bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipidomics reveals perturbations in the liver lipid profile of iron-overloaded mice
Authors: Ding Haoxuan , Zhang Qian , Yu Xiaonan , Chen Lingjun , Wang Zhonghang , Feng Jie 
Published: September 2021

Abstract
Iron overload is an important contributor to disease. The liver, the major site of iron storage in the body, is a key organ impacted by iron overload. While several studies have reported perturbations in liver lipids in iron overload, it is not clear, on a global scale, how individual liver lipid ions are altered. Here, we used lipidomics to study the changes in hepatic lipid ions in iron-overloaded mice. Iron overload was induced by daily intraperitoneal injections of 100 mg/kg body weight iron dextran for 1 week. Iron overload was verified by serum markers of iron status, liver iron quantitation, and Perls stain. Compared with the control group, the serum of iron-overload mice exhibited low levels of urea nitrogen and high-density lipoprotein (HDL), and high concentrations of total bile acid, low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), suggestive of liver injury. Moreover, iron overload disrupted liver morphology, induced reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, caused lipid peroxidation, and led to DNA fragmentation. Iron overload altered the overall composition of lipid ions in the liver, with significant changes in over 100 unique lipid ions. Notably, iron overload selectively increased the overall abundance of glycerolipids and changed the composition of glycerophospholipids and sphingolipids. This study, one of the first to report iron-overload induced lipid alterations on a global lipidomics scale, provides early insight into lipid ions that may be involved in iron overload-induced pathology.
UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair
Authors: Micheli Consuelo , Parma Alice , Tani Chiara , Di Bello Domenica , Falaschi Aurora , Chiaramonte Anna , Testi Serena , Mosca Marta , Scarpato Roberto 
Published: September 2021

AbstractImmunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterise SLE and UCTD, aiming to improve the treatment plan and the quality of the patients’ life.
The IDEAL trial in Australia and New Zealand: clinical and economic impact
Authors: Dansie Kathryn B , Davies Christopher E , Morton Rachael L , Hawley Carmel M , Johnson David W , Craig Jonathan C , Chapman Jeremy R , Cooper Bruce A , Pollock Carol A , Harris David C H , McDonald Stephen P 
Published: September 2021

ABSTRACT

Background
The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry.

Methods
We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000–2010) and following (2010–2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice.

Results
From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19–0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [−0.01 mL/min/1.73 m2/year (95% CI −0.03–0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year.

Conclusions
The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.
The Effect of Nomenclature Revision of Streptococcus bovis to Streptococcus gallolyticus on Subsequent Colon Cancer Screening
Authors: Thind Sharanjeet K , Shibib Dena R , Gentry Chris A 
Published: September 2021

Abstract

Background
Lack of awareness of the taxonomic revision from the familiar Streptococcus bovis to the less familiar Streptococcus gallolyticus may be associated with a decrease in recommended colon cancer screening in patients with bacteremia from this organism. This could subsequently lead to a delay in diagnosis or underdiagnosis of colon cancer and other serious underlying gastrointestinal diseases. The aim of this study was to determine whether the nomenclature change of S. bovis to S. gallolyticus resulted in decreased colon cancer screening.

Methods
This study was a retrospective, observational, nationwide analysis of patients who had positive blood cultures for S. bovis/S. gallolyticus from any Veterans Affairs Medical Center (VAMC) between January 1, 2002, and December 31, 2017.

Results
There was no difference in the primary end point of intent for colonoscopy between the S. gallolyticus and S. bovis groups (66.5% [117/176] vs 62.1% [624/1005], respectively; P = .26). The overall mortality rate was 33.8% among 1181 patients included in the study, with a significantly lower mortality in patients with evidence of intent for colonoscopy (29.6% vs 42.5%; P ≤ .001), gastroenterology (GI) consultation (29.8% vs 41.4%; P &lt; .001), infectious diseases (ID) consultation (29.4% vs 39.0%; P = .001), or either consultation (31.9% vs 40.7%; P = .013), compared to those that did not.

