Miracle-dz/UniFAR-FTUs huggingface dataset:
Anatomical connections among the depressor supercilii, levator labii superioris alaeque nasi, and inferior fibers of orbicularis oculi: Implications for variation in human facial expressions

The aim of this study was to determine how the depressor supercilii (DS) connects to the levator labii superioris alaeque nasi (LLSAN) and inferior fibers of the orbicularis oculi (OOc INF) in the human midface. While grimacing, contraction of the DS with fibers connecting to the LLSAN and OOc INF can assist in pulling the medial eyebrow downward more than when these connecting fibers are not present. Contraction of these distinct connecting fibers between the DS and the LLSAN can also slightly elevate the nasal ala and upper lip. The DS was examined in 44 specimens of embalmed adult Korean cadavers. We found that the DS connected to the LLSAN or the OOc INF by muscle fibers or thin aponeuroses in 33 (75.0%) of the 44 specimens. The DS was connected to both the LLSAN and OOc INF by muscle fibers or aponeuroses and had no connection to either in 5 (11.4%) and 11 (25.0%) specimens, respectively. The DS was connected to the LLSAN by the muscle fibers and thin aponeuroses in 6 (13.6%) and 4 (9.1%) specimens, respectively. The DS was connected to the OOc INF by the muscle fibers and thin aponeuroses in 5 (11.4%) and 23 (52.3%) specimens, respectively. Our findings regarding the anatomical connections of the glabellar region DS to the midface LLSAN and OOc INF provide insights on the dynamic balance between the brow depressors such as the DS and brow-elevating muscle and contribute to understanding the anatomical origins of individual variation in facial expressions. These results can also improve the safety, predictability, and aesthetics of treatments for the glabellar region with botulinum toxin type A and can be helpful when performing electromyography.
Factors that mediate the relationships between household socio-economic status and childhood Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents: A systematic review

Background ADHD is one of the most prevalent mental health disorders among children and adolescents. Household socio-economic status (SES) in early childhood is inversely related to ADHD later in childhood or adolescence. We conducted a systematic review to examine psychological, social and behavioural factors that mediate these relationships (PROSPERO Registration number: CRD42020182832). Methods and findings We searched Medline, EMBASE, PsychINFo, and Web of Science from inception until May 2020. Both authors independently reviewed abstracts and identified papers for inclusion. We sought primary observational studies (cohort, cross-sectional and case control studies) of general population-based samples of children and adolescents aged 18 and under that investigated potential mediators of the relationships between SES and ADHD. Studies based upon non-general population-based samples, twins or biochemical/physiological changes were excluded. Direct and indirect effects derived from standard validated mediation analysis were extracted for potential mediators. We assessed risk of bias using a modified NIH tool and synthesised quantitative data without meta-analysis according to the (SWiM) protocol because of heterogeneity between included studies. Family adversity, paternal and maternal ADHD symptoms, Home Learning Environment, breastfeeding duration and a combined fine motor and language score at age 2 may lie on the SES-ADHD pathway. Evidence concerning the influence of maternal depression/anxiety and adverse parenting was inconsistent across studies. There was no evidence that mother’s health-related behaviour, family characteristics, child’s consumption of fizzy drinks or other developmental characteristics at birth/during infancy lie on the SES-ADHD pathway. Publication bias may have been introduced by our decision not to search grey literature, not to approach study authors and limit the search to the English language. Conclusions Evidence for mediation of the SES-ADHD pathway in childhood/adolescence is under-researched. Maternal mental health, family adversity, parenting and health-related behaviours warrant further research based on longitudinal data and employing the most advanced mediation analysis methods.
lncRNA RUNDC3A-AS1 Regulates Proliferation and Apoptosis of Thyroid Cancer Cells via the miR-151b/SNRPB Axis

