Miracle-dz/UniFAR-FTUs huggingface dataset:
Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer

Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.
Preservation of a Dust Crystal as it Falls in an Afterglow Plasma

In an experiment, the power that sustains a plasma was extinguished, so that microspheres, which had been levitated, fell downward toward a lower electrode. At the beginning of their fall, the microspheres were self-organized with a crystalline structure. This structure was found to be preserved as the microspheres accelerated all the way to the lower electrode. Although microspheres had, in this afterglow plasma, large positive charges of 12,500 e, their interparticle repulsion was unable to significantly alter the crystalline arrangement of the microspheres, as they fell. After their impact on the lower electrode, the microspheres bounced upward, and only then was the crystalline structure lost.
Testing for Antibodies Against Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in the Diagnosis of Patients With Suspected Autoimmune Myelopathy

Autoimmune myelopathies are immune-mediated disorders of the spinal cord that can cause significant neurologic disability. Discoveries of antibodies targeting aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) have facilitated the diagnosis of autoimmune myelopathies that were previously considered to be atypical presentations of multiple sclerosis (MS) or idiopathic, and represent major advancements in the field of autoimmune neurology. The detection of these antibodies can substantially impact patient diagnosis and management, and increasing awareness of this has led to a dramatic increase in testing for these antibodies among patients with suspected autoimmune myelopathy. In this review we discuss test methodologies used to detect these antibodies, the role of serum vs. cerebrospinal fluid testing, and the value of antibody titers when interpreting results, with the aim of helping laboratorians and clinicians navigate this testing when ordered as part of the diagnostic evaluation for suspected autoimmune myelopathy.
Nexus of Ethical Leadership, Career Satisfaction, Job Embeddedness, and Work Engagement in Hospitality Industry: A Sequential Mediation Assessment

The paper proposes a research model explaining the sequential mediation effect of job embeddedness (JE) and work engagement (WENG) between ethical leadership (EL) and career satisfaction (CS). The model also examines whether JE heightens WENG, a factor indirectly influenced by ethical practices ending in employee satisfaction. The study used a time-lagged data collection procedure and survey responses of 247 hotel workers in China. Data were analyzed through structural equation modeling. The results showed that EL directly and indirectly (through sequential mediation effect of JE and WENG) contributes to employee CS. The present empirical framework extends the hospitality industry literature by explaining the precise mechanism (i.e., JE and WENG) through which EL generates CS among hospitality workers in China. The paper offers theoretical and practical implications and future research directions.
Infanticide by Adult Females Causes Sexual Conflict in a Female-Dominated Social Mammal

Infanticide by adult females includes any substantial contribution to the demise of young and inevitably imposes fitness costs on the victim’s genetic fathers, thereby generating sexual conflict with them. Few if any studies have quantified the impact of infanticide by females on male reproductive success, the magnitude of sexual conflict this causes and possible counterstrategies males use against infanticidal females. We examine these topics in spotted hyena (Crocuta crocuta) clans, where females socially dominate breeding males and strong female mate-choice is independent of male social status. We consider two causes of infanticide by females, violent attacks on cubs and fatal maternal neglect. Violent attacks are predicted during periods of social instability at the top of the female linear dominance hierarchy and victims are expected to predominantly have mothers above median rank. Fatal maternal neglect, when starving litters are abandoned, is associated with monopolization of food in clan territories by high-ranking females, and victims are predicted to have mothers below median rank. Female perpetrators of violent attacks are expected to reduce the reproductive success of the fathers of their victims more than perpetrators of fatal maternal neglect. We tested these predictions using 30 + years of data (54 recorded violent attacks, 43 cases of fatal maternal neglect, DNA profiling of 1,671 individuals). Using long-term observations at communal dens we investigated whether males use counterstrategies against infanticide reported in other mammals. Due to female social dominance over breeding males, strong female mate-choice and prolonged offspring dependence on lactation in spotted hyenas, we predicted that these counterstrategies were unlikely to be used by males against females, thus no incidences of them were likely to be observed. Our results revealed that breeding males lost cubs to violent attacks at all stages of their reproductive tenure and to perpetrators with whom they did not sire offspring. Amongst known sources of paternity loss, violent attacks comprised 12.2% and maternal neglect 9.8% of cases. Violent attacks significantly reduced offspring production rates of breeding males, suggesting that infanticide by females generates sexual conflict. As predicted, no evidence of males using counterstrategies against infanticide by females were observed.
Modeling the Significance of Sustainability Orientation on the Sustainability Performance of Micro-Enterprises in an Emerging Economy

