bluuebunny/crossref_metadata_2025 huggingface dataset:
Psoas abscess: an uncommon disorder
Authors: Xu Chengan , Zhou Zhewen , Wang Shouhao , Ren Wenya , Yang Xingdi , Chen Hanzhu , Zheng Wei , Yin Qiaoqiao , Pan Hongying
Published: February 2024

Background

Psoas abscess (PA) is an uncommon disease that has been increasingly reported in the recent years. We reviewed patients with PA and analyzed their clinical characteristics to improve our understanding of this rare disorder.

Methods

We retrospectively reviewed the clinical presentations, microbiology, and outcomes of patients with PA between 2011 and 2022 at the Zhejiang Provincial People’s Hospital in China.

Results

There were 40 adult patients identified with the discharge diagnosis of PA. The mean age was 60 years, and 67.5% of the patients were male. Primary symptoms were typically nonspecific. In all, 20 abscesses were considered secondary, and the most common was infective spondylitis. The most common causative organism for primary PA was Staphylococcus aureus, followed by Escherichia coli, whereas multiple bacterial species were found in secondary abscesses. The overall in-hospital mortality rate was 5%. Patients with secondary PA had a longer hospital stay.

Conclusion

PA, as a serious infectious condition, usually presents with nonspecific symptoms and laboratory test results, making early diagnosis difficult. These profiles differed from those reported in the present study. The initial clinical status and subsequent imaging studies can lead to favorable outcomes.
The Cautionary Account of Supererogation
Authors: Eslami Seyyed Mohsen , Archer Alfred
Published: February 2024

The problem of supererogation has attracted significant attention from contemporary moral philosophers. In this paper, we show that this problem was outlined in different terms in the work of the 11th century Persian philosopher Abū Alī Miskawayh. As well as identifying this problem, Miskawayh also developed a unique solution cashed out in terms of virtue ethics that has not yet been considered in the contemporary literature. We will argue that this solution, which is in its general form independent of virtue ethics, provides a plausible explanation of what makes some acts supererogatory and faces two important advantages over the most popular response to the problem of supererogation, The Sacrifice View. Unlike The Sacrifice View, The Cautionary Account can class acts of benevolence that advance the agent's own interests as supererogatory and easily explain why certain acts of sacrifice are neither permissible nor praiseworthy.
‘Just The Facts’: Thick Concepts and Hermeneutical Misfit
Authors: Bell Rowan
Published: February 2024

Oppressive ideology regularly misrepresents features of structural injustice as normal or appropriate. I argue that resisting such injustice therefore requires critical examination of the evaluative judgments encoded in shared concepts. I diagnose a mechanism of ideological misevaluation, which I call hermeneutical misfit. Hermeneutical misfit occurs when thick concepts, or concepts which both describe and evaluate, mobilise ideologically warped evaluative judgments which do not fit the facts (e.g. slutty). These ill-fitted thick concepts in turn are regularly deployed as if they merely describe (hence ‘just the facts’). I argue that, via this descriptive masquerade, ill-fitted thick concepts smuggle in warped evaluative judgments alongside apparently value-neutral ‘mere facts’, a process which both reinforces those judgments and increases the difficulty of critique. I suggest that, to resist this process, we should develop collective consciousness and articulate ‘meta-hermeneutical resources,’ or thick concepts which encode critique of other, ill-fitted concepts (e.g. slut-shaming).
Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues
Authors: Wu Jian , Wang Chaoye , Sun Shuhui , Ren Tianmin , Pan Lijie , Liu Hongyi , Hou Simeng , Wu Shen , Yan Xuejing , Zhang Jingxue , Zhao Xiaofang , Liu Weihai , Zhu Sirui , Wei Shuwen , Zhang Chi , Jia Xu , Zhang Qi , Yu Ziyu , Zhuo Yehong , Zhao Qi , Yang Chenlong , Wang Ningli
Published: February 2024

The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in-depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.
First Study of the PIKACHU Project: Development and Evaluation of High-Purity Gd3Ga3Al2O12:Ce Crystals for 160Gd Double Beta Decay Search
Authors: Omori Takumi , Iida Takashi , Gando Azusa , Hosokawa Keishi , Kamada Kei , Mizukoshi Keita , Shoji Yasuhiro , Yoshino Masao , Fushimi Ken-Ichi , Suzuki Hisanori , Takahashi Kotaro
Published: February 2024

