bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term weight loss outcome of laparoscopic Roux-en-Y gastric bypass predicted by weight loss at 6 months in Chinese patients with BMI ≥ 32.5 kg/m2
Authors: Wuyun Qiqige , Wang Dezhong , Tian Chenxu , Xu Guangzhong , Amin Buhe , Lian Dongbo , Du Dexiao , Zhang Weihua , Jiang Min , Chen Guanyang , Zhang Nengwei , Wang Liang
Published: March 2023

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is classic bariatric procedure with long-term safety and efficacy. However, no studies have focused on predicting long-term weight loss after LRYGB in Chinese patients with body mass index (BMI) ≥ 32.5 kg/m2. To explore the relationship between initial and long-term weight loss after LRYGB in patients with BMI ≥ 32.5 kg/m2. All patients were followed-up to evaluate BMI, percentage of excess weight loss (%EWL), and comorbidities. Linear and logistic regression were performed to assess the relationship between initial and long-term weight loss. Receiver operating characteristic curve was used to determine optimal cutoff value. We enrolled 104 patients. The median preoperative BMI was 41.44 (37.92–47.53) kg/m2. %EWL ≥ 50% at 5 years was considered as successful weight loss, and 75.00% of the patients successfully lost weight. The cure rates of hypertension, hyperlipidemia, and type 2 diabetes mellitus at 1 year were 84.38%, 33.93%, and 60.82%, respectively. %EWL at 6 months and 5 years were positively correlated and its relationship could be described by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months (P < .001; r2 = 0.166). The best cutoff %EWL at 6 months after LRYGB to predict 5-year successful weight loss was 63.93% (sensitivity, 53.85%; specificity, 84.62%; area under the curve (AUC) = 0.671). In Chinese patients with BMI ≥ 32.5 kg/m2, %EWL at 6 months and 5 years were positively correlated and %EWL at 5 years could be calculated by following linear equation: %EWL5 years = 43.934 + 0.356 × %EWL6 months.
Identifying occupational health and safety risks among environmental health officers in Australia and New Zealand through an online survey
Authors: Dine Garry , Reed Sue , Oosthuizen Jacques , Masaka Edmore
Published: March 2023

To identify the occupational health and safety (OHS) risks among environmental health officers (EHOs) in Australia and New Zealand. The objectives were to profile and compare OHS experiences from different countries and regions to gain a regional perspective on OHS hazards that impact EHOs.

An online hazard exposure survey was conducted among 339 EHOs (Australia: n = 301, 88.8%; New Zealand: n = 38, 11.2%). The Mann–Whitney U test was used to compare 2 ordinal data groups, the Kruskal–Wallis H test was used for more than 2 ordinal groups, and the independent samples t test was used to compare the means of 2 independent groups where the dependent variables were normally distributed. Multiple regression techniques were used to analyze workplace incidents and age groups. A high degree of similarity in the types of workplace exposures and risk perceptions as well as concerns with organizational OHS management commitment were observed among EHOs from the 2 countries. Workplace violence and physical and psychosocial demands were the most commonly reported OHS hazards. Employer type, sex, and age group were significantly related to workplace exposure and OHS experience among EHOs in both countries. This study provides a profile of workplace exposure in the environmental health profession in the 2 countries and offers recommendations for the implementation of preventive action.
Early versus late surgical intervention for cervical spinal cord injury: A protocol for systematic review and meta-analysis
Authors: Yang Chaowei , Yang Xinming
Published: March 2023

Background:

Acute traumatic cervical spinal cord injury (SCI) is a catastrophic event with substantial physical, emotional, and economic burdens to patients, families, and society. Spinal cord decompression is recommended for the treatment of acute SCI. However, the optimal surgical timing remains controversial. Therefore, we perform a protocol for systematic review and meta-analysis to compare the efficacy of early and late surgical intervention for acute SCI.

Methods:

This systematic review and meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement, which have been registered in advance in the International prospective register of systematic reviews (registration number: CRD42023397592). We will search the following databases for randomized controlled trials: the Cochrane Skin Group Trials Register, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese Medical Current Content, and China National Knowledge Infrastructure. The risk of bias of the included studies will be appraised using the Cochrane Collaboration tool for randomized controlled trials. Statistical analysis will be performed using IBM SPSS Statistics (Armonk, NY).

Result:

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:

This systematic review will provide evidence regarding the optimal timing for spinal cord decompression in patients with acute SCI.
Multidisciplinary nutritional management improves nutritional and hospitalized outcomes of patients with esophageal cancer undergoing chemoradiotherapy: A randomized control trial
Authors: Wang Shu-An , Li Fuchao , Zhu Jiayu , Chen Xiaotian , Ren Wei , Gao Bo
Published: March 2023

Background:

This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy.

Methods:

A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann–Whitney U and chi-square tests.

