bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the REDS score in hospitalised patients who deteriorated and were admitted to the intensive care unit—a retrospective cohort study
Authors: Sivayoham Narani , O’Mara Harriet , Trenchard Turner Natasha , Sysum Katie , Wicks Georgina , Mason Oliver 
Published: January 2025

BackgroundHospitalised patients are at risk of deterioration and death. Delayed identification and transfer to the intensive care unit (ICU) are known to be associated with increased mortality rates. The Risk-stratification of Emergency Department suspected Sepsis (REDS) score was derived and validated in emergency department patients with suspected sepsis. It is unknown if the REDS score would risk-stratify undifferentiated hospitalised patients who deteriorate.ObjectivesTo validate the REDS score in hospitalised patients who deteriorate.MethodsThis retrospective cohort single-centre study involved hospitalised adult patients who deteriorated and were transferred to the ICU between 1 April 2022 and 31 March 2023. The first admission to the ICU was studied. The National Early Warning Score2 (NEWS2), REDS, Sequential Organ Failure Assessment (SOFA) and change-in-SOFA (ΔSOFA) scores were calculated at the time of referral to the Critical Care Outreach Team (CCOT). The primary outcome measure was in-hospital all-cause mortality. The area under the receiver operator characteristic (AUROC) curves for the scores were compared. Test characteristics at the cut-off points individually and in combination were noted.ResultsOf the 289 patients studied, 91 died. The REDS score had the largest AUROC curve at 0.70 (95% CI 0.65 to 0.75), greater than the NEWS2 score at 0.62 (95% CI 0.56 to 0.68), p=0.03, and similar to the SOFA score 0.67 (95% CI 0.61 to 0.72), p=0.3. The cut-off points for the NEWS2, REDS, SOFA and ΔSOFA scores were >9, >3, >6 and >4, respectively. The sensitivity and specificity for a ΔSOFA≥2 was 91.2% (95% CI 83.4 to 96.1) and 15.7% (95% CI 10.9 to 21.5), respectively. REDS≥4 or NEWS2≥7 had a sensitivity of 87.9% (95% CI 79.4 to 93.8) and specificity of 29.3% (95% CI 23.1 to 36.2).ConclusionThe prognostic performance of the REDS score was similar to the SOFA score, but greater than the NEWS2 score. The REDS score could be used in addition to the established NEWS2 score to risk-stratify hospitalised patients for mortality.
Benefits, problems, and optimal timing of administration of indocyanine green fluorescence cholangiography in laparoscopic cholecystectomy
Authors: Kinami Shinichi , Maruyama Kaori , Sannomiya Yuta , Saito Hitoshi , Takamura Hiroyuki 
Published: January 2025

ObjectivesThe advantages of indocyanine green (ICG) fluorescence cholangiography have been emphasized, but its disadvantages remain unclear. This study investigated the advantages and disadvantages of this modality, particularly the optimal timing of administration of ICG fluorescence.DesignThis was a retrospective analysis of prospectively collected patient data.SettingData were gathered from a single institution.Participants69 patients scheduled for cholecystectomy were included.InterventionsWe administered intravenous ICG injections at three different times: preoperatively (5 mg/body weight (BW), 15 min before incision), morning of the surgery (12.5 mg/BW 4 hours before surgery), and on the day before the surgery (25 mg/BW, 20 hours before surgery). The PINPOINT or SPY-PHI (Stryker) systems were used for fluorescence imaging.Main outcome measuresThe course of the common bile and cystic ducts was identified using fluorescence imaging. The visualization quality was graded on a three-point scale: good, poor, and unobservable.ResultsThere were 17 patients for preoperative administration, 14 on the morning of the surgery, and 38 on the day before the surgery. The cystic duct could not be visualized in five patients because of insufficient dose, impacted gallstones, cystic duct stones, after endoscopic retrograde biliary drainage (ERBD), and severe cholecystitis. The observations were poor in 14 patients. The reasons for the poor visualization were cholecystitis after ERBD and a low signal-to-noise ratio due to intense light emission from the liver, which is a characteristic of preoperative administration.ConclusionThe cystic and common bile ducts were well visualized using ICG fluorescence cholangiography, except in patients with impacted gallstones, cystic duct stones, ERBD, and severe cholecystitis. The most effective timing for ICG administration was the day before the surgery. ICG fluorescence cholangiography is not a substitute for intraoperative cholangiography or preoperative biliary imaging; however, it would be desirable in all patients who undergo cholecystectomy.Trial registration numberjRCTs041180006.
Insular infraorbital neurovascular pedicle labial salivary gland transplantation for the treatment of severe dry eye disease: an IDEAL stage 0, 1 and 2a study
Authors: Yang Ke , Zhou Jing , Wang Yinghui , Piao Yingshi , Li Mei , Cheng Yun , Chen Xiaohong , Jie Ying 
Published: January 2025

