bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research hotspots and trends in internal fixation of femoral neck fractures from 2010 to 2022: A 12-year bibliometric analysis
Authors: Ling Wenkang , Chen Leilei 
Published: June 2023

Background:
This study endeavors to scrutinize the hotspots and trends in the literature concerning the internal fixation of femoral neck fractures (INFNF) through a comprehensive bibliometric analysis. Notably, this analytical process encompasses both qualitative and quantitative components.

Methods:
The present study has utilized the Science Citation Index-Expanded from the Web of Science Core Collection to extract datasets ranging from January 1, 2010, to August 31, 2022. Quantitative analysis was carried out using sophisticated analytical tools such as the Bibliographic Item Co-Occurrence Matrix Builder, the Online Analysis Platform of Literature Metrology, and CiteSpace software. Further, the major Medical Subject Headings terms and their subheading counterparts associated with INFNF were extracted from the PubMed2XL website using the corresponding PMIDs. These Medical Subject Headings terms were employed in conducting a co-word clustering analysis. Ultimately, the Graphical CLUstering TOolkit program was utilized to execute a co-word biclustering analysis to discern the prevailing hotspots in this domain.

Results:
Between January 1, 2010, and August 31, 2022, a total of 463 publications were issued on INFNF. The INJURY-INTERNAL JOURNAL OF THE CARE OF THE INJURED stood out as the most extensively perused journal in this area. Notably, China emerged as the foremost contributor to publishing articles within the last 12 years, followed by the United States and Canada. McMaster University was identified as the leading institution in INFNF research, while Bhandari M emerged as the most prolific author in this field. Moreover, the study identified five notable research hotspots within the domain of INFNF.

Conclusions:
This study has identified five critical areas of research in the field of INFNF. It suggests that the primary focus of future research is likely to center on advancing internal fixation methods and robot-assisted instrumentation for femoral neck fractures. As such, this study provides valuable insights into future research directions and ideas for those working in this field.
Outcomes of Gastrostomy and Tracheostomy in Infants Undergoing Truncus Arteriosus Repair: Database Study Using the Pediatric Health Information System
Authors: Hook Jessica E. , Delany Dennis R. , Buckley Jason R. , Chowdhury Shahryar M. , Kavarana Minoo N. , Costello John M. 
Published: June 2023

OBJECTIVES:
We sought to determine the prevalence of and factors associated with gastrostomy tube placement and tracheostomy in infants undergoing truncus arteriosus repair, and associations between these procedures and outcome.

DESIGN:
Retrospective cohort study.

SETTING:
Pediatric Health Information System database.

PATIENTS:
Infants less than 90 days old who underwent truncus arteriosus repair from 2004 to 2019.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Multivariable logistic regression models were used to identify factors associated with gastrostomy tube and tracheostomy placement and to identify associations between these procedures and hospital mortality and prolonged postoperative length of stay (LOS; > 30 d). Of 1,645 subjects, gastrostomy tube was performed in 196 (11.9%) and tracheostomy in 56 (3.4%). Factors independently associated with gastrostomy tube placement were DiGeorge syndrome, congenital airway anomaly, admission age less than or equal to 2 days, vocal cord paralysis, cardiac catheterization, infection, and failure to thrive. Factors independently associated with tracheostomy congenital airway anomaly, truncal valve surgery, and cardiac catheterization. Gastrostomy tube was independently associated with prolonged postoperative LOS (odds ratio [OR], 12.10; 95% CI, 7.37–19.86). Hospital mortality occurred in 17 of 56 patients (30.4%) who underwent tracheostomy versus 147 of 1,589 patients (9.3%) who did not (p < 0.001), and median postoperative LOS was 148 days in patients who underwent tracheostomy versus 18 days in those who did not (p < 0.001). Tracheostomy was independently associated with mortality (OR, 3.11; 95% CI, 1.43–6.77) and prolonged postoperative LOS (OR, 9.85; 95% CI, 2.16–44.80).