Conclusions
There was no difference in colon cancer screening rates between patients with episodes of bacteremia reported as S. bovis and those reported as S. gallolyticus. Overall mortality was lower in patients who had ID consultation, GI consultation, or evidence of colonoscopy.
Outstanding Questions on the Beneficial Role of Silicon in Crop Plants
Authors: Shivaraj S M , Mandlik Rushil , Bhat Javaid Akhter , Raturi Gaurav , Elbaum Rivka , Alexander Lux , Tripathi Durgesh Kumar , Deshmukh Rupesh , Sonah Humira 
Published: September 2021

AbstractSilicon (Si) is widely accepted as a beneficial element for plants. Despite the substantial progress made in understanding Si transport mechanisms and modes of action in plants, several questions remain unanswered. In this review, we discuss such outstanding questions and issues commonly encountered by biologists studying the role of Si in plants in relation to Si bioavailability. In recent years, advances in our understanding of the role of Si-solubilizing bacteria and the efficacy of Si nanoparticles have been made. However, there are many unknown aspects associated with structural and functional features of Si transporters, Si loading into the xylem, and the role of specialized cells like silica cells and compounds preventing Si polymerization in plant tissues. In addition, despite several 1,000 reports showing the positive effects of Si in high as well as low Si-accumulating plant species, the exact roles of Si at the molecular level are yet to be understood. Some evidence suggests that Si regulates hormonal pathways and nutrient uptake, thereby explaining various observed benefits of Si uptake. However, how Si modulates hormonal pathways or improves nutrient uptake remains to be explained. Finally, we summarize the knowledge gaps that will provide a roadmap for further research on plant silicon biology, leading to an exploration of the benefits of Si uptake to enhance crop production.
In action—an early warning system for the detection of unexpected or novel pathogens
Authors: Santos Pauline Dianne , Ziegler Ute , Szillat Kevin P , Szentiks Claudia A , Strobel Birte , Skuballa Jasmin , Merbach Sabine , Grothmann Pierre , Tews Birke Andrea , Beer Martin , Höper Dirk 
Published: September 2021

Abstract
Proactive approaches in preventing future epidemics include pathogen discovery prior to their emergence in human and/or animal populations. Playing an important role in pathogen discovery, high-throughput sequencing (HTS) enables the characterization of microbial and viral genetic diversity within a given sample. In particular, metagenomic HTS allows the unbiased taxonomic profiling of sequences; hence, it can identify novel and highly divergent pathogens such as viruses. Newly discovered viral sequences must be further investigated using genomic characterization, molecular and serological screening, and/or invitro and invivo characterization. Several outbreak and surveillance studies apply unbiased generic HTS to characterize the whole genome sequences of suspected pathogens. In contrast, this study aimed to screen for novel and unexpected pathogens in previously generated HTS datasets and use this information as a starting point for the establishment of an early warning system (EWS). As a proof of concept, the EWS was applied to HTS datasets and archived samples from the 2018–9 West Nile virus (WNV) epidemic in Germany. A metagenomics read classifier detected sequences related to genome sequences of various members of Riboviria. We focused the further EWS investigation on viruses belonging to the families Peribunyaviridae and Reoviridae, under suspicion of causing co-infections in WNV-infected birds. Phylogenetic analyses revealed that the reovirus genome sequences clustered with sequences assigned to the species Umatilla virus (UMAV), whereas a new peribunyavirid, tentatively named ‘Hedwig virus’ (HEDV), belonged to a putative novel genus of the family Peribunyaviridae. In follow-up studies, newly developed molecular diagnostic assays detected fourteen UMAV-positive wild birds from different German cities and eight HEDV-positive captive birds from two zoological gardens. UMAV was successfully cultivated in mosquito C6/36 cells inoculated with a blackbird liver. In conclusion, this study demonstrates the power of the applied EWS for the discovery and characterization of unexpected viruses in repurposed sequence datasets, followed by virus screening and cultivation using archived sample material. The EWS enhances the strategies for pathogen recognition before causing sporadic cases and massive outbreaks and proves to be a reliable tool for modern outbreak preparedness.
Managing Human Subjects Research During a Global Pandemic at an Academic Center: Lessons Learned From COVID-19
Authors: Stiles Deborah F. , Ruotolo Brenda L. , Kim Helen , Cho Jane , Appelbaum Paul S. , Green Nancy S. 
Published: September 2021

