bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing duplicate genetic testing in inpatient and outpatient settings across a large safety-net system
Authors: Alarcon Manchego Peter , Krouss Mona , Alaiev Daniel , Talledo Joseph , Zaurova Milana , Chandra Komal , Tsega Surafel , Garcia Mariely , Ford Kenra , Apfelroth Stephen , Bajaj Komal , Shin Dawi , Cho Hyung J
Published: May 2023

Objectives

To develop a system-wide electronic health record (EHR) intervention at a large safety-net hospital system to reduce wasteful duplicate genetic testing.

Methods

This project was initiated at a large urban public health care system. An EHR alert was designed to be triggered when a clinician attempted to order any of 16 specified genetic tests for which a previous result existed within the EHR system. Measurements included the proportion of completed genetic tests that were duplicates and alerts per 1,000 tests. Data were stratified by clinician type, specialty, and inpatient vs ambulatory setting.

Results

Across all settings, the rate of duplicate genetic testing decreased from 2.35% (1,050 of 44,592 tests) to 0.09% (21 of 22,323 tests) (96% relative reduction, P < .001). The alert rate per 1,000 tests was 277 for inpatient orders and 64 for ambulatory orders. Among clinician types, residents had the highest alert rate per 1,000 tests at 166 and midwives the lowest at 51 (P < .01). Among clinician specialties, internal medicine had the highest alert rate per 1,000 tests at 245 and obstetrics and gynecology the lowest at 56 (P < .01).

Conclusions

The EHR intervention successfully reduced duplicate genetic testing by 96% across a large safety-net setting.
A self-knowledge distillation-driven CNN-LSTM model for predicting disease outcomes using longitudinal microbiome data
Authors: Fung Daryl L X , Li Xu , Leung Carson K , Hu Pingzhao
Published: May 2023

Motivation

Human microbiome is complex and highly dynamic in nature. Dynamic patterns of the microbiome can capture more information than single point inference as it contains the temporal changes information. However, dynamic information of the human microbiome can be hard to be captured due to the complexity of obtaining the longitudinal data with a large volume of missing data that in conjunction with heterogeneity may provide a challenge for the data analysis.

Results

We propose using an efficient hybrid deep learning architecture convolutional neural network—long short-term memory, which combines with self-knowledge distillation to create highly accurate models to analyze the longitudinal microbiome profiles to predict disease outcomes. Using our proposed models, we analyzed the datasets from Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) study and DIABIMMUNE study. We showed the significant improvement in the area under the receiver operating characteristic curve scores, achieving 0.889 and 0.798 on PROTECT study and DIABIMMUNE study, respectively, compared with state-of-the-art temporal deep learning models. Our findings provide an effective artificial intelligence-based tool to predict disease outcomes using longitudinal microbiome profiles from collected patients.

Availability and implementation

The data and source code can be accessed at https://github.com/darylfung96/UC-disease-TL.
Supervised Machine Learning Classifies Inflammatory Bowel Disease Patients by Subtype Using Whole Exome Sequencing Data
Authors: Stafford Imogen S , Ashton James J , Mossotto Enrico , Cheng Guo , Mark Beattie Robert , Ennis Sarah
Published: May 2023

Background

Inflammatory bowel disease [IBD] is a chronic inflammatory disorder with two main subtypes: Crohn’s disease [CD] and ulcerative colitis [UC]. Prompt subtype diagnosis enables the correct treatment to be administered. Using genomic data, we aimed to assess machine learning [ML] to classify patients according to IBD subtype.

Methods

Whole exome sequencing [WES] from paediatric/adult IBD patients was processed using an in-house bioinformatics pipeline. These data were condensed into the per-gene, per-individual genomic burden score, GenePy. Data were split into training and testing datasets [80/20]. Feature selection with a linear support vector classifier, and hyperparameter tuning with Bayesian Optimisation, were performed [training data]. The supervised ML method random forest was utilised to classify patients as CD or UC, using three panels: 1] all available genes; 2] autoimmune genes; 3] ‘IBD’ genes. ML results were assessed using area under the receiver operating characteristics curve [AUROC], sensitivity, and specificity on the testing dataset.

Results

A total of 906 patients were included in analysis [600 CD, 306 UC]. Training data included 488 patients, balanced according to the minority class of UC. The autoimmune gene panel generated the best performing ML model [AUROC = 0.68], outperforming an IBD gene panel [AUROC = 0.61]. NOD2 was the top gene for discriminating CD and UC, regardless of the gene panel used. Lack of variation in genes with high GenePy scores in CD patients was the best classifier of a diagnosis of UC.

