bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical Macular Hole Closure Without a Gas Tamponade
Authors: Grant Scott , Adrean Sean D. 
Published: June 2021

Purpose: This work aims to evaluate the outcomes of a series of macular hole (MH) surgical procedures in patients who had pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peel and without gas tamponade. Methods: Patients from a retina specialty clinic who had MHs were identified for this interventional case series. Patients with small MHs were offered inclusion into the trial. Patients with larger MHs were excluded. They underwent standard 3-port PPV and ILM peel without gas or air to treat small MHs. The main outcomes that we measured were closure of MH and visual results. Results: Small MHs in 5 patients were managed with PPV and ILM peel alone. The average preoperative hole size at its narrowest width was 227 µm (range, 173-294 µm). Four of 5 patients (80%) had successful hole closure without a gas tamponade and improved vision; 1 patient did not have hole closure and was treated with an in-office gas bubble to close the hole. The average preoperative vision at 3 months was 20/80– (54 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and improved to 20/30–2 (73 ETDRS letters) in the 4 patients whose MHs were closed with surgery without a gas bubble. This was statistically significant ( P = .003). The hole that did not close initially without gas tamponade was the largest in the series. Conclusions: Patients with small MHs can be successfully treated with a vitrectomy and ILM peel alone without a gas tamponade.
Ischemia Developing in a Fibrotic Finger Following the Use of Anesthetic With Epinephrine, Salvaged by Hyperbaric Oxygen Therapy
Authors: Engwall Abigail J. , Oakes Tannur C. , Torabi Mohammad , Schank Kyle J. , Kuhns Benjamin W. , Haan Pam , Clarkson James H. W. 
Published: June 2021

Background: The use of epinephrine for hand surgery has been rising over the past decade following the popularization of Wide Awake Local Anesthetic No Tourniquet (WALANT). Traditional teaching from the 20th century forbade the use of epinephrine claiming it could induce digital ischemia, yet trial data now contradicts this assumption. Purpose: Digital ischemia after epinephrine injection cases are important to report because epinephrine is being used increasingly in finger anesthesia. We wish to communicate to a growing number of hand surgeons who may be new to WALANT that epinephrine may have adverse effects in a fibrotic poorly perfused environment which is salvageable by hyperbaric oxygen therapy (HBOT). Case presentation: A 22-year-old male sustained a crush injury resulting in right index phalanx fracture. Acute open reduction with K wire fixation was performed under WALANT using 1% lidocaine with 1:100,000 epinephrine. After removal of wires, he was found to require elective open reduction and internal fixation with bone graft for delayed union, which was performed tension free using general anesthetic plus bupivacaine and 1:200,000 epinephrine. Despite mild congestion, phentolamine was not acutely administered when it might have been justified. The patient presented to the clinic five days later with blistering ischemic necrosis of the pulp, which was salvaged by HBOT. Summary: This case of digital ischemia following a crush injury with fibrotic scarring treated with lidocaine and epinephrine is reported as a warning to other hand surgeons performing WALANT. Epinephrine should be used with caution for digital blocks associated with scarred or fibrotic tissue and phentolamine should be used to reverse acute ischemia. HBOT can still salvage compromised tissue once the subacute process of ischemic necrosis has begun.
CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease
Authors: Hecker Judith S. , Hartmann Luise , Rivière Jennifer , Buck Michèle C. , van der Garde Mark , Rothenberg-Thurley Maja , Fischer Luise , Winter Susann , Ksienzyk Bianka , Ziemann Frank , Solovey Maria , Rauner Martina , Tsourdi Elena , Sockel Katja , Schneider Marie , Kubasch Anne S. , Nolde Martin , Hausmann Dominikus , Paulus Alexander C. , Lützner Jörg , Roth Andreas , Bassermann Florian , Spiekermann Karsten , Marr Carsten , Hofbauer Lorenz C. , Platzbecker Uwe , Metzeler Klaus H. , Götze Katharina S. 
Published: June 2021

