bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Neuromuscular Ultrasound to Confirm Clinical Significance of a Genetic Variant for Charcot-Marie-Tooth Type 4C
Authors: Meiling James B. , Baute Penry Vanessa 
Published: March 2024

Abstract
Neuromuscular ultrasound has emerged as a beneficial, complementary tool to electromyography (EMG) in the diagnosis of neuromuscular diseases as it provides high-resolution anatomic imaging of peripheral nerves and muscles. It has been used previously as an adjunct to EMG to diagnose Charcot-Marie-Tooth disease. Here, we present a case of a 64-yr-old man with bilateral sensorineural hearing loss of 14 yrs who presented to an outpatient neuromuscular clinic at a tertiary medical center with very slow progressive paresthesias. This case highlights the application of neuromuscular ultrasound to help confirm the presence of a likely Charcot-Marie-Tooth disease type 4C despite indeterminate genetic testing results and challenging EMG results. He had genetic testing which revealed a normal PMP22 gene; however, he had a variant of uncertain significance in the SH3TC2 gene which has shown associations with autosomal recessive CMT4C. Neuromuscular ultrasound revealed mild median and significant tibial nerve uniform enlargement throughout their course. There may also be utility in performing neuromuscular ultrasound on similarly affected family members if the same variant of uncertain significance returns for SH3TC2, with consideration of both peripheral nerve and nerve root assessment.
The Impact of Surgical Timing in Orbital Fracture Repair: A New Paradigm
Authors: Hassan Bashar , Resnick Eric , Er Seray , Liang Fan , Redett Richard , Yang Robin , Manson Paul , Grant Michael 
Published: March 2024

Background:
For decades, there has been an ongoing debate about the ideal timing of orbital fracture repair (OFR) in adults.

Methods:
The authors conducted a retrospective review of patients who underwent OFR at 2 centers (2015 to 2019). Excluded were patients younger than 18 years and those with follow-up less than 2 weeks. The study’s primary outcome was the incidence/persistence of postoperative enophthalmos/diplopia at least 2 weeks following OFR. The association between surgical timing and postoperative ocular complications was assessed in patients with extraocular muscle (EOM) entrapment, enophthalmos and/or diplopia, and different fracture sizes.

Results:
Of 253 patients, 13 (5.1%) had preoperative EOM entrapment. Of these, patients who had OFR within 2 days of injury were less likely to develop postoperative diplopia compared with patients who had OFR within 8 to 14 days (1 of 8 patients [12.5%] versus 3 of 3 patients [100%]; P = 0.018). Patients who had OFR for nearly total defects within 1 week of injury were significantly less likely to have postoperative enophthalmos (0 patients [0.0%]) compared with those who had surgery after 2 weeks (2 patients [33.3%] after 15 to 28 days versus 8 patients [34.8%] after 28 days from injury; P < 0.001). Patients who had delayed OFR for large fractures smaller than nearly total defects, preoperative persistent diplopia, or enophthalmos were not at significantly greater likelihood of postoperative ocular complications compared with those who had early OFR.

Conclusions:
The authors recommend OFR within 2 days of injury for EOM entrapment and 1 week for nearly total defects. Surgical delay up to at least 4 weeks is possible in case of less severe fractures, preoperative persistent diplopia, or enophthalmos.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, IV.
An overview of risk factors, management and prevention of cochlear implant infections
Authors: MacKay Conor I. , Kuthubutheen Jafri , Campbell Anita J. 
Published: March 2024

Purpose of review
With cochlear implantation becoming increasingly performed worldwide, an understanding of the risk factors, preventive measures, and management of cochlear implant (CI) infection remains important given the significant morbidity and cost it conveys.

Recent findings
At the turn of the 21st century there was a decrease in rates of CI infection, particularly meningitis, following the discontinuation of positioner use for CI. However, in more recent years rates of CI infection have remained largely static. Recently, studies evaluating preventive measures such as pneumococcal vaccination, S. aureus decolonization and surgical antibiotic prophylaxis have emerged in the literature.

