bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is myocardial strain an early marker of systolic dysfunction in obstructive sleep apnoea? Findings from a meta-analysis of echocardiographic studies
Authors: Tadic Marijana , Gherbesi Elisa , Faggiano Andrea , Sala Carla , Carugo Stefano , Cuspidi Cesare 
Published: July 2022

Aim:
We investigated the association between obstructive sleep apnoea (OSA) and subclinical systolic dysfunction through a meta-analysis of echocardiographic studies that provided data on left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS).

Design:
The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from inception to 31 December 2021. Studies were detected by using the following terms: ‘obstructive sleep apnea’, ‘sleep quality’, ‘sleep disordered breathing’, ‘cardiac damage’, ‘left ventricular hypertrophy’, ‘systolic dysfunction’, ‘global longitudinal strain’, ‘left ventricular mechanics’, ‘echocardiography’ and ‘speckle tracking echocardiography’.

Results:
The meta-analysis included 889 patients with OSA and 364 non-OSA controls from 12 studies. Compared with controls, GLS was significantly reduced in the pooled OSA group (SMD −1.24 ± 0.17, CI: −1.58 to −0.90, P < 0.0001), as well as in the normotensive OSA subgroup (SMD: −1.17 ± 0.12 CI:−1.40 to −0.95, P < 0.0001). Similar findings were obtained in sub-analyses performed separately in mild, moderate and severe OSA. This was not the case for LV ejection fraction (LVEF) (i.e. comparisons between controls vs. mild OSA, mild vs. moderate OSA, moderate vs. severe OSA).

Conclusion:
GLS is impaired in patients with OSA (independently from hypertension), worsening progressively from mild to moderate and severe forms, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF. Therefore, myocardial strain assessment should be implemented systematically in the OSA setting to timely detect systolic dysfunction.
Ultrasound Cyclo Plasty in Glaucoma: 2-Year Outcomes
Authors: Almobarak Faisal A. , Alrubean Ahmed , Alsarhani Waleed K. , Aljenaidel Abdullah , Osman Essam A. 
Published: July 2022

Précis:
UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.

Purpose:
The purpose of this study is to evaluate the 2-year outcomes of Ultrasound Cyclo Plasty (UCP) in uncontrolled glaucoma.

Materials and Methods:
A retrospective cohort study included patients with uncontrolled primary or secondary glaucoma who underwent UCP at King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, between 2016 and 2021. The main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, and presence of vision-threatening complications. The surgical outcome of each eye was classified as complete success, qualified success, or failure based on the main outcome measures.

Results:
One hundred and eighty-two eyes of 158 patients were included in the study. The mean follow-up period was 29.71 months (±18.1). The IOP and the number of antiglaucoma medications decreased significantly from a mean of 23.46 mm Hg (±6.3) and 3.33 (±0.9) to 17.33 (±7.1) and 2.14 (±1.4), and 16.24 (±6.3) and 1.90 (±1.5) on the 12th and 24 months, respectively. The overall success rates were 78.0% (143/182) and 85.6% (95/111), and the failure rates were 21.4% (39/182) and 14.4% (16/111) on the 12th and 24th months, respectively. The most common complications were cataract development/progression and anterior chamber reaction.

Conclusions:
UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.
Effects of Smoking on Optic Nerve Head Microvasculature Density in Glaucoma
Authors: Eslani Medi , Nishida Takashi , Weinreb Robert N. , Baxter Sally , Mahmoudinezhad Golnoush , Kamalipour Alireza , Yarmohammadi Adeleh , Zangwill Linda M. , Moghimi Sasan 
Published: July 2022

Précis:Decreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity.Purpose:To investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG.Methods:In this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density.Results:A total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with −0.54 (−1.06, −0.02) % lower whole image capillary density (P=0.041).Conclusions:Smoking intensity is associated with reduced optic nerve vessel density in glaucoma.
The Group A Streptococcus Interleukin-8 Protease SpyCEP Promotes Bacterial Intracellular Survival by Evasion of Autophagy
Authors: Bergmann René , Gulotta Giuseppe , Andreoni Federica , Sumitomo Tomoko , Kawabata Shigetada , Zinkernagel Annelies S. , Chhatwal Gursharan S. , Nizet Victor , Rohde Manfred , Uchiyama Satoshi 
Published: July 2022

