalytic domain of MT2-MMP (active site and MT-LOOP) were identified through molecular docking, QM-MM and molecular dynamics simulations from a set of compounds in Analyticon library, IBS library, Maybridge screening fragment library and drugbank library. Moreover, ADME estimation showed that pharmacokinetic properties of inhibitors are in the acceptable range for humans. Finally, our data suggested that compounds ‘structures.722’ (dobutamine) and ‘M2’ are suitable candidates to inhibit MT2-MMP for further examination in the laboratory. Communicated by Ramaswamy H. Sarma
[Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors].

酪氨酸激酶抑制剂（TKI）提高了胃肠间质瘤（GIST）患者的生存率，但其不良反应会影响剂量强度，从而影响临床疗效。 迄今为止，还没有关于TKI相关不良反应的指南或共识发表。 因此，中国医师协会外科医师分会胃肠道间质瘤诊疗专业委员会组织了专家讨论会，由外科学、肿瘤学、心脏病学、皮肤病学、肾病学、内分泌学、眼科学等方面的专家进行讨论，根据TKI相关不良反应的临床症状及其发病机制，形成基于证据和经验的共识，提出治疗建议，以指导临床实践中治疗TKI相关的不良反应。
Positive association between cerebral grey matter metabolism and dopamine D2/D3 receptor availability in healthy and schizophrenia subjects: An 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography study

Abstract Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental. Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups. Results: 18F-fluorodeoxyglucose uptake and 18F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis. Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.
Improved detection of diffuse glioma infiltration with imaging combinations: a diagnostic accuracy study

Abstract Background Surgical resection and irradiation of diffuse glioma are guided by standard MRI: T2/fluid attenuated inversion recovery (FLAIR)–weighted MRI for non-enhancing and T1-weighted gadolinium-enhanced (T1G) MRI for enhancing gliomas. Amino acid PET has been suggested as the new standard. Imaging combinations may improve standard MRI and amino acid PET. The aim of the study was to determine the accuracy of imaging combinations to detect glioma infiltration. Methods We included 20 consecutive adults with newly diagnosed non-enhancing glioma (7 diffuse astrocytomas, isocitrate dehydrogenase [IDH] mutant; 1 oligodendroglioma, IDH mutant and 1p/19q codeleted; 1 glioblastoma IDH wildtype) or enhancing glioma (glioblastoma, 9 IDH wildtype and 2 IDH mutant). Standardized preoperative imaging (T1-, T2-, FLAIR-weighted, and T1G MRI, perfusion and diffusion MRI, MR spectroscopy and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET) was co-localized with multiregion stereotactic biopsies preceding resection. Tumor presence in the biopsies was assessed by 2 neuropathologists. Diagnostic accuracy was determined using receiver operating characteristic analysis. Results A total of 174 biopsies were obtained (63 from 9 non-enhancing and 111 from 11 enhancing gliomas), of which 129 contained tumor (50 from non-enhancing and 79 from enhancing gliomas). In enhancing gliomas, the combination of apparent diffusion coefficient (ADC) with [18F]FET PET (area under the curve [AUC], 95% CI: 0.89, 0.79‒0.99) detected tumor better than T1G MRI (0.56, 0.39‒0.72; P < 0.001) and [18F]FET PET (0.76, 0.66‒0.86; P = 0.001). In non-enhancing gliomas, no imaging combination detected tumor significantly better than standard MRI. FLAIR-weighted MRI had an AUC of 0.81 (0.65–0.98) compared with 0.69 (0.56–0.81; P = 0.019) for [18F]FET PET. Conclusion Combining ADC and [18F]FET PET detects glioma infiltration better than standard MRI and [18F]FET PET in enhancing gliomas, potentially enabling better guidance of local therapy.
Effects of CD133 Silencing on Survival and Migration of HT-29 Colorectal Cancer Cells.

BACKGROUND Colorectal cancer (CRC) is attributed as one of the most common malignancies worldwide. CD133 molecule, as a pentaspan transmembrane glycoprotein, confers stem cell-related characteristics, including self-renewal and multi-directional differentiation capability. CD133 plays important roles in the progression of CRC by conferring apoptotic resistance and migration ability. OBJECTIVE To investigate the anti-apoptotic and anti-angiogenic effect of CD-133 targeted siRNA in a colorectal cancer cell line. METHODS In this study, CD133-targeted siRNA transfection was conducted into HT-29 cells. MTT assay was employed to evaluate the cytotoxic effects of transfection on the cells. Flow cytometry was used to evaluate the apoptosis rate. The mRNA expression of apoptosis and metastasis related genes were assessed by quantitative Real-Time PCR (qRT-PCR). Wound healing assay was used to assess the migration potency of the infected cells. RESULTS Expression of CD133 was significantly downregulated after transfection of CD133-specific siRNA. Moreover, the rate of apoptosis was significantly increased after transfection. The migration potential of cells was diminished after transfection. siRNA delivery resulted in the modulation of expression of apoptosis and metastasis-related genes. CONCLUSION siRNA mediated targeting of CD133 could be considered as a promising approach to treat CRC through suppressing the cancerous behavior of tumor cells.
Quantitation and Simulation of Single Action Potential-Evoked Ca2+ Signals in CA1 Pyramidal Neuron Presynaptic Terminals

Abstract Presynaptic Ca2+ evokes exocytosis, endocytosis, and synaptic plasticity. However, Ca2+ flux and interactions at presynaptic molecular targets are difficult to quantify because fluorescence imaging has limited resolution. In rats of either sex, we measured single varicosity presynaptic Ca2+ using Ca2+ dyes as buffers, and constructed models of Ca2+ dispersal. Action potentials evoked Ca2+ transients with little variation when measured with low-affinity dye (peak amplitude 789 ± 39 nM, within 2 ms of stimulation; decay times, 119 ± 10 ms). Endogenous Ca2+ buffering capacity, action potential-evoked free [Ca2+]i, and total Ca2+ amounts entering terminals were determined using Ca2+ dyes as buffers. These data constrained Monte Carlo (MCell) simulations of Ca2+ entry, buffering, and removal. Simulations of experimentally-determined Ca2+ fluxes, buffered by simulated calbindin28K well fit data, and were consistent with clustered Ca2+ entry followed within 4 ms by diffusion throughout the varicosity. Repetitive stimulation caused free varicosity Ca2+ to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while local diffusion dominated. Thus, Ca2+ within tens of nanometers of entry, did not accumulate. A model of synaptotagmin1 (syt1)-Ca2+ binding indicates that even with 10 µM free varicosity evoked Ca2+, syt1 must be within tens of nanometers of channels to ensure occupation of all its Ca2+-binding sites. Repetitive stimulation, evoking short-term synaptic enhancement, does not modify probabilities of Ca2+ fully occupying syt1’s C2 domains, suggesting that enhancement is not mediated by Ca2+-syt1 interactions. We conclude that at spatiotemporal scales of fusion machines, Ca2+ necessary for their activation is diffusion dominated.