bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivering on NIH data sharing requirements: avoiding Open Data in Appearance Only
Authors: Watson Hope , Gallifant Jack , Lai Yuan , Radunsky Alexander P , Villanueva Cleva , Martinez Nicole , Gichoya Judy , Huynh Uyen Kim , Celi Leo Anthony 
Published: January 2024

IntroductionIn January, the National Institutes of Health (NIH) implemented a Data Management and Sharing Policy aiming to leverage data collected during NIH-funded research. The COVID-19 pandemic illustrated that this practice is equally vital for augmenting patient research. In addition, data sharing acts as a necessary safeguard against the introduction of analytical biases. While the pandemic provided an opportunity to curtail critical research issues such as reproducibility and validity through data sharing, this did not materialise in practice and became an example of ‘Open Data in Appearance Only’ (ODIAO). Here, we define ODIAO as the intent of data sharing without the occurrence of actual data sharing (eg, material or digital data transfers).ObjectivePropose a framework that states the main risks associated with data sharing, systematically present risk mitigation strategies and provide examples through a healthcare lens.MethodsThis framework was informed by critical aspects of both the Open Data Institute and the NIH’s 2023 Data Management and Sharing Policy plan guidelines.ResultsThrough our examination of legal, technical, reputational and commercial categories, we find barriers to data sharing ranging from misinterpretation of General Data Privacy Rule to lack of technical personnel able to execute large data transfers. From this, we deduce that at numerous touchpoints, data sharing is presently too disincentivised to become the norm.ConclusionIn order to move towards Open Data, we propose the creation of mechanisms for incentivisation, beginning with recentring data sharing on patient benefits, additional clauses in grant requirements and committees to encourage adherence to data reporting practices.
Road map for clinicians to develop and evaluate AI predictive models to inform clinical decision-making
Authors: Hassan Nehal , Slight Robert , Morgan Graham , Bates David W , Gallier Suzy , Sapey Elizabeth , Slight Sarah 
Published: January 2024

BackgroundPredictive models have been used in clinical care for decades. They can determine the risk of a patient developing a particular condition or complication and inform the shared decision-making process. Developing artificial intelligence (AI) predictive models for use in clinical practice is challenging; even if they have good predictive performance, this does not guarantee that they will be used or enhance decision-making. We describe nine stages of developing and evaluating a predictive AI model, recognising the challenges that clinicians might face at each stage and providing practical tips to help manage them.FindingsThe nine stages included clarifying the clinical question or outcome(s) of interest (output), identifying appropriate predictors (features selection), choosing relevant datasets, developing the AI predictive model, validating and testing the developed model, presenting and interpreting the model prediction(s), licensing and maintaining the AI predictive model and evaluating the impact of the AI predictive model. The introduction of an AI prediction model into clinical practice usually consists of multiple interacting components, including the accuracy of the model predictions, physician and patient understanding and use of these probabilities, expected effectiveness of subsequent actions or interventions and adherence to these. Much of the difference in whether benefits are realised relates to whether the predictions are given to clinicians in a timely way that enables them to take an appropriate action.ConclusionThe downstream effects on processes and outcomes of AI prediction models vary widely, and it is essential to evaluate the use in clinical practice using an appropriate study design.
From measures to action: can integrating quality measures provide system-wide insights for quality improvement decision making?
Authors: Khayal Inas S , Sanz Jordan T. 
Published: January 2024

