bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Vibration Therapy on the Physical Function of Critically Ill Adults Trial: A Randomized Controlled Trial
Authors: Doi Satoshi , Nakanishi Nobuto , Kawahara Yoshimi , Nomura Keiko , Shima Mamiko , Shiraishi Mie , Oto Jun
Published: January 2024

Objectives:

Vibration therapy uses vibration to rehabilitate physical functions. Recently, it has been demonstrated to be safe for critically ill patients. However, its effects on physical functions are unclear.

Design:

Randomized controlled trial.

Setting:

A single-center, ICU.

Patients:

Patients were randomly assigned to either vibration therapy coupled with protocolized mobilization or protocolized mobilization alone. We included patients who could sit at the edge of the bed or in a wheelchair during their ICU stay. The exclusion criteria were based on the early mobilization inhibition criteria.

Interventions:

The primary outcome was the Functional Status Score for the ICU (FSS-ICU) at ICU discharge. Secondary outcomes were the Medical Research Council score, ICU-acquired weakness, delirium, ICU Mobility Scale (IMS), and ventilator- and ICU-free days. For safety assessment, vital signs were monitored during the intervention.

Measurements and Main Results:

Among 180 patients, 86 and 90 patients remained in the vibration therapy and control groups, respectively. The mean age was 69 ± 13 vs. 67 ± 16 years in the vibration therapy and control groups, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (14–25) vs. 18 (13–23). The total FSS-ICU at ICU discharge was 24 (18–27) and 21 (17–26) in the intervention and control groups, respectively (p = 0.09), and the supine-to-sit ability significantly improved in the intervention group (p < 0.01). The secondary outcomes were not significantly different. Vital signs remained stable during vibration therapy. In the predefined subgroup analysis, FSS-ICU improved in the population with a higher body mass index (≥ 23 kg/m2), lower APACHE II scores (< 19), and higher IMS scores (≥ 6).

Conclusions:

Vibration therapy did not improve the total FSS-ICU. However, the supine-to-sit ability in the FSS-ICU improved without any adverse event.
Factors Associated With Performing Ileal Pouch-Anal Anastomosis After Total Colectomy for Ulcerative Colitis
Authors: Chen Kevin A. , Pak Joyce , Agala Chris B , Stem Jonathan M. , Guillem Jose G. , Barnes Edward L , Herfarth Hans H. , Kapadia Muneera R.
Published: January 2024

BACKGROUND:

Ileal pouch-anal anastomosis is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of ileal pouch-anal anastomosis within individual states, but not at the national level in the United States.

OBJECTIVE:

Assess the rate of ileal pouch-anal anastomosis after total colectomy for ulcerative colitis in a national population and identify factors associated with ileal pouch-anal anastomosis.

DESIGN:

This was a retrospective cohort study.

SETTINGS:

This study was performed in the United States.

PATIENTS:

Patients who were ≥18 years old who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients >65 years old with Medicare.

MAIN OUTCOME MEASURES:

The primary outcome was ileal pouch-anal anastomosis. Multivariable logistic regression was used to assess the association between covariates and likelihood of undergoing ileal pouch-anal anastomosis.

RESULTS:

In total, 2,816 patients were included of whom 1414 (50.2%) underwent ileal pouch-anal anastomosis, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with ileal pouch-anal anastomosis, but not socioeconomic status.

LIMITATIONS:

This retrospective study included only patients with commercial insurance.

CONCLUSIONS:

A total of 50.2% of patients undergo ileal pouch-anal anastomosis and younger age, lower co-morbidities, and elective cases are associated with a higher rate of ileal pouch-anal anastomosis placement. This emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract.
Endoscopic Evaluation of the Ileal Pouch
Authors: Shen Bo
Published: January 2024

BACKGROUND:

Structural and inflammatory adverse sequelae are common after restorative proctocolectomy and ileal pouch-anal anastomosis. On rare occasions, neoplasia can occur in patients with ileal pouches. Pouchoscopy plays a key role in the diagnosis, differential diagnosis, disease monitoring, assessment of treatment response, surveillance, and delivery of therapy.

OBJECTIVE:

A systemic review of the literature was performed and principles and techniques of pouchoscopy were described.

DATA SOURCES:

PubMed, Google Scholar, and Cochrane database.

STUDY SELECTION:

Relevant articles on endoscopy in ileal pouches published between Jan 2000 and May 2023 were including based on PRISMA guidelines.

INTERVENTION:

Diagnostic, surveillance, and therapeutic endoscopy in ileal pouch disorders were included.

MAIN OUTCOME MEASURES:

Accurate characterization of the ileal pouch at the healthy or diseased states.

RESULTS:

The main anatomic structures of a J or S pouch are the stoma closure site, prepouch ileum, inlet, tip of the “J,” pouch body, anastomosis, cuff, and anal transition zone. Each anatomic location can be prone to the development of structural, inflammatory, or neoplastic disorders. For example, ulcers and strictures are common at the stoma closure site, inlet, and anastomosis. Leaks are commonly detected at the tip of the “J” and anastomosis. Characterization of the anastomotic distribution of inflammation is critical for the differential diagnosis of subtypes of pouchitis and other inflammatory disorders of the pouch. Neoplastic lesions, albeit rare, mainly occur at the cuff, anal transition zone, or anastomosis.