CONCLUSIONS:
In infants undergoing truncus arteriosus repair, tracheostomy is associated with greater odds of mortality; while gastrostomy and tracheostomy are strongly associated with greater odds of prolonged postoperative LOS.
Gaps Between the Indication and the Home Execution of Massage Therapy in Children in the Postsurgical Stage of Primary Cheiloplasty or Rhinocheiloplasty
Authors: Montero-Orellana María José , Fuentes-Orellana María Rosa , Ossa-Cox Matías 
Published: June 2023

Purpose:
This study describes the compliance rate with home massage therapy in children in the postsurgical stage of primary cheiloplasty or rhinocheiloplasty and the factors that facilitate or hinder its execution.

Methods:
The parents of 15 children treated at the Gantz Foundation - Children’s hospital for cleft lip and palate in Santiago, Chile were recruited. Parents received instructions to perform massages at home 5 times daily and were followed up for 3 months by recording in a log. Qualitative information on facilitators and barriers was collected in a focus group session.

Results:
Compliance rate was close to 75%, and the factors that facilitated the execution were performing the massage with some distracting activity and noticing the positive changes in the appearance of the scars. The most important factors that hindered the execution were the infant’s crying and changes in the routine.

Conclusion:
The authors conclude that the compliance rate is high and suggest that parents and guardians identify and implement a routine with a distracting activity that allows the massage to be carried out effectively.
Single-cell transcriptomic and TCR analysis of human Cytomegalovirus (hCMV)-specific memory T cells reveals effector and pre-effectors of CD8+- and CD4+-cytotoxic T cells
Authors: Kar Raunak , Chattopadhyay Somdeb , Sharma Anjali , Sharma Kirti , Sinha Shreya , Arimbasseri Gopalakrishnan Aneeshkumar , Patil Veena S. 
Published: June 2023

AbstractBackgroundLatent human Cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Though, T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking.ResultsHere, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analyzing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental and functional memory T cell subsets such as, long-term memory precursors and effectors, T helper-17, T regulatory cells (TREGs) and cytotoxic T lymphocytes (CTLs) of both CD4 and CD8 origin. The hCMV-specific TREGs, in addition to being enriched for molecules known for their suppressive functions, showed enrichment for the interferon response signature gene sets. The hCMV-specific CTLs were of two types, the pre-effector and effector-like. The co-clustering of hCMV-specific CD4-CTLs and CD8-CTLs in both pre-effector as well as effector clusters suggest shared transcriptomic signatures between them. The huge TCR clonal expansion of cytotoxic clusters suggest a dominant role in protective immune response to CMV.ConclusionsThe study uncovers the heterogeneity in the hCMV-specific memory T cells reveling many functional subsets with potential implications in better understanding of hCMV-specific T cell immunity. The data presented can serve as a knowledge base for designing vaccines and therapeutics.
A prognostic matrix code defines functional glioblastoma phenotypes and niches
Authors: Vishnoi Monika , Dereli Zeynep , Yin Zheng , Kong Elisabeth K. , Kinali Meric , Thapa Kisan , Babur Ozgun , Yun Kyuson , Abdelfattah Nourhan , Li Xubin , Bozorgui Behnaz , Rostomily Robert C. , Korkut Anil 
Published: June 2023

AbstractInteractions among tumor, immune and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Here, we characterize functional and clinical relevance of genes encoding CMPs in GBM at bulk, single cell, and spatial anatomical resolution. We identify a “matrix code” for genes encoding CMPs whose expression levels categorize GBM tumors into matrisome-high and matrisome-low groups that correlate with worse and better survival, respectively, of patients. The matrisome enrichment is associated with specific driver oncogenic alterations, mesenchymal state, infiltration of pro-tumor immune cells and immune checkpoint gene expression. Anatomical and single cell transcriptome analyses indicate that matrisome gene expression is enriched in vascular and leading edge/infiltrative anatomic structures that are known to harbor glioma stem cells driving GBM progression. Finally, we identified a 17-gene matrisome signature that retains and further refines the prognostic value of genes encoding CMPs and, importantly, potentially predicts responses to PD1 blockade in clinical trials for GBM. The matrisome gene expression profiles may provide biomarkers of functionally relevant GBM niches that contribute to mesenchymal-immune cross talk and patient stratification to optimize treatment responses.
Trophic ecology of the African riverine elephant fishes (Mormyridae)
Authors: Sommer Gina Maria , Njom Samuel Didier , Indermaur Adrian , Bitja Nyom Arnold Roger , Horká Petra , Kukla Jaroslav , Musilova Zuzana 
Published: June 2023

AbstractMultiple species of the elephant fishes (Mormyridae) commonly coexist in sympatry in most African tropical rivers and lakes. In this study, we investigated the trophic ecology and potential trophic niche partitioning of eleven mormyrid fish species from the Sanaga River system (Cameroon) using the stable isotopes of carbon and nitrogen of muscles and of trophic prey samples. Albeit mormyrids mainly feed on invertebrates, we found differences in isotope signals and the trophic niche partitioning in the studied species. We further show that species with elongated snout tend to show higher carbon and nitrogen isotope signals, suggesting a potential role of snout shape in their trophic preferences. Furthermore, we found significant differences in isotopic signatures within theMormyrusgenus, highlighting ecological niche diversification among three closely related species. We also report on different isotopic signals between seasons of the year in four species, possibly caused by species migration and/or anthropogenic agricultural activities. Overall, our research presents robust evidence of the trophic niche partitioning within the entire mormyrid species community, shedding light on the enigmatic evolutionary history of these fascinating African fishes.
Automated cell annotation in multi-cell images using an improved CRF_ID algorithm
Authors: Lee Hyun Jee , Liang Jingting , Chaudhary Shivesh , Moon Sihoon , Yu Zikai , Wu Taihong , Liu He , Choi Myung-Kyu , Zhang Yun , Lu Hang 
Published: June 2023

AbstractCell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance inC. eleganswhole-brain images (Chaudhary et al, 2021). However, because the method was optimized for whole-brain imaging, comparable performance could not be guaranteed for application in commonly usedC. elegansmulti-cell images that display a subpopulation of cells. Here, we present an advance CRF_ID 2.0 that expands the generalizability of the method to multi-cell imaging beyond whole-brain imaging. To illustrate the application of the advance, we show the characterization of CRF_ID 2.0 in multi-cell imaging and cell-specific gene expression analysis inC. elegans. This work demonstrates that high accuracy automated cell annotation in multi-cell imaging can expedite cell identification and reduce its subjectivity inC. elegansand potentially other biological images of various origins.
Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments
Authors: Flanagan Louise M. , Horton James S. , Taylor Tiffany B. 
Published: June 2023

ABSTRACTThe observed mutational spectrum of adaptive outcomes can be constrained by many factors. For example, mutational biases can narrow the observed spectrum by increasing the rate of mutation at isolated sites in the genome. In contrast, complex environments can shift the observed spectrum by defining fitness consequences of mutational routes. We investigate the impact of different nutrient environments on the evolution of motility in the bacteriaPseudomonas fluorescensPf0-2x (an engineered non-motile derivative of Pf0-1) in the presence and absence of a strong mutational hotspot. Previous work has shown that this mutational hotspot can be built and broken via six silent mutations, which provide rapid access to a mutation that rescues swimming motility and confers the strongest swimming phenotype in specific environments. Here, we evolved a hotspot and non-hotspot variant strain of Pf0-2x for motility under nutrient rich (LB) and nutrient limiting (M9) environmental conditions. We observed the hotspot strain consistently evolved faster across all environmental conditions and its mutational spectrum was robust to environmental differences. However, the non-hotspot strain had a distinct mutational spectrum that changed depending on the nutrient environment. Interestingly, while alternative adaptive mutations in nutrient-rich environments were equal to, or less effective than, the hotspot mutation, the majority of these mutations in nutrient-limited conditions produced superior swimmers. Our competition experiments mirrored these findings, underscoring the role of environment in defining both the mutational spectrum and the associated phenotype strength. This indicates that while mutational hotspots working in concert with natural selection can speed up access to robust adaptive mutations (which can provide a competitive advantage in evolving populations) they can limit exploration of the mutational landscape, restricting access to potentially stronger phenotypes in specific environments.DATA SUMMARYAll data is available at OSF: DOI 10.17605/OSF.IO/8BT2W, and in supplementary materials.
Dysfunctional T Follicular Helper Cells Cause Intestinal and Hepatic Inflammation in NASH
Authors: Wang Haiguang , Barrow Fanta , Fredrickson Gavin , Florczak Kira , Nguyen Huy , Parthiban Preethy , Herman Adam , Adeyi Oyedele , Staley Christopher , Ikramuddin Sayeed , Ruan Hai-Bin , Jameson Stephen C. , Revelo Xavier S. 
Published: June 2023

