bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Exercise in the Management of Postpartum Diastasis Recti: A Systematic Review
Authors: Berg-Poppe Patti , Hauer Michaela , Jones Cassandra , Munger Mattison , Wethor Cassidy
Published: February 2022

Background:

Diastasis rectus abdominis (DRA) is a condition commonly prevalent in the immediate postpartum period and decreasing in prevalence during the first year after delivery. The condition is pathologic when it interferes with activities and quality of life. The condition is frequently assessed using the interrectus distance.

Objectives:

The purpose of this systematic review was to pool and analyze studies examining the use of exercise and companion modalities for the treatment of DRA among postpartum women.

Study Design:

Systematic review (PROSPERO CRD42021277067).

Methods:

A systematic search for articles published in CINAHL, MEDLINE, and PubMed was conducted. Included articles identified exercise as a component of treatment for DRA for postpartum women. The quality of the studies was evaluated using the appropriate NHLBI quality assessment tool. Risk of bias was assessed using the Cochrane ROB-2 and ROBINS-1 tools.

Results:

The database search yielded 38 titles; 16 more were located as secondary searches. Fourteen articles remained for final inclusion: 9 randomized controlled trials (RCT) and 5 cross-sectional studies. Interventions with significant DRA improvements included traditional abdominal exercises (AE) with deep core stability, AE with pelvic floor muscle exercises, crunch exercises, drawing-in exercises with AE, and neuromuscular electrical stimulation with AE. Article quality varied from poor to good across RCTs and poor to fair for non-RCTs.

Conclusion:

Although these findings support the use of AE to reduce interrectus distance and improve quality of postpartum life, future research should investigate exercise selection based on the results of more multifaceted and clinically meaningful assessments.
Clinical Practice Guidelines for Pelvic Girdle Pain in the Postpartum Population
Authors: Simonds Adrienne H. , Abraham Karen , Spitznagle Theresa
Published: February 2022

Background:

Pelvic girdle pain (PGP) is defined as pain experienced between the posterior iliac crest and the gluteal fold, particularly in the vicinity of the sacroiliac joint. Pelvic girdle pain is common postpartum, may result from pregnancy-related factors, and is a leading cause of disability postpartum. The purpose of this clinical practice guideline is to provide evidence-based recommendations for physical therapist management of PGP in the postpartum population.

Key Points:

Postpartum individuals may experience PGP beginning during pregnancy, immediately after childbirth, or up to 2 years after delivery. Although most cases of PGP in pregnancy resolve spontaneously, a subset of postpartum individuals may experience persistent pain. Based upon critical appraisal of literature and expert opinion, 23 action statements for risk factors, systems screening, examination, diagnosis, prognosis, theoretical models of care, and intervention for postpartum individuals with PGP are linked with explicit levels of evidence.

A significant body of evidence exists to support physical therapist intervention with postpartum clients with PGP to reduce pain and disability. Emerging evidence suggests that further investigation of biopsychosocial factors is warranted, especially factors that influence the development of persistent pain in the postpartum population. Future research is needed in several areas to optimize examination and intervention strategies specific to postpartum individuals and guided by a classification system for PGP that includes elements of pain, movement, and biopsychosocial factors.

The authors provide clinical practice guidelines for providing physical therapy to postpartum individuals with PGP.
Helicobacter pylori‐negative Chronic Gastritis in Children
Authors: Assa Amit , Borrelli Osvaldo , Broekaert Ilse , Saccomani Marco Deganello , Dolinsek Jernej , Martin‐de‐Carpi Javier , Mas Emmanuel , Miele Erasmo , Sila Sara , Thomson Mike , Tzivinikos Christos , Benninga Marc A. ,   The Gastrointestinal Committee of ESPGHAN
Published: February 2022

Objectives:

To systematically review the current evidence on Helicobacter pylori‐negative chronic gastritis including natural history, available therapies and outcomes.

Methods:

Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori‐negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included.

Results:

A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross‐sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%–45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses.

