Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphological structure of the aortic wall in three Delphinid species with shallow or intermediate diving habits: Evidence for diving adaptation

Some modifications in the vascular system of marine mammals provide adaptive advantages for diving. This study analyses the organisation of the aortic wall in dolphins, observing artery changes in volume and blood pressure for diving behaviour. Samples of three aortic segments (ascending, thoracic and abdominal) of three dolphin species were processed for histological and morphometric studies. The three dolphin species used, striped dolphin (Stenella coeruleoalba), Atlantic spotted dolphin (Stenella frontalis) and common dolphin (Delphinus delphis), have shallow or intermediate diving habits. Our results indicated that the components of the aortic wall of the dolphins had different dispositions in the three selected segments. The aortic wall decreased in thickness along its length due to a loss of the lamellar units in the tunica media and a thinning of the main elements of the lamellar units along the artery. The life stage had little influence on the thickness of the aortic wall except for the ascending aorta. The weight, body length, species or sex of the specimen did not significantly influence the thickness of the wall or the lamellar units. In summary, the histological and morphometric aortic structure in dolphins, in relation to the studied parameters, seems to be similar to that previously described of terrestrial mammals such as pigs, except for a larger difference in the proportion of lamellar units between the ascending and thoracic segments.
Improving Tumor Accumulation of Aptamers by Prolonged Blood Circulation.

Developing cancer targeted medicine depends on increasing delivery efficiency and tumor site accumulation of theranostic agents. To accomplish this, we report a modification of PTK7 receptor-specific aptamer Sgc8 with the small molecule Evans Blue (EB), thus implementing an albumin binding hitchhike strategy for prolonged blood circulation. The EB molecule could insert into the hydrophobic region of serum albumin and form an aptamer/albumin complex. This complex showed superior physiological stability, facilitating longer blood half-life, and maintaining its targeting capacity. Successful conjugation of EB-aptamers was confirmed by a serial of characterization methods. Targeting performance was tested on a xenografted mouse tumor model. Taking advantage of the long circulating aptamer/HSA complex, improved accumulation and delivery efficiency to the tumor site were achieved. Through ex vivo quantification of the EB-Sgc8 aptamers' biodistribution, the mechanism of improved targeting performance was illuminated. Therefore, the increased aptamers tumor delivery efficiency and accumulation indicate that prolonging blood circulation is a promising strategy to improve aptamers' targeted delivery performance in the future clinical translation.
Associations between amygdala reactivity to social threat, perceived stress and C-reactive protein in breast cancer survivors

Abstract Chronic inflammation in women diagnosed with breast cancer is critically linked with tumor progression, metastasis and survival. C-reactive protein (CRP)—a circulating marker of inflammation—is an important prognostic marker for cancer-related outcomes in breast cancer survivors (e.g. recurrence, fatigue). Psychological stress, which increases circulating markers of inflammation following sympathetic nervous system (SNS) activation, may modulate tumor-relevant inflammatory processes. However, little is known about neural mechanisms that might link stress and downstream SNS-initiated proinflammatory processes, such as elevated CRP. Past work suggests that threat-related neural regions, such as the amygdala, may be key in translating psychological stress into SNS activity and subsequent peripheral inflammation. Thus, we examined amygdala reactivity to socially threatening stimuli in association with perceived stress and plasma CRP levels to further elucidate neuro-immune pathways of social threat processing within breast cancer survivors (N = 37). Significant positive correlations were found between left amygdala reactivity in response to socially threatening stimuli (e.g. angry/fearful faces vs happy faces) and perceived stress in the previous month (r = 0.32, P = 0.025) and between left amygdala reactivity and CRP (r = 0.33, P = 0.025). This work builds on prior research implicating the amygdala as a key structure in crosstalk between threat-related neural circuitries and peripheral inflammation, particularly within cancer survivors.
The role of SLITRK6 in the pathogenesis of Tourette syndrome: From the conclusion of a family‐based study in the Chinese Han population

Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family‐based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population.
Small Nucleolar RNA Host Gene 1 (SNHG1) and Chromosome 2 Open Reading Frame 48 (C2orf48) as Potential Prognostic Signatures for Liver Cancer by Constructing Regulatory Networks

