bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using set visualisation to find and explain patterns of missing values: a case study with NHS hospital episode statistics data
Authors: Ruddle Roy A , Adnan Muhammad , Hall Marlous 
Published: November 2022

ObjectivesMissing data is the most common data quality issue in electronic health records (EHRs). Missing data checks implemented in common analytical software are typically limited to counting the number of missing values in individual fields, but researchers and organisations also need to understand multifield missing data patterns to better inform advanced missing data strategies for which counts or numerical summaries are poorly suited. This study shows how set-based visualisation enables multifield missing data patterns to be discovered and investigated.DesignDevelopment and evaluation of interactive set visualisation techniques to find patterns of missing data and generate actionable insights. The visualisations comprised easily interpretable bar charts for sets, heatmaps for set intersections and histograms for distributions of both sets and intersections.Setting and participantsAnonymised admitted patient care health records for National Health Service (NHS) hospitals and independent sector providers in England. The visualisation and data mining software was run over 16 million records and 86 fields in the dataset.ResultsThe dataset contained 960 million missing values. Set visualisation bar charts showed how those values were distributed across the fields, including several fields that, unexpectedly, were not complete. Set intersection heatmaps revealed unexpected gaps in diagnosis, operation and date fields because diagnosis and operation fields were not filled up sequentially and some operations did not have corresponding dates. Information gain ratio and entropy calculations allowed us to identify the origin of each unexpected pattern, in terms of the values of other fields.ConclusionsOur findings show how set visualisation reveals important insights about multifield missing data patterns in large EHR datasets. The study revealed both rare and widespread data quality issues that were previously unknown, and allowed a particular part of a specific hospital to be pinpointed as the origin of rare issues that NHS Digital did not know exist.
Respiratory diseases in survivors of adult cancer compared with the general population: a systematic review protocol
Authors: Andresen Kirsty , Carreira Helena , Quint Jennifer K , Bhaskaran Krishnan 
Published: November 2022

IntroductionThere is concern that survivors of adult cancers may be at increased risk of respiratory infections and of exacerbations of pre-existing respiratory conditions. Considering the high prevalence of respiratory disease in the general population, increased respiratory disease risk in survivors of adult cancers could translate into an important impact on morbidity and mortality. The aim of this systematic review is to summarise and assess the quality of all studies comparing respiratory outcomes between adult cancer survivors and individuals with no history of cancer.Methods and analysisThis systematic literature review will be conducted using Medline, EMBASE and Cochrane. We will include cohort or case–control studies that provide a comparative estimate of the risk of a respiratory disease of interest in survivors of adult cancer against a comparator cohort of cancer-free individuals. No geographic, time or language restrictions will be applied. We will assess the risk of bias using the Scottish Intercollegiate Guidelines Network methodology checklists. Results will be summarised by type of respiratory outcome, cancer type and cancer survivorship definition. If sufficient numbers of homogeneous studies are found, summary measures of association will be calculated using random effects meta-analysis models.Ethics and disseminationEthical approval is not applicable to our study. The results will be used to identify evidence gaps and priorities for future research to understand respiratory morbidity in survivors of adult cancers and identify possible mitigation strategies. Results from this review will be disseminated to clinical audiences and submitted to a peer-reviewed journal when completed.Trial registration numberThis study has been registered on PROSPERO (registration number: CRD42022311557).
Blaming, naming and a just culture
Authors: Tasker Adam 
Published: November 2022

BackgroundProblematic cultures within NHS trusts are repeatedly cited as contributing to failures in patient safety and care. The NHS has attempted to address this through promotion of a Just Culture having recognised the improvements made by other safety critical sectors, including aviation, following its adoption. Changing the culture of an organisation is a significant leadership challenge that goes far beyond the revision of management processes.Story of selfI served as a Helicopter Warfare Officer in the Royal Navy prior to commencing medical training. In this article, I reflect on a near miss incident that I was involved in during my previous career and examine the attitudes of myself and my colleagues, and the practices and behaviours of the squadron’s leaders.ConclusionThis article compares my experience within aviation to that of my medical training. Lessons are identified that are relevant to medical training, professional expectations, and the management of clinical incidents to support the implementation of a Just Culture within the NHS.
Gaming for Adherence to Medication using Ehealth in Rheumatoid arthritis (GAMER) study: a randomised controlled trial
Authors: Pouls Bart P H , Bekker Charlotte L , Gundogan Fatma , Hebing Renske CF , van Onzenoort Hein AW , van de Ven Liesbeth I , Vonkeman Harald E , Tieben Rob , Vriezekolk Johanna E , van Dulmen Sandra , Van den Bemt Bart 
Published: November 2022