Uncovering neutrinoless double beta decay (0ν2β) is crucial for confirming neutrinos’ Majorana characteristics. The decay rate of 0νββ is theoretically uncertain, influenced by nuclear matrix elements that vary across nuclides. To reduce this uncertainty, precise measurement of the half-life of neutrino-emitting double beta decay (2ν2β) in different nuclides is essential. We have launched the PIKACHU (Pure Inorganic scintillator experiment in KAmioka for CHallenging Underground sciences) project to fabricate high-purity Ce-doped Gd3Ga3Al2O12 (GAGG) single crystals and use them to study the double beta decay of 160Gd. Predictions from two theoretical models on nuclear matrix element calculations for 2ν2β in 160Gd show a significant discrepancy in estimated half-lives, differing by approximately an order of magnitude. If the lower half-life estimation holds true, detecting 2ν2β in 160Gd could be achievable with a sensitivity enhancement slightly more than an order of magnitude compared to prior investigations using Ce-doped Gd2SiO5 (GSO) crystal. We have successfully developed GAGG crystals with purity levels surpassing previous standards through refined purification and selection of raw materials. Our experiments with these crystals indicate the feasibility of reaching sensitivities exceeding those of earlier studies. This paper discusses the ongoing development and scintillator performance evaluation of high-purity GAGG crystals, along with the anticipated future prospects of the PIKACHU experiment.
Treatment of Women With Primary Dysmenorrhea With Manual Therapy and Electrotherapy Techniques: A Systematic Review and Meta-Analysis
Authors: González-Mena Ángela , Leirós-Rodríguez Raquel , Hernandez-Lucas Pablo
Published: February 2024

Objective

The objective of this study was to evaluate the efficacy of electrotherapy and manual therapy for the treatment of women with primary dysmenorrhea.

Methods

Systematic searches were conducted in Scopus, Web of Science, PubMed, CINAHL, and MEDLINE. The articles must have been published in the last 10 years, had a sample exclusively of women with primary dysmenorrhea, had a randomized controlled trial design, and used interventions that included some form of manual therapy and/or electrotherapy techniques. Two reviewers independently screened articles for eligibility and extracted data. Difference in mean differences and their 95% CIs were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity.

Results

Twelve selected studies evaluated interventions, with 5 evaluating electrotherapy techniques and 7 evaluating manual therapy techniques. All studies analyzed identified improvements in pain intensity and meta-analysis confirmed their strong effect.

Conclusions

Manual therapy and electrotherapy are effective for the treatment of women with primary dysmenorrhea. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage stands out for its effects on the intensity and duration of pain with the application of a few sessions and their long-term effects.

Impact

Manual therapy techniques and electrotherapy methods reduce the pain intensity of women with primary dysmenorrhea. Quality of life and degree of anxiety improved significantly with manual therapy interventions. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage are the interventions with which positive effects were achieved with fewer sessions.
Incorporation of age into patient early warning scores significantly improves mortality prediction
Authors: Martín-Conty J L , Castro Villamor M A , Sanz-García A , Polonio-López B , López-Izquierdo R , Sáez Belloso S , Delgado Benito J F , Del Pozo Vegas C , Conty-Serrano R , Eichinger M , Martín-Rodríguez F
Published: February 2024

Background

Age is a critical factor for the assessment of patients attended by emergency medical services (EMSs). However, how age modifies early warning scores’ (EWSs) predictive ability should be unveiled.

Aim

To determine how age influences the performance of EWS [National Early Warning Score 2 (NEWS2), VitalPAC-Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and modified Rapid Emergency Medicine Score (mREMS)] to predict 2-day mortality. The secondary objective was to determine the performance of EWSs at different age ranges.

Design

A prospective, observational study performed between November 2019 and July 2023.

Methods

A multicenter, ambulance-based study, considering 38 basic life support units and six advanced life support units referring to four tertiary care hospitals. Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments. The primary outcome was 2-day in-hospital mortality (includes all-cause mortality). The main measures were demographical and vital signs needed for EWS calculation.

Results and discussion

A total of 8028 participants fulfilled the inclusion criteria, with 7654 survivors and 374 non-survivors. Among age ranges, the 2-day mortality was 2.8% for the ≤44 years, 3.3% for the 45–64 years, 4.1% for the 65–74 years and 6.7% for the ≥75-year age group. The inclusion of age significantly improved the Area Under the Curve (AUC) in all the scores (P = 0.006 for non-age-adjusted mREMS, P = 0.001 for NEWS2, P = 0.002 for ViEWS, P = 0.028 for RAPS, all compared with their counterparts with age).