ABSTRACTNonalcoholic steatohepatitis (NASH), characterized by hepatic inflammation and cellular damage, is the most severe form of nonalcoholic fatty liver disease and the fastest-growing indication for a liver transplant. The intestinal immune system is a central modulator of local and systemic inflammation. In particular, Peyer’s patches (PPs) contain T follicular helper (Tfh) cells that support germinal center (GC) responses required for the generation of high-affinity intestinal IgA and the maintenance of intestinal homeostasis. However, our understanding of the mechanisms regulating mucosal immunity during the pathogenesis of NASH is incomplete. Here, using a preclinical mouse model that resembles the key features of human disease, we discovered an essential role for Tfh cells in the pathogenesis of NASH. We have found that mice fed a high-fat high-carbohydrate (HFHC) diet have an inflamed intestinal microenvironment, characterized by enlarged PPs with an expansion of Tfh cells. Surprisingly, the Tfh cells in the PPs of NASH mice showed evidence of dysfunction, along with defective GC responses and reduced IgA+B cells. Tfh-deficient mice fed the HFHC diet showed compromised intestinal permeability, increased hepatic inflammation, and aggravated NASH, suggesting a fundamental role for Tfh cells in maintaining gut-liver homeostasis. Mechanistically, HFHC diet feeding leads to an aberrant increase in the expression of the transcription factor KLF2 in Tfh cells which inhibits its function. Thus, transgenic mice with reduced KLF2 expression in CD4 T cells displayed improved Tfh cell function and ameliorated NASH, including hepatic steatosis, inflammation, and fibrosis after HFHC feeding. Overall, these findings highlight Tfh cells as key intestinal immune cells involved in the regulation of inflammation in the gut-liver axis during NASH.
ER stress and lipid imbalance drive embryonic cardiomyopathy in a human heart organoid model of pregestational diabetes
Authors: Kostina Aleksandra , Lewis-Israeli Yonatan R. , Abdelhamid Mishref , Gabalski Mitchell A. , Volmert Brett D. , Lankerd Haley , Huang Amanda R. , Wasserman Aaron H. , Lydic Todd , Chan Christina , Olomu Isoken , Aguirre Aitor 
Published: June 2023

ABSTRACTCongenital heart defects constitute the most common birth defect in humans, affecting approximately 1% of all live births. The incidence of congenital heart defects is exacerbated by maternal conditions, such as diabetes during the first trimester. Our ability to mechanistically understand these disorders is severely limited by the lack of human models and the inaccessibility to human tissue at relevant stages. Here, we used an advanced human heart organoid model that recapitulates complex aspects of heart development during the first trimester to model the effects of pregestational diabetes in the human embryonic heart. We observed that heart organoids in diabetic conditions develop pathophysiological hallmarks like those previously reported in mouse and human studies, including ROS-mediated stress and cardiomyocyte hypertrophy, among others. Single cell RNA-seq revealed cardiac cell type specific-dysfunction affecting epicardial and cardiomyocyte populations, and suggested alterations in endoplasmic reticulum function and very long chain fatty acid lipid metabolism. Confocal imaging and LC-MS lipidomics confirmed our observations and showed that dyslipidemia was mediated by fatty acid desaturase 2 (FADS2) mRNA decay dependent on IRE1-RIDD signaling. We also found that the effects of pregestational diabetes could be reversed to a significant extent using drug interventions targeting either IRE1 or restoring healthy lipid levels within organoids, opening the door to new preventative and therapeutic strategies in humans.
IL-22 promotes acute kidney injury through activation of the DNA damage response and cell death in proximal tubule cells
Authors: Taguchi Kensei , Sugahara Sho , Elias Bertha C. , Pabla Navjot , Canaud Guillaume , Brooks Craig R. 
Published: June 2023

