bluuebunny/crossref_metadata_2025 huggingface dataset:
Akaluc bioluminescence offers superior sensitivity to trackin vivodynamics of SARS-CoV-2 infection
Authors: Tamura Tomokazu , Ito Hayato , Torii Shiho , Wang Lei , Suzuki Rigel , Tusjino Shuhei , Kamiyama Akifumi , Oda Yoshitaka , Morioka Yuhei , Suzuki Saori , Shirakawa Kotaro , Sato Kei , Yoshimatsu Kumiko , Matsuura Yoshiharu , Iwano Satoshi , Tanaka Shinya , Fukuhara Takasuke
Published: October 2023

Monitoringin vivoviral dynamics can improve our understanding of pathogenicity and tissue tropism. For positive-sense, single-stranded RNA viruses, several studies have attempted to monitor viral kineticsin vivousing reporter genomes. The application of such recombinant viruses can be limited by challenges in accommodating bioluminescent reporter genes in the viral genome. Conventional luminescence also exhibits relatively low tissue permeability and thus less sensitivity for visualizationin vivo. Here we show that unlike NanoLuc bioluminescence, the improved method, termed AkaBLI, allows visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Syrian hamsters. By successfully incorporating a codon-optimized Akaluc luciferase gene into the SARS-CoV-2 genome, we visualizedin vivoinfection, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of neutralizing antibodies and mRNA vaccination by monitoring changes in Akaluc signals. Overall, AkaBLI is an effective technology for monitoring viral dynamics in live animals.
THI1Gene Evolutionary Trends: A Comprehensive Plant-Focused Assessment via Data Mining and Large-Scale Analysis
Authors: Dias Henrique Moura , de Toledo Naiara Almeida , Mural Ravi V. , Schnable James C. , Van Sluys Marie-Anne
Published: October 2023

Molecular evolution analysis typically involves identifying selection pressure and reconstructing evolutionary trends. This process usually necessitates access to specific data related to a target gene or gene family within a particular group of organisms. While recent advancements in high-throughput sequencing techniques have resulted in the rapid accumulation of extensive genomics and transcriptomics data and the creation of new databases in public repositories, extracting valuable insights from such vast datasets remains a significant challenge for researchers. Here, we elucidated the evolutionary history ofTHI1, a gene responsible for encoding thiamine thiazole synthase. The thiazole ring is a precursor for vitamin B1 and crucial cofactor in primary metabolic pathways. We conducted a comprehensive search forTHI1information within public repositories with careful curation to achieve this. Our searches reveal an evolutionary trend of 702THI1homologs of Archaea and Eukarya, with a detailed focus on plants. The green lineage of these organisms preserved the THI4 protein domain throughout its diversification by incorporating the N-terminus and targeting chloroplasts. Furthermore, evolutionary pressures and lifestyle appear to be associated with retention of TPP-riboswitch sites and consequent dual post-transcriptional regulation of thede novobiosynthesis pathway in basal groups. Multicopy retention ofTHI1is not a typical plant pattern, even successive rounds of genome duplications. Additionally, we identified the diversification of cis-regulatory sites in plants with the conservation of biological processes associated with the initial stages of seed development and preservation of the transcriptional pattern during the diurnal cycle. Our data mining of 484 transcriptome datasets supports this finding and brings a new look at public repositories and evolutionary trends toTHI1.
Assessing the quality ofde novoparasite genomes assembled using only Oxford Nanopore Technologies MinION data
Authors: Herzog Kaylee S. , Wu Rachel , Hawdon John M. , Nejsum Peter , Fauver Joseph R.
Published: October 2023

Parasitic nematode infections represent a significant burden of disease in impoverished populations. Genomic studies of parasitic nematodes have revealed novel drug and vaccine targets and provided unprecedented insights into parasite biology. A key component of these studies is the availability of high-quality reference genomes (i.e., genomes that are contiguous, complete, and accurate) that capture the biological diversity contained within species. However, relatively few genomic resources exist for parasitic nematodes and few species are represented by more than a single reference genome. Streamlined laboratory and computational workflows to generate high-quality reference genomes from individual specimens using a single data source have the potential to increase the availability of genomic data from parasitic nematodes. The Oxford Nanopore Technologies (ONT) MinION is an accessible sequencing platform capable of generating ultra-long read data ideal for assembling genomes. However, lower read-level accuracy of ONT data has previously required assemblies to be error-corrected with more accurate short-read data. In this study, we assessed the quality ofde novogenome assemblies for three species of parasitic nematodes (Brugia malayi, Trichuris trichiura,andAncylostoma caninum) generated using only ONT MinION data. Assemblies were benchmarked against current reference genomes and against additional assemblies that were supplemented with short-read Illumina data through polishing or hybrid assembly approaches. For each species, assemblies generated using only MinION data had similar or superior measures of contiguity, completeness, and gene content. In terms of gene composition, depending on the species, between 88.9–97.6% of complete coding sequences predicted in MinION data only assemblies were identical to those predicted in assemblies polished with Illumina data. Polishing MinION data only assemblies with Illumina data therefore improved gene-level accuracy to a degree. Furthermore, modified DNA extraction and library preparation protocols produced sufficient genomic DNA fromB. malayiandT. trichiurato generatede novoassemblies from individual specimens.