Conclusion

Our results demonstrated that the incorporation of age into the EWS improved the performance of the scores. These results will allow the EMS to improve patient management and resource optimization by including an easy-to-obtain variable.
Profinite completions of free-by-free groups contain everything
Authors: Bridson Martin R
Published: February 2024

Given an arbitrary, finitely presented, residually finite group Γ, one can construct a finitely generated, residually finite, free-by-free group $M_\Gamma = F_\infty\rtimes F_4$ and an embedding $M_\Gamma \hookrightarrow (F_4\ast \Gamma)\times F_4$ that induces an isomorphism of profinite completions. In particular, there is a free-by-free group whose profinite completion contains $\widehat{\Gamma}$ as a retract.
Real-world experience of IL-17Ai drug survival in a large cohort of axial spondyloarthritis and psoriatic arthritis
Authors: Weddell Jake , Din Naw Ra Aung , Harrison Stephanie R , Michelena Xabier , McGonagle Dennis , Barr Andrew , Vandevelde Claire , Freeston Jane , Marzo-Ortega Helena
Published: February 2024

Objective

The aim was to assess the use and drug survival of IL-17Ai in a real-world cohort of axial SpA (axSpA) and PsA patients.

Methods

Patients ever commenced on an IL-17Ai (secukinumab or ixekizumab) for axSpA or PsA at the Leeds Specialist Spondyloarthritis Service were identified. Demographics, IL-17Ai treatment length and reason for cessation were collected. Drug survival data were plotted as a Kaplan–Meier curve, with log rank test of median survival compared between axSpA and PsA. Cox regression analysis was performed to investigate the relationship between diagnosis and length of drug survival.

Results

In total, 228 patients (91 axSpA and 137 PsA) were exposed to IL-17Ai. Drug survival for all patients at 12 months was 69% (95% Confidence Interval (CI) 63, 75%) and at 24 months 60% (95% CI 54, 67%). In axSpA and PsA, drug survival at 12 months was 63% (CI 54, 74%) and 73% (CI 66, 81%), respectively, and at 24 months it was 53% (CI 44, 65%) and 65% (CI 57, 75%), respectively. Median survival did not differ significantly between both diseases (log rank test 0.65). There was no association between diagnosis and survival (hazard ratio 0.92, 95% CI 0.63, 1.33), including when adjusting for age, previous biologic DMARD usage and sex (hazard ratio 0.89, 95% CI 0.61, 1.13).

Conclusion

This is the first study, to our knowledge, to analyse and compare real-world IL-17Ai drug survival in patients with axSpA and PsA from a single centre. We demonstrate that there is no difference in IL-17Ai survival rates and no relationship between diagnosis and drug survival. These results contribute to the body of real-world evidence confirming the role of IL-17Ai in the management of axSpA and PsA.
A transferrin receptor targeting dual-modal MR/NIR fluorescent imaging probe for glioblastoma diagnosis
Authors: Hao Jiaqi , Cai Huawei , Gu Lei , Ma Yiqi , Li Yan , Liu Beibei , Zhu Hongyan , Zeng Fanxin , Wu Min
Published: February 2024

The prognosis of glioblastoma (GBM) remains challenging, primarily due to the lack of a precise, effective imaging technique for comprehensively characterization. Addressing GBM diagnostic challenges, our study introduces an innovative dual-modal imaging that merges near-infrared (NIR) fluorescent imaging with magnetic resonance imaging (MRI). This method employs superparamagnetic iron oxide nanoparticles coated with NIR fluorescent dyes, specifically Cyanine 7, and targeted peptides. This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles, provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions, offering a comprehensive diagnostic tool for GBM. Notably, the probe traverses the blood–brain barrier, targeting GBM in vivo via peptides, producing clear and discernible images in both modalities. Cytotoxicity and histopathology assessments confirm the probe’s favorable safety profile. These findings suggest that the dual-modal MR\NIR fluorescent imaging probe could revolutionize GBM prognosis and survival rates, which can also be extended to other tumors type.
A Survey of Private Debt Funds
Authors: Block Joern , Jang Young Soo , Kaplan Steven N , Schulze Anna
Published: February 2024