Summary
Prompt recognition of CI infection and appropriate investigation and management are key, however at present treatment is largely informed by cohort and case-control studies and expert opinion. Preventive measures including pneumococcal vaccination, S. aureus decolonization and preoperative antibiotic prophylaxis play a role in reducing rates of CI infection. However, there remains a need for well designed clinical trials to provide higher level evidence to better guide preventive measures for, and management decisions of, CI infections in the future.
The shared and disorder-specific resting state functional connectivity associated with emotion regulation between ADHD and bipolar disorder
Authors: Zhuang Qian , Xu Chuxian , Xu Nuo , Wang Tongtong , Lock Matthew , Chen Shuaiyu 
Published: March 2024

AbstractBackgroundEmotion regulation deficits have been frequently observed between ADHD (Attention-deficit/hyperactivity disorder, ADHD) and BD (bipolar disorder, BD) adults, however, common and distinguishable alterations in functional connectivity during rest remain poorly understood.ObjectivesThe current study was performed to determine the shared and disorder-specific resting state functional connectivity (rsFC) features within the proposed hierarchical emotion regulation model.MethodThe whole-brain seed-to-voxel functional connectivity analyses were performed on the neuroimaging data from the OpenFMRI project included 40 ADHD adults, 49 BD adults, as well as 49 age and gender matched healthy controls.ResultsOur findings showed significantly shared and disorder-specific rsFC circuits mainly linking to the processes of emotion perception and interception during emotion regulation but not response inhibition or executive control. Such as, the results found significantly enhanced functional connectivity strength between inferior occipital gyrus (IOG)-lingual/fusiform gyrus as well as superior parietal lobule (SPL)-insula circuits in ADHD group compared to healthy group (HG) and BD group, which suggests impaired emotional facial perception and interoceptive processing in ADHD than BD adults. In addition, the connectivity between precuneus and fusiform was significantly lower in both of ADHD and BD group compared to HG and no significant difference was found between patient groups. This indicates similar neural patterns underlying the impairment in emotion classification and emotional experience for ADHD and BD adults.ConclusionsTogether these findings can promote the understanding of common and disorder-specific neural mechanism underlying emotion dysregulations and facilitate neuroimaging-based clinical evaluation for ADHD and BD adults.
The iPhylo Suite: An Interactive Platform for Building and Annotating Biological and Chemical Taxonomic Trees
Authors: Li Yueer , Peng Chen , Chi Fei , Huang Zinuo , Yuan Mengyi , Jiang Chao 
Published: March 2024

AbstractAccurate and rapid taxonomic classifications are essential for systematically exploring organisms and metabolites in diverse environments. Many tools have been developed for biological taxonomic trees, but limitations apply, and a streamlined method for constructing chemical taxonomic trees is lacking. We present the iPhylo suite (https://www.iphylo.net/), a comprehensive, automated, and interactive platform for biological and chemical taxonomic analysis. The iPhylo suite includes the Tree and Visual web-based modules for interactive building and annotating biological and chemical taxonomic trees, and a stand- alone command-line interface (CLI) module for local use and deployment on high-performance computing clusters. Furthermore, the iPhylo visualization module is fully implemented in R, allowing users to save progress locally and modify the underlying R codes. Finally, the iPhylo CLI module extends the analysis to all hierarchical relational databases. In summary, the iPhylo suite provides an integrated interactive framework for in-depth taxonomic analyses of biological and chemical features and beyond.HighlightsA platform for both biological and chemical classification analysis and visualizations.A stand-alone Command line interface module for local or HPC deployment.R-based interactive visualization module with session-saving options.Supports customized hierarchical databases for analysis beyond taxonomy.
Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis
Authors: Jirouskova Marketa , Harant Karel , Cejnar Pavel , Ojha Srikant , Korelova Katerina , Sarnova Lenka , Sticova Eva , Mayr Christoph H. , Schiller Herbert B. , Gregor Martin 
Published: March 2024

