Miracle-dz/UniFAR-FTUs huggingface dataset:
MISSO: Minimization by Incremental Stochastic Surrogate for large-scale nonconvex Optimization

Many nonconvex optimization problems can be solved using the MajorizationMinimization (MM) algorithm that consists in upper bounding, at each iteration of the algorithm, the objective function by a surrogate that is easier to minimize. When the objective function can be expressed as a large sum of individual losses, incremental version of the MM algorithm is often used. However, in many cases of interest (Generalized Linear Mixed Model or Variational Bayesian inference) those surrogates are intractable. In this contribution, we propose a generalization of incremental MM algorithm using Monte Carlo approximation of these surrogates. We establish the convergence of our unifying scheme for possibly nonconvex objective. Finally, we apply our new framework to train a logistic regression and a Bayesian neural network on the MNIST dataset and compare its convergence behaviour with state-of-the-art optimization methods.
EGR 1 , EGFR and IGF 1 R protein expressions in non-small cell lung cancer and their clinical significances

The purpose of this study was to investigate the incidence and clinical significance of alterations in EGFR, IGF1R and the cell signaling pathway activities induced by them, as well as EGR1 expression in resected non-small cell lung cancer (NSCLC). The protein expressions of biomarker were evaluated by Western blotting in tissues from 19 surgically resected NSCLCs. High expressions of EGR1, EGFR and IGF1R were detected in more than 30% tumor tissues. High expressions of pErk and pAkt were detected in more than 50% paracancer tissues. There were significant correlations between the NSCLC target factors detected (p<0.05). Alterations of protein expressions of target factor detected in NSCLC were significantly associated with alterations in pathological subtype, differentiation, pathological stage, and smoking history. Positive EGR1 might be associated with good survival, while positive pErk might be associated with poor prognosis. Article Info Received: 16 January 2016 Accepted: 30 January 2016 Available Online: 9 March 2016 DOI: 10.3329/bjp.v11iS1. 26413 Cite this article: Yu D, Tan P, Yu M, Shi S, Wang X. EGR1, EGFR and IGF1R protein expressions in non-small cell lung cancer and their clinical significances. Bangladesh J Pharmacol. 2016; 11: S123-S130. EGR1, EGFR and IGF1R protein expressions in non-small cell lung cancer and their clinical significances Dujuan Yu1, Ping Tan1, Min Yu2, Shaomin Shi1 and Xue Wang3 The Department of Respiration, China Japan Union Hospital of Jilin University, Changchun, Jilin, 130 033, China; The Department of Cardiology, Affiliated Hospital of Beihua University, Jilin, Jilin, 1340 00, China; The Center of Physical Examination, China Japan Union Hospital of Jilin University, Changchun, Jilin, 130 033, China. This paper was presented in the 3rd International Conference on Biomedicine and Pharmaceutics in Zhuhai, China, on December 11-13, 2015. cal resections for NSCLC from 2010 to 2011 in China Japan Union Hospital of Jilin University. The patients’ clinical and histopathological information was presented in Table I. No patients underwent antineoplastic therapy prior to surgery. Totally 38 resected tissue specimens were obtained from 19 patients. All the patients donated their primary lung squamous cell carcinoma (SCC) tissues (S1-S10), corresponding paracancer tissues (SP1–SP10), primary lung adenocarcinoma tissues (A1-A9) and the corresponding paracancer tissues (AP1–AP9). HE staining was obtained (Figure 1). All the patients gave the informed consent.
Inflammation Induced Sensory Nerve Growth and Pain Hypersensitivity Requires the N-Type Calcium Channel Cav2.2