LIMITATIONS:

This is a qualitative, not quantitative review of mainly case series.

CONCLUSIONS:

Most structural, inflammatory, and neoplastic disorders can be reliably diagnosed with a careful pouchoscopy. The endoscopist and other clinicians taking care of pouch patients should be familiar with the anatomy of the ileal pouch, and recognize common abnormalities. See video from symposium. See Video.
Exosomes miRNA-499a-5p targeted CD38 to alleviate anthraquinone induced cardiotoxicity: experimental research
Authors: Ma Chunhua , Yang Zhaocong , Wang Jing , She Han , Tan Lei , Ye Qing , Wang Fei , Feng Xiaochun , Mo Xuming , Liu Kun , Liu Liangming
Published: January 2024

Background:

The purpose of this study was to investigate the effects of cardiac homing peptide (CHP) engineered bone marrow mesenchymal stem cells (BMMSc) derived exosomes (B-exo) loaded miRNA-499a-5p on doxorubicin (DOX) induced cardiotoxicity.

Methods:

miRNA chip analysis was used to analyze the differences between DOX induced H9c2 cells and control group. CHP engineering was performed on BMMSc derived exosomes to obtain C-B-exo. miRNA-499a-5p mimic was introduced into C-B-exo by electroporation technology to obtain C-B-exo-miRNA-499a-5p. DOX was used to establish a model of cardiotoxicity to evaluate the effects of C-B-exo- miRNA-499a-5p in vivo and in vitro. Western blot, immunohistochemistry, immunofluorescence, and other molecular biology methods were used to evaluate the role and mechanism of C-B-exo-miRNA-499a-5p on DOX induced cardiotoxicity.

Results:

miRNA chip analysis revealed that miRNA-499a-5p was one of the most differentially expressed miRNAs and significantly decreased in DOX induced H9c2 cells as compared to the control group. Exo-and B-exo have a double-layer membrane structure in the shape of a saucer. After engineering the CHP of B-exo, the results showed that the delivery of miRNA-499a-5p significantly increased and significantly reached the target organ (heart). The experimental results showed that C-B-exo-miRNA-499a-5p significantly improved electrocardiogram, decreased myocardial enzyme, serum and cardiac cytokines, improved cardiac pathological changes, inhibited CD38/MAPK/NF-κB signal pathway.

Conclusions:

In this study, C-B-exo-miRNA-499a-5p significantly improved DOX-induced cardiotoxicity via CD38/MAPK/NF-κB signal pathway, providing a new idea and method for the treatment of DOX induced cardiotoxicity.
C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden
Authors: Bay Benjamin , Arnold Natalie , Waldeyer Christoph
Published: January 2024

Purpose of review

This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.

Recent findings

Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.

Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.
Raccoon Eyes Presentation in a Child Diagnosed With Acute Lymphoblastic Leukemia: A Case Report
Authors: Terzi Özlem , Bayram Cengiz , Solgun Hüseyin Avni , Yildirgan Duygu , Ayçiçek Ali
Published: January 2024

Raccoon’s eyes (periorbital ecchymosis) may present as the first sign in patients with skull base/base/facial fractures and tumors. In childhood, orbital metastases of neuroblastoma should be considered in the absence of trauma history. Herein, we report a 3-year-old girl diagnosed with acute lymphoblastic leukemia who presented with periorbital ecchymosis. To the best of our knowledge, this is the first pediatric patient with acute lymphoblastic leukemia in the literature who presented with raccoon eyes.
Wilson’s disease causing acute-onset of optic neuropathy in a child: a case report and literature review
Authors: Albostani Ammar , Warda Hamza , Alhashemi Fares , Rajabieh Manar , Abdulrazzak Mohammed , Kanjo Muhamad
Published: January 2024

Introduction and importance:

Wilson disease (WD) is a rare genetic disorder with a wide range of clinical manifestations, including hepatic, neurologic, and psychiatric symptoms. To date, there have been five cases (including our case) representing optic neuropathy caused by WD.

Case presentation:

A 15-year-old female presented to the emergency department with neurological symptoms. The patient exhibited confusion but maintained stable vital signs, and physical examinations were all normal. Abdominal ultrasound and axial brain computed tomography (CT) scan were both normal. The patient’s neurological condition and laboratory test results suggested diagnoses of WD. After 2 days, the patient experienced sudden bilateral blindness. The patient’s condition deteriorated rapidly, and was subsequently referred to the ICU.

Clinical discussion:

The incidence of the disease varies by ethnicity, with a higher prevalence in Eastern Asian populations. Diagnosis can be challenging due to the diverse presentation of symptoms, but it is important to consider WD as a differential diagnosis in patients presenting with acute hepatitis and/or neurologic abnormalities.