ABSTRACTAccumulation of extracellular matrix (ECM) in liver fibrosis is associated with changes in protein abundance and composition depending upon etiology of the underlying liver disease. Current efforts to unravel etiology-specific mechanisms and pharmacological targets rely on several models of experimental fibrosis. Here, we characterize and compare dynamics of hepatic proteome remodeling during fibrosis development and spontaneous healing in experimental models of hepatotoxic (carbon tetrachloride (CCl4) intoxication) and cholestatic (3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding) injury. Using detergent-based tissue extraction and mass spectrometry, we identified compartment-specific changes in the liver proteome with detailed attention to ECM composition and changes in protein solubility. Our analysis revealed distinct time-resolved CCl4and DDC signatures, with identified signaling pathways suggesting limited healing and a potential for carcinogenesis associated with cholestasis. Correlation of protein abundance profiles with fibrous deposits revealed extracellular chaperone clusterin with implicated role in fibrosis resolution. Dynamics of clusterin expression was validated in the context of human liver fibrosis. Atomic force microscopy of fibrotic livers complemented proteomics with profiles of disease-associated changes in local liver tissue mechanics. This study determined compartment-specific proteomic landscapes of liver fibrosis and delineated etiology-specific ECM components, providing thus a foundation for future antifibrotic therapies.
Aurora B inhibition promotes a hyper-polyploid state and continued endomitotic cycles in RB and p53 defective cells
Authors: Vora Shivam , Andrew Ariel , Kumar Ramyashree Prasanna , Nazareth Deborah , Fernando Madushan , Jones Mathew JK , He Yaowu , Hooper John D. , McMillan Nigel AJ , Urosevic Jelena , Saeh Jamal , Travers Jon , Gabrielli Brian 
Published: March 2024

AbstractPolyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether this is a source of increased chemotherapy resistance and aggressive disease, or a benign or even favorable outcome. We have used Aurora B kinase (AURKB) inhibitors that efficiently promote polyploidy in many cell types to investigate the fate of polyploid cells. We demonstrate AURKB inhibitor treatment of cells that have loss of RB and p53 function causes them to become hyper-polyploid, undergoing continuous rounds of growth, replication and failed mitosis/cytokinesis (endomitosis), whereas RB and p53 functional cells will eventually exit the cell cycle. These hyper-polyploid cells (>4n DNA content) are viable and undergo continuous endomitotic cycles, but have lost the ability to form viable coloniesin vitroor form tumoursin vivo. Investigation of mitosis in these cells revealed that centrosome duplication remained coupled to DNA replication, with the hyper-polyploid cells containing high numbers of centrosome that were capable of supporting functional mitotic spindle poles, but these failed to progress to anaphase/telophase structures even when AURKB inhibitor was removed after 2-3 days. However, when AURKB inhibitor was removed after 1 day and cells had failed a single cytokinesis to become tetraploid, they retained long term colony forming ability. Collectively, these findings demonstrate that tetraploidy is well tolerated by tumour cells but higher ploidy states are incompatible with long term proliferative potential.
Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis
Authors: Lauer David , Magnin Cheryl Yael , Kolly Luca , Wang Huijuan , Brunner Matthias , Charbria Mamta , Cereghetti Grazia Maria , Gabryś Hubert , Tanadini-Lang Stephanie , Uldry Anne-Christine , Heller Manfred , Verleden Stijn E , Klein Kerstin , Sarbu Adela-Cristina , Funke-Chambour Manuela , Ebner Lukas , Distler Oliver , Maurer Britta , Gote-Schniering Janine 
Published: March 2024

AbstractAntifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we used an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed two distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing ILD patients, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a non-invasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.
PTENandARID1Ahaploinsufficiency equip colonic epithelium for oncogenic transformation
Authors: Skoufou-Papoutsaki Nefeli , Adler Sam , Mehmed Shenay , Tume Claire , Olpe Cora , Morrissey Edward , Kemp Richard , Girard Anne-Claire , Moutin Elisa B , Chilamakuri Chandra Sekhar Reddy , Miller Jodi L , Lindskog Cecilia , Werle Fabian , Marks Kate , Perrone Francesca , Zilbauer Matthias , Tourigny David S , Winton Douglas J 
Published: March 2024

AbstractNormal aged tissues are thought to exist as a patchwork of mutant clones. However, the relevance of driver mutations in normal tissue in terms of cancer initiation has not been well described. Here, we sought a quantitative understanding of how different cancer drivers achieve an age-related mutational footprint in the human colonic epithelium and to relate the clonal behaviours they generate to cancer risk. Metanalysis of contemporary multiregional sampling studies of colorectal tumours revealed many of the weak or moderate cancer drivers are trunk mutations present in the last common ancestor from which cancers arise. To study the processes by which such driver mutations could contribute to cancer predisposition, immunohistochemistry was used to detect PTEN, SMAD4 and ARID1A deficient clones in normal colon FFPE surgical resection samples (N=182 patients). Age-related changes in clone size and frequency identified positive biases in clone dynamics that acted to increase the mutational footprint for ARID1A and PTEN but not SMAD4.In vitroengineered monoallelic loss ofPTENandARID1Aimplicated specific altered downstream pathways and acquired pro-oncogenic cellular fates corresponding to haploinsufficiency for these genes.In situanalysis confirmed enhanced proliferation in both PTEN and ARID1A deficient clones and creation of an immune exclusive microenvironment associated with ARID1A deficiency. The behaviours resulting from haploinsufficiency ofPTENandARID1Aexemplify how priming of the tissue through somatic mosaicism could contribute alternative combinations of genetic events leading to transformation.
Altruistic feeding and cell-cell signaling during bacterial differentiation actively enhance phenotypic heterogeneity
Authors: Updegrove Taylor B. , Delerue Thomas , Anantharaman Vivek , Cho Hyomoon , Chan Carissa , Nipper Thomas , Choo-Wosoba Hyoyoung , Jenkins Lisa M. , Zhang Lixia , Su Yijun , Shroff Hari , Chen Jiji , Bewley Carole A. , Aravind L. , Ramamurthi Kumaran S. 
Published: March 2024

ABSTRACTStarvation triggers bacterial spore formation, a committed differentiation program that transforms a vegetative cell into a dormant spore. Cells in a population enter sporulation non-uniformly to secure against the possibility that favorable growth conditions, which puts sporulation-committed cells at a disadvantage, may resume. This heterogeneous behavior is initiated by a passive mechanism: stochastic activation of a master transcriptional regulator. Here, we identify a cell-cell communication pathway that actively promotes phenotypic heterogeneity, whereinBacillus subtiliscells that start sporulating early utilize a calcineurin-like phosphoesterase to release glycerol, which simultaneously acts as a signaling molecule and a nutrient to delay non-sporulating cells from entering sporulation. This produced a more diverse population that was better poised to exploit a sudden influx of nutrients compared to those generating heterogeneity via stochastic gene expression alone. Although conflict systems are prevalent among microbes, genetically encoded cooperative behavior in unicellular organisms can evidently also boost inclusive fitness.
A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective Against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy
Authors: Wu Bocheng , Tapadar Subhasish , Ruan Zhiping , Sun Carrie Q. , Arnold Rebecca S. , Johnston Alexis , Olugbami Jeremiah O. , Arunsi Uche , Gaul David A. , Petros John A. , Kobayashi Tatsuya , Duda Dan G. , Oyelere Adegboyega K. 
Published: March 2024

