bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 20-year bibliometric analysis of Fuchs endothelial corneal dystrophy: from 2001 to 2020
Authors: Lin Feng , Zhang Luoli , Wang Yimin , Fu Dan , Wang Yuliang , Zhou Xingtao 
Published: June 2022

Abstract
Purpose
The aim of this study was to identify trends and focuses in the field of Fuchs endothelial corneal dystrophy (FECD) research.

Methods
A bibliometric analysis based on the Web of Science Core Collection was conducted. All publications related to FECD from 2001 to 2020 were extracted and analyzed. VOSviewer v.1.6.17 was used to construct a visualization map and evaluate the trends and focuses in FECD research.

Results
A total of 1,041 publications were extracted. The rate of global publications has steadily increased. The United States produced the highest number of publications (461), the highest number of citations (18,757), and the highest H index (69). Melles GRJ published the highest number of papers (60), and Price FW had the highest number of citations (4,154) in the FECD research field. The highest number of publications came from the journal Cornea (279). Keywords were classified into four clusters: (1) corneal transplantation surgery, (2) surgical techniques and instruments, (3) corneal parameter measurement, and (4) genetic and molecular pathomechanisms. The average appearing years (AAYs) of the keywords were evaluated. Recently appearing keywords included “Tcf4 gene” (AAY of 2018.3), “ctg18.1” (AAY of 2017.2), “trinucleotide repeat expansion” (AAY of 2018.3), “rock inhibitor” (AAY of 2017.4), and “descemetorhexis” (AAY of 2017.4).

Conclusions
The United States has a dominant position in FECD research. Although corneal transplantation surgery has been the most mainstream area of FECD research field for a long time, gene mutations such as the TCF4 CTG trinucleotide repeat expansion, nonsurgical interventions such as rho-associated kinase inhibitors, and newer surgical methods such as descemetorhexis without endothelial keratoplasty are potential research hotspots.
Rasch analysis of the brief Michigan Hand Questionnaire in patients with thumb osteoarthritis
Authors: Killip Shannon C. , MacDermid Joy C. , Wouters Robbert M. , Sinden Kathryn E. , Gewurtz Rebecca E. , Selles Ruud W. , Packham Tara L. 
Published: June 2022

Abstract
Background
The brief Michigan Hand Questionnaire (brief MHQ) is a 12-item self-reported measure of hand function for patients with hand disorders which has been validated using Classical Test Theory. Rasch analysis can provide more detailed psychometric information. The purpose of this Rasch analysis is to assess the psychometric properties of the brief MHQ for patients with thumb osteoarthritis, and to make recommendations for improvements to the questionnaire if needed.

Methods
The Michigan Hand Questionnaire and demographic data were collected from 923 thumb osteoarthritis patients treated in specialized clinics for hand surgery and therapy in the Netherlands. Rasch analysis was performed on the 12 items of the brief MHQ using RUMM 2030 to assess the fit of the brief MHQ to the Rasch model. To determine fit, analysis of fit summary statistics, individual person fit and individual item fit were assessed. Threshold distributions were assessed to identify if any items required rescoring. The Person Separation Index was calculated to measure reliability of the questionnaire. Differential item functioning was assessed to identify item bias, and Principal Component Analysis was performed to identify unidimensionality and local dependence.

Results
The brief MHQ showed misfit (χ2 = 1312.5, p < 0.0001) with 6 items having disordered thresholds and 9 items requiring rescoring. After deleting 3 of the rescored items due to significant item fit residuals, the brief MHQ had an acceptable reliability (Cronbach’s alpha = 0.79). Misfit to the model (χ2 = 49.6, p = 0.0001), multidimensionality (10.2% of t-tests were significant), and item bias from non-uniform differential item functioning for 7 items across many person variables were still found.

