bluuebunny/crossref_metadata_2025_split huggingface dataset:
q2-metnet: QIIME2 package to analyse 16S rRNA data via high-quality metabolic reconstructions of the human gut microbiota
Authors: Balzerani Francesco , Blasco Telmo , Pérez-Burillo Sergio , Francino M Pilar , Rufián-Henares José Á , Valcarcel Luis V , Planes Francisco J 
Published: July 2024

Abstract

Motivation
16S rRNA gene sequencing is the most frequent approach for the characterization of the human gut microbiota. Despite different efforts in the literature, the inference of functional and metabolic interpretations from 16S rRNA gene sequencing data is still a challenging task. High-quality metabolic reconstructions of the human gut microbiota, such as AGORA and AGREDA, constitute a curated resource to improve functional inference from 16S rRNA data, but they are not typically integrated into standard bioinformatics tools.

Results
Here, we present q2-metnet, a QIIME2 plugin that enables the contextualization of 16S rRNA gene sequencing data into AGORA and AGREDA. In particular, based on relative abundances of taxa, q2-metnet determines normalized activity scores for the reactions and subsystems involved in the selected metabolic reconstruction. Using these scores, q2-metnet allows the user to conduct differential activity analysis for reactions and subsystems, as well as exploratory analysis using PCA and hierarchical clustering. We apply q2-metnet to a dataset from our group that involves 16S rRNA data from stool samples from lean, allergic to cow’s milk, obese and celiac children, and the Belgian Flemish Gut Flora Project cohort, which includes faecal 16S rRNA data from obese and normal-weight adult individuals. In the first case, q2-metnet outperforms existing algorithms in separating different clinical conditions based on predicted pathway abundances and subsystem scores. In the second case, q2-metnet complements competing approaches in predicting functional alterations in the gut microbiota of obese individuals. Overall, q2-metnet constitutes a powerful bioinformatics tool to provide metabolic context to 16S rRNA data from the human gut microbiota.

Availability and implementation
Python code of q2-metnet is available in https://github.com/PlanesLab/q2-metnet and https://figshare.com/articles/dataset/q2-metnet_package/26180446.
Protease expression in the human and rat cumulus–oocyte complex during the periovulatory period: a role in cumulus–oocyte complex migration
Authors: Shrestha Ketan , Puttabyatappa Muraly , Wynn Michelle A , Hannon Patrick R , Al-Alem Linah F , Rosewell Katherine L , Akin James , Curry Thomas E 
Published: July 2024

Abstract
The migratory and matrix-invading capacities of the cumulus–oocyte complex have been shown to be important for the ovulatory process. In metastatic cancers, these capacities are due to increased expression of proteases, however, there is limited information on protease expression in the cumulus–oocyte complexes. The present study examined cumulus–oocyte complex expression of plasmins, matrix metalloproteases, and A Disintegrin and Metalloproteinase with Thrombospondin Motifs family members in the rat and human. In the rat, human chorionic gonadotropin (hCG) administration increased cumulus–oocyte complex expression of Mmp2, Mmp9, Mmp13, Mmp14, Mmp16, Adamts1, and the protease inhibitors Timp1, Timp3, and Serpine1 by 8–12 h. This ovulatory induction of proteases in vivo could be mimicked by forskolin and ampiregulin treatment of cultured rat cumulus–oocyte complexes with increases observed in Mmp2, Mmp13, Mmp14, Mmp16, Mmp19, Plat, and the protease inhibitors Timp1, Timp3, and Serpine1. Comparison of expression between rat cumulus–oocyte complexes and granulosa cells at the time of ovulation showed decreased Mmp9 and increased Mmp13, Mmp14, Mmp16, Adamts1, Timp1, and Timp3 expression in the cumulus–oocyte complexes. In human, comparison of expression between cumulus and granulosa cells at the time of in vitro fertilization retrieval showed decreased MMP1, MMP2, MMP9, and ADAMTS1, while expression of MMP16, TIMP1, and TIMP3 were increased. Treatment of expanding rat cumulus–oocyte complexes with a broad spectrum matrix metalloproteases inhibitor, GM6001, significantly reduced the migration of cumulus cells in vitro. These data provide evidence that multiple proteases and their inhibitors are expressed in the cumulus–oocyte complex and play an important role in imparting the migratory phenotype of the cumulus–oocyte complex at the time of ovulation.
Summary Sentence
Multiple proteases and their inhibitors are induced in the cumulus–oocyte complex (COC) during the periovulatory period and potentially play an important role in imparting the migratory phenotype of the COC at the time of ovulation.
Multiply robust estimation of marginal structural models in observational studies subject to covariate-driven observations
Authors: Coulombe Janie , Yang Shu 
Published: July 2024

