bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Implementation of a Neonatal Pain Management Guideline for Minor Surgeries
Authors: David Lebanon , Forest Sharron 
Published: January 2022

Background:
Although opioids are effective for neonatal postoperative pain management, cumulative opioid exposure may be detrimental. Pain management practices vary among providers, but practice guidelines may promote consistency and decrease opioid use.

Purpose:
To develop a pain management guideline (PMG) for neonates undergoing minor surgical procedures with the overarching goal of reducing opioid use without compromising the pain experience. The specific aim was for neonatal intensive care unit providers to adhere to the PMG at least 50% of the time.

Methods:
An interdisciplinary pain and sedation work group in a large level IV neonatal intensive care unit developed an evidence-based PMG for minor surgical procedures. Nurses and providers were educated on the new guideline, and rapid cycle quality improvement methodology provided an opportunity to adjust interventions over 3 months.

Results:
The PMG was used for 32 neonates following minor surgical procedures: 18 (56%) of the neonates received only acetaminophen and no opioids, 32% required 0.15 mg/kg dose equivalent of morphine or less, and only 9% required more than 0.15 mg/kg dose equivalent of morphine. Overall, opioid use decreased by 88% compared with rates before implementation of the PMG. Providers adhered to the PMG approximately 83.3% of time.

Implications for Practice:
A PMG is a systematic approach to direct nurses and providers to appropriately assess, prevent, and treat neonatal pain following minor surgery while alleviating opioid overuse.

Implications for Research:
Future research should focus on determining and mitigating barriers to nurse/provider use of the PMG and developing and implementing a PMG for major surgical procedures.
Trends in Venous Thromboembolism and Associated Risk Factors During Delivery Hospitalizations From 2000 to 2018
Authors: Krenitsky Nicole , Friedman Alexander M. , Yu Kathleen , Gyamfi-Bannerman Cynthia , Williams-Kane Jamila , O'Shaugnessy Fergal , Huang Yongmei , Wright Jason D. , D'Alton Mary E. , Wen Timothy 
Published: January 2022

OBJECTIVE:
To characterize trends in and risk factors for venous thromboembolism (VTE) during delivery hospitalizations in the United States.

METHODS:
The 2000–2018 National Inpatient Sample was used for this repeated cross-sectional analysis. Venous thromboembolism (including deep vein thrombosis [DVT] and pulmonary embolism) during delivery hospitalizations for women aged 15 to 54 years was determined by year. Temporal trends in VTE were characterized using joinpoint regression with estimates presented as the average annual percent change. Temporal trends in common VTE risk factors were also analyzed. The proportion of vaginal and cesarean deliveries by year that had VTE risk factors was determined, and average annual percent changes with 95% CIs were calculated. The relationship between risk factors and the likelihood of VTE events was determined with adjusted and unadjusted logistic regression models.

RESULTS:
Of 73,109,789 delivery hospitalizations, 48,546 VTE events occurred (6.6/10,000 deliveries), including 37,312 DVT diagnoses and 12,487 pulmonary embolism diagnoses. Rates increased significantly for vaginal (average annual percent change 2.5%, 95% CI 1.5–3.5%) but not for cesarean delivery hospitalizations (average annual percent change 0.3%, 95% CI −1.0 to 1.6%) over the study period. Pulmonary embolism increased for both vaginal delivery (average annual percent change 8.7%, 95% CI 6.0–11.5%) and cesarean delivery (average annual percent change 4.9%, 95% CI 3.6–6.2%). The proportion of cesarean deliveries with at least one VTE risk factor increased from 27.2% in 2000 to 43.6% in 2018 (average annual percent change 2.6%, 95% CI 2.2–3.1%) and for vaginal deliveries, from 17.7% to 31.4% (average annual percent change 3.4%, 95% CI 2.3–4.4%). The 5.9% of deliveries with at least two VTE risk factor diagnoses accounted for 25.4% of VTE diagnoses. Factors with the highest VTE risk included transfusion (adjusted odds ratio [aOR] 4.1, 95% CI 3.7–4.5), infection (aOR 5.8, 95% CI 5.3–6.3), history of VTE (aOR 7.2, 95% CI 6.2–8.4), and thrombophilias (aOR 9.6, 95% CI 8.5–11.0).

CONCLUSION:
Both risk factors for VTE and rate of pulmonary embolism increased over the study period. Deep vein thrombosis increased during vaginal delivery hospitalizations but not during cesarean delivery hospitalizations.
Temporality and Patterns of Metastatic Recurrence in Node-Positive Breast Cancer Following Trimodality Therapy
Authors: Ariani Rojine , Hwang Lindsay , Maliglig Ana M. , Ragab Omar , Ye Jason C. 
Published: January 2022

Objectives:
There is evidence that detection and treatment of oligometastases (≤5 lesions) may improve survival in breast cancer patients. However, there are no current national guidelines for screening of early, asymptomatic metastases. This study examined the patterns and timing of recurrence with respect to survival in node-positive breast cancer (NPBC) patients at higher risk for developing metastases.

