bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding ethnic inequalities in stillbirth rates: a UK population-based cohort study
Authors: Matthews Ruth J , Draper Elizabeth S , Manktelow Bradley N , Kurinczuk Jennifer J , Fenton Alan C , Dunkley-Bent Jacqueline , Gallimore Ian , Smith Lucy K 
Published: March 2022

ObjectivesTo investigate inequalities in stillbirth rates by ethnicity to facilitate development of initiatives to target those at highest risk.DesignPopulation-based perinatal mortality surveillance linked to national birth and death registration (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK).SettingUK.Participants4 391 569 singleton births at ≥24+0 weeks gestation between 2014 and 2019.Main outcome measuresStillbirth rate difference per 1000 total births by ethnicity.ResultsAdjusted absolute differences in stillbirth rates were higher for babies of black African (3.83, 95% CI 3.35 to 4.32), black Caribbean (3.60, 95% CI 2.65 to 4.55) and Pakistani (2.99, 95% CI 2.58 to 3.40) ethnicities compared with white ethnicities. Higher proportions of babies of Bangladeshi (42%), black African (39%), other black (39%) and black Caribbean (37%) ethnicities were from most deprived areas, which were associated with an additional risk of 1.50 stillbirths per 1000 births (95% CI 1.32 to 1.67). Exploring primary cause of death, higher stillbirth rates due to congenital anomalies were observed in babies of Pakistani, Bangladeshi and black African ethnicities (range 0.63–1.05 per 1000 births) and more placental causes in black ethnicities (range 1.97 to 2.24 per 1000 births). For the whole population, over 40% of stillbirths were of unknown cause; however, this was particularly high for babies of other Asian (60%), Bangladeshi (58%) and Indian (52%) ethnicities.ConclusionsStillbirth rates declined in the UK, but substantial excess risk of stillbirth persists among babies of black and Asian ethnicities. The combined disadvantage for black, Pakistani and Bangladeshi ethnicities who are more likely to live in most deprived areas is associated with considerably higher rates. Key causes of death were congenital anomalies and placental causes. Improved strategies for investigation of stillbirth causes are needed to reduce unexplained deaths so that interventions can be targeted to reduce stillbirths.
Enablers and barriers to newborn screening for sickle cell disease in Africa: results from a qualitative study involving programmes in six countries
Authors: Archer Natasha M , Inusa Baba , Makani Julie , Nkya Siana , Tshilolo Léon , Tubman Venee N , McGann Patrick T , Ambrose Emmanuela Eusebio , Henrich Natalie , Spector Jonathan , Ohene-Frempong Kwaku 
Published: March 2022

ObjectivesGiven the fundamental role of newborn bloodspot screening (NBS) to enable prompt diagnosis and optimal clinical management of individuals with sickle cell disease (SCD), we sought to systematically assess enablers and barriers to implementation of NBS programmes for SCD in Africa using established qualitative research methods.SettingChildbirth centres and NBS laboratories from six countries in East, West and Southern Africa.ParticipantsEight programme leaders involved with establishing and operating NBS programmes for SCD in Angola, Democratic Republic of Congo, Ghana, Liberia, Nigeria and Tanzania.Primary and secondary outcome measuresData obtained through a structured, phased interview approach were analysed using a combination of inductive and deductive codes and used to determine primary themes related to the implementation and sustainability of SCD NBS programmes.ResultsFour primary themes emerged from the analysis relating to governance (eg, pragmatic considerations when deploying overcommitted clinical staff to perform NBS), technical (eg, design and execution of operational processes), cultural (eg, variability of knowledge and perceptions of community-based staff) and financial (eg, issues that can arise when external funding may effectively preclude government inputs) aspects. Key learnings included perceived factors that contribute to long-term NBS programme sustainability.ConclusionsThe establishment of enduring NBS programmes is a proven approach to improving the health of populations with SCD. Organising such programmes in Africa is feasible, but initial implementation does not assure sustainability. Our analysis suggests that future programmes should prioritise government partner participation and funding from the earliest stages of programme development.
Early mobilisation using a mobile patient lift in the intensive care unit: protocol for a randomised controlled trial
Authors: Suzuki Ginga , Kanayama Hiromi , Ichibayashi Ryo , Arai Yoshiaki , Iwanami Yuji , Masuyama Yuka , Yamamoto Saki , Serizawa Hibiki , Nakamichi Yoshimi , Watanabe Masayuki , Honda Mitsuru , Ebihara Satoru 
Published: March 2022