Results:

The ALB and Hb levels of the patients in the control group decreased significantly [ALB: −2.6 (−5.6, 0), P = .01; Hb: −12.0 (−27.0, −2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004).

Conclusion:

Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.
The concept of detection of dynamic lung hyperinflation using cardiopulmonary exercise testing
Authors: Kominami Kazuyuki , Noda Kazuki , Minagawa Nanaho , Yonezawa Kazuya , Akino Masatoshi
Published: March 2023

Dynamic lung hyperinflation (DLH) caused by air trapping, which increases residual air volume, is a common cause of shortness of breath on exertion in chronic obstructive pulmonary disease (COPD). DLH is commonly evaluated by measuring the decrease in maximal inspiratory volume during exercise, or using the hyperventilation method. However, only few facilities perform these methods, and testing opportunities are limited. Therefore, we investigated the possibility of visually and qualitatively detecting DLH using data from a cardiopulmonary exercise test (CPET). Four men who underwent symptom-limiting CPET were included in this study, including a male patient in his 60s with confirmed COPD, a 50s male long-term smoker, and 2 healthy men in their 20s and 70s, respectively. We calculated the difference between the inspiratory tidal volume (TV I) and expiratory tidal volume (TV E) per breath (TV E-I) from the breath-by-breath data of each CPET and plotted it against the time axis. No decrease in TV E-I was observed in either of the healthy men. However, in the patient with COPD and long-term smoker, TV E-I began to decrease immediately after the initiation of exercise. These results indicate that DLH can be visually detected using CPET data. However, this study was a validation of a limited number of cases, and a comparison with existing evaluation methods and verification of disease specificity are required.
The association between statin use and prognosis in esophageal cancer patients: A meta-analysis
Authors: Lv Jing , Chen Peirui , Wu Jianqiang , Wen Zhi , Zhao Changming
Published: March 2023

Background:

The impact of statin use on the survival of esophageal cancer patients remains unclear now. The aim of this study was to identify the relationship between statin use and the long-term survival of esophageal cancer patients.

Methods:

The PubMed, EMBASE, and Web of Science databases were searched up to August 20, 2022, for relevant studies. The endpoints included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival, and hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to assess the association between statin use and the prognosis of esophageal cancer patients. Subgroup analysis based on the pathological type (adenocarcinoma vs squamous cell carcinoma), dose of statin use and tumor stage (tumor-node-metastasis I–III vs IV) was further performed. All statistical analyses were conducted using STATA 12.0 software.

Results:

A total of 7 retrospective studies involving 25,711 participants were included in this meta-analysis. The pooled results indicated that statin use was significantly associated with improved OS (HR = 0.80, 95% CI: 0.74–0.87, P < .001), CSS (HR = 0.77, 95% CI: 0.74–0.89, P < .001), and recurrence-free survival (HR = 0.38, 95% CI: 0.16–0.87, P = .022). Furthermore, subgroup analysis stratified by the pathological type, dose of statin use and tumor stage for OS and CSS showed similar results and indicated the protective role of statin use in the prognosis of esophageal cancer patients.

Conclusion:

Statin use is significantly associated with improved long-term survival of esophageal cancer patients and might serve as a promising prognostic indicator in esophageal cancer. However, more prospective high-quality studies are still needed to verify our findings.
Development and assessment of a predictive model for early diagnosis of rheumatoid arthritis in southwest China: A new nomogram
Authors: Zhang Naidan , Ji Chaixia , Bao Xiao , Yuan Chengliang
Published: March 2023

Rheumatoid arthritis (RA) is a disease complicated with inflammatory synovitis, which seriously affects the life quality of patients. Early diagnosis is important for prognosis of RA. Here, we aimed to develop and assess a model for early diagnosis of RA in southwest China. A nomogram including 44 patients with an early diagnosis of RA was developed. Variables were filtered by least absolute contraction selection operator and multiple logistic regression. The efficiency and clinical application range were evaluated. This nomogram showed that rheumatoid factor, erythrocyte sedimentation rate, RA33, facet joint and knee joint had high positive predictive value for RA. The area under curve was 0.920 [95% confidence interval (CI): 0.865–0.975]. In the validation model, area under curve was 0.942 (95% CI: 0.893–0.991). Calibration and decision curve suggested that this nomogram was helpful within the threshold probability range of 0.02 to 1.00. Using this nomogram will help clinicians in the early diagnosis of RA. Laboratory indicators such as rheumatoid factor, erythrocyte sedimentation rate, RA33, and clinical symptoms such as morning stiffness, facet joint and knee joint are very important, which deserves the attention of clinicians.
Vibration Controlled Transient Elastography to Evaluate Steatosis in Candidate Living Donors for Liver Transplantation
Authors: Palte Eytan , Duong Jimmy K. , Remotti Helen , Burt Joseph , Makkar Jasnit , Samstein Benjamin , Verna Elizabeth C. , Marratta Douglas , Emond Jean C. , Fox Alyson N.
Published: March 2023

Background.