Data Availability Statement

Quality-controlled MinION and Illumina data for each species are deposited in the NCBI Sequence Read Archive (SRA) under the BioProject accession ID PRJNA1074771 under BioSample accession nos. SAMN39888962 (Brugia malayi), SAMN39888963 (Trichuris trichiura) and SAMN39888964 (Ancylostoma caninum). Final assemblies for each species are publicly available on GenBank.
Staphylococcus epidermidisenablesCutibacterium acnesto form biofilms under aerobic conditions
Authors: Kaplan Jeffrey B.
Published: October 2023

Staphylococcus epidermidisandCutibacterium acnesare among the most abundant members of the human skin microbiome. Both species are associated with skin health and disease. Although skin microbes typically grow in surface-associated biofilms, few studies on the interaction betweenS. epidermidisandC. acnesin biofilms have been reported. In the present study we measured the ability ofS. epidermidisandC. acnes, either individually or jointly, to form biofilms in glass culture tubes. SinceS. epidermidisis a facultative anaerobe andC. acnesis an aerotolerant anaerobe, tubes were incubated both aerobically and anaerobically to assess the role of atmosphere in biofilm forma4on. When cultured individually, we found thatS. epidermidisformed biofilms under both aerobic and anaerobic conditions, whereasC. acnesformed biofilms only under aerobic conditions. When co-cultured, the presence ofC. acneshad no effect onS. epidermidisbiofilm formation under either aerobic or anaerobic conditions. However, the presence ofS. epidermidissignificantly enhanced the growth ofC. acnesbiofilms under anaerobic conditions and enabledC. acnesto form biofilms under aerobic condi2ons. This finding may be clinically relevant to the interaction betweenS. epidermidisandC. acneson human skin.
Liver size is predetermined in the neonate by adding lobules at the periphery
Authors: Azizoglu D. Berfin , Perez Karina , Zheng Sherry Li , Rahman Shahadat , Rim Ellen Youngsoo , Anbarchian Teni , Fish Matt , Loh Kyle M. , Red-Horse Kristy , Nusse Roel
Published: October 2023

Organs vary in size between and within species to match organismal needs1,2. Decades-old theoretical work has proposed that scaling of organs and body parts relative to the body relies on the features of energy-transport systems, the vascular system in mammals3. Yet, experimental studies on whether or how vascularization helps determine organ size have lagged behind. The mammalian liver is a remarkable example, as liver size scales proportionally with high precision between individuals4. Here, we use quantitative clonal mapping, volumetric imaging, and genetic perturbations combined with novel molecular and genetic tools to identify the temporal and spatial constraints that establish mouse liver size. We find that adult liver size is predetermined during a neonatal period when new functional units, termed lobules, are added to the organ. New lobules are vascularized by prominent sprouting angiogenesis of the hepatic vein, restricted to the periphery of the organ. When Wnt signals are ablated in the single cell-layered mesothelium at the periphery, lobule growth fails, and the organ adopts a compromised size set point. Remarkably, within a week after birth and well before hepatocyte division stops, vein sprouting rapidly declines and lobule addition concludes, setting a limit on the final liver size. These findings posit that vascularization in the neonate constrains and helps determine adult liver size. Together, these results propose a novel, vasculature-centric experimental framework for studying organ size control and scaling in mammals.
Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice
Authors: Sokolowski Dustin J. , Hou Huayun , Yuki Kyoko E. , Roy Anna , Chan Cadia , Faykoo-Martinez Mariela , Hudson Matt , Uusküla-Reimand Liis , Goldenberg Anna , Palmert Mark R. , Wilson Michael D.
Published: October 2023

Although the hypothalamus plays a critical role in the regulation of puberty, more research is needed to identify the gene regulatory networks that control pubertal timing. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition. We used RNA-seq to profile hypothalamic gene expression in male and female mice at five time points spanning the onset of puberty (postnatal days (PD) 12, 22, 27, 32, and 37). By combining this data with hypothalamic scRNA-seq data of pre- and post-pubertal mice, we were able to assign gene expression changes to their cell types of origin. In our colony, pubertal onset occurs earlier in male mice allowing us to focus on genes whose expression is dynamic across ages and offset between sexes and to explore bases of sex effects. Our age-by- sex pattern of expression enriched for biological pathways involved hormone production, neuronal activation, and glial maturation. Additionally, we found a dramatic expansion of oligodendrocytes precursor cells into mature oligodendrocytes spanning the pre-pubertal (PD12) to peri-pubertal (PD27) timepoints, and that genes driving this expansion enrich for genes involved in pubertal regulation. Together, by incorporating multiple biological timepoints with male and female mice simultaneously, our work furthers the understanding of gene and cell-type changes that accompany the development of secondary sex characteristics in both sexes.
Live soil ameliorated the negative effects of biodegradable but not non-biodegradable microplastics on the growth of plant communities
Authors: Fu Yanmei , Oduor Ayub M. O. , Jiang Ming , Liu Yanjie
Published: October 2023