Conclusions:

Helicobacter pylori‐negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult‐paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.
Creating Interdisciplinary Engagement Through a Hospital-Based Endowed Chair in Nursing Research
Authors: Engh Eileen P. , Freedenberg Vicki , Ring Lisa M. , Lafond Deborah A. , Agazio Janice , Geiger-Brown Jeanne , Hinds Pamela S.
Published: February 2022

Although clinical nurses' involvement in research is a role expectation, efforts to engage clinical nurses in nurse-led research have had notably mixed results. These efforts have most typically been single discipline–focused (nursing), although nursing care is a collaborative, interdisciplinary practice. Adding an interdisciplinary strategy to multiple other efforts to engage clinical nurses in research may contribute to more nurse involvement. Here, we describe the use of a hospital-based endowed chair in nursing research to simultaneously engage nursing and other disciplines in a monthly dialogue about clinically relevant, research-related challenges and solutions. Outcomes indicate that the research-related dialogue among nurses and interprofessional colleagues would likely not have taken place without this approach.
Navigating COVID-19 Educational Challenges
Authors: Shermont Herminia , Pignataro Shelly , Moonan Marilyn , Memmolo Shauna , Murphy Jane M.
Published: February 2022

Nursing professional development practitioners and leadership staff implemented a second Transitional Mentor Education Program. The pilot program was classroom based; however, with pandemic restrictions, a shift to deliver a hybrid mentoring program was needed. Learning needs, clinician well-being, and professional development were addressed. Regardless of the method of educational delivery, the nurses in Phase 2 achieved the same outcomes as the pilot program, including increased clinical confidence, communication, integration of stress reduction strategies, and reflective practice.
Randomized Trial of a Web-Based Tobacco Treatment and Online Community Support for People With HIV Attempting to Quit Smoking Cigarettes
Authors: Shuter Jonathan , Chander Geetanjali , Graham Amanda L. , Kim Ryung S. , Stanton Cassandra A.
Published: February 2022

Background:

Persons with HIV (PWH) in the United States (US) smoke cigarettes at approximately triple the rate of the general adult population and are less successful in their quit attempts than other smokers. This randomized trial tested whether a novel web-based cessation program for PWH yielded higher cigarette quit rates compared with a control program.

Setting:

Two urban HIV care sites in NYC and Baltimore.

Methods:

Between 2016 and 2020, 506 PWH were randomized to either Positively Smoke Free on the Web (PSFW+; N = 255), a multimodal platform, interactive web intervention hosted within an online social network to support quitting among PWH who smoke, and an attention-matched web-based control intervention (American Heart Association Getting Healthy; N = 251). All participants were offered 12 weeks of nicotine patch. Our primary outcome was biochemically confirmed exhaled carbon monoxide < 10 parts per million (ppm) 7-day point prevalence abstinence at 6 months.

Results:

Participants were middle-aged (mean 50.2 years; range 23–73 years), 57% male, 19% Latinx, 83% Black, and 13% White. At 6 months, a significantly greater percentage of PSFW+ participants (14.9%) achieved biochemically confirmed 7-day point prevalence abstinence in intent-to-treat analysis compared with 8.8% of American Heart Association Getting Healthy participants [odds ratio =1.82 (95% confidence interval =1.04 to 3.18), P = 0.03].

Conclusions:

PSFW+ is a promising cessation intervention composed of empirically tested content and real-time social support through an online social network that was found to promote abstinence. This digital approach has broad reach and scalability, can be easily integrated into comprehensive HIV care, and represents an advance in the fight against tobacco use among PWH.
Risk of Immune Reconstitution Inflammatory Syndrome With Integrase Inhibitors Versus Other Classes of Antiretrovirals: A Systematic Review and Meta-analysis of Randomized Trials
Authors: Zhao Ying , Hohlfeld Ameer , Namale Phiona , Meintjes Graeme , Maartens Gary , Engel Mark E.
Published: February 2022

Background:

Integrase strand transfer inhibitors (InSTIs) decrease HIV plasma viral load faster than other antiretroviral classes. More rapid viral load decline has been associated with higher risk of immune reconstitution inflammatory syndrome (IRIS). There are conflicting reports on the association between InSTI and IRIS. We performed a systematic review and meta-analysis to compare the risk of IRIS among treatment-naive HIV-positive patients starting InSTI versus non-InSTI regimens.

Methods:

We searched PubMed, Scopus, Web of Science, Africa-Wide, and Cochrane databases from earliest available date to 26 November 2021, for randomized controlled trials (RCTs) having intervention arms with InSTI versus control arms without InSTI in patients initiating first-line antiretroviral therapy. The primary outcome was relative risk (RR) of IRIS, whereas the secondary outcome was RR of paradoxical tuberculosis-associated IRIS (TB-IRIS). Data were combined by random-effects meta-analysis according to the Mantel–Haenszel method. The protocol for this study is registered with PROSPERO, CRD42020213976.

Results:

We included 14 RCTs comprising 8696 participants from 6 continents for the primary outcome of IRIS and a subset of 674 participants (from 3 RCTs) for the secondary outcome of paradoxical TB-IRIS. Risk of IRIS was similar between InSTI and non-InSTI regimens (RR, 0.93; 95% confidence interval: 0.75 to 1.14). There was a trend towards a lower risk of paradoxical TB-IRIS with InSTI versus efavirenz regimens that was not statistically significant (RR, 0.64; 95% confidence interval: 0.34 to 1.19).