Despite its large and increasing size in the United States and Europe, the private debt (PD) market, compared to the bank and syndicated loan markets, has been researched little. In this paper, we survey U.S. and European investors with private debt assets under management (AuM) of over $390 billion. These investors are primarily direct lending funds. We ask the general partners (GPs) how they source, select, and evaluate deals; how they think of private debt relative to bank and syndicated loan financing; how they monitor their investments; how they interact with private equity (PE) sponsors; and how they view the future of the market. Respondents provide primarily cash-flow-based loans and believe that they finance companies and leverage levels that banks would not fund. Direct lending funds target unlevered returns that appear high relative to their risk. They use leverage in their funds, but appreciably less than banks and collateralized loan obligation funds (CLOs). They use and negotiate for both financial and negative covenants to monitor their investments. The presence of PE sponsors helps them lend more and craft more effective covenants. U.S. and European funds are similar along many dimensions, but European funds rely less on PE sponsors and compete more with banks. Overall, the private debt market is both different from and shares characteristics with bank loan and syndicated loan markets. (JEL G23, G30, G32)
Activity Shocks and Corporate Liquidity: the Role of Trade Credit
Authors: Bureau Benjamin , Duquerroy Anne , Vinas Frédéric
Published: February 2024

We show both theoretically and empirically how trade credit financing may magnify the impact of activity shocks on corporate liquidity. Using unique daily data on payment defaults on suppliers in France, we quantify the magnitude of the short-term cyclical liquidity stress induced by trade payment obligations, exploiting the COVID-19 crisis as an exogenous shock. A one-standard-deviation rise in net trade credit position increases firms’ default probability by 10% during the lockdown. We find higher impacts for downstream sectors – up to 30% increase in the retail trade – for financially constrained firms, and a contraction in investment. (JEL E32, G32, G33, H12, H32)
Late-Medieval Commonplace Culture, the Pastoral Compendium, and the Form of Richard Rolle’s The Form of Living
Authors: Glover Timothy
Published: February 2024

This article examines the disjointed textual form of Richard Rolle’s The Form of Living, one of the most widely circulated English texts of the Middle Ages. It argues that The Form reflects the traditions of the pastoral miscellany and compendium, which were new kinds of texts that emerged following pastoral reforms in late-medieval Europe. Expanding book ownership among parish priests led to the development of a clerical ‘commonplace culture’ in which priests excerpted useful passages from larger reference works to fill blank spaces in their books, or transformed them into streamlined compendia for devotional reading. This article argues that an important facet of Rolle’s process of composing The Form of Living involved his excerpting and reshaping larger pastoral reference works and whatever else he had to hand. This challenges the way that past scholarship has often understood the work in terms of Rolle’s individuality and personal touch: instead, this article seeks to locate Rolle’s creativity in his unlikely transformation of rote pastoral fare into ambitious devotional literature. Contextualizing The Form in this way offers a richer understanding of its form, giving insights into why Rolle chose this format and why it was valued by medieval readers. It also suggests that developing new models for late-medieval compilatio can offer new ways to think about textual organization and authorial composition more broadly.
Organizational changes and research performance: A multidimensional assessment
Authors: Jiménez-Andrade José Luis , Arencibia-Jorge Ricardo , Robles-Pérez Miguel , Tagüeña Julia , Govezensky Tzipe , Carrillo-Calvet Humberto , Barrio Rafael A , Kaski Kimmo
Published: February 2024

This paper analyzes the research performance evolution of a scientific institute, from its genesis through various stages of development. The main aim is to obtain, and visually represent, bibliometric evidence of the correlation of organizational changes on the development of its scientific performance; particularly, structural and leadership changes. The study involves six bibliometric indicators to multidimensionally assess the evolution of the institution’s performance profile. For a case study, we selected the Renewable Energy Institute at the National Autonomous University of Mexico, created 35 years ago as a small laboratory, then it evolved to a research center and finally to a formal institute, which over the last 8 years changed from the traditional departmental structure to a network-based structure. The evolution of the multidimensional performance profiles is analyzed, and graphically represented, using a novel artificial intelligence-based approach. We analyzed the performance profiles evolution yearly, using Principal Components Analysis, and a self-organizing neural network mapping technique. This approach, combining bibliometric and machine learning techniques, proved to be effective for the assessment of the institution’s evolution process. The results were represented with a series of graphs and maps that clearly reveal the magnitude and nature of the performance profile evolution, as well as its correlation with each of the structural and leadership transitions. These exploratory results have provided us data and insights into the probable effects of these transitions on academic performance, that have been useful to create a dynamical model.
Labour Market Screening and the Design of Social Insurance: An Equilibrium Analysis of the Labour Market for the Disabled
Authors: Aizawa Naoki , Kim Soojin , Rhee Serena
Published: February 2024