Abstract
Autophagy serves an innate immune function in defending the host against invading bacteria, including group A Streptococcus (GAS). Autophagy is regulated by numerous host proteins, including the endogenous negative regulator calpain, a cytosolic protease. Globally disseminated serotype M1T1 GAS strains associated with high invasive disease potential express numerous virulence factors and resist autophagic clearance. Upon in vitro infection of human epithelial cell lines with representative wild-type GAS M1T1 strain 5448 (M1.5448), we observed increased calpain activation linked to a specific GAS virulence factor, the interleukin-8 protease SpyCEP. Calpain activation inhibited autophagy and decreased capture of cytosolic GAS in autophagosomes. In contrast, the serotype M6 GAS strain JRS4 (M6.JRS4), which is highly susceptible to host autophagy-mediated killing, expresses low levels of SpyCEP and does not activate calpain. Overexpression of SpyCEP in M6.JRS4 stimulated calpain activation, inhibited autophagy, and significantly decreased bacterial capture in autophagosomes. These paired loss- and gain-of-function studies reveal a novel role for the bacterial protease SpyCEP in enabling GAS M1 evasion of autophagy and host innate immune clearance.
Violence Is a Public Health and Healthcare Issue
Authors:   International Association of Forensic Nurses
Published: July 2022

ABSTRACT
Violence is a global issue that destroys the quality of life in communities and societies. Violence includes intentional and unintentional injury found in individuals who seek health care after acts of family violence, intimate partner violence, child abuse, elder abuse, sexual assault, trafficking, youth-on-youth violence, gang warfare, terror, war, disaster, and violence in schools, workplaces and prisons. The nature of violence is evolving. Death as a result of crime victimization now exceeds that of armed conflict. It is the position of the International Association of Forensic Nurses that forensic nurses are uniquely positioned to improve health outcomes that result from violence, including early identification of patients at risk of victimization or perpetration.
Liver-Intestinal Involvement in Graft Versus Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients: Ten Years of Experience in 2 Centers of Latin America
Authors: Sepúlveda Andrea , Tagliaferro Gustavo , Arancibia Gabriel , Barriga Francisco , Busoni Verónica , Orsi Marina 
Published: July 2022

Objectives:
To describe the behavior and characteristics of children with diagnosis of graft versus host disease (GVHD) with liver-intestinal involvement.

Methods:
Retrospective cohort study of pediatric patients with history of hematopoietic stem cell transplantation for diagnosis of GVHD with gastrointestinal (GI) or liver involvement, from 2 pediatric centers.

Results:
Between 2007 and 2017, 57 pediatric patients presented with liver or intestinal GVHD; 74% with GI GVHD, 11% with liver GVHD, and 15% with liver-intestinal involvement. Diarrhea (96%) and abdominal pain (55%) were the most frequent symptoms. Endoscopies were performed in 88%, and 35% required a second procedure to confirm diagnosis. Normal-appearing mucosa was observed in 17% of upper GI endoscopies and in 29% of colonoscopies. Endoscopic pathological findings were observed mainly in colon (62%). There was greater severity on colonoscopic classification in those with liver-intestinal compromise than in those with GI compromise only. Overall mortality was 26%.

Conclusion:
GI and liver GVHD diagnosis may present serious complications. GI involvement tends to manifest early, so it is appropriate to suspect it in the first days after transplantation, unlike liver involvement, which occurs late when other organs are involved. We did not observe a direct relationship between endoscopic and histological classification. Both GI and liver involvement in GVHD could predict greater target organ involvement.
Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy
Authors: Hensel Jonathan , Metts Jonathan , Gupta Ajay , Ladle Brian H. , Pilon-Thomas Shari , Mullinax John 
Published: July 2022

Abstract
Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy. As we improve our understanding of the orchestrated cellular and molecular mechanisms involved in ACT, this will provide biologic insight and improved ACT strategies for pediatric malignancies. This review focuses on ACT strategies outside of chimeric antigen receptor T-cell therapy, including completed and ongoing clinical trials, and highlights promising preclinical data in tumor-infiltrating lymphocytes that enhance the clinical efficacy of ACT for high-risk pediatric solid tumors.
Neoantigen-Specific T Cells in Adoptive Cell Therapy
Authors: Tran Eric 
Published: July 2022

Abstract
The holy grail of cancer therapeutics is the destruction of cancer cells while avoiding harm to normal cells. Cancer is unique from normal tissues because of the presence of somatic mutations that accumulate during tumorigenesis. Some nonsynonymous mutations can give rise to mutated peptide antigens (hereafter referred to as neoantigens) that can be specifically recognized by T cells. Thus, the immunological targeting of neoantigens represents a safe and promising strategy to treat patients with cancer. This article reviews the clinical application of adoptive cell therapy targeting neoantigens in patients with epithelial cancers.
γδ T Cell–Based Adoptive Cell Therapies Against Solid Epithelial Tumors
Authors: Bustos Xiomar , Snedal Sebastian , Tordesillas Leticia , Pelle Eleonora , Abate-Daga Daniel 
Published: July 2022

Abstract
Conventionally, adoptive cell therapies have been developed and optimized using αβ T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell–based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of discussion in the field, pertaining to their use in adoptive immunotherapy. We aimed to compile information about γδ T-cell enhancement in terms of expansion, phenotype, and inhibitory receptors, in addition to the latest advances in preclinical and clinical research using γδ T cells specifically against solid epithelial tumors.
Current State of Cell Therapies for Breast Cancer
Authors: Gautam Namrata , Elleson Kelly M. , Ramamoorthi Ganesan , Czerniecki Brian J. 
Published: July 2022

Abstract
Metastatic breast cancer (BC) is an aggressive form of cancer and is an absolute challenge to treat. This review discusses the standard treatments available for metastatic BC. It further highlights the rationale for targeting oncodrivers, tumor-associated antigens, and neoantigens in BC. Explaining the significance of immune response in successful immunotherapeutic studies, it draws attention towards how adoptive cell therapy can be a useful immunotherapeutic tool. We focus on adoptive cell therapy in BC covering tumor-infiltrating lymphocyte therapy, engineered T cell receptor therapy, chimeric antigen receptor therapy, dendritic cell therapy and natural killer cell therapy. In this work, we aim to provide an overview of clinical data regarding the use of cellular immunotherapies in BC. Eventually, we conclude by proposing future adoptive cell therapy approaches, which can be used to cure BC.
Preclinical In Vitro and In Vivo Models for Adoptive Cell Therapy of Cancer
Authors: Kaushik Garima , Venkatesha Shivaprasad , Verma Bhavna , Vishwakarma Bandana , Zhang Ai-Hong , Wesa Amy 
Published: July 2022

Abstract
Adoptive cellular therapies are making major strides in the treatment of cancer, both for hematologic and solid tumors. These cellular products include chimeric antigen receptor T cells and T-cell receptor–modified T cells, tumor-infiltrating lymphocytes, marrow-infiltrating T cells, natural killer cells as well as macrophage-based therapeutics. Advancement in genomics, computational biology, immunology, and cell therapy manufacturing has facilitated advancement of adoptive T cell therapies into the clinic, whereas clinical efficacy has driven Food and Drug Administration approvals. The growth of adoptive cellular therapy has, in turn, led to innovation in the preclinical models available, from ex vivo cell-based models to in vivo xenograft models of treatment. This review focuses on the development and application of in vitro models and in vivo models (cell line xenograft, humanized mice, and patient-derived xenograft models) that directly evaluate these human cellular products.
Natural Killer Cell Recognition and Control of Epithelial Cancers
Authors: de Souza Fernandez Pereira Marcelo , Carr David R. , Gatti-Mays Margaret E. , Olsen Mallery R. , Setty Bhuvana A. , Shahwan Kathryn T. , Lee Dean A. 
Published: July 2022

Abstract
Natural killer (NK) cells possess an innate ability to recognize cancer and are key mediators of cytotoxic efficacy for anticancer antibodies. Recent advances in the ability to generate, qualify, and safely infuse NK cells have led to a wide variety of clinical trials in oncology. Although their efficacy is best established for liquid cancers, their potential application in solid cancers has received increased attention. Here, we provide general background across a disparate group of exemplary solid tumors for which there is evidence for an NK cell role, discuss NK cell recognition motifs specific to each and murine and human studies of each that are supportive of NK cell adoptive immunotherapy, and end with special considerations relevant to the solid tumor microenvironment.
The Split Hypoglossal Nerve and Cross-Face Nerve Graft for Dual Innervation of the Functional Muscle Transfer in Facial Reanimation
Authors: Amer Tarek A. , ElSharkawy Omar A. 
Published: July 2022

Facial paralysis is a disabling deformity. The affected individual is seriously affected both esthetically and functionally. Free functional muscle transfer is currently the corner stone in the management of long-standing facial nerve paralysis. Several nerve options are available to supply the free muscle transfer. These nerves can be used alone or in combination. The aim of this work is to study the possibility and results of dually innervating the free functioning muscle transfer. The dual innervation is done using the split hypoglossal nerve and cross-face nerve graft (CFNG) both sutured in an end-to-end manner to the nerve to gracilis. Twenty-nine patients with unilateral long-standing facial nerve paralysis (more than 1 y) were treated using free gracilis muscle transfer dually supplied by the split hypoglossal nerve and CFNG, both sutured in an end-to-end manner. The gained excursion after the free gracilis transfer was 9 to 29 mm (mean: 17.24 mm). A statistically significant increase (P-value=0.0001) in the distance from where the midline crosses the lower vermilion border to commissure occurred from preoperative (mean: 16.55 mm) to postoperative setting (mean: 33.79 mm). Spontaneity was achieved in 26 patients (89.6%). In conclusion, dual innervation of the free muscle transfer using both the split hypoglossal nerve and CFNG (both sutured in an end-to-end manner to the nerve to gracilis) is a good possible option to treat long-standing cases of facial nerve paralysis. It yields adequate muscle excursion with acceptable spontaneity.
Accuracy of Detecting Obstructive Sleep Apnea Using Ambulatory Sleep Studies in Patients With Syndromic Craniosynostosis
Authors: Yang Sumin , de Goederen Robbin , Bredero-Boelhouwer Hansje , Joosten Koen F.M. , Mathijssen Irene M.J. 
Published: July 2022

