bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should Dehydroepiandrosterone Be Administered to Women?
Authors: Wierman Margaret E , Kiseljak-Vassiliades Katja 
Published: March 2022

Abstract

Context
Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of menopausal status. Investigators have examined their potential beneficial effects in normal women and those with DHEA-deficient states.

Evidence Acquisition
A review of the literature from 1985 to 2021 on the potential benefits and risks of androgen prohormones in women.

Evidence Synthesis
Studies have examined the potential benefit of DHEA therapy for anti-aging, sexual dysfunction, infertility, metabolic bone health, cognition, and wellbeing in hormone-deficient states such as primary adrenal insufficiency, hypopituitarism, and anorexia as well as administration to normal women across the lifespan.

Conclusions
Data support small benefits in quality of life and mood but not for anxiety or sexual function in women with primary or secondary adrenal insufficiency or anorexia. No consistent beneficial effects of DHEA administration have been observed for menopausal symptoms, sexual function, cognition, or overall wellbeing in normal women. Local administration of DHEA shows benefit in vulvovaginal atrophy. Use of DHEA to improve induction of ovulation response in women with diminished ovarian reserve is not recommended. Risks of high physiologic or pharmacologic use of DHEA include androgenic and estrogenic side effects which are of concern for long-term administration.

Clinical Case
A 49-year-old woman with Addison’s disease who is on low dose estrogen with cyclic progesterone therapy for menopausal symptoms returns for follow-up. She is on a stable glucocorticoid replacement strategy of hydrocortisone 10 mg in the morning and 5 mg in the early afternoon and fludrocortisone 0.05 mg each morning. She has read on the internet that additional therapy with DHEA may help her overall quality of life and libido. She asks whether she should add this therapy to her regimen and at what dose.
Molecular divergence of mammalian astrocyte progenitor cells at early gliogenesis
Authors: Liu Jiancheng , Wu Xiwei , Lu Qiang 
Published: March 2022

ABSTRACT
During mammalian brain development, how different astrocytes are specified from progenitor cells is not well understood. In particular, whether astrocyte progenitor cells (APCs) start as a relatively homogenous population or whether there is early heterogeneity remains unclear. Here, we have dissected subpopulations of embryonic mouse forebrain progenitors using single-cell transcriptome analyses. Our sequencing data revealed two molecularly distinct APC subgroups at the start of gliogenesis from both dorsal and ventral forebrains. The two APC subgroups were marked, respectively, by specific expression of Sparc and Sparcl1, which are known to function in mature astrocytes with opposing activities for regulating synapse formation. Expression analyses showed that SPARC and SPARCL1 mark APC subgroups that display distinct temporal and spatial patterns, correlating with major waves of astrogliogenesis during development. Our results uncover an early molecular divergence of APCs in the mammalian brain and provide a useful transcriptome resource for the study of glial cell specification.
Circulating Lipid- and Inflammation-Based Risk (CLIR) Score: A Promising New Model for Predicting Outcomes in Complete Colorectal Liver Metastases Resection
Authors: Bai Long , Yan Xiao-Luan , Lu Yun-Xin , Meng Qi , Rong Yu-Ming , Ye Liu-Fang , Pan Zhi-Zhong , Xing Bao-Cai , Wang De-Shen 
Published: March 2022

Abstract
Background
Colorectal cancer liver metastasis (CRLM) is a determining factor affecting the survival of colorectal cancer (CRC) patients. This study aims at developing a novel prognostic stratification tool for CRLM resection.

Methods
In this retrospective study, 666 CRC patients who underwent complete CRLM resection from two Chinese medical institutions between 2001 and 2016 were classified into the training (341 patients) and validation (325 patients) cohorts. The primary endpoint was overall survival (OS). Associations between clinicopathological variables, circulating lipid and inflammation biomarkers, and OS were explored. The five most significant prognostic factors were incorporated into the Circulating Lipid- and Inflammation-based Risk (CLIR) score. The predictive ability of the CLIR score and Fong’s Clinical Risk Score (CRS) was compared by time-dependent receiver operating characteristic (ROC) analysis.

Results
Five independent predictors associated with worse OS were identified in the training cohort: number of CRLMs >4, maximum diameter of CRLM >4.4 cm, primary lymph node-positive, serum lactate dehydrogenase (LDH) level >250.5 U/L, and serum low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C) ratio >2.9. These predictors were included in the CLIR score and each factor was assigned one point. Median OS for the low (score 0–1)-, intermediate (score 2–3)-, and high (score 4–5)-risk groups was 134.0 months, 39.9 months, and 18.7 months in the pooled cohort. The CLIR score outperformed the Fong score with superior discriminatory capacities for OS and RFS, both in the training and validation cohorts.

