On the Meaning of the “P Factor” in Symmetrical Bifactor Models of Psychopathology: Recommendations for Future Research From the Bifactor-(S−1) Perspective

Symmetrical bifactor models are frequently applied to diverse symptoms of psychopathology to identify a general P factor. This factor is assumed to mark shared liability across all psychopathology dimensions and mental disorders. Despite their popularity, however, symmetrical bifactor models of P often yield anomalous results, including but not limited to nonsignificant or negative specific factor variances and nonsignificant or negative factor loadings. To date, these anomalies have often been treated as nuisances to be explained away. In this article, we demonstrate why these anomalies alter the substantive meaning of P such that it (a) does not reflect general liability to psychopathology and (b) differs in meaning across studies. We then describe an alternative modeling framework, the bifactor-( S−1) approach. This method avoids anomalous results, provides a framework for explaining unexpected findings in published symmetrical bifactor studies, and yields a well-defined general factor that can be compared across studies when researchers hypothesize what construct they consider “transdiagnostically meaningful” and measure it directly. We present an empirical example to illustrate these points and provide concrete recommendations to help researchers decide for or against specific variants of bifactor structure.

Secreted ORF8 is a pathogenic cause of severe Covid-19 and potentially targetable with select NLRP3 inhibitors

ABSTRACTDespite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe Covid-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in patients with newly diagnosed Covid-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14+/CD16+ monocytes to induce an inflammasomal cytokine response. The levels of ORF8 protein in the blood correlate with disease mortality in patients with acute infection, and the disease trajectory in patients with severe Covid-19. Furthermore, in vitro the ORF8-induced inflammasome response can be readily inhibited by the select NLRP3 inhibitor MCC950. Our results identify the pathogenic cause and mechanism of severe disease, and a potential new treatment of severe Covid-19.

The opposing action of stromal cell proenkephalin and stem cell transcription factors in prostate cancer differentiation

Background Loss of prostate cancer differentiation or de-differentiation leads to an untreatable disease. Patient survival would benefit if this can be prevented or reversed. Cancer de-differentiation transforms luminal-like (differentiated) adenocarcinoma into less luminal-like and more stem-like (undifferentiated) small cell carcinoma through a sequential activation of stem cell transcription factors (scTF) POU5F1, LIN28A, SOX2 and NANOG. Like stem cells, prostate small cell carcinoma express this quartet of scTF as well as a 10-fold lower level of β2-microglobulin (B2M) than that of differentiated cell types. In organ development, prostate stromal mesenchyme cells mediate epithelial differentiation in part by secreted factors. Methods The identified prostate stromal-specific factor proenkephalin (PENK) was cloned, and transfected into scTF+B2Mlo stem-like small cell carcinoma LuCaP 145.1, reprogrammed luminal-like scTF−B2Mhi LNCaP, and luminal-like scTF−B2Mhi adenocarcinoma LuCaP 70CR. The expression of scTF, B2M and anterior gradient 2 (AGR2) was analyzed in the transfected cells. Results PENK caused down-regulation of scTF and up-regulation of B2M to indicate differentiation. When transfected into reprogrammed LNCaP, PENK reversed the reprogramming by down-regulation of scTF with attendant changes in cell appearance and colony morphology. When transfected into LuCaP 70CR, PENK up-regulated the expression of adenocarcinoma antigen AGR2, a marker associated with cancer cell differentiation. Conclusions Prostate cancer cells appear to retain their responsiveness to stromal PENK signaling. PENK can induce differentiation to counter de-differentiation caused by scTF activation. The many mutations and aneuploidy characteristic of cancer cells appear not to hinder these two processes. Loss of prostate cancer differentiation is like reprogramming from luminal-like to stem-like.

AN ANALYSIS OF FACTORS AFFECTING NON-PERFORMING ASSETS IN INDIAN BANKING SECTOR

Deterioration of asset quality destabilizes the financial system by adversely affecting the efficiency, profitability, solvency and liquidity of the banking sector. Both macroeconomic and bank specific factors should be analysed properly to know their strength and direction of impact on the bad assets to have effective NPA resolution mechanism. Unemployment Rate Inflation, Economic Growth, Export rate, Exchange rate, Fiscal Deficit ratio are the macroeconomic indicators and Return on Assets, Credit Deposit ratio, Net Interest Margin are the bank specific factor that are taken from 2003-04 to 2019-20 to explain the variability in Non-performing assets of Public sector and Private sector banks. Fixed effect estimation with robust clustered standard error is used for the panel data regression. Paper found that except unemployment rate all other variables have significant impact on bad assets. Bank specific factor have strong negative impact on the dependent variables. Only exchange rate affects the non-performing loans positively but other macroeconomic variables are negatively associated. KEYWORDS: Non-Performing Assets, Macroeconomic indicators, bank specific factors, Fixed effect

Person- and situation-specific factors in discounting science via scientific impotence excuses