Discussion

We demonstrate promising classification of patients by subtype using random forest and WES data. Focusing on specific subgroups of patients, with larger datasets, may result in better classification.
Cardiac magnetic resonance imaging of pericardial diseases: a comprehensive guide
Authors: Antonopoulos Alexios S , Vrettos Apostolos , Androulakis Emmanouil , Kamperou Christina , Vlachopoulos Charalambos , Tsioufis Konstantinos , Mohiaddin Raad , Lazaros George
Published: May 2023

Cardiac magnetic resonance (CMR) imaging has been established as a valuable diagnostic tool in the assessment of pericardial diseases by providing information on cardiac anatomy and function, surrounding extra-cardiac structures, pericardial thickening and effusion, characterization of pericardial effusion, and the presence of active pericardial inflammation from the same scan. In addition, CMR imaging has excellent diagnostic accuracy for the non-invasive detection of constrictive physiology evading the need for invasive catheterization in most instances. Growing evidence in the field suggests that pericardial enhancement on CMR is not only diagnostic of pericarditis but also has prognostic value for pericarditis recurrence, although such evidence is derived from small patient cohorts. CMR findings could also be used to guide treatment de-escalation or up-titration in recurrent pericarditis and selecting patients most likely to benefit from novel treatments such as anakinra and rilonacept. This article is an overview of the CMR applications in pericardial syndromes as a primer for reporting physicians. We sought to provide a summary of the clinical protocols used and an interpretation of the major CMR findings in the setting of pericardial diseases. We also discuss points that are less well clear and delineate the strengths and weak points of CMR in pericardial diseases.
Weight retention and glucose intolerance in early postpartum after gestational diabetes
Authors: Minschart Caro , Myngheer Nele , Maes Toon , De Block Christophe , Van Pottelbergh Inge , Abrams Pascale , Vinck Wouter , Leuridan Liesbeth , Driessens Sabien , Mathieu Chantal , Billen Jaak , Matthys Christophe , Laenen Annouschka , Bogaerts Annick , Benhalima Katrien
Published: May 2023

Objectives

To determine risk factors for early postpartum weight retention (PPWR) and glucose intolerance (GI) in women with gestational diabetes (GDM).

Design and Methods

Prospective, multicentre (n = 8) cohort study in 1201 women with a recent history of GDM. Pregnancy and postpartum characteristics, and data from self-administered questionnaires were collected at the 6-16 weeks postpartum 75 g oral glucose tolerance test.

Results

Of all participants, 38.6% (463) had moderate (>0 and ≤5 kg) and 15.6% (187) had high (>5 kg) PPWR. Independent predictors for early PPWR were excessive gestational weight gain (GWG), lack of breastfeeding, higher dietary fat intake, insulin use during pregnancy, multiparity, lower prepregnancy body mass index (BMI), and lower education degree. Compared to PPWR <5 kg, women with high PPWR had a more impaired postpartum metabolic profile, breastfed less often, had higher depression rates (23.1% [43] vs 16.0% [74], P = .035) and anxiety levels, and lower quality of life. Of all participants, 28.0% (336) had GI (26.1% [313] prediabetes and 1.9% [23] diabetes). Women with high PPWR had more often GI compared to women without PPWR (33.7% [63] vs 24.9% [137], P = .020). Only 12.9% (24) of women with high PPWR perceived themselves at high risk for diabetes but they were more often willing to change their lifestyle than women with moderate PPWR.

Conclusions

Modifiable risk factors such as lifestyle, prepregnancy BMI, GWG, and mental health can be used to identify a subgroup of women with GDM at the highest risk of developing early PPWR, allowing for a more personalized follow-up.
Synthesizing the phylogenetic evidence for mutualism-associated diversification
Authors: Kaur Katrina M , Pennell Matt
Published: May 2023

Mutualisms are associations in which interacting species provide services or resources to each other. It has been suggested that being party to a mutualism can spur the diversification of the interacting species due to several potential hypothesized mechanisms. There is empirical evidence to both support and refute this prediction. However, this evidence comes from a variety of different methodologies, some of which have been found to be unreliable when the phylogenetic model is misspecified, and different data types and it is therefore difficult to weigh together. Here, we synthesize phylogenetic comparative datasets and analyze the data in a consistent manner using both sister-clade comparisons and hidden-trait state-dependent speciation and extinction models. The results are mixed—for the majority of the datasets we find no evidence for an effect on diversification rates in either direction, with several showing significant positive associations and a few showing significant negative associations. In contrast to the generally mixed findings between datasets, we find that qualitative results to be consistent when analyzing taxonomically overlapping datasets using different methods, suggesting that the detected variation in diversification is due to the nature of the mutualism and not due to differences in methodology.
Tectonic evolution of the Yangsan Fault, SE-Korea, by gravity field interpretation
Authors: Choi Sungchan , Kim Sung-Wook , Yoon Jeoung-Seok , Choi Eun-Kyeong
Published: May 2023