Voltage-gated calcium channels (VGCCs) are important mediators of pain hypersensitivity during inflammatory states, but their role in sensory nerve growth remains underexplored. Here, we assess the role of the N-type calcium channel Cav2.2 in the complete Freund’s adjuvant (CFA) model of inflammatory pain. We demonstrate with in situ hybridization and immunoblotting, an increase in Cav2.2 expression after hind paw CFA injection in sensory neurons that respond to thermal stimuli, but not in two different mechanosensitive neuronal populations. Further, Cav2.2 upregulation post-CFA correlates with thermal but not mechanical hyperalgesia in behaving mice, and this hypersensitivity is blocked with a specific Cav2.2 inhibitor. Voltage clamp recordings reveal a significant increase in Cav2.2 currents post-CFA, while current clamp analyses demonstrate a significant increase in action potential frequency. Moreover, CFA-induced sensory nerve growth, which involves the extracellular signal-related kinase (ERK1/2) signaling pathway and likely contributes to inflammation-induced hyperalgesia, was blocked with the Cav2.2 inhibitor. Together, this work uncovers a role for Cav2.2 during inflammation, demonstrating that VGCC activity can promote thermal hyperalgesia through both changes in firing rates of sensory neurons as well as promotion of new neurite outgrowth.
Integrative Analysis of miRNA and mRNA Expression Profiles Associated With Human Atrial Aging

Background Limited findings have been reported to systematically study miRNA and mRNA expression profiles in aged human atria. In this study, we aimed to identify miRNAs, genes, and miRNA-mRNA interaction networks for human atrial aging (AA). Methods Right atrial appendages from twelve patients who received aortic valve replacement were subjected to miRNA-seq and RNA-seq. All the patients were in sinus rhythm (SR) and stratified by age into four groups. Differential expression analysis was carried out to identify miRNAs and genes for human AA. The miRNA-mRNA interactions for human AA were identified by Pearson correlation analysis and miRNA target prediction programs. Results Seven miRNAs (4 upregulation and 3 downregulation) and 42 genes (23 upregulation and 19 downregulation) were differentially expressed in human right atrial tissues between older samples and younger samples. Bioinformatic analysis identified 114 pairs of putative miRNA-mRNA interactions on AA and four types of correlation. Pathway enrichment analysis identified over 40 significant pathways and the top three pathways included rhythmic process (P = 7.5 × 10–5, Q = 0.034), senescence and autophagy in cancer (P = 9.0 × 10–5, Q = 0.034), and positive regulation of cytokine biosynthetic process (P = 1.1 × 10–4, Q = 0.034). Conclusion Our study revealed novel miRNA-mRNA interaction networks and signaling pathways for AA, providing novel insights into the development of human AA. Future studies are needed to investigate the potential significance of these miRNA-mRNA interactions in human AA or AA-related cardiovascular diseases.
Identification of SPP1 as an Extracellular Matrix Signature for Metastatic Castration-Resistant Prostate Cancer

Resistance to androgen deprivation therapy (ADT) is the main challenge for advanced fatal prostate cancer (PCa), which can gradually develop into metastatic castration-resistant prostate cancer (mCRPC). However, the pathologic mechanisms of mCRPC are still far from clear. Given the high incidence and mortality related to mCRPC, understanding the causes and pathogenesis of this condition as well as identifying potential biomarkers are of great importance. In the research reported here, we integrated several gene expression profiles from hormone sensitive prostate cancer (HSPC) and mCRPC datasets to identify differentially expressed genes (DEGs), key biological pathways, and cellular components. We found that extracellular matrix (ECM) genes were significantly enriched, and further filtered them using Pearson correlation analysis and stepwise regression to find ECM signatures to differentiate between the HSPC and mCRPC phenotypes. Six ECM signatures were input into K-nearest neighbor, logistic regression, naive Bayes, and random forest classifiers models. Random forest algorithm with the six-gene prognostic signatures showed best performance, which had high sensitivity and specificity for HSPC and mCRPC classification and further the six ECM signatures were validated in organoid models. Among the six ECM genes, SPP1 was identified as the key hub signature for PCa metastasis and drug resistance development; we found that both protein and mRNA expression levels of SPP1 were remarkably up-regulated in mCRPC compared with HSPC in organoid models and could regulate the androgen receptor signaling pathway. Therefore, SPP1 is a potential novel biomarker and therapeutic target for mCRPC. Further understanding of the role of SPP1 in mCRPC development may help to explore effectively therapeutic approaches for the prevention and intervention of drug resistance and metastasis.
A nano-liposome formulation of the PARP inhibitor Talazoparib enhances treatment efficacy and modulates immune cell populations in mammary tumors of BRCA-deficient mice

