bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing gaps in our understanding of the drowning patient: a protocol for the retrospective development of an Utstein style database and multicentre collaboration
Authors: Thom Ogilvie , Roberts Kym , Leggat Peter A , Devine Susan , Peden Amy E , Franklin Richard Charles 
Published: February 2023

IntroductionThis retrospective observational study aims to create a comprehensive database of the circumstances of drowning (including care provided and outcomes of care) to report against the Utstein style for drowning (USFD) for patients presenting to the emergency department (ED). Four areas will be examined: a feasibility study of the USFD; a comparison of classification and prognostication systems; examination of indications and efficacy of different ventilation strategies; and differences in the circumstances, severity, treatment and outcomes of drowning by sex and gender.Methods and analysisThis protocol outlines retrospective data collection for all patients presenting to EDs of the Sunshine Coast Hospital and Health Service in Queensland, Australia with the presenting problem or discharge diagnosis of drowning or immersion between 2015 and 2022. Patients computerised health records (emergency medical service record, pathology, radiology results, medical and nursing notes for ED, inpatient units and intensive care units) will be used to extract data for entry into an USFD database. Descriptive (eg, median, IQR) and inferential statistical analyses (eg, analysis of variance) will be used to answer the separate research questions. Development of an International Drowning Registry using the USFD dataset and the Research Electronic Data Capture (REDCap) web application is discussed.Ethics and disseminationThis study has been approved by Metro North Human Research and Ethics Committee (Project No: 49754) and James Cook University Human Research Ethics Committee (H8014). It has been endorsed by national drowning prevention organisations Royal Life Saving Society Australia (RLSSA) and Surf Life Saving Australia (SLSA). Study findings will provide data to better inform clinical management of drowning patients and provide an evidence base on sex and gender differences in drowning. Results will be disseminated through peer review publications, conference presentations and media releases. Results will also be disseminated through RLSSA and SLSA membership of the Australian and New Zealand Resuscitation Council and the Australian Water Safety Council.
Development and validation of a prediction model for the prolonged length of stay in Chinese patients with lower extremity atherosclerotic disease: a retrospective study
Authors: Wang Xue , Yang Yu , Zhang Jian , Zang Shuang 
Published: February 2023

ObjectivesThis study aims to develop and internally validate a prediction model, which takes account of multivariable and comprehensive factors to predict the prolonged length of stay (LOS) in patients with lower extremity atherosclerotic disease (LEAD).DesignThis is a retrospective study.SettingChina.Participants, primary and secondary outcomesData of 1694 patients with LEAD from a retrospective cohort study between January 2014 and November 2021 were analysed. We selected nine variables and created the prediction model using the least absolute shrinkage and selection operator (LASSO) regression model after dividing the dataset into training and test sets in a 7:3 ratio. Prediction model performance was evaluated by calibration, discrimination and Hosmer-Lemeshow test. The effectiveness of clinical utility was estimated using decision curve analysis.ResultsLASSO regression analysis identified age, gender, systolic blood pressure, Fontaine classification, lesion site, surgery, C reactive protein, prothrombin time international normalised ratio and fibrinogen as significant predictors for predicting prolonged LOS in patients with LEAD. In the training set, the prediction model showed good discrimination using a 500-bootstrap analysis and good calibration with an area under the receiver operating characteristic of 0.750. The Hosmer-Lemeshow goodness of fit test for the training set had a p value of 0.354. The decision curve analysis showed that using the prediction model both in training and tests contributes to clinical value.ConclusionOur prediction model is a valuable tool using easily and routinely obtained clinical variables that could be used to predict prolonged LOS in patients with LEAD and help to better manage these patients in routine clinical practice.
Optimising diagnosis and treatment of tuberculosis infection in community and primary care settings in two urban provinces of Viet Nam: a cohort study
Authors: Vo Luan Nguyen Quang , Nguyen Viet Nhung , Nguyen Nga Thi Thuy , Dong Thuy Thi Thu , Codlin Andrew , Forse Rachel , Truong Huyen Thanh , Nguyen Hoa Binh , Dang Ha Thi Minh , Truong Vinh Van , Nguyen Lan Huu , Mac Tuan Huy , Le Phong Thanh , Tran Khoa Tu , Ndunda Nduku , Caws Maxine , Creswell Jacob 
Published: February 2023