The ability of vibration controlled transient elastography (VCTE) to reliably exclude significant steatosis in living donor candidates could obviate the need for invasive liver biopsies, expedite the donor approval process, and reduce recipient wait time. We therefore aimed to determine whether VCTE controlled attenuation parameter (CAP) could be used to detect steatosis in potential living donors.

Methods.

Living donor candidates who presented for evaluation between 2016 and 2019 underwent standard donor workup, VCTE, and liver biopsy if indicated. CAP scores were compared with MRI-Fat Fraction and, when available, histologic fat fraction from liver biopsy. Receiver operating characteristic curves were used to identify cutoffs with appropriate sensitivity and specificity for screening. Statistical analysis was conducted using R (version 3.6.0).

Results.

Seventy-nine candidate living donors presented during the study period, of whom 71 were included in the final analysis and of whom 20 underwent liver biopsy. There was a positive correlation between MRI-Fat Fraction and CAP scores with an observed Spearman correlation coefficient of 0.424 (P < 0.01). A CAP score of 271.5 dB/m or less was determined to have 89.8% sensitivity and 75% specificity for detecting <5% steatosis on MRI. The correlation between CAP and steatosis of available histologic samples had a Pearson correlation coefficient of 0.603 (P = 0.005). A CAP cutoff of 276.0 dB/m demonstrated 66.7% sensitivity and 85.7% specificity for detecting <15% histopathologic steatosis and positive and negative predictive values of 71.5% and 82.7%, respectively.

Conclusions.

VCTE can be integrated into living donor evaluation to accurately screen for hepatic steatosis.
Statistical inference with exchangeability and martingales
Authors: Holmes Chris C. , Walker Stephen G.
Published: March 2023

In this paper, we start by reviewing exchangeability and its relevance to the Bayesian approach. We highlight the predictive nature of Bayesian models and the symmetry assumptions implied by beliefs of an underlying exchangeable sequence of observations. By taking a closer look at the Bayesian bootstrap, the parametric bootstrap of Efron and a version of Bayesian thinking about inference uncovered by Doob based on martingales, we introduce a parametric Bayesian bootstrap. Martingales play a fundamental role. Illustrations are presented as is the relevant theory.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
The e-posterior
Authors: Grünwald Peter D.
Published: March 2023

We develop a representation of a decision maker’s uncertainty based on e-variables. Like the Bayesian posterior, thise-posteriorallows for making predictions against arbitrary loss functions that may not be specified ex ante. Unlike the Bayesian posterior, it provides risk bounds that have frequentist validity irrespective of prior adequacy: if the e-collection (which plays a role analogous to the Bayesian prior) is chosen badly, the bounds get loose rather than wrong, makinge-posterior minimaxdecision rules safer than Bayesian ones. The resulting quasi-conditional paradigm is illustrated by re-interpreting a previous influential partial Bayes-frequentist unification,Kiefer–Berger–Brown–Wolpert conditional frequentist tests, in terms of e-posteriors.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Deep bootstrap for Bayesian inference
Authors: Nie Lizhen , Ročková Veronika
Published: March 2023

For a Bayesian, the task to define the likelihood can be as perplexing as the task to define the prior. We focus on situations when the parameter of interest has been emancipated from the likelihood and is linked to data directly through a loss function. We survey existing work on both Bayesian parametric inference with Gibbs posteriors and Bayesian non-parametric inference. We then highlight recent bootstrap computational approaches to approximating loss-driven posteriors. In particular, we focus on implicit bootstrap distributions defined through an underlying push-forward mapping. We investigate independent, identically distributed (iid) samplers from approximate posteriors that pass random bootstrap weights through a trained generative network. After training the deep-learning mapping, the simulation cost of such iid samplers is negligible. We compare the performance of these deep bootstrap samplers with exact bootstrap as well as MCMC on several examples (including support vector machines or quantile regression). We also provide theoretical insights into bootstrap posteriors by drawing upon connections to model mis-specification.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Rhizohabitans arisaemae gen. nov., sp. nov., a novel actinomycete of the family Streptosporangiaceae
Authors: Yamada Yuki , Inahashi Yuki , Goda Yuki , Také Akira , Matsumoto Atsuko
Published: March 2023

An actinomycete strain K14-0274T was isolated from the root of Arisaema thunbergii Blume subsp. urashima (H. Hara) H. Ohashi et J. Murata collected in Japan. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated thatK14-0274T could be distinguished from the members of all known genera, although it represented a member of the family

