bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell therapy in corneal endothelial disease
Authors: Wong Evan N. , Mehta Jodhbir S. 
Published: June 2022

Purpose of review
Endothelial keratoplasty is the current gold standard for treating corneal endothelial diseases, achieving excellent visual outcomes and rapid rehabilitation. There are, however, severe limitations to donor tissue supply and uneven access to surgical teams and facilities across the globe. Cell therapy is an exciting approach that has shown promising early results. Herein, we review the latest developments in cell therapy for corneal endothelial disease.

Recent findings
We highlight the work of several groups that have reported successful functional outcomes of cell therapy in animal models, with the utilization of human embryonic stem cells, human-induced pluripotent stem cells and cadaveric human corneal endothelial cells (CECs) to generate populations of CECs for intracameral injection. The use of corneal endothelial progenitors, viability of cryopreserved cells and efficacy of simple noncultured cells, in treating corneal decompensation is of particular interest. Further additions to the collective understanding of CEC physiology, and the process of cultivating and administering effective cell therapy are reviewed as well.

Summary
The latest developments in cell therapy for corneal endothelial disease are presented. The continuous growth in this field gives rise to the hope that a viable solution to the large numbers of corneal blind around the world will one day be reality.
Factors related to preparedness for emergency hemodialysis in the event of a natural disaster
Authors: Nihonyanagi Reiko , Tsukasaki Keiko , Itatani Tomoya , Nakai Hisao , Toda Daisuke 
Published: June 2022

Abstract
This study aimed to explore patients’ preparedness for emergency hemodialysis in the event of a natural disaster and to determine the factors affecting such preparedness.
A cross-sectional study was conducted in undergoing hemodialysis at dialysis facilities in Sapporo, Hokkaido. The participants were a cohort of 256 outpatients aged 20 years or older, 186 (72.7%) were male, and the average age was 61.9 ± 10.9 years. The participants were divided into those who had prepared for emergency dialysis treatment and those who had not. Cross tabulations were performed on the 2 groups using the following participant attributes: preparedness for dialysis during a disaster, knowledge of how to protect themselves during a disaster, and intention to dialyze and evacuate during a disaster, followed by binomial logistic regression analysis.
Of the 256 study patients, 184 (71.9%) were not prepared for dialysis treatment. In logistic regression models, patients who were not prepared for dialysis treatment were found to have higher odds of being employed (odds ratio (OR): 2.469; 95% confidence interval (CI): 1.205-5.058), not being aware of disaster information acquisition methods in the event of a disaster (OR: 4.580, 95%; CI: 2.048-10.241), did not receive explanations on proper disaster response from dialysis facility staff (OR: 2.557, 95%; CI: 1.319-4.954), and believing that their family away from home would not be concerned about them (OR: 2.021; 95% CI: 1.062-3.847).
Disaster preparedness in patients undergoing dialysis remain inadequate. Dialysis facilities need to strengthen their explanations of disaster response, particularly with regard to working, middle-aged people.
External validation of Villalta score in high-middle income country patients with deep vein thrombosis
Authors: de Ávila Rafael Bernardes , Marcondes Giulianna Barreira , Dias Silfayner Victor Mathias , da Silveira Beatriz Périco , de Amorim Jorge Eduardo , Neto Henrique Jorge Guedes , Nakano Luis Carlos Uta , Flumignan Ronald Luiz Gomes 
Published: June 2022