Sustainable enterprises are essential for developing economies’ progress and prosperity. Micro-enterprises (MEs) play an important role in creating jobs and actively participating in socioeconomic activities. However, little is known about how MEs use internal capabilities to achieve long-term success. This study explores the influence of the strategic orientations (i.e., sales, consumer, competitive, emotional, business, and networking) instigating the sustainability orientation. The sustainability orientation nurtures the sustainable performance of the MEs. The cross-sectional data collected from the 450 MEs with the structured interviews and samples were randomly selected from the list of MEs registered in seven districts of Kelantan, Malaysia. The collected data were analyzed with partial least square structural equation modeling (PLS-SEM). The data analysis discovered that the sale, consumer, competitive, and emotional orientation significantly impact the MEs’ sustainable orientation. The business and networking orientations insignificantly facilitate the sustainable orientation among the samples. The MEs’ sustainable orientation suggestively influences the sustainable performance among the MEs. Furthermore, the study analysis postulated a significant mediating effect of sustainable orientation among the orientations (sale, consumer, competitive, and emotional) on the MEs’ sustainable performance. Our study offers a better understanding of the RBV in the MEs and brings significant empirical evidence to attain sustainable performance with the firm’s level orientation for the MEs. The study brings forward the practical implication for business and policymakers that the MEs require internal and external support to align the business and networking orientation to harness the sustainable performance among the MEs. In the end, the study limitations and future research options are highlighted.
Efficacy and In Vitro Activity of Novel Antibiotics for Infections With Carbapenem-Resistant Gram-Negative Pathogens

Infections by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat using available antibiotics. Overuse of carbapenems has contributed to widespread resistance to these antibiotics; as a result, carbapenem-resistant Enterobacterales (CRE), A. baumannii (CRAB), and P. aeruginosa (CRPA) have become common causes of healthcare-associated infections. Carbapenems, tigecycline, and colistin are the last resource antibiotics currently used; however, multiple reports of resistance to these antimicrobial agents have been documented worldwide. Recently, new antibiotics have been evaluated against Gram-negatives, including plazomicin (a new aminoglycoside) to treat CRE infection, eravacycline (a novel tetracycline) with in vitro activity against CRAB, and cefiderocol (a synthetic conjugate) for the treatment of nosocomial pneumonia by carbapenem-non-susceptible Gram-negative isolates. Furthermore, combinations of known β-lactams with recently developed β-lactam inhibitors, such as ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime-tazobactam, and meropenem-vaborbactam, has been suggested for the treatment of infections by extended-spectrum β-lactamases, carbapenemases, and AmpC producer bacteria. Nonetheless, they are not active against all carbapenemases, and there are reports of resistance to these combinations in clinical isolates.This review summarizes and discusses the in vitro and clinical evidence of the recently approved antibiotics, β-lactam inhibitors, and those in advanced phases of development for treating MDR infections caused by Gram-negative multi-drug resistant (MDR) bacterial species.
Free Versus Fixed-Ratio Combination of Basal Insulin and GLP-1 Receptor Agonists in Type 2 Diabetes Uncontrolled With GLP-1 Receptor Agonists: A Systematic Review and Indirect Treatment Comparison

Introduction This study evaluates the efficacy and safety of the free up-titration of basal insulin and fixed-ratio combination (FRC) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients inadequately controlled with GLP-1RA. Methods With the use of a systematic literature review of PubMed, Embase, Web of Science, and the Cochrane Library databases through July 2021, randomized controlled trials that compared the free up-titration or FRC with remaining on GLP-1RA in T2DM patients uncontrolled with GLP-1RA were included. A comparison of adding basal insulin to maintaining GLP-1RA and an indirect comparison between the two strategies were conducted on the change in HbA1c, fasting plasma glucose (FPG), target achievement [HbA1c < 7.0%], and the risk of confirmed hypoglycemia. The Cochrane Collaboration’s tool was used to assess the risk of bias. Results Two free up-titration and two FRC trials involving 1,612 participants, all lasting 26 weeks, were included. Both approaches significantly lowered HbA1c levels (weighted mean difference [WMD] −0.75%, 95% CI −0.97 to −0.53) but increased hypoglycemic risk [risk ratio (RR) 7.59, 95% CI 3.35−17.17] compared to the unchanged GLP-1RA. No significant differences were discovered between the two methods regarding the decrease in HbA1c (WMD 0.08%, 95% CI −1.07% to 1.23%), FPG (WMD −2.29 mg/dl, 95% CI −45.07 to 40.49 mg/dl), target achievement (RR 1.03, 95% CI 0.50−2.14), and hypoglycemic risk (RR 0.32, 95% CI 0.03−3.59). Conclusion In patients who failed to reach target HbA1c levels despite the GLP-1RA treatment, both strategies of adding basal insulin, free up-titration and FRC, are comparable options are comparable options.
Prescription Patterns of Asthma Preventers Among Children and Adolescents Between Australia and South Korea