ObjectivesTo address the lack of nerve and blood supply after labial salivary gland transplantation (LSGT) resulting in glandular atrophy. We designed a modified LSGT, called insular infraorbital neurovascular pedicle LSGT, and evaluated the postoperative efficacy.DesignThis is a prospective, single-centre, self-contained study.SettingThe research was conducted at Beijing Tongren Hospital, Capital Medical University from July 2019 to March 2024.ParticipantsEight patients (nine eyes) with severe dry eye disease (DED) were enrolled in this study.InterventionsAll patients underwent insular infraorbital neurovascular pedicle LSGT and were followed up for at least 6 months postoperatively.Main outcome measureKey evaluation indices were best-corrected visual acuity (BCVA), Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), Corneal Fluorescence Staining (CFS) score, and Schirmer I test (SIT).ResultsWith a mean follow-up of 17.56±11.72 months, BCVA improved in four eyes and stabilized in five. OSDI score decreased from 59.33±14.37 to 26.27±10.14 (p<0.001). SIT improved from 0.00±0.00 mm to 5.44±2.01 mm (p<0.0001). TBUT increased from 0.23±0.48 s to 5.48±4.67 s (p=0.008). CFS scores decreased from 12.56±2.65 to 7.56±3.09 (p<0.001). All glands remained viable with good blood supply, and no serious complications were observed.ConclusionInsular infraorbital neurovascular pedicle LSGT for severe DED is a feasible and effective treatment, maintaining good secretory capacity and blood supply long-term.Trial registration numberChiCTR2200056015.
Gaps in the evidence for interventions in global drowning research
Authors: Vearing Rebecca , Scarr Justin , Queiroga Ana Catarina , Jagnoor Jagnoor 
Published: January 2025

BackgroundSince 2014, drowning has received increased political attention. Translating this political commitment to saving lives needs policy-supported evidence-informed interventions. An evidence gap map (EGM) was developed, which aims to facilitate the strategic prioritisation of future research and efficient commissioning of interventions.MethodsAvailable evidence was sought by searching four electronic databases using drowning key terms from 2005 to 2023. Peer-reviewed studies, which measured the outcome of a drowning prevention intervention, were included in the EGM. Classification of interventions was guided by the WHO’s recommendations for drowning prevention interventions and strategies. Intervention outcomes were classified into health, social, economic, policy and other supporting outcomes.Results49 intervention studies were identified. Of these, 25 studies were conducted in high-income countries (HICs), 19 in low- and middle-income countries (LMICs), 3 in both HICs and LMICs and 2 were not country specific. Interventions, which used community education, were the most common (n=29, 27%), followed by teaching school-age children swimming and water safety skills (n=13, 12%) and others combined (n=66, 61%). Majority of interventions focused on process outcomes such as knowledge acquisition (n=42, 39%) in comparison with objective outcomes such as incidence of drowning mortality (n=21, 19%). No studies reported on interventions that manage flood risks.ConclusionsKnowledge gaps of effective drowning prevention interventions were identified using an EGM, emphasising the need for methodological advancements reporting on outcomes measures, implementation research and targeted research among high-risk populations in LMICs.
XCL1-secreting CEA CAR-T cells enhance endogenous CD8+T cell responses to tumor neoantigens to confer a long-term antitumor immunity
Authors: Li Xing-Ning , Wang Feifei , Chen Kun , Wu Zhiyuan , Zhang Ruochan , Xiao Chentong , Zhao Fei , Wang Dongmei , Zhao Hong , Ran Yuliang , Qu Chunfeng 
Published: January 2025