Abstract
Post-thrombotic syndrome (PTS) is a late complication that does not have a cure yet, with a prevalence estimated between 20 to 75%, associated with previous deep vein thrombosis event. Although the Villalta score (VS) is the gold-standard clinical tool for diagnostic and prognostic evaluation of PTS, there are currently no VS intra-rater agreement established and no validation studies for VS’ application into Brazilian Portuguese. We sought to translate and validate VS reliability systematically; and, secondarily, to compare the ultrasound findings with the severity of PTS.
We systematically translated the original VS into Brazilian Portuguese (BP). Fifty participants who underwent two outpatient visits were evaluated using the translated VS. We assessed its intra-rater and inter-rater agreement and compared BP VS versus CEAP clinical component (CEAP C), and the clinical PTS severity versus the duplex ultrasound (DUS) findings. The study and its report followed the Guidelines for Reporting Reliability and Agreement Studies.
The intra-rater evaluation of VS grades had a simple Kappa coefficient of 0.73, and the simple Kappa coefficient inter-rater for VS grades was 0.67. When VS was compared to CEAP C, it established a remarkably high correlation over 0.9. There was difference among VS values compared to DUS initial deep vein thrombosis territory, with femoropopliteal showing higher values than distal veins. Higher VS values were correlated to DUS venous recanalization and reflux.
There was a substantial inter-rater and intra-rater agreement when the BP VS was applied; and when compared to CEAP C, VS showed a high correlation. When VS grading was compared to DUS characteristics, there were significant statistical and clinical correlation, with presence of reflux and recanalization showing higher VS values. This external VS validation also changes the clinical practice allowing the VS use in a different population and establishes the VS intra-rater agreement.
Superb microvascular imaging for distinguishing thyroid nodules
Authors: Jin Hui , Wang Cong , Jin Xin 
Published: June 2022

Abstract

Background:
Earlier studies have shown that the superb microvascular imaging (SMI) can detect tumor angiogenesis to distinguish thyroid nodules, but there is no systematic review. This meta-analysis aimed to identify the accuracy of ultrasound SMI for the diagnosis of thyroid nodules.

Methods:
We searched PubMed, Cochrane Library, and CBM databases. A meta-analysis was conducted using STATA version 14.0 and Meta-Disc version 1.4 software. We calculated the summary statistics for sensitivity, specificity, positive and negative likelihood ratio (LR+/LR−), diagnostic odds ratio, and the synthetic receiver operating characteristic curve. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification.

Results:
11 studies that met the inclusion criteria were included in this meta-analysis. The quality assessment of the study of diagnostic accuracy studies scores of all included studies were ≥22. A total of 1003 thyroid malignant nodules and 957 thyroid benign nodules were assessed. The main outcome included: the pooled sensitivity was 0.81 (95% confidence intervals (CI) = 0.79–0.84), and the pooled specificity was 0.86 (95% CI = 0.84–0.88); the pooled LR+ was 5.79 (95% CI = 4.44–7.54), and the pooled negative LR− was 0.23 (95% CI = 0.20–0.26); the pooled diagnostic odds ratio of SMI in the diagnosis of thyroid nodules was 26.84 (95% CI = 19.13–37.60). The area under the synthetic receiver operating characteristic curve was 0.89 (95% CI = 0.86–0.91). We found no evidence for publication bias (t = 0.72, P = .49).

Conclusion:
Our meta-analysis indicates that SMI may have high diagnostic accuracy in distinguishing benign and malignant thyroid nodules.

Systematic review registration:
INPLASY202080084.
Hypocomplementemia during tocilizumab treatment
Authors: Bieber Amir , Markovits Doron , Toledano Kohava , Tavor Yonit , Mader Reuven , Balbir-Gurman Alexandra , Braun-Moscovici Yolanda 
Published: June 2022

