bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elements of the Philosophy of ‘Right’
Authors: Westphal Jonathan 
Published: December 2022

AbstractIn the following paper, I discuss the adjectival uses of the English word ‘right’, in ethical and nonethical settings. I distinguish four distinct but related uses. In the central use, which includes the typical ethical applications, what is right is what conforms to a norm, or rule. The emphasis can be on the norm itself, or on the conforming to the norm. The view I offer is not original. It is to be found in the works of T.M. Scanlon, T.H. Green, R.M. Hare and W.D. Ross.1
Exploring the utility of synthetic data to extract more value from sensitive health data assets: A focused example in perinatal epidemiology
Authors: Braddon Amy Elise , Robinson Suzanne , Alati Rosa , Betts Kim S. 
Published: December 2022

AbstractBackgroundPrivacy, access and security concerns can hinder the availability of health data for research. The use of synthesised data in place of de‐identified electronic health records (EHRs) presents an opportunity to conduct research while minimising privacy concerns.ObjectivesTo examine whether synthesised data can replicate two prenatal epidemiological associations: between prenatal smoking and lower birthweight, and between prenatal mood disorders and lower birthweight, using data synthesised from de‐identified health administrative data collections.MethodsWe generated two synthetic datasets, using parametric and non‐parametric data generating methods, and examined the synthetic data for evidence of privacy concerns. Next, univariable and multivariable logistic regression was utilised to estimate the associations in both synthetic datasets, with results then compared to the real data.ResultsBoth synthesised datasets performed well in identifying the reduction in birthweight associated with prenatal smoking, while the non‐parametric data underestimated the reduction in birthweight associated with prenatal mood disorders. Improbable relationships between some variables were identified in the parametric synthesised data, however, these can be addressed with simple rules during data synthesis. No duplicate rows (i.e., exact copies of de‐identified data) were found in the parametric data, while only 0.6% of the rows in the non‐parametric data were duplicated.ConclusionsBoth synthesised datasets performed well in replicating the statistical properties of the original data while addressing privacy issues. Data synthesis methods provide an opportunity for researchers to utilise health data while managing privacy and security concerns.
Reduced Klotho expression and its prognostic significance in canine hepatocellular carcinoma
Authors: Kim Geonuk , Chung Heaji , Lee Sungin , Kim Wan Hee 
Published: December 2022

AbstractKlotho is an anti‐ageing gene and is known to act as a tumour suppressor in human hepatocellular carcinoma (HCC). According to a previous study, Klotho is present in normal canine mammary glands, and down‐expression in tumours is positively associated with negative prognosis. However, the presence and significance of Klotho in canine HCC has not yet been reported. This study aimed to confirm Klotho expression in normal canine liver tissues using western blotting and immunohistochemistry, and whether the expression differed in non‐neoplastic liver disease and HCC. Furthermore, correlation between clinicopathologic features and expression of Klotho was evaluated. All of the normal liver tissues showed the presence of Klotho, and Klotho expression was significantly decreased in the HCC tissue as compared to the non‐neoplastic hepatic tissue. Additionally, Klotho expression was significantly associated with tumour size (P = .045), liver enzyme (alanine aminotransferase (ALT)) (P = .018), and metastasis (P = .024). Analysis of the survival curve revealed that reduced Klotho expression was significantly associated with poor disease‐free survival (P = .041) in HCC. These results show that Klotho expression is present in normal canine liver tissue and that reduced Klotho expression is associated with poor prognosis in canine HCC. Thus, Klotho was presumed to be a potential clinical prognostic marker for canine HCC.
One health zoonotic disease prioritization and systems mapping: An integration of two One Health tools
Authors: Varela Kate , Goryoka Grace , Suwandono Agus , Mahero Michael , Valeri Linda , Pelican Katharine , Salyer Stephanie J. 
Published: December 2022