Background Liver cancer is a common malignant tumor with poor prognosis. The present study sought to identify potential signatures that can predict the prognosis of patients with liver cancer. Material/Methods The RNA sequencing (RNA-seq) and clinical information of liver cancer patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were identified between liver cancer and adjacent normal tissues. After predicting lncRNA–miRNA and miRNA–mRNA pairs using online databases, the competing endogenous RNA (ceRNA) networks were constructed. Furthermore, the prognostic value of these differentially expressed genes was evaluated using univariate and multivariate Cox regression analyses. Results After constructing the ceRNA network, 2 lncRNAs small nucleolar RNA host gene 1 (SNHG1) and chromosome 2 open reading frame 48 (C2orf48) with the most nodes were identified. Correlation analysis revealed that SNHG1 was correlated with miR-195 and C2orf48 was correlated with miR-195 and miR-93. High expression of SNHG1, C2orf48, and miR-93 can contribute to poorer clinical outcomes compared to low expression. Furthermore, low miR-195 expression was correlated with shorter survival time than was high expression. SNHG1 and C2orf48 were closely associated with histology grade. Univariate and multivariate Cox regression analyses confirmed that SNHG1 and C2orf48 are risk factors for liver cancer. Conclusions Our findings revealed that SNHG1 and C2orf48 possess potential prognostic value and should be considered as possible biomarkers for predicting clinical outcomes for patients with liver cancer.
Health-Related Correlates of Demonstrated Smartphone Expertise in Community-Dwelling Older Adults

Smartphone use in the older population is understudied, despite a growing use of technology in this age group. This study characterized the relation of demonstrated smartphone expertise to self-reported health attitudes and behaviors in 85 community-dwelling adults, mean age 77.24 (7.64) years. Self-report instruments included a demographic survey, a health attitudes measure, and a mobility checklist. Participants completed a behavioral challenge, the Smartphone Task for Older Adults (STOA). Demonstrated expertise in smartphone use (STOA-DESU), familiarity with apps, and ability to replicate functions after demonstration showed differential relations with health outcomes. DESU was positively associated with education, income, Altarum Consumer Engagement Measure (ACE), and Life Space Questionnaire (LSQ) scores and was negatively associated with age and daily medications. Additional findings replicated aspects of the well-known digital divide, and showed that those older adults with restricted mobility or diabetes had less knowledge of and more difficulties in using smartphones. Despite these problems, health-related functions must be optimized for older populations.
Peripheral Blood Leukocyte RNA-Seq Identifies a Set of Genes Related to Abnormal Psychomotor Behavior Characteristics in Patients with Schizophrenia

Background Schizophrenia is a multigene disease with a complex etiology and different clinical manifestations. It is of great significance to understand the etiology and pathogenesis of schizophrenia patients from different clinical dimensions and to interpret the potential molecular changes of schizophrenia patients from different clinical dimensions. Material/Methods RNA-Seq was performed on peripheral blood leukocytes of 50 patients with schizophrenia and 50 healthy controls. Phenotypic information of patients with schizophrenia was collected during blood sampling. Differentially expressed genes (DEGs) were screened by the edgeR package of R software. To better analyze the correlation between DEG expression values, explore the potential association between differential genes and clinical dimensions of schizophrenia, and identify hub genes, we constructed a DEG co-expression network using weighted gene co-expression network analysis (WGCNA). Results We provide the transcription profiles of peripheral blood leukocytes in patients with schizophrenia and found a gene module (including 89 genes) closely related to the clinical dimension of abnormal psychomotor behavior in schizophrenia. Conclusions The findings enhance our understanding of the biological processes of schizophrenia, enabling us to identify specific clinical dimensions of genes for diagnosis and prognostic markers and possibly for targeted therapy.
Inter‐ and intramolecular regulation of protein depupylation in Mycobacterium smegmatis