Plastic pollution has become a global environmental problem. Alternative use of biodegradable plastics has been proposed to mitigate the pollution problem caused by the traditional non-biodegradable plastics but the relative impacts of both types of microplastics on plant community productivity and diversity remain unknown. Microplastics can affect growth of individual plants directly by altering plant physiological processes and indirectly by altering soil biota that in turn influence plant growth. However, it remains unknown whether soil biota can mediate impact of biodegradable and non-biodegradable microplastics on plant community productivity and diversity due to a lack of studies on the topic.

Here, we performed a greenhouse experiment with six plant communities and five biodegradable and five non-biodegradable microplastics to test whether: 1) biodegradable microplastics have a less negative effect on plant community biomass production and diversity than non-biodegradable microplastics, and 2) soil microorganisms differentially mediate the effects of non-biodegradable and biodegradable microplastics on plant community biomass production and diversity. We employed a fully crossed factorial design to grow the six plant communities in the presencevs. absence of the 10 microplastics individually and in live soilvs. sterilized soil.

Results show that live soil ameliorated the negative effects of biodegradable microplastics on shoot biomass of the plant communities, but microplastics suppressed plant community diversity more strongly in live soil than in sterilized soil regardless of microplastics types under averaged across all treatments. Furthermore, the specific microplastics polymers were the main drivers of these results.

Synthesis and applications:Overall, our findings indicate that even biodegradable microplastics, e.g. PBS, which are considered environmentally friendly, still pose significant ecological risks to the structure and productivity of plant communities with potential implications for functioning of terrestrial ecosystems. Future studies may identify the specific taxa of soil microorganisms that may have degraded the microplastics that we studied, their rates of biodegradation, and the effects thereof on plant community structure and productivity under more natural field conditions in contrasting climatic conditions.
Wellbeing After Stroke (WAterS): feasibility testing of a co-developed Acceptance and Commitment Therapy (ACT) intervention, to support psychological adjustment after stroke
Authors: Patchwood Emma , Foote Hannah , Vail Andy , Cotterill Sarah , Hill Geoff ,   members of the WAterS PCPI Group, Bowen Audrey
Published: October 2023

Objective

Feasibility test a co-developed intervention based on Acceptance and Commitment Therapy (ACT) to support psychological adjustment post-stroke, delivered by a workforce with community in-reach.

Design

Observational feasibility study utilising Patient, Carer, Public Involvement (PCPI).

Setting

Online. UK.

Participants

Stroke survivors with self-reported psychological distress 4+ months post-stroke

Interventions

The co-developed Wellbeing After Stroke (WAterS) intervention includes: nine weekly, structured, online, group sessions for stroke survivors, delivered via a training programme to upskill staff without previous ACT experience, under Clinical Psychology supervision.

Main measures

Feasibility of recruitment and retention; data quality from candidate measures; safety. Clinical and demographic information at baseline; Patient Reported Outcome Measures (PROMs) via online surveys (baseline, pre- and post-intervention, 3 and 6 months after intervention end) including Mood (HADS), Wellbeing (ONS4), Health-Related Quality of Life (EQ5D5L), Psychological Flexibility (AAQ-ABI) and Values-Based Living (VQ).

Results

We trained eight staff and recruited 17 stroke survivors with mild-to-moderate cognitive and communication difficulties. 12/17 (71%) joined three intervention groups with 98% attendance and no related adverse events. PROMS data were well-completed. The HADS is a possible future primary outcome (self-reported depression lower on average by 1.3 points: 8.5 pre-group to 7.1 at 3 month follow up; 95% CI 0.4 to 3.2).

Conclusion

The WAterS intervention warrants further research evaluation. Staff can be trained and upskilled to deliver. It appears safe and feasible to deliver online to groups, and study recruitment and data collection are feasible. Funding has been secured to further develop the intervention, considering implementation and health equality.
Serious mental health diagnoses in children on the Child Protection Register: a record linkage study
Authors: Ball William P , Anderson Caroline , Black Corri , Gordon Sharon , Lackenby Michael , Murchie Martin , Ostrovska Bārbala , O’Sullivan Katherine , Rowlands Helen , Díaz Magdalena Rzewuska , Butler Jessica E
Published: October 2023

Purpose

Children with experience of maltreatment, abuse or neglect are known to have a higher prevalence of poor mental health. Child Protection Services identify children most at risk of harm and in need of intervention. Mental healthcare usage in this population is not well understood as registration data is not routinely linked to health records.