ObjectiveTo examine the effect on adherence to disease modifying anti-rheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) of a serious game that targeted implicit attitudes toward medication.MethodsA multicentre randomised controlled trial (RCT) was performed with adults with RA that used DMARDs and possessed a smartphone/tablet. Control and intervention groups received care as usual. The intervention group played the serious game at will during 3 months. Game play data and online questionnaires Compliance Questionnaire on Rheumatology (CQR), Beliefs about Medicine Questionnaire (BMQ), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI) were collected. Primary outcome was DMARD implementation adherence operationalised as the difference in proportion of non-adherent participants (<80% taking adherence) between intervention and control group after 3 months using a Chi-squared test. Two sample t-tests and Wilcoxon rank-sum test were performed to test for differences on secondary outcomes.ResultsOf the 110 intervention participants that started the study, 87 participants (79%) installed the game and had a median playtime of 9.7 hours at 3 months. Overall, 186 participants completed the study. Adherence in intervention group (63%) and control group (54%) did not differ significantly (p=0.13) at 3 months. Neither were there differences oberved in CQR continuous score, beliefs about medication (BMQ) or clinical outcomes (HAQ and RADAI).ConclusionA serious game aimed at reinterpreting attitudes toward medication failed to show an effect on adherence to DMARDs or clinical outcomes in patients with RA. The game was played frequently indicating that it can be an effective channel for reaching patients.Trial registration numberNL7217.
The Paleoproterozoic Amer supergroup, Amer Fold Belt, Nunavut: stratigraphy, structure, correlations, and uranium metallogeny
Authors: Jefferson C.W. , Rainbird R.H. , Young Grant M. , White J.C. , Tschirhart V. , Creaser R.A. 
Published: November 2022

The Amer Belt, hosting eleven informal formations of the Amer supergroup, is proposed as type area for four regional Paleoproterozoic sequences (Ps1–Ps4) in central Rae Craton, western Churchill Province. The ca. 1.9–1.865 Ga Snowbird orogeny (DP1) affected only Ps1–Ps3, whereas the ca. 1.87–1.81 Ga Hudsonian orogeny (DP2) affected all four. Sequence Ps1 Ayagaq Lake formation (<2.3 Ga quartzite) initiates as schistose basal polymict orthoconglomerate unconformably overlying paleoweathered Neoarchean rocks. It transitions upward to lower Ps2 Resort Lake formation: gossanous, recessive, graphitic, pyritic-metalliferous phyllite (Re–Os age: 2126 ± 24 Ma). Ps2 conductors beneath the <1.74 Ga Thelon formation have been drilled for unconformity-related uranium. Gradationally overlying siliceous dolomitic marble (Aluminium River formation) completes Ps2. The gradationally overlying lower Ps3 is either foliated calcareous tholeiitic basalt (Five Mile Lake formation) or grey phyllite (Three Lakes formation). These lateral equivalents host strong linear aeromagnetic markers. The Oora Lake formation foliated feldspathic calcareous sandstone gradationally overlies only the Three Lakes formation and underlies the upper Ps3 Showing Lake formation (interbedded phyllite and foliated calcareous arkose) whose two arkose members host laterally continuous disseminated uraninite + magnetite forming linear aeromagnetic markers. Pristine sequence Ps4 molasse, deposited and weakly deformed during DP2, comprises four formations of rhythmically interbedded, deep maroon to pink and green, feldspathic-lithic arenite, conglomerate, and mudstone that unconformably overlie and include clasts of DP1-deformed Ps1–Ps3 + Neoarchean basement. Ps4 detrital zircon (3.05–1.90 Ga) suggests local + distal provenance from south Rae and Slave Cratons, and Taltson–Thelon magmatic zone.
Renormalization of supersymmetric chiral theories in rational spacetime dimensions
Authors: Gracey J. A. 
Published: November 2022