Streptosporangiaceae

. K14-0274T produced sporangium-like spherical vesicles with spores on white aerial mycelia. MK-9 (H4) and MK-9 (H6) were the major menaquinones. The whole-cell hydrolysates contained madurose, glucose, mannose, rhamnose and ribose. The cell-wall amino acids comprise l-alanine, d-alanine, d-glutamic acid and meso-diaminopimelic acid. The N-acyl type of muramic acid was acetyl. Mycolic acids were not detected. Phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositolmannoside were detected. The predominant fatty acids were iso-C16 : 0, 10-methyl-C18 : 0 and C16 : 0. The G+C content of the genomic DNA was 69.7 mol%. On the basis of morphological, phylogenetic and chemotaxonomic characteristics, strain K14-0427T represents a novel genus in the family

Streptosporangiaceae

, for which the name Rhizohabitans arisaemae gen. nov., sp. nov. is proposed. The type strain is K14-0247T (=NBRC 114594T =TBRC 12948T).
Global scenario of the RmtE pan-aminoglycoside-resistance mechanism: emergence of the rmtE4 gene in South America associated with a hospital-related IncL plasmid
Authors: Delgado-Blas Jose F. , Ovejero Cristina M. , David Sophia , Serna Carlos , Pulido-Vadillo Mario , Montero Natalia , Aanensen David M. , Abadia-Patiño Lorena , Gonzalez-Zorn Bruno
Published: March 2023

Antimicrobial resistance (AMR) mechanisms, especially those conferring resistance to critically important antibiotics, are a great concern for public health. 16S rRNA methyltransferases (16S-RMTases) abolish the effectiveness of most clinically used aminoglycosides, but some of them are considered sporadic, such as RmtE. The main goals of this work were the genomic analysis of bacteria producing 16S-RMTases from a ‘One Health’ perspective in Venezuela, and the study of the epidemiological and evolutionary scenario of RmtE variants and their related mobile genetic elements (MGEs) worldwide. A total of 21 samples were collected in 2014 from different animal and environmental sources in the Cumaná region (Venezuela). Highly aminoglycoside-resistant

Enterobacteriaceae

isolates were selected, identified and screened for 16S-RMTase genes. Illumina and Nanopore whole-genome sequencing data were combined to obtain hybrid assemblies and analyse their sequence type, resistome, plasmidome and pan-genome. Genomic collections of rmtE variants and their associated MGEs were generated to perform epidemiological and phylogenetic analyses. A single 16S-RMTase, the novel RmtE4, was identified in five

Klebsiella

isolates from wastewater samples of Cumaná. This variant possessed three amino acid modifications with respect to RmtE1–3 (Asn152Asp, Val216Ile and Lys267Ile), representing the most genetic distant among all known and novel variants described in this work, and the second most prevalent. rmtE variants were globally spread, and their geographical distribution was determined by the associated MGEs and the carrying bacterial species. Thus, rmtE4 was found to be confined to

Klebsiella

isolates from South America, where it was closely related to ISVsa3 and an uncommon IncL plasmid related with hospital environments. This work uncovered the global scenario of RmtE and the existence of RmtE4, which could potentially emerge from South America. Surveillance and control measures should be developed based on these findings in order to prevent the dissemination of this AMR mechanism and preserve public health worldwide.
Feasibility Study of Ferumoxtyol for Contrast-enhanced MRI of Retroplacental Clear Space Disruption in Placenta Accreta Spectrum (PAS)
Authors: Badachhape Andrew A. , Burnett Brian , Bhandari Prajwal , Devkota Laxman , Bhavane Rohan , Ghaghada Ketan B. , Yallampalli Chandrasekhar , Fox Karin A. , Annapragada Ananth V.
Published: March 2023

Introduction

Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation, but visualization with conventional imaging techniques is a challenge. In this study, we investigate use of an FDA-approved iron oxide nanoparticle, ferumoxytol, for contrast-enhanced magnetic resonance imaging of the RPCS in mouse models of normal pregnancy and PAS. We then demonstrate the translational potential of this technique in human patients presenting with severe PAS (FIGO Grade 3C), moderate PAS (FIGO Grade 1), and no PAS.

Methods

A T1-weighted gradient recalled echo (GRE) sequence was used to determine the optimal dose of ferumoxytol in pregnant mice. Pregnant Gab3-/-mice, which demonstrate placental invasion, were then imaged at day 16 of gestation alongside wild-type (WT) pregnant mice which do not demonstrate invasion. Signal-to-noise ratio (SNR) was computed for placenta and RPCS for all fetoplacental units (FPUs) with ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) and used for the determination of contrast-to-noise ratio (CNR). Fe-MRI was also performed in 3 pregnant subjects using standard T1 and T2 weighted sequences and a 3D magnetic resonance angiography (MRA) sequence. RPCS volume and relative signal were calculated in all three subjects.