AbstractAcute kidney injury (AKI) affects over 13 million people world-wide annually and is associated with a fourfold increase in mortality. Our lab and others have shown that DNA damage response (DDR) governs the outcome of AKI in a bimodal manner. Activation of DDR sensor kinases protects against AKI, while hyperactivation of DDR effector proteins, such as p53, induces to cell death and worsens AKI. The factors that trigger the switch from pro-reparative to pro-cell death DDR remain to be resolved. Here we investigate the role of interleukin 22 (IL-22), an IL-10 family member whose receptor (IL-22RA1) is expressed on proximal tubule cells (PTCs), in DDR activation and AKI. Using cisplatin and aristolochic acid (AA) induced nephropathy as models of DNA damage, we identify PTCs as a novel source of urinary IL-22, making PTCs the only epithelial cells known to secret IL-22, to our knowledge. Functionally, IL-22 binding its receptor (IL-22RA1) on PTCs amplifies the DDR. Treating primary PTCs with IL-22 alone induces rapid activation of the DDRin vitro. The combination of IL-22 + cisplatin or AA treatment on primary PTCs induces cell death, while the same dose of cisplatin or AA alone does not. Global deletion of IL-22 protects against cisplatin or AA induced AKI. IL-22 deletion reduces expression of components of the DDR and inhibits PTC cell death. To confirm PTC IL-22 signaling contributes to AKI, we knocked out IL-22RA1 in renal epithelial cells by crossing IL-22RA1floxed mice with Six2-Cre mice. IL-22RA1 KO reduced DDR activation, cell death, and kidney injury. These data demonstrate that IL-22 promotes DDR activation in PTCs, switching pro-recovery DDR responses to a pro-cell death response and worsening AKI. Targeting IL-22 represents a novel therapeutic approach to prevent the negative consequences of the DDR activation while not interfering with the processes necessary for repair of damaged DNA.Translational statementAcute kidney injury, which affects 10-20% of hospitalized patients, is associated with a fourfold increase in mortality and predisposes patients to chronic kidney disease. In the present study, we identify interleukin 22 as a cofactor which worsens acute kidney injury. Interleukin 22 activates the DNA damage response, which in combination with nephrotoxic drugs amplifies the injury response in kidney epithelial cells and increases cell death. Deletion of interleukin 22 from mice or its receptor from mouse kidneys ameliorates cisplatin induced nephropathy. These findings may help clarify the molecular mechanisms of DNA damage induced kidney injury and identify interventions that can help treat acute kidney injury.
A mutational atlas for Parkin proteostasis
Authors: Clausen Lene , Voutsinos Vasileios , Cagiada Matteo , Johansson Kristoffer E. , Grønbæk-Thygesen Martin , Nariya Snehal , Powell Rachel L. , Have Magnus K. N. , Oestergaard Vibe H. , Stein Amelie , Fowler Douglas M. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: June 2023

AbstractThe delicate balance of protein homeostasis can be disturbed by mutations that affect folding and stability of the encoded protein. More than half of disease-causing missense variants are thought to lead to protein degradation, but determining which and the molecular mechanisms involved remain enigmatic. To examine these issues, we selected the ubiquitin-protein ligase Parkin, where known missense variants result in an autosomal recessive, early onset Parkinsonism. We used the variant abundance by massively parallel sequencing (VAMP-seq) approach to quantify the abundance of Parkin missense variants in cultured human cells. The resulting mutational map, covering 9219 out of the 9300 possible single-site amino acid substitutions and nonsense Parkin variants, show that most low abundance variants are located within the structured domains of the protein, while the flexible linker regions are more tolerant. The vast majority of low abundance Parkin variants are degraded through the ubiquitin-proteasome system and are stabilized at a lowered temperature. The cellular abundance data correlate with thermodynamic stability, evolutionary conservation, and show that half of the known disease-linked variants are found at low abundance. Systematic mapping of degradation signals (degrons) shows that inherent primary degrons in Parkin largely overlap with regions that are buried, and highly sensitive to mutations. An exposed degron region proximal to the so-called “activation element” is enhanced by substitutions to hydrophobic residues and destroyed by introduction of hydrophilic residues. The data provide examples of how missense variants may cause degradation either via destabilization of the native protein, or by introducing local signals for degradation. Combined with the computational methods based on Parkin structure and conservation, our abundance map sheds light on the mechanisms that cause loss of function, and points to variants where function potentially can be restored.