Methods:
A single-institution retrospective review of NPBC patients treated with trimodality therapy was performed to collect patient and disease characteristics, recurrence location, method of detection, and survival outcome. Univariate and multivariate analyses were done to identify factors associated with recurrence.

Results:
Ninety-four NPBC patients treated at a safety-net hospital between 2008 and 2019 were identified. Twenty-one developed recurrence and were divided into oligometastatic (OM) (n=10) or diffusely metastatic (DM) (n=11) subgroups. Median recurrence-free survival in OM and DM was 18 and 36 months, respectively. Median overall survival (OS) for OM was not reached. Median OS for DM was 57 months. Four patients with OM progressed to diffuse disease in a median period of 17 months; median survival thereafter was 57 months. All patients with recurrence had distant metastases on initial detection, with the most common site being bone (14). Recurrence was most frequently detected by computed tomography (CT) (13), with the majority of disease located within the thorax region.

Conclusions:
All NPBC patients had distant metastasis at time of recurrence. Patients with OM had shorter interval to recurrence yet longer OS compared with DM. This study highlights improved surveillance imaging for timely detection of OM breast cancer that may yet be amenable to aggressive local salvage therapy to prevent progression to diffuse disease.
Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer
Authors: Park Joo-Hwan , Yeo Ja Hyun , Kim Young Saing , Park Inkeun , Ahn Hee Kyung , Cho Eun Kyung , Shin Dong Bok , Yang Jun-Young , Kim Hyung-Sik , Lee Woon Kee , Sym Sun Jin 
Published: January 2022

Objectives:
Treatment with trastuzumab and chemotherapy significantly improves the outcome in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). CT-P6 (trastuzumab-pkrb; Herzuma) is a trastuzumab biosimilar approved for the treatment of HER2-positive gastric cancer. In this study, we aimed to compare the efficacy and safety of CT-P6 and reference trastuzumab as first-line treatment for HER2-positive AGC.

Materials and Methods:
The medical records of 102 patients with HER2-positive AGC treated with first-line trastuzumab-based chemotherapy were retrospectively reviewed. These patients were treated with either reference trastuzumab (n=72) or a biosimilar (n=30). Treatment outcomes, such as objective response rate, progression-free survival (PFS), and overall survival (OS), were compared between the reference and biosimilar groups.

Results:
The objective response rate of both groups (52.8% and 56.8% in the reference and biosimilar groups, respectively) were comparable (P=0.72). No statistically significant difference was observed with the reference versus biosimilar trastuzumab for PFS (median PFS, 6.9 vs. 5.4 mo; P=0.98) or OS (median OS, 12.3 mo vs. not reached; P=0.42). Safety profiles were similar between the 2 groups.

Conclusions:
Biosimilar trastuzumab showed equivalent outcome to reference trastuzumab, with similar adverse events. Biosimilar trastuzumab can suitably and safely replace trastuzumab as a reference for the treatment of HER2-positive AGC.
Inflammation Subtypes and Translating Inflammation-Related Genetic Findings in Schizophrenia and Related Psychoses: A Perspective on Pathways for Treatment Stratification and Novel Therapies
Authors: Bishop Jeffrey R. , Zhang Lusi , Lizano Paulo 
Published: January 2022

Abstract
Dysregulation of immunological and inflammatory processes is frequently observed in psychotic disorders. Numerous studies have examined the complex components of innate and adaptive immune processes in schizophrenia and related psychoses. Elevated inflammation in these conditions is related to neurobiological phenotypes and associated with both genetics and environmental exposures. Recent studies have utilized multivariate cytokine approaches to identify what appears to be a subset of individuals with elevated inflammation. The degree to which these findings represent a general process of dysregulated inflammation or whether there are more refined subtypes remains unclear. Brain-imaging studies have attempted to establish the link between peripheral inflammation and gray matter disruption, white matter abnormalities, and neuropsychological phenotypes. However, the interplay between peripheral inflammation and neuroinflammation, as well as the consequences of this interplay, in the context of psychosis remains unclear and requires further investigation. This Perspectives article reviews the following elements of immune dysregulation and its clinical and therapeutic implications: (1) evidence supporting inflammation and immune dysregulation in schizophrenia and related psychoses; (2) recent advances in approaches to characterizing subgroups of patients with elevated inflammation; (3) relationships between peripheral inflammation and brain-imaging indicators of neuroinflammation; (4) convergence of large-scale genetic findings and peripheral inflammation findings; and (5) therapeutic implications: anti-inflammation interventions leveraging genetic findings for drug discovery and repurposing. We offer perspectives and examples of how multiomics technologies may be useful for constructing and studying immunogenetic signatures. Advancing research in this area will facilitate biomarker discovery, disease subtyping, and the development of etiological treatments for immune dysregulation in psychosis.
The Normal Lung Index From Quantitative Computed Tomography for the Evaluation of Obstructive and Restrictive Lung Disease
Authors: Barros Marcelo C. , Hochhegger Bruno , Altmayer Stephan , Zanon Matheus , Sartori Gabriel , Watte Guilherme , do Nascimento Marcos H. Sant’Ana , Chatkin Jose M. 
Published: January 2022