IntroductionIt is important to prevent the deterioration of activities of daily living to improve the long-term prognoses of patients in the intensive care unit (ICU). The patients’ conditions, along with the lack of human and technical resources, often become barriers to achieving early mobilisation after the introduction of mechanical ventilation. We plan to verify the usefulness of a mobile patient lift for early mobilisation.Methods and analysisWe will conduct a single-centre, open-label, randomised controlled trial. The inclusion criteria are as follows: age ≥18 years, independent walking before admission and expected mechanical ventilation for at least 48 hours. The participants will be randomly divided into groups with (intervention group) or without (control group) a mobile lift protocol. A mobile lift will be used in the intervention group. The primary endpoint will be the number of days required to achieve an ICU mobility scale of ≥4 (standing position). The results of the two groups will be analysed using the Student’s t-test.Ethics and disseminationThis study will be conducted in accordance with the Declaration of Helsinki and with the approval of the Toho University Omori Medical Center Ethics Committee (approval number M20259). The results of this study will be presented internationally at academic conferences and published in the literature.Trial registration numberUMIN000044965.
Sex differences in clinical outcomes for obstructive hypertrophic cardiomyopathy in the USA: a retrospective observational study of administrative claims data
Authors: Butzner Michael , Leslie Douglas , Cuffee Yendelela , Hollenbeak Christopher S , Sciamanna Christopher , Abraham Theodore P 
Published: March 2022

ObjectivesTo evaluate sex differences in demographic and clinical characteristics, treatments and outcomes for patients with diagnosed obstructive hypertrophic cardiomyopathy (oHCM) in the USA.SettingRetrospective observational study of administrative claims data from MarketScan Commercial Claims and Encounters Database from IBM Watson Health.ParticipantsOf the 28 million covered employees and family members in MarketScan, 9306 patients with oHCM were included in this analysis.Main outcome measuresoHCM-related outcomes included heart failure, atrial fibrillation, ventricular tachycardia/ fibrillation, sudden cardiac death, septal myectomy, alcohol septal ablation (ASA) and heart transplant.ResultsAmong 9306 patients with oHCM, the majority were male (60.5%, p<0.001) and women were of comparable age to men (50±15 vs 49±15 years, p<0.001). Women were less likely to be prescribed beta blockers (42.7% vs 45.2%, p=0.017) and undergo an implantable cardioverter-defibrillator (1.7% vs 2.6%, p=0.005). Septal reduction therapy was performed slightly more frequently in women (ASA: 0.08% vs 0.05%, p=0.600; SM: 0.35% vs 0.18%, p=0.096), although not statistically significant. Women were less likely to have atrial fibrillation (6.7% vs 9.9%, p<0.001).ConclusionWomen were less likely to be prescribed beta blockers, ACE inhibitors, anticoagulants, undergo implantable cardioverter-defibrillator and have ventricular tachycardia/fibrillation. Men were more likely to have atrial fibrillation. Future research using large, clinical real-world data are warranted to understand the root cause of these potential treatment disparities in women with oHCM.
Factors associated with female genital mutilation: a systematic review and synthesis of national, regional and community-based studies
Authors: El-Dirani Zeinab , Farouki Leen , Akl Christelle , Ali Ubah , Akik Chaza , McCall Stephen J 
Published: March 2022