By March 2020, New York City became the early epicenter of the COVID-19 pandemic in the United States. Consequently, Columbia University, with its large portfolio of human subjects research, had to address the challenges of protecting thousands of research participants and research staff from potential exposure to COVID-19 while facilitating essential biomedical research, especially pandemic-related studies. The authors describe, from the perspective of Columbia’s research administration leadership, how the University and its primary teaching hospital ramped down—and later ramped up—human subjects research and reflect on lessons learned.
As the pandemic unfolded, only studies offering the prospect of direct benefit to subjects were permitted to continue with in-person contact. New in-person participant enrollment ceased, except for COVID-19 prevention or treatment studies. Centralized, frequently updated communication about policies and procedures was disseminated to the Columbia research community. Procedural efficiencies were rapidly developed and implemented for review and oversight of human subjects research and contractual agreements for clinical trials. More frequent institutional review board meetings and 24-hour support markedly reduced turnaround time for COVID-19 studies, without delaying approvals of non–COVID-19 research. Research administration worked closely with relevant principal federal agencies, whose regulatory flexibility facilitated the efficient implementation of COVID-19–related research.
Overall, the ramp-down and ramp-up of the majority of human subjects research, with specified priorities and accelerated processes, worked well. Adjustments were made to handle the increase in administrative tasks, the need to respond rapidly to added oversight responsibilities, and the management of the many new COVID-19–related research protocols. Timely, centralized communication, support for staff needs, prioritization, and collaboration were critical to successful research oversight at a large-scale academic setting in the midst of a pandemic. These perspectives may be useful to academic research centers addressing the current and future pandemics.
Advancing Social Mission Research: A Call to Action
Authors: Erikson Clese , Ziemann Margaret 
Published: September 2021

Social mission efforts in health professions education are designed to advance health equity and address the health disparities of the society in which they exist. While there is growing evidence that social mission–related interventions are associated with intended outcomes such as practice in underserved communities, student diversity, and students graduating with skills and knowledge that prepare them to address societal needs, critical evidence gaps remain that limit the possibility of generalizing findings and using social mission strategically to advance health equity. At a time when COVID-19 has been laying bare health disparities related to systemic racism and maldistribution of resources, understanding how health professions training can produce the workforce needed to advance health equity becomes even more imperative. Yet, data and methods limitations are hindering progress in this critical research.
The authors present an overview of the social mission research landscape; their review of the research led them to conclude that more rigorous research and data collection are needed to determine the link between social mission activities in health professions education and advances in health equity. To accelerate understanding of how health professions education and training can advance health equity, the authors propose a social mission research road map that includes (1) creating a social mission research community by consolidating stakeholders, (2) building a solid foundation for the research through development of a consensus-driven logic framework and research agenda, and (3) laying out the data and methodological needs that are imperative to strengthening the social mission evidence base and identifying opportunities to address these needs. Core to achieving these milestones is leadership from an organizing body that can serve as a hub for social mission research and engage stakeholder groups in building the evidence base for social mission strategies that will ultimately advance health equity.
Accelerating drug access from advanced to early breast cancer: the special case of oral selective estrogen receptor degraders
Authors: Wilson Brooke E. , Cescon David W. 
Published: September 2021

Purpose of review
For hormone receptor positive breast cancer, the development of endocrine resistance commonly occurs, presenting as either disease progression in the metastatic setting or recurrence during or following adjuvant endocrine therapy. Various mechanisms of resistance have been described. In order to reduce or overcome endocrine resistance, there has been substantial interest in developing potent and orally bioavailable selective estrogen receptor degraders (SERDs) for metastatic disease and select patients with early-stage estrogen receptor positive breast cancer.

Recent findings
At least 11 oral SERDs have entered clinical development. We review current studies in both the metastatic and neoadjuvant/adjuvant setting and present the available evidence of benefit and toxicity for these novel agents. Further characterization of changes to tissue-based biomarkers such as estrogen receptor, progesterone receptor and Ki67 expression and blood-based biomarkers such as ctDNA and estrogen receptor 1 mutation may help to refine therapeutic strategies, combinations, and patient selection to identify women who are most likely to benefit from these novel endocrine agents.

Summary
Although SERDs have clear therapeutic potential based on nonclinical studies and have demonstrated early signs of activity in phase I and II studies in the metastatic setting, ongoing research is needed to clarify when and in whom these agents may have greatest clinical benefit.
Improving Care Delivery: Location Timestamps to Enhance Process Measurement of a Clinical Workflow
Authors: Barrick Lindsey , Wu Danny T.Y. , Frey Theresa , Shu Derek , Abbu Ruthvik , Porter Stephen C. , Overmann Kevin M. 
Published: September 2021

Introduction:
Traditional quality improvement (QI) strategies to describe workflow processes rely primarily upon qualitative methods or human-driven observations. These methods may be limited in scope and accuracy when applied to time-based workflow processes. This study sought to evaluate the utility of integrating objective time measurements to augment traditional QI strategies using procedural sedation workflow in a pediatric emergency department as an archetype.