Conclusion:

Healthcare professionals should be educated about the diverse clinical manifestations of WD to help in early recognition and diagnosis of the disease.
The Healthy Label
Authors: Velasquez Juan A. , Thompson Jacob M. , Hicks Emily M. , Morales-Juárez Analí , Mendoza Ivan , Savaiano Dennis A.
Published: January 2024

The US Food and Drug Administration is considering an update of a front-of-pack voluntary “healthy” designation that received little use or attention by the food industry. Effective communication to consumers is crucial in promoting healthy diet and lifestyle patterns. In the current food landscape, it is difficult for consumers to determine what foods are healthy. Furthermore, the healthy definition should fit the current science based on the Dietary Guidelines for Americans. We present an argument for required front-of-pack labeling, rooted squarely in the Dietary Guidelines.
The Role of Guar Fiber in Improving the Management of Irritable Bowel Syndrome, Functional Constipation, and Functional Diarrhea
Authors: Tupper Lara , Terol Monique , Utter Jennifer , Morley Shannon
Published: January 2024

Background and Aims

Guar fiber is a soluble fiber that has been used for symptom management of irritable bowel syndrome (IBS), functional constipation (FC), and functional diarrhea (FD). However, the effect of guar fiber supplementation on symptom management is currently unclear. The aim of this review is to determine the effect of guar fiber supplementation compared with any other nutrition intervention on gastrointestinal (GI) symptoms with individuals diagnosed with IBS, FC, and FD. A secondary aim is to determine the dosage of guar fiber supplementation required to elicit an improvement in associated symptoms.

Methods

A systematic review (CRD42022374730) was performed with literature from inception. PubMed, EMBASE, CINAHL, and Web of Science were searched on October 28, 2022, to identify eligible studies which reported guar fiber supplementation in patients diagnosed with IBS, FC, and/or FD using the Rome criterion. Findings were synthesized narratively. Study quality was assessed using the Johanna Briggs Institute quality assessment tools.

Results

Nine articles reported on stool consistency, defecation frequency, laxative use, bloating, abdominal pain, flatulence, and quality of life (QOL). All pre-post studies (n = 5) reported statistically significant improvements for GI symptoms and QOL. Two of 4 randomized controlled trial studies reported improvements in GI symptoms when supplemented daily with 5 to 6 g of guar fiber for 4 to 12 weeks.

Conclusions

Our study shows that guar fiber supplementation appears effective in improving symptom management of IBS and FC with a 5-g/d dosage most used. Future studies are required to more clearly understand the benefits of guar fiber supplementation and elucidate dosing strategies. This review provides the grounds for further well-designed studies to investigate the impact of guar fiber supplementation in populations with IBS, FC, and FD.
Virtual geriatric and frailty assessment for older adults with cancer
Authors: Tejero Isabel , Amor Eva , Vázquez-Ibar Olga
Published: January 2024

Purpose of review

Since SARS-CoV2 pandemic, many specialties have introduced virtual assessments within clinical practice. Conducting an online geriatric assessment, or relying on self-reported questionnaires, may be more challenging than a conventional medical appointment. This review aims to discuss the state of research on virtual assessment and self-reported questionnaires in the general geriatric population and specifically in Oncology.

Recent findings

Virtual assessment of older adults has been the focus of two separate position papers. Aside from videoconferences or phone appointments, self-reported questionnaires have emerged in recent years as reliable tools to screen for frailty and triage patients who would benefit from a comprehensive in-person assessment, with adequate correlation with in-person tests, good acceptance by the respondents and being well received by healthcare providers. Although some have been tried in geriatric oncology, many still lack validation, and their widespread use may be limited by digital literacy, cognitive impairment, and social supports.

The development, validation and adoption of self-reported questionnaires and virtual assessment in the care of older adults with cancer may overcome the staffing limitations and time constrains that frequently hampers the widespread evaluation of this population to improve their care.
Is Pilates effective in improving depressive disorders? A comprehensive overview
Authors: Legnani Francesca , Tassi Lorenzo , Surace Teresa , Capuzzi Enrico , Caldiroli Alice , Clerici Massimo , Buoli Massimiliano
Published: January 2024

Depressive disorders are disabling conditions that account for high social costs. Pilates demonstrated to have several beneficial effects on health. Objective of this manuscript was to systematically review the literature about the effects of Pilates on depressive disorders. A bibliographic search was conducted in the main database sources (Pubmed, Medline, and Scopus). The inclusion criteria consisted of articles written in English language about the effectiveness of Pilates on depressive symptoms. Most of included studies are randomized controlled trials (10 out of 12). The available literature agrees in indicating that Pilates is effective in improving depressive symptoms especially when compared to inactivity and when this practice is administered for a medium-long period (8–16 weeks). In addition, Pilates seems to have at least comparable effectiveness than aerobic exercise. Pilates can be considered a reliable complementary treatment for people with depressive disorders. These findings should be interpreted considering the different types of practice administered as well as the different duration of the programs or rating scales used to assess mood symptoms. Studies with a more homogenous design are needed to confirm and make generalizable the results presented in this review.
The Relationship between microbial population adenosine triphosphate and quantitative polymerase chain reaction bioburdens in diesel fuel microcosms
Authors: Passman Frederick Jay , Schmidt Jordan , Nicoletti Danika
Published: January 2024

