bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of transurethral prostate resection instrumentation for treating rectal anastomotic stenosis: Case series
Authors: Xu Wenshan , Qin Yujie , Yang Faying , Qian Jun , Dong Yanbo , Tu Song , Yao Jiaxi
Published: May 2023

Background:

Anastomotic stenosis is a common complication of colorectal surgery with anastomosis. To explore a minimally invasive novel approach surgical method for the treatment of rectal anastomotic strictures using transurethral prostate resection instrumentation.

Methods:

From 2012 to 2022, 18 patients for the treatment of rectal anastomotic strictures using transurethral prostate resection instrumentation. The transurethral prostate resection instrumentation enters the rectum through the anus to incise the narrow anastomotic orifice in a 4-point radial manner under the resectoscope.

Results:

The surgery was successfully completed in 18 patients, and there were no postoperative complications. Postoperatively, 12 patients achieved satisfactory improvement in defecation after 1 incision, and 4 patients underwent another incision 3 months later. Two patients underwent incisions thrice, and the ease of defecation improved in a short period; however, they later underwent permanent colostomy due to repeated stenosis and pain.

Conclusion:

The transanal 4-point radial incision of the prostate using transurethral prostate resection instrumentation is a minimally invasive, safe, effective, and simple surgical method for the treatment of rectal anastomotic stenosis supplemented by postoperative dilatation, and is worthy of clinical application.
Strokes and Transient Ischemic Attacks Occurrence During Annual Dual Antiplatelet Therapy
Authors: Serebruany Victor L. , Tanguay Jean-Francois , Gurvich Milana L. , Marciniak Thomas A. , Atar Dan
Published: May 2023

Background:

The incidence of stroke/TIA during annual dual antiplatelet therapy (ADAPT) for acute coronary syndrome (ACS) remains high. Some evidence suggests that shorter than ADAPT may diminish such risk, still providing adequate vascular protection. However, the precise timing of strokes/TIA occurrences during ADAPT is unclear but may be important for determining optimal preventive treatment duration.

Study Question:

The precise timing of secondary cerebrovascular events over ADAPT.

Study Design:

Access was gained to the FDA-issued Platelet Inhibition and Outcomes (PLATO) trial data set on which post hoc analyses of stroke/TIA timing after ticagrelor and clopidogrel on top of aspirin was explored.

Measures and Outcomes:

Events were counted and plotted over time from day 1 till day 365 after the index ACS event.

Results:

Among 18,624 enrollees, 252 strokes and 49 TIAs were reported. After the exclusion of entries with missing dates, unclear randomization codes, and events beyond 1-year follow-up, 238 strokes and 45 TIAs were analyzed. Overall, most frequent strokes/TIAs occurred within the first day after qualifying ACS, with the gradual declines after day 7 and day 40 reaching background counts thereafter. The strokes/TIAs patterns did not differ much between P2Y12 inhibitors except for twice more events at day 1 and excess exclusions after day 365 in the ticagrelor arm.

Conclusions:

Most cerebrovascular events emerged very early after ACS despite ADAPT. This large hypothesis-generating evidence may justify shorter than the ADAPT duration after ACS. Twice more events at day 1 and excess late ticagrelor exclusions in PLATO deserve further scrutiny.

Registration:

URL: https://www.clinicaltrials.gov; Unique identifier: NCT 00391872.
Factors Affecting the Gut Microbiome in Pediatric Intestinal Failure
Authors: Talathi Saurabh , Wilkinson Linda , Meloni Katie , Shroyer Michelle , Zhang Li , Ding Zhenying , Eipers Peter , Van Der Pol William , Martin Colin , Dimmitt Reed , Yi Nengjun , Morrow Casey , Galloway David
Published: May 2023

Background:

There is little data on gut microbiome and various factors that lead to dysbiosis in pediatric intestinal failure (PIF). This study aimed to characterize gut microbiome in PIF and determine factors that may affect microbial composition in these patients.

Methods:

This is a single-center, prospective cohort study of children with PIF followed at our intestinal rehabilitation program. Stool samples were collected longitudinally at regular intervals over a 1-year period. Medical records were reviewed, and demographic and clinical data were collected. Medication history including the use of acid blockers, scheduled prophylactic antibiotics, and bile acid sequestrants was obtained. Gut microbial diversity among patients was assessed and compared according to various host characteristics of interest.

Results:

The final analysis included 74 specimens from 12 subjects. Scheduled prophylactic antibiotics, presence of central line associated bloodstream infection (CLABSI) at the time of specimen collection, use of acid blockers, and ≥50% calories delivered via parenteral nutrition (PN) was associated with reduced alpha diversity, whereas increasing age was associated with improved alpha diversity at various microbial levels (P value <0.05). Beta diversity differed with age, presence of CLABSI, use of scheduled antibiotics, acid blockers, percent calories via PN, and presence of oral feeds at various microbial levels (P value <0.05). Single taxon analysis identified several taxa at several microbial levels, which were significantly associated with various host characteristics.

Conclusion:

Gut microbial diversity in PIF subjects is influenced by various factors involved in the rehabilitation process including medications, percent calories received parenterally, CLABSI events, the degree of oral feeding, and age. Additional investigation performed across multiple centers is needed to further understand the impact of these findings on important clinical outcomes in PIF.
Palliative Care Needs of Families of Adults With Advanced Cancer
Authors: Rojas-Garcia Carolina , Vargas-Escobar Lina María , Giraldo-Castro Mónica
Published: May 2023

Diagnosis and treatment of a terminal illness can significantly impact patients and their families, as well as their functionality and daily routines. This study aimed to understand the palliative care needs of a group of families with an adult relative with advanced cancer receiving palliative care. A qualitative approach was used to conduct a content analysis. Fourteen semistructured interviews were carried out with family members in Cundinamarca (Colombia) between March and April 2022. The information was analyzed by coding and categorizing the emerging themes using NVivo. Three main categories emerged: the diagnosis' harsh surprise, the family's coping with the disease, and the palliative care needs of families. Identifying the resources available to families to care for relatives with advanced cancer can facilitate the work of palliative care teams. It is necessary to prevent the family from giving up on caring, which can result from exhaustion due to various causes. Families who have an adult relative with advanced cancer in palliative care face significant challenges. Their situation involves accepting the diagnosis, changing family routines, dealing with the disease and the health care system, and coping with circumstances that create needs of different kinds.
Analyzing Apparent Causes of 30-Day Readmissions to Acute Care From Skilled Nursing Facilities
Authors: Bakken Keith , Klopp Audrey , Shehan Mary , Jacob Laura , Tell Dina
Published: May 2023

This quality improvement project implemented a bidirectional apparent cause analysis of patients readmitted to 1 hospital from 8 skilled nursing facilities (SNFs). The purpose of the project was to receive input from both hospital and SNF nursing staff to critically examine the apparent causes of SNF readmissions from both settings and identify opportunities for improvement. Nurse-led measures to prevent readmissions can be found in 5 domains: improved collaboration, communication, coordination, clarification, and cause analysis.
Which Groups of Plastic Surgery Patients are Impacted by Social Media Use: An In-Depth Review of Social Media Engagement
Authors: Kinney JacqueLyn R. , Kim Erin , Friedman Rosie , Bustos Valeria , Hassell Natalie , Elmer Nicholas , Lee Bernard T. , Lin Samuel J.
Published: May 2023

Background:

Empowerment is the process in which patients gain greater control of their health through active and informed decision making. Greater patient empowerment has shown to be positively correlated with improved healthcare outcomes and experiences. It is unclear how social media impacts plastic and reconstructive surgery (PRS) patients' healthcare decision making. This study aims to help quantify how social media sites influence levels of PRS patient empowerment.

Methods:

In this cross-sectional study, a modified Cyber Info-Decisional Empowerment Scale (CIDES)survey was distributed through Amazon Mechanical Turk (mTurk) to U.S. adults. Sociodemographics, PRS history, social media usage and data collected. Wilcoxon signed-rank test and Kruskal-Wallis tests were used to assess for heterogeneity for categorical variables. ANOVA and t-tests were used to evaluate differences in means for Likert scale-based responses.

Results:

473 survey responses were included. The participants were grouped based on their surgical history: cosmetic (187, 39.5%), reconstructive (107, 22.6%), both cosmetic and reconstructive (36, 7.6%), and non-PRS (143, 30.2%). There was increased empowerment depending on the online resources used. Specifically, social media was associated with significantly greater empowerment in six of seven CIDES categories. Of the social media platforms, Facebook was associated with higher empowerment in three of seven CIDES categories.

Conclusion:

Social media use appears to positively impact PRS patients' empowerment, which may reflect better patient decision making and autonomy when consulting with their plastic surgeon.
Can Anterior Osteophyte Fractures Be Distinguished From Fracture Mimics in the Subaxial Cervical Spine? A Retrospective Analysis Evaluating Reported Fractures With Clinical Management Correlation
Authors: Rao Dinesh , Godreau Jean-Paul , Jenson Matthew , Rahmathulla Gazanfar , Fiester Peter , Patel Jeet , Hernandez Mauricio
Published: May 2023

Objective

This study aimed to retrospectively distinguish true- from false-positive fractures of anterior subaxial cervical osteophytes, which were reported on noncontrast computed tomography reports, and to correlate the imaging findings with patient symptoms and analyze the downstream impact on management of both true and false positive fractures.

Methods

A total of 127 patients had computed tomography reports of anterior osteophyte fractures. Radiology reports and imaging studies were evaluated to distinguish true fractures from fracture mimics. We analyzed imaging features including rigid spine (RS), prevertebral soft tissue swelling (PVSTS), and instability. We categorized symptoms and examination findings into 3 groups (0, asymptomatic; 1, neck pain; 2, neurological symptoms). Management was categorized into 3 groups (0, no treatment; 1, external bracing; 2, surgery). Associations between imaging features, fracture classification, clinical symptoms, magnetic resonance imaging utilization, and management were calculated using χ2 with Cramer V test to determine effect size.

Results

Eighty patients had false-positive fractures, and 47 were true positive. There were significant associations between magnetic resonance imaging utilization and fracture classification (P ≤ 0.001), PVSTS (P ≤ 0.005), patient symptoms (P ≤ 0.001), and patient management (P ≤ 0.001). There were significant associations between patient management and fracture classification (P ≤ 0.001), patient symptoms (P ≤ 0.001), PVSTS (P ≤ 0.001), imaging findings of instability (P ≤ 0.001), and RS (P ≤ 0.021). There were significant associations between fracture classification and patient symptoms (P ≤ 0.045), and RS (P ≤ 0.006).

Conclusions

Subaxial isolated anterior osteophyte fractures fell into 3 major categories. By our methodology, if a suspected fracture was determined to be a fracture mimic in an asymptomatic patient, it was unlikely to be clinically significant. Isolated anterior osteophyte fractures without neurological symptoms or more concerning imaging findings can be treated conservatively. Finally, fractures that demonstrate indirect signs of instability or are associated with RS are more associated with surgical management.
ERAS Protocol Applied to Oncological Colorectal Mini-invasive Surgery Reduces the Surgical Stress Response and Improves Long-term Cancer-specific Survival
Authors: Crippa Jacopo , Calini Giacomo , Santambrogio Gaia , Sassun Richard , Siracusa Claudia , Maggioni Dario , Mari Giulio ,   on behalf of AIMS Academy Clinical Research Network
Published: May 2023

Background:

Enhanced recovery after surgery (ERAS) protocols are known to reduce postoperative complications and improve short-term outcomes by minimizing the surgical stress response (SSR). Retrospective reviews of large cohorts suggest that they may also have an impact on long-term oncological outcomes. In 2016, Mari et al published a randomized trial on ERAS protocol and the impact on the SSR; they found that IL-6 was less expressed in patients who undergo laparoscopic colorectal surgery within an ERAS protocol compared with controls. The aim of the present study is to report the long-term oncological outcomes of patients enrolled 5 years after the conclusion of the study.

Methods:

Patients enrolled had received the indication for major colorectal surgery, aged between 18 and 80 years, with American Society of Anesthesiologists (ASA) grades I to III, autonomous for mobilization and walking, eligible for laparoscopic technique. In total, 140 patients were enrolled and randomized into 2 groups of 70 patients each. Among these patients, 52 in the ERAS group (EG) and 53 in the Standard group (SG) had colorectal cancer. For them, a 5-year oncological follow-up according to the NCCN16 guidelines was planned. IL-6, C-reactive protein, prolactine, white blood cell count, albumin, and prealbumin were compared between oncological patients in the EG and in the SG.

Results:

EG showed lower IL-6 on postoperative day 1 (21.2±9.1 vs. 40.3 ±11.3; P<0.05) and on day 5 (14.9±6.2 vs. 38.7±8.9; P<0.05), lower C-reactive protein on day 1 (48.3±15.7 vs. 89.4±20.3; P<0.05) and on day 5 (38.3±11.4 vs. 74.3±19.7; P<0.05), and lower pre-albumine on day 5 (18.9±7.2 vs. 12.3±6.9; P<0.05) compared with SG. Median oncological follow-up was 57 months [46.5 to 60]. There was no statistically significant difference in overall survival (log rank=0.195) and disease-free survival (Log rank=0.089) between groups. Cancer-specific survival was significantly better (log rank=0.038) in the EG compared with patients in the SG.

Conclusions:

ERAS protocol applied to colorectal laparoscopic surgery for cancer is able to minimize the SSR. As a possible result, cancer-specific survival seems to be improved in patients within enhanced protocols. However, even though there may be an association between an excess of SSR and worse oncological outcomes, the favorable effect of ERAS protocols toward better overall and disease-free survival is yet to be demonstrated.
Modularity, homology, heterochrony: Gavin de Beer's legacy to the mammalian skull
Authors: Hall Brian K. , Hanken James
Published: May 2023

Modularity (segmentation), homology and heterochrony were essential concepts embraced by Gavin de Beer in his studies of the development and evolution of the vertebrate skull. While his pioneering contributions have stood the test of time, our understanding of the biological processes that underlie each concept has evolved. We assess de Beer's initial training as an experimental embryologist; his switch to comparative and descriptive studies of skulls, jaws and middle ear ossicles; and his later research on the mammalian skull, including his approach to head segmentation. The role of cells of neural crest and mesodermal origin in skull development, and developmental, palaeontological and molecular evidence for the origin of middle ear ossicles in the evolutionary transition from reptiles to mammals are used to illustrate our current understanding of modularity, homology and heterochrony.

This article is part of the theme issue ‘The mammalian skull: development, structure and function’.
Developmental origin underlies evolutionary rate variation across the placental skull
Authors: Goswami Anjali , Noirault Eve , Coombs Ellen J. , Clavel Julien , Fabre Anne-Claire , Halliday Thomas J. D. , Churchill Morgan , Curtis Abigail , Watanabe Akinobu , Simmons Nancy B. , Beatty Brian L. , Geisler Jonathan H. , Fox David L. , Felice Ryan N.
Published: May 2023

The placental skull has evolved into myriad forms, from longirostrine whales to globular primates, and with a diverse array of appendages from antlers to tusks. This disparity has recently been studied from the perspective of the whole skull, but the skull is composed of numerous elements that have distinct developmental origins and varied functions. Here, we assess the evolution of the skull's major skeletal elements, decomposed into 17 individual regions. Using a high-dimensional morphometric approach for a dataset of 322 living and extinct eutherians (placental mammals and their stem relatives), we quantify patterns of variation and estimate phylogenetic, allometric and ecological signal across the skull. We further compare rates of evolution across ecological categories and ordinal-level clades and reconstruct rates of evolution along lineages and through time to assess whether developmental origin or function discriminate the evolutionary trajectories of individual cranial elements. Our results demonstrate distinct macroevolutionary patterns across cranial elements that reflect the ecological adaptations of major clades. Elements derived from neural crest show the fastest rates of evolution, but ecological signal is equally pronounced in bones derived from neural crest and paraxial mesoderm, suggesting that developmental origin may influence evolutionary tempo, but not capacity for specialisation.

This article is part of the theme issue ‘The mammalian skull: development, structure and function’.
Multiple modes of inference reveal less phylogenetic signal in marsupial basicranial shape compared with the rest of the cranium
Authors: Weisbecker Vera , Beck Robin M. D. , Guillerme Thomas , Harrington Arianna R. , Lange-Hodgson Leonie , Lee Michael S. Y. , Mardon Karine , Phillips Matthew J.
Published: May 2023

Incorporating morphological data into modern phylogenies allows integration of fossil evidence, facilitating divergence dating and macroevolutionary inferences. Improvements in the phylogenetic utility of morphological data have been sought via Procrustes-based geometric morphometrics (GMM), but with mixed success and little clarity over what anatomical areas are most suitable. Here, we assess GMM-based phylogenetic reconstructions in a heavily sampled source of discrete characters for mammalian phylogenetics—the basicranium—in 57 species of marsupial mammals, compared with the remainder of the cranium. We show less phylogenetic signal in the basicranium compared with a ‘Rest of Cranium’ partition, using diverse metrics of phylogenetic signal (
K
mult
, phylogenetically aligned principal components analysis, comparisons of UPGMA/neighbour-joining/parsimony trees and cophenetic distances to a reference phylogeny) for scaled, Procrustes-aligned landmarks and allometry-corrected residuals. Surprisingly, a similar pattern emerged from parsimony-based analyses of discrete cranial characters. The consistent results across methods suggest that easily computed metrics such as
K
mult
can provide good guidance on phylogenetic information in a landmarking configuration. In addition, GMM data may be less informative for intricate but conservative anatomical regions such as the basicranium, while better—but not necessarily novel—phylogenetic information can be expected for broadly characterized shapes such as entire bones.

This article is part of the theme issue ‘The mammalian skull: development, structure and function’.
Evolution and development of the cetacean skull roof: a case study in novelty and homology
Authors: Roston R. A. , Boessenecker R. W. , Geisler J. H.
Published: May 2023

Skulls of living whales and dolphins (cetaceans) are telescoped—bones of the skull roof are overlapped by expanded facial bones and/or anteriorly extended occipital bones. Evolution of the underlying skull roof (calvarium), which lies between the telescoped regions, is relatively unstudied. We explore the evolution and development of the calvarium of toothed whales (odontocetes) by integrating fetal data with Oligocene odontocete fossils from North America, including eight neonatal and juvenile skulls of
Olympicetus
†. We identified two potential synapomorphies of crown Cetacea: contact of interparietals with frontals, and a single anterior median interparietal (AMI) element. Within Odontoceti, loss of contact between the parietals diagnoses the clade including Delphinida, Ziphiidae and Platanistidae (=Synrhina). Delphinida is characterized by a greatly enlarged interparietal. New fetal series of delphinoids reveal a consistent developmental pattern with three elements: the AMI and bilateral posterior interparietals (PIs). The PIs most resemble the medial interparietal elements of terrestrial artiodactyls, suggesting that the AMI of cetaceans could be a unique ossification. More broadly, the paucity of conserved anatomical relationships of the interparietals, as well as the fact that the elements often do not coalesce into a single bone, demonstrates that assessing homology of the interparietals across mammals remains challenging.

This article is part of the theme issue ‘The mammalian skull: development, structure and function’.
Vallitalea longa sp. nov., an anaerobic bacterium isolated from marine sediment
Authors: Hirano Shiori , Terahara Takeshi , Mori Koji , Hamada Moriyuki , Matsumoto Ryo , Kobayashi Takeshi
Published: May 2023

A novel bacterium, strain SH18-1T, was isolated from marine sediment collected near Sado Island in the Sea of Japan. This strain was strictly anaerobic, Gram-stain-negative, non-spore-forming, rod-shaped, motile, and mesophilic. It grew at 15–40 °C (optimum, 30–35 °C), at a NaCl concentration of 0.2–5.0 % (w/v; optimum, 1.5–2.5 %), and at pH 5.5–8.5 (optimum, pH 7.0). Results of 16S rRNA gene phylogenetic analysis showed a similarity value of 97.49 % between strain SH18-1T and

Vallitalea guaymasensis

Ra1766G1T, which was the most closely related species. The genome size of strain SH18-1T was 5.71 Mb and its G+C content was 30.2 mol%. Genome sequence analyses for comparison between strain SH18-1T and

V. guaymasensis

Ra1766G1T showed values lower than the threshold for species demarcation determined using the Genome-to-Genome Distance Calculator and the Average Nucleotide Identity Calculator. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, and nitrite were not used as terminal electron acceptors. The major fatty acids in strain SH18-1T were iso-C15 : 0, anteiso-C15 : 0, and C16 : 0, and the detected polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipid, glycolipid, three unidentified phospholipids, and one unidentified polar lipid. From these results, strain SH18-1T (=NBRC 115488T=DSM 114058T) is suggested to represent a novel species of the genus

Vallitalea

and the name Vallitalea longa sp. nov. is proposed.
Summary statistics from large-scale gene-environment interaction studies for re-analysis and meta-analysis
Authors: Pham Duy T. , Westerman Kenneth E. , Pan Cong , Chen Ling , Srinivasan Shylaja , Isganaitis Elvira , Vajravelu Mary Ellen , Bacha Fida , Chernausek Steve , Klug Rose Gubitosi- , Divers Jasmin , Pihoker Catherine , Marcovina Santica M. , Manning Alisa K. , Chen Han
Published: May 2023

Summary statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions (GEIs), there is a need for GEI-specific methods that manipulate and use summary statistics. We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study (GWIS) to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in GWIS in the UK Biobank as well as by conducting a multi-exposure GWIS meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex GEI studies.
Risk factors affecting polygenic score performance across diverse cohorts
Authors: Hui Daniel , Dudek Scott , Kiryluk Krzysztof , Walunas Theresa L. , Kullo Iftikhar J. , Wei Wei-Qi , Tiwari Hemant K. , Peterson Josh F. , Chung Wendy K. , Davis Brittney , Khan Atlas , Kottyan Leah , Limdi Nita A. , Feng Qiping , Puckelwartz Megan J. , Weng Chunhua , Smith Johanna L. , Karlson Elizabeth W. , Center Regeneron Genetics , Jarvik Gail P. , Ritchie Marylyn D.
Published: May 2023

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed effects of covariate stratification and interaction on body mass index (BMI) PGS (PGSBMI) across four cohorts of European (N=491,111) and African (N=21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R2differences among strata. Covariates with the largest differences included age, sex, blood lipids, physical activity, and alcohol consumption, with R2being nearly double between best and worst performing quintiles for certain covariates. 28 covariates had significant PGSBMI-covariate interaction effects, modifying PGSBMIeffects by nearly 20% per standard deviation change. We observed overlap between covariates that had significant R2differences among strata and interaction effects – across all covariates, their main effects on BMI were correlated with their maximum R2differences and interaction effects (0.56 and 0.58, respectively), suggesting high-PGSBMIindividuals have highest R2and increase in PGS effect. Using quantile regression, we show the effect of PGSBMIincreases as BMI itself increases, and that these differences in effects are directly related to differences in R2when stratifying by different covariates. Given significant and replicable evidence for context-specific PGSBMIperformance and effects, we investigated ways to increase model performance taking into account non-linear effects. Machine learning models (neural networks) increased relative model R2(mean 23%) across datasets. Finally, creating PGSBMIdirectly from GxAge GWAS effects increased relative R2by 7.8%. These results demonstrate that certain covariates, especially those most associated with BMI, significantly affect both PGSBMIperformance and effects across diverse cohorts and ancestries, and we provide avenues to improve model performance that consider these effects.
“It All Rolls Downstream: Upstream Control of Physical Activity Regulation”
Authors: Breidenbach Brianne M. , Liu Liwen , La Troy , Castro-Padovani Tatiana N. , Keller Nathan , Pescatello Linda S , Robinson Matthew M. , Kelly Scott A. , Gerrish Kevin , Lightfoot J. Timothy
Published: May 2023

Physical activity is regulated by a variety of genetic molecules. However, the pathways through which those molecules work to regulate activity is largely unknown. The purpose of this study was to gather the known genetic molecules that are associated with activity regulation and define overall upstream regulator pathways through which these molecules work. We conducted a systematic review to gather all available published datasets related to physical activity regulation, standardized the data for genomic location and species, and used this data, in an unbiased manner to create a dataset that was used: (1) to physically map and visualize all identified molecules to homologous chromosome locations and (2) as the dataset for which an Upstream Regulator Analysis (URA) was conducted using Qiagen Ingenuity Pathway Analysis (IPA) software. Our search resulted in 469 genetic molecules (e.g. genomic variant, transcript, protein, micro-RNA) that were split into brain (n=366) and muscle (n=345) sub-groups, which was our attempt to separate differences in central vs peripheral pathways. The brain and muscle data sets had several potential upstream regulators, the top-rated being β-estradiol as a regulator for 19.5% and 21% of the brain and muscle datasets respectively. To our knowledge, β-estradiol’s identification as a potential regulator, is the first evidence to link the well-known effects of sex hormones on physical activity with genetic regulation of physical activity. There were a variety of potential upstream regulators for the molecules collected in this review, but interestingly, three of the top five for both brain and muscle are nuclear receptor binding ligands; estradiol (estrogen receptor), dexamethasone (glucocorticoid receptor), and tretinoin (retinoic acid receptor), indicating a potential role of nuclear receptors in the regulation of physical activity. Selective nuclear receptor modulation may be an area of interest in future mechanistic studies of the genetic regulation of physical activity.
Cytoplasmic polyadenylation is an ancestral hallmark of early development in animals
Authors: Rouhana Labib , Edgar Allison , Hugosson Fredrik , Dountcheva Valeria , Martindale Mark Q. , Ryan Joseph F.
Published: May 2023

Differential regulation of gene expression has produced the astonishing diversity of life on Earth. Understanding the origin and evolution of mechanistic innovations for control of gene expression is therefore integral to evolutionary and developmental biology. Cytoplasmic polyadenylation is the biochemical extension of polyadenosine at the 3’-end of cytoplasmic mRNAs. This process regulates the translation of specific maternal transcripts and is mediated by the Cytoplasmic Polyadenylation Element Binding Protein family (CPEBs). Genes that code for CPEBs are amongst a very few that are present in animals but missing in non-animal lineages. Whether cytoplasmic polyadenylation is present in non bilaterian animals (i.e., sponges, ctenophores, placozoans, cnidarians) remains unknown. We have conducted phylogenetic analyses of CPEBs and our results show that CPEB1 and CPEB2 subfamilies originated in the animal stem lineage. Our assessment of expression in the sea anemone,Nematostella vectensis(Cnidaria), and the comb jelly,Mnemiopsis leidyi(Ctenophora), demonstrates that maternal expression of CPEB1 and the catalytic subunit of the cytoplasmic polyadenylation machinery (GLD2) is an ancient feature that is conserved across animals. Furthermore, our measurements of poly(A)-tail elongation reveal that key targets of cytoplasmic polyadenylation are shared between vertebrates, cnidarians, and ctenophores, indicating that this mechanism orchestrates a regulatory network that is conserved throughout animal evolution. We postulate that cytoplasmic polyadenylation through CPEBs was a fundamental innovation that contributed to animal evolution from unicellular life.
Antimitotic Activity ofSamanea samanLeaf Extract in the In Vitro Development ofTripneustes gratillaEmbryo
Authors: Lam Justin Riley Y. , Casimpan Guinevere A. , Batoy Christine May L. , Cebedo Ma. Felaine , Cuesta Jann Ycleo T. , Gervacio Jecell , Grapa Joshua Benjamin R. , Mabelin Ma. Katrina Ada F. , Pepito Merry Grace S. , Rama Justine Mae A. , Simporios Daniel Joseph Z. , Villanueva Zackaree Michael A. , Villaruel Jolienne Abbygail M. , Gwendolyn D. Pepito , Adrian Christopher A. Lu
Published: May 2023

TITLE

Antimitotic Activity ofSamanea samanLeaf Extract in the In Vitro Development ofTripneustes gratillaEmbryo

INTRODUCTION

Commercially available anticancer drugs are expensive and may have side effects. This led the researchers to look into alternative plant sources. One of these is acacia orS. saman.

OBJECTIVE

To determine whetherS. samanleaf extract possesses antimitotic activity onT. gratillaembryos using vincristine sulfate as positive control.

METHODOLOGY

S. samanleaves were extracted using hexane, CCl4, CHCl3, and water.T. gratillaembryos were fertilized in vitro. The fractions, vincristine sulfate, and DMSO in filtered sea water were added with the fertilized embryos in petri dishes. Samples were taken at 15 minutes after fertilization and every 30 minutes thereafter until the negative control reached a 32-cell stage. Fifty cells and their mean cell stage was evaluated per treatment. One-way ANOVA and Tukey tests were performed.

RESULTS

Significant differences were seen starting at 75 minutes post fertilization up until the 165thminute using One-way ANOVA. The Tukey test showed that all aqueous and CCl4as well as hexane (200, 400, 800 ppm) extracts had no significant difference compared to vincristine sulfate; while all CHCl3, hexane (100 ppm), and CCl4(100 ppm) extracts showed a significant difference compared to vincristine

CONCLUSION

The aqueous, hexane, and carbon tetrachloride extracts possess potential antimitotic activity onT. gratillaembryos. Thus, it is a potential alternative to vincristine sulfate as an antimitotic agent.
Improvised AChE assay on homogenized rectal biopsy: An Alibi to AChE histochemistry in the diagnosis of Hirschsprung’s disease?
Authors: Kuvelkar Neha , Souza Serena D , Bukelo Maria Frances , Jadhav Vinay , Babu Narendra , Shankar Gowri , Noronha Santosh , Kini Usha
Published: May 2023

The surgical treatment of Hirschsprung’s disease (HD) is reliant on the accurate tissue diagnosis based on increased acetylcholine esterase enzyme (AChE) activity in frozen rectal biopsy sections demonstrated by histochemical staining techniques. The latter techniques used for ascertaining the presence of AChE mandates the use of inaccessible sophisticated instruments thereby limiting the performance of this technique to urban resource rich settings. This bottleneck translates into delayed treatment for patients who live in suburban, resource limited regions. Given the indispensable nature of the surgical treatment, scope for improving accessibility is restricted to the diagnostic modality of the disease.

In our study, we attempted to quantitatively estimate AChE in homogenized rectal mucosal biopsy samples of paediatric population (n=68) using an in-house modified AChE (mACHE) assay. The assay procedure for homogenization of the tissue was modified to selectively extract the mucosal portion of the rectal mucosal biopsy sample to be used for the assay. The efficiency of specific mucosal extraction was confirmed by the absence of neurotrophic AChE nerve fibres in remnant tissue obtained post homogenization by histochemical AChE staining. The mAChE assay was carried out in a blinded manner and the results were compared with the gold standard histochemical AChE (hAChE) assay.