To estimate the tectonic displacement history of the Yangsan Fault (YSF) in the Cretaceous Gyeongsang Basin (GB), SE-Korea, gravity field measurements were implemented and interpreted. A total of 8000 ground-measured gravity data were compiled and deployed to calculate the Bouguer and residual gravity field. The residual field shows that the mean value in the southern segment of the YSF is very similar to that of the northern segment, meanwhile that of the central segmentation is significantly lower than those of the other segmentations. This implies that the crustal structure and petrophysical properties of the central segment differ significantly from those of the other segments. Applying dip curvature analysis to enhance the image of the residual gravity field, we find that (1) the Gaum fault system (GF) in the western and middle part of the GB extends up to the YSF, where A-type granite outcrops are observed. (2) The middle- and eastern segments of the GF that formed before tectonic motion of the YSF are revealed in turn in areas east of the YSF, which were now covered by the younger sedimentary basin. (3) The middle segment of the GF which occupies between the YSF and the Yeonil tectonic line (YTL) has been displaced approximately 25 km southward from the main GF trace. (4) The easternmost segment is revealed buried in the eastern side of the YTL, which is displaced southward about 18 km from the main GF trace. Comparing all the available geoscientific data sets, we conclude that the right-lateral tectonic movement of the YSF, and the deeply buried middle segment of the GF remained stationary, while the most eastern segment of the GF is reversely moved to the north through left-lateral strike movement of the YTL.
Evolution and phylogenetic distribution of endo-α-mannosidase
Authors: Sobala Łukasz F
Published: May 2023

While glycans underlie many biological processes, such as protein folding, cell adhesion, and cell–cell recognition, deep evolution of glycosylation machinery remains an understudied topic. N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. It is unique as the only endo-acting mannosidase found in this organelle. Relatively little is known about its origins and evolutionary history; so far it was reported to occur only in vertebrates. In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. The endomannosidase was found to be more widely distributed in animals and other eukaryotes. The protein motif changes in context of the canonical animal enzyme were tracked. Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. Finally, a framework where N-glycosylation co-evolved with complex multicellularity is described. A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. This systematic analysis of the endomannosidase evolution is one step toward this goal.
Exploration, exploitation, and mode of market entry: acquisition versus internal development by Amazon and Alphabet
Authors: Lee Gwendolyn K , Lieberman Marvin B
Published: May 2023

Research on the tension between exploration and exploitation has made fundamental contributions to our understanding of firm growth via entry into new businesses. While there is consensus about the merits of balancing exploration and exploitation, there has been debate about the best means for achieving balance. In our prior analysis of firms’ choices between acquisition and internal development as entry modes, we found that the role of acquisitions tends to differ inside versus outside a firm’s primary business domain: firms use within-domain acquisitions largely for exploitation, while out-of-domain acquisitions support exploration. To examine these issues in greater depth, we focus here on the historical use of acquisition versus internal development by two major technology firms, Amazon and Alphabet. We show that the two firms have been remarkably different in their use of acquisitions versus internal development. Consistent with our prior analysis, Amazon has emphasized internal development but has used acquisitions to strengthen its existing businesses and to enter new products and services that were (initially) outside Amazon’s primary business domain. In contrast, Alphabet has relied heavily on acquisitions to enter new businesses within its primary domain but has emphasized internal development of “moonshot” businesses outside this domain. These differences illuminate the use of acquisitions in market entry and make clear that there is no single right way to utilize acquisition versus internal development in the pursuit of balance between exploration and exploitation.
Medial Prefrontal Cortex to Medial Septum Pathway Activation Improves Cognitive Flexibility in Rats
Authors: Bortz David M , Feistritzer Catalina M , Grace Anthony A
Published: May 2023

Background

The medial prefrontal cortex (mPFC) is necessary for cognitive flexibility and projects to medial septum (MS). MS activation improves strategy switching, a common measure of cognitive flexibility, likely via its ability to regulate midbrain dopamine (DA) neuron population activity. We hypothesized that the mPFC to MS pathway (mPFC-MS) may be the mechanism by which the MS regulates strategy switching and DA neuron population activity.

Methods

Male and female rats learned a complex discrimination strategy across 2 different training time points: a constant length (10 days) and a variable length that coincided with each rat meeting an acquisition-level performance threshold (males: 5.3 ± 0.3 days, females: 3.8 ± 0.3 days). We then chemogenetically activated or inhibited the mPFC-MS pathway and measured each rat’s ability to inhibit the prior learned discrimination strategy and switch to a prior ignored discrimination strategy (strategy switching).

Results

Activation of the mPFC-MS pathway improved strategy switching after 10 days of training in both sexes. Inhibition of the pathway produced a modest improvement in strategy switching that was quantitatively and qualitatively different from pathway activation. Neither activation nor inhibition of the mPFC-MS pathway affected strategy switching following the acquisition-level performance threshold training regimen. Activation, but not inhibition, of the mPFC-MS pathway bidirectionally regulated DA neuron activity in the ventral tegmental area and substantia nigra pars compacta, similar to general MS activation.