Conclusions:

In this meta-analysis among treatment-naive patients commencing first-line antiretroviral therapy, InSTI regimens were not associated with higher risk of IRIS.
Bone and Lymph Node Flare to Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer on 18F–Prostate-Specific Membrane Antigen PET/CT With Decreasing Prostate-Specific Antigen of 0.7 ng/mL
Authors: Lu Yang
Published: February 2022

A 72-year-old man with prostate cancer was found to have prostate-specific membrane antigen (PSMA)–avid oligometastasis on initial staging with 18F-DCFPyL PET/CT. Meanwhile, his prostate-specific antigen was 10.0 ng/mL, and testosterone level was 381 ng/dL. Six weeks after initiation of treatment on androgen deprivation therapy plus abiraterone, his restaging 18F-DCFPyL PET/CT showed decreased PSMA uptake in primary prostate lesion, but increased uptake in bone and lymph node metastases, whereas his prostate-specific antigen decreased to 0.7 ng/mL, and testosterone level was <3 ng/dL. This case illustrates hormone-sensitive metastatic bone and lymph node flare on 18F-PSMA PET/CT.
Characterization of an avian rotavirus A strain isolated from a velvet scoter (Melanitta fusca): implication for the role of migratory birds in global spread of avian rotaviruses
Authors: Fujii Yuji , Hirayama Mihoko , Nishiyama Shoko , Takahashi Tatsuki , Okajima Misuzu , Izumi Fumiki , Takehara Kazuaki , Masatani Tatsunori , Sugiyama Makoto , Ito Naoto
Published: February 2022

Avian G18P[17] rotaviruses with similar complete genome constellation, including strains that showed pathogenicity in mammals, have been detected worldwide. However, it remains unclear how these strains spread geographically. In this study, to investigate the role of migratory birds in the dispersion of avian rotaviruses, we analysed whole genetic characters of the rotavirus strain RK1 that was isolated from a migratory species of birds [velvet scoter (Melanitta fusca)] in Japan in 1989. Genetic analyses revealed that the genotype constellation of the RK1 strain, G18-P[17]-I4-R4-C4-M4-A21-N4-T4-E4-H4, was highly consistent with those of other G18P[17] strains detected in various parts of the world, supporting the possibility that the G18P[17] strains spread via migratory birds that move over a wide area. Furthermore, the RK1 strain induced diarrhoea in suckling mice after oral gastric inoculation, indicating that at least some of the rotaviruses that originated from migratory birds are infectious to and pathogenic in mammals. In conclusion, it was demonstrated that migratory birds may contribute to the global spread of avian rotaviruses that are pathogenic in mammalian species.
A new pterosaur from Skye, Scotland and the early diversification of flying reptiles
Authors: Martin-Silverstone Elizabeth , Unwin David M. , Cuff Andrew R. , Brown Emily E. , Allington-Jones Lu , Barrett Paul M.
Published: February 2022

The Middle Jurassic was a critical time in pterosaur evolution, witnessing the inception of major morphological innovations that underpinned successive radiations by rhamphorhynchids, basal monofenestratans and pterodactyloids. Frustratingly, this interval is particularly sparsely sampled, with a record consisting almost exclusively of isolated fragmentary remains. Here, we describe new material from the Bathonian-aged Kilmaluag Formation of Skye, Scotland, which helps to close this gap.REDACTED(gen. et sp. nov.) is based on a three-dimensionally preserved partial skeleton, which represents the first associated Middle Jurassic pterosaur.REDACTEDis one of the first pterosaurs to be fully digitally prepared and μCT scanning reveals multiple elements of the skeleton that remain fully embedded within the matrix, which are otherwise inaccessible. Novel anatomical features of this new Middle Jurassic pterosaur help to confirm the existence of the controversial clade Darwinoptera, greatly clarifying our understanding of Jurassic pterosaur evolution.
Editing the CsDMR6 Gene in Citrus Results in Resistance to the Bacterial Disease Citrus Canker
Authors: Parajuli Saroj , Huo Heqiang , Gmitter Fred G. , Duan Yongping , Luo Feng , Deng Zhanao
Published: February 2022