BackgroundQuality improvement decision makers are left to develop an understanding of quality within their healthcare system from a deluge of narrowly focused measures that reflect existing fragmentation in care and lack a clear method for triggering improvement. A one-to-one metric-to-improvement strategy is intractable and leads to unintended consequences. Although composite measures have been used and their limitations noted in the literature, what remains unknown is ‘Can integrating multiple quality measures provide a systemic understanding of care quality across a healthcare system?’MethodsWe devised a four-part data-driven analytic strategy to determine if consistent insights exist about the differential utilisation of end-of-life care using up to eight publicly available end-of-life cancer care quality measures across National Cancer Institute and National Comprehensive Cancer Network-designated cancer hospitals/centres. We performed 92 experiments that included 28 correlation analyses, 4 principal component analyses, 6 parallel coordinate analyses with agglomerative hierarchical clustering across hospitals and 54 parallel coordinate analyses with agglomerative hierarchical clustering within each hospital.ResultsAcross 54 centres, integrating quality measures provided no consistent insights across different integration analyses. In other words, we could not integrate quality measures to describe how the underlying quality constructs of interest—intensive care unit (ICU) visits, emergency department (ED) visits, palliative care use, lack of hospice, recent hospice, use of life-sustaining therapy, chemotherapy and advance care planning—are used relative to each other across patients. Quality measure calculations lack interconnection information to construct a story that provides insights about where, when or what care is provided to which patients. And yet, we posit and discuss why administrative claims data—used to calculate quality measures—do contain such interconnection information.ConclusionWhile integrating quality measures does not provide systemic information, new systemic mathematical constructs designed to convey interconnection information can be developed from the same administrative claims data to support quality improvement decision making.
Quantifying digital health inequality across a national healthcare system
Authors: Zhang Joe , Gallifant Jack , Pierce Robin L , Fordham Aoife , Teo James , Celi Leo , Ashrafian Hutan 
Published: January 2024

ObjectivesDigital health inequality, observed as differential utilisation of digital tools between population groups, has not previously been quantified in the National Health Service (NHS). Deployment of universal digital health interventions, including a national smartphone app and online primary care services, allows measurement of digital inequality across a nation. We aimed to measure population factors associated with digital utilisation across 6356 primary care providers serving the population of England.MethodsWe used multivariable regression to test association of population and provider characteristics (including patient demographics, socioeconomic deprivation, disease burden, prescribing burden, geography and healthcare provider resource) with activation of two independent digital services during 2021/2022.ResultsWe find a significant adjusted association between increased population deprivation and reduced digital utilisation across both interventions. Multivariable regression coefficients for most deprived quintiles correspond to 4.27 million patients across England where deprivation is associated with non-activation of the NHS App.ConclusionResults are concerning for technologically driven widening of healthcare inequalities. Targeted incentive to digital is necessary to prevent digital disparity from becoming health outcomes disparity.
Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via Circulating Tumor DNA
Authors: Liu Li-Peng , Zong Su-Yu , Zhang Ao-Li , Ren Yuan-Yuan , Qi Ben-Quan , Chang Li-Xian , Yang Wen-Yu , Chen Xiao-Juan , Chen Yu-Mei , Zhang Li , Zou Yao , Guo Ye , Zhang Ying-Chi , Ruan Min , Zhu Xiao-Fan 
Published: January 2024

Abstract

Purpose:
Patient-tailored minimal residual disease (MRD) monitoring based on circulating tumor DNA (ctDNA) sequencing of leukemia-specific mutations enables early detection of relapse for pre-emptive treatment, but its utilization in pediatric acute myelogenous leukemia (AML) is scarce. Thus, we aim to examine the role of ctDNA as a prognostic biomarker in monitoring response to the treatment of pediatric AML.

Experimental Design:
A prospective longitudinal study with 50 children with AML was launched, and sequential bone marrow (BM) and matched plasma samples were collected. The concordance of mutations by next-generation sequencing–based BM-DNA and ctDNA was evaluated. In addition, progression-free survival (PFS) and overall survival (OS) were estimated.

Results:
In 195 sample pairs from 50 patients, the concordance of leukemia-specific mutations between ctDNA and BM-DNA was 92.8%. Patients with undetectable ctDNA were linked to improved OS and PFS versus detectable ctDNA in the last sampling (both P &lt; 0.001). Patients who cleared their ctDNA post three cycles of treatment had similar PFS compared with persistently negative ctDNA (P = 0.728). In addition, patients with &gt;3 log reduction but without clearance in ctDNA were associated with an improved PFS as were patients with ctDNA clearance (P = 0.564).

Conclusions:
Thus, ctDNA-based MRD monitoring appears to be a promising option to complement the overall assessment of pediatric patients with AML, wherein patients with continuous ctDNA negativity have the option for treatment de-escalation in subsequent therapy. Importantly, patients with &gt;3 log reduction but without clearance in ctDNA may not require an aggressive treatment plan due to improved survival, but this needs further study to delineate.
Monitoring Minimal Residual Disease in Patients with Multiple Myeloma by Targeted Tracking Serum M-Protein Using Mass Spectrometry (EasyM)
Authors: Fan Huishou , Wang Bing , Shi Lihui , Pan Ni , Yan Wenqiang , Xu Jingyu , Gong Lixin , Li Lingna , Liu Yuntong , Du Chenxing , Cui Jian , Zhu Guoqing , Deng Shuhui , Sui Weiwei , Xu Yan , Yi Shuhua , Hao Mu , Zou Dehui , Chen Xiequn , Qiu Lugui , An Gang 
Published: January 2024

Abstract

Purpose:
We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma.