Methods

We undertook data linkage to describe the population on the register, their mental healthcare usage and to calculate age- and sex-specific incidence rates of mental health outcomes. We analysed records from the Aberdeen City Council Child Protection Register and for mental health prescribing and referrals to child and adolescent mental health services (CAMHS) for the NHS Grampian region between 1stJanuary 2012 and 31stDecember 2022.

Results

We identified 1,498 individuals with a Child Protection Register registration, of which 70% were successfully matched to health records. 20% of registrations occurred before birth and the median age of registration was 3 years. 10.1% of children with a registration ever received a mental health prescription, 5.1% for treatment of attention deficit hyperactivity disorder and 1.7% for treatment of depression. 18.9% received a referral to specialist outpatient Child and Adolescent Mental Health Services. Age- and sex- standardised incidence rates for mental health prescribing and referrals are higher for children with a child protection registration compared to the general population.

Conclusion

Children identified as being at significant risk of harm and involved with child protection services are at greater risk of seeking or receiving professional mental health support than their peers. Clinical services should investigate additional ways to support this population’s mental well-being as a priority. Efforts to reduce the exposure of children to potentially harmful environments at a societal level should also be pursued.
Investigation of BRCA1 exon 11 genetic variations in breast cancer among Libyan women
Authors: Elshwekh Halla , Alhudiri Inas , Abdul Jalil Hamza Musbah , Mohamed Abdenaser A. , Elkikli Ahmed , Jornaz Naji , Enattah Nabil
Published: October 2023

Introduction

The majority of hereditary breast and ovarian cancers are associated with mutations in two genes, breast cancer type 1 and 2 susceptibility genes (BRCA1 and BRCA2). Here, we describe for the first time analysis of BRCA1 exon 11 in 48 Libyan breast cancer patients with a family history of cancer.

Methods

All patients had a family history of cancer and were included in the study only if they have a family history of breast or ovarian cancer, male breast cancer, or triple negative tumors. PCR was performed using specific primer pairs spanning BRCA1 exon 11 followed by Sanger sequencing. Genetic analysis was done using Sequencher® 5.1.

Results

We identified 12 genetic variants in BRCA1 exon 11. Three variants were novel (c.1019T>C, c.2363T>G, and c.3192T>C). c.2363T>G was predicted by SIFT as damaging. Six variants were of unknown significance (c.918T>C, c.1853G>C, c.1886G>A, c.2215A>G, c.2612C>T, c.3113A>C and c.3784T>C), and 3 were classified as benign in ClinVar database (c.918T>C, c.2082C>T and c.2311T>C).

Conclusions

Scanning of the entire BRCA1 is needed to identify any associated deleterious mutations. Although the clinical importance of unclassified variants is unknown, the association of certain variants with deleterious mutations and contralateral breast cancer warrants genetic testing and counseling in the Libyan population.
Salience network and cognitive impairment in Parkinson’s disease
Authors: Yeager Brooke E , Twedt Hunter P , Bruss Joel , Schultz Jordan , Narayanan Nandakumar S
Published: October 2023

Parkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We tested the hypothesis that cognitive impairments in PD involve altered connectivity of the salience network (SN), a key cortical network that detects and integrates responses to salient stimuli. We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. We report two major results. First, in 82 PD patients we found significant relationships between lower intra-network connectivity of the frontoparietal network (FPN; comprising the dorsolateral prefrontal and posterior parietal cortices bilaterally) with lower MoCA scores. Second, we found significant relationships between lower inter-network connectivity between the SN and the basal ganglia network (BGN) and the default mode network (DMN) with lower MoCA scores. These data support our hypothesis about the SN and provide new insights into the brain networks contributing to cognitive impairments in PD.

Highlights

Cognitive dysfunction is a prominent clinical symptom in Parkinson’s disease

Functional connectivity of the salience network is important for cognition

Salience network dynamics are altered in patients with Parkinson’s disease

Salience network connectivity with other networks is linked to worse cognition in PD
Harnessing consumer wearable digital biomarkers for individualized recognition of postpartum depression using theAll of UsResearch Program dataset
Authors: Hurwitz Eric , Butzin-Dozier Zachary , Master Hiral , O’Neil Shawn T. , Walden Anita , Holko Michelle , Patel Rena C. , Haendel Melissa A.
Published: October 2023

