The ownership of digital infrastructure: Exploring the deployment of software libraries in a digital innovation cluster

Boundary resources have been shown to enable the arm’s-length relationships between platform owners and third-party developers that underlie digital innovation in platform ecosystems. While boundary resources that are owned by open-source communities and smaller-scale software vendors are also critical components in the digital infrastructure, their role in digital innovation has yet to be systematically explored. In particular, software libraries are popular boundary resources that provide functionality without the need for continued interaction with their owners. They are used extensively by commercial vendors to enable customization of their software products, by communities to disseminate open-source software, and by big-tech platform owners to provide functionality that does not involve control. This paper reports on the deployment of such software libraries in the web and mobile (Android) contexts by 107 startup companies in London. Our findings show that libraries owned by big-tech companies, product vendors, and communities coexist; that the deployment of big-tech libraries is unaffected by the scale of the deploying startup; and that context evolution paths are consequential for library deployment. These findings portray a balanced picture of digital infrastructure as neither the community-based utopia of early open-source research nor the dystopia of the recent digital dominance literature

Analysis of common and rare VPS13C variants in late-onset Parkinson disease

Objective We aimed to study the role of coding VPS13C variants in a large cohort of patients with lateonset Parkinson disease (PD) (LOPD). Methods VPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 patients with PD and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis. Results No biallelic carriers of rare VPS13C variants were found among patients, and 2 carriers of compound heterozygous variants were found in 2 controls. There was no statistically significant burden of rare (minor allele frequency [MAF] <1%) or very rare (MAF <0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V [odds ratio = 0.48, 95% confidence interval = 0.28–0.82, p = 0.0052]). This haplotype was not in linkage disequilibrium with the known genome-wide association study top hit. Conclusions Our results do not support a role for rare heterozygous or biallelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD

Routine Laboratory Results and Thirty Day and One-Year Mortality Risk Following Hospitalization with Acute Decompensated Heart Failure

INTRODUCTION: Several blood tests are performed uniformly in patients hospitalized with acute decompensated heart failure and are predictive of the outcomes: complete blood count, electrolytes, renal function, glucose, albumin and uric acid. We sought to evaluate the relationship between routine admission laboratory tests results, patient characteristics and 30-day and one-year mortality of patients admitted for decompensated heart failure and to construct a simple mortality prediction tool. METHODS: A retrospective population based study. Data from seven tertiary hospitals on all admissions with a principal diagnosis of heart failure during the years 2002-2005 throughout Israel were captured. RESULTS: 8,246 patients were included in the study cohort. Thirty day mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7% (2,365 patients). Addition of five routine laboratory tests results (albumin, sodium, blood urea, uric acid and WBC) to a set of clinical and demographic characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72 to 0.76 for one-year mortality prediction (both p-values <0.0001). Three dichotomized abnormal laboratory results with highest odds ratio for one-year mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to construct a simple prediction score, capable of discriminating from 1.1% to 21.4% in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients with a score of 0 (1,477 patients) vs. score of 3 (544 patients). DISCUSSION: A small set of abnormal routine laboratory results upon admission can risk-stratify and independently predict 30-day and one-year mortality in patients hospitalized with acute decompensated heart failure

BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling

Tumors initiate by mutations in cancer cells, and progress through interactions of the cancer cells with non-malignant cells of the tumor microenvironment. Major players in the tumor microenvironment are cancer-associated fibroblasts (CAFs), which support tumor malignancy, and comprise up to 90% of the tumor mass in pancreatic cancer. CAFs are transcriptionally rewired by cancer cells. Whether this rewiring is differentially affected by different mutations in cancer cells is largely unknown. Here we address this question by dissecting the stromal landscape of BRCA-mutated and BRCA Wild-type pancreatic ductal adenocarcinoma. We comprehensively analyze pancreatic cancer samples from 42 patients, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA Wild-type tumors. In particular, we detect an increase in a subset of immune-regulatory clusterin-positive CAFs in BRCA-mutated tumors. Using cancer organoids and mouse models we show that this process is mediated through activation of heat-shock factor 1, the transcriptional regulator of clusterin. Our findings unravel a dimension of stromal heterogeneity influenced by germline mutations in cancer cells, with direct implications for clinical research

Evaluation of the Virtual Interviews for Resident Recruitment Due to COVID-19 Travel Restrictions: A Nationwide Survey of US Senior Medical Students