The number of thyroid cancer (THCA) cases has increased dramatically worldwide. Many previous reports have confirmed that lncRNA is involved in the pathogenesis of THCA. However, the role and mechanism of lncRNA RUNDC3A-AS1 in THCA have not been studied. We intended to explore the effect of RUNDC3A-AS1 on the proliferation and apoptosis of THCA cells. Relative expression levels of RUNDC3A-AS1, microRNA (miR)-151b, and small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) were examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in THCA cells. The localization of RUNDC3A-AS1 in THCA cells was detected by subcellular fractionation assay. The cell proliferation was tested by 5-ethynyl-2′-deoxyuridine (EdU), cell counting kit-8 (CCK-8), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Flow cytometry was used to examine the cell apoptosis capacity. The relationships between RUNDC3A-AS1 and miR-151b or miR-151b and SNRPB were verified by luciferase reporter assay. The protein level was detected by Western blot analysis. RUNDC3A-AS1 exhibited high expression in THCA cells. RUNDC3A-AS1 knockdown suppressed cell proliferation but induced cell apoptosis. Importantly, RUNDC3A-AS1 targeted miR-151b to regulate the SNRPB expression. In rescue assays, SNRPB overexpression partially reversed the suppressive effect of RUNDC3A-AS1 knockdown on cell proliferation and the promotive effect of RUNDC3A-AS1 knockdown on cell apoptosis. The RUNDC3A-AS1/miR-151b/SNRPB axis regulated THCA cell proliferation and apoptosis, which provides novel insight into THCA investigation at the molecular level.
Evidence supporting a role for the immune checkpoint protein B7-H3 in NK cell-mediated cytotoxicity against AML.

We observed that the immune checkpoint protein B7-H3 is overexpressed in acute myeloid leukemia (AML) patients with poor treatment outcomes. Inhibition of B7-H3 expression or blocking of its activity using a novel monoclonal antibody (T-1A5) in AML cells significantly enhanced NK cell-mediated cytotoxicity in AML cells in vitro and in vivo. Moreover, human-mouse chimera of this antibody (ChT-1A5) induced antibody-dependent cell-mediated cytotoxicity (ADCC) in B7-H3+ primary AML cells, but not in normal hematopoietic cells, suggesting the specify of this antibody for AML cells. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft models. Our results suggest that ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.
Effects of ABCG1 knockout on proteomic composition of HDL in mice on a chow diet and a high‐fat diet

ATP‐binding cassette transporter G1 (ABCG1) is a cellular transmembrane protein that transports oxysterol efflux from cells to high‐density lipoprotein (HDL) particles in the plasma. Previous studies have demonstrated that an ABCG1 deficiency exerts an antiatherosclerotic function through the effects of oxysterol accumulation in cells to enhance apoptosis and regulate inflammatory processes. However, whether the deficiency of ABCG1 and the corresponding changes in the efflux of oxysterols could take a series of impacts on the proteomic composition of HDL remains unclear. Here, plasma HDL of ABCG1(−/−) mice and their wild‐type controls on a normal chow diet (NCD) or a high‐fat diet (HFD) were isolated by ultracentrifugation. The proportion of 7‐ketocholesterol and the proteomic composition of samples were comparatively analyzed by LC‐MS/MS. In NCD‐fed mice, lipid metabolism‐related protein (arachidonate 12‐lipoxygenase) and antioxidative protein (pantetheinase) exhibited increased accumulation, and inflammatory response protein (alpha‐1‐antitrypsin) was decreased in accumulation in ABCG1(−/−) mice HDL. In HFD‐fed mice, fewer proteins were detected than that of NCD‐fed mice. The ABCG1(−/−) mice HDL exhibited increased accumulation of lipid metabolism‐related proteins (e.g., carboxylesterase 1C, apolipoprotein (apo)C‐4) and decreased accumulation of alpha‐1‐antitrypsin, as well as significantly reduced proportion of 7‐ketocholesterol. Additionally, positive correlations were found between 7‐ketocholesterol and some essential proteins on HDL, such as alpha‐1‐antitrypsin, apoA‐4, apoB‐100, and serum amyloid A (SAA). These results suggest a detrimental impact of oxysterols on HDL composition, which might affect the antiatherosclerotic properties of HDL.
Patch testing in drug reaction with eosinophilia and systemic symptoms (DRESS): A literature review