This article studies how firms’ screening incentives in the labour market affect the optimal design of social insurance programs and quantitatively assesses the U.S. disability policies accounting for firms’ screening of the disabled. We develop an equilibrium search model where workers with different productivities have heterogeneous preferences over non-wage benefits and firms cannot offer an employment contract that explicitly depends on worker types. In this environment, firms may use contracts to screen out a certain type of workers, distorting employment rates and contracts in equilibrium. Therefore, the optimal structure of social insurance policies depends on firms’ screening incentives. We extend and structurally estimate this framework to quantitatively understand the inefficiencies arising from firms’ incentives to screen out disabled workers and examine the optimal joint design of disability insurance (DI) and various forms of firm subsidies. We find that hiring subsidies mitigate screening distortions; at the same time, they interact with DI by reducing the labour supply disincentives it generates. The optimal policy structure leads to a considerable welfare gain by simultaneously making firm subsidies and DI benefits more generous.
Follow-up ultrasound examination in patients with newly diagnosed giant cell arteritis
Authors: Schäfer Valentin S , Dejaco Christian , Karakostas Pantelis , Behning Charlotte , Brossart Peter , Burg Lara C
Published: February 2024

Objectives

Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only a few studies have investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima–media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period.

Methods

Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after 3, 6, 9 and 12 months. Changes of IMT, total number of affected arteries and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days.

Results

Fifty patients were enrolled and 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after 7 days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below 1 after 6 months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in four patients. At relapse, mean IMT and OGUS were higher as compared to the preceding assessment. No predictive values indicating a relapse were identified.

Conclusion

Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.
Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study
Authors: Cho Soo-Kyung , Song Yeo-Jin , Kim Hye Won , Nam Eunwoo , Jeon Ja-Young , Yoo Hyun-Jeong , Sung Yoon-Kyoung
Published: February 2024

Objective

The objective of this study was to assess the effectiveness of tofacitinib vs TNF inhibitors (TNFis) in Korean patients with RA.

Methods

The study used data from a single academic referral hospital’s registries of biologic DMARDs (bDMARDs) and tofacitinib and examined remission rates based on the DAS28-ESR after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders.

Results

This analysis included 665 patients (200 on tofacitinib and 455 on TNFis) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, P = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% CI 0.720–2.013). In the subpopulation naïve to Janus kinase inhibitors (JAKis) and bDMARDs, tofacitinib showed better remission rates than TNFis (OR 1.867, 95% CI 1.033–3.377). Tofacitinib had more adverse events but similar rates of serious adverse events to TNFis.

Conclusion

In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of adverse events compared with TNFis, while the occurrence of serious adverse events was comparable between the groups.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT02602704.
The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials
Authors: Takase-Minegishi Kaoru , Böhringer Stefan , Nam Jackie L , Kaneko Yuko , Behrens Frank , Saevarsdottir Saedis , Detert Jacqueline , Leirisalo-Repo Marjatta , van der Heijde Désirée , Landewé Robert , Ramiro Sofia , van der Woude Diane
Published: February 2024

Objective

To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.

Methods

Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF+ vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses.

Results

Data from 28 eligible RCTs were analysed, pooling 23 studies in three subgroups: six including csDMARD-naive patients, 14 csDMARD-IR and three TNFi-IR patients. In csDMARD-naive and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88–1.18) and 1.09 (0.90–1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on three trials, the 6-month ACR20 RRR was 2.28 (1.31–3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs.

Conclusion

The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.
Peer-review procedures as practice, decision, and governance—the road to theories of peer review
Authors: Reinhart Martin , Schendzielorz Cornelia
Published: February 2024

Peer review is an ubiquitous feature of science with three interrelated roles: first, as a mechanism to assess quality through expert judgement (process); second, to decide on the distribution of scarce resources, e.g. publication space (outcome); and, third, to self-govern science (context). This is poorly reflected in public and academic debates, where attention is focused on alleged deficits. Moving beyond a ‘deficit model’, we, first, divide the peer-review process into eight different practices, which, in combination, can make up a wide variety of peer-review procedures. Second, we claim that peer review not only provides evaluative decisions, but, more importantly, also provides the legitimacy for these decisions. Thus, an encompassing theoretical view of peer review should integrate process, outcome, and context. Such a view could start by theorizing peer review as a form of government, not unlike democracy, grown historically around concerns for legibility, responsibility, and responsiveness akin to the Mertonian norms.
Data-driven, generalizable prediction of adolescent sleep disturbances in the multisite Adolescent Brain Cognitive Development Study
Authors: McCurry Katherine L , Toda-Thorne Katherine , Taxali Aman , Angstadt Mike , Hardi Felicia A , Heitzeg Mary M , Sripada Chandra
Published: February 2024

Study Objectives

Sleep disturbances are common in adolescence and associated with a host of negative outcomes. Here, we assess associations between multifaceted sleep disturbances and a broad set of psychological, cognitive, and demographic variables using a data-driven approach, canonical correlation analysis (CCA).