ABSTRACT
Electronic health records and other sources of observational data are increasingly used for drawing causal inferences. The estimation of a causal effect using these data not meant for research purposes is subject to confounding and irregularly-spaced covariate-driven observation times affecting the inference. A doubly-weighted estimator accounting for these features has previously been proposed that relies on the correct specification of two nuisance models used for the weights. In this work, we propose a novel consistent multiply robust estimator and demonstrate analytically and in comprehensive simulation studies that it is more flexible and more efficient than the only alternative estimator proposed for the same setting. It is further applied to data from the Add Health study in the United States to estimate the causal effect of therapy counseling on alcohol consumption in American adolescents.
“Under the hood”: artificial intelligence in personalized radiotherapy
Authors: Gianoli Chiara , De Bernardi Elisabetta , Parodi Katia 
Published: July 2024

Abstract
This review presents and discusses the ways in which artificial intelligence (AI) tools currently intervene, or could potentially intervene in the future, to enhance the diverse tasks involved in the radiotherapy workflow. The radiotherapy framework is presented on 2 different levels for the personalization of the treatment, distinct in tasks and methodologies. The first level is the clinically well-established anatomy-based workflow, known as adaptive radiation therapy. The second level is referred to as biology-driven workflow, explored in the research literature and recently appearing in some preliminary clinical trials for personalized radiation treatments. A 2-fold role for AI is defined according to these 2 different levels. In the anatomy-based workflow, the role of AI is to streamline and improve the tasks in terms of time and variability reductions compared to conventional methodologies. The biology-driven workflow instead fully relies on AI, which introduces decision-making tools opening uncharted frontiers that were in the past deemed challenging to explore. These methodologies are referred to as radiomics and dosiomics, handling imaging and dosimetric information, or multiomics, when complemented by clinical and biological parameters (ie, biomarkers). The review explicitly highlights the methodologies that are currently incorporated into clinical practice or still in research, with the aim of presenting the AI’s growing role in personalized radiotherapy.
Voices of Refugee Families from Ukraine Currently Living in the Czech Republic
Authors: Racko Veronika , Mikulcová Kateřina 
Published: July 2024

Abstract
The living situation of Ukrainian refugees in the Czech Republic can be explored from various perspectives. However, the currently available data are not able to provide a sufficient view of the refugee situation. These data are rather economic (related to financial situation, employment, wage disadvantage, use of state aid, etc) and do not provide, for example, information on daily needs. Our goal is therefore to give a voice to refugees from Ukraine to describe their current perception of their life situation and based on this establish implications for social work. The data were created through the perspective of participatory research using the photovoice method (individual and group) interviews (n = 13), online responsive questionnaire survey (n = 41) and a final photo exhibition. According to the available data, the context of life situation was created by economic well-being. But the key theme of life situation of Ukrainian refugees was loneliness. An interesting aspect is the gender dimension of activities coping with loneliness, which especially includes the ‘typically female role’ of childcare.
The involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network
Authors: Pedersen Nigel P , Raghu Ashley , Shivamurthy Veeresh Kumar N , Chern Joshua J , Gross Robert E , Willie Jon T , Dingledine Raymond J , Kheder Ammar 
Published: July 2024

Abstract
The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children’s Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy.
Patterns of brain volume and metabolism predict clinical features in the progressive supranuclear palsy spectrum
Authors: Ali Farwa , Clark Heather , Machulda Mary , Senjem Matthew L , Lowe Val J , Jack Clifford R , Josephs Keith A , Whitwell Jennifer , Botha Hugo 
Published: July 2024