Postpartum depression (PPD), afflicting one in seven women, poses a major challenge in maternal health. Existing approaches to detect PPD heavily depend on in-person postpartum visits, leading to cases of the condition being overlooked and untreated. We explored the potential of consumer wearable-derived digital biomarkers for PPD recognition to address this gap. Our study demonstrated that intra-individual machine learning (ML) models developed using these digital biomarkers can discern between pre-pregnancy, pregnancy, postpartum without depression, and postpartum with depression time periods (i.e., PPD diagnosis). When evaluating variable importance, calories burned from the basal metabolic rate (calories BMR) emerged as the digital biomarker most predictive of PPD. To confirm the specificity of our method, we demonstrated that models developed in women without PPD could not accurately classify the PPD-equivalent phase. Prior depression history did not alter model efficacy for PPD recognition. Furthermore, the individualized models demonstrated superior performance compared to a conventional cohort-based model for the detection of PPD, underscoring the effectiveness of our individualized ML approach. This work establishes consumer wearables as a promising avenue for PPD identification. More importantly, it also emphasizes the utility of individualized ML model methodology, potentially transforming early disease detection strategies.
Spatial and temporal analysis of cholera cases in high-risk areas of Kenya
Authors: Mageto Lydia M , Mutono Nyamai , Aboge Gabriel , Gathura Peter , Okunga Emmanuel , Muange Annastacia , Mbae Cecilia , Thumbi SM , Kariuki Samuel
Published: October 2023

Cholera outbreaks remain an important public health challenge in Kenya, especially in areas with poor sanitation and hygiene including urban informal settlements, refugee camps and rural areas bordering large water bodies. Even in endemic settings, the distribution of cases exhibits spatial and temporal variations. Utilizing a Poisson discrete space-time scan statistic (SaTScan), this study investigated the temporal trends and the nature of spatial spread of cholera within selected high-risk areas in Kenya. The study was conducted in an urban informal settlement in Nairobi (Mukuru), a refugee camp in Northern Kenya (Dadaab) and the four counties bordering Lake Victoria region. Retrospective cholera line list data from January 2012 to December 2022 in the selected high-risk areas was used. SaTScan v10.1.2 was used to carry out Spatiotemporal analysis and generate spatial clusters. Throughout the study period, a total of 7,372 cholera cases were reported, corresponding to a lower annual incidence rate of 12.2 per 100,000 people compared to a mean annual incidence of 25 cases per 100,000 population previously reported in Kenya. The highest number of cases (n=5934) were reported between 2015 and 2018 with an annual incidence rate of 27.0 per 100,000 people, indicating a relative risk (RR) of 7.22 and a log-likelihood ratio (LLR) of 3015.17 (p< 0.001). The risky clusters (RR>1) were in Dadaab, Fafi, Suna West, Nyatike, Ugunja, Ndhiwa and Suna East sub counties with annual cases of 111.6, 164.1, 28.4, 19.9, 19.4, 14.0 and 13.9 per 100,000, respectively. The sub-counties of Nyakach, Nyando, Rachuonyo East, Kisumu East and Kisumu Central were reported as low-risk clusters, with a relative risk of 0.055 and an annual incidence rate of 1.1 cases per 100,000 individuals. Out of the thirty-two sub-counties included in the study, ten of them did not report any cases of cholera during the study period. Cholera cases waxed every three years in the selected high-risk areas. This data on hotspots specific to endemic settings forms a basis for prompt public health response and resource allocation by prioritizing the significantly high-risk clusters to control and eventually eliminate the disease.
Electrocardiogram sleep staging on par with expert polysomnography
Authors: Jones Adam M. , Itti Laurent , Sheth Bhavin R.
Published: October 2023

Accurate classification of sleep stages is crucial in sleep medicine and neuroscience research, providing valuable insights for diagnoses and understanding of brain states. The current gold standard for this task is polysomnography (PSG), an expensive and cumbersome process involving numerous electrodes, often performed in an unfamiliar clinic and professionally annotated. Although commercial devices like smartwatches track sleep, their performance compares poorly with PSG. To address this, we present a neural network that achieves gold-standard levels of agreement using a single lead of electrocardiogram (ECG) data (five-stage Cohen’s kappa = 0.725 on subjects 5 to 90 years old). Our method offers an inexpensive, automated, and convenient alternative. Cardiosomnography, or a sleep study conducted with electrocardiography only, could take expert-level sleep studies outside the confines of clinics and laboratories and into realistic settings. This would render higher-quality studies accessible to a broader community, enabling improved sleep research and sleep-related healthcare interventions.
Polygenic Embryo Screening: High Approval Despite Substantial Concerns from the U.S. Public
Authors: Furrer Rémy A. , Barlevy Dorit , Pereira Stacey , Carmi Shai , Lencz Todd , Lázaro-Muñoz Gabriel
Published: October 2023