Methods

Baseline data from 9093 participants from the Adolescent Brain Cognitive Development (ABCD) Study were examined using CCA, a multivariate statistical approach that identifies many-to-many associations between two sets of variables by finding combinations for each set of variables that maximize their correlation. We combined CCA with leave-one-site-out cross-validation across ABCD sites to examine the robustness of results and generalizability to new participants. The statistical significance of canonical correlations was determined by non-parametric permutation tests that accounted for twin, family, and site structure. To assess the stability of the associations identified at baseline, CCA was repeated using 2-year follow-up data from 4247 ABCD Study participants.

Results

Two significant sets of associations were identified: (1) difficulty initiating and maintaining sleep and excessive daytime somnolence were strongly linked to nearly all domains of psychopathology (r2 = 0.36, p < .0001); (2) sleep breathing disorders were linked to BMI and African American/black race (r2 = 0.08, p < .0001). These associations generalized to unseen participants at all 22 ABCD sites and were replicated using 2-year follow-up data.

Conclusions

These findings underscore interwoven links between sleep disturbances in early adolescence and psychological, social, and demographic factors.
Design thinking for engaged learning in animal science: lessons from five semesters of a senior capstone course
Authors: Brandão Alice Poggi , Donaldson Jonan Phillip , Dunlap Kathrin Anson , Wiegert Jeffrey Glennon , Kao Sean , Paudyal Sushil
Published: February 2024

This study presents a design-based research approach involving five iterations (semester) of implementing design thinking for engaged learning (DTEL) in an animal science capstone course. DTEL scaffolds design thinking into 10 stages for collaborative project-based learning to foster skills like problem solving and teamwork. Across five semesters (spring 2021 to spring 2023), student reflections (n = 276) were analyzed to identify aspects that worked well or were challenging. Network analysis visualized relationships (P < 0.05; Q > 0.4) between codes representing strengths, struggles, and alignment with principles from learning theories. Utilizing the relationships between strengths and theory-based principles to address struggles, resulted in changes to the design of the capstone course each iteration (time that the course was taught). The complexity of maps increased over iterations. Initially, struggles were prominent but decreased as responsive design refinements were made. Alignment of student experiences with principles from learning theories grew substantially from the first iteration to the last (theory-related nodes representing 11.4% vs. 24.4% in each network map, respectively), with learning theories also occupying more central positions in the last map (iteration five) compared to earlier ones (iterations one through four). These changes suggest student experiences increasingly aligned with principles of cognitive constructivism, social constructivism, constructionism, situated learning, and transformative learning. Design principles derived from the five-iteration study include: (1) allocating most time to hands-on lab work vs. lecture, (2) designating a coordinator faculty, (3) scaffolding for instructors unfamiliar with DTEL, (4) emphasizing consistency in processes over grades, and (5) intentionally developing teamwork skills. The study demonstrates the value of design-based research for iteratively refining and studying learning experiences to foster critical skills for undergraduate students in animal science.
Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function
Authors: Cary C M , Fournier S B , Adams S , Wang X , Yurkow E J , Stapleton P A
Published: February 2024

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.
Quantitation and identification of microplastics accumulation in human placental specimens using pyrolysis gas chromatography mass spectrometry
Authors: Garcia Marcus A , Liu Rui , Nihart Alex , El Hayek Eliane , Castillo Eliseo , Barrozo Enrico R , Suter Melissa A , Bleske Barry , Scott Justin , Forsythe Kyle , Gonzalez-Estrella Jorge , Aagaard Kjersti M , Campen Matthew J
Published: February 2024