Whereas intracellular proteolysis is essential for proper cellular function, it is a destructive process, which must be tightly regulated. In some bacteria, a Pup‐proteasome system tags target proteins for degradation by a bacterial proteasome. Pup, a small modifier protein, is attached to target proteins by PafA, the sole Pup ligase, in a process termed pupylation. In mycobacteria, including Mycobacterium smegmatis and Mycobacterium tuberculosis, Pup undergoes a deamidation step by the enzyme Dop prior to its PafA‐mediated attachment to a target. The catalytic mechanism of Pup deamidation is also used by Dop to perform depupylation, namely the removal of Pup from already tagged proteins. Hence, Dop appears to play contradictory roles: On the one hand, deamidation of Pup promotes pupylation, while on the other hand, depupylation reduces tagged protein levels. To avoid futile pupylation–depupylation cycles, Dop activity must be regulated. An intramolecular regulatory mechanism directs Dop to catalyze deamidation more effectively than depupylation. A complementary intermolecular mechanism results in Dop depletion under conditions where protein pupylation and degradation are favorable. In this work, we studied these regulatory mechanisms and identified a flexible loop in Dop, previously termed the Dop‐loop, that acts as an intramolecular regulatory element that allosterically controls substrate preference. To investigate regulation at the intermolecular level, we used the CRISPR interference system to knock down the expression of M. smegmatis ATP‐dependent intracellular proteases and found that the ClpCP protease is responsible for Dop depletion under starvation conditions. These findings clarify previous observations and introduce a new level for the regulation of Dop activity.
c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells

RORγt+ group 3 innate lymphoid cells (ILC3s) maintain intestinal homeostasis through secretion of type 3 cytokines such as interleukin (IL)−17 and IL-22. However, CCR6- ILC3s additionally co-express T-bet allowing for the acquisition of type 1 effector functions. While T-bet controls the type 1 programming of ILC3s, the molecular mechanisms governing T-bet are undefined. Here, we identify c-Maf as a crucial negative regulator of murine T-bet+ CCR6- ILC3s. Phenotypic and transcriptomic profiling of c-Maf-deficient CCR6- ILC3s revealed a hyper type 1 differentiation status, characterized by overexpression of ILC1/NK cell-related genes and downregulation of type 3 signature genes. On the molecular level, c-Maf directly restrained T-bet expression. Conversely, c-Maf expression was dependent on T-bet and regulated by IL-1β, IL-18 and Notch signals. Thus, we define c-Maf as a crucial cell-intrinsic brake in the type 1 effector acquisition which forms a negative feedback loop with T-bet to preserve the identity of CCR6- ILC3s.
Cancer Patients’ and Survivors’ Perceptions of the Calm App: Cross-Sectional Descriptive Study

Background There is a need for tools to decrease cancer patients’ and survivors’ long-term symptom burden. Complementary strategies, such as meditation, can accompany pharmacologic therapy to improve symptoms. Although support programs with targeted content have wider reach, higher adherence, and greater impact, there are no consumer-based meditation apps designed specifically for cancer. Objective This study aimed to gather information to advise the development of a cancer-specific meditation app in a small convenience sample of cancer patients and survivors who currently use the Calm app. Methods Adult cancer patients and survivors who are Calm users (N=82) were recruited through the Daily Calm Facebook page. Participants completed a Web-based survey related to Calm app use and satisfaction, interest in and ideas for a cancer-specific Calm app, and demographic characteristics. Open-ended responses were inductively coded. Results Participants were aged between 18 and 72 years (mean 48.60 years, SD 15.20), mostly female (77/82, 94%), white (65/79, 82%), and non-Hispanic (70/75, 93%), and reported using Calm at least 5 times per week (49/82, 60%). Although rates of satisfaction with current Calm components were high (between 65/82, 79% and 51/81, 63%), only 49% (40/82) of participants used guided meditations that they felt specifically helped with their cancer-related symptoms and survivorship, and 40% (33/82) would prefer more cancer-related content, with guided meditations for cancer-specific anxieties (eg, fear of recurrence; n=15) and coping with strong emotions (n=12) being the most common suggestions. A majority of participants (51/82, 62%) reported that they would be interested in becoming a member of a Calm cancer community (eg, in-app discussion boards: 41/46, 89%; and social media communities: 35/42, 83%). Almost half of the participants (37/82, 45%) reported that they would benefit from features that tracked symptoms in concurrence with app usage, but respondents were divided on whether this information should be shared with health care providers through the app (49/82, 60% would share). Conclusions Responses suggest ways in which the current Calm app could be adapted to better fit cancer patients’ and survivors’ needs and preferences, including adding cancer-specific content, increasing the amount of content focusing on coping with strong emotions, developing communities for Calm users who are cancer patients and survivors, and including features that track cancer-related symptoms. Given differences in opinions about which features were desirable or would be useful, there is a clear need for future cancer-specific apps to be customizable (eg, ability to turn different features on or off). Although future research should address these topics in larger, more diverse samples, these data will serve as a starting point for the development of cancer-specific meditation apps and provide a framework for evaluating their effects.
Microglial NMDA receptors drive pro‐inflammatory responses via PARP‐1/TRMP2 signaling