AbstractWe renormalize models with scalar chiral superfields with an odd superpotential to several orders in perturbation theory. These extensions of the cubic Wess–Zumino model are renormalizable in spacetime dimensions which are rational. When endowed with an O(N) symmetry it is shown that they share the same property as their non-supersymmetric counterparts in that at a particular fixed point there is an emergent $$OSp(1|n-1)$$

O
S
p
(
1
|
n
-
1
)

symmetry, where n is the power of the superpotential. This is shown at a loop order beyond that for which it was established in the parallel non-supersymmetric theory.
Evaluation of Krill Meal in Commercial Diets for Juvenile Swimming Crab (Portunus trituberculatus)
Authors: Guo Chen , Jin Min , Jiao Lefei , Xie Shichao , Zhang Xiangsheng , Luo Jiaxiang , Zhu Tingting , Zhou Qicun 
Published: November 2022

An 8-week feeding trial was carried out to assess the effect of dietary krill meal on growth performance and expression of genes related to TOR pathway and antioxidation of swimming crab (Portunus trituberculatus). Four experimental diets (45% crude protein and 9% crude lipid) were formulated to obtain different replacements of fish meal (FM) with krill meal (KM); FM was replaced with KM at 0% (KM0), 10% (KM10), 20% (KM20), and 30% (KM30); fluorine concentration in diets were analyzed to be 27.16, 94.06, 153.81, and 265.30 mg kg-1, respectively. Each diet was randomly divided into 3 replicates; ten swimming crabs were stocked in each replicate (initial weight,

5.62
±
0.19

g

). The results indicated that crabs fed with the KM10 diet had the highest final weight, percent weight gain (PWG), and specific growth rate (SGR) among all treatments (

P
<
0.05

). Crabs fed with the KM0 diet had the lowest activities of total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), glutathione (GSH), and hydroxyl radical scavenging activity and had the highest concentration of malondialdehyde (MDA) in the hemolymph and the hepatopancreas (

P
<
0.05

). In the hepatopancreas, the highest content of 20:5n-3 (EPA) and the lowest content of 22:6n-3 (DHA) were shown in crabs fed with the KM30 diet among all treatments (

P
<
0.05

). With the substitution level of FM with KM gradually increasing from 0% to 30%, the color of the hepatopancreas changed from pale white to red. Expression of tor, akt, s6k1, and s6 in the hepatopancreas was significantly upregulated, while 4e-bp1, eif4e1a, eif4e2, and eif4e3 were downregulated with dietary replacement of FM with KM increasing from 0% to 30% (

P
<
0.05

). Crabs fed with the KM20 diet had notably higher expression of cat, gpx, cMnsod, and prx than those fed with the KM0 diet (

P
<
0.05

). Results demonstrated that 10% replacement of FM with KM can promote growth performance and antioxidant capacity and notably upregulate the mRNA levels of genes related to TOR pathway and antioxidant of swimming crab.
Electroacupuncture Promotes Neuroplasticity of Central Auditory Pathway: An Auditory Evoked Potentials Study
Authors: Chang Chia-Hao , Lin Chia-Der , Hsieh Ching-Liang 
Published: November 2022

Our previous studies found that electroacupuncture at the right Zhongzhu acupoint (TE3) can enhance auditory recovery in rats with noise-induced hearing loss. Here, we investigated the changes in auditory brainstem response (ABR) and long late latency (LLR) evoked potential to explain the mechanisms of electroacupuncture at TE3. The auditory evoked potentials were recorded, including ABR and LLR, at baseline and on day 3 (D3), D5, and D8 after baseline. The 2-Hz electroacupuncture at the right TE3 was applied on D3, D4, and D5 in the electroacupuncture group but not in the control group. In ABR, compared with the control group, the latency shift of waves I (0.298 ± 0.033 vs −0.045 ± 0.057 ms), III (0.718 ± 0.038 vs −0.163 ± 0.130 ms), and V (1.160 ± 0.082 vs −0.207 ± 0.138 ms) on D3 (all

