bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the safety and efficacy of transradial approach for thrombectomy in posterior circulation stroke. A systematic literature review and meta-analysis
Authors: Marlowe Frederick J A , Powell Eloise
Published: June 2022

Background

Transradial access (TRA) is becoming more popular in neurointerventional radiology procedures and has been associated with reduced mortality, morbidity and access site complications. Guidelines state that TRA is a feasible option for posterior circulation thrombectomy however the evidence base is limited and no systematic literature review has yet been undertaken to evaluate its safety and efficacy.

Methods

The Cochrane Library, PubMed, Web of Science, Scopus, TRIP and Embase databases were searched. Outcomes collected included TICI scores, puncture to recanalisation time, mRS scores at 90 days and access site complications.

Results

291 records were identified and 31 full text articles were assessed for eligibility. Eight studies met the inclusion criteria and were meta-analysed. The rate of TICI 2b-3 was 94.7% (89.7–99.8% at 95% CI), TICI 3 was 67.9% (42.2–93.6% at 95% CI) and mRS 0–2 at 90 days was 49.8% (31.5–68.1% at 95% CI). Median puncture to reperfusion times were extracted from three studies as 24 (IQR 18–40), 24 (IQR 17.5–56.5) and 27 (IQR 24–33.5) minutes. No access site complications were reported. TICI 2b-3, TICI 3 and mRS scores were comparable to data for transfemoral access (TFA) from a large systematic review. Puncture to recanalisation times appeared lower than the TFA data but statistical comparison of this outcome was not possible.

Conclusions

The use of TRA in posterior circulation thrombectomy is safe and effective with comparable results to TFA. Further research with a larger sample size is required to fully investigate the potential for shortened puncture to recanalisation times.
‘No difference between journalism and suicide’: Challenges for journalists covering conflict in Balochistan
Authors: Agha Sidra , Demeter Márton
Published: June 2022

The safety of journalists reporting from conflict zones is a complex issue as they are exposed to a variety of challenges on a daily basis. This research aims to identify those multi-dimensional challenges that make Balochistan one of the world’s riskiest places for journalists. Based on 30 in-depth interviews with journalists working in the area, the authors found that the dynamics of conflict in Balochistan are different from those in other parts of Pakistan. Their findings reveal that different threatening agents – nationalist movements, separatist groups, the international agencies active there and the high level of extremism – all mean that journalists often cannot even identify the exact sources of threats. Moreover, journalists state that they receive no help from their media houses when they are reporting from conflict zones and look to the Pakistani army to protect the interests of the Baloch people while facing such challenges and risks.
Towards a resonant theory of memory politics
Authors: Ranger Jamie , Ranger Will
Published: June 2022

It is argued that Hartmut Rosa’s theory of resonance provides memory activists (those actors engaged in memory politics) with both a normative justification and qualitative metric by which sites of memory may be compared and evaluated. Resonance is a plausible candidate for an assessing concept on the grounds that there is overlap between Rosa’s sociological approach and the implicit appeal to resonance in the memory studies literature.
Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome–associated glioma
Authors: Cabezas-Camarero Santiago , Pérez-Alfayate Rebeca , García-Barberán Vanesa , Polidura María Carmen , Gómez-Ruiz María Natividad , Casado-Fariñas Isabel , Subhi-Issa Issa Ahmad , Hernández José Carlos Plaza , Garre Pilar , Díaz-Millán Isabel , Pérez-Segura Pedro
Published: June 2022

Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted.
Therapy Response of the Yttrium-90 (Y-90) Colloid and Rhenium-186 (Re-186) Sulphur Colloid Radiosynovectomy in Hemophilic Arthropathy
Authors: Kamarulzaman Kamalia , Boon Nang Lee , Shuaib Ibrahim L. , Abdul Karim Faraizah , Wan Zainon Wan Mohd Nazlee , Mat Nawi Norazlina
Published: June 2022

Introduction

Radiosynovectomy (also known as radiosynoviorthesis) is a local form of radiotherapy that is used in chronic hemophilic synovitis in the absence of radiological evidence of extensive joint damage and in patients that have failed conservative therapy with clotting factor replacement and physiotherapy.