The literature on positive patch test results in drug reaction with eosinophilia and systemic symptoms (DRESS) is reviewed. One hundred and five drugs were identified that have together caused 536 positive patch tests in 437 DRESS patients. By far, the most reactions (n = 145) were caused by carbamazepine, followed by amoxicillin, isoniazid, phenytoin, ethambutol, fluindione, phenobarbital, rifampicin, and ceftriaxone; 43 drugs each caused a single case only. The drug classes causing the highest number of reactions were anticonvulsants (39%), beta‐lactam antibiotics (20%), antituberculosis agents (11%), non‐beta‐lactam antibiotics (6%), and iodinated contrast media (5%). The sensitivity of patch testing (percentage of positive reactions) is high for anticonvulsants (notably carbamazepine), beta‐lactam antibiotics (notably amoxicillin), and, possibly, iodinated contrast media. Allopurinol and sulfasalazine frequently cause DRESS but never give positive patch tests. Patch testing in DRESS appears to be safe, although mild recurrence of DRESS symptoms, mostly skin reactions, may not be rare. Multiple drug hypersensitivity was found to occur in 16% of all patients, but it is argued that the true frequency is higher. Clinical aspects of DRESS, including diagnosing the disease and identifying culprit drugs (patch tests, intradermal tests, in vitro tests, challenge tests) are also provided, emphasizing the role of patch testing.
Clinical validation of the Aarhus Side effect Assessment Questionnaire(ASAQ)

Background: Psychotropic medications are essential in the treatment of mental illness. Unfortunately, these medications are associated with side effects that may reduce adherence to treatment and quality of life. Therefore, systematic screening for side effects is fundamental to optimize treatment with psychotropic medications. Self-report of side effects is a practical alternative to time-consuming clinical assessments. We developed the Aarhus Side effect Assessment Questionnaire (ASAQ) in an attempt to strike the balance between extensive coverage of side effects and reasonable application time. Aim: The aim of the study was to validate the ASAQ using the clinician-rated Udvalg for Kliniske Undersøgelser (UKU) Side Effect Scale as gold standard reference. Methods: A total of 122 inpatients and outpatients—mainly with psychotic (39%) and affective disorders (43%)—receiving treatment with psychotropic medication completed the ASAQ and the World Health Organization–Five Well-Being Index (WHO-5) and were subsequently rated on the UKU by trained raters. Results: Using the UKU as the gold standard reference, the ASAQ demonstrated sensitivity values >75% for 77% of its 30 items (ranging from 37% for cutaneous disturbances to 98% for increased sweating) and specificity values >75% for 47% of its 30 items (ranging from 28% for reduced sleep to 98% for micturition disturbances). While 17% of the participants considered discontinuing their medication, 24% had recently refrained from taking their medication as prescribed. A negative correlation was found between the ASAQ and the WHO-5 and total scores (Pearson’s correlation coefficient = –0.44). Conclusions: The self-reported ASAQ seems to be a sensitive tool for detecting side effects of psychotropic medications.
Reinforcement Learning in Patients With Mood and Anxiety Disorders vs Control Individuals

Key Points Question Are there differences in reinforcement learning between patients with mood and anxiety disorders and control individuals? Findings In this systematic review and meta-analysis, a novel computational simulation method showed differences in reinforcement learning between patients and control individuals. In particular, patients showed elevated punishment learning rates compared with control individuals. Meaning These findings show that patients may be more likely than control individuals to modify their behavior in response to punishments, suggesting a possible mechanistic treatment target for negative affective bias symptoms.
Interaction of background Ca2+ influx, sarcoplasmic reticulum threshold and heart failure in determining propensity for Ca2+ waves in sheep heart

