bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathology of Labyrinthitis Ossificans From an Intralabyrinthine Surgical Specimen
Authors: Leong Stephen , Teh Bing M. , Del Portillo Armando , Lalwani Anil K. 
Published: August 2022

Objective
Histologic characterization of labyrinthitis ossificans (LO) has mostly been limited to postmortem samples. In this report, we describe the histology of LO from a surgical specimen obtained from a patient undergoing labyrinthectomy with simultaneous cochlear implantation.

Patient
A 38-year-old woman initially presenting to the emergency room with acute vertigo, left-sided hearing loss, tinnitus, and aural fullness.

Interventions
Contrast-enhanced magnetic resonance imaging (MRI) and computerized tomography (CT) were performed for the patient before labyrinthectomy and cochlear implantation. Audiometric testing was performed before and after surgical intervention. Histologic analysis was performed on a specimen obtained from the left lateral semicircular canal (SCC) during surgery.

Main Outcome Measures
Preoperative CT and MRI findings, preoperative and postoperative hearing thresholds via air conduction and bone conduction, hematoxylin and eosin (H&E) stain of the surgical sample, and CD45 immunostain of the surgical sample.

Results
Preoperative CT and MRI confirmed the diagnosis of isolated LO of the left lateral SCC. Audiometric testing revealed significant improvement in hearing after labyrinthectomy and cochlear implantation. H&E stain demonstrated fibrosis and ossification in the left lateral SCC, and CD45 immunostain was negative.

Conclusions
Histopathology of LO based on a surgical sample is comparable to heterotopic ossification (HO) seen in other human tissue. Given the similarities between LO and HO, agents effective in preventing HO may have utility in preventing LO.
Cross-Modal Reorganization From Both Visual and Somatosensory Modalities in Cochlear Implanted Children and Its Relationship to Speech Perception
Authors: Hennesy Theresa , Cardon Garrett , Campbell Julia , Glick Hannah , Bell-Souder Don , Sharma Anu 
Published: August 2022

Hypothesis
We hypothesized that children with cochlear implants (CIs) who demonstrate cross-modal reorganization by vision also demonstrate cross-modal reorganization by somatosensation and that these processes are interrelated and impact speech perception.

Background
Cross-modal reorganization, which occurs when a deprived sensory modality's cortical resources are recruited by other intact modalities, has been proposed as a source of variability underlying speech perception in deaf children with CIs. Visual and somatosensory cross-modal reorganization of auditory cortex have been documented separately in CI children, but reorganization in these modalities has not been documented within the same subjects. Our goal was to examine the relationship between cross-modal reorganization from both visual and somatosensory modalities within a single group of CI children.

Methods
We analyzed high-density electroencephalogram responses to visual and somatosensory stimuli and current density reconstruction of brain activity sources. Speech perception in noise testing was performed. Current density reconstruction patterns were analyzed within the entire subject group and across groups of CI children exhibiting good versus poor speech perception.

Results
Positive correlations between visual and somatosensory cross-modal reorganization suggested that neuroplasticity in different sensory systems may be interrelated. Furthermore, CI children with good speech perception did not show recruitment of frontal or auditory cortices during visual processing, unlike CI children with poor speech perception.

Conclusion
Our results reflect changes in cortical resource allocation in pediatric CI users. Cross-modal recruitment of auditory and frontal cortices by vision, and cross-modal reorganization of auditory cortex by somatosensation, may underlie variability in speech and language outcomes in CI children.
Development and Validation of the Modified Motion Sensitivity Test
Authors: Heusel-Gillig Lisa , Santucci Vincent , Hall Courtney D. 
Published: August 2022

Objective
The aim of this study was to develop and validate an outcome measure for individuals with motion-provoked dizziness.

Study Design
Methodological.

Setting
Academic outpatient vestibular and dizziness clinic.

Patients/Subjects
Adults with and without motion-provoked dizziness.

Main Outcome Measures
Scores from the modified Motion Sensitivity Test (mMST) were compared between those with motion-provoked dizziness and controls without complaints of dizziness to evaluate the validity of the mMST. Intrarater and interrater reliability of the total Motion Sensitivity Quotient scores were assessed. Baseline and discharge total Motion Sensitivity Quotient scores were collected in a group of patients to determine the sensitivity of the mMST to measure change in motion-provoked dizziness after vestibular rehabilitation.