Results

Ferumoxytol administered at 5 mg/kg produced strong T1 shortening in blood and led to strong placental enhancement in Fe-MRI images. Gab3-/-mice demonstrated loss of hypointense region characteristic of the RPCS relative to WT mice in T1w Fe-MRI. CNR between RPCS and placenta was lower in FPUs of Gab3-/-mice compared to WT mice, indicating higher degrees of vascularization and interruptions throughout the space. In human patients, Fe-MRI at a dose of 5 mg/kg enabled high uteroplacental vasculature signal and quantification of the volume and signal profile in severe and moderate invasion of the placenta relative to a non-PAS case.

Discussion

Ferumoxytol, an FDA-approved iron oxide nanoparticle formulation, enabled visualization of abnormal vascularization and loss of uteroplacental interface in a murine model of PAS. The potential of this non-invasive visualization technique was then further demonstrated in human subjects. Diagnosis of placental invasion using Fe-MRI may provide a sensitive method for clinical detection of PAS.
The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation inC. elegans
Authors: Emerson Felicity J. , Chiu Caitlin , Lin Laura Y. , Riedel Christian G. , Zhu Ming , Lee Siu Sylvia
Published: March 2023

SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity inC. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
Flexible parsing, interpretation, and editing of technical sequences with splitcode
Authors: Sullivan Delaney K. , Pachter Lior
Published: March 2023

Next-generation sequencing libraries are constructed with numerous synthetic constructs such as sequencing adapters, barcodes, and unique molecular identifiers. Such sequences can be essential for interpreting results of sequencing assays, and when they contain information pertinent to an experiment, they must be processed and analyzed. We present a tool called splitcode, that enables flexible and efficient parsing, interpreting, and editing of sequencing reads. This versatile tool facilitates simple, reproducible preprocessing of reads from libraries constructed for a large array of single-cell and bulk sequencing assays.

Availability and Implementation

The splitcode program is free, open source, and available for download athttp://github.com/pachterlab/splitcode.
VMAP: Vaginal Microbiome Atlas During Pregnancy
Authors: Parraga-Leo Antonio , Oskotsky Tomiko T. , Oskotsky Boris , Wibrand Camilla , Roldan Alennie , Tang Alice , Ha Connie W.Y. , Wong Ronald J. , Minot Samuel S. , Andreoletti Gaia , Kosti Idit , Theis Kevin R. , Ng Sherrianne , Lee Yun S. , Diaz-Gimeno Patricia , Bennett Phillip R. , MacIntyre David A. , Lynch Susan V. , Romero Roberto , Tarca Adi L. , Stevenson David K. , Aghaeepour Nima , Golob Jonathan , Sirota Marina
Published: March 2023

The vaginal microbiome has been shown to be associated with pregnancy outcomes including preterm birth (PTB) risk. Here we present VMAP: Vaginal Microbiome Atlas during Pregnancy (http://vmapapp.org), an application to visualize features of 3,909 vaginal microbiome samples of 1,416 pregnant individuals from 11 studies, aggregated from raw public and newly generated sequences via an open-source tool, MaLiAmPi. Our visualization tool (http://vmapapp.org) includes microbial features such as various measures of diversity, VALENCIA community state types (CST), and composition (via phylotypes and taxonomy). This work serves as a resource for the research community to further analyze and visualize vaginal microbiome data in order to better understand both healthy term pregnancies and those associated with adverse outcomes.
An extended wave of global mRNA deadenylation sets up a switch in translation regulation across the mammalian oocyte-to-embryo transition
Authors: Lee Katherine , Cho Kyucheol , Morey Robert , Cook-Andersen Heidi
Published: March 2023

The oocyte-to-embryo transition (OET) occurs in the absence of new transcription and relies on post-transcriptional gene regulation, including translational control by mRNA poly(A) tail regulation, where cytoplasmic polyadenylation activates translation and deadenylation leads to translational repression and decay. However, how the transcriptome-wide landscape of mRNA poly(A) tails shapes translation across the OET in mammals remains unknown. Here, we performed long-read RNA sequencing to uncover poly(A) tail lengths and mRNA abundance transcriptome-wide in mice across five stages of development from oocyte to embryo. Integrating these data with recently published ribosome profiling data, we demonstrate that poly(A) tail length is coupled to translational efficiency across the entire OET. We uncover an extended wave of global deadenylation during fertilization, which sets up a switch in translation control between the oocyte and embryo. In the oocyte, short-tailed maternal mRNAs that resist deadenylation in the oocyte are translationally activated, whereas large groups of mRNAs deadenylated without decay in the oocyte are later readenylated to drive translation activation in the early embryo. Our findings provide an important resource and insight into the mechanisms by which cytoplasmic polyadenylation and deadenylation dynamically shape poly(A) tail length in a stage-specific manner to orchestrate development from oocyte to embryo in mammals.
A novel computational pipeline forvargene expression augments the discovery of changes in thePlasmodium falciparumtranscriptome during transition fromin vivoto short-termin vitroculture
Authors: Andradi-Brown Clare , Wichers-Misterek Jan Stephan , von Thien Heidrun , Höppner Yannick D. , Scholz Judith A. M. , Hansson Helle , Hocke Emma Filtenborg , Gilberger Tim-Wolf , Duffy Michael F. , Lavstsen Thomas , Baum Jake , Otto Thomas D. , Cunnington Aubrey J. , Bachmann Anna
Published: March 2023