Methods:
We applied the FOCUS-Plan-Do-Check-Act framework to reduce the time from arrival to sedation for long-bone fractures. First, we added supplementary framework-defining steps to repeat the Clarifying and Understanding steps. We then extracted objective time-based data from an electronic health record (EHR) system and a real-time locating system (RTLS). We then compared and contrasted the findings of traditional surveys with analyses of timed steps within the sedation workflow.

Results:
When identifying the source of delays, traditional survey techniques yielded ambiguous and even conflicting results based on clinical roles. The timestamps supported 5 measurable clinical role of subworkflows. By measuring the time to completion for 54 sedation cases, workflow patterns and significant bottlenecks were identified.

Conclusions:
Analyzing the time to complete individual tasks provided a more nuanced description of workflow delays and clarity when traditional survey results conflicted. Augmenting traditional QI process maps with EHR and RTLS timestamps better explained workflow bottlenecks, informing the QI team when selecting targets for subsequent Plan-Do-Check-Act work.
Initiative to Reduce Antibiotic Exposure of Asymptomatic Infants Born to Mothers with Intraamniotic Infection
Authors: Weiss Katherine J. , Song Richard S. , DeVries Nikole M. , McLean Amy L. , Moyer Laurel B. 
Published: September 2021

Introduction:
Infants born to mothers with intraamniotic infection (IAI) received antibiotic treatment per the Centers for Disease Control and Prevention and American Academy of Pediatrics guidelines in our neonatal intensive care unit (NICU) for early-onset bacterial sepsis evaluation. We conducted a quality improvement project to decrease antibiotic use and NICU admission in infants born to mothers with IAI.

Methods:
We aimed to decrease the antibiotic exposure for asymptomatic infants born to mothers with IAI from 100% to 20% in 6 months. We obtained baseline data on these infants from January 2018 to January 2019, with the intervention starting in February 2019. A new standardized guideline to clinically monitor and follow laboratories on asymptomatic infants in couplet care was created with a multidisciplinary team’s help and implemented after provider education. The team reviewed data monthly and used PDSA cycles to make necessary changes, including updating order sets, more educational handouts, and real-time coaching to both nurses and physicians.

Results:
There was a dramatic decline (93%–0%) in antibiotic exposure and NICU admission after implementing this guideline. There was also a decrease in IAI diagnosis. There were no readmissions of infants for infection within 30 days of discharge, and there were no positive blood cultures.

Conclusions:
Implementing best antibiotic stewardship practices through a standardized guideline, testing, implementation of processes, and education by a multidisciplinary team limited the antibiotic exposure and NICU admissions for infants born to mothers with IAI with no known increase in readmissions.
Effect of combination therapy with neural stem cell transplantation and teramethylpyrazine in rats following acute spinal cord injury
Authors: Zhang Haocong , Huang Zijun , Guo Mingming , Meng Lingzhi , Piao Meihui , Zhang Meng , Yu Hailong 
Published: September 2021

Objectives
This study was to explore the effects of teramethylpyrazine (TMP) administered in conjunction with neural stem cell transplantation on motor function, pathological lesions and the Janus kinase (JAK)2/signal transducer and activator of transcription 3 signal transduction pathway in rats following acute spinal cord injury (SCI).

Methods
Female Sprague–Dawley rats were randomly divided into sham, model, neural stem cells (NSCs) and NSCs+TMP groups. Motor function was evaluated using the Basso, Beattie, Bresnahan scale. Spinal cord neuropathies and neuron apoptosis were observed by HE and TUNEL staining. The brain-derived neurotrophic factor (BDNF), Nogo-A, JAK2 and p-JAK2 protein levels were measured by western blot analysis.

Results
NSCs+TMP significantly improved rat motor function, attenuated impaired spinal cords, and decreased cellular apoptosis, compared with NSCs therapy alone (P < 0.05). In addition, expression of BDNF protein was significantly higher in NSCs+TMP rats compared with other groups regardless of time postinjury (P < 0.05). The highest expression levels of Nogo-A protein were observed in the model group. The expression of p-JAK2 in the NSCs+TMP group was relatively lower than the model and NSCs groups (P < 0.05).

Conclusions
In rats with SCI, NSCs+TMP effectively improved motor function and offered spinal cord protection by increasing BDNF and decreasing Nogo-A levels, as well as inhibiting the JAK2/STAT3 signal transduction pathway, suggesting that TMP could be a useful agent in NSCs transplantation in the treatment of SCI.