Fluid samples drawn from the fuel, interface, and water phases of fuel over water microcosms were tested for cellular adenosine triphosphate concentration ([cATP]), and quantitative polymerase chain reaction (qPCR) bioburdens.  Additionally, surface swab samples from steel corrosion coupon surfaces exposed to each of these three phases were collected and tested for total ATP concentration ([tATP]) and qPCR bioburdens.  Statistical relationships between ATP and qPCR bioburdens were examined.  Correlation coefficients between the two variables were matrix dependent and ranged from negligible (|r| = 0.2) to strong (|r| = 0.7).  When results were categorized into negligible, moderate, and heavy bioburdens, parameter agreement was again matrix dependent.  Percent agreement between [ATP] and qPCR gene copies ranged from 11 % to 89 % – with qPCR-bioburden ratings typically being greater than ATP-bioburden ratings.
Functional impairment of “helpless” CD8+memory T cells is transient and driven by prolonged but finite cognate antigen presentation
Authors: van der Heide Verena , Davenport Bennett , Cubitt Beatrice , Roudko Vladimir , Choo Daniel , Humblin Etienne , Jhun Kevin , Angeliadis Krista , Dawson Travis , Furtado Glaucia , Kamphorst Alice , Ahmed Rafi , de la Torre Juan Carlos , Homann Dirk
Published: January 2024

Generation of functional CD8+T cell memory typically requires engagement of CD4+T cells. However, in certain scenarios, such as acutely-resolving viral infections, effector (TE) and subsequent memory (TM) CD8+T cell formation appear impervious to a lack of CD4+T cell help during priming. Nonetheless, such “helpless” CD8+TMrespond poorly to pathogen rechallenge. At present, the origin and long-term evolution of helpless CD8+T cell memory remain incompletely understood. Here, we demonstrate that helpless CD8+TEdifferentiation is largely normal but a multiplicity of helpless CD8 TMdefects, consistent with impaired memory maturation, emerge as a consequence of prolonged yet finite exposure to cognate antigen. Importantly, these defects resolve over time leading to full restoration of CD8+TMpotential and recall capacity. Our findings provide a unified explanation for helpless CD8+T cell memory and emphasize an unexpected CD8+TMplasticity with implications for vaccination strategies and beyond.
Forest growth resistance and resilience to the 2018-2020 drought depend on tree diversity and mycorrhizal type
Authors: Sachsenmaier Lena , Schnabel Florian , Dietrich Peter , Eisenhauer Nico , Ferlian Olga , Quosh Julius , Richter Ronny , Wirth Christian
Published: January 2024

The frequency of consecutive drought years is predicted to increase due to climate change. These droughts have strong negative impacts on forest ecosystems. Mixing tree species is proposed to increase the drought resistance and resilience of tree communities. However, this promising diversity effect has not yet been investigated under extreme drought conditions and in the context of complementary mycorrhizal associations and their potential role in enhancing water uptake.

Here, we investigate whether tree diversity promotes growth resistance and resilience to extreme drought and whether drought responses are modulated by mycorrhizal associations. We used inventory data (2015 – 2021) of a young tree diversity experiment in Germany, manipulating tree species richness (1, 2, 4 species) and mycorrhizal type (communities containing arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) tree species, or both). For all tree communities, we calculated basal area increment (BAI) in the periods before, during, and after the drought and used the concepts of resistance and resilience to quantify growth responses to drought.

We found strong growth declines during the extreme 2018-2020 drought for most of the tree communities. Contrary to our hypothesis, we did not find that tree species richnessper secan buffer the negative impacts of extreme drought on tree growth. However, while for EM communities, drought resistance, and resilience decreased with tree species richness, they increased for AM communities and communities comprising both mycorrhizal types. We highlight that among various tree species mixtures, only those with mixed mycorrhizal types outperformed their respective monocultures during and after drought. Further, under extreme drought, the community tends to segregate into “winner” and “loser” tree species in terms of diversity, indicating a potential intensification of competition.

While we cannot disentangle the underlying mechanisms, or clarify the role of mycorrhiza during drought, our findings suggest that mixtures of mycorrhizal types within tree communities could help safeguard forests against increasing drought frequency.

Synthesis: Drought resistance and resilience of tree communities depend on tree diversity and mycorrhizal association types. Mixing tree species with diverse mycorrhizal types holds promise for forest restoration in the face of climate change.
Cross-species genomic survey reveals a single origin of the soft-shelled turtles
Authors: Li Wei , Zhu Junxian , Gao Zijian , Ji Liqin , Liu Yanchao , Liu Haiyang , Liu Xiaoli , Hong Xiaoyou , Wei Chengqing , Chen Jiehu , Chen Chen , Zhu Xinping
Published: January 2024