BackgroundThis systematic review aimed to identify and describe the factors that influence female genital mutilation/cutting (FGM/C).MethodsSearches were conducted in Medline, PsycInfo, Web of Science, Embase and the grey literature from 2009 to March 2020 with no language restrictions, using related MESH terms and keywords. Studies were included if they were quantitative and examined factors associated with FGM/C. Two researchers independently screened studies for inclusion, extracted data and assessed study quality. The direction, strength and consistency of the association were evaluated for determinants, presented as a descriptive summary, and were disaggregated by age and region.ResultsOf 2230 studies identified, 54 published articles were included. The majority of studies were from the African Region (n=29) followed by the Eastern Mediterranean Region (n=18). A lower level of maternal education, family history of FGM/C, or belonging to the Muslim religion (in certain contexts) increased the likelihood of FGM/C. The majority of studies that examined higher paternal education (for girls only) and living in an urban region showed a reduced likelihood of FGM/C, while conflicting evidence remained for wealth. Several studies reported that FGM/C literacy, and low community FGM/C prevalence were associated with a reduced likelihood of FGM/C.ConclusionsThere were several characteristics that appear to be associated with FGM/C, and these will better enable the targeting of policies and interventions. Importantly, parental education may be instrumental in enabling communities and countries to meet the Sustainable Development Goals.
PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment
Authors: Collins Natalie B , Al Abosy Rose , Miller Brian C , Bi Kevin , Zhao Qihong , Quigley Michael , Ishizuka Jeffrey J , Yates Kathleen B , Pope Hans W , Manguso Robert T , Shrestha Yashaswi , Wadsworth Marc , Hughes Travis , Shalek Alex K , Boehm Jesse S , Hahn William C , Doench John G , Haining W Nicholas 
Published: March 2022

BackgroundOncogenes act in a cell-intrinsic way to promote tumorigenesis. Whether oncogenes also have a cell-extrinsic effect on suppressing the immune response to cancer is less well understood.MethodsWe use anin vivoexpression screen of known cancer-associated somatic mutations in mouse syngeneic tumor models treated with checkpoint blockade to identify oncogenes that promote immune evasion. We then validated candidates from this screenin vivoand analyzed the tumor immune microenvironment of tumors expressing mutant protein to identify mechanisms of immune evasion.ResultsWe found that expression of a catalytically active mutation in phospho-inositol 3 kinase (PI3K),PIK3CAc.3140A>G (H1047R) confers a selective growth advantage to tumors treated with immunotherapy that is reversed by pharmacological PI3K inhibition. PIK3CA H1047R-expression in tumors decreased the number of CD8+T cells but increased the number of inhibitory myeloid cells following immunotherapy. Inhibition of myeloid infiltration by pharmacological or genetic modulation of Ccl2 in PIK3CA H1047R tumors restored sensitivity to programmed cell death protein 1 (PD-1) checkpoint blockade.ConclusionsPI3K activation enables tumor immune evasion by promoting an inhibitory myeloid microenvironment. Activating mutations in PI3K may be useful as a biomarker of poor response to immunotherapy. Our data suggest that some oncogenes promote tumorigenesis by enabling tumor cells to avoid clearance by the immune system. Identification of those mechanisms can advance rational combination strategies to increase the efficacy of immunotherapy.
Enhanced antigen cross-presentation in human colorectal cancer-associated fibroblasts through upregulation of the lysosomal protease cathepsin S
Authors: Harryvan Tom J , Visser Marten , de Bruin Linda , Plug Léonie , Griffioen Lisa , Mulder Arend , van Veelen Peter A , van der Heden van Noort Gerbrand J , Jongsma Marlieke LM , Meeuwsen Miranda H , Wiertz Emmanuel JHJ , Santegoets Saskia J , Hardwick James CH , Van Hall Thorbald , Neefjes Jacques , Van der Burg Sjoerd H , Hawinkels Lukas JAC , Verdegaal Els ME 
Published: March 2022

BackgroundCross-presentation of exogenous antigens in HLA-class I molecules by professional antigen presenting cells (APCs) is crucial for CD8+ T cell function. Recent murine studies show that several non-professional APCs, including cancer-associated fibroblasts (CAFs) also possess this capacity. Whether human CAFs are able to cross-present exogenous antigen, which molecular pathways are involved in this process and how this ultimately affects tumor-specific CD8+ T cell function is unknown.MethodsIn this study, we investigated the ability of human colorectal cancer (CRC)-derived CAFs to cross-present neoantigen-derived synthetic long peptides (SLPs), corresponding to tumor-derived mutant peptides, and how this affects tumor-specific T-cell function. Processing of the SLP was studied by targeting components of the cross-presentation machinery through CRISPR/Cas9 and siRNA-mediated genetic ablation to identify the key molecules involved in fibroblast-mediated cross-presentation. Multispectral flow cytometry and killing assays were performed to study the effect of fibroblast cross-presentation on T cell function.ResultsHere, we show that human CRC-derived CAFs display an enhanced capacity to cross-present neoantigen-derived SLPs when compared with normal colonic fibroblasts. Cross-presentation of antigens by fibroblasts involved the lysosomal protease cathepsin S. Cathepsin S expression by CAFs was detected in situ in human CRC tissue, was upregulated in ex vivo cultured CRC-derived CAFs and showed increased expression in normal fibroblasts after exposure to CRC-conditioned medium. Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD137) and increased exhaustion (TIM3, LAG3 and CD39) marker expression.ConclusionThese data indicate that CAFs may directly suppress tumor-specific T cell function in an antigen-dependent fashion in human CRC.
Necroptosis-driving genesRIPK1, RIPK3andMLKL-pare associated with intratumoral CD3+and CD8+T cell density and predict prognosis in hepatocellular carcinoma
Authors: Nicolè Lorenzo , Sanavia Tiziana , Cappellesso Rocco , Maffeis Valeria , Akiba Jun , Kawahara Akihiko , Naito Yoshiki , Radu Claudia Maria , Simioni Paolo , Serafin Davide , Cortese Giuliana , Guido Maria , Zanus Giacomo , Yano Hirohisa , Fassina Ambrogio 
Published: March 2022