Purpose:
Our objective was to evaluate whether the normal lung index (NLI) from quantitative computed tomography (QCT) analysis can be used to predict mortality as well as pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).

Materials and Methods:
Normal subjects (n=20) and patients with COPD (n=172) and ILD (n=114) who underwent PFTs and chest CT were enrolled retrospectively in this study. QCT measures included the NLI, defined as the ratio of the lung with attenuation between –950 and –700 Hounsfield units (HU) over the total lung volume (−1024 to −250 HU, mL), high-attenuation area (–700 to –250 HU, %), emphysema index (>6% of pixels < –950 HU), skewness, kurtosis, and mean lung attenuation. Coefficients of correlation between QCT measurements and PFT results in all subjects were calculated. Univariate and multivariate survival analyses were performed to assess mortality prediction by disease.

Results:
The Pearson correlation analysis showed that the NLI correlated moderately with the forced expiratory volume in 1 second in subjects with COPD (r=0.490, P<0.001) and the forced vital capacity in subjects with ILD (r=0.452, P<0.001). Multivariate analysis revealed that the NLI of <70% was a significant independent predictor of mortality in subjects with COPD (hazard ratio=3.14, P=0.034) and ILD (hazard ratio=2.72, P=0.005).

Conclusion:
QCT analysis, specifically the NLI, can also be used to predict mortality in individuals with COPD and ILD.
Should rapid antigen tests be government funded in Australia? An economic evaluation
Authors: Karnon Jonathan , Afzali Hossein , Bonevski Billie 
Published: January 2022

AbstractObjectiveEasy and equitable access to testing is a cornerstone of the public health response to COVID-19. Currently in Australia, testing using Polymerase Chain Reaction (PCR) tests for COVID-19 is free-to-the-user, but the public purchase their own Rapid Antigen Tests (RATs). We conduct an economic analysis of government-funded RATs in Australia.DesignAn interactive decision tree model was developed to compare one policy in which government-funded RATs are free-to-the-user, and one in which individuals purchase their own RATs. The decision tree represents RAT and PCR testing pathways for a cohort of individuals without COVID-19-like symptoms, to estimate the likelihood of COVID-19 positive individuals isolating prior to developing symptoms and the associated costs of testing, from a government perspective.Data sourcesTest costs and detection rates were informed by published studies, other input parameter values are unobservable and uncertain, for which a range of scenario analyses are presented.Data synthesisAssuming 10% prevalence of COVID-19 in a cohort of 10,000 individuals who would use government-funded RATs, the model estimates an additional 464 individuals would isolate early at a cost to the government of around $52,000. Scenario analyses indicate that the incremental cost per additional COVID-19 positive individual isolating with no symptoms remains at a few hundred dollars at 5% prevalence, rising to $2,052 at 1% prevalence.ConclusionsBased on the presented decision tree model, even only minor reductions in COVID-19 transmission rates due to early isolation would justify the additional costs associated with a policy of government-funded RATs.
The epidemiological impact of the Canadian COVID Alert App
Authors: Sun Shuo , Shaw Mairead , Moodie Erica EM , Ruths Derek 
Published: January 2022

AbstractObjectivesWe analyzed the effectiveness of the Canadian COVID Alert app on reducing COVID-19 infections and deaths due to the COVID-19 virus.MethodsTwo separate, but complementary approaches, were taken. First, we undertook a comparative study to assess how the adoption and usage of the COVID Alert app compared to those of similar apps deployed in other regions. Next, we used data from the COVID Alert server and a range of plausible parameter values to estimate the numbers of infections and deaths averted in Canada using a model that combines information on number of notifications, secondary attack rate, expected fraction of transmissions that could be prevented, quarantine effectiveness, and expected size of the full transmission chain in the absence of exposure notification.ResultsThe comparative analysis revealed that the COVID Alert app had among the lowest adoption levels among apps that reported usage. Our model indicates that use of the COVID Alert app averted between 6,284 and 10,894 infections across the six Canadian provinces where app usage was highest during the March - July 2021 period. This range is equivalent to 1.6%-2.9% of the total recorded infections across Canada in that time. Using province-specific case fatality rates, 57-101 deaths were averted during the same period. The number of cases and deaths averted was greatest in Ontario, whereas the proportion of cases and death averted was greatest in Newfoundland and Labrador. App impact measures were reported so rarely and so inconsistently by other countries that the relative assessment of impact is inconclusive.ConclusionsWhile the nationwide rates are low, provinces with widespread adoption of the app showed high ratios of averted cases and deaths (upper bound was greater than 60% of averted cases). This finding suggests that the COVID Alert app, when adopted at sufficient levels, can be an effective public health tool for combatting a pandemic such as COVID-19.
Differential Effects of Race/Ethnicity and Social Vulnerability on COVID-19 Positivity, Hospitalization, and Death in the San Francisco Bay Area
Authors: Tam Cho Wendy K. , Hwang David G. 
Published: January 2022