p

<

0.01

) and of wave V (0.616 ± 0.433 vs −0.352 ± 0.209 ms,

p

<

0.05

) on D5 was greater in the electroacupuncture group than that in the control group. Moreover, the interpeak latency shift of I–III (0.420 ± 0.041 vs −0.118 ± 0.177 ms) and I–V (0.863 ± 0.088 vs −0.162 ± 0.156 ms) on D3 (both

p

<

0.05

) and of III–V (0.342 ± 0.193 vs −0.190 ± 0.110 ms) and I–V (0.540 ± 0.352 vs −0.343 ± 0.184 ms) on D5 (both

p

<

0.05

) was greater in the electroacupuncture group than that in the control group. In LLR, the latency shift of P0 was greater in the electroacupuncture group than in the control group on D3 (3.956 ± 2.975 vs −1.178 ± 1.358 ms,

p

<

0.01

) and D5 (2.200 ± 1.889 vs −0.311 ± 1.078 ms,

p

<

0.05

). These findings indicate that electroacupuncture at the right TE3 can modulate the neuroplasticity of the central auditory pathway, including the brain stem and the primary and secondary auditory cortex.
The Oncogenic FOXL2 C134W Mutation Is a Key Driver of Granulosa Cell Tumors
Authors: Llano Elena , Todeschini Anne Laure , Felipe-Medina Natalia , Corte-Torres María D. , Condezo Yazmine B. , Sanchez-Martin Manuel , López-Tamargo Sara , Astudillo Aurora , Puente Xose S. , Pendas Alberto M. , Veitia Reiner A. 
Published: November 2022

AbstractAdult-type granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex cord–stromal tumors. Most AGCTs carry the somatic variant c.402C&gt;G (p.C134W) affecting the transcription factor FOXL2. Germline dominant variants in FOXL2 are responsible for blepharophimosis syndrome, which is characterized by underdevelopment of the eyelid. In this work, we generated a mouse model harboring the C134W variant of FOXL2 to evaluate in vivo the poorly understood oncogenic role of FOXL2. The mutation was dominant regarding eyelid hypoplasia, reminiscent of blepharophimosis syndrome. Interestingly, Foxl2+/C134W female mice had reduced fertility and developed AGCTs through a progression from abnormal ovaries with aberrant granulosa cells to ovaries with stromal hyperplasia and atypia and on to tumors in adut mice. The genes dysregulated in mouse AGCTs exhibited the hallmarks of cancer and were consistent with a gain-of-function of the mutated allele affecting TGFβ signaling. A comparison of these data with previous results on human AGCTs indicated similar deregulated pathways. Finally, a mutational analysis of mouse AGCT transcriptomic data suggested the absence of additional driver mutations apart from FOXL2-C134W. These results provide a clear in vivo example in which a single mutational hit triggers tumor development associated with profound transcriptomic alterations.Significance:A newly generated mouse model carrying a FOXL2 mutation characteristic of adult-type granulosa cell tumors shows that FOXL2 C134W shifts the transcriptome towards a signature of granulosa cell cancer and drives tumorigenesis.
Longitudinal Changes in Immune Activation Serum Biomarkers Prior to Diagnosis and Risk of B-cell NHL Subtypes
Authors: Levin Lynn I. , Ramirez Christina M. , Liao Eileen L. , Guo Hongyu , Kim Bong K. , Marrogi Aizen J. , Magpantay Larry I. , Breen Elizabeth C. , Martínez-Maza Otoniel 
Published: November 2022

Abstract

Background:
To examine the contribution of B-cell activation molecules to B-cell follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), a prospective study was conducted using pre-diagnosis serial serum samples from the US Department of Defense Serum Repository.

Methods:
Each case (n = 142 FL, n = 211 DLBCL) was matched to two controls on age, gender, race, military branch, and blood collection dates. Immune activation molecules (IL1β, IL2, IL4, IL5, IL6, IL10, IL12, CXCL13, IL8, TNFα, IFNγ, GM-CSF, VEGF, sCD30, IgE) were quantified using ELISA or multiplex immunometric (Luminex) assay. Longitudinal data were analyzed using linear mixed modeling. As serial specimens were collected over several years before diagnosis, we evaluated the temporal dynamics of these markers.