Objectives

To evaluate the effectiveness of the Yttrium-90 (Y-90) colloid and Rhenium-186 (Re-186) sulphur colloid radiosynovectomy in hemophilic arthropathy in terms of bleeding frequency, pain score, range of motion and performance score.

Methodology

This was a prospective cohort trial. A total of 68 hemophilic arthropathy patients who had been treated with radiosynovectomy for knee, ankle, elbow and hip joint were included in this study. Patients were followed up to assess their bleeding frequency, pain score, range of motion of the affected joint and Karnofsky or Lansky performance scale at pre and 6 months post therapy.

Result

A marked decrease (80–100%) in bleeding frequency was seen in 66.2% of patients, 14.7% of patients had moderate decrease (51–79%) and mild decrease (30–50%) was seen in 14.7% of patients. The frequency of intraarticular bleeding and pain score were significantly reduced at 6 months follow up ( p<0.005). The Karnofsky and Lansky performance scales were also improved at 6 months follow up ( p<0.005). There was no significant difference between percentage of range of motion measured before and after the therapy ( p>0.005).

Conclusion

Radiosynovectomy is a safe and effective procedure in limiting bleeding frequency, reducing pain and increasing performance scale.
Facebook algorithm changes may have amplified local republican parties
Authors: Reuning Kevin , Whitesell Anne , Hannah A. Lee
Published: June 2022

In this research note we document changes to the rate of comments, shares, and reactions on local Republican Facebook pages. Near the end of 2018, local Republican parties started to see a much higher degree of interactions on their posts compared to local Democratic parties. We show how this increase in engagement was unique to Facebook and happened across a range of over a thousand local parties. In addition, we use a changepoint model to identify when the change happened and find it lines up with reported information about the change in Facebook’s algorithm in 2018. We conclude that it seems possible that changes in how Facebook rated content led to a doubling of the total shares of local Republican party posts compared to local Democratic party posts in the first half of 2019 even though Democratic parties posted more often during this period. Regardless of Facebook’s motivations, their decision to change the algorithm might have given local Republican parties greater reach to connect with citizens and shape political realities for Americans. The fact that private companies can so easily control the political information flow for millions of Americans raises clear questions for the state of democracy.
Living with cows, sheep and endemic disease in the North of England: Embodied care, biosocial collectivities and killability
Authors: Holloway Lewis , Mahon Niamh , Clark Beth , Proctor Amy
Published: June 2022

This paper engages with debates surrounding practices of care in complex situations where human and non-human lives are entangled. Focusing on the embodied practices of care involving farmers, their advisers and cows and sheep in the North of England, the paper explores how biosocial collectivities fabricate care around endemic health conditions in specific farming situations. Based on in-depth research with farmers and advisers, the paper examines how Bovine Viral Diarrhoea (BVD) and lameness are made ‘visible’ and become cared about, what practices are mobilised in response to an evident need to care, and how some animals are, paradoxically, made ‘killable’ in the practising of care for populations of cows and sheep. The paper discusses how the perspectives of farmers and advisers are aligned in developing practices of care for animals, although there are some tensions and differences between these groups. Advisers focus on making endemic diseases important to farmers, so that they become enrolled into taking prescribed action. However, the sets of competing priorities farmers have to address, in complex on-farm situations, along with some resistance to taking prescribed action, produces other perspectives on and practices of care. The paper concludes by emphasising the problematics of practising care in farming, showing how care for endemic disease coexists with harm to some animals and the reproduction of modes of farming which make it more likely that endemic conditions persist.
Change in axial length after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment
Authors: Shi Jiemei , Wu Kaicheng , Wen Huiming , Wei Jiaojiao , Zong Yuan , Yu Jian , Zhu Haohao , Jiang Chunhui
Published: June 2022

Background

We aimed to explore the changes in the axial length and related factors after vitrectomy for rhegmatogenous retinal detachment (RRD).