Abstract
Hypocomplementemia has been reported in patients with rheumatoid arthritis treated with tocilizumab (TCZ), but its long-term consequences are unknown. We assessed the long-term outcome of patients treated with TCZ who developed hypocomplementemia regarding serious bacterial infections or autoimmune diseases (AID).
The charts of patients treated with TCZ at two rheumatology centers were reviewed retrospectively. Data regarding patients’ age, gender, disease duration, autoantibodies status, previous or concomitant treatments, blood counts, liver enzymes, C3 and C4 levels at baseline and during TCZ treatment, episodes of infections, allergic reactions, and AID were analyzed. Univariate analysis was used to compare patients with low C3, C4 levels versus patients with normal C3, C4 levels. Variables that were statistically significant associated or tended to be associated with low C3 or C4 were included in multiple variable logistic regression.
Of 132 patients treated with TCZ, 108 had serial measurements of serum complement concentration. Thirty-three (30%) patients developed low C4 levels and 23 (21%) had also low C3. Mean TCZ treatment period was 4.9 years (range, 1–14 years). All patients had normal complement levels at baseline. Leukopenia occurred in 18 (16.7%) patients, 14 of whom (77%) had low complement. Persistent leukopenia was observed in 8% and 5.3% of patients with normal C3 and C4 levels, respectively, as opposed to 47% and 42% of patients with low C3 or low C4, respectively. Low C3, C4 levels correlated with prolonged TCZ treatment retention time and effectiveness. There were no serious bacterial infections or new onset AID.
Hypocomplementemia during TCZ treatment was accompanied by leukopenia that correlated with treatment duration. Hypocomplementemia was not associated with serious bacterial infections or new onset AID. Decreased complement levels were associated with treatment longevity. The role of monitoring complement level in predicting treatment response or assessing disease activity deserves further investigation.
Comparison of the Neer classification to the 2018 update of the Orthopedic Trauma Association/AO fracture classification for classifying proximal humerus fractures
Authors: Marmor Meir T. , Agel Julie , Dumpe Jarrod , Kellam James F. , Marecek Geoffrey S. , Meinberg Eric , Nguyen Mai P. , Sims Stephen , Soles Gillian L. , Karam Matthew D. 
Published: June 2022

Abstract

Background:
The classification of fractures is necessary to ensure a reliable means of communication for clinical interaction, education and research. The Neer classification is the most commonly used classification for proximal humerus fractures. In 2018 the Orthopedic Trauma Association (OTA) and the AO Foundation provided an update to the OTA/AO Fracture Classification Scheme addressing many of the concerns about the previous versions of the classification. The objective of the present study was to evaluate the rater reliability of the 2 classifications and if the classifications subjectively better characterized the fracture patterns.

Methods:
X-rays and CT scans of 24 proximal humerus fractures were given to 7 independent raters for classification according to the Neer and 2018 OTA/AO classification. Both full-forms and short-forms of the classifications were tested. The Fleiss Kappa statistic was used to assess inter-rater agreement and intra-rater consistency for the 2 classifications. For each case the raters subjectively commented on how well each classification was able to characterize the fracture pattern.

Results:
All raters graded the 2018 OTA/AO classification as good as or better than the Neer classification for an adequate description of the fracture patterns. The short-form 2018 OTA/AO classification had the most 4 rater and 5 rater agreement cases and the second most 6 rater agreement cases. The short-form Neer classification had the second most 4 rater and 5 rater agreement cases and the most 6 rater agreement cases. The full 2018 OTA/AO had the least 4, 5, or 6 rater agreement cases of all the classification systems. Inter-rater agreement was fair for the full and short form of both the Neer and 2018 OTA/AO classification. The full and short Neer classifications together with the short 2018 OTA/AO classification had moderate intra-rater consistency, while the full 2018 OTA/AO classification only had slight intra-rater consistency.

Conclusions:
The 2018 OTA/AO classification is equivalent in its short-form to the Neer classification in inter-rater reliability and intra-rater consistency; and is superior in its full form for characterizing specific fracture types. The low inter-rater reliability of the full 2018 OTA/AO classification is a concern that may need to be addressed in the future.
Enhanced Recovery After Surgery Pathway in Kidney Transplantation: The Road Less Traveled
Authors: Elsabbagh Ahmed M. , Ghoneim Islam , Moiz Abdul , Welch Kristen , Brown J. Sidni 
Published: June 2022

Background.
Enhanced recovery after surgery (ERAS) pathway is a multimodal perioperative care pathway designed to achieve early recovery after surgery. ERAS protocols have not yet been well recognized in kidney transplantation. The aim of this study was to investigate the impact of ERAS pathway on early recovery and short-term clinical outcomes of kidney transplant.

Methods.
This is a single-center retrospective analysis comparing the outcomes of 20 adult kidney transplant recipients subjected to ERAS pathway with 20 adult recipients operated before ERAS with traditional standard of care.