BackgroundTherapeutic efficacy of carcinoembryonic antigen (CEA)-specific chimeric antigen receptor (CAR) T cells against colorectal cancer (CRC) remains limited due to the unique characteristics and distinct microenvironments of tumor tissues. We modified CEA-specific CAR-T cells, aiming to stimulate endogenous CD8+T cell responses against neoantigens that were derived from CEA-positive tumors destroyed by the CAR T cells.MethodsIn a conventional CEA CAR (reg-CAR), we modified it to express lymphotactin XCL1 and interleukin (IL)-7 genes, constructing a modified 7XCL1-CAR. By generating the CEA-specific 7XCL1-CAR T cells, we assessed their antitumor efficacy against CRC cells with varying levels of CEA expression, both in cell-cultures and in two strains of tumor-bearing syngeneic mice.ResultsFollowing retroviral transduction, 7XCL1-CAR T cells and reg-CAR T cells exhibited similar positive proportions of CEA-CAR and CD4:CD8 ratios. In co-culture system with CEA-negative CT26 cells, no differences in cytotoxicity were observed between 7XCL1-CAR and reg-CAR T cells. However, in co-culture with CT26.CEAhighand CT26.CEAintcells, 7XCL1-CAR T cells displayed higher cytotoxicity than that reg-CAR T cells after 60 hours. On interaction with CT26.CEA-positive cells, 7XCL1-CAR T cells secreted higher levels of XCL1 and IL-7, effectively recruited the most potent cross-presenting cDC1s (type-I conventional dendritic cells), and sustained the antitumor activity of CAR-T cells. In treating mice that carried tumors derived from universally CEA-positive cells, 7XCL1-CAR T cells exhibited no difference compared with reg-CAR T cells. However, in treating mice with tumors containing both CEA-positive and CEA-negative cells, 7XCL1-CAR T cells displayed greater inhibition than that of reg-CAR-T cells. After treatment of 7XCL1-CAR T cells, tumor-bearing mice exhibited enhanced infiltration of cDC1s, maintained CAR-T activity, and generation of endogenous neoantigen-specific T cells. Consequently, 7XCL1-CAR T cell-treated mice demonstrated resistance to challenge with CEA-negative CT26 cells.ConclusionTreatment with CEA-specific, XCL1-secreting CAR-T cells for CEA-positive tumors promoted the generation of CD8+T cells against tumor neoantigens, mediating a long-term antitumor immunity against heterogeneous CRCs.
Burden of coronary artery calcification in ANCA-associated vasculitis
Authors: Hendrickson Michael , Parakh Anushri , Weber Brittany , Cook Claire , Ahola Catherine , Hedgire Sandeep , Lu Michael , Wallace Zachary S. 
Published: January 2025

BackgroundCardiovascular disease (CVD) is a leading cause of death in ANCA-associated vasculitis (AAV). Screening and primary cardiovascular prevention may improve outcomes.MethodsWe identified patients in the 2002–2019 Mass General Brigham AAV cohort with thoracic CT scans obtained for other clinical purposes. Coronary artery calcium (CAC) scores and age, sex and race-standardised CAC percentiles were calculated. Quantile regression was used to identify differences by ANCA type, and Gray’s test examined differences in major adverse cardiac events by CAC score.ResultsOf 175 included patients, 127 (73%) were MPO-ANCA+and 48 (27%) were PR3-ANCA+. The median CAC score was 17 (IQR 0, 334) and CAC percentile was 45 (IQR 0, 78); 65 (39%) patients had CAC of ≥100. The total CAC score was higher in patients with MPO-ANCA+AAV vs PR3-ANCA+AAV (median 24 vs 1, p=0.003), as was the standardised CAC percentile (50th vs 34th, p=0.02). Of 116 (66%) patients with non-zero CAC scores, only 29 (25%) were on a statin. In a time-to-event analysis, CAC of 100 or higher trended towards association with higher risk of major adverse cardiovascular events (χ2=1.9, p=0.16).ConclusionA majority of patients with AAV had clinically significant CAC. There were differences in CAC burden among those with MPO-ANCA+AAV versus PR3-ANCA+AAV. Although CAC is associated with CVD risk and an indication for statins, the use was inconsistent. The role of CT imaging to screen for CVD and guide primary prevention in AAV requires further study.
Reference intervals of work ability and productivity loss and their use in patients with inflammatory rheumatic and musculoskeletal diseases
Authors: Capelusnik Dafne , Smeets Wouter , Webers Casper , Ramiro Sofia , Nikiphorou Elena , Braekers Roel , Boekel Laura , Wolbink Gertjan , Boonen Annelies 
Published: January 2025

