bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence
Authors: Coronado Gloria D , Jenkins Charisma L , Shuster Elizabeth , Johnson Cheryl , Amy David , Cook Jennifer , Sahnow Samantha , Zepp Jamilyn M , Mummadi Rajasekhara 
Published: January 2024

ObjectiveWe evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative.DesignStudy participants were patients aged 45–75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3–9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups.ResultsWe randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001).ConclusionAmong adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests.Trial registration numberNCT05987709.
Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review
Authors: Kwan Melanie C , Pitman Martha Bishop , Fernandez-del Castillo Carlos , Zhang M Lisa 
Published: January 2024

ObjectiveElevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts.Design1169 pancreatic cysts (1999–2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstratedKRAS,GNAS, orRNF43mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts.ResultsMedian CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases withKRAS/GNAS/RNF43mutations only.ConclusionCyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.
Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial
Authors: Decraecker Lisse , De Looze Danny , Hirsch David P , De Schepper Heiko , Arts Joris , Caenepeel Philip , Bredenoord Albert J , Kolkman Jeroen , Bellens Koen , Van Beek Kim , Pia Fedrica , Peetermans Willy , Vanuytsel Tim , Denadai-Souza Alexandre , Belmans Ann , Boeckxstaens Guy 
Published: January 2024

ObjectiveWe evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study.MethodsNon-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API (‘GRS+API’, composite endpoint) and for GRS and API separately.Results202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081).ConclusionsOur study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS.Trial registration numberThe study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier:NCT01908465).
Comparison of the number of pedestrian and cyclist injuries captured in police data compared with health service utilisation data in Toronto, Canada 2016–2021
Authors: Macpherson Alison K , Zagorski Brandon , Saskin Refik , Howard Andrew William , Harris M Anne , Namin Sima , Rothman Linda 
Published: January 2024

IntroductionPedestrian and cyclist injuries represent a preventable burden to Canadians. Police-reported collision data include information on where such collisions occur but under-report the number of collisions. The primary objective of this study was to compare the number of police-reported collisions with emergency department (ED) visits and hospitalisations in Toronto, Canada.MethodsPolice-reported collisions were provided by Toronto Police Services (TPS). Data included the location of the collision, approximate victim age and whether the pedestrian or cyclist was killed or seriously injured. Health services data included ED visits in the National Ambulatory Care Reporting System and hospitalisations from the Discharge Abstract Database using ICD-10 codes for pedestrian and cycling injuries. Data were compared from 2016 to 2021.ResultsInjuries reported in the health service data were higher than those reported in the TPS for cyclists and pedestrians. The discrepancy was the largest for cyclists treated in the ED, with TPS capturing 7.9% of all cycling injuries. Cyclist injuries not involving a motor vehicle have increased since the start of the pandemic (from 3629 in 2019 to 5459 in 2020 for ED visits and from 251 in 2019 to 430 for hospital admissions).ImplicationsWhile police-reported data are important, it under-reports the burden. There have been increases in cyclist collisions not involving motor vehicles and decreases in pedestrian injuries since the start of the pandemic. The results suggest that using police data alone when planning for road safety is inadequate, and that linkage with other health service data is essential.
‘Every turn can be the last one I do’ - Perceptions of injury risk in high-performance snow sports and its implication for injury prevention
Authors: Bonell Monsonís Oriol , Verhagen Evert , Spörri Jörg , Gouttebarge Vincent , Bolling Caroline 
Published: January 2024