Turtles have a have a complicated sex determination system; however, Trionychidae species, as a unique group, have evolved a conserved genetic sex determination, which provides an excellent case to study the evolution of environmental sex determination to genetic sex determination. Analysis of the chromosome-level genome assembly, construction of the first sex chromosomes of Trionychidae, and embryonic transcriptome revealed thatP. sinensishas a ZW-type sex determination system, and that the key sex-determining genes, includingDmrt1,Amh,Foxl2, etc., and their homologs, are not located on the sex chromosomes, which rejects the involvement ofDmrt1’s SDGs or dosage compensation effect in the sex determination ofP. sinensisZW system and also indicates that the ZW chromosomes in birds, turtles, frogs, and fishes originated from different chromosome pairs in the common ancestors. Subsequently, comparative genomic studies demonstrated that a conserved ZW-type sex determination system exists in Trionychidae species, and inferred that their sex chromosomes originate from the same chromosome pair of the common ancestor. More importantly, we found a single origin of the sex chromosomes in Trionychidae species, approximately 56 million years ago, which is highly coincident with the Paleocene-Eocene thermal maximum, PETM, event. Therefore, we hypothesize that the PETM event and the loss of embryonic self-thermal regulation are two critical dynamics that drive the adaptive evolution of sex chromosomes for the common ancestor of Trionychidae species in response to extreme temperature changes. Finally, we link the ancestral sex chromosome origin time, the species divergence time, the PETM event, and the continental plate movements to paint a picture of a single origin and radiation route for extant Trionychidae species. Collectively, our findings provide novel insights into the mechanisms of sex determination inP. sinensis, and the single origin of sex chromosomes and species in extant soft-shelled turtles.
Peptidoform analysis of IP-MS data allows detection of differentially present bait proteoforms
Authors: Kourtis Savvas , Cianferoni Damiano , Serrano Luis , Sdelci Sara
Published: January 2024

While it is recognised that protein functions are determined by their proteoform state, such as mutations and post-translational modifications, methods to determine their differential abundance between conditions are limited. Here, we present a novel workflow for classical immunoprecipitation coupled to mass spectrometry (IP-MS) data that focuses on identifying differential peptidoforms of the bait protein between conditions, providing additional information about protein function.
YamOmics: A comprehensive data resource on yam multi-omics
Authors: Liu Jinding , Wang Mengda , Zhao Yi , Shen Danyu , Yang Qingxiang , Yang Tiegang , Yin Jianmei , He Longfei , Dou Daolong
Published: January 2024

Yams (Dioscorea spp.) are a highly important class of horticultural crops, serving as a staple food for millions of people in Africa and contributing significantly to food security. They are also widely cultivated in East Asia as medicinal herbs, bringing substantial economic incomes. Diverse omics data play a pivotal role in advancing yam research and breeding. However, these data are often scattered, lacking in systematic organization and analysis, which underscores the need for centralized and comprehensive data management. In view of this, we gathered extensive omics data and developed the Yam Omics Database (YamOmics;https://biotec.njau.edu.cn/yamdb). The database currently offers a vast and diverse range of omics data, covering genomic, transcriptomic and plastomic data from 41 distinct yam species, along with detailed records of genomic variants from ∼1000 germplasms, and gene expression profiles from ∼200 samples. Additionally, the database features thorough annotations, encompassing aspects like genome synteny, ortholog groups, signaling pathways, gene families and protein interactions. To support yam basic biology and breeding research, it is also equipped with a suite of user-friendly online tools, including PCR primer design, CRISPR design, expression analysis, enrichment analysis, and kinship analysis tools.
Erythrocyte TLR9 is upregulated in metabolic associated fatty liver disease, and is linked to an inflammatory immunometabolic signature
Authors: Papadopoulos Charalampos , Mimidis Konstantinos , Tentes Ioannis , Anagnostopoulos Konstantinos
Published: January 2024

Metabolic associated fatty liver disease (MAFLD) consists of lipid accumulation in the liver. Lipotoxicity, supported by aberrant amino acid metabolism, induces TLR9 upregulation, and activation, driving inflammation. Relatively, erythrocyte TLR9 activation leads to membrane rearrangement, surface CD47 loss, and pro-inflammatory erythrophagocytosis. Erythrocyte surface protein loss is accompanied by chemokine release. In addition, CD47 binds circulating TSP-1, a molecule controlling arginine and glutamine metabolism, along with metabolic inflammation. Based on these, we speculated that in MAFLD, lipotoxicity would drive erythrocyte TLR9 upregulation and activation, leading to immunometabolic remodeling.

Twenty-four patients (15 men and 9 women) with MAFLD and 9 healthy controls (4 men and 5 women) were enrolled. Erythrocytes were isolated from EDTA-containing blood. Protein levels were measured in erythrocyte lysates (triton X-100 0.01% v/v) or plasma with enzyme-linked immunosorbent assays, whereas lipids and enzyme activities were measured in erythrocyte hemoglobin-free membranes by a semi-quantitative thin layer chromatography and assay kits, respectively.

The levels of TLR9 were increased (p=0.002) and positively correlated with sphingosine levels, albeit not statistically significantly (p=0.060). The erythrocyte membrane PC/PE ratio was decreased (p=0.002) and inversely correlated to TLR9 levels. Erythrocyte TLR9 levels correlated inversely with CD47, and positively with MCP-1 release. TSP-1 was decreased in MAFLD erythrocytes (p=0.0017) and correlated positively with CD47 and negatively with TLR9 levels. In vitro, erythrocytes of MAFLD patients bound less TSP-1 molecules. Erythrocytes of MAFLD patients also exhibit decreased arginase-1 protein (p=0.009) and activity (p=0.042). Glutaminase activity was increased, albeit to not statistically significantly different levels (p=0.25). The levels of CD35 were not different (p=0.65), excluding the role of erythrocyte aging for explaining these events.