Purpose: Inhaled Corticosteroids (ICSs) and oral Leukotriene Receptor Antagonists (LTRAs) are commonly prescribed asthma preventers, however, concerns have been raised as to whether montelukast (LTRA) is associated with an increase in occurrences of neuropsychiatric side effects in children. Our study was conducted to observe prescribing patterns of asthma preventers among paediatric patients specifically focusing on ICSs and LTRAs between Australia and South Korea to see intercountry differences in the use of these medicines. Materials and Methods: The Health Insurance Review and Assessment Paediatric Patients Sample dataset for South Korea and data provided by Services Australia were used in the study. Paediatric patients aged between 3 and 19 with more than one dispensing of an asthma preventer and at least one reliever between 1 Jan 2018 and 31 December 2018 were selected. Prevalence per 1,00,000 persons and standardised prevalence were estimated. Results: A total of 3,58,470 patients (2,04,270 from South Korea and 1,54,200 from Australia) were included in the study. A higher prevalence of ICS-based inhalers was seen in Australia with 80.1% compared to 13.5% in South Korea. In addition, Australia showed a stronger tendency of prescribing high dose ICS-based inhalers compared to South Korea with 22.9% vs. 4.9%. In contrast, use of LTRAs was more prevalent in South Korea with 57.6% while in Australia, montelukast was the only LTRA dispensed at a proportion of 18.9%. Moreover, 29.9% of xanthines which are orally available preventers, were prescribed more frequently in South Korea compared to Australia (0.1%). Conclusion: Australia showed a tendency of prescribing ICS-based preventers whereas South Korea exhibited a preference towards the oral LTRAs. Given the potential risk of neuropsychiatric side effects among paediatric patients with montelukast, reasons for the high use of montelukast in South Korea should be investigated further.
Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci

Background: Plasma lipid levels are a major risk factor for cardiovascular diseases. Although international efforts have identified a group of loci associated with the risk of dyslipidemia, Latin American populations have been underrepresented in these studies. Objective: To know the genetic variation occurring in lipid-related loci in the Mexican population and its association with dyslipidemia. Methods: We searched for single-nucleotide variants in 177 lipid candidate genes using previously published exome sequencing data from 2838 Mexican individuals belonging to three different cohorts. With the extracted variants, we performed a case-control study. Logistic regression and quantitative trait analyses were implemented in PLINK software. We used an LD pruning using a 50-kb sliding window size, a 5-kb window step size and a r2 threshold of 0.1. Results: Among the 34251 biallelic variants identified in our sample population, 33% showed low frequency. For case-control study, we selected 2521 variants based on a minor allele frequency ≥1% in all datasets. We found 19 variants in 9 genes significantly associated with at least one lipid trait, with the most significant associations found in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster on chromosome 11. Notably, all 11 variants associated with hypertriglyceridemia were within this cluster; whereas variants associated with hypercholesterolemia were located at chromosome 2 and 19, and for low high density lipoprotein cholesterol were in chromosomes 9, 11, and 19. No significant associated variants were found for low density lipoprotein. We found several novel variants associated with different lipemic traits: rs3825041 in BUD13 with hypertriglyceridemia, rs7252453 in CILP2 with decreased risk to hypercholesterolemia and rs11076176 in CETP with increased risk to low high density lipoprotein cholesterol. Conclusions: We identified novel variants in lipid-regulation candidate genes in the Mexican population, an underrepresented population in genomic studies, demonstrating the necessity of more genomic studies on multi-ethnic populations to gain a deeper understanding of the genetic structure of the lipemic traits.
Hashimoto’s Thyroiditis Is Associated With Central Lymph Node Metastasis in Classical Papillary Thyroid Cancer: Analysis from a High-Volume Single-Center Experience