Methods

This study retrospectively evaluated patients who underwent vitrectomy with silicone oil (SO) tamponade for RRD and subsequent silicone oil removal at our clinic. Using a Zeiss IOLMaster 700, axial length was measured before vitrectomy for RRD and SO removal. The change in axial length (ΔAL) was calculated, and multivariate binary logistic regression analysis was performed to investigate the potential correlation between ΔAL and clinical factors, such as preoperative hypotony, extreme myopia, age, macular involvement, choroidal detachment, operation duration, and operation history.

Results

In total, 213 eyes from 213 patients were included. The mean axial length changed significantly pre- and post-vitrectomy (25.98 ± 2.87 mm and 26.25 ± 3.07 mm, respectively, P < 0.001); the mean ΔAL was 0.37 ± 0.62 mm. Multivariate binary logistic regression analysis showed that preoperative hypotony and extreme myopia were significantly correlated with the ΔAL (P = 0.001 and P = 0.001, respectively). A higher proportion of hypotonic eyes had ΔAL ≥ 0.3 mm (33/76 in hypotony eyes and 32/137 in others; P = 0.003). A higher proportion of extremely myopic eyes also had a ΔAL ≥ 0.3 mm (23/46 in extremely myopic eyes and 42/167 in others; P = 0.002).

Conclusion

For patients with RRD and cataracts, as axial length changed significantly after vitrectomy in those with hypotony or extreme myopia, secondary lOL implantation should be considered.
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

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

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

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

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

I 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

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

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]
Ionic Liquids Assisted Topical Drug Delivery for Permeation Enhancement: Formulation Strategies, Biomedical Applications, and Toxicological Perspective
Authors: Navti Prerana D. , Pandey Abhijeet , Nikam Ajinkya Nitin , Padya Bharath Singh , Kalthur Guruprasad , Koteshwara Kunnatur B. , Mutalik Srinivas
Published: June 2022

Topical drug delivery provides several benefits over other conventional routes by providing localizing therapeutic effects and also avoids the gastrointestinal tract circumventing the first-pass metabolism and enzymatic drug degradation. Being painless, the topical route also prevents the difficulties linked with the parenteral route. However, there are limitations to the current topical systems which necessitate the need for further research to find functional excipients to overcome these limitations. This review deals in depth with the ionic liquids concerning their physicochemical properties and applicability as well as their role in the arena of topical drug delivery in permeation enhancement, bioavailability enhancement of the drugs by solvation, and drug moiety modification. The review gives a detailed insight into the recent literature on ionic liquid–based topical formulations like ionic liquid–based emulsions, active pharmaceutical ingredient-ionic liquids, ionic liquid–based bacterial cellulose membranes, topical small interfering RNA (siRNA) delivery, and ionogels as a possible solutions for overcoming the challenges associated with the topical route. This review also takes into account the toxicological aspects and biomedical applications of ionic liquids.

Graphical Abstract
My Modern Age: The Constructed Photographs of Eiko Yamazawa
Authors: Yamagata Mihoko
Published: June 2022

Curated by Mihoko Yamagata

Introduction by Kyoko Jimbo

Text in italics = curator’s commentary
Management Development and Workers’ Efficiency of Insurance Companies In Nigeria
Authors: Alagah A D Alagah A D
Published: June 2022

This study sought to examine the stimulating influence of management development on workers' efficiency of the insurance industry in Rivers State. Correctional research design was applied. The Krejcie and Morgan sample size determination table was employed in a bid to determine the sample size. Hence, the sample size is fifty-six; 27 managers and 28 supervisors drawn from the population size of 62 from the 10 insurance companies under review. The outcome of the analysis led to the finding that experiential learning, management training, and technology has significant effects on workers’ efficiency. The Spearman’ Rank Order Correlation Coefficient was used via the aid of Statistical Package for Social Sciences. It was recommended that: Experiential learning should be encouraged as it gives room for critical thinking, enhances problem solving and increases decision making skills which will translate into workers' efficiency for the insurance companies. Management should be consistent with having management trainings as this will help boost employees’ confidence, while creating the ability of the trainee to implement company strategies and mitigate avoidable damages that could result in workers' inefficiency. Technology should be introduced into management development as will improve existing processes, while revealing newer ways to accomplish tasks with the aim of harnessing the potentials of the employees despite seeking workers’ efficiency.
Physiotherapy and medicines management: A pilot study
Authors: Waldock Colin , Thomas Trudy , Amrani-Chtiar Camilia
Published: June 2022

Aim

Only 2.7% of UK registered physiotherapists are qualified to prescribe. This pilot study explored attitudes to medicine use, barriers to prescribing in practice for physiotherapists and training needs.