BackgroundHepatocellular carcinoma (HCC) is a highly lethal cancer and the second leading cause of cancer-related deaths worldwide. As demonstrated in other solid neoplasms and HCC, infiltrating CD8+T cells seem to be related to a better prognosis, but the mechanisms affecting the immune landscape in HCC are still mostly unknown. Necroptosis is a programmed, caspase-independent cell death that, unlike apoptosis, evokes immune response by releasing damage-associated molecular factors. However, in HCC, the relationship between the necroptotic machinery and the tumor-infiltrating lymphocytes has not been fully investigated so far.MethodsWe investigated the association between the main necroptosis-related genes, that is,RIPK1,RIPK3, MLKL-p, and CD3+/CD8+tumor-infiltrating T cell by RNA-seq data analysis in 371 patients with primary HCC from The Cancer Genome Atlas and then by immunohistochemistry in two independent cohorts of HCC patients from Italy (82) and Japan (86).ResultsOur findings highlighted the immunogenetic role of necroptosis and its potential prognostic role in HCC: RIPK1, RIPK3 and MLKL-p were found significantly associated with intratumoral CD3+and CD8+T cells. In addition, multivariate survival analysis showed that the expression of RIPK1, RIPK3 and MLKL-p was associated with better overall survival in the two independent cohorts.ConclusionsOur results confirmed the immunogenetic properties of necroptosis (NCP) in human HCC, showing that tumor-infiltrating lymphocytes (TILs) and, specifically, CD8+ T cells accumulate in tumors with higher expression of the necroptosis-related genes. These results suggest the importance of further studies to better assess the specific composition, as well as the functional features of the immune environment associated with a necroptotic signature in order to explore new possible diagnostic and immunotherapeutic scenarios.
Spatial profiling reveals association between WNT pathway activation and T-cell exclusion in acquired resistance of synovial sarcoma to NY-ESO-1 transgenic T-cell therapy
Authors: Campbell Katie M , Thaker Maneesha , Medina Egmidio , Kalbasi Anusha , Singh Arun , Ribas Antoni , Nowicki Theodore Scott 
Published: March 2022

BackgroundGenetically engineered T-cell immunotherapies for adoptive cell transfer (ACT) have emerged as a promising form of cancer treatment, but many of these patients develop recurrent disease. Furthermore, delineating mechanisms of resistance may be challenging since the analysis of bulk tumor profiling can be complicated by spatial heterogeneity.MethodsTumor samples were collected from a patient with synovial sarcoma who developed acquired resistance to ACT targeting NY-ESO-1. Biopsies (primary, progressive metastasis, and recurrence) were subjected to bulk tumor DNA and RNA sequencing, as well as high-dimensional spatial profiling of RNA and protein targets. Untreated and progressive lesions were compared with identified patterns associated with acquired resistance to ACT.ResultsGene expression patterns due to immune activity and infiltration were diluted in bulk tumor sequencing. The metastasis was enriched for tumor regions with increasedCTNNB1(encoding beta-catenin), which were negatively associated with the expression of T-cell surface proteins and antigen presentation machinery. Spatial profiling was most highly concordant with bulk sequencing in the lesions with decreased spatial heterogeneity.ConclusionsComplementary use of bulk and spatial profiling enables more accurate interrogation of tumor specimens, particularly to address complex questions regarding immunotherapeutic mechanisms. Our study uses this approach to demonstrate a mechanism of T-cell exclusion and resistance to cellular immunotherapy in synovial sarcoma.
Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy
Authors: Taylor Peter C. , Alten Rieke , Álvaro Gracia Jose María , Kaneko Yuko , Walls Chad , Quebe Amanda , Jia Bochao , Bello Natalia , Terres Jorge Ross , Fleischmann Roy 
Published: March 2022