Ventricular arrhythmias can cause death in heart failure (HF). A trigger is the occurrence of Ca2+ waves which activate a Na+‐Ca2+ exchange (NCX) current, leading to delayed after‐depolarisations and triggered action potentials. Waves arise when sarcoplasmic reticulum (SR) Ca2+ content reaches a threshold and are commonly induced experimentally by raising external Ca2+, although the mechanism by which this causes waves is unclear and was the focus of this study. Intracellular Ca2+ was measured in voltage‐clamped ventricular myocytes from both control sheep and those subjected to rapid pacing to produce HF. Threshold SR Ca2+ content was determined by applying caffeine (10 mM) following a wave and integrating wave and caffeine‐induced NCX currents. Raising external Ca2+ induced waves in a greater proportion of HF cells than control. The associated increase of SR Ca2+ content was smaller in HF due to a lower threshold. Raising external Ca2+ had no effect on total influx via the L‐type Ca2+ current, ICa‐L, and increased efflux on NCX. Analysis of sarcolemmal fluxes revealed substantial background Ca2+ entry which sustains Ca2+ efflux during waves in the steady state. Wave frequency and background Ca2+ entry were decreased by Gd3+ or the TRPC6 inhibitor BI 749327. These agents also blocked Mn2+ entry. Inhibiting connexin hemi‐channels, TRPC1/4/5, L‐type channels or NCX had no effect on background entry. In conclusion, raising external Ca2+ induces waves via a background Ca2+ influx through TRPC6 channels. The greater propensity to waves in HF results from increased background entry and decreased threshold SR content.
Sleep apnea in postmenopausal women is associated with joint pain severity and fatigability: a cross-sectional study

Abstract Objective: This study aimed to investigate the relationships between sleep apnea parameters and various symptoms in postmenopausal women who had treatment-resistant sleep disorders. Methods: The respiratory disturbance index (RDI), the number of times apnea-hypopnea occurred in an hour, and transcutaneous oxygen saturation (SpO2) were monitored during one night of sleep using a portable monitoring device in 51 postmenopausal women who did not have an improved subjective sleep quality with the use of hypnotics. Physical and psychological health statuses and subjective sleep disturbance were evaluated using validated questionnaires, including the Epworth Sleepiness Scale, the Cornell Medical Index, and the Questionnaire for Assessment of Climacteric Syndrome in Japanese Women. The associations between RDI, nadir SpO2 and various symptoms, as well as cardiovascular parameters, such as blood pressure, serum lipid profile, and glucose tolerance, were analyzed separately. Results: Among the 51 study participants, seven (13.7%) were diagnosed with obstructive sleep apnea. After adjustment for age, body mass index, and the background factors related to RDI and nadir SpO2, the association remained significant between a higher RDI and joint pain (Questionnaire for Assessment of Climacteric Syndrome in Japanese Women) (standardized partial regression coefficient [β] = 0.423, P = 0.016), and between lower nadir SpO2 and fatigability (Cornell Medical Index) (β = –0.472, P = 0.007). Conclusions: Detailed examination of sleep-disordered breathing is warranted in women with severe joint pain and fatigability.
Machine Learning Classifies Ferroptosis and Apoptosis Cell Death Modalities with TfR1 Immunostaining

Determining cell death mechanisms occurring in patient and animal tissues is a longstanding goal that requires suitable biomarkers and accurate quantification. However, effective methods remain elusive. To develop more powerful and unbiased analytic frameworks, we developed a machine learning approach for automated cell death classification. Image sets were collected of HT-1080 fibrosarcoma cells undergoing ferroptosis or apoptosis and stained with an anti-transferrin receptor 1 (TfR1) antibody, together with nuclear and F-actin staining. Features were extracted using high-content-analysis software, and a classifier was constructed by fitting a multinomial logistic lasso regression model to the data. The prediction accuracy of the classifier within three classes (control, ferroptosis, apoptosis) was 93%. Thus, TfR1 staining, combined with nuclear and F-actin staining, can reliably detect both apoptotic and ferroptotis cells when cell features are analyzed in an unbiased manner using machine learning, providing a method for unbiased analysis of modes of cell death.
Understanding Gene-Lifestyle Interaction in Obesity: The Role of Mediation versus Moderation