Results.
There were no significant differences between both groups regarding age, gender, race, dialysis status, living donor percentage, cold ischemia time, and warm ischemia time. Median hospital stay for ERAS patients was 2 d. Overall median pain scores were significantly lower in the ERAS group versus non-ERAS group (morning after surgery pain score 2 versus 5; peak pain score 4.5 versus 10; lowest pain score 0 versus 2; P = 0.0001). ERAS patients had earlier ambulation (walking) and oral nutrition (regular diet) (first versus second day postoperatively in traditional group). Earlier bowel movement was observed in ERAS patients. There were no significant differences in graft function or 30-d readmission rates between both groups.

Conclusions.
Implementation of ERAS pathway in kidney transplantation is feasible. Using ERAS is associated with less pain, earlier ambulation and advancement of oral nutrition, and short hospital stay.
Lipoprotein profile and metabolic fine-mapping of genetic lipid risk loci
Authors: Suhre Karsten , Al-Ishaq Raghad , Belkadi Aziz , Habib Tanwir , Halama Anna , Stephan Nisha , Thareja Gaurav , Zaghlool Shaza , Fauman Eric B. , Najafi-Shoushtari S. Hani 
Published: June 2022

AbstractDysregulated blood lipid levels sit at the nexus of cardiometabolic disorders and are major predictors of human cardiovascular health. Using five major lipid traits (HDL-C, LDL-C, non- HDL-C, TC, and TG), a recent genome-wide association study (GWAS) in 1.65 million individuals identified and fine-mapped over 1,000 genetic loci that may be implicated in the etiology of dyslipidemia and related cardiovascular disease. However, a deeper functional understanding of these associations is needed to assess their therapeutic potential as druggable targets. Here we leveraged data from over 98,000 participants of UK Biobank for deep molecular phenotypic refinement and identified 225 lipid risk variants that associated with 168 distinct NMR-derived lipoprotein and metabolic traits, doubling the number of loci that are discoverable when using the five “classical” lipid traits alone. Hypothesis-free testing of >14,000 ratios between metabolite pairs significantly increased statistical power (p-gain) at 72% of the loci, revealing distinct groups of variants with functionally matching NMR-ratios that affect lipoprotein metabolism, transport, and remodeling (LPmtr). We demonstrate how these NMR- trait and -ratio associations can be used in the functional interpretation of the respective lipid risk loci and their evaluation as potential drug targets. Our study reveals a comprehensive picture of the biological roles that the different genetic variants play in LPmtr and supports the emerging view that lipoprotein size and core composition are essential for the understanding, prevention and treatment of lipid-related disorders, beyond the “classical” five major lipid traits currently used in clinical practice.
Targeting aggressive B-cell lymphomas through pharmacological activation of the mitochondrial protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David , Liesa Marc , Kostura Matthew J. 
Published: June 2022

AbstractConstitutive activation of the ATF4-mediated integrated stress response (ATF4-ISR) is common in cancer and buffers the metabolic challenges imposed by rapid proliferation. However, hyperactivation of the ISR can induce apoptosis. Here we demonstrate that novel pyrazolo-thiazole derivates activate the mitochondrial protease OMA1 which subsequently induces apoptosis in diffuse large B-cell lymphoma (DLBCL) cells. Apoptosis is dependent on the OMA1 mediated cleavage of DELE1 which leads to activation of HRI and induction of the ATF4 ISR. Screening in 406 cancer cell lines identified an inverse correlation between sensitivity to OMA1 activators and expression of the mitochondrial protein FAM210B. Ectopic overexpression of FAM210B specifically blocks OMA1 activation and apoptosis induction by pyrazolo-thiazole activators in DLBCL. OMA1 activators, including the preclinical candidate BTM-3566, selectively killed ABC, GCB, and double-hit DLBCL lines and induced complete tumor regression across a panel of DLBCL patient-derived xenografts.SignificanceHere we describe a novel class of small molecules that activate the mitochondrial protease OMA1 and induce therapeutic responses in DLBCL preclinical models in vitro and in vivo. OMA1 activation drives apoptosis through ATF4-ISR, an orthogonal mechanism to current therapies.
Development and Effectiveness Testing of a Mobile Health Education Package for Stroke Prevention Among Stroke Survivors
Authors: Odetunde Marufat Oluyemisi , Ibrahim Sekinat Omowumi , Oluwagbade Gideon Tolu , Odole Adesola Christiana , Mbada Chidozie Emmanuel , Komolafe Morenikeji A. 
Published: June 2022