AbstractOne Health is a collaborative approach that requires synergies between human, animal and environmental health sectors, other key sectors, and partners supporting these capacity‐building efforts. Multiple One Health capacity‐building tools are available that can be used independently or together. Two tools that have been used in sequence to inform each other include the US Centers for Disease Control and Prevention's One Health Zoonotic Disease Prioritization (OHZDP) Process and University of Minnesota/US Department of Agriculture's One Health Systems Mapping and Analysis Resource Toolkit™ (OH‐SMART). In August 2017, a workshop was held in Islamabad, Pakistan, that integrated these two tools for the first time. In this integrated workshop, we used the OHZDP to develop a list of priority zoonotic diseases for Pakistan and OH‐SMART™ to conduct a partner assessment and disease‐specific gap analysis. Both tools were used to identify areas for One Health collaboration for the priority zoonotic diseases. Additionally, we trained 11 in‐country facilitators representing the human and animal health sectors on both tools. This manuscript describes the integration of these two tools—using the Pakistan workshop as a process case study—to inform future efforts to implement One Health tools synergistically. Implementation of the technical and logistical aspects of the integrated workshop was detailed: (1) workshop preparation, (2) facilitator training, (3) workshop implementation and (4) workshop outcomes. Sixteen months after the workshop, we conducted an in‐country facilitator survey to follow‐up on the utility of both tools and the training for facilitators. We evaluated facilitator survey results using a qualitative analysis software Atlas.ti. Using the OHZDP Process and OH‐SMART™ together achieved continuity between the two processes and provided a professional development opportunity for in‐country facilitators. Based on the success of this integrated workshop, partners developing and implementing One Health tools should recognize the importance of collaboration to maximize outcomes.
Incidence, aetiology and neurodisability associated with severe microcephaly: a national surveillance study
Authors: Knowles Rachel L , Solebo Ameenat Lola , Sampaio Mariana Autran , Brown Charlotte Rebecca , Sargent Jenefer , Oluonye Ngozi , Rahi Jugnoo 
Published: December 2022

ObjectiveTo determine the incidence, causes and neurodevelopmental impact of severe microcephaly (head circumference <–3SD) up to age 2 years.DesignBinational active paediatric surveillance study undertaken in 2017–2018 to identify and characterise new diagnoses of severe microcephaly.SettingUK and Ireland.ParticipantsInfants aged under 12 months at diagnosis.InterventionsObservational study.Main outcome measuresIncidence, aetiology and neurodevelopmental outcomes at age 2 years.ResultsFifty-nine infants met the case definition, of whom 30 (51%) were girls; 24 (41%) were born preterm (<37 weeks’ gestation); and 34 (58%) were of ‘white’ ethnicity. Eight (14%) children died before 12 months of age. Incidence of severe microcephaly was 5.5 per 100 000 infants (95% CI 4.0 to 7.3). Higher relative risk (RR) was associated with preterm birth (RR 7.7, 95% CI 3.8 to 15.1) and British Asian ethnicity (RR 3.6, 95% CI 1.6 to 7.8). Microcephaly was mainly due to genetic causes (59%), brain ischaemia/hypoxia (10%) and congenital infection (8%), and 19% remained undetermined. Each child was referred on average to eight specialists, and 75% had abnormal brain imaging. By 2 years of age, 55 children experienced neurodevelopmental abnormalities, including feeding problems (68%), motor delay (66%), visual impairment (37%), hearing loss (24%) and epilepsy (41%).ConclusionsAlthough severe microcephaly is uncommon, it is associated with high mortality, complex multimorbidity and neurodisability, thus representing a significant ongoing burden for families and healthcare services. Potentially preventable causes include preterm birth, hypoxic/ischaemic brain injury and congenital infections. Clinical guidelines are essential to standardise aetiological investigation and optimise multidisciplinary management.
Utilisation, effectiveness, and safety of immediate postpartum intrauterine device insertion: a systematic literature review
Authors: Rosa Bolling Kristina , Wahdan Yesmean , Warnock Neal , Lott Jason , Schoendorf Juliane , Pisa Federica , Gomez-Espinosa Evelyn , Kistler Kristin , Maiese Brett 
Published: December 2022