Conclusions

This study presents a potential top-down circuit from the prefrontal cortex to the midbrain by which DA activity can be manipulated to promote cognitive flexibility.
Environmental Impact Assessment for the Use of an Orally Aerosolized Adenovirus Type-5 Vector-Based COVID-19 Vaccine in Randomized Clinical Trials
Authors: Xia Xin , Tan Zhong-Ming , Wan Peng , Zheng Hao , Tang Rong , Chen Xiao-Qin , Guo Xi-Ling , Zhu Tao , Feng Jia-Lu , Zhong Jin , Li Xiao-Long , Zhang Zhen-Yu , Zhu Feng-Cai , Li Jing-Xin
Published: May 2023

Background

An orally aerosolized adenovirus type-5 vector-based coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolized Ad5-nCoV.

Methods

We collected air samples from rooms, swabs from the desks on which the vaccine nebulizer was set, mask samples from participants, and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in serum were detected.

Results

Only one (4.00%) air sample collected before initiation of vaccination was positive and most air samples collected during and after vaccination were positive (97.96%, 100%, respectively). All nurses in trial A showed at least 4-fold increase of the neutralizing antibody against SARS-CoV-2 after initiation of the study. In trial B, the proportion of positive mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7.

Conclusions

Vaccination with the orally aerosolized Ad5-nCoV could result in some spillage of the vaccine vector viral particles in the environment and cause human exposure.

Clinical Trials Registration. NCT04840992 and NCT05303584.
Prevalence of Giardia duodenalis among Asian children: a systematic review and meta-analysis
Authors: Kalavani Sara , Matin Sara , Rahmanian Vahid , Meshkin Ahmad , Taghipour Ali , Abdoli Amir
Published: May 2023

Giardia duodenalis is one of the major causes of diarrhea among children. We performed a systematic review and meta-analysis to assess the prevalence of G. duodenalis and associated risk factors among Asian children. We searched online databases (PubMed, Scopus and Web of Science) and Google Scholar search engine for studies published from 1 January 2000 to 15 March 2022 that measured the prevalence of G. duodenalis among Asian children. Accordingly, the pooled prevalence and 95% CIs were estimated using a random-effects meta-analysis model for the included studies. A total of 182 articles from 22 Asian countries met the inclusion criteria. The pooled prevalence of G. duodenalis infection among Asian children was estimated as 15.1% (95% CI 14.1 to 16%). The highest and lowest pooled prevalence values of G. duodenalis infection were estimated for Tajikistan and China as 26.4% (95% CI 22.9 to 30%) and 0.6% (95% CI 0.001 to 1.02%), respectively. The infection had a higher prevalence in males than in females (OR=1.24; 95% CI 1.16 to 1.31; p<0.001), which was statistically significant. Giardiasis is common among Asian children, hence, a prevention and control scheme of this protozoan in children should be considered by health officials and health policymakers, especially in Asian countries where the prevalence is highest.
A Typology of Ontological Insecurity Mechanisms: Russia's Military Engagement in Syria
Authors: von Essen Hugo , Danielson August
Published: May 2023

Because of the novel explanations it generates for states’ security- and identity-related behavior, the concept of ontological security has been used increasingly in the International Relations (IR) literature in recent years. However, the abundance of interpretations of the concept means that it is often used in conflicting ways. To counter the risk of conceptual stretching and provide the foundation for a common research agenda, this article constructs a typology of ontological security mechanisms. Two dimensions of ontological insecurity are highlighted: the sources and the causes of anxiety. We argue that the source of anxiety can be reflexive, relational, or systemic, while the cause of anxiety can be either shame or discontinuity. These two dimensions produce six mechanisms of ontological insecurity that reflect how the concept is used in the contemporary ontological security literature in IR. By specifying these mechanisms, we argue that the typology offers IR scholars the ability to produce even more nuanced and fine-grained explanations of state behavior driven by ontological insecurity. Finally, to demonstrate the utility of this typology, the article provides an illustrative case study of Russia's engagement in the conflict in Syria in 2015–2017.
Reproductive performance and transcriptome analysis of ovaries at different parities in female rabbits
Authors: Chen Yang , Wang Fan , Bai Shaocheng , Chen Xin , Han Xudong , Cai Jiawei , Bao Zhiyuan , Cao Chao , Zhao Bohao , Wu Xinsheng
Published: May 2023