Abstract
Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA). THA-derived hip bones serve as a major source of healthy hematopoietic cells in experimental hematology. We prospectively investigated frequency and clinical associations of CH in 200 patients without known hematologic disease who were undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variant allele frequencies [VAFs] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF, 1% to 2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%), and ASXL1 (3.5%). CHIP is significantly associated with lower hemoglobin, higher mean corpuscular volume, previous or present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AIDs; multivariable adjusted odds ratio, 6.6; 95% confidence interval, 1.7-30; P = .0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for managing patients with OA and AIDs or mild anemia and question the use of hip bone–derived cells as healthy experimental controls.
Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding
Authors: Saavedra Belén , Mambuque Edson , Nguenha Dinis , Gomes Neide , Munguambe Shilzia , García Juan Ignacio , Izco Santiago , Acacio Sozinho , Murias-Closas Adrià , Cossa Marta , Losada Irene , Pernas-Pardavila Hadrián , Oliveras Laura , Theron Grant , García-Basteiro Alberto L. 
Published: June 2021

AimsWe present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF (“Xpert”) and Xpert MTB/RIF Ultra (“Ultra”) using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique.MethodsSingle respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificityviatheir recategorisation to negative (in all and just among those previously treated individuals).Results1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90–0.98)versus0.88 (96% CI 0.82–0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71–0.93)versus0.63 (96% CI 0.48–0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95–0.97)versus0.98 (96% CI 0.97–0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22–0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252)versus2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort.ConclusionThese results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.
The sputum transcriptome better predicts COPD exacerbations after the withdrawal of inhaled corticosteroids than sputum eosinophils
Authors: Ditz Benedikt , Sarma Aartik , Kerstjens Huib A.M. , Liesker Jeroen J.W. , Bathoorn Erik , Vonk Judith M. , Bernal Victor , Horvatovich Peter , Guryev Victor , Caldera Saharai , Langelier Chaz , Faiz Alen , Christenson Stephanie A. , van den Berge Maarten 
Published: June 2021

IntroductionContinuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions.MethodsWe performed transcriptional profiling of sputum to explore the molecular biology and compared the predictive value of an unbiased gene signatureversussputum eosinophils for exacerbations after ICS withdrawal in COPD patients. RNA-sequencing data of induced sputum samples from 43 COPD patients were associated with the time to exacerbation after ICS withdrawal. Expression profiles of differentially expressed genes were summarised to create gene signatures. In addition, we built a Bayesian network model to determine coregulatory networks related to the onset of COPD exacerbations after ICS withdrawal.ResultsIn multivariate analyses, we identified a gene signature (LGALS12,ALOX15,CLC,IL1RL1,CD24,EMR4P) associated with the time to first exacerbation after ICS withdrawal. The addition of this gene signature to a multiple Cox regression model explained more variance of time to exacerbations compared to a model using sputum eosinophils. The gene signature correlated with sputum eosinophil as well as macrophage cell counts. The Bayesian network model identified three coregulatory gene networks as well as sex to be related to an earlyversuslate/nonexacerbation phenotype.ConclusionWe identified a sputum gene expression signature that exhibited a higher predictive value for predicting COPD exacerbations after ICS withdrawal than sputum eosinophilia. Future studies should investigate the utility of this signature, which might enhance personalised ICS treatment in COPD patients.
Development and validation of a mouse model of contemporary cannabis smoke exposure
Authors: Fantauzzi Matthew F. , Cass Steven P. , McGrath Joshua J.C. , Thayaparan Danya , Wang Peiyao , Stampfli Martin R. , Hirota Jeremy A. 
Published: June 2021

Cannabis is widely used for both recreational and medicinal purposes. Inhalation of combusted cannabis smoke is the most common mode of drug consumption, exposing the lungs to the pharmacologically active ingredients, including tetrahydrocannabinol (THC) and cannabidiol (CBD). While the relationship between cannabis smoke exposure and compromised respiratory health has yet to be sufficiently defined, previous investigations suggest that cannabis smoke may dysregulate pulmonary immunity. Presently, there exist few preclinical animal models that have been extensively validated for contemporary cannabis smoke exposure. To address this need, we developed a mouse model with readouts of total particulate matter, serum cannabinoid and carboxyhaemoglobin levels, lung cellular responses, and immune-mediator production. Using a commercially available smoke exposure system and a cannabis source material of documented THC/CBD composition, we exposed mice to a mean±sdtotal particulate matter of 698.89±66.09 µg·L−1and demonstrate increases in serum cannabinoids and carboxyhaemoglobin. We demonstrate that cannabis smoke modulates immune cell populations and mediators in both male and female BALB/c mice. This modulation is highlighted by increases in airway and lung tissue macrophage populations, including tissue-resident alveolar macrophages, monocyte-derived alveolar macrophages, and interstitial macrophage subpopulations. No changes in airway or lung tissue infiltration of neutrophils were observed. Immune-mediator analysis indicated significant upregulation of macrophage-derived chemokine, thymus and activation-regulated chemokine, and vascular endothelial growth factor within the lung tissue of cannabis smoke-exposed mice. This accessible and reproducible smoke-exposure model provides a foundation to explore the impact of chronic cannabis exposures and/or co-exposures with pathogens of clinical relevance, such as influenza.
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough
Authors: Ludbrook Valerie J. , Hanrott Kate E. , Kreindler James L. , Marks-Konczalik Joanna E. , Bird Nick P. , Hewens Debbie A. , Beerahee Misba , Behm David J. , Morice Alyn , McGarvey Lorcan , Parker Sean M. , Birring Surinder S. , Smith Jaclyn 
Published: June 2021