The exponential increase in global plastic usage has led to the emergence of nano- and microplastic (NMP) pollution as a pressing environmental issue due to its implications for human and other mammalian health. We have developed methodologies to extract solid materials from human tissue samples by saponification and ultracentrifugation, allowing for highly specific and quantitative analysis of plastics by pyrolysis-gas chromatography and mass spectrometry (Py-GC-MS). As a benchmark, placenta tissue samples were analyzed using fluorescence microscopy and automated particle count, which demonstrated the presence of >1-micron particles and fibers, but not nano-sized plastic particles. Analyses of the samples (n = 10) using attenuated total reflectance-Fourier transform infrared spectroscopy indicated presence of rayon, polystyrene, polyethylene, and unclassified plastic particles. By contrast, among 62 placenta samples, Py-GC-MS revealed that microplastics were present in all participants’ placentae, with concentrations ranging widely from 6.5 to 685 µg NMPs per gram of placental tissue, averaging 126.8 ± 147.5 µg/g (mean±SD). Polyethylene was the most prevalent polymer, accounting for 54% of total NMPs and consistently found in nearly all samples (mean 68.8 ± 93.2 µg/g placenta). Polyvinyl chloride and nylon each represented approximately 10% of the NMPs by weight, with the remaining 26% of the composition represented by 9 other polymers. Together, these data demonstrate advancements in the unbiased quantitative resolution of Py-GC-MS applied to the identification and quantification of NMP species at the maternal-fetal interface. This method, paired with clinical metadata, will be pivotal to evaluating potential impacts of NMPs on adverse pregnancy outcomes.
Evaluation of organophosphorus pesticide tyrosine adducts for postmortem change by human serum albumin with liquid chromatography quadrupole Orbitrap mass spectrometry
Authors: Yamagishi Yoshikazu , Nagasawa Sayaka , Iwase Hirotaro , Ogra Yasumitsu
Published: February 2024

Organophosphorus pesticides (OPPs) having a phosphate ester moiety, such as malathion (MA) and methidathion (DMTP), are widely used and have been detected in many fatal cases of accidental exposure or suicide in Japan. In forensic toxicology, the accurate determination of blood OPP concentration is mandatory to prove death by OPP poisoning. However, fatal pesticide concentration in blood at autopsy varies depending on the circumstances surrounding the dead body. In this study, we found that 16 OPPs were degraded by human serum albumin (HSA) in a temperature-dependent fashion. The mechanism underlying MA, DMTP, azinphos-methyl, etrimfos, fenthion (MPP), pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, edifenphos (EDDP), fosthiazate, and pyraclofos degradation involves the formation of adducts with tyrosine residues in HSA. The mass spectra obtained by liquid chromatography quadrupole Orbitrap mass spectrometry revealed that phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5 were formed in HSA solution incubated with OPPs. These results indicate that the 16 OPPs are postmortem changed by HSA. The detection of phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5, instead of MA, DMTP, azinphos-methyl, etrimfos, MPP, pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, EDDP, fosthiazate, and pyraclofos per se, may be used to determine death by these OPPs poisoning.
Effect of NaCl on ammonium and nitrate uptake and transport in salt-tolerant and salt-sensitive poplars
Authors: Liu Jian , Li Jing , Deng Chen , Liu Zhe , Yin Kexin , Zhang Ying , Zhao Ziyan , Zhao Rui , Zhao Nan , Zhou Xiaoyang , Chen Shaoliang
Published: February 2024

Nitrogen (N) plays an important role in mitigating salt stress in tree species. We investigate the genotypic differences in the uptake of ammonium (NH4+) and nitrate (NO3−) and the importance for salt tolerance in two contrasting poplars, salt-tolerant Populus euphratica Oliv. and salt-sensitive P. simonii × (P. pyramidalis ×Salix matsudana) (P. popularis cv. 35-44, P. popularis). Total N content, growth and photosynthesis were significantly reduced in P. popularis after 7 days of exposure to NaCl (100 mM) supplied with 1 mM NH4+ and 1 mM NO3−, while the salt effects were not pronounced in P. euphratica. The 15NH4+ trace and root flux profiles showed that salt-stressed poplars retained ammonium uptake, which was related to the upregulation of ammonium transporters (AMTs) in roots, as two of the four AMTs tested significantly increased in salt-stressed P. euphratica (i.e., AMT1.2, 2.1) and P. popularis (i.e., AMT1.1, 1.6). It should be noted that P. euphratica differs from salt-sensitive poplar in the maintenance of NO3− under salinity. 15NO3− tracing and root flux profiles showed that P. euphratica maintained nitrate uptake and transport, while the capacity to uptake NO3− was limited in salt-sensitive P. popularis. Salt increased the transcription of nitrate transporters (NRTs), NRT1.1, 1.2, 2.4, 3.1, in P. euphratica, while P. popularis showed a decrease in the transcripts of NRT1.1, 2.4, 3.1 after 7 days of salt stress. Furthermore, salt-stimulated transcription of plasmalemma H+-ATPases (HAs), HA2, HA4 and HA11 contributed to H+-pump activation and NO3− uptake in P. euphratica. However, salt stimulation of HAs was less pronounced in P. popularis, where a decrease in HA2 transcripts was observed in the stressed roots. We conclude that the salinity-decreased transcripts of NRTs and HAs reduced the ability to uptake NO3− in P. popularis, resulting in limited nitrogen supply. In comparison, P. euphratica maintains NH4+ and NO3− supply, mitigating the negative effects of salt stress.
Reassessment of the enigmatic Late Cretaceous theropod dinosaur, Bagaraatan ostromi
Authors: Słowiak Justyna , Brusatte Stephen L , Szczygielski Tomasz
Published: February 2024