ObjectivesHigh-performance snow sports (HPSS) athletes compete in a performance-driven context with a high risk of injury. While there is a lack of evidence on effective prevention measures in snow sports, this study explored the perspectives and perceptions of HPSS stakeholders on sports injury prevention.MethodsWe conducted an exploratory qualitative study based on the grounded theory principles through 11 semistructured interviews with athletes, coaches and healthcare providers from different national teams about sports injury prevention. The interviews were inductively analysed through constant comparative data analysis.ResultsParticipants defined risk management as a central concept in which they approached injury prevention by assessing, managing and sometimes accepting risks. Many factors, such as athlete-related and external factors, are considered in this process, ultimately influencing their decision-making. Participants acknowledged the value of experience when managing and dealing with risks, a key aspect of their learning process and career development. Within this context, open and trustworthy communication and shared responsibilities among all stakeholders influenced and shaped injury prevention strategies and behaviours. Understanding and balancing out speed and risks was considered pivotal in their daily practice. Therefore, injury prevention awareness, ownership, communication, teamwork and shared responsibilities may contribute to the success of sports injury prevention in HPSS.ConclusionThese findings substantiate the significance of such contextual factors in sports injury prevention. Considering the high-risk nature of HPSS, injury prevention suggests a shift towards risk management strategies, with a strong emphasis on contextual factors and their interactions. Young athletes might benefit from educational interventions centred on developing skills to assess and manage risks.
Predictors of an informative or actionable cytological diagnosis on repeat breast aspiration after an insufficient aspirate: a multicentre retrospective review
Authors: Li Joshua , Lai Billy S W , Ng Joanna K M , Tsang Julia Y S , Tse Gary M K 
Published: January 2024

An insufficient/inadequate diagnosis on fine-needle aspiration cytology (FNAC) of the breast is not an uncommon diagnostic dilemma. This study aims to review the rate and clinical features predicting an informative or actionable diagnosis on repeating breast aspiration after an insufficient aspirate.MethodsUnsatisfactory/insufficient/inadequate or equivalent breast aspirates were retrieved from the involved institutions, and those with a repeat aspiration performed within 365 days were included. Clinical and radiological information were retrieved. Available cytological slides were reviewed.ResultsTotally 539 paired aspirates were retrieved, with 61.2% (n=330/539) and 10.9% (n=59/539) cytological diagnosis being informative (not insufficient) and actionable (not insufficient nor benign) on repeat aspiration. Younger age (p=0.005) was associated with an informative diagnosis and prior radiotherapy (p=0.097) and insufficient aspirates performed under free-hand (p=0.097) trended with an actionable diagnosis. Radiological findings of calcification (p=0.026) and hyperechogenicity (p=0.045), a small lesion size on initial (p=0.037) and repeat (p=0.059) radiological assessment and interval size increment (p=0.019) correlated with informative/actionable diagnoses. Cytomorphological parameters, except for a trend with crushing artefact (p=0.063), do not correlate with the cytologic diagnosis of the repeat aspirate.ConclusionsRepeating breast FNAC on patients after an insufficient diagnosis yields an informative (‘sufficient’) result in over 60% of cases. Small lesions with calcification, hyperechogenicity and/or interval size increment are more likely to yield diagnostic results on repeat aspiration and indicate select patients suitable for repeat FNAC over more invasive procedures. The lack of associations with cytomorphological parameters cautions against overinterpretation of insufficient breast aspirates.
Accuracy of GPT-4 in histopathological image detection and classification of colorectal adenomas
Authors: Laohawetwanit Thiyaphat , Namboonlue Chutimon , Apornvirat Sompon 
Published: January 2024

AimsTo evaluate the accuracy of Chat Generative Pre-trained Transformer (ChatGPT) powered by GPT-4 in histopathological image detection and classification of colorectal adenomas using the diagnostic consensus provided by pathologists as a reference standard.MethodsA study was conducted with 100 colorectal polyp photomicrographs, comprising an equal number of adenomas and non-adenomas, classified by two pathologists. These images were analysed by classic GPT-4 for 1 time in October 2023 and custom GPT-4 for 20 times in December 2023. GPT-4’s responses were compared against the reference standard through statistical measures to evaluate its proficiency in histopathological diagnosis, with the pathologists further assessing the model’s descriptive accuracy.ResultsGPT-4 demonstrated a median sensitivity of 74% and specificity of 36% for adenoma detection. The median accuracy of polyp classification varied, ranging from 16% for non-specific changes to 36% for tubular adenomas. Its diagnostic consistency, indicated by low kappa values ranging from 0.06 to 0.11, suggested only poor to slight agreement. All of the microscopic descriptions corresponded with their diagnoses. GPT-4 also commented about the limitations in its diagnoses (eg, slide diagnosis best done by pathologists, the inadequacy of single-image diagnostic conclusions, the need for clinical data and a higher magnification view).ConclusionsGPT-4 showed high sensitivity but low specificity in detecting adenomas and varied accuracy for polyp classification. However, its diagnostic consistency was low. This artificial intelligence tool acknowledged its diagnostic limitations, emphasising the need for a pathologist’s expertise and additional clinical context.
A national cohort study of community belonging and its influence on premature mortality
Authors: Michalski Camilla , Hurst Mack , Diemert Lori , Mah Sarah M , Helliwell John , Kim Eric S , Rosella Laura C 
Published: January 2024

BackgroundCommunity belonging, an important constituent of subjective well-being, is an important target for improving population health. Ageing involves transitioning across different social conditions thus, community belonging on health may vary across the life course. Using a nationally representative cohort, this study estimates the life stage-specific impact of community belonging on premature mortality.MethodsSix cycles of the Canadian Community Health Survey (2000–2012) were combined and linked to the Canadian Vital Statistics Database (2000–2017). Respondents were followed for up to 5 years. Multivariable-adjusted modified Poisson regression models were used to estimate the relative risk of premature mortality for three life stages: early adulthood (18–35 years), middle adulthood (36–55 years) and late adulthood (56–70 years).ResultsThe final analytical sample included 477 100 respondents. Most reported a ‘somewhat strong’ sense of belonging (45.9%). Compared with their ‘somewhat strong’ counterparts, young adults reporting a ‘somewhat weak’ sense of belonging exhibited an increased relative risk (RR) of 1.76 (95% CI 1.27 to 2.43) for premature mortality, whereas middle-aged adults reporting the same exhibited a decreased RR of 0.82 (95% CI 0.69, 0.98). Among older adults, groups reporting a ‘very strong’ (RR 1.10, 95% CI 1.01, 1.21) or a ‘very weak’ sense (RR 1.14, 95% CI 1.01, 1.28) of belonging exhibited higher RRs for premature mortality.ConclusionThe results demonstrate how community belonging relates to premature mortality differs across age groups underscoring the importance of considering life stage-specific perspectives when researching and developing approaches to strengthen belonging.
Type 2 diabetes, glycaemic traits and upper gastrointestinal cancer risk: a prospective cohort study
Authors: Cao Luyao , Wang Tianpei , Li Huizhang , El Hafa Fadoua , Zhu Xia , Yu Yuhui , Yan Caiwang , Du Lingbin , Zhu Meng , Jin Guangfu 
Published: January 2024

BackgroundType 2 diabetes (T2D) has been linked with site-specific upper gastrointestinal (UGI) cancers during the past decades, but associations are still inconclusive. This study aimed to determine the association between T2D, glycaemic traits (random blood glucose and HbA1c) and UGI cancer (oesophageal and gastric cancer).MethodsIn the present study, based on the large-scale prospective cohort of UK Biobank, we included 452 631 eligible participants. T2D was defined according to baseline self-report data, clinical data and biochemistry data. Random blood glucose and HbA1c were measured at baseline. Polygenic risk score was used to classify individuals into different UGI cancer genetic risks. Multivariable Cox regression models were used to estimate HRs and 95% CIs.ResultsDuring a median follow-up of 10.26 years (IQR: 9.47–10.97), 1392 incident UGI cancer cases were identified. T2D was significantly associated with a 44% increment in UGI cancer risk (95% CI 1.22 to 1.70, p<0.001). Moreover, per SD increase in random blood glucose and HbA1c was associated with 7% (95% CI 1.03 to 1.12, p<0.001) and 6% (95% CI 1.04 to 1.09, p<0.001) increased hazards of developing UGI cancer, respectively. Patients with T2D at high genetic risk had a 2.33-fold hazard of UGI cancer (95% CI 1.66 to 3.28, p<0.001), compared with non-T2D individuals at low genetic risk.ConclusionOur results indicate that T2D and elevated levels of glycaemic traits may be risk factors for incident UGI cancer. Individuals with a high genetic risk and T2D have a significantly increased risk of developing UGI cancer.
Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models
Authors: Hu Jiemiao , Lazar Alexander J , Ingram Davis , Wang Wei-Lien , Zhang Wendong , Jia Zhiliang , Ragoonanan Dristhi , Wang Jian , Xia Xueqing , Mahadeo Kris , Gorlick Richard , Li Shulin 
Published: January 2024

BackgroundThe extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma.MethodIn this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate stroma-enriched osteosarcoma tumors.ResultsRNA sequencing demonstrated that attIL12-T cell treatment altered ECM-related gene expression. Immunohistochemistry staining revealed disruption or elimination of high-density CAFs and ECM in osteosarcoma xenograft tumors following attIL12-T cell treatment, and CAF/ECM density was inversely correlated with T-cell infiltration. Other IL12-armed T cells, such as wild-type IL-12-targeted or tumor-targeted IL-12-T cells, did not disrupt the ECM because this effect depended on the engagement between CSV on the tumor cell and its ligand on the attIL12-T cells. Mechanistic studies found that attIL12-T cell treatment elevated IFNγ production on interacting with CSV+tumor cells, suppressing transforming growth factor beta secretion and in turn upregulating FAS-mediated CAF apoptosis. CAF destruction reshaped the tumor stroma to favor T-cell infiltration and tumor inhibition.ConclusionsThis study unveiled a novel therapy—attIL12-T cells—for targeting CAFs/ECM. These findings are highly relevant to humans because CAFs are abundant in human osteosarcoma.
Adoptive transfer of CMV-specific TCR-T cells for the treatment of CMV infection after haploidentical hematopoietic stem cell transplantation
Authors: Ma Chao , Chen Peng , Du Jishan , Wang Lu , Lu Ning , Sun Jiaojun , Qilong Xu , Wang Yu , Dou Liping , Liu Dai-Hong 
Published: January 2024

BackgroundCytomegalovirus (CMV) reactivation after unmanipulated haploidentical stem cell transplantation (SCT) frequently occurs, causing life-threatening morbidities and transplantation failure. Pre-emptive therapy upon the detection of CMV viremia using antiviral agents is currently the standard of care but it was associated with significant toxicity. The CMV antigen-specific cytotoxic T lymphocyte therapy was limited by the time-consuming manufacture process and relatively low success rate. More effective and safer approaches for the treatment of CMV reactivation after haploidentical SCT are in urgent need.MethodsA single-arm, open-label, phase I clinical trial evaluating the safety and efficacy of CMV-targeting T cell receptor-engineered T (CMV-TCR-T) cell therapy as the first-line pre-emptive therapy for patients with CMV reactivation after haploidentical peripheral blood SCT (PBSCT) was conducted in the Chinese PLA General Hospital. Six patients with CMV reactivation after haploidentical SCT were adoptively transferred by one to three doses of SCT donors-derived CMV-TCR-T cells. This trial was a dose-escalation study with doses ranging from 1×103CMV-TCR-T cells/kg body weight per dose to 5×105CMV-TCR-T cells/kg per dose.ResultsExcept for the grade 1 cytokine release syndrome observed in one patient and mild fever in two patients, no other adverse events were observed. Four patients had response within a month after CMV-TCR-T cell infusion without the administration of any antiviral agents. The other two patients who initially did not respond to CMV-TCR-T cell therapy had salvage ganciclovir and foscarnet administration and then had rapid CMV clearance. The CMV-TCR-T cells displayed overall robust expansion and persistence in the peripheral blood after infusion. The CMV-TCR-T cells were first detected in the peripheral blood of these patients 3–7 days after the first dose of CMV-TCR-T infusion, rapidly expanded and persisted for at least 1–4 months, providing long-term protection against CMV reactivation. In one patient, the CMV-TCR-T cells started to expand even when the anti-graft-versus-host disease reagents were still being used, further indicating the proliferation potential of CMV-TCR-T cells.ConclusionsOur study first showed CMV-TCR-T cell as a highly feasible, safe and effective first-line pre-emptive treatment for CMV reactivation after haploidentical PBSCT.Trial registration numberClinicalTrials.gov Registry (NCT05140187).