Conclusion
Although no satisfactory solutions were found to correct the misfit to the Rasch model, it is recommended that the response options of the brief MHQ be rescored, and that items 6, 9 and 10 be removed. The lack of unidimensionality indicates that the items do not represent the singular construct of hand disability and that totalling the scores of the brief MHQ does not provide a valid measure of hand disability for people with thumb osteoarthritis. The 37-item Michigan Hand Questionnaire may provide a better assessment of hand disability for patients with thumb osteoarthritis.
Dehydroepiandrosterone in fibrotic interstitial lung disease: a translational study
Authors: Guler Sabina A. , Machahua Carlos , Geiser Thomas K. , Kocher Gregor , Marti Thomas M. , Tan Benjamin , Trappetti Verdiana , Ryerson Christopher J. , Funke-Chambour Manuela 
Published: June 2022

Abstract
Background
Dehydroepiandrosterone (DHEA) is a precursor sex hormone with antifibrotic properties. The aims of this study were to investigate antifibrotic mechanisms of DHEA, and to determine the relationship between DHEA-sulfate (DHEAS) plasma levels, disease severity and survival in patients with fibrotic interstitial lung diseases (ILDs).

Methods
Human precision cut lung slices (PCLS) and normal human lung fibroblasts were treated with DHEA and/or transforming growth factor (TGF)-β1 before analysis of pro-fibrotic genes and signal proteins. Cell proliferation, cytotoxicity, cell cycle and glucose-6-phosphate dehydrogenase (G6PD) activity were assessed. DHEAS plasma levels were correlated with pulmonary function, the composite physiologic index (CPI), and time to death or lung transplantation in a derivation cohort of 31 men with idiopathic pulmonary fibrosis (IPF) and in an independent validation cohort of 238 men and women with fibrotic ILDs.

Results
DHEA decreased the expression of pro-fibrotic markers in-vitro and ex-vivo. There was no cytotoxic effect for the applied concentrations, but DHEA interfered in proliferation by modulating the cell cycle through reduction of G6PD activity. In men with IPF (derivation cohort) DHEAS plasma levels in the lowest quartile were associated with poor lung function and higher CPI (adjusted OR 1.15 [95% CI 1.03–1.38], p = 0.04), which was confirmed in the fibrotic ILD validation cohort (adjusted OR 1.03 [95% CI 1.00–1.06], p = 0.01). In both cohorts the risk of early mortality was higher in patients with low DHEAS levels, after accounting for potential confounding by age in men with IPF (HR 3.84, 95% CI 1.25–11.7, p = 0.02), and for age, sex, IPF diagnosis and prednisone treatment in men and women with fibrotic ILDs (HR 3.17, 95% CI 1.35–7.44, p = 0.008).

Conclusions
DHEA reduces lung fibrosis and cell proliferation by inducing cell cycle arrest and inhibition of G6PD activity. The association between low DHEAS levels and disease severity suggests a potential prognostic and therapeutic role of DHEAS in fibrotic ILD.
Global water quality changes posing threat of increasing infectious diseases, a case study on malaria vector Anopheles stephensi coping with the water pollutants using age-stage, two-sex life table method
Authors: Fazeli-Dinan Mahmoud , Azarnoosh Mostafa , Özgökçe Mehmet Salih , Chi Hsin , Hosseini-Vasoukolaei Nasibeh , Haghi Farzad Motevalli , Zazouli Mohamad Ali , Nikookar Seyed Hassan , Dehbandi Reza , Enayati Ahmadali , Zaim Morteza , Hemingway Janet 
Published: June 2022

Abstract
Background
Water pollution due to uncontrolled release of chemical pollutants is an important global problem. Its effect on medically important insects, especially mosquitoes, is a critical issue in the epidemiology of mosquito-borne diseases.

Methods
In order to understand the effect of water pollutants on the demography of Anopheles stephensi, colonies were reared in clean, moderately and highly polluted water for three consecutive generations at 27 °C, 75% RH, and a photoperiod of 12:12 h (L:D). The demographic data of the 4th generation of An. stephensi were collected and analysed using the age-stage, two-sex life table.