Two recently approved PARP inhibitors provide an important new therapeutic option for patients with BRCA-mutated metastatic breast cancer. PARP inhibitors significantly prolong progression-free survival in patients, but conventional oral delivery of PARP inhibitors is hindered by limited bioavailability and off-target toxicities, thus compromising the therapeutic benefits and quality of life for patients. Here, we developed a new delivery system, in which the PARP inhibitor Talazoparib is encapsulated in the bilayer of a nano-liposome, to overcome these limitations. Methods: Nano-Talazoparib (NanoTLZ) was characterized both in vitro and in vivo. The therapeutic efficacy and toxicity of Nano-Talazoparib (NanoTLZ) were evaluated in BRCA-deficient mice. The regulation of NanoTLZ on gene transcription and immunomodulation were further investigated in spontaneous BRCA-deficient tumors. Results: NanoTLZ significantly (p<0.05) prolonged the overall survival of BRCA-deficient mice compared to all of the other experimental groups, including saline control, empty nanoparticles, and free Talazoparib groups (oral and i.v.). Moreover, NanoTLZ was better tolerated than treatment with free Talazoparib, with no significant weight lost or alopecia as was observed with the free drug. After 5 doses, NanoTLZ altered the expression of over 140 genes and induced DNA damage, cell cycle arrest and inhibition of cell proliferation in the tumor. In addition, NanoTLZ favorably modulated immune cell populations in vivo and significantly (p<0.05) decreased the percentage of myeloid derived suppressor cells in both the tumor and spleen compared to control groups. Conclusions: Our results demonstrate that delivering nanoformulated Talazoparib not only enhances treatment efficacy but also reduces off-target toxicities in BRCA-deficient mice; the same potential is predicted for patients with BRCA-deficient breast cancer.
Traditional Ecological Knowledge Supports Ecosystem-Based Management in Disturbed Coastal Marine Social-Ecological Systems

A growing number of studies suggest a participatory ecosystem approach to support decision-making towards resilience and sustainability in social-ecological systems. Social-ecological resilience (SER) principles and practices are recommended to manage natural crises. However, it is necessary to broaden our understanding of SER on human-induced disturbances driven by economic development projects. In this paper we present the social-ecological system of Araca Bay (Brazil), a small-scale fishery community that has experienced successive disturbances due to development projects since the 1930s. There was a lack of studies about the impacts of development projects in this bay. As part of a major project that aimed to build an ecosystem-based management plan for Araca Bay through a participatory planning process, we focused on investigating fishers’ traditional ecological knowledge (TEK) to understand Araca Bay’s small-scale fisheries social-ecological system. The objectives were to: (1) investigate fishers’ TEK regarding management practices and linked social mechanisms, human-induced disturbances and their consequences for the social-ecological system, ecosystem goods and services, and future threats; and (2) provide information based on TEK to the participatory planning process and analyze its contribution to Araca Bay’s ecosystem-based management plan. Combined methods were used during 3 years of intense research-action (2014-2017): in-depth ethno-oceanographic interviews with expert fishers; monitoring Araca Bay participatory meetings; and participant observation. Genuine local practices and social mechanisms from traditional culture were recorded, as well as TEK about 57 target fish species and methods to protect habitats and natural resources. Fishers also reported ecosystem disturbances and recovery processes. TEK was codified through SWOT analysis to assist the participatory planning process. Ecosystem services and threats based on TEK were brought to the participatory process, acknowledged by the participants, and incorporated into the management plan. TEK analysis proved to be an important methodology to provide historical environmental data regarding the impacts of development projects and support planning in disturbed ecosystems. In order to support coastal marine ecosystem-based management strategies towards SER and sustainability, researchers and practitioners should consider traditional territories in planning, recognize local practices and social mechanisms, and consider TEK on ecosystem goods and services and on historical human-induced disturbances.
Propagation of Spermatogonial Stem Cell-Like Cells From Infant Boys