Results
A 10-item motion sensitivity test was developed and demonstrated discriminant validity to differentiate patients with motion-provoked dizziness and control subjects without dizziness and demonstrated construct validity compared with the Dizziness Handicap Inventory (r = 0.64, p < 0.001). Internal validity of the mMST was excellent (Cronbach α = 0.95). The mMST demonstrated excellent reliability between raters (intraclass correlation coefficient = 1.00) and test sessions (intraclass correlation coefficient = 0.95).

Conclusions
The results indicated that the mMST can be used reliably in clinical practice to develop exercise programs for patients with motion-provoked dizziness and to provide evidence of intervention efficacy. mMST is a valid, reliable measure to use in the clinic for patients with motion-provoked dizziness.
Is Parental Presence in the Ambulance Associated With Parental Satisfaction During Emergency Pediatric Intensive Care Retrieval? A Cross-Sectional Questionnaire Study
Authors: Evans Ruth E. C. , Barber Victoria , Seaton Sarah , Ramnarayan Padmanabhan , Davies Patrick , Wray Jo ,   on behalf of the DEPICT Study Group
Published: August 2022

OBJECTIVES:
Quality standards for pediatric intensive care transport services in the U.K. state that at least one parent should be allowed to travel with their child during emergency transport to a PICU. We aimed to identify the reasons why parents do, or do not, accompany their child and whether there is an association between parental presence in the ambulance and their satisfaction with the transport.

DESIGN:
National cross-sectional parent questionnaire.

SETTING:
Pediatric Critical Care Transport (PCCT) teams and PICUs in England and Wales.

PARTICIPANTS:
Parents of children transferred to one of 24 participating PICUs between January 2018 and January 2019.

INTERVENTIONS:
None.

MEASUREMENTS and MAIN RESULTS:
A parent feedback questionnaire was completed by parents whose child received an emergency interhospital transfer. As part of the questionnaire, a brief nine-item scale was developed to summarize parental transport experience (ranging from 1 to 5). The association between parental presence in the ambulance and parental experience was analyzed. A total of 4,558 children were transported during the study. Consent was obtained from 2,838 parents, and questionnaires received in 2,084 unique transports (response rate: 45.7%). In 1,563 transports (75%), at least one parent traveled in the ambulance. Parents did not travel in 478 transports (23%) and, in most instances (442 transports; 93%), offered reasons (emotional, practical, and health-related) for declining to travel or explanations why they were not permitted to travel (mainly due to space restrictions). Most parents rated their experience with the retrieval teams very highly, and within this context, we found evidence of greater variability in experience ratings if parents were not present in the ambulance and if this was not their choice.

CONCLUSIONS:
Most parents who completed questionnaires rated their experience with their PCCT team highly. Parental presence and choice to travel in the ambulance were associated with a more positive experience.
T-cell activation and B-cell interaction signatures in rectal tissues are associated with HIV replication in ex-vivo model of infection
Authors: Smith S. Abigail , Murray Phillip M. , Amancha Praveen K. , Ackerley Cassie G. , Tharp Gregory K. , Bosinger Steven E. , Amara Rama R. , Kelley Colleen F. 
Published: August 2022

Objective:
The rectal mucosa is a critical site of HIV vulnerability. We sought to identify transcriptomic features of rectal mucosal tissue prior to exposure associated with support or restriction of HIV replication.

Design:
Rectal tissue from HIV-negative cisgender men (n = 57) underwent concurrent RNAseq transcriptomic analyses (two biopsies/participant) and challenge with HIV in the ex-vivo explant model of infection (three biopsies challenged/participant) as part of a larger cohort study to understand the rectal mucosal immune environment among MSM.

Methods:
P24 was quantified in the explant supernatants over a culture period of 18 days via ELISA. Participant median p24 log area under the curve was correlated with bulk transcriptomic data (Illumina HiSeq3000) to identify associations between gene expression and p24 production. Significant differentially expressed genes (DEGs) were identified via DESeq2 analysis and analyzed with Reactome to identify pathways of interest.