Conclusions
The CLIR score demonstrated a promising ability to predict the long-term survival of CRC patients after complete hepatic resection.
Sustained ethical analysis of global dilemmas and country-level decision making during and post the COVID-19 pandemic: A systematic review
Authors: Sarfraz Azza , Sarfraz Zouina , Ashraf Mohammad , Ashraf Huma 
Published: March 2022

The COVID-19 pandemic has highlighted the vulnerability of countries worldwide and their abilities to cope with the fast-paced demands of the research and medical community. A key to promoting ethical decision-making frameworks is by calibrating the sustainability at regional, national, and global levels to incorporate coordinated reforms. We performed a sustained ethical analysis and critically reviewed evidence addressing country-level responses to practices during the COVID-19 pandemic using PubMed (MEDLINE), Scopus, and CINAHL. The World Health Organization’s ethical framework proposed for the entire population during the pandemic was applied to thematically delineate findings under equality, best outcomes (utility), prioritizing the worst off, and prioritizing those tasked with helping others. The findings demarcate ethical concerns about the validity of drug and vaccine trials in developing and developed countries, hints of unjust healthcare organizational policies, lack of equal allocation of pertinent resources, miscalculated allocation of resources to essential workers and stratified populations.
doi: https://doi.org/10.12669/pjms.38.4.4755
How to cite this:Sarfraz A, Sarfraz Z, Ashraf M, Ashraf H. Sustained ethical analysis of global dilemmas and country-level decision making during and post the COVID-19 pandemic: A systematic review. Pak J Med Sci. 2022;38(4):---------. doi: https://doi.org/10.12669/pjms.38.4.4755
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effectiveness of lever sign test for diagnosing anterior cruciate ligament rupture
Authors: Shair Naveed Ali , Siddiq Umair Abubakar , Tariq Abdullah , Khalid Muhammad 
Published: March 2022

Objective: To evaluate the effectiveness of the Lever Sign test (LST) for diagnosing anterior cruciate ligament (ACL) ruptures.
Methods: This prospective trial was conducted from January to December 2020. A total of 73 patients, aged 18 to 65 years, presenting with chief complaint as acute knee pain rated < 7/10 on a verbal numerical rating scale, having a minimum 20 to 1200 range of motion and undergoing magnetic resonance imaging (MRI) were enrolled. Detailed history, physical examination and standard radiographic evaluation were done in all subjects. For the assessment of the integrity of the ACL, the anterior drawer, Lachman, pivot-shift and LST were performed on each symptomatic knee by a senior orthopedic consultant with a minimum five years post-fellowship experience. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the LST were recorded with respect to standard reference MRI findings.
Results: Out of a total of 73 patients, there were 49 (67.1%) males. Mean age was noted to be 34.5±8.1 years. Area of residence was rural among 42 (57.5%) patients. Mean time since injury was noted to be 11.2±4.6 months. The MRI findings showed ACL intact among 31 (42.4%) patients while it showed ACL torn among 42 (57.5%) patients. The LST showed positive findings for ACL rupture in 39 (53.5%) patients while it was negative in remaining 34 (46.5%). The sensitivity, specificity, PPV, NPV and accuracy of LST with respect to standard reference finding (MRI) was found to be 86%, 90%, 92%, 82% and 88% respectively.
Conclusion: The LST was found to have good specificity, sensitivity, PPV, NPV and accuracy to detect the status of the ACL. The LST is easy to perform can be used along with other standard assessment techniques to further increase the validation of the status of the ACL diagnosis.
doi: https://doi.org/10.12669/pjms.38.4.4993
How to cite this:Shair NA, Siddiq UA, Tariq A, Khalid M. Effectiveness of lever sign test for diagnosing anterior cruciate ligament rupture. Pak J Med Sci. 2022;38(4):---------. doi: https://doi.org/10.12669/pjms.38.4.4993
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Performance of the T cell senescence markers in predicting the active disease of systemic lupus erythematosus
Authors: Handono Kusworini , Pratama Mirza Zaka , Partan Radiyati Umi , Susianti Hani , Firdaningrum Nimas Eka , Famuji Siti Roziah Ria , Fachry Ade Wildan Rizky , Sumarta Norma Hanifah , Kalim Handono 
Published: March 2022