Results
The intrinsic rate of increase (r), finite rate of increase (λ), mean fecundity (F) and net reproductive rate (R0) of An. stephensi in clean water were 0.2568 d−1, 1.2927 d−1, 251.72 eggs, and 109.08 offspring, respectively. These values were significantly higher than those obtained in moderately polluted water (r = 0.2302 d−1, λ = 1.2589 d−1, 196.04 eggs, and R0 = 65.35 offspring) and highly polluted water (r = 0.2282 d−1, λ = 1.2564 d−1, 182.45 eggs, and R0 = 62.03 offspring). Female adult longevity in moderately polluted (9.38 days) and highly polluted water (9.88 days) were significantly shorter than those reared in clean water (12.43 days), while no significant difference in the male adult longevity was observed among treatments.

Conclusions
The results of this study showed that An. stephensi can partially adapt to water pollution and this may be sufficient to extend the range of mosquito-borne diseases.
Robot-assisted gait training: more randomized controlled trials are needed! Or maybe not?
Authors: Labruyère Rob 
Published: June 2022

AbstractI was encouraged by the recent article by Kuo et al. entitled “Prediction of robotic neurorehabilitation functional ambulatory outcome in patients with neurological disorders” to write an opinion piece on the possible further development of stationary robot-assisted gait training research. Randomized clinical trials investigating stationary gait robots have not shown the superiority of these devices over comparable interventions regarding clinical effectiveness, and there are clinical practice guidelines that even recommend against their use. Nevertheless, these devices are still widely used, and our field needs to find ways to apply these devices more effectively. The authors of the article mentioned above feed different machine learning algorithms with patients’ data from the beginning of a robot-assisted gait training intervention using the robot Lokomat. The output of these algorithms allows predictions of the clinical outcome (i.e., functional ambulation categories) while the patients are still participating in the intervention. Such an analysis based on the collection of the device’s data could optimize the application of these devices. The article provides an example of how our field of research could make progress as we advance, and in this opinion piece, I would like to present my view on the prioritization of upcoming research on robot-assisted gait training. Furthermore, I briefly speculate on some drawbacks of randomized clinical trials in the field of robot-assisted gait training and how the quality and thus the effectiveness of robot-assisted gait training could potentially be improved based on the collection and analysis of clinical training data, a better patient selection and by giving greater weight to the motivational aspects for the participants.
Herpesvirus and neurological manifestations in patients with severe coronavirus disease
Authors: Carneiro Vanessa Cristine de Souza , Alves-Leon Soniza Vieira , Sarmento Dmitry José de Santana , Coelho Wagner Luis da Costa Nunes Pimentel , Moreira Otacilio da Cruz , Salvio Andreza Lemos , Ramos Carlos Henrique Ferreira , Ramos Filho Carlos Henrique Ferreira , Marques Carla Augusta Barreto , da Costa Gonçalves João Paulo , Leon Luciane Almeida Amado , de Paula Vanessa Salete 
Published: June 2022

Abstract
Background
Certain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms.

Methods
We analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method.

Results
Among the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034).

Conclusions
The findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.
Social determinants of health and cancer screening implementation and outcomes in the USA: a systematic review protocol
Authors: Korn Ariella R. , Walsh-Bailey Callie , Pilar Meagan , Sandler Brittney , Bhattacharjee Prema , Moore W. Todd , Brownson Ross C. , Emmons Karen M. , Oh April Y. 
Published: June 2022

Abstract
Background
Improving the delivery, uptake, and implementation of cancer screening to meet evidence-based recommendations is needed to reduce persistent cancer health disparities in the USA. Current national public health targets emphasize the role of social determinants of health (SDOH) on cancer screening. However, there remains a need to explicate these linkages, toward the goal of identifying and implementing effective interventions that target and address SDOH to reduce inequities in cancer screening.

Methods
We will conduct a systematic review of English language peer-reviewed original research articles published between 2010 and 2021 that describe observational (qualitative and quantitative) and intervention studies conducted in the USA. In alignment with Healthy People 2030, we will include studies of breast, cervical, colorectal, and/or lung cancer screening. Guided by multiple SDOH frameworks, we will broadly define SDOH by five domain areas: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social and community context. Following systematic literature searches in five databases (Ovid MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library) and piloting of screening procedures, reviewers will independently screen titles/abstracts for potential relevance. Reviewer pairs will then screen full text articles for eligibility criteria. We will extract data items from included articles, including study characteristics, cancer screening intervention information, and coding of SDOH constructs. We will assess study quality using the Mixed Methods Appraisal Tool and synthesize our findings using narrative, descriptive statistics, tables, and figures. Our approach will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations.

Discussion
By completing this systematic review, we will summarize recent literature on SDOH and cancer screening, identify research gaps for inclusion of SDOH, and propose future opportunities for advancing equity in cancer screening by integrating SDOH as part of the implementation context to promote uptake, sustainability, and scale-up in the implementation of screening guidelines.

Systematic review registration
PROSPERO CRD42021276582.
CALYPSO: A three-arm randomized phase II study of durvalumab alone or with savolitinib or tremelimumab in previously treated advanced clear cell renal cancer.
Authors: Powles Thomas , Mendez-Vidal Maria Jose , Rodriguez-Vida Alejo , Pérez-Valderrama Begoña , Esteban Emilio , Thistlethwaite Fiona , Patel Poulam M. , Anido Herranz Urbano , Srinivasan Gopalakrishnan , Hamid Abdel , Larkin James , Ralph Christy , Symeonides Stefan N. , Puente Javier , Hartmaier Ryan , Markovets Aleksandra , Prendergast Aaron , Mousa Kelly , Suarez Cristina 
Published: June 2022

LBA4503 Background: New drug combinations are required in advanced clear cell renal cancer (RCC). These potentially include MET inhibition with savolitinib (S) or CTLA-4 inhibition with tremelimumab (T). In this study these agents were given alone or in combination with the PD-L1 inhibitor durvalumab (D). Methods: A multinational open-label randomised phase II study assigning patients to one of D, S, DT or DS was performed. Patients with RCC, who had previously received VEGF targeted therapy but not immune checkpoint inhibitors or MET inhibitors were included. Confirmed response rate (cRR) was the primary endpoint. A response rate of at least 50% was required for further exploration. The S arm was closed early due to a lack of efficacy. DNA alterations were measured using Foundation One and PD-L1 analysis was performed with SP263. This abstract details the pre-planned 12-month interim analyses after the cohort completed randomisation. Results: Between 2017 and 2021, 139 patients were randomised (D N=39, S N=22, DT N=39, DS N=39). The median age was 62 years (range: 28 – 85). cRRs for the 4 arms were D=10%, S=5%, DT=28%, DS=13%, which did not meet the primary objective. cRRs in the MET-driven patients (N=17) were D=0% (0/7), S=0% (0/2), DT=50% (1/2), DS=17% (1/6). cRRs in PD-L1+ves for DT and D were 14% (1/7) and 33% (2/6) respectively. 12-month progression-free survival (PFS) rates were D=26% (80% confidence interval [CI]: 17% - 36%), S=21% (80% CI: 10% - 35%), DT=33% (80% CI: 24% - 43%), DS=17% (80% CI: 10% - 26%). Median overall survival for D=26.1 (80% CI: 16.2 – 32.0) months, S=23.1 (80% CI: 20.6 – 29.7) months, DT=21.9 (80% CI: 16.3 – 31.5) months, DS=16.1 (80% CI: 10.3 – 18.8) months. There was 1 treatment related death in the DT arm. Of the 136 patients who received treatment, grade 3 or more treatment related adverse events occurred in D=10% (4/39), S=26% (5/19), DT=23% (9/39), DS=23% (9/39). Conclusions: This randomised phase II study did not demonstrate significant efficacy for S alone or in combination with D in RCC. The addition of T to D did not demonstrate clearly superior efficacy to D in this setting. Clinical trial information: NCT02819596.
Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer.
Authors: Cercek Andrea , Lumish Melissa Amy , Sinopoli Jenna Cohen , Weiss Jill A. , Shia Jinru , Stadler Zsofia Kinga , Yaeger Rona , Smith Jesse Joshua , Saltz Leonard B. , El Dika Imane H. , Crane Christopher H. , Romesser Paul Bernard , Iyer Kirshna , Paty Philip , Garcia-Aguilar Julio , Gonen Mithat , Gollub Marc J , Weiser Martin R. , Schalper Kurt A. , Diaz Luis A. 
Published: June 2022