ObjectivesTo end tuberculosis (TB), the vast reservoir of 1.7–2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the feasibility of using interferon-γ release assays (IGRAs) at lower healthcare levels and the comparative performance of 3-month and 9-month daily TPT regimens (3HR/9H).Design, setting, participants and interventionThis cohort study was implemented in two provinces of Viet Nam from May 2019 to September 2020. Participants included household contacts (HHCs), vulnerable community members and healthcare workers (HCWs) recruited at community-based TB screening events or HHC investigations at primary care centres, who were followed up throughout TPT.Primary and secondary outcomesWe constructed TBI care cascades describing indeterminate and positivity rates to assess feasibility, and initiation and completion rates to assess performance. We fitted mixed-effects logistic and stratified Cox models to identify factors associated with IGRA positivity and loss to follow-up (LTFU).ResultsAmong 5837 participants, the indeterminate rate was 0.8%, and 30.7% were IGRA positive. TPT initiation and completion rates were 63.3% (3HR=61.2% vs 9H=63.6%; p=0.147) and 80.6% (3HR=85.7% vs 9H=80.0%; p=0.522), respectively. Being male (adjusted OR=1.51; 95% CI: 1.28 to 1.78; p<0.001), aged 45–59 years (1.30; 1.05 to 1.60; p=0.018) and exhibiting TB-related abnormalities on X-ray (2.23; 1.38 to 3.61; p=0.001) were associated with positive IGRA results. Risk of IGRA positivity was lower in periurban districts (0.55; 0.36 to 0.85; p=0.007), aged <15 years (0.18; 0.13 to 0.26; p<0.001), aged 15–29 years (0.56; 0.42 to 0.75; p<0.001) and HCWs (0.34; 0.24 to 0.48; p<0.001). The 3HR regimen (adjusted HR=3.83; 1.49 to 9.84; p=0.005) and HCWs (1.38; 1.25 to 1.53; p<0.001) showed higher hazards of LTFU.ConclusionProviding IGRAs at lower healthcare levels is feasible and along with shorter regimens may expand access and uptake towards meeting TPT targets, but scale-up may require complementary advocacy and education for beneficiaries and providers.
Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects
Authors: Bai Haiyan , Padron Alvaro S , Deng Yilun , Liao Yiji J , Murray Clare J , Ontiveros Carlos , Kari Suresh J , Kancharla Aravind , Kornepati Anand V R , Garcia Myrna , Reyes Ryan Michael , Gupta Harshita B , Conejo-Garcia Jose R , Curiel Tyler 
Published: February 2023

BackgroundTumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies.MethodsWe performed a drug screen for tumor cell PDL1 depleting drugs that identified Food and Drug Administration (FDA)-approved chlorambucil and also 9-[2-(phosphonomethoxy)ethyl] guanine. We used in vitro and in vivo assays to evaluate treatment and signaling effects of pharmacological tumor PDL1 depletion focused on chlorambucil as FDA approved, alone or plus αPDL1.ResultsPDL1-expressing mouse and human ovarian cancer lines and mouse melanoma were more sensitive to chlorambucil-mediated proliferation inhibition in vitro versus corresponding genetically PDL1-depleted lines. Orthotopic peritoneal PDL1-expressing ID8agg ovarian cancer and subcutaneous B16 melanoma tumors were more chlorambucil-sensitive in vivo versus corresponding genetically PDL1-depleted tumors. Chlorambucil enhanced αPDL1 efficacy in tumors otherwise αPDL1-refractory, and improved antitumor immunity and treatment efficacy in a natural killer cell-dependent manner alone and plus αPDL1. Chlorambucil-mediated PDL1 depletion was relatively tumor-cell selective in vivo, and treatment efficacy was preserved in PDL1KO hosts, demonstrating tumor PDL1-specific treatment effects. Chlorambucil induced PDL1-dependent immunogenic tumor cell death which could help explain immune contributions. Chlorambucil-mediated PDL1 reduction mechanisms were tumor cell-type-specific and involved transcriptional or post-translational mechanisms, including promoting PDL1 ubiquitination through the GSK3β/β-TRCP pathway. Chlorambucil-mediated tumor cell PDL1 depletion also phenocopied genetic PDL1 depletion in reducing tumor cell mTORC1 activation and tumor initiating cell content, and in augmenting autophagy, suggesting additional treatment potential.ConclusionsPharmacological tumor PDL1 depletion with chlorambucil targets tumor-intrinsic PDL1 signaling that mediates treatment resistance, especially in αPDL1-resistant tumors, generates PDL1-dependent tumor immunogenicity and inhibits tumor growth in immune-dependent and independent manners. It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including αPDL1-refractory cancers, and is rapidly clinically translatable.
Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases
Authors: Zhang Chong , Wang Xiang-Yu , Zuo Jie-Liang , Wang Xue-Fu , Feng Xiao-Wen , Zhang Bo , Li Yi-Tong , Yi Chen-He , Zhang Peng , Ma Xiao-Chen , Chen Zhen-Mei , Ma Yue , Han Jia-Hao , Tao Bao-Rui , Zhang Rui , Wang Tian-Qi , Tong Li , Gu Wang , Wang Si-Yu , Zheng Xiao-Fei , Yuan Wen-Kang , Kan Zi-Jie , Fan Jie , Hu Xiang-Yang , Li Jun , Zhang Chao , Chen Jin-Hong 
Published: February 2023

BackgroundTertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).Methods603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.ResultsT score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.ConclusionsThe distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.
Deployment of whole genome next-generation sequencing of SARS-CoV-2 in a military maritime setting
Authors: Bosworth Andrew , Robson J , Lawrence B , Casey A L , Fair A , Khanam S , Hudson C , O'Shea M K 
Published: February 2023

BackgroundSARS-CoV-2 can spread rapidly on maritime platforms. Several outbreaks of SARS-CoV-2 have been reported on warships at sea, where transmission is facilitated by living and working in close quarters. Core components of infection control measures such as social distancing, patient isolation and quarantine of exposed persons are extremely difficult to implement. Whole genome sequencing (WGS) of SARS-CoV-2 has facilitated epidemiological investigations of outbreaks, impacting on outbreak management in real time by identifying transmission patterns, clusters of infection and guiding control measures. We suggest such a capability could mitigate against the impact of SARS-CoV-2 in maritime settings.MethodsWe set out to establish SARS-CoV-2 WGS using miniaturised nanopore sequencing technology aboard the Royal Fleet Auxiliary ARGUS while at sea. Objectives included designing a simplified protocol requiring minimal reagents and processing steps, the use of miniaturised equipment compatible for use in limited space, and a streamlined and standalone data analysis capability to allow rapid in situ data acquisition and interpretation.ResultsEleven clinical samples with blinded SARS-CoV-2 status were tested at sea. Following viral RNA extraction and ARTIC sequencing library preparation, reverse transcription and ARTIC PCR-tiling were performed. Samples were subsequently barcoded and sequenced using the Oxford Nanopore MinION Mk1B. An offline version of the MinKNOW software was used followed by CLC Genomics Workbench for downstream analysis for variant identification and phylogenetic tree construction. All samples were correctly classified, and relatedness identified.ConclusionsIt is feasible to establish a small footprint sequencing capability to conduct SARS-CoV-2 WGS in a military maritime environment at sea with limited access to reach-back support. This proof-of-concept study has highlighted the potential of deploying such technology in the future to military environments, both maritime and land-based, to provide meaningful clinical data to aid outbreak investigations.
Lipid management in systemic lupus erythematosus according to risk classifiers suggested by the European Society of Cardiology and disease-related risk factors reported by the EULAR recommendations
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G 
Published: February 2023