Background: Accelerated immunosenescence has been observed in several autoimmune diseases, including systemic lupus erythematosus (SLE). T cell senescence plays an essential role in the destruction of organs in SLE patients. This study aimed to identify the ability of immunosenescence markers to predict SLE disease activity. Methods: Overall, 61 SLE patients and 60 healthy subjects were enrolled in this cross-sectional study. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score assessed disease activity. Senescence surface markers of CD4 and CD8 T lymphocytes were measured by flow cytometry (CD4/CD8 ratio, CD28null, CD57, CD45 isoforms [CD45RA and CD45RO], and KLRG1). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum cytokines (IFNγ and IL-2) and cytomegalovirus (CMV) serology. Complement and anti-dsDNA levels were also evaluated as the comparator for predicting active disease in SLE. Logistic regression models were used to identify the independent predictive factors for active SLE status. Performance of the senescence markers in predicting active disease in SLE was analyzed by receiver operating characteristic (ROC) curve as the area under curve (AUC). Results: SLE patients with active disease had significantly higher CD8+CD28null, CD8+CD57+, CD8+CD45RA+, CD8+CD45RO+, and CD8+KLRG1+ percentages with lower CD4/CD8 ratio than healthy subjects and SLE patients with inactive disease. The highest AUC and sensitivity were seen in CD8+CD28null (AUC 0.801 [0.662-0.940], sensitivity 91.9%, cut off >6.85%) with comparable results to serum complement and anti-dsDNA in predicting active disease. Multivariate analysis showed that CD4/CD8 ratio, CD8+CD28null, and C3 had significantly increased OR for active SLE. Combination models of CD4/CD8 ratio, CD8+CD28null, and C3 yielded the best results for predicting the active SLE (AUC 0.923 [0.848-0.997], sensitivity 81.2%, specificity 84.0%, LR+ 5.08 and LR- 0.22). Conclusions: Our findings demonstrated that combining immunosenescence markers, including CD4/CD8 ratio and CD8+CD28null with C3 levels could increase the odds of predicting active disease in SLE.
A visual approach towards forward collision warning for autonomous vehicles on Malaysian public roads
Authors: Wong Man Kiat , Connie Tee , Goh Michael Kah Ong , Wong Li Pei , Teh Pin Shen , Choo Ai Ling 
Published: March 2022

Background: Autonomous vehicles are important in smart transportation. Although exciting progress has been made, it remains challenging to design a safety mechanism for autonomous vehicles despite uncertainties and obstacles that occur dynamically on the road. Collision detection and avoidance are indispensable for a reliable decision-making module in autonomous driving. Methods: This study presents a robust approach for forward collision warning using vision data for autonomous vehicles on Malaysian public roads. The proposed architecture combines environment perception and lane localization to define a safe driving region for the ego vehicle. If potential risks are detected in the safe driving region, a warning will be triggered. The early warning is important to help avoid rear-end collision. Besides, an adaptive lane localization method that considers geometrical structure of the road is presented to deal with different road types. Results: Precision scores of mean average precision (mAP) 0.5, mAP 0.95 and recall of 0.14, 0.06979 and 0.6356 were found in this study. Conclusions: Experimental results have validated the effectiveness of the proposed approach under different lighting and environmental conditions.
eTRANSAFE: Building a sustainable framework to share reproducible drug safety knowledge with the public domain
Authors: Sarntivijai Sirarat , Blomberg Niklas , Lauer Katharina B. , Briggs Katharine , Steger-Hartmann Thomas , van der Lei Johan , Sauer John-Michael , Liwski Richard , Mourby Miranda , Camprubi Montse ,   The eTRANSAFE Consortium
Published: March 2022

Integrative drug safety research in translational health informatics has rapidly evolved and included data that are drawn in from many resources, combining diverse data that are either reused from (curated) repositories, or newly generated at source. Each resource is mandated by different sets of metadata rules that are imposed on the incoming data. Combination of the data cannot be readily achieved without interference of data stewardship and the top-down policy guidelines that supervise and inform the process for data combination to aid meaningful interpretation and analysis of such data. The eTRANSAFE Consortium's effort to drive integrative drug safety research at a large scale hereby present the lessons learnt and the proposal of solution at the guidelines in practice at this Innovative Medicines Initiative (IMI) project. Recommendations in these guidelines were compiled from feedback received from key stakeholders in regulatory agencies, EFPIA companies, and academic partners. The research reproducibility guidelines presented in this study lay the foundation for a comprehensive data sharing and knowledge management plans accounting for research data management in the drug safety space - FAIR data sharing guidelines, and the model verification guidelines as generic deliverables that best practices that can be reused by other scientific community members at large. FAIR data sharing is a dynamic landscape that rapidly evolves with fast-paced technology advancements. The research reproducibility in drug safety guidelines introduced in this study provides a reusable framework that can be adopted by other research communities that aim to integrate public and private data in biomedical research space.
Quantitative methods for group bibliotherapy research: a pilot study
Authors: Troscianko Emily T. , Holman Emily , Carney James 
Published: March 2022