Chronic neuroinflammation driven by microglia is a characteristic feature associated with numerous neurodegenerative diseases. While acute inflammation can assist with recovery and repair, prolonged microglial pro‐inflammatory responses are known to exacerbate neurodegenerative processes. Yet, detrimental outcomes of extended microglial activation are counterbalanced by beneficial outcomes including phagocytosis and release of trophic factors promoting neuronal viability. Our past work has shown that the nuclear enzyme poly(ADP‐ribose) polymerase‐1 (PARP‐1) is a key signaling hub driving pro‐inflammatory microglia responses, but the signaling pathway maintaining PARP‐1 activation remains elusive. While best understood for its role in promoting DNA repair, our group has shown that PARP‐1 activity can be stimulated via Ca2+ influx‐dependent ERK1/2‐mediated phosphorylation. However, to date, the route of Ca2+ entry responsible for stimulating PARP‐1 has not been identified. A likely candidate is via Ca2+‐permeable transient receptor potential melastatin 2 (TRPM2) channels activated downstream of PARP‐1 in a cascade that involves ADP‐ribose (ADPR) production by poly(ADP‐ribose) glycohydrolase (PARG). Here we demonstrate that NMDA receptor (NMDAR) stimulation in primary cultured microglia induces their proliferation, morphological activation and release of pro‐inflammatory mediators. These responses were contingent on the recruitment of PARP‐1, PARG and Ca2+ permeable TRPM2 channels. Furthermore, we show that Ca2+ influx is necessary to activate PARP‐1/TRPM2 signaling, in an ERK1/2‐dependent, but DNA damage independent, manner. Our findings, showing that PARP‐1/TRPM2 mediate the pro‐inflammatory effects of NMDAR stimulation, provides a unifying mechanism linking elevated glutamate levels to chronic neuroinflammation.
African American Older Adults Living with HIV: Exploring Stress, Stigma, and Engagement in HIV Care

Abstract:Limited information is available about factors that affect care engagement among African American older people living with HIV (OPLWH), despite the fact that this is the racial/ethnic group most disproportionally living with HIV/AIDS in the United States. The present mixed methods study examined the experiences of stress, HIV-related stigma, and engagement in care in a sample of 35 African American OPLWH. Quantitative methods measured global stress, HIV-stigma, and engagement in care, while in-depth qualitative interviews captured the lived experiences of HIV care engagement. Engagement in care was moderately correlated with overall stigma (r = –0.33, p = .05) and perceived stress (r = –0.42, p = .01). Qualitative interviews revealed that stigma was not the most significant stressor in the elders' lives, but instead a present and underlying force that was overshadowed by everyday life stressors that affected care engagement. Recommendations include that a retention specialist work alongside health care providers to increase engagement.
Geriatric Anxiety Scale: Development and Preliminary Validation of a Long-Term Care Anxiety Assessment Measure