Results:
In total, 183 DEG (181 upregulated, two downregulated) were associated with higher p24 accumulation in the ex-vivo challenge model, including T-cell activation, B-cell function, and chemokine DEG. Reactome analysis of the upregulated genes identified ‘Adaptive Immune System’, ‘Cytokine Signaling in Immune System’, and ‘Innate Immune System’ as significantly upregulated pathways.

Conclusion:
For the first time, we identified rectal tissue transcriptomic signatures associated with increased p24 production utilizing an ex-vivo model. Our findings are highly relevant to HIV transmission and the early establishment of HIV reservoirs in humans, and future studies should examine the identified pathways as targets for new or improved biomedical prevention or treatment interventions.
A Review of Microsurgical Resection of Recurrent Laryngeal Neurilemmoma Under Nerve Monitoring
Authors: Wang Tianyu , Xie Kaipeng , Lin Bojian , Zha Xudong , Peng Hu , Liu Huanhai , Zhang Guomin , Liao Jianchun 
Published: August 2022

Background:
Laryngeal neurilemmoma, especially recurrent laryngeal neurilemmoma, is a rare neural sheath tumor in head and neck. The most common symptom of laryngeal neurilemmoma is hoarseness or dysphonia, followed by dysphagia, dyspnea, and foreign body sensation. At present, surgical resection is the most effective treatment for this kind of tumor, thus making how to remove it become the most concerned problem of surgeons.

Case Presentation:
On February 18, 2021, a 64-year-old male presented to our clinic with recurrent sore throat and intermittent hoarseness for 3 years. The results of electronic laryngoscope and magnetic resonance imaging showed a 25×10×21 mm well-defined tumor in the left pyriform sinus without laryngeal cartilage destruction and enlarged lymph nodes. After the initial diagnosis of recurrent laryngeal neurilemmoma, to preserve the continuity of recurrent laryngeal nerve as much as possible, the authors determine to perform anatomical resection of recurrent laryngeal neurilemmoma with operating microscope under the monitoring of recurrent laryngeal nerve function. Finally, the patient recovered completely from hoarseness during postoperative follow-up.

Conclusion:
A complete diagnosis and treatment process of recurrent laryngeal neurilemmoma was presented by the case. Particularly, it shows the application of recurrent laryngeal nerve monitoring in the operation helps to protect the continuity of the recurrent laryngeal nerve, which lays a anatomical bases for the follow-up nerve repair.
Actionable Factors Fostering Health Value Generation and Scalability of Prehabilitation
Authors: Risco Raquel , González-Colom Rubèn , Montané-Muntané Mar , Cano Isaac , Vela Emili , Sebio Raquel , Dana Fernando , Faner Joan , Coca Miquel , Laxe Sara , Roca Josep , Martínez-Pallí Graciela 
Published: August 2022

Importance:
Prehabilitation has potential for improving surgical outcomes as shown in previous randomized controlled trials. However, a marked efficacy-effectiveness gap is limiting its scalability. Comprehensive analyses of deployment of the intervention in real-life scenarios are required.

Objective:
To assess health outcomes and cost of prehabilitation.

Design:
Prospective cohort study with a control group built using propensity score–matching techniques.

Setting:
Prehabilitation Unit in a tertiary-care university hospital.

Participants:
Candidates for major digestive, cardiac, thoracic, gynecologic, or urologic surgeries.

Intervention:
Prehabilitation program, including supervised exercise training, promotion of physical activity, nutritional optimization, and psychological support.

Main Outcomes and Measures:
The comprehensive complication index, hospital and intensive care unit length of stay, and hospital costs per patient until 30 days after surgery. Patients were classified by the degree of program completion and level of surgical aggression for sensitivity analysis.

Results:
The analysis of the entire study group did not show differences in study outcomes between prehabilitation and control groups (n=328 each). The per-protocol analysis, including only patients completing the program (n=112, 34%), showed a reduction in mean hospital stay [9.9 (7.2) vs 12.8 (12.4) days; P=0.035]. Completers undergoing highly aggressive surgeries (n=60) additionally showed reduction in mean intensive care unit stay [2.3 (2.7) vs 3.8 (4.2) days; P=0.021] and generated mean cost savings per patient of €3092 (32% cost reduction) (P=0.007). Five priority areas for action to enhance service efficiencies were identified.