ObjectivesTo establish reference intervals (RIs) for work ability, at-work productivity loss and overall productivity loss in the general working population and to compare work ability and at-work productivity loss of patients with inflammatory rheumatic and musculoskeletal disease (iRMD) with this population.MethodsCross-sectional analysis among patients with iRMDs and population controls without iRMDs having paid work and participating in a Dutch cohort study. They reported on three work outcomes: work ability (0–10), at-work productivity loss and overall productivity loss (0%–100%). A generalised additive model for location, shape and scale parameters was used to establish age-specific RIs and percentile curves for controls. The proportion of patients and controls below each percentile curve was compared.Results413 controls were included; 73% female, with mean age 53 (SD 10) years, 60% had high education, mean work ability was 8.7 (1.6), at-work productivity loss 6.3% (7.2) and overall work productivity loss 11% (25.6).Percentile curves illustrated that work ability and at-work/overall work productivity loss were worse with increasing age. For instance, for work ability, the 95% RI for 22 to 29-year individuals was 5.9–10, while for individuals between 50 and 59 years, it was 4.9–9.1. Patients compared with controls had worse work outcomes, especially for at-work and overall productivity loss.ConclusionWork ability and productivity are not perfect in the general population, based on the newly developed RIs for the three work outcomes. This calls for caution to not overestimate the iRMD impact on work outcomes. Nevertheless, iRMD patients have worse work ability and higher work productivity loss, compared with controls.
Chronic Viral Mimicry Induction following p53 Loss Promotes Immune Evasion
Authors: Ishak Charles A. , Marhon Sajid A. , Tchrakian Naïri , Hodgson Anjelica , Loo Yau Helen , Gonzaga Isabela M. , Peralta Melanie , Lungu Ilinca M. , Gomez Stephanie , Liang Sheng-Ben , Shen Shu Yi , Chen Raymond , Chen Jocelyn , Chatterjee Biji , Wanniarachchi Kevin N. , Lee Junwoo , Zehrbach Nicholas , Hosseini Amir , Mehdipour Parinaz , Sun Siyu , Solovyov Alexander , Ettayebi Ilias , Francis Kyle E. , He Aobo , Wu Taiyi , Feng Shengrui , da Silva Medina Tiago , Campos de Almeida Felipe , Bayani Jane , Li Jason , MacDonald Spencer , Wang Yadong , Garcia Sarah S. , Arthofer Elisa , Diab Noor , Srivastava Aneil , Austin Paul Tran , Sabatini Peter J.B. , Greenbaum Benjamin D. , O’Brien Catherine A. , Shepherd Trevor G. , Tsao Ming Sound , Chiappinelli Katherine B. , Oza Amit M. , Clarke Blaise A. , Rottapel Robert , Lheureux Stephanie , De Carvalho Daniel D. 
Published: January 2025

Abstract
Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through “viral mimicry” responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription toward cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following the loss of the p53 tumor suppressor protein. We report that p53 loss permits the transcription of immunogenic repetitive elements and chronic viral mimicry activation that increases cellular tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity. This selection process can be partially attenuated pharmacologically. Altogether, these results reveal that viral mimicry conditioning following p53 loss promotes immune evasion and may represent a pharmacologic target for early cancer interception.

Significance:
Our landmark discovery of viral mimicry characterized repetitive elements as immunogenic stimuli that cull cancer cells. If expressed repetitive elements cull cancer cells, why does every human cancer express repetitive elements? Our report offers an exciting advancement toward understanding this paradox and how to exploit this mechanism for cancer interception.
Endogenous CD4+ T Cells That Recognize ALK and the NPM1::ALK Fusion Protein Can Be Expanded from Human Peripheral Blood
Authors: Stadler Serena , Blasco Rafael B. , Singh Vijay Kumar , Damm-Welk Christine , Ben-Hamza Amin , Welters Carlotta , Hansmann Leo , Chiarle Roberto , Woessmann Wilhelm 
Published: January 2025

