bluuebunny/crossref_metadata_2025_split huggingface dataset:
National census of UK endoscopy services 2021
Authors: Ravindran Srivathsan , Thomas-Gibson Siwan , Bano Madeline , Robinson Emma , Jenkins Anna , Marshall Sarah , Ashrafian Hutan , Darzi Ara , Coleman Mark , Healey Chris 
Published: May 2022

IntroductionThe Joint Advisory Group on Gastrointestinal (GI) Endoscopy (JAG) biennial census provides a unique view of UK endoscopy. The 2021 census was conducted to understand the impact of ongoing pressures, highlighted in the previous census, as well as COVID-19.MethodsThe census was sent to all JAG-registered services in April 2021. Data were analysed across the domains of activity, waiting time targets, workforce, COVID-19, safety, GI bleeding, anaesthetic support, equipment and decontamination. Statistical methods were used to determine associations between domain-specific outcome variables and core demographic data.Results321 services completed the census (79.2% response rate). In the first 3 months of 2021, 57.9% of NHS services met urgent cancer waits, 17.9% met routine waits and 13.4% met surveillance waits. Workforce redeployment was the predominant reason cited for not meeting targets. There were significant regional differences in the proportion of patients waiting 6 or more weeks (p=0.001). During the pandemic, 64.8% of NHS services had staff redeployed and there was a mean sickness rate of 8.5%. Services were, on average, at 79.3% activity compared with 2 years ago. JAG-accredited services are more likely to meet urgent cancer waits, with a lower proportion of patient waiting 6 weeks or more (p=0.03). Over 10% of services stated that equipment shortage interfered with service delivery.ConclusionsServices are adapting to continued pressure and there are signs of a focused response to demand at a time of ongoing uncertainty. This census’ findings will inform ongoing guidance from JAG and relevant stakeholders.
Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study
Authors: Honap Sailish , Al-Hillawi Lulia , Baillie Samantha , Bancil Aaron , Matini Lawrence , Lau Rebecca , Kok Klaartje Bel , Patel Kamal , Walsh Alissa , Irving Peter M , Samaan Mark A 
Published: May 2022

ObjectiveUstekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness of ustekinumab in UC in a real-world setting.Design/methodThis was a multicentre, retrospective, observational cohort study between February 2020 and January 2022. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical remission was defined as a SCCAI≤2. The primary endpoints were rates of corticosteroid-free remission (CSFR) at week 16 and at week 26. Objective outcomes, including faecal calprotectin (FCAL), were also collected.Results110 patients with UC (65% male; median age 40 (IQR range 29–59); 96% with prior biologic and/or tofacitinib exposure) had a median follow-up of 28 weeks (IQR 17–47). CSFR was 36% (18/50) at week 16% and 33% (13/39) at week 26, corresponding with a significant fall in SCCAI from 6 (IQR 4–8) at baseline to 3 (IQR 0–5) at week 26, p<0.001. By week 16, there was improvement of median FCAL measurements, which fell from a baseline of 610 µg/g (IQR 333–1100) to 102 µg/g (IQR 54–674) at week 16. At the end of follow-up, 15% (17/110) had discontinued treatment; 13 patients due to primary non-response or loss of response, and 1 patient for family planning. Treatment was discontinued in three patients due to adverse events.ConclusionIn the largest real-world study to date, ustekinumab was effective with a reassuring safety profile in a refractory cohort of patients.
Impact of adverse childhood experiences on the symptom severity of different mental disorders: a cross-diagnostic study
Authors: Gu Wenjie , Zhao Qing , Yuan Chengmei , Yi Zhenghui , Zhao Min , Wang Zhen 
Published: May 2022