Study Objectives:
Obstructive sleep apnea (OSA) is seen in up to two-third of the patients with syndromic craniosynostosis. Gold standard to diagnose OSA is the hospital-based polysomnography, although alternatively ambulatory home sleep apnea devices are available. Aim of this study was to assess (1) accuracy of ambulatory sleep studies, (2) clinical decision making following sleep studies, and (3) course of OSA during long-term follow-up.

Materials and Methods:
A retrospective cohort study was performed in children with syndromic craniosynostosis, of whom polysomnographies and home sleep apnea device recordings were collected. Measurements of apnea-hypopnea index, respiratory event index, total sleep/recording time, heart rate, oxygen saturation, and oxygen desaturation index were derived from the sleep studies. Primary clinical care subsequent to the sleep studies was determined using electronic patient files.

Results:
In total, 123 patients were included, with 149 polysomnographies and 108 ambulatory studies. Performing an ambulatory study was associated with increased age at time of measurement (OR=1.1, 95% CI=1.02 to 1.17, P=0.01). No significant difference was found between the 2 types of sleep studies regarding sleep study parameters. Subsequent to sleep studies, patients with no-mild OSA had expectant care whereas patients with moderate-severe OSA underwent OSA-related treatment. OSA was most prevalent up to the age of 5 years, but also noticeable after the age of 10 years in patients with the Crouzon syndrome.

Conclusions:
Ambulatory sleep studies are reliable for diagnosing OSA in older children and can be used to determine clinical decision-making. Hence, we recommend implementing ambulatory sleep studies in a protocolized management.
Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients
Authors: Billeter Adrian T. , Scheurlen Katharina M. , Israel Barbara , Straub Beate K. , Schirmacher Peter , Kopf Stefan , Nawroth Peter P. , Müller-Stich Beat P. 
Published: July 2022

Objective:
Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.

Methods:
Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m2, glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.

Results:
MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P=0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.

Conclusions:
RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.
Identification of an EMT-related Gene Signature Predicting Recurrence in Stage II/III Colorectal Cancer
Authors: Ren Haoyu , Bösch Florian , Pretzsch Elise , Jacob Sven , Westphalen C. Benedikt , Walter Holch Julian , Werner Jens , Angele Martin K. 
Published: July 2022

Objective:
To identify a prognostic significant gene signature for predicting colorectal cancer (CRC) recurrence.

Background:
Traditional prognostic risk assessment in stage II/III CRC patients remains controversial. Epithelial-mesenchymal transition is thought to be closely related to the malignant progression of tumors. Thus, it is promising to establish a prognostic model based on epithelial-mesenchymal transition–related gene (ERG) signature.

Materials and Methods:
We retrospectively analyzed transcriptome profiles and clinical information of 1780 stage II/III CRC patients from 15 public datasets. Coefficient variant analysis was used to select reference genes for normalizing gene expression levels. Univariate, LASSO, and multivariate Cox regression analyses were combined to develop the ERG signature predicting disease-free survival (DFS). The patients were divided into high-risk and low-risk based on the ERG signature recurrence risk score. The survival analysis was performed in different CRC cohorts.

Results:
The proposed ERG signature contained 7 cancer-related ERGs and 3 reference genes. The ERG signature recurrence risk score was prognostically relevant in all cohorts (P<0.05) and proved as an independent prognostic factor in the training cohort. In the pooled cohort, high-risk CRC patients exhibited worse DFS (P<0.0001) and overall survival (P=0.0058) than low-risk patients. The predictive performance of the ERG signature was superior to Oncotype DX colon cancer. An integrated decision tree and nomogram were developed to improve prognosis evaluation.

Conclusions:
The identified ERG signature is a promising and powerful biomarker predicting recurrence in CRC patients. Moreover, the presented ERG signature might help to stratify patients according to their tumor biology and contribute to personalized treatment.