Background Gonadotoxic treatment of malignant diseases as well as some non-malignant conditions such as cryptorchidism in young boys may result in infertility and failure to father children later in life. As a fertility preserving strategy, several centers collect testicular biopsies to cryopreserve spermatogonial stem cells (SSCs) world-wide. One of the most promising therapeutic strategies is to transplant SSCs back into the seminiferous tubules to initiate endogenous spermatogenesis. However, to obtain sufficient numbers of SSC to warrant transplantation, in vitro propagation of cells is needed together with proper validation of their stem cell identity. Materials and Methods A minute amount of testicular biopsies (between 5 mg and 10 mg) were processed by mechanical and enzymatic digestion. SSCs were enriched by differential plating method in StemPro-34 medium supplemented with several growth factors. SSC-like cell clusters (SSCLCs) were passaged five times. SSCLCs were identified by immunohistochemical and immunofluorescence staining, using protein expression patterns in testis biopsies as reference. Quantitative polymerase chain reaction analysis of SSC markers LIN-28 homolog A (LIN28A), G antigen 1 (GAGE1), promyelocytic leukemia zinc finger protein (PLZF), integrin alpha 6 (ITGA6), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and integrin beta 1 (ITGB1) were also used to validate the SSC-like cell identity. Results Proliferation of SSCLCs was achieved. The presence of SSCs in SSCLCs was confirmed by positive immunostaining of LIN28, UCHL1 and quantitative polymerase chain reaction for LIN28A, UCHL1, PLZF, ITGA6, and ITGB1, respectively. Conclusion This study has demonstrated that SSCs from infant boys possess the capacity for in vitro proliferation and advance a fertility preservation strategy for pre-pubertal boys who may otherwise lose their fertility.
Chronic Model of Inflammatory Bowel Disease in IL-10-/- Transgenic Mice: Evaluation with Ultrasound Molecular Imaging

Objective: Acute mouse models of inflammatory bowel disease (IBD) fail to mirror the chronic nature of IBD in patients. We sought to develop a chronic mouse IBD model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI) by using dual P- and E-selectin targeted microbubbles (MBSelectin). Materials and Methods: Interleukin 10 deficient (IL-10-/- on a C57BL/6 genetic background; n=55) and FVB (n=16) mice were used. In IL-10-/-mice, various experimental regimens including piroxicam, 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS), respectively were used for promoting colitis; colitis was induced with DSS in FVB mice. Using clinical and small animal ultrasound scanners, evolution of inflammation in proximal, middle and distal colon, was monitored with USMI by using MBSelectin at multiple time points. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E staining and for P-selectin expression on immunofluorescence staining. Results: Sustained colitis was not detected with USMI in IL-10-/- or FVB mice with various experimental regimens. USMI signals either gradually decreased after the colitis enhancing/inducing drug/agents were discontinued, or the mortality rate of mice was high. Inflammation was observed on H&E staining in IL-10-/- mice with piroxicam promotion, while stable overexpression of P-selectin was not found on immunofluorescence staining in the same mice. Conclusion: Sustained colitis in IL-10-/- mice induced with piroxicam, TNBS or DSS, and in FVB mice induced with DSS, was not detected with USMI using MBSelectin, and this was verified by immunofluorescence staining for inflammation marker P-selectin. Thus, these models may not be appropriate for long-term monitoring of chronic colitis and subsequent treatment response with dual-selectin targeted USMI.
Neurocognitive and Quality of Life Improvements Associated With Aerobic Training for Individuals With Persistent Symptoms After Mild Traumatic Brain Injury: Secondary Outcome Analysis of a Pilot Randomized Clinical Trial