Polygenic embryo screening (PES) is a novel – yet commercially available – technology that can compute genetic likelihood estimates of polygenic conditions (e.g., diabetes, depression) and traits (e.g., height, cognitive ability) in embryos. Patients undergoing in vitro fertilization (IVF) can use these polygenic scores to select which embryos to transfer for implantation with the goal of having a child. We conducted a survey of the U.S. public to examine attitudes toward PES encompassing acceptance, interest, potential uses, and concerns (n=1435). Our results indicate 72% public approval for PES, with 82% expressing some interest in using PES if already undergoing IVF. Approval for using PES for embryo selection is notably high for physical health (77%) and psychiatric conditions (72%). In contrast, there is minority approval for embryo selection based on PES for behavioral traits (36%) and physical traits (30%). Nevertheless, concerns about PES leading to false expectations, eugenic practices, and stigma are pronounced (54-55% find them “very” to “extremely” concerning). In a second sample of participants (n=192), presenting concerns at survey onset (vs. end) reduced approval (−28%) by mostly increasing ambivalence (+24%), and only slightly increasing disapproval (+4%). Given its commercial availability, practical limitations, and ethical concerns among physicians, patients, geneticists, bioethicists, and legal scholars, it is notable that there is such high public approval and interest in using PES. Understanding these attitudes is essential for informing policymakers, healthcare professionals, and researchers about the public’s perspectives on this novel biotechnology and debate about the role of medicine in regulating the use of PES.
Rurality Modifies the Association Between Symptoms and the Diagnosis of Amyotrophic Lateral Sclerosis
Authors: Hart Alexander A , Swenson Andrea , Narayanan Nandakumar S. , Simmering Jacob E.
Published: October 2023

Objective

We utilized national claims-based data to identify the change in hazard of diagnosis of ALS following a possible ALS-related diagnosis (e.g., falls) and whether the change in hazard varies whether the patient lives in an urban or rural area.

Methods

Health insurance claims data from both the commercial insurance market and Medicare supplemental market were obtained from the Merative MarketScan Commercial Claims and Encounters and Medicare Coordination of Benefits databases. Individuals with a diagnosis of ALS were identified and matched on age, sex, and enrollment period to individuals without ALS. For all individuals, inciting events such as falls, muscle related symptoms, or bulbar symptoms were also extracted. We then used fixed-effects regression to estimate the risk of being diagnosed with ALS following one of these events controlling for urban-rural status. Additionally, we utilized interaction terms to evaluate the effect of rurality on odds of diagnosis.

Results

19,126 individuals with ALS were included with 96,126 controls. Patients with ALS were more likely than matched controls to live in an urban area (87 vs 85%). Of those with ALS 84% had a symptom code preceding their diagnosis as compared to 51% in the general population. The association between having any symptoms and future diagnosis of ALS remained statistically significant after adjustment for confounders and an odds ratio of nearly 5. Odds ratios for the individual symptoms varied from 1.2 to over 10. In all models, living in an urban area was associated with increased odds of diagnosis with ALS while the effect of having a symptom was smaller among urban dwellers. Urban dwellers who are diagnosed with ALS are diagnosed at younger ages.

Conclusions

Early diagnosis of ALS is vital for connecting patients with research and treatment options. These results suggest symptoms appear in the administrative health record potentially years before the diagnosis of ALS. Additionally, rural patients are diagnosed at later ages with a greater dependence on major symptoms than urban patients. These results highlight potential improvements for surveillance and screening for ALS.
Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective review
Authors: Schiavo Simone , Brenna Connor T. A. , Albertini Lisa , Djaiani George , Marinov Anton , Katznelson Rita
Published: October 2023

Background

Hyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications.

Methods

Research Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed.

Results

Twenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6 – 62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n=11) or at 2.4 ATA (n=12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n=5), moderate/severe tricuspid regurgitation (n=3), or pulmonary hypertension (n=5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT.

Conclusions

Patients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.
A novel reperfusion method in patients with acute ST elevation myocardial infarction during primary percutaneous coronary intervention: A randomized control trial
Authors: He Ji-Fang , Yang Yi-Xing , Liu Yu , Guo Zong-Sheng , Sun Hao , Liang Lu , Jiang Tao , Yang Qi , Lin Xiang-Min , Chen Mu-Lei , Su Pi-Xiong , Yang Xin-Chun , Xu Li , Wang Le-Feng
Published: October 2023

BACKGROUND

Reperfusion injury is associated with larger infarct size and drawback of long-term outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Volume-Controlled Reperfusion (VCR) is our original reperfusion method combined with accurate gentle reperfusion and active protection for unstable plaque. A single center, prospective, randomized clinical trial was conducted to demonstrate the feasibility, clinical safety, and potential effects of VCR in STEMI patients during PPCI.