Background: Obesity results from complex interactions between genetic susceptibility to weight gain and poor eating and lifestyle behaviors. The approach that has been traditionally used in genetics to investigate gene-environment/lifestyle interaction in obesity is based on the concept of moderation or effect modification. Another approach called mediation analysis can be used to investigate gene-environment interaction in obesity. The objective of this review article is to explain the differences between the concepts of moderation and mediation and summarize the studies that have used mediation analysis to support the role of eating or lifestyle behaviors as putative mediators of genetic susceptibility to obesity. Summary: Moderation is used to determine whether the effect of an exposure (genes associated with obesity) on an outcome (obesity phenotype) differs in magnitude and/or direction across the spectrum of environmental exposure. Mediation analysis is used to assess the extent to which the effect of the exposure on the outcome is explained by a given set of hypothesized mediators with the aim of understanding how the exposure could lead to the outcome. In comparison with moderation, relatively few studies used mediation analyses to investigate gene-environment interaction in obesity. Most studies found evidence that traits related to appetite or eating behaviors partly mediated genetic susceptibility to obesity in either children or adults. Key Messages: Moderation and mediation represent two complementary approaches to investigate gene-environment interaction in obesity and address different research questions pertaining to the cause-effect relationship between genetic susceptibility to obesity and various obesity outcomes. More studies relying on mediation are needed to better understand the role of eating and lifestyle habits in mediating genetic susceptibility to obesity.
Discovery of a species-specific partial duplicate gene in Arabidopsis thaliana helps explain how new functions evolve.

Gene duplications are common in plants and create a potential repertoire for functional novelty. Gene duplicates can arise from a variety of mechanisms and place the newly copied gene in a new chromatin environment with different regulatory contexts. After gene duplication, several fates are possible, but in the overwhelming majority of cases, one of the gene copies accumulates degenerative mutations leading to pseudogenization (Lynch and Conery 2003). Sometimes, both copies survive, and the duplicated copy accumulates beneficial mutations to gain a novel function. These cases of neo-functionalization of duplicate copies are commonly reported in plants as a source for molecular innovations (Panchy et al. 2016). Partial gene duplications or changes in gene structure following duplication can contribute to such innovations. These partially duplicated and chimeric genes may be important for the formation of novel genes with new functions, but studies characterizing such duplication events are still scarce, especially in plants.
Determinants of Location of Death: A Secondary Analysis Utilizing Multinomial Logistic Regression

Statement of Problem: A discrepancy exists between where people would like to die and what actually occurs. More research about the factors influencing the location of death is required. Sources of Data and Research Design: Multinomial logistic regression was used to examine a sample taken from the fourth round of data collection performed by the National Health and Aging Trends Study conducted in 2014. Conclusions Reached: Census location, age, dementia, and use of hospice were found to have a statistically significant (P < .05) influence on the location of death (P = .000). The results suggest that the use of hospice increased the odds of dying at home (OR = 17.467, CI = 7.43–41.063) and in a nursing home (OR = 34.334, CI = 12.444–94.727) as compared to dying in the hospital. Further research is required on the topic of geographic location and place of death.
Opioid-related adverse drug events in surgical patients: risk factors and association with clinical outcomes

ABSTRACT Background Opioid analgesics are commonly used to treat acute post-operative pain. The primary objective of this study was to identify the risk factors for opioid-related adverse drug events (ORADEs) in surgical patients and the association between ORADEs and clinical outcomes. Research design and methods A retrospective cohort study was conducted using data from July 2016 to April 2020. ORADEs were defined using the International Classification of Diseases 10th Revision Australian Modification codes. Multivariate logistic regression was performed to identify ORADE risk factors. To investigate the association between ORADEs and clinical outcomes, propensity score matching was performed. Results Among 17,886 surgical patients who received opioid analgesics during hospital stay, 1,814 patients (10.2%) experienced ORADEs. Risk factors for general ORADEs included advanced age, comorbidities, concurrent use of benzodiazepines or gabapentinoids and a higher opioid daily dose. Patients who experienced ORADEs were associated with longer length of stay (Rate Ratio 3.00, 95% CI 2.97–3.04) but similar 28-day readmission rate (Odds Ratio 0.89, 95% CI 0.71–1.11). Conclusions Risk factors for general ORADEs were advanced age, specific comorbidities, use of benzodiazepines or gabapentinoids and higher opioid dose. Routine use of opioids with gabapentinoids should be avoided and only used after careful consideration.