This study investigated the reproductive performance and ovarian molecular regulation associated with parity in commercial rabbit systems. The pregnancy data of 658 female rabbits from the first to sixth parities (P1 to P6) under the same mating pattern were analyzed, showing a significant decrease in the conception rate in P6. Compared to P1 (N = 120) and P2 (N = 105), P6 (N = 99) had significantly lower performance indices in terms of total litter size, live litter size, survival rate at birth, and weight of 3 and 5 wk old kits (P < 0.05). Using H&E staining, we found that the ovarian primordial follicle reservoir of P6 was significantly lower than that of P1 and P2, and the number of atretic follicles at P6 was significantly higher (P < 0.05). Blood (N = 30 per group) and ovaries (N = 6 per group) in P1, P2, and P6 were collected for measurement of the serum anti-oxidant capacity and indices of ovarian function by ELISA. It was found that serum glutathione, ovarian Klotho protein, and telomeres of P1 and P2 were significantly higher than those of P6 (P < 0.05). The serum levels of ROS and MDA at P1 and P2 were significantly lower than those at P6 (P < 0.05). Additionally, transcriptome analysis showed 213 up-regulated and 747 down-regulated differentially expressed genes (DEGs) between P2 and P6 ovaries. Several DEGs were related to reproduction, including CYP21A2, PTGFR, SGK1, PIK3R6, and SRD5A2. These results demonstrate the influence of parity on reproduction in female rabbits, reflected in a loss of follicle reservoir, disordered levels of anti-oxidants, and indices associated with ovarian function and molecular regulation. This study provides a basis for the strategies to increase reproductive rate in female rabbits.
Computationally efficient and data-adaptive changepoint inference in high dimension
Authors: Wang Guanghui , Feng Long
Published: May 2023

High-dimensional changepoint inference that adapts to various change patterns has received much attention recently. We propose a simple, fast yet effective approach for adaptive changepoint testing. The key observation is that two statistics based on aggregating cumulative sum statistics over all dimensions and possible changepoints by taking their maximum and summation, respectively, are asymptotically independent under some mild conditions. Hence, we are able to form a new test by combining the p-values of the maximum- and summation-type statistics according to their asymptotic null distributions. To this end, we develop new tools and techniques to establish the asymptotic distribution of the maximum-type statistic under a more relaxed condition on componentwise correlations among all variables than those in existing literature. The proposed method is simple to use. It is adaptive to different levels of the sparsity of change signals, and is comparable to or even outperforms existing approaches as revealed by our numerical studies.
Catastrophic outcomes of thrombus ‘bumper’ ball in neglected severe rheumatic mitral stenosis: report of three cases
Authors: Agoumy Zineb , Bachri Houda , Mhadi Samah E L , Chraibi Hamza , Fehri Zineb F , Bakamel Lamyaa , El Assili Hala , Berrag Kaoutar , Es-sebany Sanae , Leghlimi Hasna , Lachhab Fadwa , Tribak Mohamed , Bensouda Adil , Chaib Ali , Bendagha Nesma , Soufiani Aida , Moughil Said
Published: May 2023

Patients with rheumatic mitral stenosis (MS) often present complications such as atrial fibrillation and thrombus formation with significant morbi-mortality. Rarely, a free-floating ‘ball thrombus’ is found with possible catastrophic outcomes. We describe three cases of documented left atrial ‘ping-pong’ shaped ‘thrombus ball’ within MS: a 51 year old presented with acute heart failure with a fatal outcome due to the huge round thrombus closing the tight mitral valve, a 67-year-old and a 68-year-old male who were both urgently rushed to the operating room after accidental finding. The surgery was successful and consisted on mitral valve repair and thrombectomy. Our aim is to show that gigantic unattached thrombus ball within neglected rheumatism MS is a rare life-threatening entity, thus highlighting the importance of early diagnosis of such conditions present in endemic countries. A prompt surgery should be considered to avoid an eventual embolization and sudden death.
The design of synthetic gene circuits in plants: new components, old challenges
Authors: Vazquez-Vilar Marta , Selma Sara , Orzaez Diego
Published: May 2023

The fascination produced by the possibility of engineering plants with augmented capabilities has accompanied plant biotechnology since its origins. This prospect has become even more relevant in present times under the pressure imposed by climate change and population growth. Today’s plant biotechnologists approach this challenge with the tools of synthetic biology, which facilitate the assembly of synthetic gene circuits (SGCs) from their modular components. Transcriptional SGCs take environmental or endogenous inputs and operate them using transcriptional signals in ways that do not necessarily occur in nature, generating new physiological outputs. Many genetic components have been developed over the years that can be employed in the design and construction of plant SGCs. This review aims to provide an updated view of the components available, proposing a general scheme that facilitates the classification of circuit components in sensor, processor, and actuator modules. Following this analogy, we review the latest advances in the design of SGCs and discuss the main challenges ahead.
Vitamin D Status in Palindromic Rheumatism: A Propensity Score Matching Analysis
Authors: Khabbazi Alireza , Mahmoudi Maryam , Esalatmanesh Kamal , Asgari-Sabet Masoomeh , Safary Azam
Published: May 2023

Objective

To determine whether there is a correlation between vitamin D levels and palindromic rheumatism (PR) as an at-risk phenotype of rheumatoid arthritis (RA).

Methods

A total of 308 participants were enrolled in this cross-sectional study. We recorded their clinical characteristics and performed propensity-score matching (PSM). Serum 25(OH)D3 levels were determined via enzyme-linked immunosorbent assay.