Methods

An online questionnaire was distributed via professional networks. Descriptive statistics were used to quantify data with t-tests and Mann-Whitney-U tests were used to explore correlations in data. Qualitative (free text) data were analysed for common themes using thematic analysis.

Findings

A total of 51 physiotherapists (37% n= 19) prescribers completed the questionnaire. Attitudes towards medicines were similar. Respondents understood the benefits of prescribing but identified personal, professional and organisational barriers. Lack of pharmacology knowledge was reported by 56.7% (n=25) and identified as a training need among physiotherapists who had qualified in the UK (n=44), 40% (n= 20) of respondents identified a lack of support for physiotherapist prescribing in the workplace.

Conclusions

Exploring physiotherapists' attitudes towards medicines and barriers to implementation of prescribing offers the potential for supportive interventions and future research.
What are dietitians prescribing? An evaluation of the prescribing practice of a nutrition support dietitian
Authors: Culkin Alison
Published: June 2022

Background

In 2016, registered dietitians in the UK were granted supplementary prescribing rights. There is currently little published data on the prescribing practices of dietitians.

Aim

The prescribing practice of a nutrition support dietitian specialising in intestinal rehabilitation was evaluated.

Methods

Over a six-month period, the dietitian collected data on her prescribing practice using the hospital proforma and then transferred the information to Excel.

Findings

Over a 6 month period, the dietitian prescribed for 24 patients. The most common prescriptions included parenteral nutrition, intravenous fluids and electrolytes, oral rehydration solutions and micronutrients. Medications deprescribed included codeine phosphate, loperamide, lansoprazole, forceval and folic acid.

Conclusion

The evaluation demonstrated that a nutrition support dietitian was able to prescribe a range of different medications related to the nutritional management of patients with intestinal failure. Further work is required to assess patient satisfaction, economic impact and attitude of other healthcare professionals.
Traveling tunable laser projector for UV-blue disinfection dose determinations
Authors: Larason Thomas , Grantham Steven , Zarobila Clarence , Zong Yuqin , Schuit Michael , Holland Brian , Wood Stewart , Krause Melissa , Miller C. Cameron
Published: June 2022

As the COVID-19 pandemic was overtaking the world in the spring of 2020, the National Institute of Standards and Technology (NIST) began collaborating with the National Biodefense Analysis and Countermeasures Center to study the inactivation of SARS-CoV-2 after exposure to different ultraviolet (UV) and blue light wavelengths. This paper describes a 1 kHz pulsed laser and projection system used to study the doses required to inactive SARS-CoV-2 over the wavelength range of 222 to 488 nm. This paper builds on NIST’s previous work for water pathogen inactivation using UV laser irradiation. The design of the laser and projection system and its performance in a Biosafety Level 3 (BSL-3) laboratory are given. The SARS-CoV-2 inactivation results (published elsewhere by Schuit, M.A., et al., expected 2022) demonstrate that a tunable laser projection system is an invaluable tool for this research.
Raman gain control in optical fibers with orbital-angular-momentum-induced chirality of light
Authors: Liu Xiao , Ma Zelin , Antikainen Aku , Ramachandran Siddharth
Published: June 2022

Stimulated Raman scattering is a particularly robust nonlinearity, occurring in virtually every material because its spectral linewidth and associated frequency shift do not typically depend on phases or directions (i.e. wavevectors) of the interacting light beams. In amorphous materials such as glass fibers, Raman bandwidths are large, enabling its use as a broadband gain element. This ubiquity makes it a versatile means for achieving optical amplification or realizing lasers over a large range of pulsewidths at user-defined colors. However, this ease of deploying the effect also presents itself as a stubborn source of noise in fiber-based quantum sources or parasitic emission in fiber lasers. Here, we show that orbital angular momentum carrying light beams experiencing spin-orbit interactions yield novel phase-matching criteria for Raman scattering. This enables tailoring its spectral shape (by over half the Raman shift in a given material) as well as strength (by ∼ 100×) simply by controlling light’s topological charge – a capability of utility across the multitude of applications where modulating Raman scattering is desired.
Prism-based approach to create intensity-interferometric non-diffractive cw light sheets
Authors: Hildén Panu , Kaivola Matti , Shevchenko Andriy
Published: June 2022