BACKGROUND AND OBJECTIVES: Due to COVID-19, residency programs could not conduct in-person interviews during the 2020-2021 match and were forced to implement a virtual format. We conducted a nationwide survey of US senior medical students to evaluate their perception of the virtual interview process and to solicit their recommendations for future virtual interview best practices. METHODS: This study was administered to US fourth-year medical students currently participating in the residency match using Survey Monkey during March 2021. Students were contacted through their respective student affairs deans. Surveys solicited demographic information, 26 4-point Likert-scale questions, and four free-response questions. RESULTS: A total of 357 surveys were completed. Most respondents stated that they could confidently represent themselves to the program (71.7%) using a virtual platform. However, only 11.6% stated that they could confidently assess a program\u27s facility using a virtual platform. Although most respondents (58.26%) found that virtual meet and greets helped them better assess their fit for the program, less than half (46%) confidently believed they could assess their fit into the program after the conclusion of the virtual interview. Regarding potential disparities introduced by virtual interviews, 40.6% believed that the virtual interviews introduce greater inequalities into the match process. Two-thirds of respondents (239, 66.95%), believed that there should be a limit on the number of interview offers an applicant can accept, with the maximum number of interviews per specialty capped at 25.7 (10-150). Finally, just over two-thirds (69.47%), claimed they could confidently prepare their rank-order list at the conclusion of the interview. CONCLUSIONS: Most respondents found virtual interviews financially beneficial, however difficulty in assessing fit was a challenge. Best practice recommendations from the respondents include shorter interviews, more engaging resident-led social hours without faculty present, and preinterview packages to include video representations of the program facilities

Evaluation of the Virtual Interview Format for Resident Recruitment as a Result of COVID-19 Restrictions: Residency Program Directors\u27 Perspectives

PURPOSE: Due to the COVID-19 pandemic, residency programs could not conduct in-person interviews during the 2020-2021 Match cycle and were forced to implement a virtual format. The authors conducted a nationwide survey of residency program directors (PDs) to assess their confidence in using a virtual platform to holistically evaluate applicants during the 2020-2021 Match cycle and their desire to continue virtual recruitment during forthcoming interview seasons. METHOD: This prospective study was conducted by email questionnaire administered through the survey tool Survey Monkey to residency PDs from March 7, 2021-March 27, 2021. The residency PDs surveyed represented these subspecialties: internal medicine, general surgery, obstetrics and gynecology, pediatrics, psychiatry, and other. Email addresses of PDs were collected from a public list developed by the Accreditation Council for Graduate Medical Education. Surveys contained demographic questions, 4-point Likert scale questions evaluating several factors regarding the interview and matching process, and free-response questions. RESULTS: A total of 463 surveys were sent; response rate was 402 /463 (86.8%). Most PDs were less confident assessing an applicant\u27s interpersonal skills (247, 61.4%) and professionalism (239, 59.5%) using a virtual platform. Assessment of an applicant\u27s fit into the program was also challenging: 44.3% (178) of those surveyed disagreed with the statement that they could do so confidently. Additionally, 73.9% (297) of PDs found it challenging to gauge an applicant\u27s genuine interest and only 41.3% (166) strongly agreed or agreed that they could accurately represent their own program using a virtual platform. More than half of PDs (220, 54. 7%) found it more difficult to rank interviewees compared with previous in-person Match cycles. CONCLUSIONS: Most residency PDs found virtual interviews convenient. However, difficulties in assessing fit virtually, gauging applicants\u27 interest, and showcasing their respective programs were challenges that may persist should virtual interviews continue post-pandemic

Heme-Oxygenase and Lipid Mediators in Obesity and Associated Cardiometabolic Diseases: Therapeutic Implications

Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its effect on lipid metabolism. HO-1 has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin and leptin sensitivity. Recent reports indicate that HO-1 with its antioxidants via the effect of bilirubin increases formation of biologically active lipid metabolites such as epoxyeicosatrienoic acid (EET), omega-3 and other polyunsaturated fatty acids (PUFAs). Similarly, HO-1and bilirubin are potential therapeutic targets in the treatment of fat-induced liver diseases. HO-1-mediated upregulation of EET is capable not only of reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, a hallmark of the metabolic syndrome. This process involves browning of white fat tissue (i.e. formation of healthy adipocytes) and reduced lipotoxicity, which otherwise will be toxic to the heart. More importantly, this review examines the activity of EET in biological systems and a series of pathways that explain its mechanism of action and discusses how these might be exploited for potential therapeutic use. We also discuss the link between cardiac ectopic fat deposition and cardiac function in humans, which is similar to that described in obese mice and is regulated by HO-1-EET-PGC1α signaling, a potent negative regulator of the inflammatory adipokine NOV