Samples with activity lesser than 1 × 10-6mole/min/g wet weight of tissue were diagnosed as Non Hirschsprung’s Disease (NHD) and those above 1 × 10-6mole/min/g wet weight of tissue were diagnosed as HD. mAChE assay was found to have a specificity, sensitivity of 81.08 % and 92.85%; positive, negative predictive values of 78.78% and 93.75 % respectively. The mAChE assay was able to diagnose three cases which were deemed inconclusive as per hAChE.

The improvised in-house mAChE assay had a mutually exclusive range to differentiate between control and test, thus crediting its use as a diagnostic tool for Hirschsprung’s Disease.
Late- life shift in caloric intake affects fly longevity and metabolism
Authors: Li Michael , Macro Jacob , Meadows Kali , Mishra Dushyant , Martin Dominique , Olson Sara , Huggins Billy Joe , Graveley Brenton , Li James Y. H. , Rogina Blanka
Published: May 2023

Caloric restriction (CR) delays the onset of age-related changes and extends lifespan in most species, but how late in life organisms benefit from switching to a low-calorie (L) diet is unexplored. We transferred wild type male flies from a high- (H) to a L-calorie diet (HL) or vice versa (LH) at different times. Late-life HL shift immediately and profoundly reduces fly mortality rate to briefly lower rate than in flies on a constant L diet, and increases lifespan. Conversely, a LH shift increases mortality and hazard rate, which is temporarily higher than in flies aged on a H diet, and leads to shorter lifespan. Transcriptomic changes within 48 hours following diet shift uncover physiological adaptations to available nutrients. Unexpectedly, more abundant transcriptomic changes accompanied LH shift, including ribosome biogenesis, and promotion of growth, which likely contributes to higher mortality rate. Considering that the beneficial effects of CR on physiology and lifespan are conserved across many organisms, our findings suggest that CR interventions in older humans may counteract the detrimental effects of H diets even when initiated later in life.
Influence of oceanography and geographic distance on genetic structure: how varying the sampled domain influences conclusions inLaminaria digitata
Authors: Fouqueau L. , Reynes L. , Tempera F. , Bajjouk T. , Blanfuné A. , Chevalier C. , Laurans M. , Mauger S. , Sourisseau M. , Assis J. , Lévêque L. , Valero M.
Published: May 2023

Understanding the environmental processes shaping connectivity can greatly improve management and conservation actions which are essential in the trailing edge of species’ distributions. In this study, we used a dataset built from 32 populations situated in the southern limit of the kelp speciesLaminaria digitata. By extracting data from 11 microsatellite markers, our aim was to (1) refine the analyses of population structure, (2) compare connectivity patterns and genetic diversity between island and mainland populations and (3) evaluate the influence of sampling year, hydrodynamic processes, habitat discontinuity, spatial distance and sea surface temperature on the genetic structure using a distance-based redundancy analysis (db-RDA). Analyses of population structure enabled to identify well connected populations associated to high genetic diversity, and others which appeared genetically isolated from neighboring populations and showing signs of genetic erosion verifying contrasting ecological (and demographic) status in Brittany and the English Channel. By performing db-RDA analyses on various sampling sizes, geographic distance appeared as the dominant factor influencing connectivity between populations separated by great distances, while hydrodynamic processes were the main factor at smaller scale. Finally, Lagrangian simulations enabled to study the directionality of gene flow which has implications on source-sink dynamics. Overall, our results have important significance in regard to the management of kelp populations facing pressures both from global warming and their exploitation for commercial use.
Cardiac Effects of a Novel pH-Insensitive Sodium-Calcium Exchanger Mouse
Authors: Zhang Rui , Wu Xiaokang , Kim Brian , Xie Catherine , Gonzalez Devina , Norris Raven , Chin Nicholas , Li Liang , John Scott , Philipson Kenneth D. , Ottolia Michela , Goldhaber Joshua I.
Published: May 2023

BACKGROUND

Cardiac sodium-calcium exchange (NCX1) is the dominant calcium (Ca) efflux mechanism in cardiomyocytes and is strongly regulated by pH. However, the role of NCX1 pH sensitivity in normal cardiac function is unknown.

METHODS

We used CRISPR/Cas9 to produce a pH-resistant NCX1 mouse by replacing the histidine at position 165 of NCX1 with an alanine (H165A). Hearts were studied using echocardiography and ECG. RNA and protein expression levels were assessed using qPCR and Western blotting. Isolated ventricular cardiomyocytes were loaded with Ca indicators and patch clamped to record intracellular Ca transients and membrane current and voltage.

RESULTS

H165A mice live into adulthood with slightly reduced LV systolic function, normal heart rate and shortened QT interval. Both male and female animals exhibit reduced growth, but females eventually reach normal body weight. In patch clamped myocytes, NCX current (INCX) evoked by voltage ramps was reduced by 35% (at +80 mV). Lowering pHito 6.5 using Na-Acetate hadno effecton INCXin H165A myocytes, whereas the same intervention in wildtype (WT) inhibited INCXby 69% (at +80 mV, p<0.01). There was no change in H165A ventricular cardiomyocyte Ca transients measured with fura-2 AM. However, action potential duration was reduced 68%, consistent with the shorter QT interval. This coincided with a 37% reduction in L-type Ca current and increased expression of repolarizing K+channels. H165A mice are also resistant to ischemia/reperfusion injury.