Experimental Design:
A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10−5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated.

Results:
Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp &gt;0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (&lt;1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26–7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12–0.52) and overall survival (HR, 0.16; 0.06–0.40).

Conclusions:
EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.
Transverse Colon Primary Tumor Location as a Biomarker in Metastatic Colorectal Cancer: A Pooled Analysis of CCTG/AGITG CO.17 and CO.20 Randomized Clinical Trials
Authors: Solar Vasconcelos Joao Paulo , Chen Nan , Titmuss Emma , Tu Dongsheng , Brule Stephanie Y. , Goodwin Rachel , Jonker Derek J. , Price Timothy , Zalcberg John R. , Moore Malcolm J. , Karapetis Christos S. , Siu Lillian , Shapiro Jeremy , Simes John , Gill Sharlene , O'Callaghan Chris J. , Loree Jonathan M. 
Published: January 2024

Abstract

Purpose:
Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC.

Experimental Design:
Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapy-refractory mCRC. Outcomes of patients with RAS/BRAF wild-type (WT) mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location.

Results:
A total of 553 patients were analyzed, 32 (5.8%) with cancers from the transverse, 101 (18.3%) from right, and 420 from (75.9%) left colon. Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care (BSC) for overall survival [OS; median, 5.9 vs. 2.1 months; HR, 0.63; 95% confidence interval (CI), 0.28–1.42; P=0.26] and progression-free survival (PFS; median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26–1.28; P=0.16). Analyzing exclusively patients randomized to cetuximab, right-sided and transverse had comparable outcomes for OS (median, 5.6 vs. 5.9 months; HR, 0.82; 95% CI, 0.50–1.34; P=0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49–1.26; P=0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27–0.67; P=0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31–0.76; P=0.001). Location was not prognostic in patients treated with BSC alone.

Conclusions:
Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.
Spacetime Is Doomed: Time Is an Artifact
Authors: Hoffman Donald D. 
Published: January 2024

Abstract
It is well known that spacetime has no operational meaning beyond the Planck scale. In consequence, many high-energy theoretical physicists are seeking, and finding, new structures entirely beyond spacetime. In light of these advances, we propose that time is not fundamental. The arrow of time is an artifact of projection of a stationary dynamics, entirely beyond spacetime and quantum theory, whose entropy does not increase.
Baltic Abstracts in *-ī-bā
Authors: Ostrowski Norbert 
Published: January 2024

Baltic abstracts in -ība (e.g. Lith. dial. gyvýba ‘life’ / Latv. dzīvība ‘life’) are built on the basis of the old abstract formations in *-ī < IDE *-ih2, acc.sg. *-ijan. From the acc.sg. *-ijan, a new nom.sg. was formed in *-ijā, which supplanted the inherited nom.sg. *-ī. This, in turn, led to the merger of three different categories of derivatives: adjectival abstracts in *-ī (=> *-ijā), adjectival abstracts in *-ijā, and deverbal abstracts in *-ijā. In the current Lithuanian language, all these types are continued by adjectival abstracts in -ė and deverbal abstracts in -ė.
The Politics of State-level COVID-19 Responses in India: Evidence from the First Wave in 2020
Authors: Jain Ritika , Chatterjee Tirtha 
Published: January 2024

We examine if policy interventions to curb the spread of COVID-19 were driven by political factors. We focus on the period between 1 June and 31 August 2020 when lockdowns and testing were the only responses available with governments and policymakers across the world. These instruments are costly. Stringent lockdowns post challenges to livelihoods while only testing without any lockdown accentuates health risks. This choice between life and livelihood becomes all the more pertinent in a developing country like India. We find that state governments in India that had upcoming elections, faced close margin victory in the last election, were non-incumbents and were aligned with the party at the centre adhered to aggressive testing as a strategy and did not impose strict lockdowns to avert losses in economic activity. Such policy responses indicate an attempt to avert possible losses in future elections. These findings confirm the strong role of political factors in policy decisions. JEL Codes: P52, P16, P36
Carbon dioxide production index (VCO2i) predicts hyperlactatemia during cardiopulmonary bypass in pediatric carDiac surGery (pGDP- VCO2i): Study protocol for a nested case-control trial
Authors: Zhang Yan , Xiong Hui , Wang Bo , Luo Ming , Liu Ting , Qin Zhen , Fan Jin-Ge , Zhou Rong-Hua 
Published: January 2024