Abstract
Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that presents with highly heterogenous clinical syndromes. We perform cross-sectional data-driven discovery of independent patterns of brain atrophy and hypometabolism across the entire PSP spectrum. We then use these patterns to predict specific clinical features and to assess their relationship to phenotypic heterogeneity. We included 111 patients with PSP (60 with Richardson syndrome and 51 with cortical and subcortical variant subtypes). Ninety-one were used as the training set and 20 as a test set. The presence and severity of granular clinical variables such as postural instability, parkinsonism, apraxia and supranuclear gaze palsy were noted. Domains of akinesia, ocular motor impairment, postural instability and cognitive dysfunction as defined by the Movement Disorders Society criteria for PSP were also recorded. Non-negative matrix factorization was used on cross-sectional MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans. Independent models for each as well as a combined model for MRI and FDG-PET were developed and used to predict the granular clinical variables. Both MRI and FDG-PET were better at predicting presence of a symptom than severity, suggesting identification of disease state may be more robust than disease stage. FDG-PET predicted predominantly cortical abnormalities better than MRI such as ideomotor apraxia, apraxia of speech and frontal dysexecutive syndrome. MRI demonstrated prediction of cortical and more so sub-cortical abnormalities, such as parkinsonism. Distinct neuroanatomical foci were predictive in MRI- and FDG-PET-based models. For example, vertical gaze palsy was predicted by midbrain atrophy on MRI, but frontal eye field hypometabolism on FDG-PET. Findings also differed by scale or instrument used. For example, prediction of ocular motor abnormalities using the PSP Saccadic Impairment Scale was stronger than with the Movement Disorders Society Diagnostic criteria for PSP oculomotor impairment designation. Combination of MRI and FDG-PET demonstrated enhanced detection of parkinsonism and frontal syndrome presence and apraxia, cognitive impairment and bradykinesia severity. Both MRI and FDG-PET patterns were able to predict some measures in the test set; however, prediction of global cognition measured by Montreal Cognitive Assessment was the strongest. MRI predictions generalized more robustly to the test set. PSP leads to neurodegeneration in motor, cognitive and ocular motor networks at cortical and subcortical foci, leading to diverse yet overlapping clinical syndromes. To advance understanding of phenotypic heterogeneity in PSP, it is essential to consider data-driven approaches to clinical neuroimaging analyses.
Synthesis of cyclic organosilicon compounds by palladium-catalyzed reactions of 2-silylaryl triflates
Authors: Shintani Ryo 
Published: July 2024

Abstract
2-Silylaryl triflates are widely employed as effective aryne precursors in organic synthesis, but their use as substrates for the synthesis of organosilicon compounds by retaining their silicon substituents is another attractive usage of these reagents. In particular, cyclic compounds with a silicon atom in the ring are promising candidates for various biologically active substances and optoelectronic functional materials. In this context, new synthetic methods for silicon-containing cyclic compounds have been actively investigated through the development of palladium-catalyzed reactions of 2-silylaryl triflates without generating aryne intermediates. As a result, selective synthesis of various silacyclic compounds has been achieved via C–H and/or C–Si bond activations as well as intramolecular exchange between these bonds and C–Pd bonds that are formed as reaction intermediates. An overview of this topic is described, including the mechanistic insights.
Right atrial and right ventricular strain: prognostic value depends on the severity of tricuspid regurgitation
Authors: Curtis Elizabeth , Lemarchand Léo , Lee K Charlotte , Galli Elena , L’Official Guillaume , Auffret Vincent , Leurent Guillaume , Oger Emmanuel , Donal Erwan 
Published: July 2024

Abstract

Aims
Assessing right heart function is challenging, particularly when significant tricuspid regurgitation (TR) is present. Amongst available echocardiographic techniques for assessment, literatures suggest that strain imaging may be more reliable and less susceptible to loading conditions. Thus, we aimed to assess the validity of right atrial (RA) and right ventricular (RV) strain relative to conventional metrics as well as their utility in predicting patient outcomes in TR.

Methods and results
We studied 262 consecutive patients (mean age 74 ± 11.2 years, 53% male) who underwent same-day echocardiography and right heart catheterization between 2018 and 2023. We compared right heart strain to traditional metrics of RV function and subsequently correlated RA and RV strain to heart failure (HF)-related death or hospitalization, whichever came first. Over a mean follow-up of 34 ± 15 months, there were 103 deaths and HF hospitalizations. Both RA strain and RV strain were correlated with echocardiographic and invasive measures of right heart function. Across all patients, preserved RA strain was associated with lower risk of adverse outcomes [hazard ratio (HR) 0.763, 95% confidence interval (CI) 0.618–0.943]. Similarly, preserved RV strain was correlated with better outcomes, although this was only statistically significant in patients without severe TR or pulmonary hypertension (HR 2.450, 95% CI 1.244–4.825). Moreover, abnormal ratios of RV strain to pulmonary pressures and RV size were significantly correlated with adverse outcomes (P &lt; 0.05 each).