The Late Cretaceous Bagaraatan ostromi, described by Osmólska in 1996, is one of the most enigmatic theropod dinosaurs. The holotype possesses a peculiar combination of features, which Osmólska suggested were indicative of a primitive position among theropods that could not be resolved further. Other researchers have pointed to affinities with either derived bird-like coelurosaurs or tyrannosaurids. Here, we reanalyse all material collected by Osmólska, which reveals it to be a chimaera of multiple theropod taxa. The femur, tibiotarsus, one pedal phalanx, and most of the bones undescribed in Osmólska’s paper are identified as Caenagnathidae indet. The mandible, cervical vertebrae, pelvis, tail, and one pedal phalanx, which we consider the holotype of B. ostromi, show tyrannosaurid affinities, which are here supported by phylogenetic analyses. We find only two potentially unique diagnostic features of the Bagaraatan holotype: double surangular foramina and a horizontal ridge on the lateral surface of the postacetabular process of the ilium. Both, however, may be ontogenetically or intraspecifically variable, and thus we conclude that the holotype of B. ostromi represents an indeterminate tyrannosaurid. The small size of the holotype and its possession of many features known to characterize juvenile Tyrannosaurus rex indicate that the skeleton belongs to a juvenile, which is one of the smallest juvenile tyrannosaurids currently known.
Abdominal Pain After Cardiac Surgery Caused by Crohn Disease, Intestinal Ischemia, and Colonic Diverticulitis, Respectively: A Report of 3 Cases
Authors: Liu Huanan , Lin Zhaoming , Zhang Xiaoshen
Published: February 2024

Abdominal complications following cardiac surgery are rare events, but can be fatal if not diagnosed and managed in time. Aggressive treatments offer a better chance for survival in patients with risk factors. This case report describes the clinical presentation and details of 3 recently operated patients who suffered acute abdominal pain after cardiac surgery. The underlying causes were Crohn disease-associated ileal perforation, intestinal necrosis, and diverticulitis-associated colonic perforation. The presentation and management of these severe conditions are discussed.
Role of T Cells in Viral and Immune-mediated Myocarditis
Authors: Cheng Chunyan , Baritussio Anna , Giordani Andrea Silvio , Marcolongo Renzo , Caforio Alida L.P. , Iliceto Sabino
Published: February 2024

Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.
Dose Monitoring of Lamotrigine Monotherapy in Pregnancy: Are Pregnant Women with Epilepsy Currently Optimally Managed? A Systematic Review
Authors: Goo Yeonkyung , der Nederlanden Anne Marijn , Bleasel Andrew , Alffenaar Jan-Willem , Kim Hannah Yejin
Published: February 2024

Background:

Lamotrigine monotherapy is the first-line treatment for epilepsy in pregnant women. However, altered pharmacokinetics during pregnancy can lead to suboptimal drug levels and increased seizure risk. This systematic review aimed to evaluate current therapeutic drug monitoring (TDM) strategies for lamotrigine monotherapy in pregnant women with epilepsy and provide guidance for monitoring and dose adjustments.

Methods:

A systematic search was performed using the Ovid-MEDLINE, Ovid-EMBASE, and Ovid-Cochrane Central Register of Controlled Trials databases. Studies were included if data on lamotrigine dosing, concentration, TDM strategies, efficacy, or safety were available.

Results:

Eleven studies were analyzed, revealing heterogeneity in outcomes with selective reporting of TDM strategies; however, clear similarities were observed. Blood samples were collected every 1–3 months during pregnancy to maintain prepregnancy baseline drug levels. Lamotrigine's apparent and relative clearance increased across trimesters, particularly in the second and third trimesters, coinciding with a period of increased seizure frequency and required dose adjustments. Details on dose adjustments were limited. Some studies have proposed using the threshold of the ratio to the target concentration to predict increased seizure risk. No distinct association was observed between adverse newborn outcomes and lamotrigine dose or serum concentration. Few maternal adverse effects have been reported after delivery, confirming the necessity of empirical postpartum tapering.

Conclusions:

Further studies are required to establish evidence-based standardized protocols encompassing all aspects of TDM. Early interventions, such as empirical dose increases during pregnancy and postpartum tapering, and routine monitoring from preconception to the postpartum period may enhance seizure control, reducing the risk of breakthrough seizures for the mother and unborn child.