CONCLUSIONS

The H165A mutation attenuates pH regulation of NCX1 in mice, is associated with reduced growth and accelerates cardiac repolarization without compromising excitation-contraction coupling. The mutation also confers cardioprotection. The H165A mouse is the first evidence that pH regulation of NCX1 affects cardiac physiology and is a potential model for studying the role of NCX1 pH-sensitivity on both physiological and pathophysiological cardiac function.
Septin 7 Interacts With Numb To Preserve Sarcomere Structural Organization And Muscle Contractile Function
Authors: Gasperi Rita De , Csernoch Laszlo , Dienes Beatrix , Gonczi Monika , Chakrabarty Jayanta K. , Goeta Shahar , Aslan Abdurrahman , Toro Carlos A. , Karasik David , Brown Lewis M. , Brotto Marco , Cardozo Christopher P.
Published: May 2023

Here, we investigated mechanisms by which aging-related reductions of the levels of Numb in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development including asymmetric cell division, cell-type specification and termination of intracellular signaling. Numb expression is reduced in old humans and mice. We previously showed that, in mouse skeletal muscle fibers, Numb is localized to sarcomeres where it is concentrated near triads; conditional inactivation of Numb and a closely related protein Numb-like (NumbL) in mouse myofibers caused weakness, disorganization of sarcomeres and smaller mitochondria with impaired function. Here, we found that a single knockout of Numb in myofibers causes reduction in tetanic force comparable to a double Numb, NumbL knockout. We found by proteomics analysis of protein complexes isolated from C2C12 myotubes by immunoprecipitation using antibodies against Numb, that Septin 7 is a potential Numb binding partner. Septin 7 is a member of the family of GTP-binding proteins that organize into filaments, sheets and rings, and is considered part of the cytoskeleton. Immunofluorescence evaluation revealed a partial overlap of staining for Numb and Septin 7 in myofibers. Conditional, inducible knockouts of Numb led to disorganization of Septin 7 staining in myofibers. These findings indicate that Septin 7 is a Numb binding partner and suggest that interactions between Numb and Septin 7 are critical for structural organization of the sarcomere and muscle contractile function.
Chromosome evolution in Lepidoptera
Authors: Wright Charlotte J. , Stevens Lewis , Mackintosh Alexander , Lawniczak Mara , Blaxter Mark
Published: May 2023

Chromosomes are a central unit of genome organisation. One tenth of all described species on Earth are Lepidoptera, butterflies and moths, and these generally possess 31 holocentric chromosomes. However, a subset of lepidopteran species display dramatic variation in chromosome counts. By analysing 210 chromosomally-complete lepidopteran genomes, the largest analysis of eukaryotic chromosomal-level reference genomes to date, we show that the diverse karyotypes of extant species are derived from 32 ancestral linkage groups, which we term Merian elements. Merian elements have remained largely intact across 250 million years of evolution and diversification. Against this stable background, we identify eight independent lineages that have evaded constraint and undergone extensive reorganisation - either by numerous fissions or a combination of fusion and fission events. Outside these lineages, fusions are rare and fissions are rarer still. Fusions tend to involve small, repeat-rich Merian elements and/or the Z chromosome. Together, our results reveal the constraints on genome architecture in Lepidoptera and enable a deeper understanding of the importance of chromosomal rearrangements in shaping the evolution of eukaryotic genomes.
Transcriptomic profiling reveals host-specific evolutionary pathways promoting enhanced fitness in the plant pathogenRalstonia pseudosolanacearum
Authors: Gopalan-Nair Rekha , Jardinaud Marie-Françoise , Legrand Ludovic , Lopez-Roques Céline , Bouchez Olivier , Genin Stéphane , Guidot Alice
Published: May 2023

The impact of host diversity on the genotypic and phenotypic evolution of broad-spectrum pathogens is a remaining issue. Here, we used populations of the plant pathogenRalstonia pseudosolanacearumthat were experimentally evolved on five types of host plants, either belonging to different botanical families or differing in their susceptibility or resistance to the pathogen. We investigated whether changes in transcriptomic profiles dissociated from genetic changes could occur during the process of host adaptation, and whether transcriptomic reprogramming was dependent on host type. Genomic and transcriptomic variations were established for 31 evolved clones that showed a better fitness in their experimental host than the ancestral clone. Few genomic polymorphisms were detected in these clones, but significant transcriptomic variations were observed, with a high number of differentially expressed genes (DEGs). In a very clear way, a group of genes belonging to the network of regulation of the bacterial virulence such asefpR, efpHorhrpB, among others, were deregulated in several independent evolutionary lineages and appeared to play a key role in the transcriptomic rewiring observed in evolved clones. A double hierarchical clustering based on the 400 top DEGs for each clone revealed two major patterns of gene deregulation that depend on host genotype, but not on host susceptibility or resistance to the pathogen. This work therefore highlights the existence of two major evolutionary paths that result in a significant reorganization of gene expression during adaptive evolution and underscore clusters of co-regulated genes associated to bacterial adaptation on different host lines.

Data summary

The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.