METHODS AND RESULTS

A total of 60 patients with STEMI presenting within 12 h of symptom onset undergoing PPCI were randomized enrolled to VCR group (n=30) or control group (n=30). Patients in VCR group recanalized with VCR followed by routine PCI. Patients in control group recanalized with routine PCI procedure only. The primary endpoint was all-cause death and major adverse cardiac events (MACE) during hospitalization and followed up, the main second endpoints were MVO extent measured 5-7 days post PPCI and left ventricular function. Baseline characteristics were well matched between two groups. No MACE from in-hospital to 1 year followed up in VCR group. In-hospital echocardiography based left ventricular eject fraction (LVEF) in VCR group compared with control group was (57.6 ± 6.2) % vs (52.9 ± 8.5) %, p = 0.018; especially in anterior STEMI VCR subgroup (55.1 ± 6.3) % v (s 48.6 ± 6.4) %, p = 0.003. There was no significant difference in infarct size, MVO mass or MVO mass/infarct mass ratio by late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-CMR). In hospital CMR based LVEF in anterior STEMI VCR subgroup was (50.55 ± 7.55) % vs (40.53 ± 7.39) %, p = 0.002. Follow up echocardiography based LVEF were (64.12 ± 6.35) % vs (59.44 ± 8.20) %, p = 0.025 between two groups and (62.07 ± 7.06) % vs (55.94 ± 6.70) %, p = 0.016 between anterior STEMI subgroups.

CONCLUSIONS

This is the pilot RCT study demonstrated that VCR method was feasibility and clinical safe among patients with acute STEMI during PPCI to 12-month follow-up, indicated potential attenuate effect in reperfusion injury as well. Staged II RCT is needed to verify clinical benefit.

REGISTRATION

URL:http://www.chictr.org.cn. Unique identifier: ChiCTR00052856
Microbiota-dependent indole production is required for the development of collagen-induced arthritis
Authors: Seymour Brenda J. , Trent Brandon , Allen Brendan , Berlinberg Adam J. , Tangchittsumran Jimmy , Jubair Widian K. , Chriswell Meagan E. , Liu Sucai , Ornelas Alfredo , Stahly Andrew , Alexeev Erica E. , Dowdell Alexander S. , Sneed Sunny L. , Fechtner Sabrina , Kofonow Jennifer M. , Robertson Charles E. , Dillon Stephanie M. , Wilson Cara C. , Anthony Robert M. , Frank Daniel N. , Colgan Sean P. , Kuhn Kristine A.
Published: October 2023

Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model we identify alterations in tryptophan metabolism, and specifically indole, that correlate with disease. We demonstrate that both bacteria and dietary tryptophan are required for disease, and indole supplementation is sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1β; splenic RORγt+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colon lymphocytes to indole increased expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a novel therapeutic pathway for RA and SpA.
Using the pan-genomic framework for the discovery of genomic islands in the haloarchaeonHalorubrum ezzemoulense
Authors: Feng Yutian , Arsenault Danielle , Louyakis Artemis S. , Altman-Price Neta , Gophna Uri , Papke R. Thane , Gogarten Johann Peter
Published: October 2023

In this study, we use pan-genomics to characterize the organized variability from the widely dispersed halophilic archaeal speciesHalorubrum ezzemoulense. We include a multi-regional sampling of newly sequenced, high-quality draft genomes. Using the pan-genome graph of the species, we discover 50 genomic islands which represent rare accessory genetic capabilities available to members of the species. 19 of these islands are likely the remnant of mobile genetic elements and are enriched for genomic dark matter. 10 islands encode for niche adapting solute transporters, with a cosmopolitan but limited distribution throughout the strains. We also observe rearrangements which have led to the insertion/recombination/replacement of mutually exclusive genomic islands in equivalent genome positions (“homeocassettes”). These conflicting islands encode for similar functions, but homologs from islands located between the same core genes exhibit extreme divergence on the amino acid level. Homeocasettes provide variations for a homologous function, which may confer a greater range of adaptability to the species group. We observe some islands that appear geographically restricted; however, we also observe the coexistence of genomes, in a single geographic region, with and without certain genomic islands, demonstrating the retention and spread of rare genes in the pan-genome.

Importance

Understanding the evolution of genome content is a key puzzle in evolutionary biology. Despite its importance, this area hasn’t received thorough investigation. This is especially true of Archaeal organisms, which constitute a large fraction of Earth’s diversity, but are often referred to as the “forgotten” or “third” domain of life. This study dives into those questions by finding rare genes amongst a group of closely related Archaeal species, and describes how their transfer, utilization and persistence may contribute to the speciation and specialization of the group.
High confidence glycosomal membrane protein inventory unveils trypanosomal Peroxin PEX15
Authors: Krishna Chethan K. , Das Hirak , Hohnen Lisa , Schliebs Wolfgang , Oeljeklaus Silke , Warscheid Bettina , Kalel Vishal C. , Erdmann Ralf
Published: October 2023

