Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods

Supplemental Digital Content is available in the text Abstract Background: Acute myocardial infarction (AMI) is a common disease leading threat to human health around the world. Here we aimed to explore new biomarkers and potential therapeutic targets in AMI through adopting integrated bioinformatics tools. Methods: The gene expression Omnibus (GEO) database was used to obtain genes data of AMI and no-AMI whole blood. Furthermore, differentially expressed genes (DEGs) were screened using the “Limma” package in R 3.6. 1 software. Functional and pathway enrichment analyses of DEGs were performed via “Bioconductor” and “GOplot” package in R 3.6. 1 software. In order to screen hub DEGs, the STRING version 11.0 database, Cytoscape and molecular complex detection (MCODE) were applied. Correlation among the hub DEGs was evaluated using Pearson's correlation analysis. Results: By performing DEGs analysis, 289 upregulated and 62 downregulated DEGs were successfully identified from GSE66360, respectively. And they were mainly enriched in the terms of neutrophil activation, immune response, cytokine, nuclear factor kappa-B (NF-κB) signaling pathway, IL-17 signaling pathway, and tumor necrosis factor (TNF) signaling pathway. Based on the data of protein–protein interaction (PPI), the top 10 hub genes were ranked, including interleukin-8 (CXCL8), TNF, N-formyl peptide receptor 2 (FPR2), growth-regulated alpha protein (CXCL1), transcription factor AP-1 (JUN), interleukin-1 beta (IL1B), platelet basic protein (PPBP), matrix metalloproteinase-9 (MMP9), toll-like receptor 2 (TLR2), and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G). What's more, the results of correlation analysis demonstrated that there was positive correlation between the 10 hub DEGs. Conclusion: Ten DEGs were identified as potential candidate diagnostic biomarkers for patients with AMI in present study. However, further experiments are needed to confirm the functional pathways and hub genes associated with AMI.
No linear correlation between pelvic incidence and acetabular orientation

Abstract Links between sagittal spinal alignment and acetabular orientation attract considerable research attention with the goal of understanding “hip-spine syndrome. ” However, whether pelvic incidence (PI) is related to acetabular orientation remains debatable. The purpose of the present study was to determine1. whether the correlation between PI and acetabular orientation is present in pelvises of young healthy adults, and2. whether the correlation is present in subgroups of sex, or between the left and right pelvis. We analyzed 100 abdominopelvic computed tomography (CT) scans of skeletally healthy young adults. We measured PI and acetabular orientation with three-dimensional (3D) measurements. The orientation of 200 acetabula was measured using 3D reconstructed models of 100 pelvises in the coordinate system based on the anterior pelvic plane (APP). To quantify the acetabular orientation, the radiographic definitions of anteversion and inclination were used. To examine the correlation between acetabular orientation and PI, Pearson's correlation was used. The mean PI was 46.9° ± 10.2°, and the mean acetabular orientation 15.3° ± 5.7° anteverted and 37.5° ± 3.9° inclined. While no significant difference in the PI was observed, the average acetabular orientation of female pelvises (anteversion, 17.5° ± 5.6°; inclination, 36.7° ± 3.7°) was more anteverted and less inclined compared to that of male pelvises (anteversion, 13.2° ± 4.9°; inclination, 38.3° ± 3.9°, respectively; P values < .05). The correlation between PI and acetabular orientation was statistically not significant. After division of study group by sex, the linear correlation between PI and acetabular orientation was not statistically supported. The asymmetry of the acetabular orientation between the left and right sides was not significant. The linear relationship between anatomical acetabular orientation and PI was not evident in the normal population. Our finding thus proves the absence of a linear relationship between the upper and lower articular orientation of the pelvic segment and deepens the understanding of the characteristics of acetabular orientation and PI.
Temporal Contribution of Myeloid-Lineage TLR4 to the Transition to Chronic Pain: A Focus on Sex Differences

Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We demonstrate that systemic TLR4 antagonism is more effective at improving chronic allodynia trajectory when administered at the time of injury (early) in the tibial fracture model of CRPS in both sexes. In order to clarify the contribution of myeloid-lineage cells peripherally (macrophages) or centrally (microglia), we rigorously characterize a novel spatiotemporal transgenic mouse line, Cx3CR1-CreERT2-eYFP;TLR4fl/fl (TLR4 cKO) to specifically knock out TLR4 only in microglia and no other myeloid-lineage cells. Using this transgenic mouse, we find that early TLR4 cKO results in profound improvement in chronic, but not acute, allodynia in males, with a significant but less robust effect in females. In contrast, late TLR4 cKO results in partial improvement in allodynia in both sexes, suggesting that downstream cellular or molecular TLR4-independent events may have already been triggered. Overall, we find that the contribution of TLR4 is time- and microglia-dependent in both sexes; however, females also rely on peripheral myeloid-lineage (or other TLR4 expressing) cells to trigger chronic pain. SIGNIFICANCE STATEMENT The contribution of myeloid cell TLR4 to sex-specific pain progression remains controversial. We used complementary pharmacologic and transgenic approaches to specifically manipulate TLR4 based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We discovered that microglial TLR4 contributes to early pain progression in males, and to a lesser extent in females. We further found that maintenance of chronic pain likely occurs through myeloid TLR4-independent mechanisms in both sexes. Together, we define a more nuanced contribution of this receptor to the acute-to-chronic pain transition in a mouse model of complex regional pain syndrome.
Effect of acupuncture on essential hypertension

Abstract Background: Essential hypertension is a risk factor for early cardiovascular disease and is a major preventable risk factor for premature death and disability worldwide. However, some antihypertensive drugs cannot be used for treatment because of their cost-effectiveness or side effects. Non-drug treatments for hypertension include weight loss, salt restriction, smoking cessation, alcohol withdrawal, and exercise, although these methods are difficult to maintain and to achieve. This study will investigate the efficacy and safety of acupuncture and moxibustion in the treatment of different grades of essential hypertension. Methods and analysis: A systematic search of the Cochrane, PubMed, EMBASE, CNKI, WanFang, VIP, and CBM databases will be performed, which will include randomized controlled trials on acupuncture for essential hypertension. The main results will include systolic and diastolic blood pressure before and after treatment, whereas the secondary outcomes will be efficacy rate and adverse events. The possible adverse reactions include dizziness, headache, edema, cough, nausea, electrolyte disorders, and hypotension. RevMan Manager 5.3 (Cochrane Collaboration) and STATA 16.0 software will be used to calculate mean deviation, standard deviation, confidence interval, and P values. For continuous variables, we will use the standardized mean difference of 95% confidence intervals as the summary statistics of the meta-analysis. Results: This study will assess the efficacy and safety of acupuncture for essential hypertension. Conclusions: Our study will determine the efficacy and safety of acupuncture in treating primary hypertension, and provide the basis for clinical decision-making. INPLASY registration number: INPLASY202130042.
Lung Cancer Mortality and Styrene Exposure in the Reinforced Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias.

The evidence of styrene as a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced plastics industry are an ideal population to study this association due to relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. We studied a cohort of 5163 boatbuilders exposed to styrene in Washington state employed between 1959 and 1978; prior regression analyses demonstrated little evidence for an exposure-response between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB we estimated that one year of exposure >30 ppm accelerates time to lung cancer death by 2.3 years (95% Confidence intervals=1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene exposed workers may suffer similar biases, warranting a re-assessment of the evidence of long-term health effects of styrene exposure.
Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

PURPOSE The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported. METHODS Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety. RESULTS Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label. CONCLUSION Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.
Sex differences in synaptic plasticity underlying learning