ObjectivesThis post hoc analysis assessed speed, magnitude and maintenance of pain improvement in patients with early rheumatoid arthritis (RA) receiving baricitinib, baricitinib and methotrexate (MTX), or MTX over 1 year. Cumulative pain and quality of life benefits were also assessed.MethodsRandomised, double-blind, phase 3 study RA-BEGIN (NCT01711359) compared baricitinib 4 mg (N=159), baricitinib 4 mg +MTX (N=215) and MTX (N=210) in patients with RA who had no or limited prior disease-modifying antirheumatic drug treatment. Pain was assessed on a 0–100 mm Visual Analogue Scale (VAS). Proportion of patients with ≥30%, ≥50% and ≥70% pain improvement from baseline; ≤20 mm and ≤10 mm on the pain VAS; and time to achieve pain improvement thresholds were assessed over 52 weeks, as were Patient Global Assessment (PtGA) and 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS) outcomes.ResultsBaricitinib monotherapy or combination with MTX provides greater (least square mean changes (LSM) from baseline −40 mm and −43 mm, respectively) and more rapid (median 12 and 8 weeks to ≥70% improvement, respectively) pain relief than MTX alone (LSM −31 mm, median 20 weeks to ≥70% improvement) over 52 weeks. Baricitinib, alone or combination, provides 9–10 additional weeks of limited to no pain, similar gain in achievable wellness measured through PtGA, and 5–7 additional weeks with change in SF-36 PCS ≥5 vs MTX over 1 year.ConclusionsPatients treated with baricitinib reported significantly greater and more rapid pain relief, more weeks with limited to no pain, and clinically meaningful improvements in physical health than patients treated with MTX alone over 1 year.
Geometric features of middle cerebral artery are associated with spontaneous basal ganglia intracerebral haemorrhage
Authors: Liu Dehan , Zhang Guopeng , Wang Yingliang , Li Jing , Cao Peng , Yin Xiaoxv , Zhou Changjun , Wang Mengdie 
Published: March 2022

Background and purposeHaemodynamics around the middle cerebral artery (MCA) and lenticulostriate arteries is believed to play important roles in the vascular rupture and local haemodynamics is subject to vascular geometry. Nonetheless, the relationship between the geometric features of MCA and spontaneous basal ganglia intracerebral haemorrhage (ICH) has not been investigated. To examine the relationship between the MCA geometric features and spontaneous basal ganglia ICH.MethodsThis study was of retrospective and observational nature. The study recruited 158 consecutive hospitalised patients with consecutive CT-confirmed unilateral spontaneous basal ganglia ICH. Clinical data were extracted from electronic medical records, and imaging data were evaluated by two trained radiologists. The MCA-related geometric features were examined and their relationship with spontaneous basal ganglia ICH was analysed. Haemodynamic analyses under different MCA structural features were conducted.ResultsCompared with the contralateral MCA, the ipsilateral MCA had greater M1 diameter ratio (proximal/distal) and a smaller M1/M2 angle and MCA bifurcation angle (p＜0.01). Imaging study showed differences in the MCA shape in both sides on coronal plane (p＜0.05). These MCA features were significantly correlated with the spontaneous ICH in basal ganglia. The greater M1 diameter ratio (proximal/distal), the inferior-oriented M1, the smaller M1/M2 angle and the superior-oriented M1 conditions increased the pressure, from high to low. The greater M1 diameter ratio (proximal/distal) and the inferior-oriented M1 increased the shear stress at the distal end of M1 segment.ConclusionsThe geometric features of MCA were significantly related to the spontaneous ICH in basal ganglia. The risk of haemorrhage, from high to low, included the greater M1 diameter ratio (proximal/distal), the inferior-oriented M1 (distal end), the smaller M1/M2 angle and the superior-oriented M1. Mechanistically, these vascular structural features contribute to increased vascular wall pressure and shear stress, which eventually lead to haemorrhage.