BackgroundIntrauterine devices (IUDs) are highly effective contraception. IUDs inserted directly following delivery provide immediate birth control and may decrease unintended pregnancies, including short-interval pregnancies, thereby mitigating health risks and associated economic burden.MethodsThis systematic literature review included published global data on the utilisation, effectiveness, and safety of postpartum intrauterine devices (PPIUDs) of any type. English language articles indexed in MEDLINE, Embase, and Cochrane from January 2010–October 2021 were included.Results133 articles met the inclusion criteria (46% interventional studies; 54% observational; n=87 from lower-income countries; n=46 from higher-income countries). PPIUD use was low in higher-income countries (6/10 000 US deliveries in 2013–2016) and varied widely in lower-income countries (2%-46%). Across both higher- and lower-income countries, in most studies (79%), >80% of women with PPIUDs had an IUD in place by 3 months; at 6 and 12 months, 76% and 54% of included studies reported that >80% of women had an IUD in place; reason for discontinuation was infrequently reported. Pregnancies were rare (96 pregnancies across 12 191 women from 37 studies reporting data) and were generally unrelated to device failure, but rather occurred in women no longer using a PPIUD. Expulsions occurred mainly in the early outpatient period and ranged widely (within 3 months: 0–41%). Abnormal bleeding, infections, or perforations were rare.ConclusionsPPIUDs are safe and effective. Long-term follow-up data are limited. Future research elucidating reasons underlying lack of PPIUD use is warranted.
Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study
Authors: Arevalo Salaet Marta , López-Medina Clementina , Moreno Mireia , Navarro-Compan Victoria , Calvet Fontova Joan , Llop Maria , Dougados Maxime , Gratacós Jordi 
Published: December 2022

ObjectiveTo analyse the influence of HLA-B27 in the phenotypical expression of peripheral spondyloarthritis (pSpA).MethodThis is an observational cross-sectional study using data from the Assessment of SpondyloArthritis international Society perSpA registry, including all patients with an available HLA-B27 test result and with a diagnosis of pSpA or psoriatic arthritis (PsA) as per rheumatologist’s judgement. Demographic and clinical data, presence of extra musculoskeletal manifestations (EMM) and fibromyalgia were the variables included in a simple and multiple logistic regression model to assess their association to HLA-B27 positivity.ResultsFrom the 4465 patients included in the registry, 790 were classified as having either pSpA or PsA and had the HLA-B27 typing available. HLA-B27-positive patients presented a male predominance, had an earlier disease onset and a shorter diagnostic delay compared with the negatives. HLA-B27-positive patients presented a higher frequency of axial involvement, radiographic sacroiliitis, enthesitis and uveitis. Also, root joint involvement, poliarticular joint patern and tarsitis were significantly higher within HLA-B27-positive patients. Furthermore, we did not observe any association between the presence of HLA-B27 and peripheral joint damage, dactylitis, other EMM (psoriasis, inflammatory bowel disease) or fibromyalgia.The multivariable analysis confirmed the independent association of HLA-B27 positivity with male sex, an earlier onset of the disease, the presence of axial involvement, tarsitis and uveitis.SummaryIn summary, the presence of HLA-B27 in pSpA patients was associated with earlier disease onset and higher axial involvement, tarsitis and uveitis, but not with other EMM, fibromyalgia or peripheral structural damage.
Racial and ethnic variation in emergent surgical care and outcomes during the COVID-19 pandemic: post hoc analysis of an EAST MCT
Authors: Winicki Nolan M , Dahan Alden , Maheshwari Somiya , Crowley Brandon , Gelbard Rondi , Burruss Sigrid 
Published: December 2022