The pathogenesis of severePlasmodium falciparummalaria involves cytoadhesive microvascular sequestration of infected erythrocytes, mediated byP. falciparumerythrocyte membrane protein 1 (PfEMP1). PfEMP1 variants are encoded by the highly polymorphic family ofvargenes, the sequences of which are largely unknown in clinical samples. Previously, we published new approaches forvargene profiling and classification of predicted binding phenotypes in clinicalP. falciparumisolates (Wicherset al., 2021), which represented a major technical advance. Building on this, we report here a novel method forvargene assembly and multidimensional quantification from RNA-sequencing that outperforms the earlier approach of Wicherset al., 2021 on both laboratory and clinical isolates across a combination of metrics. Importantly, the tool can interrogate thevartranscriptome in context with the rest of the transcriptome and can be applied to enhance our understanding of the role ofvargenes in malaria pathogenesis. We applied this new method to investigate changes invargene expression through early transition of parasite isolates toin vitroculture, using paired sets ofex vivosamples from our previous study, cultured for up to three generations. In parallel, changes in non-polymorphic core gene expression were investigated. Modest but unpredictablevargene switching and convergence towardsvar2csawere observed in culture, along with differential expression of 19% of the core transcriptome between pairedex vivoand generation 1 samples. Our results cast doubt on the validity of the common practice of using short-term cultured parasites to make inferences aboutin vivophenotype and behaviour.
Microsaccades track location-based object rehearsal in visual working memory
Authors: de Vries Eelke , van Ede Freek
Published: March 2023

Besides controlling eye movements, the brain’s oculomotor system has been implicated in the control of covert spatial attention and the rehearsal of spatial information in working memory. We investigated whether the oculomotor system also contributes to rehearsing visual objects in working memory when object location is never asked about. To address this, we tracked the incidental use of locations for mnemonic rehearsal via directional biases in microsaccades while participants maintained two visual objects (coloured oriented gratings) in working memory. By varying the stimulus configuration (horizontal, diagonal, and vertical) at encoding, we could quantify whether microsaccades were more aligned with the configurational axis of the memory contents, as opposed to the orthogonal axis. Experiment 1 revealed that microsaccades continued to be biased along the axis of the memory content several seconds into the working-memory delay. In Experiment 2, we confirmed that this directional microsaccade bias was specific to memory demands, ruling out lingering effects from passive and attentive encoding of the same visual objects in the same configurations. Thus, by studying microsaccade directions, we uncover oculomotor-driven rehearsal of visual objects in working memory through their associated locations.

SIGNIFICANCE STATEMENT

How humans rehearse information in working memory is a foundational question in psychology and neuroscience. To provide insight into the cognitive and neural bases of working-memory rehearsal, we turned to microsaccades – small eye-movements produced by the brain’s oculomotor system. We reveal how microsaccades track the locations of visual objects during memory rehearsal, even when object locations are never asked about. This brings three advances. From a psychology standpoint, it demonstrates how memory rehearsal automatically engages object locations. From a neuroscience standpoint, it demonstrates how such location-based rehearsal relies on brain circuitry that also controls our eyes. Finally, from a practical standpoint, it demonstrates how microsaccades can be utilised to track the properties of working-memory rehearsal across space and time.
Plastome-based Phylogenomic analyses provide insights into the germplasm resource diversity ofCibotiumin China
Authors: Jiang Ri-Hong , Liang Si-Qi , Wu Fei , Tang Li-Ming , Qin Bo , Chen Ying-Ying , Huang Yao-Heng , Li Kai-Xiang , Zhang Xian-Chun
Published: March 2023