Conclusion
RA and RV strain are independently correlated with echocardiographic and invasive measures of cardiac function. Moreover, preserved RA and RV strain is likely associated with better clinical outcomes.
Regulatory role of VvsB protein on serine protease activity of VvsA in Vibrio vulnificus
Authors: Kawase Tomoka , Debnath Anusuya , Okamoto Keinosuke 
Published: July 2024

Abstract
Background: Vibrio vulnificus NCIMB2137, a Gram-negative, metalloprotease negative estuarine strain was isolated from a diseased eel. A 45 kDa chymotrypsin-like alkaline serine protease known as VvsA has been recently reported as one of the major virulence factor responsible for the pathogenesis of this strain. The vvsA gene along with a downstream gene vvsB, whose function is still unknown constitute an operon designated as vvsAB. Objective: This study examines the contribution of VvsB to the functionality of VvsA. Method: In this study, VvsB was individually expressed using Rapid Translation System (RTS system), followed by an analysis of its role in regulating the serine protease activity of VvsA. Result: The proteolytic activity of VvsA increased upon the addition of purified VvsB to the culture supernatant of V. vulnificus. However, the attempts of protein expression using an E. coli system revealed a noteworthy observation that protein expression from the vvsA gene exhibited higher protease activity compared to that from the vvsAB gene within the cytoplasmic fraction. These findings suggest an intricate interplay between VvsB and VvsA, where VvsB potentially interacts with VvsA inside the bacterium and suppress the proteolytic activity. While outside the bacterial milieu, VvsB appears to stimulate the activation of inactive VvsA. Conclusion: The findings suggest that Vibrio vulnificus regulates VvsA activity through the action of VvsB, both intracellularly and extracellularly, to ensure its survival.
Chromosome-Level Genome Assembly of the Viviparous Eelpout Zoarces viviparus
Authors: Fuhrmann Nico , Brasseur Marie V , Bakowski Christina E , Podsiadlowski Lars , Prost Stefan , Krehenwinkel Henrik , Mayer Christoph 
Published: July 2024

Abstract
The viviparous eelpout Zoarces viviparus is a common fish across the North Atlantic and has successfully colonized habitats across environmental gradients. Due to its wide distribution and predictable phenotypic responses to pollution, Z. viviparus is used as an ideal marine bioindicator organism and has been routinely sampled over decades by several countries to monitor marine environmental health. Additionally, this species is a promising model to study adaptive processes related to environmental change, specifically global warming. Here, we report the chromosome-level genome assembly of Z. viviparus, which has a size of 663 Mb and consists of 607 scaffolds (N50 = 26 Mb). The 24 largest represent the 24 chromosomes of the haploid Z. viviparus genome, which harbors 98% of the complete Benchmarking Universal Single-Copy Orthologues defined for ray-finned fish, indicating that the assembly is highly contiguous and complete. Comparative analyses between the Z. viviparus assembly and the chromosome-level genomes of two other eelpout species revealed a high synteny, but also an accumulation of repetitive elements in the Z. viviparus genome. Our reference genome will be an important resource enabling future in-depth genomic analyses of the effects of environmental change on this important bioindicator species.
Testing times: disentangling admixture histories in recent and complex demographies using ancient DNA
Authors: Williams Matthew P , Flegontov Pavel , Maier Robert , Huber Christian D 
Published: July 2024

Abstract
Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches—firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes—and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P-values and f3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f-statistic estimations.
Psychological safety is associated with better work environment and lower levels of clinician burnout
Authors: de Lisser Rosalind , Dietrich Mary S , Spetz Joanne , Ramanujam Rangaraj , Lauderdale Jana , Stolldorf Deonni P 
Published: July 2024

Abstract
Burnout is attributed to negative work environments and threatens patient and clinician safety. Psychological safety is the perception that the work environment is safe for interpersonal risk-taking and may offer insight into the relationship between the work environment and burnout. In this cross-sectional analysis of survey data from 621 nurse practitioners in California, we found that one-third (34%) experienced high burnout. Four factors in the work environment were negatively associated with burnout and positively associated with psychological safety. Significant mediation effects of psychological safety were observed on the relationships between each work environment factor and both emotional exhaustion and depersonalization. The largest mediation effects were observed on the total effects of Nurse Practitioner–Physician Relations and Practice Visibility on Emotional Exhaustion (37% and 32%, respectively) and Independent Practice and Support and NP-Administration Relations on Depersonalization (32% and 29%, respectively). We found, overall, that psychological safety decreased the strength of the negative relationship between work environment and burnout. We argue that research, practice, and policy efforts to mitigate burnout and improve the work environment should consider psychological safety as a metric for system-level well-being.