Objective: To report secondary neurocognitive and quality of life outcomes for a pilot randomized clinical trial (RCT) of aerobic training for management of prolonged symptoms after a mild traumatic brain injury (mTBI) in adolescents. Setting: Outpatient research setting. Participants: Thirty adolescents between the ages of 12 and 17 years who sustained a mTBI and had between 4 and 16 weeks of persistent post-concussive symptoms. Design: Secondary outcome analysis of a partially masked RCT of sub-symptom exacerbation aerobic training compared with a full-body stretching program highlighting cognitive and quality of life outcomes. Main Measures: The secondary outcomes assessed included neurocognitive changes in fluid and crystallized age-adjusted cognition using the National Institutes of Health (NIH) toolbox and self and parent-reported total quality of life using the Pediatric Quality of Life Inventory. Results: Twenty-two percent of eligible participants enrolled in the trial. General linear models did not reveal statistically significant differences between groups. Within group analyses using paired t-tests demonstrated improvement in age-adjusted fluid cognition [t(13) = 3.39, p = 0.005, Cohen's d = 0.61] and crystallized cognition [t(13) = 2.63, p = 0.02, Cohen's d = 0.70] within the aerobic training group but no significant improvement within the stretching group. Paired t-tests demonstrated significant improvement in both self-reported and parent-reported total quality of life measures in the aerobic training group [self-report t(13) = 3.51, p = 0.004, Cohen's d = 0.94; parent-report t(13) = 6.5, p < 0.0001, Cohen's d = 1.80] and the stretching group [self-report t(14) = 4.20, p = 0.0009, Cohen's d = 1.08; parent-report t(14) = 4.06, p = 0.0012, Cohen's d = 1.045]. Conclusion: Quality of life improved significantly in both the aerobic exercise and stretching groups; however, this study suggests that only sub-symptom exacerbation aerobic training was potentially beneficial for neurocognitive recovery, particularly the fluid cognition subset in the NIH Toolbox. Limited sample size and variation in outcomes measures limited ability to detect between group differences. Future research should focus on developing larger studies to determine optimal timing post-injury and intensity of active rehabilitation to facilitate neurocognitive recovery and improve quality of life after mTBI. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT02035579.
Winter bird-window collisions: mitigation success, risk factors, and implementation challenges

Millions of birds die in bird-window collisions in the United States each year. In specialized test settings, researchers have developed methods to alter window designs to mitigate collisions. However, few published studies provide pretest and posttest evaluations of mitigation treatment areas and untreated control areas on existing buildings. We initially monitored bird-window collisions at a single building on the University of Utah campus in Salt Lake City, Utah, USA, during winter 1 (November 9, 2017–January 2, 2018). We found 15 bird-window collisions, most under a portion of the building with a mirrored façade. To test a mitigation treatment, we installed Feather Friendly® bird deterrent film on part of the mirrored façade after winter 1. The unmitigated areas of the same building served as a control area. We continued monitoring during the following winter 2 (November 15, 2018–January 12, 2019). The treated area collisions declined from seven before mitigation to two after mitigation, a 71% reduction. The control area had eight collisions at both times. Results of a generalized estimating equation yielded a significant area by season interaction effect (p = 0.03) and fewer collisions in the mitigated area than the control area at winter 2 (p = 0.03), supporting efficacy of the mitigation. In winter 2 we also expanded monitoring to eight total buildings to evaluate the risks of mirrored windows and proximity to fruiting pear trees (Prunus calleryana) and the benefits of bird-friendly glass. Bird-friendly glass, found on two buildings, included windows with permanent fritted dots or embedded ultraviolet patterns. We counted 22 collisions across the eight buildings. Mirrored windows and proximity to fruiting pear trees related to higher odds of bird-window collisions, based on separate generalized estimating equations. The best fit model included mirrored windows and pear trees. The two buildings with bird-friendly glass had only one collision, suggesting that these designs deter collisions, although the difference was not statistically significant. To publicize the study and to receive reports of additional bird collisions or fatalities on campus, we created a citizen science project on iNaturalist and engaged in additional outreach efforts that yielded 22 ad hoc reports. Many previous studies have documented Cedar Waxwing (Bombycilla cedrorum) collisions, but at relatively low numbers. Cedar Waxwings accounted for 31 of 34 identifiable collisions from the monitoring study and 4 of 21 identifiable collisions or fatalities from ad hoc reports.