Germplasm resource is the source of herbal medicine production. Cultivation of superior germplasm resources helps to resolve the serious conflict between long-term population persistence and growing market demand by producing materials with high quality consistently.Cibotium barometzis the original plant of cibotii rhizoma (“Gouji”), a traditional Chinese medicine used in the therapy of pain, weakness, and numbness of lower extremity. Long-history use ofCibotiumhas rendered wild populations of this species declined seriously in China. Without sufficient understanding of species and lineage diversity ofCibotium, it is difficult to propose a targeted conservation scheme at present, let alone selecting high-quality germplasm resources. In order to fill such a knowledge gap, this study sampledC. barometzand relative species throughout their distribution in China, performed genome skimming to obtain plastome data, and conducted phylogenomic analyses. We constructed a well-supported plastome phylogeny of ChineseCibotium, which showed that three species with significant genetic difference distributed in China, namelyC. barometz,C. cumingii, andC. sino-burmaense, a cryptic species endemic to NW Yunnan and adjacent region of NE Myanmar. Moreover, our results revealed two differentiated lineages ofC. barometzdistributed in the east and west side of a classic phylogeographic boundary that probably shaped by monsoons and landforms in China. We also evaluated the resolution of nine traditional barcode loci, and designed five new DNA barcodes based on the plastome data which can discriminate all these species and lineages of ChineseCibotiumaccurately. These novel findings integrated genetic basis will guide conservation planners and medicinal plant breeders to build systematic conservation plans and exploit germplasm resources ofCibotiumin China.
Guidelines for Evaluating the Comparability of Down-Sampled GWAS Summary Statistics
Authors: Williams Camille M. , Poore Holly , Tanksley Peter T. , Kweon Hyeokmoon , Courchesne-Krak Natasia S. , Londono-Correa Diego , Mallard Travis T. , Barr Peter , Koellinger Philipp D. , Waldman Irwin D. , Sanchez-Roige Sandra , Harden K. Paige , Palmer Abraham A , Dick Danielle M. , Linnér Richard Karlsson
Published: March 2023

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci, while the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses are robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers’ use of the summary statistics.
A mechanistic-statistical approach to infer dispersal and demography from invasion dynamics, applied to a plant pathogen
Authors: Saubin Méline , Coville Jérome , Xhaard Constance , Frey Pascal , Soubeyrand Samuel , Halkett Fabien , Fabre Frédéric
Published: March 2023

Dispersal, and in particular the frequency of long-distance dispersal (LDD) events, has strong implications for population dynamics with possibly the acceleration of the colonisation front, and for evolution with possibly the conservation of genetic diversity along the colonised domain. However, accurately inferring LDD is challenging as it requires both large-scale data and a methodology that encompasses the redistribution of individuals in time and space. Here, we propose a mechanistic-statistical framework to estimate dispersal from one-dimensional invasions. The mechanistic model takes into account population growth and grasps the diversity in dispersal processes by using either diffusion, leading to a reaction-diffusion (R.D.) formalism, or kernels, leading to an integro-differential (I.D.) formalism. The latter considers different dispersal kernels (e.g. Gaussian, Exponential, and Exponential-power) differing in their frequency of LDD events. The statistical model relies on dedicated observation laws that describe two types of samples, clumped or not. As such, we take into account the variability in both habitat suitability and occupancy perception. We first check the identifiability of the parameters and the confidence in the selection of the dispersal process. We observed good identifiability for all parameters (correlation coefficient>0.9 between true and fitted values). The dispersal process that is the most confidently identified is Exponential-Power (i.e. fat-tailed) kernel. We then applied our framework to data describing an annual invasion of the poplar rust disease along the Durance River valley over nearly 200 km. This spatio-temporal survey consisted of 12 study sites examined at seven time points. We confidently estimated that the dispersal of poplar rust is best described by an Exponential-power kernel with a mean dispersal distance of 1.94 km and an exponent parameter of 0.24 characterising a fat-tailed kernel with frequent LDD events. By considering the whole range of possible dispersal processes our method forms a robust inference framework. It can be employed for a variety of organisms, provided they are monitored in time and space along a one-dimension invasion.
An improved rhythmicity analysis method using Gaussian Processes detects cell-density dependent circadian oscillations in stem cells
Authors: Sahay Shabnam , Adhikari Shishir , Hormoz Sahand , Chakrabarti Shaon
Published: March 2023

Detecting oscillations in time series remains a challenging problem even after decades of research. In chronobiology, rhythms in time series (for instance gene expression, eclosion, egg-laying and feeding) datasets tend to be low amplitude, display large variations amongst replicates, and often exhibit varying peak-to-peak distances (non-stationarity). Most currently available rhythm detection methods are not specifically designed to handle such datasets. Here we introduce a new method, ODeGP (OscillationDetection usingGaussianProcesses), which combines Gaussian Process (GP) regression with Bayesian inference to provide a flexible approach to the problem. Besides naturally incorporating measurement errors and non-uniformly sampled data, ODeGP uses a recently developed kernel to improve detection of non-stationary waveforms. An additional advantage is that by using Bayes factors instead of p-values, ODeGP models both the null (non-rhythmic) and the alternative (rhythmic) hypotheses. Using a variety of synthetic datasets we first demonstrate that ODeGP almost always outperforms eight commonly used methods in detecting stationary as well as non-stationary oscillations. Next, on analyzing existing qPCR datasets that exhibit low amplitude and noisy oscillations, we demonstrate that our method is more sensitive compared to the existing methods at detecting weak oscillations. Finally, we generate new qPCR time-series datasets on pluripotent mouse embryonic stem cells, which are expected to exhibit no oscillations of the core circadian clock genes. Surprisingly, we discover using ODeGP that increasing cell density can result in the rapid generation of oscillations in theBmal1gene, thus highlighting our method’s ability to discover unexpected patterns. In its current implementation, ODeGP (available as an R package) is meant only for analyzing single or a few time-trajectories, not genome-wide datasets.
Molecular heterogeneity of C. elegans glia across sexes
Authors: Purice Maria D , Quitevis Elgene J.A. , Manning R Sean , Severs Liza J , Tran Nina Tuyen , Sorrentino Violet , Setty Manu , Singhvi Aakanksha
Published: March 2023