Background: Bibliotherapy is under-theorized and under-tested: its purposes and implementations vary widely, and the idea that ‘reading is good for you’ is often more assumed than demonstrated. One obstacle to developing robust empirical and theoretical foundations for bibliotherapy is the continued absence of analytical methods capable of providing sensitive yet replicable insights into complex textual material. This pilot study offers a proof-of-concept for new quantitative methods including VAD (valence–arousal–dominance) modelling of emotional variance and doc2vec modelling of linguistic similarity. Methods: VAD and doc2vec modelling were used to analyse transcripts of reading-group discussions plus the literary texts being discussed, from two reading groups each meeting weekly for six weeks (including 9 participants [5 researchers (3 authors, 2 collaborators), 4 others] in Group 1, and 8 participants [2 authors, 6 others] in Group 2). Results: We found that text–discussion similarity was inversely correlated with emotional volatility in the group discussions (arousal: r = -0.25; p = ns; dominance: r = 0.21; p = ns; valence: r = -0.28; p = ns), and that enjoyment or otherwise of the texts and the discussion was less significant than other factors in shaping the perceived significance and potential benefits of participation. That is, texts with unpleasant or disturbing content that strongly shaped subsequent discussions of these texts were still able to sponsor ‘healthy’ discussions of this content, as evidenced by the combination of low arousal plus high dominance despite low valence in the emotional qualities of the discussion. Conclusions: Our methods and findings offer for the field of bibliotherapy research both new possibilities for hypotheses to test, and viable ways of testing them. In particular, the use of natural language processing methods and word norm data offer valuable complements to intuitive human judgement and self-report when assessing the impact of literary materials.
Respecting values and perspectives in biobanking and genetic research governance: Outcomes of a qualitative study in Bengaluru, India
Authors: Vaz Manjulika , Warrier Prasanna , Wai-Loon Ho Calvin , Bull Susan 
Published: March 2022

Background: The promise of biobanking and genetic research (BGR) in the context of translational research towards improving public health and personalised medicine has been recognised in India. Worldwide experience has shown that incorporating stakeholders’ expectations and values into the governance of BGR is essential to address ethical aspects of BGR. This paper draws on engagement with various stakeholders in the South Indian city of Bengaluru to understand how incorporating people’s values and beliefs can inform policy making decisions and strengthen BGR governance within India. Methods: We adopted a qualitative research approach and conducted six focus group discussions with civil society members and seven in-depth interviews with key informants in BGR, identified through a targeted web search and snowballing methods, until data saturation was reached. Data were thematically analysed to identify emergent patterns. Results: Specific themes relating to the ethics and governance of BGR emerged. Fears and uncertainty about future sample and data use, possibilities of discrimination and exploitation in the use of findings and the lack of comprehensive data protection policies in India along with expectations of enhanced contributor agency, control in future use of samples and data, benefit sharing, enhanced utility of samples, sustained BGR and public good, reflected tensions between different stakeholders’ values and beliefs. Fair governance processes through an independent governance committee for biobanks and a system of ongoing engagement with stakeholders emerged as best practice towards building trust and respecting diversity of views and values. Conclusions: Ensuring public trust in BGR requires listening to stakeholders’ voices, being open to counter narratives, and a commitment to long term engagement embedded in principles of participatory democracy. This is central to a ‘people-centred governance framework’ involving a negotiated middle ground and an equilibrium of governance which promotes social justice by being inclusive, transparent, equitable, and trustworthy.
Economics of Ransomware: Risk Interdependence and Large-Scale Attacks
Authors: August Terrence , Dao Duy , Niculescu Marius Florin 
Published: March 2022

Recently, the development of ransomware strains and changes in the marketplace for malware have greatly reduced the entry barrier for attackers to conduct large-scale ransomware attacks. In this paper, we examine how this mode of cyberattack impacts software vendors and consumer behavior. When victims face an added option to mitigate losses via a ransom payment, both the equilibrium market size and the vendor’s profit under optimal pricing can actually increase in the ransom demand. Profit can also increase in the scale of residual losses following a ransom payment (which reflect the trustworthiness of the ransomware operator). We show that for intermediate levels of risk, the vendor restricts software adoption by substantially hiking up price. This lies in stark contrast to outcomes in a benchmark case involving traditional malware (non-ransomware) where the vendor decreases price as security risk increases. Social welfare is higher under ransomware compared with the benchmark in both sufficiently low- and high-risk settings. However, for intermediate risk, it is better from a social standpoint if consumers do not have an option to pay ransom. We also show that the expected ransom paid is nonmonotone in risk, increasing when risk is moderate despite a decreasing ransom-paying population. For ransomware attacks on other vectors (beyond patchable vulnerabilities), there can still be an incentive to hike price. However, market size and profits instead weakly decrease in the ransom amount. When studying a generalized model that includes both traditional and ransomware attacks, our results remain robust to a wide range of scenarios, including threat landscapes where ransomware has only a small presence. This paper was accepted by Kartik Hosanagar, information systems. Funding: This work has been supported by the Haskayne School of Business' Dean's Research Grant and by an award from the Georgia Institute of Technology Center of International Business Education & Research as part of its funded research program. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4300 .