Abstract
Anaplastic lymphoma kinase (ALK) fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. Although ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about ALK-specific CD4+ T cells. We screened peripheral blood of 10 patients with ALK-positive anaplastic large-cell lymphoma in remission and six healthy donors for CD4+ T-cell responses to the whole ALK fusion protein, nucleophosmin 1 (NPM1)::ALK. ALK-specific CD4+ T cells were detected in 15 individuals after stimulation with autologous dendritic cells pulsed with long-overlapping ALK peptide pools. CD4+ T-cell epitopes were predominantly located within three specific regions (p102-188, p257-356, and p593-680) in the ALK portion of the fusion protein. We detected CD4+ T cells in one patient that recognized the NPM1::ALK fusion neoepitope and identified a corresponding T-cell receptor (TCR) by TCRαβ single-cell sequencing. The NPM1::ALK fusion–specific TCR was HLA-DR13–restricted and conferred antigen specificity when expressed in a TCR− reporter cell line (58α−β−). Together, our data provide evidence of ALK-specific CD4+ T cells in human peripheral blood, describe target epitopes in patients, and support the consideration of CD4+ T cells in the development of ALK-specific immunotherapies.
Comprehensive Non-invasive Versus Invasive Approach to Evaluate Cardiac Allograft Vasculopathy in Heart Transplantation: The CCTA-HTx Study
Authors: Belmonte Marta , Paolisso Pasquale , Viscusi Michele Mattia , Beles Monika , Bergamaschi Luca , Sansonetti Angelo , Ohashi Hirofumi , Seki Ruiko , Gallinoro Emanuele , Esposito Giuseppe , Shumkova Monika , Leone Attilio , Masetti Marco , Barbato Emanuele , Verstreken Sofie , Dierckx Riet , Heggermont Ward , Van Keer Jan , Potena Luciano , Pizzi Carmine , Bartunek Jozeph , Vanderheyden Marc 
Published: January 2025

BACKGROUND:
Coronary computed tomography angiography (CCTA) is emerging as a valuable tool for noninvasive surveillance of cardiac allograft vasculopathy (CAV) in patients with heart transplant (HTx). We assessed the diagnostic performance of a comprehensive CCTA-based approach compared with the invasive reference, which includes invasive coronary angiography, intravascular ultrasound, and fractional flow reserve, for detecting CAV.

METHODS:
This was a multicenter prospective study including 37 patients with HTx who underwent CCTA, invasive coronary angiography, intravascular ultrasound, and fractional flow reserve. The comprehensive CCTA-based approach included quantitative and qualitative plaque analysis and functional assessment by fractional flow reserve derived from coronary computed tomography. CAV was diagnosed based on invasive coronary angiography (International Society for Heart and Lung Transplantation criteria) and intravascular ultrasound. Univariable logistic regression analysis was performed to test CCTA-derived predictors of CAV. The area under the curve and accuracy indicators were calculated to evaluate the performance and best cutoffs of CCTA predictors of CAV.

RESULTS:
The median interval between CCTA and HTx was 5 years. Among the 37 recipients, 23 (62.2%) were diagnosed with CAV. The integration of diameter stenosis and plaque morphology (including plaque burden at minimum lumen area >42% and percent atheroma volume >23%) at CCTA yielded the highest diagnostic performance (accuracy, 84%; sensitivity, 83%; specificity, 86%). The integration of ∆fractional flow reserve derived from coronary computed tomography trans-vessel gradient led to increased sensitivity, albeit with decreased specificity and overall accuracy. The noninvasive approach was associated with a lower contrast and radiation dose, compared with the invasive approach.

CONCLUSIONS:
A noninvasive strategy based on CCTA is accurate for managing patients with HTx. CCTA might be considered the preferred imaging modality for annual CAV surveillance after the first year post-HTx.
Dos or Pretium?
Authors: Morelli Ettore 
Published: January 2025

Abstract
During the nineteenth century European missionaries harshly criticised several core components of the African societies they attempted to evangelise, including marriage practices. When bridewealth was involved, marriage was often likened to forms of slavery. However, there were exceptions. This article studies the previously unknown intervention of the Roman Inquisition on the 1867 proposal by the Catholic vicar of Natal in southern Africa to consider marriage as practiced in the kingdom of Lesotho, which included bridewealth, ‘licit’ and acceptable in Catholic rite. By looking in detail at the sources available, the article reconstructs the different positions of three Catholic clergymen on the matter, relates them to the political situation of Lesotho facing colonialism and with the debate within the Catholic Church in the international context of nineteenth-century abolitionism. It thus offers a reflection on the global and local tangle of contradictions and resistances surrounding the status and liberties of women in marriage.