ABSTRACT Objectives: Anxiety is a significant problem for many individuals in various long-term care (LTC) settings and is often undetected and under-treated. This study examined the psychometric properties of a new quantitative anxiety screening measure specifically designed for use in long-term care settings, the Geriatric Anxiety Scale – Long Term Care Version (GAS-LTC). Method: Data were collected from LTC residents (N = 66; M age = 84.4 years, range = 59 to 100 years; 74.2% women) who completed the GAS-LTC, the Geriatric Anxiety Inventory (GAI), the Geriatric Depression Scale-15 (GDS-15), and the Prospective and Retrospective Memory Questionnaire (PRMQ). Results: The GAS-LTC demonstrated good internal consistency (α = .80), and good convergent validity with the GAI (r = .70, p < .01), the GDS-15 (r = .67, p < .01), and the PRMQ (r = .54, p < .01). Internal consistency on the GAS-LTC did not significantly vary between groups with high (α = .75) and low (α = .77) self-reported subjective memory impairment. Conclusions: The results from this study preliminarily indicate that the GAS-LTC is reliable and valid for use with older adults in LTC settings. Clinical Implications: Use of the GAS-LTC in LTC settings may help improve detection and treatment for individuals experiencing elevated anxiety in LTC.
Comparison of Diagnostic Performances Between Cerebrospinal Fluid Biomarkers and Amyloid PET in a Clinical Setting.

The diagnostic performances of cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) were compared by examining the association and concordance or discordance between CSF Aβ1-42 and amyloid PET, after determining our own cut-off values for CSF Alzheimer's disease (AD) biomarkers. Furthermore, we evaluated the ability of CSF biomarkers and amyloid PET to predict clinical progression. CSF Aβ1-42, t-tau, and p-tau levels were analyzed in 203 individuals [27 normal controls, 38 mild cognitive impairment (MCI), 62 AD dementia, and 76 patients with other neurodegenerative diseases] consecutively recruited from two dementia clinics. We used both visual and standardized uptake value ratio (SUVR)-based amyloid PET assessments for analyses. The association of CSF biomarkers with amyloid PET SUVR, hippocampal atrophy, and cognitive function were investigated by linear regression analysis, and the risk of conversion from MCI to AD dementia was assessed using a Cox proportional hazards model. CSF p-tau/Aβ1-42 and t-tau/Aβ1-42 exhibited the best diagnostic accuracies among the CSF AD biomarkers examined. Correlations were observed between CSF biomarkers and global SUVR, hippocampal volume, and cognitive function. Overall concordance and discordance between CSF Aβ1-42 and amyloid PET was 77% and 23%, respectively. Baseline positive CSF Aβ1-42 for MCI demonstrated a 5.6-fold greater conversion risk than negative CSF Aβ1-42 . However, amyloid PET findings failed to exhibit significant prognostic value. Therefore, despite presence of a significant correlation between the CSF Aβ1-42 level and SUVR of amyloid PET, and a relevant concordance between CSF Aβ1-42 and amyloid PET, baseline CSF Aβ1-42 better predicted AD conversion.
Geographic Variation in Outcomes After Burn Injury

Background Geography is an important yet underexplored factor that may influence the care and outcomes of burn survivors. This study aims to examine the impact of geography on physical and psychosocial function after burn injury. Methods Data from the Burn Model Systems National Database (1997–2015) were analyzed. Individuals 18 years and older who were alive at discharge were included. Physical and psychosocial functions were assessed at 6, 12, and 24 months postinjury using the following patient-reported outcome measures: Community Integration Questionnaire, Physical Composite Scale and Mental Composite Scale of the 12-Item Short Form Health Survey, Satisfaction with Appearance Scale, and Satisfaction with Life Scale. Descriptive statistics were generated for demographic and medical data, and mixed regression models were used to assess the impact of geography on long-term outcomes. Results The study included 469 burn survivors from the Centers for Medicare and Medicaid Services regions 10, 31 from region 8, 477 from region 6, 267 from region 3, and 41 from region 1. Participants differed significantly by region in terms of race/ethnicity, burn size, burn etiology, and acute care length of stay (P < 0.001). In adjusted mixed model regression analyses, scores of all 5 evaluated outcome measures were found to differ significantly by region (P < 0.05). Conclusions Several long-term physical and psychosocial outcomes of burn survivors vary significantly by region. This variation is not completely explained by differences in population characteristics. Understanding these geographical differences may improve care for burn survivors and inform future policy and resource allocation.