Results:
Increased serum levels of sCD30, CXCL13, and to a lesser extent IL10, were associated with both FL and DLBCL in cases compared with controls, with a median follow-up of 5.5 years from the earliest specimen collection to diagnosis date. Significant increasing sCD30 and CXCL13 trajectories for FL and DLBCL subtypes were noted starting at the earliest time points and with IL10 levels increasing significantly at time points closer to diagnosis.

Conclusions:
These results suggest that sCD30, CXCL13, and IL10 may contribute to the etiology of FL and DLBCL and are potential biomarkers for these non–Hodgkin lymphoma subtypes.

Impact:
The increasing trajectories of the B-cell activation molecules, sCD30, CXCL13, and to a lesser extent IL10, may indicate early disease-induced effects or reflect the chronic stimulation of B-cells that promotes the development of FL and DLBCL subtypes.
The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain
Authors: Bowman-Kirigin Jay A. , Desai Rupen , Saunders Brian T. , Wang Anthony Z. , Schaettler Maximilian O. , Liu Connor J. , Livingstone Alexandra J. , Kobayashi Dale K. , Durai Vivek , Kretzer Nicole M. , Zipfel Gregory J. , Leuthardt Eric C. , Osbun Joshua W. , Chicoine Michael R. , Kim Albert H. , Murphy Kenneth M. , Johanns Tanner M. , Zinselmeyer Bernd H. , Dunn Gavin P. 
Published: November 2022

Abstract

The central nervous system (CNS) antigen-presenting cell (APC) that primes antitumor CD8+ T-cell responses remains undefined. Elsewhere in the body, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain parenchyma cDC1 are extremely rare; cDCs localize to the choroid plexus and dura. Thus, whether the cDC1 play a function in presenting antigen derived from parenchymal sources in the tumor setting remains unknown. Using preclinical glioblastoma (GBM) models and cDC1-deficient mice, we explored the presently unknown role of cDC1 in CNS antitumor immunity. We determined that, in addition to infiltrating the brain tumor parenchyma itself, cDC1 prime neoantigen-specific CD8+ T cells against brain tumors and mediate checkpoint blockade-induced survival benefit. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1 equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same APC subsets, we identified a tumor-specific fluorescent metabolite of 5-aminolevulinic acid, which fluorescently labeled tumor cells during fluorescence-guided GBM resection. Together, these data elucidate the specialized behavior of cDC1 and suggest that cDC1 play a significant role in CNS antitumor immunity.
CD73 Inhibits cGAS–STING and Cooperates with CD39 to Promote Pancreatic Cancer
Authors: Jacoberger-Foissac Célia , Cousineau Isabelle , Bareche Yacine , Allard David , Chrobak Pavel , Allard Bertrand , Pommey Sandra , Messaoudi Nouredin , McNicoll Yannic , Soucy Geneviève , Koseoglu Secil , Masia Ricard , Lake Andrew C. , Seo Heewon , Eeles Christopher B. , Rohatgi Neha , Robson Simon C. , Turcotte Simon , Haibe-Kains Benjamin , Stagg John 
Published: November 2022

Abstract

The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells. In mouse transplanted KPC tumors, both CD39 and CD73 on myeloid cells, as well as CD73 on tumor cells, promoted polarization of infiltrating myeloid cells towards an M2-like phenotype, which enhanced tumor growth. CD39 on tumor-specific CD8+ T cells and pancreatic stellate cells also suppressed IFNγ production by T cells. Although therapeutic inhibition of CD39 or CD73 alone significantly delayed tumor growth in vivo, targeting of both ectonucleotidases exhibited markedly superior antitumor activity. CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Accordingly, large-scale pharmacogenomic analyses of human PDAC cell lines revealed significant associations between CD73 expression and gemcitabine chemoresistance. Strikingly, increased DNA damage in CD73-deficient tumor cells associated with activation of the cGAS–STING pathway. Moreover, cGAS expression in mouse KPC tumor cells was required for antitumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.