In MAFLD patients, erythrocyte TLR9 is upregulated and is associated with erythrocyte sphingolipid and glycerophospholipid perturbation, CD47 loss, MCP1 release, reduced TSP-1 scavenging, decreased arginase and increased glutaminase.
Repeated horizontal acquisition of lagriamide-producing symbionts in Lagriinae beetles
Authors: Uppal Siddharth , Waterworth Samantha C. , Nick Alina , Vogel Heiko , Flórez Laura V. , Kaltenpoth Martin , Kwan Jason C.
Published: January 2024

Microbial symbionts associate with multicellular organisms on a continuum from facultative associations to mutual codependency. In some of the oldest intracellular symbioses there is exclusive vertical symbiont transmission, and co-diversification of symbiotic partners over millions of years. Such symbionts often undergo genome reduction due to low effective population sizes, frequent population bottlenecks, and reduced purifying selection. Here, we describe multiple independent acquisition events of closely related defensive symbionts followed by genome erosion in a group of Lagriinae beetles. Previous work inLagria villosarevealed the dominant genome-eroded symbiont of the genusBurkholderiaproduces the antifungal compound lagriamide and protects the beetle’s eggs and larvae from antagonistic fungi. Here, we use metagenomics to assemble 11 additional genomes of lagriamide-producing symbionts from seven different host species within Lagriinae from five countries, to unravel the evolutionary history of this symbiotic relationship. In each host species, we detected one dominant genome-erodedBurkholderiasymbiont encoding the lagriamide biosynthetic gene cluster (BGC). Surprisingly, however, we did not find evidence for host-symbiont co-diversification, or for a monophyly of the lagriamide-producing symbionts. Instead, our analyses support at least four independent acquisition events of lagriamide-encoding symbionts and subsequent genome erosion in each of these lineages. By contrast, a clade of plant-associated relatives retained large genomes but secondarily lost the lagriamide BGC. In conclusion, our results reveal a dynamic evolutionary history with multiple independent symbiont acquisitions characterized by high degree of specificity. They highlight the importance of the specialized metabolite lagriamide for the establishment and maintenance of this defensive symbiosis.
Reduced hybrid survival in a migratory divide between songbirds
Authors: Blain Stephanie A. , Justen Hannah C. , Easton Wendy , Delmore Kira E.
Published: January 2024

Migratory divides, hybrid zones between populations that use different seasonal migration routes, are hypothesized to contribute to speciation. Specifically, relative to parental species, hybrids at divides are predicted to exhibit (1) intermediate migratory behavior and (2) reduced fitness as a result. We provide the first direct test of the second prediction here with one of the largest existing avian tracking datasets, leveraging a divide between Swainson’s thrushes where the first prediction is supported. Using detection rates as a proxy for survival, our results supported the migratory divide hypothesis with lower survival rates for hybrids than parental forms. This finding was juvenile-specific (vs. adults), suggesting selection against hybrids is stronger earlier in life. Reduced hybrid survival was not explained by selection against intermediate phenotypes or negative interactions among phenotypes. Additional work connecting specific features of migration is needed, but these patterns provide strong support for migration as an ecological driver of speciation.
Atypia of Undetermined Significance and ThyroSeq v3 Positive Call Rates as Quality Control Metrics for Cytology Laboratory Performance
Authors: Mejia-Mejia Odille , Bravo-Gonzalez Andres , Sanchez-Avila Monica , Tjendra Youley , Santoscoy Rodrigo , Drews-Elger Katherine , Zuo Yiqin , Arias-Abad Camilo , Gomez Carmen , Garcia-Buitrago Monica , Nadji Mehrdad , Jorda Merce , Velez-Torres Jaylou M. , Ruiz-Cordero Roberto
Published: January 2024

Background

The Bethesda system (TBS) for reporting thyroid cytopathology recommends an “atypia of undetermined significance (AUS)” rate of 10%. Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, we calculated the AUS and positive call rates for our cytology lab and each cytopathologist.

Methods

A retrospective analysis of all thyroid cytology cases in a 4.5-year period was performed. Cases were stratified by TBS category, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each cytopathologist (CP) and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition ofcurrently negativeto thepositiveresults obtained from the ThyroSeq report.

Results

7,535 cases were classified asnon-diagnostic7.6%,benign69%,AUS17.5%,follicular neoplasm / suspicious for follicular neoplasm1.4%,suspicious for malignancy0.7 %, andmalignant3.8%. The AUS rate for each cytopathologist ranged from 9.9-36.8%. The overall PCR for the cytology laboratory was 24% (range 13-35.6% per CP). When including cases withcurrently negativeresults, the PCR increased to 35.5% for the cytology laboratory (range 13-42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, under calling of higher TBS category cases.