Citrus is one of the most important fruit crops in the world. Citrus production worldwide faces challenges from devastating bacterial diseases, including citrus canker caused by Xanthomonas citri ssp. citri (Xcc). Improving citrus resistance to citrus canker and other major bacterial diseases has been a top priority in citrus biotechnology. Disabling disease susceptibility genes has emerged as a novel, promising approach to engineering disease resistance. The bottleneck for applying such an approach has been the identification of proper disease susceptibility-related genes in citrus. Here we show the first successful case of editing the CsDMR6 gene in citrus and obtaining strong resistance to citrus canker in six mutants in two citrus cultivars, ‘Duncan’ grapefruit and Carrizo citrange. Multiple types of deletions and insertions were induced in CsDMR6, resulting in frameshift of its coding region and presumably loss of gene function. The mutation frequency in most of the mutants reached 71.8% to 98.9%. The mutants showed 71.2% to 99.8% reduction in citrus canker lesion and greater than 99.7% or 2.45 to 4.95 Log10 unit reduction in Xcc bacterial cell population. Mutants also accumulated more salicylic acid and expressed much higher levels of the NPR1 gene than the wildtype with or without Xcc inoculation, which suggests potential resistance to other diseases in these mutants. The guide RNAs for targeting CsDMR6 were selected from highly conserved regions and have 100% nucleotide identity with DMR6 homologs in important citrus species; these guide RNAs are expected to work in other important citrus species and cultivars.
Optimal resistance management for mixtures of high-risk fungicides: robustness to the initial frequency of resistance and pathogen sexual reproduction
Authors: Taylor Nick P , Cunniffe Nik J
Published: February 2022

There is a strong consensus that selection for fungicide resistant pathogen strains can be most effectively limited by using applications of mixtures of fungicides designed to balance disease control against selection. However, how to do this in practice is not entirely characterised. Previous work indicates optimal mixtures of pairs of fungicides which are both at a high risk of resistance can be constructed using pairs of doses which select equally for both single resistant strains in the first year of application. What has not been addressed thus far is the important real-world case in which the initial levels of resistance to each fungicide differ, for example because the chemicals have been available for different lengths of time. We show how recommendations based on equal selection in the first year can be sub-optimal in this case. We introduce a simple alternative approach, based on equalising the frequencies of single resistant strains in the year that achieving acceptable levels of control is predicted to become impossible. We show that this strategy is robust to changes in parameters controlling pathogen epidemiology and fungicide efficacy. We develop our recommendation using a pre-existing, parameterised model ofZymoseptoria tritici(the pathogen causing Septoria leaf blotch on wheat), which exemplifies the range of plant pathogens which predominantly spread clonally, but for which sexual reproduction forms an important component of the life cycle. We show that pathogen sexual reproduction can influence the rate at which fungicide resistance develops, but does not qualitatively affect our optimal resistance management recommendation.
Quantitatively defining species boundaries with more efficiency and more biological realism
Authors: Douglas Jordan , Bouckaert Remco
Published: February 2022

We introduce a widely applicable species delimitation method based on the multispecies coalescent model that is more efficient and more biologically realistic than existing methods. We extend the phylogenetic tree collapse model to the Yule-skyline model, allowing the ancestral speciation rate to vary through time as a smooth piecewise function. Furthermore, we introduce the cutting-edge proposal kernels of StarBeast3 to this model, thus enabling rapid species delimitation on large molecular datasets and allowing the use of relaxed molecular clock models. We validate these methods with genomic sequence data and SNP data, and show they are more efficient than existing methods at achieving parameter convergence during Bayesian MCMC. Lastly, we apply these methods to two datasets and find inconsistencies with the published literature. Our methods are powerful for rapid quantitative testing of species boundaries in large multilocus datasets and are implemented as an open source BEAST 2 package called SPEEDEMON.
Dissociable roles of theta and alpha in sub-second and supra-second time reproduction: An investigation of their links to depression and anxiety
Authors: Liang Mingli , Lomayesva Sara , Isham Eve A.
Published: February 2022