ObjectivesThe COVID-19 pandemic highlighted concerns regarding the equity of medical care. We evaluated associations between race/ethnicity, timing of hospital presentation and outcomes of acute appendicitis (AP) and acute cholecystitis (AC) during the initial pandemic peak.MethodsAnalysis was performed on a prospective, observational, multicenter study of adults with AP or AC. Patients were categorized as pre-pandemic (pre-CoV: October 2019–January 2020) or during the first pandemic peak (CoV: April 2020 through 4 months following the end of local pandemic restrictions). Patient demographics, American Association for the Surgery of Trauma (AAST) imaging/pathology grade, duration of symptoms before triage, time from triage to intervention and hospital length of stay were collected.ResultsA total of 2165 patients (1496 pre-CoV, 669 CoV) were included from 19 centers. Asian and Hispanic patients with AC had a longer duration of symptoms prior to presentation during CoV than pre-CoV (100.6 hours vs 37.5 hours, p<0.01 and 85.7 hours vs 52.5 hours, p<0.05, respectively) and presented later during CoV than Black or White patients (34.3 and 37.9 hours, p<0.01). During CoV, Asian patients presented with higher AAST pathology grade for AP compared with pre-CoV (1.90 vs 1.26, p<0.01). Asian and Hispanic patients presented with higher AAST pathology grade for AC during CoV versus pre-CoV (2.57 vs 1.45, p<0.01, and 1.57 vs 1.20, p<0.05, respectively). Patients with AC and an AAST pathology grade of ≥3 were at higher odds of postoperative complications (OR 4.4, 95% CI 1.0 to 18.4) and AP (OR 2.8, 95% CI 1.3 to 6.0). Asian and Hispanic patients with AC had a higher risk of postoperative complications compared to White patients (Asian: OR 3.9, 95% CI 1.2 to 12.7; Hispanic: OR 3.3, 95% CI 1.2 to 8.9).ConclusionAsian and Hispanic patients had a longer duration of symptoms before hospital presentation during the initial COVID-19 peak, had higher odds of postoperative complications and more advanced pathologic disease.Level of evidenceIII, Prognostic/epidemiological.
Type III seesaw under $$A_4$$ modular symmetry with leptogenesis
Authors: Mishra Priya , Behera Mitesh Kumar , Panda Papia , Mohanta Rukmani 
Published: December 2022

AbstractWe make an attempt to study neutrino phenomenology in the framework of type-III seesaw by considering $$A_4$$

A
4

modular symmetry in the super-symmetric context. In addition, we have included a local $$U(1)_{B-L}$$

U

(
1
)

B
-
L

symmetry which eventually helps us to avoid certain unwanted terms in the superpotential. Hitherto, the seesaw being type-III, it involves three fermion triplet superfields $$\Sigma _R$$

Σ
R

, along with which, we have included a singlet weighton field $$(\rho )$$

(
ρ
)

. In here, modular symmetry plays a crucial role by avoiding the usage of excess flavon (weighton) fields. Also, the Yukawa couplings acquire modular forms which are expressed in terms of Dedekind eta function $$\eta (\tau )$$

η
(
τ
)

. However, for numerical analysis we use q expansion expressions of these couplings. Therefore, the model discussed here is triumphant enough to accommodate the observed neutrino oscillation data and also successfully explains observed baryon asymmetry of the universe through leptogenesis.
Casimir wormholes in modified symmetric teleparallel gravity
Authors: Hassan Zinnat , Ghosh Sayantan , Sahoo P. K. , Bamba Kazuharu 
Published: December 2022

AbstractIn recent years there has been a growing interest in the field of Casimir wormhole. In classical general relativity (GR), it is known that the null energy condition (NEC) has to be violated to have a wormhole to be stable. The Casimir effect is an experimentally verified effect that is caused due to the vacuum field fluctuations in quantum field theory. Since the Casimir effect provides the negative energy density, thus this act as an ideal candidate for the exotic matter needed for the stability of the wormhole. In this paper, we study the Casimir effect on the wormhole geometry in modified symmetric teleparallel gravity or f(Q) gravity, where the non-metricity scalar Q drives the gravitation interaction. We consider three systems of the Casimir effect such as (i) two parallel plates, (ii) two parallel cylindrical plates, and (iii) two-sphere separated by a large distance to make it more experimentally feasible. Further, we studied the obtained wormhole solutions for each case with energy conditions at the wormhole throat with radius $$r_0$$

r
0

and found that some arbitrary quantity violates the classical energy conditions at the wormhole throat. Furthermore, the behavior of the equation of state (EoS) is also analyzed for each case. Finally, we investigate the stability of the obtained Casimir effect wormhole solutions with the generalized Tolman–Oppenheimer–Volkoff (TOV) equation.
Improved Delineation of Colorectal Cancer Molecular Subtypes and Functional Profiles with a 62-Gene Panel
Authors: Bhukdee Dhup , Nuwongsri Pattarin , Israsena Nipan , Sriswasdi Sira 
Published: December 2022

AbstractSince its establishment in 2015, the transcriptomics-based consensus molecular subtype (CMS) classification has unified our understanding of colorectal cancer. Each of the four CMS exhibited distinctive high-level molecular signatures that correlated well with prognosis and treatment response. Nonetheless, many key aspects of colorectal cancer progression and intra-subtype heterogeneity remain unresolved. This is partly because the bulk transcriptomic data used to define CMS contain substantial interference from non-tumor cells. Here, we propose a concise panel of 62 genes that not only accurately recapitulates all key characteristics of the four original CMS but also identifies three additional subpopulations with unique molecular signatures. Validation on independent cohorts confirms that the new CMS4 intra-subtypes coincide with single-cell–derived intrinsic subtypes and that the panel consists of many immune cell-type markers that can capture the status of tumor microenvironment. Furthermore, a 2D embedding of CMS structure based on the proposed gene panel provides a high-resolution view of the functional pathways and cell-type markers that underlie each CMS intra-subtype and the continuous progression from CMS2 to CMS4 subtypes. Our gene panel and 2D visualization refined the delineation of colorectal cancer subtypes and could aid further discovery of molecular mechanisms in colorectal cancer.Implications: Well-selected gene panel and representation can capture both the continuum of cancer cell states and tumor microenvironment status.
LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells
Authors: Ngai Ho , Barragan Gabriel A. , Tian Gengwen , Balzeau Julien C. , Zhang Chunchao , Courtney Amy N. , Guo Linjie , Xu Xin , Wood Michael S. , Drabek Janice M. , Demberg Thorsten , Sands Caroline M. , Chauvin-Fleurence Cynthia N. , Di Pierro Erica J. , Rosen Jeffrey M. , Metelitsa Leonid S. 
Published: December 2022

Abstract

Vα24-invariant natural killer T cells (NKT) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown previously that the CD62L+ central memory-like subset of these cells drives the in vivo antitumor activity of NKTs, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that relative to CD62L– cells, CD62L+ NKTs express a higher level of the gene encoding the Wnt/β-catenin transcription factor lymphoid enhancer binding factor 1 (LEF1) and maintain active Wnt/β-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, whereas Wnt/β-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression promoted NKT expansion and limited exhaustion following serial tumor challenge and was sufficient to induce a central memory–like transcriptional program in NKTs. In mice, NKTs expressing a GD2-specific chimeric-antigen receptor (CAR) with LEF1 demonstrated superior control of neuroblastoma xenograft tumors compared with control CAR-NKTs. These results identify LEF1 as a transcriptional activator of the NKT central memory program and advance development of NKT cell–based immunotherapy.
See related Spotlight by Van Kaer, p. 144
Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1–Independent Manner
Authors: Long Yiru , Chen Runqiu , Yu Xiaolu , Tong Yongliang , Peng Xionghua , Li Fanglin , Hu Chao , Sun Jianhua , Gong Likun 
Published: December 2022

Abstract
CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) is known to be a regulator of membranal programmed death ligand 1 (PD-L1) stability and a factor associated with malignancy progression, but the effects and mechanisms of CMTM6 on tumor growth, as well as its potential as a target for therapy, are still largely unknown. Here, we show that CMTM6 expression increased with tumor progression in both patients and mice. Ablation of CMTM6 significantly reduced human and murine tumor growth in a manner dependent on T-cell immunity. Tumor CMTM6 suppression broke resistance to immune-checkpoint inhibitors and remodeled the tumor immune microenvironment, as specific antitumor cytotoxicity was enhanced and contributed primarily to tumor inhibition. Without the PD-1/PD-L1 axis, CMTM6 suppression still significantly dampened tumor growth dependent on cytotoxic cells. Furthermore, we identified that CMTM6 was widely expressed on immune cells. T-cell CMTM6 levels increased with sustained immune activation and intratumoral immune exhaustion and affected T cell–intrinsic PD-L1 levels. Host CMTM6 knockout significantly restrained tumor growth in a manner dependent on CD8+ T cells and not entirely dependent on PD-L1. Thus, we developed and evaluated the antitumor efficacy of CMTM6-targeting adeno-associated virus (AAV), which effectively mobilized antitumor immunity and could be combined with various antitumor drugs. Our findings reveal that both tumor and host CMTM6 are involved in antitumor immunity with or without the PD-1/PD-L1 axis and that gene therapy targeting CMTM6 is a promising strategy for cancer immunotherapy.