Conclusions

The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists’ performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology.
Polyploid genome assembly ofCardamine chenopodiifolia
Authors: Emonet Aurélia , Awad Mohamed , Tikhomirov Nikita , Vasilarou Maria , Pérez-Antón Miguel , Gan Xiangchao , Novikova Polina , Hay Angela
Published: January 2024

Background

Cardamine chenopodiifoliais an amphicarpic plant that develops two fruit morphs, one above and the other below ground. Above-ground fruit disperse their seeds by explosive coiling of the fruit valves, while below-ground fruit are non-explosive. Amphicarpy is a rare trait that is associated with polyploidy inC. chenopodiifolia. Studies into the development and evolution of this trait are currently limited by the absence of genomic data forC. chenopodiifolia.

Results

We produced a chromosome-scale assembly of the octoploidC. chenopodiifoliagenome using high-fidelity long read sequencing with the Pacific Biosciences platform. We successfully assembled 32 chromosomes and two organelle genomes with a total length of 597.2 Mbp and an N50 of 18.8 kbp (estimated genome size from flow cytometry: 626 Mbp). We assessed the quality of this assembly using genome-wide chromosome conformation capture (Omni-C) and BUSCO analysis (97.1% genome completeness). Additionally, we conducted synteny analysis to infer thatC. chenopodiifolialikely originated via allo-rather than auto-polyploidy and phased one of the four sub-genomes.

Conclusions

This study provides a draft genome assembly forC. chenopodiifolia, which is a polyploid, amphicarpic species within the Brassicaceae family. This genome offers a valuable resource to investigate the under-studied trait of amphicarpy and the origin of new traits by allopolyploidy.
Systemic delivery of a splice-switching oligonucleotide heteroduplex corrects splicing in central nervous system and muscle in spinal muscular atrophy mice
Authors: Halloy François , Ahlskog Nina , Wood Matthew
Published: January 2024

Oligonucleotide therapeutics are an established class of drugs for the treatment of genetic disorders. Their clinical development is challenging, however, as they typically distribute poorly to extra-hepatic tissues after systemic injection. Here we tested the heteroduplex oligonucleotide (HDO) platform for systemic delivery ofSMN2splice-switching oligonucleotides of 2’-O-methoxyethyl phosphorothioate or phosphorodiamidate morpholino oligomer chemistries. We first showed that splice-switching HDO cargoes correctSMN2splicing in cells derived from spinal muscular atrophy (SMA) patients, and validated extra-hepatic activity in spinal cord and muscle in a mouse model of SMA following systemic delivery. Our study raises prospects for delivery of nusinersen, the 2’-O-methoxylethyl phosphorothioate oligonucleotide therapy approved for SMA and currently delivered by intrathecal injection, by systemic injection exploiting the HDO chemistry platform. Our findings also suggest that oligonucleotide drugs lacking convincingin vivoefficacy in muscle tissue could be delivered effectively by the HDO technology.
Evaluating the effect of denoising submillimeter auditory fMRI data with NORDIC
Authors: Faes Lonike K. , Lage-Castellanos Agustin , Valente Giancarlo , Yu Zidan , Cloos Martijn A. , Vizioli Luca , Moeller Steen , Yacoub Essa , De Martino Federico
Published: January 2024

Functional magnetic resonance imaging (fMRI) has emerged as an essential tool for exploring human brain function. Submillimeter fMRI, in particular, has emerged as a tool to study mesoscopic computations. The inherently low signal-to-noise ratio (SNR) at submillimeter resolutions warrants the use of denoising approaches tailored at reducing thermal noise – the dominant contributing noise component in high resolution fMRI. NORDIC PCA is one of such approaches, and has been benchmarked against other approaches in several applications. Here, we investigate the effects that two versions of NORDIC denoising have on auditory submillimeter data. As investigating auditory functional responses poses unique challenges, we anticipated that the benefit of this technique would be especially pronounced. Our results show that NORDIC denoising improves the detection sensitivity and the reliability of estimates in submillimeter auditory fMRI data. These effects can be explained by the reduction of the noise-induced signal variability. However, we also observed a reduction in the average response amplitude (percent signal), which may suggest that a small amount of signal was also removed. We conclude that, while evaluating the effects of the signal reduction induced by NORDIC may be necessary for each application, using NORDIC in high resolution auditory fMRI studies may be advantageous because of the large reduction in variability of the estimated responses.
Neuroinflammation underlies the development of social stress induced cognitive deficit in sickle cell disease
Authors: DeVeaux S’Dravious A. , Vyshnya Sofiya , Propsom Katherine , Gbotosho Oluwabukola T. , Singh Asem S. , Horning Robert Z. , Sharma Mihika , Jegga Anil G. , Niu Liang , Botchwey Edward A. , Hyacinth Hyacinth I.
Published: January 2024

Cognitive deficit is a debilitating complication of SCD with multifactorial pathobiology. Here we show that neuroinflammation and dysregulation in lipidomics and transcriptomics profiles are major underlying mechanisms of social stress-induced cognitive deficit in SCD. Townes sickle cell (SS) mice and controls (AA) were exposed to social stress using the repeat social defeat (RSD) paradigm concurrently with or without treatment with minocycline. Mice were tested for cognitive deficit using novel object recognition (NOR) and fear conditioning (FC) tests. SS mice exposed to RSD without treatment had worse performance on cognitive tests compared to SS mice exposed to RSD with treatment or to AA controls, irrespective of their RSD or treatment disposition. Additionally, compared to SS mice exposed to RSD with treatment, SS mice exposed to RSD without treatment had significantly more cellular evidence of neuroinflammation coupled with a significant shift in the differentiation of neural progenitor cells towards astrogliogenesis. Additionally, brain tissue from SS mice exposed to RSD was significantly enriched for genes associated with blood-brain barrier dysfunction, neuron excitotoxicity, inflammation, and significant dysregulation in sphingolipids important to neuronal cell processes. We demonstrate in this study that neuroinflammation and lipid dysregulation are potential underlying mechanisms of social stress-related cognitive deficit in SS mice.