Light sheets are optical beam-like fields with one-dimensional intensity localization. Ideally, the field intensity should be independent of the longitudinal and one of the transverse coordinates, which is difficult to achieve even for truncated light sheets. In this work, we present a general theoretical framework for intensity-interferometric continuous wave (cw) light sheets formed by overlapping the interference fringe patterns of mutually uncorrelated frequency components of the field. We show that the key parameters of the light sheets can be calculated using simple analytical expressions. We propose a practical way to generate such light sheets with the help of prisms and demonstrate numerically the abilities of the method. Both bright and dark light sheets with an exceptionally small thickness and long divergence-free propagation distance are possible to generate. We also show that the transverse profile of the generated light sheets can be shaped by modifying the spectrum of the light. We believe our findings advance the beam-engineering technology and its applications.
Persistent visible luminescence of SrF2:Pr3+ for ratiometric thermometry
Authors: Li Leipeng , Wu Zhuqin , Lv Pinshu , Wang Chunzheng , Han Xiumei , Yang Yanmin
Published: June 2022

Luminescence-based thermometry, especially the ratiometric temperature sensing technology, has attracted considerable attention recently due to its characteristics such as non-contact operating mode and strong capacity of resisting disturbance. Differing from the conventional strategy that usually needs continuous excitation, here an optical thermometry, which we have named the persistent luminescence intensity ratio (PLIR) thermometry, is proposed. The PLIR thermometry relies on the optical material SrF2:Pr3+ that could emit luminescence for several hours and even longer after being charged by X-ray. It has been demonstrated that the PLIR is sensitive to the variation of temperature and complies with the Boltzmann distribution. More importantly, the reliability of the proposed PLIR thermometry is verified. Our work may inspire others to develop more persistent luminescence thermometry.
High bandwidth series-biased green micro-LED array toward 6 Gbps visible light communication
Authors: Lin Runze , Jin Zuxin , Qiu Pengjiang , Liao Yue , Hoo Jason , Guo Shiping , Cui Xugao , Tian Pengfei
Published: June 2022

In this Letter, a record modulation bandwidth of 1.31 GHz was achieved by a 10 µm c-plane green micro light emitting diode (micro-LED) at a current density of 41.4 kA/cm2. Furthermore, by designing a series-biased 20 µm micro-LED with higher light output power, combined with an orthogonal frequency division multiplexing modulation scheme, a maximum data rate of 5.789 Gbps was achieved at a free-space transmission distance of 0.5 m. This work demonstrates the prospect of c-plane polar green micro-LED in ultrahigh-speed visible light communication, which is expected to realize a high-performance wireless system in the future.
Large-scale few-layered MoS2 as a saturable absorber for Q-switching operation at 2.3 µm
Authors: Zha Fangyuan , Chu Hongwei , Pan Zhongben , Pan Han , Zhao Shengzhi , Yang Ming , Li Dechun
Published: June 2022

In this Letter, the fabrication of large-scale (50.8 mm in diameter) few-layered MoS2 with physical vapor deposition on sapphire is described. Open-aperture Z-scan technology with a home-made excitation source at 2275 nm was applied to explore its nonlinear saturable absorption properties. The as-grown few-layered MoS2 membrane possessed a modulation depth of 17% and a saturable intensity of 1.185 MW cm−2. As a consequence, the deposited MoS2 membrane was exploited as a saturable absorber to realize a passively Q-switched Tm:YAP laser for the first time, to the best of our knowledge. Pulses as short as 316 ns were generated with a repetition rate of 228 kHz, corresponding to a peak power of 5.53 W. Results confirmed that the two-dimensional layered MoS2 could be beneficial for mid-infrared photonic applications.