Purpose Central lymph node metastasis (CLNM) is regarded as a predictor for local recurrence in patients with papillary thyroid carcinoma (PTC) but the role of prophylactic central lymph node dissection (CLND) is controversial. Our study aims to identify the clinical factors associated with CLNM and develop a nomogram for making individualized clinical decisions. Method The perioperative data of 1,054 consecutive patients between Jan 2019 and April 2021, in our center, were reviewed and analyzed. A total of 747 patients with histopathologically confirmed classical PTC were included as the training cohort and 374 (50% training cases) patients were randomly selected to build a validating cohort via internal bootstrap analysis. Univariate and multivariate logistic regression were used to analyze the correlation between clinicopathological characteristics and CLNM. Result In the training cohort, 33.6% (251/747) of patients with classical PTC were confirmed with CLNM. And the CLNM was determined in 31.4% (168/535) of non-Hashimoto’s thyroiditis (HT) patients versus 39.2% (83/212) in HT patients (p=0.043). Four factors including gender, age, size, and HT status were confirmed significantly associated with CLNM. The established nomogram showed good discrimination and consistency with a C-index of 0.703, supported by the internal validation cohort with a C-index of 0.701. The decision curve analysis showed the nomogram has promising clinical feasibility. Conclusion Our study suggested that classical PTC patients with features like male gender, age<55 years old, tumor size>1cm, and HT condition had a higher risk of CLNM. And the nomogram we developed can help surgeons make individualized clinical decisions in classical PTC patients during preoperative and intraoperative management.
Investigation Into the Risk Factors Related to In-stent Restenosis in Elderly Patients With Coronary Heart Disease and Type 2 Diabetes Within 2 Years After the First Drug-Eluting Stent Implantation

Background The present study aims to explore risk factors related to in-stent restenosis (ISR) in elderly patients with coronary heart disease and type 2 diabetes within 2 years after the first drug-eluting stent (DES) implantation. Methods This case-control study retrospectively analyzed the clinical data of patients with coronary heart disease and diabetes undergoing percutaneous coronary intervention (PCI) in Shenzhen Sun Yat-sen Cardiovascular Hospital between January 2010 and March 2020. Univariate and multivariate models were used to assess independent factors for DES-ISR. Categorical principal component analysis of clinical variables was performed to determine important components for DES-ISR. Nomogram was constructed to quantitatively predict the probability of DES-ISR development. The diagnostic potential of clinical variables was determined by receiver operating characteristic curve. Results In the derivation cohort, 1,741 cases were included in this study, and a total of 227 pairs of cases and controls were generated by propensity score matching. In the validation cohort, 102 cases were included with 19 cases (18.6%) with DES-ISR. Glomerular filtration rate <60 ml/min/1.73 m2, fasting blood glucose ≥6.5 mmol/L, multivessel coronary artery disease, coronary artery diffuse disease, PCI operation time (≥60 min), emergency PCI were associated with ISR. High Nomogram score was associated with the increased risk of ISR. Further analysis of the validation cohort showed that higher levels of HbA1c-coefficient of variation (CV) were significantly associated with the increased risk of ISR. HbA1c-CV exhibited good predictive ability for ISR in the validation cohort. Conclusions In conclusion, the fasting blood glucose level during the perioperative period of emergency PCI and the long-term variation of HbA1c during the follow-up period are related to the incidence of DES-ISR and the degree of stenosis. Reducing blood glucose fluctuations may decrease the risk of DES-ISR.
Influence of Real Earning Management on Subsequent Dividend Payout Decisions and Corporate Returns: A Case of Developing Economy

Real earning management (REM) enhances the control of managers on the financial reporting of firms. However, its influence on financial decisions in the coming years is not well documented, especially in developing countries. This study investigates the influence of three REM activities on subsequent years’ dividend payout decisions (DPDs) and annual corporate returns of firms listed on the Pakistan Stock Exchange (PSX). The study employed panel data from 2011 to 2020 of 120 large manufacturing firms to 1) measure the extent of REM activities and 2) investigate the impact on future financial decisions of dividends and reported returns. This study used multiple proxies of return for robustness. Consistent with empirical studies, the REM negatively impacts the following years’ returns. However, its effect on dividend payout policy is insignificant. This indicates that Pakistani firms are more concerned with a smooth dividend payout to investors than reporting coherent returns. The study provides significant evidence from a developing economy and has implications for investors, analysts, and policymakers.