Results

Our PSM resulted in 48 patients with PR and 96 matched control individuals. The multivariate regression analysis we performed after the PSM did not show a significant increase in PR risk in patients with vitamin D deficiency/insufficiency. There was no significant correlation between levels of 25(OH)D3 and frequency/duration of attacks, number of joints affected, and duration of symptoms before diagnosis (P ≥ .05). Mean (SD) serum levels of 25(OH)D3 in patients with and without progression to RA were 28.7 (15.9) ng/mL and 25.1 (11.4) ng/mL, respectively.

Conclusion

Based on the results, we found no clear association between vitamin D serum levels and the risk, severity, and rate of PR progressing into RA.
Meridional circulation driven by planetary spiral wakes in radiative and magnetized protoplanetary discs
Authors: Cilibrasi Marco , Flock Mario , Szulágyi Judit
Published: May 2023

We study a Jupiter-mass planet formation for the first time in radiative magnetohydrodynamics (MHD) simulations and compare it with pure hydrodynamical simulations, and also with different isothermal configurations. We found that the meridional circulation is the same in every set-up. The planetary spiral wakes drive a vertical stirring inside the protoplanetary disc and the encounter with these shock fronts also helps in delivering gas vertically on to the Hill sphere. The accretion dynamics are unchanged: the planet accretes vertically, and there is outflow in the mid-plane regions inside the Hill sphere. We determined the effective α-viscosity generated in the disc by the various angular momentum loss mechanisms, which showed that magnetic fields produce high turbulence in the ideal MHD limit, and grows from α ∼ 10−2.5 up to ∼10−1.5 after the planet spirals develop. In the HD simulations, the planetary spirals contribute to α ∼ 10−3, making this a very important angular momentum transport mechanism. Due to the various α values in the different set-ups, the gap opening is different in each case. In the radiative MHD set-ups, the high turbulent viscosity prevents gap opening, leading to a higher Hill mass, and no clear dust trapping regions. While the Hill accretion rate is $10^{-6}~ \rm {M_{Jup}\,yr^{-1}}$ in all set-ups, the accretion variability is orders of magnitude higher in radiative runs than in isothermal ones. Finally, with higher resolution runs, the magnetorotational instability started to be resolved, changing the effective viscosity and increasing the heating in the disc.
A forecast for large-scale structure constraints on Horndeski gravity with CO line intensity mapping
Authors: Scott Bryan R , Karkare Kirit S , Bird Simeon
Published: May 2023

We consider the potential for line intensity mapping (LIM) of the rotational CO(1-0), CO(2-1), and CO(3-2) transitions to detect deviations from General Relativity from 0 < z < 3 within the framework of a very general class of modified gravity models, called Horndeski’s theories. Our forecast assumes a multitracer analysis separately obtaining information from the matter power spectrum and the first two multipoles of the redshift space distortion power spectrum. To achieve ±0.1 level constraints on the slope of the kinetic gravity braiding and Planck mass evolution parameters, a mm-wave LIM experiment would need to accumulate ≈108–109 spectrometre-hours, feasible with instruments that could be deployed in the 2030s. Such a measurement would constrain the parameters of Horndeski’s theory at a level at worst competitive to and at best an order of magnitude tighter than existing constraints from the CMB and LSS. Our modelling code is publicly available.
Quantifying the influence of bars on action-based dynamical modelling of disc galaxies
Authors: Ghosh Soumavo , Trick Wilma H , Green Gregory M
Published: May 2023

Action-based dynamical modelling, using stars as dynamical tracers, is an excellent diagnostic to estimate the underlying axisymmetric matter distribution of the Milky Way. However, the Milky Way’s bar causes non-axisymmetric resonance features in the stellar disc. Using RoadMapping (an action-based dynamical modelling framework to estimate the gravitational potential and the stellar distribution function), we systematically quantify the robustness of action-based modelling in the presence of a bar. We construct a set of test-particle simulations of barred galaxies (with varying bar properties), and apply RoadMapping to different survey volumes (with varying azimuthal position, size) drawn from these barred models. For realistic bar parameters, the global potential parameters are still recovered to within ∼1–17 per cent. However, with increasing bar strength, the best-fitting values of the parameters progressively deviate from their true values. This happens due to a combination of radial heating, radial migration, and resonance overlap phenomena in our bar models. Furthermore, the azimuthal location and the size of the survey volumes play important roles in the successful recovery of the parameters. Survey volumes along the bar major axis produce larger (relative) errors in the best-fitting parameter values. In addition, the potential parameters are better recovered for survey volumes with larger spatial coverage. As the Sun is located just ∼28°–33° behind the bar’s major axis, an estimate for the bar-induced systematic bias – as provided by this study – is therefore crucial for future modelling attempts of the Milky Way.
Fendrr synergizes with Wnt signalling to regulate fibrosis related genes during lung development via its RNA:dsDNA triplex element
Authors: Ali Tamer , Rogala Sandra , Krause Nina M , Bains Jasleen Kaur , Melissari Maria-Theodora , Währisch Sandra , Schwalbe Harald , Herrmann Bernhard G , Grote Phillip
Published: May 2023

Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via an RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and found that this FendrrBox is partially required for Fendrr function in vivo. We found that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs associated with lung fibrosis. A set of these genes contain a triplex site directly at their promoter and are expressed in lung fibroblasts. We biophysically confirmed the formation of an RNA:dsDNA triplex with target promoters in vitro. We found that Fendrr with the Wnt signalling pathway regulates these genes, implicating that Fendrr synergizes with Wnt signalling in lung fibrosis.
Structural analysis of the Candida albicans mitochondrial DNA maintenance factor Gcf1p reveals a dynamic DNA-bridging mechanism
Authors: Tarrés-Solé Aleix , Battistini Federica , Gerhold Joachim M , Piétrement Olivier , Martínez-García Belén , Ruiz-López Elena , Lyonnais Sébastien , Bernadó Pau , Roca Joaquim , Orozco Modesto , Le Cam Eric , Sedman Juhan , Solà Maria
Published: May 2023

The compaction of mitochondrial DNA (mtDNA) is regulated by architectural HMG-box proteins whose limited cross-species similarity suggests diverse underlying mechanisms. Viability of Candida albicans, a human antibiotic-resistant mucosal pathogen, is compromised by altering mtDNA regulators. Among them, there is the mtDNA maintenance factor Gcf1p, which differs in sequence and structure from its human and Saccharomyces cerevisiae counterparts, TFAM and Abf2p. Our crystallographic, biophysical, biochemical and computational analysis showed that Gcf1p forms dynamic protein/DNA multimers by a combined action of an N-terminal unstructured tail and a long helix. Furthermore, an HMG-box domain canonically binds the minor groove and dramatically bends the DNA while, unprecedentedly, a second HMG-box binds the major groove without imposing distortions. This architectural protein thus uses its multiple domains to bridge co-aligned DNA segments without altering the DNA topology, revealing a new mechanism of mtDNA condensation.
Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease
Authors: Hasegawa Takeshi , Imaizumi Takahiro , Hamano Takayuki , Murotani Kenta , Fujii Naohiko , Komaba Hirotaka , Ando Masahiko , Maruyama Shoichi , Nangaku Masaomi , Nitta Kosaku , Hirakata Hideki , Isaka Yoshitaka , Wada Takashi , Fukagawa Masafumi
Published: May 2023

Background

The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data.

Methods

We included 1416 patients ages 20–75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine–Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events.

Results

The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P = .042).

Conclusions

Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.
Sacubitril/valsartan ameliorates renal tubulointerstitial injury through increasing renal plasma flow in a mouse model of type 2 diabetes with aldosterone excess
Authors: Nishio Haruomi , Ishii Akira , Yamada Hiroyuki , Mori Keita P , Kato Yukiko , Ohno Shoko , Handa Takaya , Sugioka Sayaka , Ishimura Takuya , Ikushima Akie , Inoue Yui , Minamino Naoto , Mukoyama Masashi , Yanagita Motoko , Yokoi Hideki
Published: May 2023

Background

Aldosterone has been assumed to be one of aggravating factors in diabetic kidney disease (DKD). Natriuretic peptides/guanylyl cyclase-A/cGMP signalling has been shown to ameliorate aldosterone-induced renal injury in mice. Sacubitril/valsartan (SAC/VAL) is used clinically for chronic heart failure and hypertension, in part by augmenting natriuretic peptide bioavailability. The effects of SAC/VAL on renal pathophysiology including in DKD, however, have remained unclarified.

Methods

Eight-week-old male db/db mice fed on a high-salt diet (HSD) were treated with vehicle or aldosterone (0.2 μg/kg/min), and divided into four groups: HSD control, ALDO (aldosterone), ALDO + VAL (valsartan), and ALDO + SAC/VAL group. After 4 weeks, they were analysed for plasma atrial natriuretic peptide (ANP) levels, renal histology, and haemodynamic parameters including glomerular filtration rate (GFR) by FITC-inulin and renal plasma flow (RPF) by para-amino hippuric acid.

Results

The ALDO + SAC/VAL group showed significantly increased plasma ANP concentration and creatinine clearance, and decreased tubulointerstitial fibrosis and neutrophil gelatinase-associated lipocalin expression compared to ALDO and ALDO + VAL groups. SAC/VAL treatment increased GFR and RPF, and suppressed expression of Tgfb1, Il1b, Ccl2, and Lcn2 genes compared to the ALDO group. The percentage of tubulointerstitial fibrotic areas negatively correlated with the RPF and GFR.