BackgroundAdverse childhood experiences have a significant impact on different mental disorders.ObjectiveTo compare differences in adverse childhood experiences among those with different mental disorders and their relationships in a cross-disorder manner.MethodsThe study included 1513 individuals aged ≥18 years : 339 patients with substance use disorders, 125 patients with schizophrenia, 342 patients with depression, 136 patients with bipolar disorder, 431 patients with obsessive-compulsive disorder (OCD), and 140 healthy controls. The Early Trauma Inventory Self Report-Short Form was used to investigate childhood traumatic experiences, and the Addiction Severity Index, Positive and Negative Syndrome Scale, Hamilton Depression Scale, Young Mania Rating Scale, and Yale-Brown Obsessive-Compulsive Scale were used to assess mental disorder severity. Correlation and multivariate logistic regression were analysed between adverse childhood experiences and clinical features.ResultsLevels of adverse childhood experiences were significantly different among different mental disorders. Moreover, 25.8% of patients with substance use disorders reported childhood trauma, which was significantly higher than found in the other four psychiatric disorder groups. Emotional abuse scores were positively correlated with disease severity: the higher the total trauma score, the more severe the mental disorder.ConclusionsAdverse childhood experiences are a common phenomenon in those with mental disorders, and the level of trauma affects mental disorder severity. Emotional abuse is closely related to many mental disorders. The incidence or severity of mental disorders can be reduced in the future by reducing the incidence of adverse childhood experiences or by timely intervention in childhood trauma.
Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis
Authors: Gan Ranpiao , Wei Yanyan , Wu Guisen , Zeng Jiahui , Hu Yegang , Xu Lihua , Tang Xiaochen , Liu Xiaohua , Liu Haichun , Chen Tao , Wang Jijun , Zhang Tianhong 
Published: May 2022

BackgroundImpaired sensitivity of the skin flush response to niacin is one of the most replicated findings in patients with schizophrenia. However, prior studies have usually focused on postonset psychosis, and little is known about the clinical high-risk (CHR) phase of niacin sensitivity in psychosis.AimsTo profile and compare the niacin flush response among CHR individuals (converters and non-converters), patients with first-episode schizophrenia (FES) and healthy controls (HCs).MethodsSensitivity to four concentrations (0.1–0.0001 M) of aqueous methylnicotinate was tested in 105 CHR individuals, 57 patients with FES and 52 HCs. CHR individuals were further grouped as converters and non-converters according to the 2-year follow-up outcomes. Skin flush response scores were rated on a 4-point scale.ResultsOf the 105 CHR individuals, 21 individuals were lost during the study, leaving 84 CHR individuals; 16 (19.0%) converted to full psychosis at 2 years of follow-up. Flush response scores identified in the CHR samples were characterised as modest degree levels, intermediate between those of HC individuals and patients with FES. The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations (0.01 M, 0.1 M) and longer time points (15 min, 20 min); however, these became comparable with the responses in the HC group at the shorter time points and at lower concentrations. The converters exhibited lower mean flush response scores than the non-converters.ConclusionsAttenuated niacin-induced flushing emerged during the early phase of psychosis. New devices should be developed and verified for objective quantification of skin responses in the CHR population.
Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells
Authors: Alfarano Gabriele , Audano Matteo , Di Chiaro Pierluigi , Balestrieri Chiara , Milan Marta , Polletti Sara , Spaggiari Paola , Zerbi Alessandro , Diaferia Giuseppe Riccardo , Mitro Nico , Natoli Gioacchino 
Published: May 2022

ObjectivePancreatic ductal adenocarcinomas (PDACs) include heterogeneous mixtures of low-grade cells forming pseudoglandular structures and compact nests of high-grade cells organised in non-glandular patterns. We previously reported that low-grade PDAC cells display high expression of interferon regulatory factor 1 (IRF1), a pivotal transcription factor of the interferon (IFN) system, suggesting grade-specific, cell-intrinsic activation of IFN responses. Here, we set out to determine the molecular bases and the functional impact of the activation of IFN-regulated responses in human PDACs.DesignWe first confirmed the correlation between glandular differentiation and molecular subtypes of PDAC on the one hand, and the expression of IRF1 and IFN-stimulated genes on the other. We next used unbiased omics approaches to systematically analyse basal and IFN-regulated responses in low-grade and high-grade PDAC cells, as well as the impact of IRF1 on gene expression programmes and metabolic profiles of PDAC cells.ResultsHigh-level expression of IRF1 in low-grade PDAC cells was controlled by endodermal lineage-determining transcription factors. IRF1-regulated gene expression equipped low-grade PDAC cells with distinctive properties related to antigen presentation and processing as well as responsiveness to IFN stimulation. Notably, IRF1 also controlled the characteristic metabolic profile of low-grade PDAC cells, suppressing both mitochondrial respiration and fatty acid synthesis, which may in part explain its growth-inhibiting activity.ConclusionIRF1 links endodermal differentiation to the expression of genes controlling antigen presentation and processing as well as to the specification of the metabolic profile characteristic of classical PDAC cells.
Early and long-term outcomes of conventional and valve-sparing aortic root replacement
Authors: Jahangiri Marjan , Mani Krishna , Acharya Metesh , Bilkhu Rajdeep , Quinton Paul , Schroeder Frank , Morgan Robert , Edsell Mark 
Published: May 2022

ObjectiveTo determine the early and long-term outcomes of conventional aortic root (ARR) and valve-sparing root replacement (VSRR) using a standard perioperative and operative approach.MethodsWe present prospectively collected data of 609 consecutive patients undergoing elective and urgent aortic root surgery (470 ARR, 139 VSRR) between 2006 and 2020. Primary outcomes were operative mortality and incidence of postoperative complications. Secondary outcomes were long-term survival and requirement for reintervention. Median follow-up was 7.6 years (range 0.5–14.5).Results189 patients (31%) had bicuspid aortic valves and 17 (6.9%) underwent redo procedures. Median cross-clamp time was 88 (range 54–208) min with cardiopulmonary bypass of 108 (range 75–296) min. In-hospital mortality was 10 (1.6%), with transient ischaemic attacks/strokes occurring in 1.1%. In-hospital mortality for VSRR was 0.7%. 12 patients (2.0%) required a resternotomy for bleeding and 14 (2.3%) received haemofiltration. Intensive care unit and hospital stay were 1.7 and 7.0 days, respectively. During follow-up, redo surgery for native aortic valve replacement was required in 1.4% of the VSRR group. Overall survival was 95.1% at 3 years, 93.1% at 5 years, 91.2% at 7 years and 88.6% at 10 years.ConclusionsARR and VSRR can be performed with low mortality and morbidity as well as a low rate of reintervention during the period of long-term follow-up, if performed by an experienced team with a consistent perioperative approach. This series provides contemporary evidence to balance the risks of aortic aneurysms and their rupture at diameters of <5.5 cm against the risks and benefits of surgery.
Contemporary demographics, diagnostics and outcomes in non-bacterial thrombotic endocarditis
Authors: Quintero-Martinez Juan A , Hindy Joya-Rita , El Zein Said , Michelena Hector I , Nkomo Vuyisile T , DeSimone Daniel C , Baddour Larry M 
Published: May 2022

ObjectiveNon-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients.MethodsAdults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up.ResultsForty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively).ConclusionsNBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality.
Beyond the routine CBC: machine learning and statistical analyses identify research CBC parameter associations with myelodysplastic syndromes and specific underlying pathogenic variants
Authors: Pozdnyakova Olga , Niculescu Radu Stefan , Kroll Tracey , Golemme Lisa , Raymond Nolan , Briggs Debra , Kim Annette 
Published: May 2022

AimsGiven the time, expense and clinical expertise required for a myelodysplastic syndrome (MDS) diagnosis, there is a clear need for a cost-effective screening laboratory test that can rapidly and accurately distinguish patients with cytopenias related to MDS from other causes.MethodsWe measured conventional and research use only complete blood cell (CBC) parameters using the Sysmex XN-series haematology analyser in 102 MDS patients (70 patients with active MDS and 32 patients in remission), 43 patients with cytopenia without morphological evidence of MDS and 484 age-adjusted controls. A variety of algorithms, including random forest machine learning, were used to construct parameter-based models to predict the presence of MDS using both CBC and molecular data or CBC data alone and correlated individual pathogenic variants/genetic pathways with CBC parameters changes.ResultsUsing the CBC parameters alone, our predictive model for active MDS showed a 0.86 receiver operating characteristic curve (ROC)/area under the ROC curve (AUC), with 0.87 sensitivity and 0.72 specificity; with the addition of the molecular and demographic status, the ROC/AUC improved to 0.93, sensitivity to 0.89 and specificity to 0.84. The most discriminatory MDS parameters were reflective of dysplastic neutrophil morphology, red cell count fragmentation and degree of platelet immaturity. Specific patterns of parameters were associated with individual gene pathogenic variants or affected pathways.ConclusionsCBC research parameters can be used as an adjunct to the haematological workup of cytopenia(s) to help screen for patients with high likelihood of MDS.
Sociodemographic disparities in COVID-19 burden: changing patterns over four pandemic waves in Israel
Authors: Luxenburg Osnat , Singer Clara , Myers Vicki , Wilf-Miron Rachel , Saban Mor 
Published: May 2022

BackgroundWorldwide, the COVID-19 pandemic hit weakest populations hardest, with socioeconomic (SE), racial and ethnic disparities in COVID-19 burden. The study aimed to analyse patterns of SE and ethnic disparities in morbidity, hospitalisation, and vaccination throughout four pandemic waves.MethodsA retrospective-archive study was conducted in Israel from 11 March 2020 to 1 December 2021, with data on confirmed cases, hospitalisations, mortality and vaccinations (three doses), obtained from the Israeli Ministry of Health’s open COVID-19 database, covering 98.8% of the population, by SE and ethnic characteristics of localities.FindingsAt the outbreak of the pandemic, there was a higher caseload in Jewish, compared with Arab localities. In the second and third waves, low SE and Arab minority populations suffered 2–3 times higher morbidity, with a similar but attenuated pattern in the fourth wave. A similar trend was observed in hospitalisation of confirmed patients. COVID-19-associated mortality did not demonstrate a clear SE gradient.A strong social gradient in vaccine uptake was demonstrated throughout the period, with 71% and 74% double vaccinated in the two highest SE clusters, and 43% and 27% in the two lowest clusters by December 2021. Uptake of the third dose was 57%–60% in the highest SE clusters and 31%–25% in the lowest clusters. SE disparities in vaccine uptake were larger among the younger age groups and gradually increased from first to third doses.ConclusionsIsrael was among the first to lead a rapid vaccination drive, as well as to experience a fourth wave fuelled by diminishing immunity and the delta variant. SE and ethnic disparities were evident throughout most of the pandemic months, though less so for mortality. Despite higher COVID-19 burden, vaccine uptake was lower in disadvantaged groups, with greater disparities in the younger population which widened with subsequent doses.
Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial
Authors: Riccardo Federica , Tarone Lidia , Camerino Mariateresa , Giacobino Davide , Iussich Selina , Barutello Giuseppina , Arigoni Maddalena , Conti Laura , Bolli Elisabetta , Quaglino Elena , Merighi Irene Fiore , Morello Emanuela , Dentini Alfredo , Ferrone Soldano , Buracco Paolo , Cavallo Federica 
Published: May 2022

BackgroundMelanoma is the most lethal form of skin cancer in humans. Conventional therapies have limited efficacy, and overall response is still unsatisfactory considering that immune checkpoint inhibitors induce lasting clinical responses only in a low percentage of patients. This has prompted us to develop a vaccination strategy employing the tumor antigen chondroitin sulfate proteoglycan (CSPG)4 as a target.MethodsTo overcome the host’s unresponsiveness to the self-antigen CSPG4, we have taken advantage of the conservation of CSPG4 sequence through phylogenetic evolution, so we have used a vaccine, based on a chimeric DNA molecule encompassing both human (Hu) and dog (Do) portions of CSPG4 (HuDo-CSPG4). We have tested its safety and immunogenicity (primary objectives), along with its therapeutic efficacy (secondary outcome), in a prospective, non-randomized, veterinary clinical trial enrolling 80 client-owned dogs with surgically resected, CSPG4-positive, stage II–IV oral melanoma.ResultsVaccinated dogs developed anti-Do-CSPG4 and Hu-CSPG4 immune response. Interestingly, the antibody titer in vaccinated dogs was significantly associated with the overall survival. Our data suggest that there may be a contribution of the HuDo-CSPG4 vaccination to the improvement of survival of vaccinated dogs as compared with controls treated with conventional therapies alone.ConclusionsHuDo-CSPG4 adjuvant vaccination was safe and immunogenic in dogs with oral melanoma, with potential beneficial effects on the course of the disease. Thanks to the power of naturally occurring canine tumors as predictive models for cancer immunotherapy response, these data may represent a basis for the translation of this approach to the treatment of human patients with CSPG4-positive melanoma subtypes.
CD4+T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy
Authors: Xiao Minglu , Xie Luoyingzi , Cao Guoshuai , Lei Shun , Wang Pengcheng , Wei Zhengping , Luo Yuan , Fang Jingyi , Yang Xingxing , Huang Qizhao , Xu Lifan , Guo Junyi , Wen Shuqiong , Wang Zhiming , Wu Qing , Tang Jianfang , Wang Lisha , Chen Xiangyu , Chen Cheng , Zhang Yanyan , Yao Wei , Ye Jianqiang , He Ran , Huang Jun , Ye Lilin 
Published: May 2022

BackgroundAntitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8+T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from tumor-derived CD8+T-cell epitopes can drive the functional exhaustion of tumor-specific CD8+T cells. Tumor-specific type-I helper CD4+T (TH1) cells play an important role in the population maintenance and cytotoxic function of exhausted tumor-specific CD8+T cells in the tumor microenvironment. Nonetheless, whether the vaccination strategy targeting MHC-II-restricted CD4+T-cell epitopes to induce tumor-specific TH1 responses can confer effective antitumor immunity to restrain tumor growth is not well studied. Here, we developed a heterologous prime-boost vaccination strategy to effectively induce tumor-specific TH1 cells and evaluated its antitumor efficacy and its capacity to potentiate PD-1/PD-L1 immunotherapy.MethodsListeria monocytogenesvector and influenza A virus (PR8 strain) vector stably expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein-specific I-Ab-restricted CD4+T cell epitope (GP61–80) or ovalbumin-specific CD4+T cell epitope (OVA323-339) were constructed and evaluated their efficacy against mouse models of melanoma and colorectal adenocarcinoma expressing lymphocytic choriomeningitis virus glycoprotein and ovalbumin. The impact of CD4+T cell epitope-based heterologous prime-boost vaccination was detected by flow-cytometer, single-cell RNA sequencing and single-cell TCR sequencing.ResultsCD4+T cell epitope-based heterologous prime-boost vaccination efficiently suppressed both mouse melanoma and colorectal adenocarcinoma. This vaccination primarily induced tumor-specific TH1 response, which in turn enhanced the expansion, effector function and clonal breadth of tumor-specific CD8+T cells. Furthermore, this vaccination strategy synergized PD-L1 blockade mediated tumor suppression. Notably, prime-boost vaccination extended the duration of PD-L1 blockade induced antitumor effects by preventing the re-exhaustion of tumor-specific CD8+T cells.ConclusionCD4+T cell epitope-based heterologous prime-boost vaccination elicited potent both tumor-specific TH1 and CTL response, leading to the efficient tumor control. This strategy can also potentiate PD-1/PD-L1 immune checkpoint blockade (ICB) against cancer.