Conclusions and Relevance:
The study indicates a low rate of completion of the intervention and identifies priority areas for re-design of service delivery to enhance the effectiveness of prehabilitation.
Single-molecule sequencing of animal mitochondrial genomes reveals chloroplast-like architecture and repeat-mediated recombination
Authors: Sharbrough Joel , Bankers Laura , Cook Emily , Fields Peter D. , Jalinsky Joseph , McElroy Kyle E. , Neiman Maurine , Logsdon John M. , Boore Jeffrey L. 
Published: August 2022

AbstractRecent advances in long-read sequencing technology have allowed for single-molecule sequencing of entire mitochondrial genomes, opening the door for direct investigation of mitochondrial genome architecture and landscapes of recombination. We used PacBio sequencing to re-assemble mitochondrial genomes from two species of New Zealand freshwater snails, Potamopyrgus antipodarum and Potamopyrgus estuarinus. These assemblies revealed a ∼1.7 kb structure within the mitochondrial genomes of both species that was previously undetected by assembly of short sequencing reads and likely corresponding to a large non-coding region commonly present in mitochondrial genomes. The overall architecture of these Potamopyrgus mitochondrial genomes is reminiscent of the chloroplast genomes of land plants, harboring a large single-copy region (LSC) and a small single-copy region (SSC) separated by a pair of inverted repeats (IRa and IRb). Individual sequencing reads that spanned across the Potamopyrgus IRa–SSC–IRb structure revealed the occurrence of “flip-flop” recombination, apparently mediated by the IRs. We also detected evidence for two distinct IR haplotypes and recombination between them in wild-caught P. estuarinus, as well as extensive inter-molecular recombination between SNPs in the LSC region. Together, these observations suggest that mitochondrial inheritance is not strictly maternal in these snails. The chloroplast-like architecture and repeat-mediated mitochondrial recombination we describe here raise fundamental questions regarding the origins and commonness of such architecture, whether and how recombination mediates mitochondrial genome evolution, and the role of genome architecture in driving cytoplasmic genome biology and the maintenance of cytoplasmic genomes.
Shared Graft Versus Leukemia Minor Histocompatibility Antigens in DISCOVeRY-BMT
Authors: Olsen Kelly S , Jadi Othmane , Dexheimer Sarah , Bortone Dante , Vensko Steven , Bennett Sarah , Tang Hancong , Diiorio Marisa , Saran Tanvi , Dingfelder David , Zhu Qianqian , Wang Yiwen , Haiman Christopher A , Pooler Loreall , Sheng Xin , Webb Amy , Pasquini Marcelo C , McCarthy Philip L , Spellman Stephen R , Weimer Eric , Hahn Theresa , Sucheston-Campbell Lara , Armistead Paul , Vincent Benjamin 
Published: August 2022