ObjectiveAirway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough.MethodsA two-period randomised, double blinded, placebo-controlled crossover study was designed with interim analyses for futility and sample size adjustment. Refractory chronic cough patients received either GSK2798745 or placebo once daily for 7 days with a washout between treatments. Pharmacokinetic samples were collected for analysis of GSK2798745 at end of study. The primary end-point was total cough counts assessed objectively during day-time hours (10 h) following 7 days of dosing.ResultsInterim analysis was performed after 12 participants completed both treatment periods. This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. At this point 17 participants had been enrolled (mean 61 years; 88% female), and 15 had completed the study. Final study results for posterior median cough counts showed a 34% (90% credible interval: −3%, +85%) numerical increase for GSK2798745 compared to placebo.ConclusionThere was no evidence of an anti-tussive effect of GSK2798745. The study design allowed the decision on lack of efficacy to be made with minimal participant exposure to the investigational drug.
Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells
Authors: Chankeaw Wiruntita , Lignier Sandra , Richard Christophe , Ntallaris Theodoros , Raliou Mariam , Guo Yongzhi , Plassard Damien , Bevilacqua Claudia , Sandra Olivier , Andersson Göran , Humblot Patrice , Charpigny Gilles 
Published: June 2021

Abstract
Background
A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle.

Results
In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process.

Conclusion
The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.
Morphologic and molecular correlates of EZH2 as a predictor of platinum resistance in high-grade ovarian serous carcinoma
Authors: Reid Brett M. , Vyas Shraddha , Chen Zhihua , Chen Ann , Kanetsky Peter A. , Permuth Jennifer B. , Sellers Thomas A. , Saglam Ozlen 
Published: June 2021

Abstract
Background
Enhancer of zesta homologue 2 (EZH2) is an essential component of polycomb repressive complex 2 (PRC2) that contributes to tumor progression and chemo-resistance. The aim of this study was to comprehensively assess the prognostic value of EZH2 across the morphologic and molecular spectra of high-grade serous ovarian carcinoma (HGSOC) by utilizing both immunohistochemistry (IHC) and proteogenomic technologies.

Methods
IHC of EZH2 was performed using a tissue microarray of 79 HGSOC scored (+/−) for lymphovascular invasion (LVI), tumor-infiltrating lymphocytic aggregates ≥1 mm (TIL) and architectural growth patterns. The association of EZH2 H-score with response to therapy and overall survival was evaluated by tumor features. We also evaluated EZH2 transcriptional (RNA sequencing) and protein (mass spectrometry) expression from bulk tumor samples from 336 HGSOC from The Cancer Genome Atlas (TCGA). EZH2 expression and co-expression networks were compared by clinical outcomes.

Results
For HGSOC without TIL (58%), EZH2 expression was almost 2-fold higher in platinum resistant tumors (P = 0.01). Conversely, EZH2 was not associated with platinum resistance among TIL+ HGSOC (P = 0.41). EZH2 expression was associated with reduced survival for tumors with LVI (P = 0.04). Analysis of TCGA found higher EZH2 expression in immunoreactive and proliferative tumors (P = 6.7 × 10− 5) although protein levels were similar across molecular subtypes (P = 0.52). Both mRNA and protein levels of EZH2 were lower in platinum resistant tumors although they were not associated with survival. Co-expression analysis revealed EZH2 networks totaling 1049 mRNA and 448 proteins that were exclusive to platinum sensitive or resistant tumors. The EZH2 network in resistant HGSOC included CARM1 which was positively correlated with EZH2 at both mRNA (r = 0.33, p = 0.003) and protein (r = 0.14, P = 0.01) levels. Further, EZH2 co-expression with CARM1 corresponded to a decreased prognostic significance of EZH2 expression in resistant tumors.