BackgroundThe European Alliance of Associations for Rheumatology recommended that lipid-lowering therapy (LLT) in systemic lupus erythematosus (SLE) should follow general population guidelines. We examined the eligibility for LLT in SLE according to Systematic Coronary Risk Evaluation (SCORE), with and without the addition of vascular ultrasound (VUS) and disease-related features.Methods210 patients with SLE without prior cardiovascular events, diabetes or antiphospholipid syndrome underwent cardiovascular risk assessment with SCORE. LLT eligibility was evaluated in low-risk and moderate-risk patients following European Society of Cardiology (ESC) guidelines. Atherosclerotic plaques on carotid ultrasound (cUS)) and carotid and femoral ultrasound (cfUS), prolonged disease duration (PDD, ≥10 years), failure to achieve lupus low disease activity state (LLDASno), cumulative glucocorticoid ‘cardiovascular harm’ dose (GCCVH, optimal cut-off to predict ultrasound-detected plaques) and antiphospholipid antibody positivity (aPLpos) were tested as SCORE risk enhancers for classification ability (phi coefficient) and agreement (Cohen’s kappa) using SCORE plus cfUS as a reference modality for LLT eligibility.ResultsPlaques were detected in 9.9% of low-risk cases and 54.6% of moderate-risk cases. SCORE alone would indicate 0% of low-risk patients and 3% of moderate-risk patients for LLT eligibility. According to SCORE+cfUS, 9.9% of low-risk patients and 57.6% of moderate-risk patients, respectively, would be eligible for LLT based on ESC guidelines. Ιn low-risk/moderate-risk patients, phi values for SCORE+PDD, GCCVH(cut-off ≥11 g), LLDASnoand aPLposin antiplatelet-naïve antiphospholipid antibody-positive (aPLpos/APT−) cases were 0.06/0.13, 0.23/0.20, 0.07/0.16 and 0.06/0.33, respectively. Agreement for LLT eligibility to SCORE+cfUS was better for SCORE+PDD in moderate-risk patients and for SCORE+cUS in both groups of patients. SCORE+GCCVH and SCORE+aPLposshowed at least fair agreement (kappa ≥0.20) to SCORE+cfUS in low-risk or moderate-risk and in aPLpos/APT− moderate-risk patients, respectively.ConclusionDisease-related and VUS features, in addition to SCORE, may help to improve LLT decision making in SLE. GCCVHand aPLposimprove LLT eligibility similarly and to a greater degree than PDD or LLDASno.
OFC-Delaunay triangulation: A new efficient algorithm for merging two adjacent Delaunay triangulations
Authors: An Phan Thanh , Duc Trinh Minh , Oanh Dang Thi 
Published: February 2023

In this paper, we present an efficient algorithm, namely Orienting and Final Circles (OFC)-Delaunay Triangulation, for constructing the Delaunay triangulation of a finite planar point set using the idea of the Method of Orienting Curves (introduced by Phu in Zur Lösung einer regulären Aufgabenklasse der optimalen Steuerung im Groen mittels Orientierungskurven, Optimization 18(1) (1987) 65–81 and Ein konstruktives Lösungsverfahren für das Problem des Inpolygons kleinsten Umfangs von J. Steiner, Optimization 18(3) (1987) 349–359). The concepts of orienting and final circles are introduced. The Delaunay edges are determined by orienting circles and a final circle. Our algorithm has [Formula: see text]([Formula: see text]) worst-case running time. The algorithm is implemented in Python and some numerical examples are presented.
IL18 Receptor Signaling Regulates Tumor-Reactive CD8+ T-cell Exhaustion via Activation of the IL2/STAT5/mTOR Pathway in a Pancreatic Cancer Model
Authors: Lutz Veronika , Hellmund Veronique M. , Picard Felix S.R. , Raifer Hartmann , Ruckenbrod Teresa , Klein Matthias , Bopp Tobias , Savai Rajkumar , Duewell Peter , Keber Corinna U. , Weigert Andreas , Chung Ho-Ryun , Buchholz Malte , Menke André , Gress Thomas M. , Huber Magdalena , Bauer Christian 
Published: February 2023