AbstractT cell responses to minor histocompatibility antigens (mHAs) mediate graft versus leukemia (GvL) effects and graft versus host disease (GvHD) in allogeneic hematopoietic cell transplant (alloHCT). Therapies that boost T cell responses improve the efficacy of alloHCT; however, these have been limited by concurrent increases in the incidence and severity of GvHD. mHAs with expression restricted to hematopoietic tissue (GvL mHAs) are attractive targets for driving GvL without causing GvHD. Prior work to identify mHAs has focused on a small set of mHAs or population-level SNP association studies. We report here the discovery of a large set of novel GvL mHAs based on predicted peptide immunogenicity, restriction of expression to hematopoietic tissue or GvHD target organs, and degree of sharing among donor-recipient pairs (DRPs) in the DISCOVeRY-BMT dataset of 3231 alloHCT DRPs. The total number of predicted mHAs and count within each class of predicted mHAs significantly differed by recipient genomic ancestry group, with European American>Hispanic>African American for each. The number of mHAs also differed markedly by HLA allele, even among alleles of the same gene. From the pool of predicted mHAs, we identified the smallest sets of GvL mHAs needed to cover 100% of DRPs with a given HLA allele. We then used mass spectrometry to search for high population frequency mHAs for three common HLA alleles. We validated a total of 24 novel predicted GvL mHAs that cumulatively are found within 98.8%, 60.7%, and 78.9% of DRPs within DISCOVeRY-BMT that express HLA-A*02:01, HLA-B*35:01, and HLA-C*07:02 respectively. We also confirmed in vivo immunogenicity of one example novel mHA via coculture of healthy human CD8 T cells with mHA-pulsed dendritic cells. This work demonstrates that identification of shared mHAs is a feasible and promising technique for expanding mHA-targeting immunotherapeutics to larger numbers of patients.
High-Dose Paclitaxel and its Combination with CSF1R Inhibitor in Polymeric Micelles for Chemoimmunotherapy of Triple Negative Breast Cancer
Authors: Lim Chaemin , Hwang Duhyeong , Yazdimamaghani Mostafa , Atkins Hannah Marie , Hyun Hyesun , Shin Yuseon , Ramsey Jacob D. , Perou Charles M. , Sokolsky-Papkov Marina , Kabanov Alexander V. 
Published: August 2022

AbstractThe presence of immunosuppressive immune cells in cancer is a significant barrier to the generation of therapeutic immune responses. Similarly, in vivo triple-negative breast cancer (TNBC) models often contain prevalent tumor-associated macrophages in the tumor microenvironment (TME), resulting in breast cancer initiation, invasion, and metastasis by generating immunosuppressive environment. Here, we test systemic chemoimmunotherapy using small-molecule agents, paclitaxel (PTX), and colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397, to enhance the adaptive T cell immunity against TNBCs in immunocompetent mouse TNBC models. PTX and PLX3397 are very poorly soluble in water and shown poor therapeutic outcomes in TNBC animal models in conventional formulation. To address the challenge for the delivery of insoluble drugs to TNBC, we use high-capacity poly(2-oxazoline) (POx)-based polymeric micelles to greatly improve the solubility and widen the therapeutic index of such drugs. The results demonstrate that high-dose PTX in POx, even as a single agent, exerts strong effects on TME and induces the long-term immune memory. In addition, we demonstrate that the PTX and PLX3397 combination provides consistent therapeutic improvement across several TNBC models, resulting from the repolarization of the immunosuppressive TME and enhanced T cell immune response that suppress both the primary tumor growth and metastasis. Overall, the work emphasizes the benefit of drug reformulation and outlines potential translational path for both PTX and PTX with PLX3397 combination therapy using POx polymeric micelles for the treatment of TNBC.
Construction of a three-component regulatory network of transcribed ultraconserved regions for the identification of prognostic biomarkers in gastric cancer
Authors: Khalafiyan Anis , Emadi-Baygi Modjtaba , Wolfien Markus , Salehzadeh-Yazdi Ali , Nikpour Parvaneh 
Published: August 2022

AbstractAlthough altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs) in the pathophysiology of neoplasms has already been investigated, relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. Differential expression analysis was conducted using DESeq2. Interactions between T-UCRs, miRNAs, and mRNAs were combined into a three-component network. The Survival package was utilized to identify survival-related differentially-expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was experimentally verified. Thirty-four T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to non-tumoral counterparts. The network was composed of 34 DET-UCRs, 275 miRNAs and 796 mRNAs nodes. Five T-UCRs were significantly correlated with the overall survival. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.Simple summaryGastric cancer (GC) is one of the most common cancers in the world and is considered as a highly heterogeneous disease based on subtypes and genetic alterations. GC is mostly detected in the advanced stages, hence, identifying diagnostic and prognostic biomarkers is of urgent need. Transcribed ultraconserved regions (T-UCRs) are a type of long non-coding RNAs which are linked to human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. In the current study, by applying a systems biology approach and constructing a regulatory network, we have presented a T-UCR as a potential diagnostic biomarker. Additionally, five T-UCRs with significant correlation with patients’ overall survival were found, which can be potentially used as prognostic biomarkers in future.