Infections by trypanosomatid parasites cause Chagas disease, Human African Trypanosomiasis, and Leishmaniasis, affecting over 12 million people worldwide. Glycosomes, the unique peroxisome-related organelles of trypanosomes are essential for their survival, and hence their metabolic functions and biogenesis mediated by peroxins (PEX) are suitable as drug targets. Here we report on a comprehensive protein inventory of glycosomal membranes through advanced subcellular membrane protein profiling employing quantitative mass spectrometry. Our quantitative analysis resulted in the identification of 28 novel high confidence glycosomal membrane proteins. Our in-depth protein inventory of glycosomal membranes serves as an important resource for characterizing glycosome biology and drug development. We validated four so far unknown glycosomal membrane proteins, including two tail-anchored (TA) proteins, a homolog of human peroxisomal PXMP4, and a Macrodomain-containing protein. Using a structure-based approach, we identified one of the TA proteins as the long-soughtTrypanosomaPEX15. Despite its low sequence similarity,TrypanosomaPEX15 exhibits structural and topological similarities with its yeast (Pex15) and human counterparts (PEX26). We show that PEX15 is an essential integral glycosomal membrane protein that interacts with PEX6. Accordingly, RNAi knockdown of PEX15 in bloodstream form trypanosomes demonstrates that it is essential for glycosome biogenesis and parasite survival. Considering the low degree of conservation with its human counterpart, PEX15 is a promising molecular target for drug development.
Arrayedin vivobarcoding for multiplexed sequence verification of plasmid DNA and demultiplexing of pooled libraries
Authors: Li Weiyi , Miller Darach , Liu Xianan , Tosi Lorenzo , Chkaiban Lamia , Mei Han , Hung Po-Hsiang , Parekkadan Biju , Sherlock Gavin , Levy Sasha F
Published: October 2023

Sequence verification of plasmid DNA is critical for many cloning and molecular biology workflows. To leverage high-throughput sequencing, several methods have been developed that add a unique DNA barcode to individual samples prior to pooling and sequencing. However, these methods require an individual plasmid extraction and/orin vitrobarcoding reaction for each sample processed, limiting throughput and adding cost. Here, we develop an arrayedin vivoplasmid barcoding platform that enables pooled plasmid extraction and library preparation for Oxford Nanopore sequencing. This method has a high accuracy and recovery rate, and greatly increases throughput and reduces cost relative to other plasmid barcoding methods or Sanger sequencing. We usein vivobarcoding to sequence verify >45,000 plasmids and show that the method can be used to transform error-containing dispersed plasmid pools into sequence-perfect arrays or well-balanced pools.In vivobarcoding does not require any specialized equipment beyond a low-overhead Oxford Nanopore sequencer, enabling most labs to flexibly process hundreds to thousands of plasmids in parallel.
“Fluorescent minihelix assay for translation quantification in high-throughput cell-free systems”
Authors: Willi Jessica A , Jewett Michael C
Published: October 2023

We report the use of an optimized tetra-cysteine minihelix both as a fusion protein and as a standalone reporter in vitro with the Flash dye to study cell-free protein expression dynamics and engineered ribosome activity. The fluorescent product can be detected and quantified via its characteristic emission spectrum in a standard 96/384-well plate reader, RT-qPCR system, or gel electrophoresis. The fluorescent reporter helix is short enough to be encoded on a primer pair and can tag any protein of interest via PCR. Both tagged protein or standalone reporter can be detected in real time during and in terminal cell-free expression reactions, or in gel, without the need for staining. The fluorescent signal is stable and linearly correlates with protein concentration, thus is suitable for product quantification. Finally, we demonstrate how this reporter can be used for future efforts in engineering in vitro translation systems.

Graphical abstract
The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation
Authors: Sinha Joydeb , Nickels Jan F. , Thurm Abby R. , Ludwig Connor H. , Archibald Bella N. , Hinks Michaela M. , Wan Jun , Fang Dong , Bintu Lacramioara
Published: October 2023

Histone H3.3 is frequently mutated in cancers, with the lysine 36 to methionine mutation (K36M) being a hallmark of chondroblastomas. While it is known that H3.3K36M changes the cellular epigenetic landscape, it remains unclear how it affects the dynamics of gene expression. Here, we use a synthetic reporter to measure the effect of H3.3K36M on silencing and epigenetic memory after recruitment of KRAB: a member of the largest class of human repressors, commonly used in synthetic biology, and associated with H3K9me3. We find that H3.3K36M, which decreases H3K36 methylation, leads to a decrease in epigenetic memory and promoter methylation weeks after KRAB release. We propose a new model for establishment and maintenance of epigenetic memory, where H3K36 methylation is necessary to convert H3K9me3 domains into DNA methylation for stable epigenetic memory. Our quantitative model can inform oncogenic mechanisms and guide development of epigenetic editing tools.