Conclusions
Our findings demonstrate that EZH2 expression varies based on its interactions with immunologic pathways and tumor microenvironment, impacting the prognostic interpretation. The association between high EZH2 expression and platinum resistance in TIL- HGSOC warrants further study of the implications for therapeutic strategies.
Perceived consequences of healthcare service decentralization on access, affordability and quality of care in Khartoum locality, Sudan
Authors: Noory Bandar , Hassanain Sara , Edwards Jeffrey , Lindskog Benedikte V. 
Published: June 2021

Abstract
Background
Decentralization of healthcare services has been widely utilized, especially in developing countries, to improve the performance of healthcare systems by increasing the access and efficiency of service delivery. Experiences have been variable secondary to disparities in financial and human resources, system capacity and community engagement. Sudan is no exception and understanding the perceived effect of decentralization on access, affordability, and quality of care among stakeholders is crucial.

Methods
This was a mixed method, cross-sectional, explorative study that involved 418 household members among catchment areas and 40 healthcare providers of Ibrahim Malik Hospital (IBMH) and Khartoum Teaching Hospital (KTH). Data was collected through a structured survey and in-depth interviews from July–December 2015.

Results
Access, affordability and quality of healthcare services were all perceived as worse, compared to before decentralization was implemented. Reported affordability was found to be 53 and 55% before decentralization compared to 24 to 16% after decentralization, within KTH and IBMH catchment areas respectively, (p = 0.01). The quality of healthcare services was reported to have declined from 47 and 38% before decentralization to 38 and 28% after, in KTH and IBMH respectively (p = 0.02). Accessibility was found to be more limited, with services being accessible before decentralization approximately 59 and 52% of the time, compared to 41 and 30% after, in KTH and IBMH catchment areas respectively, (p = 0.01).
Accessibility to healthcare was reported to have decreased secondary to facility closures, reverse transference of services, and low capacity of devolved facilities. Lastly, privatized services were reported as strengthened in response to this decentralization of healthcare.

Conclusions
The deterioration of access, affordability and quality of health services was experienced as the predominant perception among stakeholders after decentralization implementation. Our study results suggest there is an urgent need for a review of the current healthcare policies, structure and management within Sudan in order to provide evidence and insights regarding the impact of decentralization.
Situational analysis of diabetic retinopathy treatment Services in Ghana
Authors: Mensah-Debrah Agatha , Amissah Arthur Kwesi Nyan , Kumah David Ben , Akuffo Kwadwo Owusu , Osei Duah Isaiah , Bascaran Covadonga 
Published: June 2021

Abstract
Background
Although the equitable distribution of diabetic retinopathy (DR) services across Ghana remains paramount, there is currently a poor understanding of nationwide DR treatment services. This study aims to conduct a situation analysis of DR treatment services in Ghana and provide evidence on the breadth, coverage, workload, and gaps in service delivery for DR treatment.

Methods
A cross-sectional study was designed to identify health facilities which treat DR in Ghana from June 2018 to August 2018. Data were obtained from the facilities using a semi-structured questionnaire which included questions identifying human resources involved in DR treatment, location of health facilities with laser, vitreoretinal surgery and Anti–vascular endothelial growth factor therapy (Anti-VEGF) for DR treatment, service utilisation and workload at these facilities, and the average price of DR treatment in these facilities.

Results
Fourteen facilities offer DR treatment in Ghana; four in the public sector, seven in the private sector and three in the Christian Health Association of Ghana (CHAG) centres. There was a huge disparity in the distribution of facilities offering DR services, the eye care cadre, workload, and DR treatment service (retinal laser, Anti-VEGF, and vitreoretinal surgery). The retinal laser treatment price was independent of all variables (facility type, settings, regions, and National Health Insurance Scheme coverage). However, settings (p = 0.028) and geographical regions (p = 0.010) were significantly associated with anti-VEGF treatment price per eye.

Conclusion
Our results suggest a disproportionate distribution of DR services in Ghana. Hence, there should be a strategic development and implementation of an eye care plan to ensure the widespread provision of DR services to the disadvantaged population as we aim towards a disadvantaged population as we aim towards a universal health coverage.