The Striatal Beat Frequency model (Matell & Meck, 2004) suggests that multiple cortical oscillators contribute to human temporal cognition. Based on the theory, the current study examined the interactions between interval timing and neural oscillations, as predicted by timing deficits found in neuropsychiatric conditions. The interaction is predicted to manifest in frontal-midline theta and occipital alpha oscillations, which are two important cortical oscillatory sources engaged in working memory and time perception. Therefore, the main goal of the study is to examine how depression and anxiety modulate frontal-midline theta and occipital data during the encoding of sub- and supra-second intervals. In the current study, participants reproduced sub- (400, 600, 800ms) and supra-second (1600, 1800, 2000ms) intervals while they underwent scalp EEG recordings. Anxiety and depression levels were measured via self-report psychometrics. We found that higher levels of self-reported anxiety and depression were associated with shorter reproduction of lengths of durations. Further, time-frequency analysis of scalp EEG revealed a dissociation where state anxiety altered the links between frontal-midline theta power and sub-second interval reproduction, while depression and trait anxiety altered the association between occipital alpha power and supra-second interval reproduction. Our results suggest that anxiety and depression alter time perception, and this differentially relates to frontal-midline theta and occipital alpha as substrates for sub- and supra-second interval timing.
Heated tobacco products and a telemedicine smoking cessation programme: A retrospective study
Authors: Nomura Akihiro , Ikeda Takaaki , Fujimoto Toshiki , Morita Yusaku , Taniguchi Chie , Ishizawa Tetsuro , Tabuchi Takahiro
Published: February 2022

Objectives

Japan is one of the largest markets for heated tobacco products (HTP), and the number of HTP users, including dual users, is burgeoning. However, it is not yet clear whether a telemedicine smoking cessation programme is helpful for nicotine-dependent people who use HTPs.

Methods

We retrospectively evaluated the effectiveness of a telemedicine smoking cessation programme for nicotine-dependent tobacco product users, comparing short- and long-term continuous abstinence rates (CAR) from 9 to 24 weeks (CAR9-24) and 9 to 52 weeks (CAR9-52). We divided programme participants into 1) exclusively cigarette users, 2) exclusively HTP users, and 3) dual users. Using logistic regression with inverse probability weighting, an adjusted odds ratio (aOR) with a 95% confidence interval (CI) for CAR was calculated to compare the differences among the three groups.

Results

We analysed 733 telemedicine smoking cessation programme participants (exclusively cigarette users, 52%; exclusively HTP users, 31%; and dual-users, 16%) dating August 2018 to October 2020. HTP users had higher CARs than the exclusively cigarettes group in CAR9-24 (aOR, 1.12; CI, 1.02–1.23; p=0.02) and CAR9-52 (aOR 1.09; CI, 0.99–1.19; p=0.08). Conversely, dual users had lower CARs than the exclusively cigarettes group in the CAR9-24 (aOR, 0.85; CI, 0.76–0.95; p=0.004) and CAR9-52 (aOR, 0.88; CI, 0.79–0.97; p=0.01).

Conclusions

Exclusively HTP users achieved higher CARs, whereas dual users had lower CARs than exclusively cigarette users over short- and long-term periods. A telemedicine smoking cessation programme may be a reasonable option for exclusively HTP users.

Key messages

What is already known on this topic

Telemedicine smoking cessation programmes can be helpful for some nicotine-dependent people.

What this study adds

Exclusively HTP users had higher continuous abstinence rates (CARs) than the exclusively cigarettes group. Conversely, dual users had lower CARs than the exclusively cigarettes group. A telemedicine smoking cessation programme may be a reasonable option for exclusive HTP users.

How this study might affect research, practice, or policy

In addition to conventional combustible cigarettes, the number of HTP users, including dual users, is burgeoning in Japan. This study could add an effective and alternative option for HTP users to remotely quit smoking in the era of COVID-19 and beyond.
Sleep duration and brain structure – phenotypic associations and genotypic covariance
Authors: Fjell Anders M. , Sørensen Øystein , Wang Yunpeng , Amlien Inge K. , Baaré William F.C. , Bartrés-Faz David , Bertram Lars , Boraxbekk Carl-Johan , Brandmaier Andreas M. , Demuth Ilja , Drevon Christian A , Ebmeier Klaus P. , Ghisletta Paolo , Kievit Rogier , Kühn Simone , Madsen Kathrine Skak , Mowinckel Athanasia M , Nyberg Lars , Sexton Claire E. , Solé-Padullés Cristina , Vidal-Piñeiro Didac , Wagner Gerd , Watne Leiv Otto , Walhovd Kristine B.
Published: February 2022

The question of how much sleep is best for the brain attracts scientific and public interest, and there is concern that insuficient sleep leads to poorer brain health. However, it is unknown how much sleep is sufficient and how much is too much. We analyzed 51,295 brain magnetic resonnance images from 47,039 participants, and calculated the self-reported sleep duration associated with the largest regional volumes and smallest ventricles relative to intracranial volume (ICV) and thickest cortex. 6.8 hours of sleep was associated with the most favorable brain outcome overall. Critical values, defined by 95% confidence intervals, were 5.7 and 7.9 hours. There was regional variation, with for instance the hippocampus showing largest volume at 6.3 hours. Moderately long sleep (> 8 hours) was more strongly associated with smaller relative volumes, thinner cortex and larger ventricles than even very short sleep (< 5 hours), but effect sizes were modest. People with larger ICV reported longer sleep (7.5 hours), so not correcting for ICV yielded longer durations associated with maximal volume. Controlling for socioeconomic status, body mass index and depression symptoms did not alter the associations. Genetic analyses showed that genes related to longer sleep in short sleepers were related to shorter sleep in long sleepers. This may indicate a genetically controlled homeostatic regulation of sleep duration. Mendelian randomization analyses did not suggest sleep duration to have a causal impact on brain structure in the analyzed datasets. The findings challenge the notion that habitual short sleep is negatively related to brain structure.

Significance statement

According to consensus recommendations, adults should sleep between 7 and 9 hours to optimize their health. We found that sleeping less than the recommended amount was associated with greater regional brain volumes relative to intracranial volume, and very short sleep was only weakly related to smaller volumes. Genetic analyses did not show causal effects of sleep duration on brain structure. Taken together, the results suggest that habitual short sleep is not an important contributor to lower brain volumes in adults on a group level, and that large individual dfferences in sleep need likely exist.
A five-fold expansion of the global RNA virome reveals multiple new clades of RNA bacteriophages
Authors: Neri Uri , Wolf Yuri I. , Roux Simon , Camargo Antonio Pedro , Lee Benjamin , Kazlauskas Darius , Chen I. Min , Ivanova Natalia , Allen Lisa Zeigler , Paez-Espino David , Bryant Donald A. , Bhaya Devaki ,   RNA Virus Discovery Consortium, Krupovic Mart , Dolja Valerian V. , Kyrpides Nikos C. , Koonin Eugene V. , Gophna Uri
Published: February 2022

High-throughput RNA sequencing offers unprecedented opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA viral contigs. Via analysis of the 330k novel RNA-dependent RNA polymerases (RdRP), this expansion corresponds to a five-fold increase of RNA virus diversity. Extended RdRP phylogeny supports monophyly of the five established phyla, reveals two putative new bacteriophage phyla and numerous putative novel classes and orders. The dramatically expandedLenarviricotaphylum, consisting of bacterial and related eukaryotic viruses, now accounts for a third of the RNA virome diversity. Identification of CRISPR spacer matches and bacteriolytic proteins suggests that subsets of picobirnaviruses and partitiviruses, previously associated with eukaryotes, infect prokaryotic hosts. Gene content analysis revealed multiple domains previously not found in RNA viruses and implicated in virus-host interactions. This vast collection of new RNA virus genomes provides insights into RNA virus evolution and should become a major resource for RNA virology.
Mathematical model of a cytokine storm
Authors: Kareva Irina , Berezovskaya Faina , Karev Georgy
Published: February 2022

Cytokine storm is a life-threatening inflammatory response that is characterized by hyperactivation of the immune system, and which can be caused by various therapies, auto-immune conditions, or pathogens, such as respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease COVID-19. While initial causes of cytokine storms can vary, late-stage clinical manifestations of cytokine storm converge and often overlap, and therefore a better understanding of how normal immune response turns pathological is warranted. Here we propose a theoretical framework, where cytokine storm phenomenology is captured using a conceptual mathematical model, where cytokines can both activate and regulate the immune system. We simulate normal immune response to infection, and through variation of system parameters identify conditions where, within the frameworks of this model, cytokine storm can arise. We demonstrate that cytokine storm is a transitional regime, and identify three main factors that must converge to result in storm-like dynamics, two of which represent individual-specific characteristics, thereby providing a possible explanation for why some people develop CRS, while others may not. We also discuss possible ecological insights into cytokine-immune interactions and provide mathematical analysis for the underlying regimes. We conclude with a discussion of how results of this analysis can be used in future research.
A network of cytosolic (co)chaperones promotes the biogenesis of mitochondrial signal-anchored outer membrane proteins
Authors: Drwesh Layla , Heim Benjamin , Graf Max , Kehr Linda , Hansen-Palmus Lea , Franz-Wachtel Mirita , Macek Boris , Kalbacher Hubert , Buchner Johannes , Rapaport Doron
Published: February 2022