Key Points

Neuroinflammation and lipid dysfunction are potential underlying mechanisms of social stress-related cognitive deficit in SCD patients.

Mitigating or ameliorating the impact of cognitive deficits in SCD needs to consider the biological changes already created by exposure to social stress.

Novelty of our Findings

We show for the first time, that neuroinflammation along with changes in the brain lipidome and transcriptome, are underlying biological mechanism contributing to the development and potentially progression of cognitive impairment among sickle cell patients. These findings also provide for the first time, a mechanistic basis for an earlier reported observation of a higher likelihood of having lower intelligence quotient scores among children with sickle cell disease exposed to social stress in the form of low parental socioeconomic status.
Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model
Authors: Carling Gillian K. , Fan Li , Foxe Nessa R. , Norman Kendra , Ye Pearly , Wong Man Ying , Zhu Daphne , Yu Fangmin , Xu Jielin , Yarahmady Allan , Chen Hao , Huang Yige , Amin Sadaf , Zacharioudakis Emmanouil , Chen Xiaoying , Holtzman David M. , Mok Sue-Ann , Gavathiotis Evripidis , Sinha Subhash C. , Cheng Feixiong , Luo Wenjie , Gong Shiaoching , Gan Li
Published: January 2024

The strongest risk factors for Alzheimer’s disease (AD) include the χ4 allele of apolipoprotein E (APOE), theR47Hvariant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combineAPOE4andTREM2R47H(R47H) in femaleP301Stauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting disease-causing mechanisms. We find that theR47Hvariant induces neurodegeneration in femaleAPOE4mice without impacting hippocampal tau load. The combination ofAPOE4andR47Hamplified tauopathy-induced cell-autonomous microglial cGAS-STING signaling and type-I interferon response, and interferon signaling converged across glial cell types in the hippocampus.APOE4-R47Hmicroglia displayed cGAS- and BAX-dependent upregulation of senescence, showing association between neurotoxic signatures and implicating mitochondrial permeabilization in pathogenesis. By uncovering pathways enhanced by the strongest AD risk factors, our study points to cGAS-STING signaling and associated microglial senescence as potential drivers of AD risk.
Zebrafishcarbohydrate sulfotransferase 6(chst6) mutants provide a preclinical model for macular corneal dystrophy
Authors: Ersoz-Gulseven Esra , Basol Merve , Özaktaş Helin , Kalyoncu Sibel , Utine Canan Asli , Cakan-Akdogan Gulcin
Published: January 2024

Macular corneal dystrophy (MCD) is a rare congenital disease caused by mutations in thecarbohydrate sulfotransferase 6(chst6) gene. Patients suffer from opaque aggregates in the cornea leading to bilateral progressive vision loss by 4thdecade of life. Corneal transplantation is the only available treatment, which is invasive, not available to every patient and recurrence of the symptoms is common. Keratocytes in the cornea express thechst6gene, which encodes a golgi enzyme that is essential for sulfation of the keratan sulfate proteoglycans (KSPG). The loss of KS sulfation leads to defects in collagen fibril organization and aggregate formation in the corneal extracellular matrix. Lack of preclinical disease models is a major limitation for the development of accessible treatment strategies. Attempts to develop mouse MCD models have failed due to lack ofchst6gene in mice and difference in proteoglycan composition of the mouse cornea. The zebrafishchst6gene has not been studied previously. Zebrafish cornea structure is highly similar to humans, containing high levels of keratan sulfate proteoglycans in the stroma. Here, loss of functionchst6mutant zebrafish were generated with CRISPR/Cas9 mediated gene editing. Severalchst6alleles were obtained, and loss of KSPG sulfation in the eye stroma was shown. Mutant zebrafish developed age-dependent, alcian blue positive, opaque accumulates in the cornea. Degeneration of corneal structure and changes in epithelial thickness were observed. The zebrafish MCD model developed here is the firstin vivomodel of the disease and opens up possibilities to develop and screen treatment strategies.

Significance Statement

Firstin vivomodel of macular corneal dystrophy (MCD) is reported in this study. Zebrafish model developed here paves the way for modeling of other corneal dystrophies in this aquatic vertebrate which is easy to apply therapeutics and imagein vivo. The clinical symptoms of MCD are well reproduced in the zebrafish MCD model. Moreover, the authors showed thatchst6gene function is not restricted to cornea, and a fraction of mutant larvae have morphological defects. The mutants developed here provide a genetic model for understanding the highly complex roles of keratan sulfate proteoglycans.