Background Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with ‘critical thresholds’ for VCO2i reported to be 60 mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults’ standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants. Methods VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3 years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5 min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared. Discussion This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery. Trial registration Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.
Integrating spiritual disposition intervention into behavioral medicine: A case report on systemic lupus erythematosus from India
Authors: Toor Ishanpreet Kaur , Rastogi Kritika , Ajmani Sajal 
Published: January 2024

Background: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. The disease manifests as the body’s immune cells start attacking healthy connective tissue, which affects the skin, kidneys, blood vessels, brain, and other vital organs. As with any other chronic illness, the disease has psychological implications. Purpose: Literature suggests patients with SLE experience anxiety, depression, anger, and stress along with physiological symptoms. There is a strong association between the occurrence of stress and the onset of the disease. These psychological symptoms can be ameliorated through spiritual activities such as meditation, mindfulness, journaling, and reading. Mehtod: This case report is based on the importance of spirituality in the healthcare system. The study focuses on the concept of a whole-person-centered approach to the medical care industry. Spirituality has been proven to have a positive effect on health and illness. Hence, a 10-week intervention with 30 sessions focusing on spiritual dispositions was provided to the patient for this study, along with regular pharmacological treatment. The present case report is of a 56-year-old woman from New Delhi, India, who was diagnosed with SLE 2 years ago. Results: The results reveal the positive effect of the intervention, as it led to a significant decrease in stress levels and depressive symptoms; it also resulted in improved quality of life, an enhanced coping style, and bolstered health hardiness. There was an increase in the score of a spiritual personality. Conlcusion: Spiritual Disposition as an intervention was sucessfull in reducing psychological implications of the disease thus leading to overall positve growth in the patient.
Genistein Alleviates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Regulating Th17/Treg Cell Balance: Implication for the G Protein-coupled Estrogen Receptor
Authors: Shu Baolian , Wu Youxing , Wang Xiaoyang , Hu Jianlan , Zhang Danxia , Gong Xianghao , He Saiqi , Xie Yangzhi , Chen Xuan , Gui Ruohu 
Published: January 2024

Objectives This study aimed to evaluate the therapeutic effects and mechanism of genistein on dextran sulfate sodium-induced mouse model of ulcerative colitis (UC). Materials and Methods A DSS-induced mouse model for UC was used in this study. Mice were then treated with genistein or a combination of genistein and the G protein-coupled estrogen receptor (GPER) antagonist G15. Colon length, disease activity index (DAI), spleen index (SI), histopathological alterations, and integrity of the colonic barrier were evaluated. The expression of inflammatory cytokines and antioxidant capacity were detected. Populations of T helper 17 cells (Th17) and Regulatory T cells (Treg) in the mesenteric lymph nodes (MLN) were analyzed. The expression of a transcription factor for Th17 and Treg in the colonic tissues was detected. Results Genistein treatment significantly alleviated DSS-induced colitis, summarized as increased colonic length, decreased DAI, SI, improved histopathological alterations, and colonic barrier integrity. Genistein treatment restrained pro-inflammatory cytokines and oxidative enzyme release while promoting anti-inflammatory and anti-oxidative enzyme release. Flow cytometry indicated that genistein significantly reduced the Th17 population while boosting Treg populations. Furthermore, genistein inhibited the expression of transcription factors associated with Th17 and promoted the expression of transcription factors associated with Treg in the colonic tissue. Intriguingly, these observed effects of genistein were abolished when UC mice were treated with a combination of genistein and GPER antagonist G15. Conclusion This study suggests that genistein is potent in protecting against DSS-induced colonic injuries by rebalancing Th17/Treg and that GPER may be a vital target for genistein-mediated immunomodulatory effects in UC.