Signal-anchored (SA) proteins are anchored into the mitochondrial outer membrane (OM) via a single transmembrane segment at their N-terminus while the bulk of the proteins is facing the cytosol. These proteins are encoded by nuclear DNA, translated on cytosolic ribosomes, and are then targeted to the organelle and inserted into its OM by import factors. Recently, research on the insertion mechanisms of these proteins into the mitochondrial OM have gained a lot of attention. In contrast, the early cytosolic steps of their biogenesis are unresolved. Using various proteins from this category and a broad set of in vivo, in organello, and in vitro assays, we reconstituted the early steps of their biogenesis. We identified a subset of molecular (co)chaperones that interact with newly synthesized SA proteins, namely, Hsp70 and Hsp90 chaperones and co-chaperones from the Hsp40 family like Ydj1 and Sis1. These interactions were mediated by the hydrophobic transmembrane segments of the SA proteins. We further demonstrate that interfering with these interactions inhibits the biogenesis of SA proteins to varying extents. Finally, we could demonstrate direct interaction of peptides corresponding to the transmembrane segments of SA proteins with the (co)chaperones and reconstitute in vitro the transfer of such peptides from the Hsp70 chaperone to the mitochondrial Tom70 receptor. Collectively, this study unravels an array of cytosolic chaperones and mitochondrial import factors that facilitates the targeting and membrane integration of mitochondrial SA proteins.
Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse
Authors: Zhang Donghang , Wei Yiyong , Liu Jin , Yang Yaoxin , Ou Mengchan , Chen Yali , Shen Jiefei , Zhu Tao , Zhou Cheng
Published: February 2022

Glial cells play a crucial role in regulating physiological and pathological functions, such as sensation, infections, acute injuries, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS) and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Despite the understanding of glial subtypes and functional heterogeneity in animal models achieved by single-cell or single-nucleus RNA sequencing, no research has investigated the transcriptomic profiles of glial cells in the human PNS and spinal cord. Here, we used high-throughput single-nucleus RNA sequencing to map the cellular and molecular heterogeneity of SGCs in the human dorsal root ganglion (DRG) and astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these human findings with those from mice. Additionally, the expression profiles of risk genes of common DRG and spinal cord diseases in glial cells were compared between humans and mice. As a result, little SGCs heterogeneity was found in both human and mouse DRG. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were respectively divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into six, five, and six distinct transcriptomic subclusters, respectively. The comparative results revealed substantial heterogeneity in all glial cells between humans and mice. Notably, we also identified transcriptomic heterogeneity in several classical genes and risk genes for neurological disorders across humans and mice. Together, the present data comprehensively profiled glial cell heterogeneity and provides a powerful resource for investigating the cellular basis of glial-related physiological and pathological conditions in peripheral somatosensory system.
Creating De Novo Overlapped Genes
Authors: Logel Dominic Y. , Jaschke Paul R.
Published: February 2022

Future applications of synthetic biology will rely on deploying engineered cells outside of lab environments for long periods of time. Currently, a significant roadblock to this application is the potential for deactivating mutations in engineered genes. A recently developed method to protect engineered coding sequences from mutation is called Constraining Adaptive Mutations using Engineered Overlapping Sequences (CAMEOS). In this chapter we provide a workflow for utilising CAMEOS to create synthetic overlaps between two genes, one essential (infA) and one non-essential (aroB), to protect the non-essential gene from mutation and loss of protein function. In this workflow we detail the methods to collect large numbers of related protein sequences, produce multiple sequence alignments (MSAs), use the MSAs to generate Hidden Markov Models and Markov Random Field models, and finally generate a library of overlapping coding sequences through CAMEOS scripts. To assist practitioners with basic coding skills to try out the CAMEOS method, we have created a virtual machine containing all the required packages already installed, that can be downloaded and run locally.
Systematic analysis and prediction of genes associated with disorders on chromosome X
Authors: Leitão Elsa , Schröder Christopher , Parenti Ilaria , Dalle Carine , Rastetter Agnès , Kühnel Theresa , Kuechler Alma , Kaya Sabine , Gérard Bénédicte , Schaefer Elise , Nava Caroline , Drouot Nathalie , Engel Camille , Piard Juliette , Duban-Bedu Bénédicte , Villard Laurent , Stegmann Alexander P.A. , Vanhoutte Els K. , Verdonshot Job A.J , Kaiser Frank J. , Mau-Them Frédéric Tran , Scala Marcello , Striano Pasquale , Frints Suzanna G.M. , Argilli Emanuela , Sherr Elliott H. , Elder Fikret , Buratti Julien , Keren Boris , Mignot Cyril , Héron Delphine , Mandel Jean-Louis , Gecz Jozef , Kalscheuer Vera M. , Horsthemke Bernhard , Piton Amélie , Depienne Christel
Published: February 2022

Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using a neural network trained to distinguish disease-associated from dispensable genes, we classify 235 genes, including 121 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.
Glycemic variability and all-cause mortality in a large prospective southern European cohort of patients with differences in glycemic status
Authors: Salinero-Fort Miguel A. , San Andrés-Rebollo F. Javier , Cárdenas-Valladolid Juan , Mostaza José M. , Lahoz Carlos , Rodriguez-Artalejo Fernando , Gómez-Campelo Paloma , Vich-Pérez Pilar , Jiménez-García Rodrigo , López de Andrés Ana , de Miguel-Yanes José M.
Published: February 2022

Background

Few studies have analyzed the relationship between glucose variability (GV) and adverse health outcomes in patients with differences in glycemic status. The present study tests the hypothesis that GV predicts all-cause mortality regardless of glycemic status after simple (age and sex) and full adjustment (age, sex, cardiovascular disease, hypertension, use of aspirin, statins, GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors, baseline FPG and average HbA1c).

Methods

Prospective cohort study with 795 normoglycemic patients, 233 patients with prediabetes, and 4,102 patients with type 2 diabetes. GV was measured using the coefficient of variation of fasting plasma glucose (CV-FPG) over 12 years of follow-up. The outcome measure was all-cause mortality.

Results

A total of 1,223 patients (657 men, 566 women) died after a median of 9.8 years of follow-up, with an all-cause mortality rate of 23.35/1,000 person-years. In prediabetes or T2DM patients, the fourth quartile of CV-FPG exerted a significant effect on all-cause mortality after simple and full adjustment. A sensitivity analysis excluding participants who died during the first year of follow-up revealed the following results for the highest quartile in the fully adjusted model: overall, HR (95%CI) =1.54 (1.26-1.89); dysglycemia (prediabetes and T2DM), HR=1.41 (1.15-1.73); T2DM, HR=1.36 (1.10-1.67).

Conclusion

We found CV-FPG to be useful for measurement of GV. It could also be used for the prognostic stratification of patients with dysglycemia.
Ingestible capsule for detecting labile inflammatory biomarkers in situ
Authors: Inda ME , Jimenez M , Liu Q , Phan NV , Ahn J , Steiger C , Wentworth A , Riaz A , Zirtiloglu T , Wong K , Ishida K , Fabian N , Jenkins J , Kuosmanen J , Madani W , McNally R , Lai Y , Hayward A , Mimee M , Nadeau P , Chandrakasan AP , Traverso G , Yazicigil RT , Lu TK
Published: February 2022

Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 μL of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.
Mechanoregulation of biofilm architecture promotes P. aeruginosa antibiotic tolerance
Authors: Cont Alice , Vermeil Joseph , Persat Alexandre
Published: February 2022

In the wild, bacteria are most frequently found in the form of multicellular structures called biofilms1. Biofilms grow at the surface of abiotic and living materials with wide-ranging mechanical properties. Despite their co-occurrence during infection, we still lack a clear understanding of how mechanics regulate biofilm architecture and the physiology of resident bacteria. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on indwelling medical device2 and on soft tissues including burn wounds and the airway mucosa3. Here, we demonstrate that mechanical properties of hydrogel material substrates define P. aeruginosa biofilm architecture. We show that hydrogel mesh size regulates twitching motility, a surface exploration mechanism priming biofilms, ultimately controlling the arrangement of single cells in the multicellular community. The resulting architectural transitions increase P. aeruginosa’s tolerance to colistin, a last resort antibiotic. Our results thereby establish material properties as a regulator of biofilm architecture and antibiotic efficacy.
Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma
Authors: Shin Jaehoon , Parker Matthew F. L. , Zhu Iowis , Alanizi Aryn , Rodriguez Carlos I. , Liu Raymond , Watchmaker Payal B. , Kalita Mausam , Blecha Joseph , Luu Justin , Wright Brian , Lapi Suzanne E. , Flavell Robert R. , Okada Hideho , Tlsty Thea D. , Roybal Kole T. , Wilson David M.
Published: February 2022

For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [18F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.
Hypothalamic astrocytes control systemic glucose metabolism and energy balance via regulation of extra-synaptic glutamate signaling
Authors: Chao Daniela Herrera Moro , Kirchner Matthew K , Pham Cuong , Foppen Ewout , Denis Raphael GP , Castel Julien , Morel Chloe , Montalban Enrica , Hassouna Rim , Bui Linh-Chi , Renault Justine , Mouffle Christine , García-Cáceres Cristina , Tschöp Matthias H. , Li Dongdong , Martin Claire , Stern Javier E , Luquet Serge H
Published: February 2022

The hypothalamus is key in the control of energy balance. However, to this day strategies targeting hypothalamic neurons failed to provide viable option to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism and energy balance. Such process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals respectively worsen or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocyte in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.