LBA5 Background: Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is mismatch repair deficient. Since mismatch repair deficient colorectal cancer is responsive to PD-1 blockade in the metastatic setting, we hypothesized that locally advanced mismatch repair deficient rectal cancer is sensitive to checkpoint blockade and may alter the requirements for chemoradiotherapy and surgery. Methods: We conducted a prospective phase II study in which single agent dostarlimab, an anti PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair deficient stage II and III rectal adenocarcinoma, to be followed by standard chemoradiation and surgery. Patients who achieved a clinical complete response were eligible for omission of chemoradiation and surgery. Results: Twelve patients initiated treatment and have at least 6 months of follow up. All 12 (100%, 95% CI:74%-100%) achieved a clinical complete response with no evidence of tumor on MRI, FDG-PET, endoscopic visualization, digital rectal exam, or biopsy, which satisfied the study’s co-primary endpoint. To date, no patients have required chemoradiation or surgery, and no cases of progression or recurrence have been noted during follow up (range 6-25 months). No serious adverse events > grade 3 were observed. Conclusions: Mismatch repair deficient locally advanced rectal cancer is exceptionally sensitive to single agent PD-1 blockade. Longer follow up is needed to assess response duration. Clinical trial information: NCT04165772.
ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer.
Authors: Monk Bradley J. , Parkinson Christine , Lim Myong Cheol , O'Malley David M. , Oaknin Ana , Wilson Michelle K. , Coleman Robert L. , Lorusso Domenica , Oza Amit M. , Ghamande Sharad A. , Christopoulou Athina , Prendergast Emily , Demirkiran Fuat , Littell Ramey D. , Chudecka-Glaz Anita M. , Morgan Mark Aloysuis , Goble Sandra M. , Hume Stephanie , Fujiwara Keiichi , Kristeleit Rebecca 
Published: June 2022

LBA5500 Background: While PARP inhibitors have shown efficacy as first-line (1L) maintenance treatment for patients (pts) with ovarian cancer (OC), questions remain about the pt population that may benefit from their use. ATHENA (NCT03522246) was designed to test if rucaparib may be effective as 1L maintenance treatment in a broad pt population, including those without BRCA mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. Here we report results from the ATHENA–MONO comparison of rucaparib vs placebo. Methods: Pts with stage III–IV high-grade OC who had completed cytoreductive surgery (R0 permitted) and 4–8 cycles of 1L platinum-doublet (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Pts were stratified by HRD status (as determined by FoundationOne CDx), residual disease status after chemotherapy, and timing of surgery. The primary endpoint of investigator-assessed PFS per RECIST was assessed in a step-down procedure first in the HRD population (BRCA mutant or BRCA wild-type/loss of heterozygosity [LOH] high carcinoma) and then in the intent-to-treat (ITT) population. Blinded independent central review (BICR)–assessed PFS was a stand-alone, secondary endpoint. PFS in BRCA mutant and HRD-negative pts (BRCA wild-type/LOH low) were exploratory endpoints. Results: As of Mar 23, 2022 (visit cutoff), 427 and 111 pts were randomized to rucaparib monotherapy or placebo (median time on treatment, 14.7 and 9.9 mo). PFS data are shown in the Table. Most common grade ≥3 TEAEs were anemia (rucaparib, 28.7% vs placebo, 0%), neutropenia (14.6% vs 0.9%), and ALT/AST increased (10.6% vs 0.9%). Rucaparib dose reduction, interruption, and discontinuation due to TEAEs occurred in 49.4%, 60.7%, and 11.8% of pts. Conclusions: Rucaparib monotherapy is effective as 1L maintenance with significant benefit vs placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of pts without known HRD. Clinical trial information: NCT03522246. [Table: see text]