Although sex differences in learning behaviors are well documented, sexual dimorphism in the synaptic processes of encoding is only recently appreciated. Studies in male rodents have built upon the discovery of long‐term potentiation (LTP), and acceptance of this activity‐dependent increase in synaptic strength as a mechanism of encoding, to identify synaptic receptors and signaling activities that coordinate the activity‐dependent remodeling of the subsynaptic actin cytoskeleton that is critical for enduring potentiation and memory. These molecular substrates together with other features of LTP, as characterized in males, have provided an explanation for a range of memory phenomena including multiple stages of consolidation, the efficacy of spaced training, and the location of engrams at the level of individual synapses. In the present report, we summarize these findings and describe more recent results from our laboratories showing that in females the same actin regulatory mechanisms are required for hippocampal LTP and memory but, in females only, the engagement of both modulatory receptors such as TrkB and synaptic signaling intermediaries including Src and ERK1/2 requires neuron‐derived estrogen and signaling through membrane‐associated estrogen receptor α (ERα). Moreover, in association with the additional ERα involvement, females exhibit a higher threshold for hippocampal LTP and spatial learning. We propose that the distinct LTP threshold in females contributes to as yet unappreciated sex differences in information processing and features of learning and memory.
Sexual dimorphism in mastoid process volumes measured from 3D models of dry crania from medieval Croatia

3D analysis of skeletal volumes has become an important field in digital anthropology studies. The volume of the mastoid process has been proposed to display significant sexual dimorphism, but it has a complex shape and to date no study has quantified the full mastoid volume for sex estimation purposes. In this study we compared three different ways to isolate the volume of the mastoid process from digital 3D models of dry crania, and then evaluated the performance of the three different volume definitions for sex estimation purposes. A total of 170 crania (86 male, 84 females) excavated from five medieval Croatian sites were CT-scanned and used to produce 3D stereolitographic models. The three different isolation techniques were based on various anatomical landmarks and planes, as well as the anatomy of the mastoid process itself. Measurements of the three different mastoid volumes yielded different accuracies and precisions. Interestingly, anatomical structures were sometimes more useful than classical landmarks as demarcators of mastoid volume. For all three volume definitions, male mastoid volumes were significantly larger than female volumes, in both relative and absolute numbers. Sex estimation based on mastoid volume showed a slightly higher precision and better accuracy (71 % correct classifications) than visual scoring techniques (67 %) and linear distance measurements (69 %) of the mastoid process. Sex estimation based on cranial size performed even better (78 %), and multifactorial analysis (skull size + mastoid volume) reached up to 81% accuracy. These results show that measurements of the mastoid volume represent a promising metric to be used in multifactorial approaches for sex estimation of human remains.
Escherichia coli GyrA Tower Domain Interacts with QnrB1 Loop B and Plays an Important Role in QnrB1 Protection from Quinolone Inhibition

The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. ABSTRACT The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. The specific QnrB1 interaction sites on DNA gyrase are not known. In this study, we investigated the interaction between GyrA and QnrB1 using site-specific photo-cross-linking of QnrB1 loop B combined with mass spectrometry. We found that amino acid residues 286 to 298 on the tower domain of GyrA interact with QnrB1 and play a key role in QnrB1 protection of gyrase from quinolone inhibition. Alanine replacement of arginine at residue 293 and a small deletion of amino acids 286 to 289 of GyrA resulted in a decrease in the QnrB1-mediated increase in quinolone MICs and also abolished the QnrB1 protection of purified DNA gyrase from ciprofloxacin inhibition.
A novel paradigm to assess storage of sources in memory: the source recognition test with reinstatement

ABSTRACT The present research aimed to devise a test of source recognition that facilitates access to source information stored in memory. Therefore, we extended the standard source-monitoring paradigm, in which items are presented in a source-neutral manner during test, by a second, subsequent test with source reinstatement. In this second test, items (i.e., words) were presented with both study sources (i.e., two speakers) consecutively such that for originally studied words, one test presentation was the exact reinstatement of the original source. To validate our assumption that the test with reinstatement primarily assesses source storage, we manipulated source storage by varying encoding frequency between-participants (repetition vs. no repetition of each item-source-pair). Additionally, we varied source similarity between-participants (similar vs. dissimilar speakers). Data analyses (N = 146) based on multinomial and signal detection models showed a source memory enhancement in the second test with reinstatement compared to the first standard test, especially for similar sources. Additionally, repetition selectively benefited source memory in the second test, validating our interpretation of the second test as a measure for source storage. Altogether, our novel source recognition test offers a promising method for investigating various well-known source memory phenomena more comprehensively.
Decoding Concurrent Representations of Pitch and Location in Auditory Working Memory