A comprehensive description of nervous system function, and sex dimorphism within, is incomplete without clear assessment of the diversity of its component cell types, neurons and glia. C. elegans has an invariant nervous system with the first mapped connectome of a multi-cellular organism and single-cell atlas of component neurons. Here we present single nuclear RNA-seq evaluation of glia across the entire adult C. elegans nervous system, including both sexes. Machine learning models enabled us to identify both sex-shared and sex-specific glia and glial subclasses. We have identified and validated molecular markers in silico and in vivo for these molecular subcategories. Comparative analytics also reveals previously unappreciated molecular heterogeneity in anatomically identical glia between and within sexes, indicating consequent functional heterogeneity. Furthermore, our datasets reveal that while adult C. elegans glia express neuropeptide genes, they lack the canonical unc-31/CAPS-dependent dense core vesicle release machinery. Thus, glia employ alternate neuromodulator processing mechanisms. Overall, this molecular atlas, available at www.wormglia.org, reveals rich insights into heterogeneity and sex dimorphism in glia across the entire nervous system of an adult animal
Brain functional characterization of response-code conflict in dual-tasking and its modulation by age
Authors: Paas Oliveros Lya K. , Cieslik Edna C. , Pieczykolan Aleks , Pläschke Rachel N. , Eickhoff Simon B. , Langner Robert
Published: March 2023

Crosstalk between conflicting response codes contributes to interference in dual-tasking, an effect exacerbated in advanced age. Here, we investigated (1) brain activity correlates of such response-code conflicts, (2) activity modulations by individual dual-task performance and related cognitive abilities, (3) task-modulated connectivity within the task network, and (4)age-related differences in all these aspects. Young and older adults underwent fMRI while responding to the pitch of tones through spatially mapped speeded button presses with one or two hands concurrently. Using opposing stimulus–response mappings between hands, we induced conflict between simultaneously activated response codes. These response-code conflicts elicited activation in key regions of the multiple-demand network. Older adults showed non-compensatory hyperactivity in left superior frontal gyrus, and higher left intraparietal sulcus activity associated with lower attentional performance. While motor and parietal areas of the conflict-related network were modulated by attentional and task-switching abilities, efficient conflict resolution in dual-tasking was linked to suppressing visual cortex activity. Finally, connectivity between premotor or parietal seed regions and the conflict-sensitive network was neither conflict-specific nor age-sensitive. Overall, resolving dual-task response-code conflict recruited substantial parts of the multiple-demand network, whose activity and coupling, however, were only little affected by individual differences in task performance or age.
Evolution of intracellular free radical load in colon adenocarcinoma cells over the course of butyrate-induced redifferentiation
Authors: Sigaeva Alina , Zijlema Eline , Zhang Yue , Schirhagl Romana
Published: March 2023

Fluorescent nanodiamonds have exceptional optical properties and are highly biocompatible, which allows to use them as labels for long-term tracking of the cells. The research fields that make use of this application of nanodiamonds include stem cell biology and cancer biology, where quiescent and differentiating cells can be tracedin vitroandin vivo. However, these studies focus on using nanodiamonds as simple labels, whereas they can serve as highly sensitive intracellular sensors for free radical species. In this study, we aimed to bring the two approaches together and to assess the free radical production in the cells over the course of their differentiation.

We report on the successful enterocytic differentiation of HT-29 colon adenocarcinoma cells, pre-loaded with fluorescent nanodiamonds. The cells were cultured in butyrate-free or butyrate-supplemented medium for 13 days. Butyrate-treated cells developed the morphological and molecular traits, characteristic for normal enterocytes. Fluorescent nanodiamonds did not have a negative effect on the process of differentiation. Moreover, the particles could be found in the cytoplasm of both undifferentiated and re-differentiated cells even after 13 days of culture. The internalized nanodiamonds were used to assess the free radical load in the undifferentiated and re-differentiated HT-29 cells at different stages of the experiment. Consistently with previous findings, re-differentiated HT-29 cells showed higher free radical load than undifferentiated ones.