AbstractBACKGROUNDHigher COVID-19 incidence and morbidity have been documented for US Black and Hispanic populations but not as clearly for other racial and ethnic groups. Efforts to elucidate the mechanisms underlying racial health disparities can be confounded by the relationship between race/ethnicity and socioeconomic status.OBJECTIVEExamine race/ethnicity and social vulnerability effects on COVID-19 out-comes in the San Francisco Bay Area, an ethnically and socioeconomically diverse region, using geocoded patient records from 2020 in the University of California, San Francisco Health system.KEY RESULTSHigher social vulnerability, but not race/ethnicity, was associated with less frequent testing yet a higher likelihood of testing positive. Asian hospitalization rates (11.5%) were double that of White patients (5.4%) and exceeded the rates for Black (9.3%) and Hispanic patients (6.9%). A modest relationship between higher hospitalization rates and increasing social vulnerability was evident only for White patients. Hispanic patients had the highest years of expected life lost due to COVID-19.CONCLUSIONSCOVID-19 outcomes were not consistently explained by greater social vulnerability. Asian individuals showed disproportionately high rates of hospitalization regardless of social vulnerability status. Study of the San Francisco Bay Area population not only provides valuable insights into the differential contributions of race/ethnicity and social determinants of health to COVID-19 outcomes but also emphasizes that all racial groups have experienced the toll of the pandemic, albeit in different ways and to varying degrees.
Citizen Science and Public Health- Can eBird data inform relationships between public health and access to biodiversity?
Authors: LaFantasie J.J. 
Published: January 2022

AbstractThe relationship between access to nature and public health outcomes has been well-studied and established in the literature. However, most studies use simple greenness indices as a proxy for access to nature, which ignores the “quality” of the nature since greenness indices are not able to predict biodiversity. My objective was to investigate the relationship between citizen scientist collected biodiversity data from the eBird platform, urban greenness and four human health outcomes (asthma, coronary heart disease, and self-assessed mental and physical health). I mapped and tested for correlations among eBird record species richness, greenness as NDVI and PLACES human health data in urban census tracts located in three metro areas/ecological zones (Albany, NY: eastern deciduous forest, Kansas City, MO: tallgrass prairie, and Phoenix, AZ: Sonoran Desert). eBird species richness was related to greenness, measures of urbanization and several human health factors; however, the correlations varied by metro area and in strength. Provided confounders are controlled for, eBird data could help to refine models surrounding relationships between public health and nature access.
Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia
Authors: Zhai Yanan , Singh Prashant , Dolnik Anna , Brazda Peter , Atlasy Nader , Gaudio Nunzio del , Döhner Konstanze , Döhner Hartmut , Minucci Saverio , Martens Joost , Altucci Lucia , Megchelenbrink Wout , Bullinger Lars , Stunnenberg Hendrik G. 
Published: January 2022

AbstractThe heterogeneity and evolution of AML blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole-exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases.The single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells.In summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.
Three amphioxus reference genomes reveal gene and chromosome evolution of chordates
Authors: Huang Zhen , Xu Luohao , Cai Cheng , Zhou Yitao , Liu Jing , Zhu Zexian , Kang Wen , Chen Duo , Pei Surui , Xue Ting , Cen Wan , Shi Chenggang , Wu Xiaotong , Huang Yongji , Xu Chaohua , Yan Yanan , Yang Ying , He Wenjing , Hu Xuefeng , Zhang Yanding , Chen Youqiang , Bi Changwei , He Chunpeng , Xue Lingzhan , Xiao Shijun , Yue Zhicao , Jiang Yu , Yu Jr-Kai , Jarvis Erich D. , Li Guang , Lin Gang , Zhang Qiujin , Zhou Qi 
Published: January 2022

AbstractThe slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding into the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention or rearrangements between descendants of whole genome duplications (WGDs), which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its 3D chromatin architecture at the onset of zygotic activation, and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes, and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.