Multivariate analyses of hemodynamic signals serve to identify the storage of specific stimulus contents in working memory (WM). Representations of visual stimuli have been demonstrated both in sensory regions and in higher cortical areas. While previous research has typically focused on the WM maintenance of a single content feature, it remains unclear whether two separate features of a single object can be decoded concurrently. Also, much less evidence exists for representations of auditory compared with visual stimulus features. To address these issues, human participants had to memorize both pitch and perceived location of one of two sample sounds. After a delay phase, they were asked to reproduce either pitch or location. At recall, both features showed comparable levels of discriminability. Region of interest (ROI)-based decoding of functional magnetic resonance imaging (fMRI) data during the delay phase revealed feature-selective activity for both pitch and location of a memorized sound in auditory cortex and superior parietal lobule. The latter region showed higher decoding accuracy for location than pitch. In addition, location could be decoded from angular and supramarginal gyrus and both superior and inferior frontal gyrus. The latter region also showed a trend for decoding of pitch. We found no region exclusively coding pitch memory information. In summary, the present study yielded evidence for concurrent representations of pitch and location of a single object both in sensory cortex and in hierarchically higher regions, pointing toward representation formats that enable feature integration within the same anatomic brain regions. SIGNIFICANCE STATEMENT Decoding of hemodynamic signals serves to identify brain regions involved in the storage of stimulus-specific information in working memory (WM). While to-be-remembered information typically consists of several features, most previous investigations have focused on the maintenance of one memorized feature belonging to one visual object. The present study assessed the concurrent storage of two features of the same object in auditory WM. We found that both pitch and location of memorized sounds were decodable both in early sensory areas, in higher-level superior parietal cortex and, to a lesser extent, in inferior frontal cortex. While auditory cortex is known to process different features in parallel, their concurrent representation in parietal regions may support the integration of object features in WM.
Novel model predicts prognosis for patients with diffuse large B-cell lymphoma in first relapse after initial R-CHOP therapy: a single-institution study in China

Objective To develop a prognostic model for Chinese patients with relapsed diffuse large B-cell lymphoma (DLBCL) after initial R-CHOP therapy. Methods We retrospectively analyzed the characteristics and survival outcomes of 79 patients with relapsed DLBCL initially treated with R-CHOP at Peking Union Medical College Hospital from February 2012 to September 2016. We used the data to develop a novel prognostic model. Results The median age at the start of salvage therapy was 59 (17–85) years and median time from diagnosis to relapse was 319 (49–1018) days. Multivariate analysis identified short time to relapse (TTR) and B symptoms as independent prognostic factors for reduced progression-free survival (PFS) and overall survival (OS). We created a new prognostic scoring system including TTR, lactate dehydrogenase, absolute lymphocyte count at relapse, and B symptoms, referred to as the TLLB model, which could separate patients into three risk groups with 2-year PFS and OS rates of 70.7%, 40.0%, and 11.1%, and 87.5%, 53.7%, and 29.4%, respectively. Conclusion TTR and B symptoms can be used as important predictors of survival in patients with DLBCL. The TLLB system provides a useful prognostic model compared with the previous TTL system.
Is Job Insecurity Worse for Mental Health Than Having a Part-time Job in Canada?

Objectives: A growing number of people depend on flexible employment, characterized by outsider employment status and perceived job insecurity. This study investigated whether there was a synergistic effect of employment status (full-time vs. part-time) and perceived job insecurity on major depressive disorder. Methods: Data were derived from the 2012 Canadian Community Health Survey-Mental Health of 12 640 of Canada’s labor force population, aged 20 to 74. By combining employment status with perceived job insecurity, we formed four employment categories: full-time secure, full-time insecure, part-time secure, and part-time insecure. Results: Results showed no synergistic health effect between employment status and perceived job insecurity. Regardless of employment status (full-time vs. part-time), insecure employment was significantly associated with a high risk of major depressive disorder. Analysis of the interaction between gender and four flexible employment status showed a gender-contingent effect on this link in only full-time insecure category. Men workers with full-time insecure jobs were more likely to experience major depressive disorders than their women counterparts. Conclusions: This study’s findings imply that perceived job insecurity may be a critical factor for developing major depressive disorder, in both men and women workers.