ABSTRACTBackgroundInterventions based on social cognitive theory are more patient-centered and focused on principles that can enlighten and encourage adoption of healthy habits. Addressing limited stroke literacy among stroke survivors based on social cognitive theory is an effective means to reduce secondary stroke risk. The use of trending Mobile Health (m-health) devices can be a valuable interventional approach to achieve this through improved stroke literacy.ObjectivesThe objectives of this study were to develop and test effectiveness of m-health based educational package for stroke prevention among stroke survivors.MethodThis was a multimodal methodology involving content development and effectiveness testing using Delphi protocol and pretest-posttest design respectively. Development involved items selection, rating and retention; script writing, translation and recording into an audio and video educational packages. Effectiveness testing involved 30 consenting, consecutively assigned SSVs in each of audio (AIG) and video (VIG) intervention group. Stroke literacy was assessed at baseline, 2nd and 4th week post-intervention. Participants’ socio-demographic data were also collected. Data was summarized using descriptive and inferential statistics. Alpha value was set at p<0.05.ResultsMajority of the participants were male (63.3%), over 60 years old (51.7%), hypertensive (83.3%) and had tertiary education (31.7%). Knowledge of stroke risk factors improved between AIG and VIG from baseline (11 23±4 01 and 10.07±3.24) to 2nd week (17 73±0.78 and 15.30±1.78) and 4th week (17.97±0.18 and 16.77±1.01) post-intervention respectively. There were significant differences between the two groups (p<0.01).ConclusionMobile-health education based on social cognitive theory effectively improves stroke literacy among SSVs and should be tested among larger samples in the community.
CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration following radiation-induced injury
Authors: McKendrick John G. , Jones Gareth-Rhys , Elder Sonia S. , Mercer Ella , Magalhaes Marlene S. , Rocchi Cecilia , Hegarty Lizi M. , Johnson Amanda L. , Schneider Christoph , Becher Burkhard , Pridans Clare , Mabbott Neil , Liu Zhaoyuan , Ginhoux Florent , Bajenoff Marc , Gentek Rebecca , Bain Calum C. , Emmerson Elaine 
Published: June 2022

AbstractThe salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in xerostomia, or chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant cell type in the salivary glands and are attractive therapeutic targets due to their unrivalled capacity to drive tissue repair and regeneration. Yet, the nature and role of macrophages in salivary gland homeostasis and whether or not they contribute to tissue repair/regeneration following injury is not well understood. Here, we have used single cell RNA-seq, multi-parameter flow cytometry and fluorescence microscopy to map the heterogeneity of the salivary gland macrophage compartment throughout development and following radiation-induced injury. We show that there are highly dynamic changes in the composition of the salivary gland macrophage compartment with age, in part due to changes in the ontogeny of these cells, determined using a suite of complementary fate mapping systems. A combination of mutant mice and antibody blockade demonstrates that salivary gland macrophages are dependent on CSF1, but not IL-34 or GM-CSF, for their development and maintenance. Finally, using an in vivo model of radiation-induced salivary gland injury combined with a novel Mafb-specific depletion system, we demonstrate an essential role for macrophages. Without macrophages the clearance of cells with DNA damage, and effective tissue repair following such injury, is severely comprised. Our data, therefore, indicate a strong case for exploring the therapeutic potential of manipulating macrophages in order to promote tissue repair and thus minimise salivary gland dysfunction after radiotherapy.