AbstractIntratumoral cytotoxic CD8+ T cells (CTL) enter a dysfunctional state characterized by expression of coinhibitory receptors, loss of effector function, and changes in the transcriptional landscape. Even though several regulators of T-cell exhaustion have been identified, the molecular mechanisms inducing T-cell exhaustion remain unclear. Here, we show that IL18 receptor (IL18R) signaling induces CD8+ T-cell exhaustion in a murine pancreatic cancer model. Adoptive transfer of Il18r−/− OT-1 CD8+ CTLs resulted in enhanced rejection of subcutaneous tumors expressing ovalbumin (OVA) as a model antigen (PancOVA), compared with wild-type OT-1 CTLs. Transferred intratumoral IL18R-deficient CTLs expressed higher levels of effector cytokines TNF and IFNγ and had reduced expression of coinhibitory receptors (PD-1, TIM-3, 2B4, LAG-3) and the transcription factors Eomes and TOX. Lower expression of coinhibitory receptors and TOX on IL18R-deficient versus IL18R-sufficient CD8+ T cells were confirmed in an orthotopic KPC model. IL18R-induced T-cell exhaustion was regulated by IL2/STAT5 and AKT/mTOR pathways, as demonstrated in an in vitro exhaustion assay. Concordantly, mice deficient in NLRP3, the molecular complex activating IL18, had decreased expression of coinhibitory receptors on intratumoral T cells and similar changes in signaling pathways at the transcriptome level. Thus, molecular pathways promoting T-cell exhaustion indicate an involvement of an NLRP3-expressing tumor microenvironment, which mediates IL18 release. The Cancer Genome Atlas analysis of patients with pancreatic carcinoma showed an association between NLRP3-mediated IL18 signaling and shorter survival. These findings indicate NLRP3-mediated IL18R signaling as a regulator of intratumoral T-cell exhaustion and a possible target for immunotherapy.See related Spotlight by Stromnes, p. 400
ОСОБЛИВОСТІ ПЕРЕБІГУ COVID-19 У ХВОРИХ НА ХРОНІЧНІ ГЕПАТИТИ В І С
Authors: Андрейчин М. А. , Копча В. С. 
Published: February 2023

Коронавірусна хвороба 2019 (COVID-19) поширилася по всьому світу. Оскільки у пацієнтів з COVID-19 ураження печінки зазвичай має змішаний генез, особливості перебігу коронавірусної хвороби при фонових хронічних гепатитах B (ХГВ) і С (ХГС) остаточно не з’ясовані.
У цьому огляді наведено відомості про порівняння демографічної характеристики, результатів фізикальних і лабораторних обстежень, у т. ч. госпітальної летальності хворих на COVID-19 із супутніми ХГВ і ХГС та без цих коморбідних захворювань.
Для вивчення факторів ризику тяжкості захворювання та летальності були використані одно- та багатозмінні логістичні та регресійні моделі Кокса.
У більшості хворих на ХГВ COVID-19 перебігав тяжко. Крім традиційних печінкових проб (рівні аланін­амінотрансферази – АлАТ, аспартатамінотрансферази – АсАТ, лужної фосфатази – ЛФ, загального білірубіну), дослідники вивчали такі фактори, як активність лактатдегідрогенази – ЛДГ (≥245 ОД/л, коефіцієнт ризику (HR) = 8,639, 95 % достовірний інтервал (ДІ) = 2,528-29,523, р<0,001) та рівень біомаркера коагуляції крові – D-димеру (≥0,5 мкг/мл, HR = 4,321, 95 % ДІ = 1,443-12,939; р<0,005), зниження показника альбуміну (<35 г/л, HR = 0,131, 95 % ДІ = 0,048-0,361; р<0,001), а також альбуміно-глобуліновий коефіцієнт (<1,5, HR = 0,123, 95 % ДІ = 0,017-0,918; р<0,05).
Встановлено, що у хворих на COVID-19 на фоні ХГВ значно вища ймовірність тяжкого перебігу хвороби, а також смерті. ХГС призводить до посилення вірулентності SARS-CoV-2, незалежно від початкових супутніх захворювань, лабораторних показників при госпіталізації чи ураження печінки, спричиненого SARS-CoV-2. Це може бути пов’язано з позапечінковими ефектами ХГС, що призводить до цитокін-опосередкованого запалення та ендотеліальної дисфункції. Таке поєднання захворювань є сильним предиктором внут­рішньолікарняної летальності.