AbstractHepatocellular cancer (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylases (HDACs) activation. However, inhibiting HDACs — an effective treatment for lymphomas — has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells. The lead compoundSTR-V-53(3) showed a favorable safety profile in mice and robustly suppressed tumor growth in orthotopic xenograft models of HCC. When combined with the anti-HCC drug sorafenib,STR-V-53showed greater in vivo efficacy. Moreover,STR-V-53combined with anti-PD1 therapy increased the CD8+to regulatory T-cell (Treg) ratio and survival in an orthotopic HCC model in immunocompetent mice. This combination therapy resulted in durable responses in 40% of the mice. Transcriptomic analysis revealed thatSTR-V-53primed HCC cells to immunotherapy through HDAC inhibition, impaired glucose-regulated transcription, impaired DNA synthesis, upregulated apoptosis, and stimulated the immune response pathway. Collectively, our data demonstrate that the novel HDACiSTR-V-53is an effective anti-HCC agent that can induce profound responses when combined with standard immunotherapy.Graphical Abstract
A Health Economic Evaluation for Implementing an Extended Half-life Monoclonal Antibody for All Infants vs. Standard Care for Respiratory Virus Syncytial Prophylaxis in Canada
Authors: Shin Thomas , Lee Jason KH , Kieffer Alexia , Greenberg Michael , Wu Jianhong 
Published: March 2024

AbstractRespiratory syncytial virus (RSV) is a highly infectious virus, and infants and young children are particularly vulnerable to its progression to severe lower respiratory tract illness (LRTI). Nirsevimab, an extended half-life monoclonal antibody, was recently approved in Canada as a passive immunization intervention for the prevention of RSV LRTI. A static decision tree model was utilized to determine the cost-effectiveness of nirsevimab in Canadian infants compared to current standard of care (palivizumab for infants born preterm, and with specific chronic conditions) and generate an optimal price per dose (PPD) at accepted willingness-to-pay (WTP) thresholds. Various health outcomes (including hospitalization, ICU, and mechanical ventilation) and healthcare costs were calculated over one RSV season, with any necessary follow-up prophylaxis in the second season for three infant categories (palivizumab-eligible, preterm, and term). All health-related parameters and costs were tailored to the Canadian environment. Compared to scenarios where only at-risk segments of the infant population received nirsevimab, the base case (administering nirsevimab to all infants in their first RSV season) was the most cost-effective versus standard care: the PPD was $692 at a $40,000/QALY WTP threshold, using average costing data assumptions across all scenarios. Compared to standard care, the base case scenario could avoid 18,249 RSV-related health outcomes (reduction of 9.96%). Variations in discount rate, distribution of monthly RSV infections, nirsevimab coverage rate for infants born at term, and palivizumab cost had the most significant model impact. Passive immunization of all infants with nirsevimab can significantly reduce RSV-related health and economic burden across Canada.
Topological obstructions to quantum computation with unitary oracles
Authors: Gavorová Zuzana , Seidel Matan , Touati Yonathan 
Published: March 2024

Algorithms with unitary oracles can be nested, which makes them extremely versatile. An example is the phase estimation algorithm used in many candidate algorithms for quantum speedup. The search for new quantum algorithms benefits from understanding their limitations: Some tasks are impossible in quantum circuits, although their classical versions are easy, for example, cloning. An example with a unitary oracle U is the if clause, the task to implement controlled U (up to the phase on U). In classical computation the conditional statement is easy and essential. In quantum circuits the if clause was shown impossible from one query to U. Is it possible from polynomially many queries? Here we unify algorithms with a unitary oracle and develop a topological method to prove their limitations: No number of queries to U and U† lets quantum circuits implement the if clause, even if admitting approximations, postselection, and relaxed causality. We also show limitations of process tomography, oracle neutralization, and UdimU, UT, and U† algorithms. Our results strengthen an advantage of linear optics, challenge the experiments on relaxed causality, and motivate new algorithms with many-outcome measurements.

Published by the American Physical Society
2024