Munro (2010, https://doi.org/10.1111/j.1559-1816.2010.00588.x) found that individuals, when confronted with belief-disconfirming scientific evidence, resist this information by concluding that the topic at hand is not amenable to scientific investigation—a scientific impotence excuse. We strived to replicate this finding and to extend this work by analyzing other factors that might lead to scientific impotence excuses. As a person-specific factor, we analyzed the role of epistemic beliefs, and as a situational factor, we focused on the contradictoriness of the evidence at hand. Three sets of hypotheses were preregistered. In an experimental 2 × 3 online study drawing on a general population sample of N = 901 participants, we first assessed our participants’ prior beliefs on the effects of acupuncture versus massaging (pro acupuncture vs. no opinion). One experimental group then read fictitious empirical evidence claiming superiority of acupuncture, another group read evidence speaking against acupuncture, and a third group read conflicting evidence (i.e., a mix of pro- and contra-findings). Scientific impotence excuses were measured by a newly developed questionnaire. Our first hypothesis, which suggested that participants believing in the superiority of acupuncture would make stronger scientific impotence excuses when confronted with belief-disconfirming findings, was confirmed. A second hypothesis suggested that scientific impotence excuses would be stronger when individuals were confronted with evidence exhibiting a “nature” that contradicts their topic-specific epistemic beliefs. This hypothesis was partially supported. A third hypothesis suggested that individuals confronted with conflicting evidence would make stronger scientific impotence excuses, and this was again confirmed. Implications for theory and practice are discussed.

Determinants of Firm Profitability in Africa

Using a large firm-level data set of 896 firms selected from 27 African countries between 2005 and 2017 and the generalized method of moments (GMM) technique, this study investigates the firm-specific, industry-level, and macroeconomic factors affecting firms’ profitability in Africa. Unlike existing studies that adopt non-standard measures of a firm’s managerial efficiency, this study introduces the standard measure of managerial efficiency into the determinants of a firm’s profitability. The empirical results show that managerial efficiency, size, age, leverage, tangibility, and firm’s growth are significant firm-level determinants of a firm’s profitability in Africa. Similarly, an industry-specific factor of competition exercises a significant effect on a firm’s profitability. However, the role of macroeconomic factors are not validated by the study. Policy recommendations follow the study.

Pneumatosis Intestinalis following Radiation Esophagitis during Chemoradiotherapy for Lung Cancer: A Case Report

Pneumatosis intestinalis (PI) is a rare disease that forms emphysema lesions under the mucosa and serosa of the gastrointestinal tract. We present the first case of PI following radiation-induced esophagitis during chemoradiotherapy (CRT) for lung cancer. A 74-year-old man with severe chronic obstructive pulmonary disease (COPD) was treated with CRT for lung cancer. During the treatment, he presented with vomiting and abdominal distention. CT showed pneumatosis from the esophagus to the small intestine. Severe radiation-induced esophagitis was observed, and gastrointestinal endoscopy revealed a circumferential esophageal ulcer. From these observations, this case was diagnosed as PI following severe esophagitis. A nasogastric tube was inserted, and conservative treatment with fasting, fluid replacement, and antibiotic was performed. Four days after the onset of PI, CT showed marked improvement of the pneumatosis. When CRT is performed for lung cancer patients, we should not only consider esophagitis but also PI. The presence of COPD may be considered a specific factor for the development of severe esophagitis and the consequent PI in this case.

SBSA: an online service for somatic binding sequence annotation

Efficient annotation of alterations in binding sequences of molecular regulators can help identify novel candidates for mechanisms study and offer original therapeutic hypotheses. In this work, we developed Somatic Binding Sequence Annotator (SBSA) as a full-capacity online tool to annotate altered binding motifs/sequences, addressing diverse types of genomic variants and molecular regulators. The genomic variants can be somatic mutation, single nucleotide polymorphism, RNA editing, etc. The binding motifs/sequences involve transcription factors (TFs), RNA-binding proteins, miRNA seeds, miRNA-mRNA 3′-UTR binding target, or can be any custom motifs/sequences. Compared to similar tools, SBSA is the first to support miRNA seeds and miRNA-mRNA 3′-UTR binding target, and it unprecedentedly implements a personalized genome approach that accommodates joint adjacent variants. SBSA is empowered to support an indefinite species, including preloaded reference genomes for SARS-Cov-2 and 25 other common organisms. We demonstrated SBSA by annotating multi-omics data from over 30,890 human subjects. Of the millions of somatic binding sequences identified, many are with known severe biological repercussions, such as the somatic mutation in TERT promoter region which causes a gained binding sequence for E26 transformation-specific factor (ETS1). We further validated the function of this TERT mutation using experimental data in cancer cells. Availability:http://innovebioinfo.com/Annotation/SBSA/SBSA.php.

Analisis Bank Specific Factor terhadap Penyaluran Kredit Perbankan Konvensional

Purpose: This research aimed to discover the influence between capital, credit risk, liquidity, and efficiency towards credit lending. Research methodology: This research includes quantitative research. The objects in this research were commercial banks listed on the Indonesia Stock Exchange (IDX), with 36 commercial banks chosen as the samples within the 2017 – 2019 period. Research hypotheses were tested with a significance level of 5% by using a panel data regression model and assisted by E-Views 11 program. Results: The result obtained within this research are (1) there is an influence between capital and credit lending, (2) credit risk does not influence credit lending, (3) liquidity has influence credit lending, and (4) efficiency does not have any influence with credit lending. Limitations: The limitations of this research were the least amount of former research both nationally and internationally containing a detailed explanation about a similar topic. Contribution: The result obtained can be used for the next researcher's references, also used as a bank’s consideration on operating their main operational activity, which is credit lending, and for investor's consideration while intended to invest in the banking sector.