Conclusion

In a mouse model of type 2 diabetes with aldosterone excess, SAC/VAL increased RPF and GFR, and ameliorated tubulointerstitial fibrosis. Furthermore, RPF negatively correlated well with tubulointerstitial injury, suggesting that the beneficial effects of SAC/VAL could be through increased renal plasma flow with enhanced natriuretic peptide bioavailability.
Toddler milk: a scoping review of research on consumption, perceptions, and marketing practices
Authors: Richter Ana Paula C , Grummon Anna H , Falbe Jennifer , Taillie Lindsey Smith , Wallace Deshira D , Lazard Allison J , Golden Shelley D , Conklin Jamie L , Hall Marissa G
Published: May 2023

Toddler milk is an ultra-processed beverage consisting primarily of powdered milk, caloric sweeteners, and vegetable oil. Pediatric health authorities do not support the use of toddler milk, and emerging evidence suggests that toddler-milk marketing practices may mislead consumers. However, studies have not synthesized the extent of toddler-milk marketing practices or how these practices affect parents’ decisions about whether to serve toddler milk. We aimed to summarize the literature about toddler milk to identify what is known about: (1) parents’ toddler-milk purchasing and feeding behaviors, (2) toddler-milk marketing, and (3) how marketing practices influence parents’ beliefs and perceptions about toddler milk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we systematically searched 8 databases (PubMed, APA PsycINFO, Scopus, Cochrane Central, Embase, CINAHL, Communication & Mass Media Complete, and Business Source Premier). We identified 45 articles about toddler milk. Studies were conducted in 25 countries across 6 continents. Five types of findings emerged: (1) consumption and feeding behaviors, (2) demographic correlates of toddler-milk purchasing and consumption, (3) misperceptions and beliefs, (4) increased sales, and (5) increased marketing and responses to marketing. The included articles suggested that toddler-milk sales are growing rapidly worldwide. Findings also revealed that toddler-milk packages (eg, labels, branding) resemble infant formula packages and that toddler-milk marketing practices may indirectly advertise infant formula. Purchasing, serving, and consumption of toddler milk were higher in Black and Hispanic populations than in non-Hispanic White populations, and parents with higher educational attainment and income were more likely to offer toddler milk to their children. Findings suggest a need for policies to prevent cross-marketing of toddler milk and infant formula, reduce provision of toddler milk to infants and toddlers, and prevent caregivers from being misled about toddler-milk healthfulness.
Unemployment insurance design with repeated choices
Authors: Kankanamge Sumudu , Weitzenblum Thomas
Published: May 2023

This article characterizes the relation between the equilibrium unemployment insurance replacement rate and the frequency of its political choice. We first use a tractable analytical model to show how insurance, incentive, and redistribution effects interact at the equilibrium. We then examine a fully repeated choices equilibrium in a quantitative heterogeneous agents model and show that unemployment persistence, whether a policy is announced first or not, and the type of the political process are key determinants of the relation between the equilibrium replacement rate and the frequency of its choice. In a utilitarian welfare context, we find that the equilibrium replacement rate is higher if the policy is chosen more frequently but this relation is reversed in a median voter context.
Nonlocal Kondo effect and two-fluid picture revealed in an exactly solvable model
Authors: Wang Jiangfan , Yang Yi-feng
Published: May 2023

Understanding the nature of local–itinerant transition of strongly correlated electrons is one of the central problems in condensed matter physics. Heavy fermion systems describe the f-electron delocalization through Kondo interactions with conduction electrons. Tremendous efforts have been devoted to the so-called Kondo-destruction scenario, which predicts a dramatic local-to-itinerant quantum phase transition of f-electrons at zero temperature. On the other hand, two-fluid behaviors have been observed in many materials, suggesting coexistence of local and itinerant f-electrons over a broad temperature range but lacking a microscopic theoretical description. To elucidate this fundamental issue, here we propose an exactly solvable Kondo-Heisenberg model in which the spins are defined in the momentum space and the k-space Kondo interaction corresponds to a highly nonlocal spin scattering in the coordinate space. Its solution reveals a continuous evolution of the Fermi surfaces with Kondo interaction and two-fluid behaviors similar to those observed in real materials. The electron density violates the usual Luttinger’s theorem, but follows a generalized one allowing for partially enlarged Fermi surfaces due to partial Kondo screening in the momentum space. Our results highlight the consequence of nonlocal Kondo interaction relevant for strong quantum fluctuation regions and provide important insight into the microscopic description of two-fluid phenomenology in heavy fermion systems.
Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis
Authors: Campanaro Francesco , Zaffaroni Andrea , Cacioppo Elettra , Cappelli Antonella , Bertù Lorenza , Donadini Marco Paolo , Squizzato Alessandro , Batticciotto Alberto
Published: May 2023

Objective

Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs).

Methods

Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143.

Results

We have included one phase I, 21 phase II, three phase II–III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage.

Conclusion

JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs.