bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of allogeneic transplantation for hemoglobin Bart’s hydrops fetalis syndrome in Hong Kong
Authors: Chan Wilson Y. K. , Lee Pamela P. W. , Lee Vincent , Chan Godfrey C. F. , Leung Wing , Ha S. Y. , Cheuk Daniel K. L.
Published: May 2021

Background

Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized local territory‐wide experience and outcomes of BHFS patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in Hong Kong.

Methods

All BHFS patients who underwent allogeneic HSCT in Hong Kong, either in one of the two former pediatric transplant centers (Queen Mary Hospital and Prince of Wales Hospital) on or before 2019 or in the single territory‐wide pediatric transplant center (Hong Kong Children's Hospital) since 2019, from January 1, 1996, till December 31, 2020, were included. Basic demographic data, perinatal history, transplant details, long‐term outcomes, and morbidities were reviewed.

Results

Total five allogeneic HSCT were performed in two males and three females at a median age of 22 months, which include one 8/8 matched‐sibling bone marrow transplant, one 5/6 matched‐sibling cord blood transplant with HLA‐DR antigenic mismatch, two 12/12 matched‐unrelated peripheral blood stem cell transplant (PBSCT), and one haploidentical PBSCT with TCRαβ/CD45RA depletion from maternal donor. Neutrophil and platelet engrafted (>20 × 109/L) at a median of 15 and 22 days, respectively. All achieved near full donor chimerism at 1 month. All patients survived and remained transfusion‐independent without significant morbidities with median follow‐up duration of 10 years.

Conclusion

To conclude, local data demonstrated favorable outcome of allogeneic HSCT for BHFS patients, but sample number is small. Non‐directive approach in counseling and international collaboration is recommended.
Myofibroblastoma of the breast showing rare palisaded morphology and uncommon desmin‐ and CD34‐negative immunophenotype: A case report
Authors: Akiya Masashi , Osako Tomo , Morizono Hidetomo , Furuta Noriyuki , Kikuchi Mari , Ueno Takayuki , Ohno Shinji , Takeuchi Kengo
Published: May 2021

Myofibroblastoma is a rare benign mesenchymal tumor typically arising in the breast. We report a diagnostically challenging case of myofibroblastoma of the breast showing a rare palisaded morphology and an uncommon desmin‐ and CD34‐negative immunophenotype. A 73‐year‐old man underwent an excision for an 8 mm‐sized breast mass. Histology revealed that the tumor was composed of fascicles of bland spindle cells showing prominent nuclear palisading and Verocay‐like bodies. First, schwannoma, malignant peripheral nerve sheath tumor, and synovial sarcoma were suspected given the palisaded morphology. However, none of them was confirmed by immunohistochemical or molecular analyses. Next, a palisaded variant of myofibroblastoma was suspected by the morphology and coexpression of estrogen, progesterone and androgen receptors, BCL2 and CD10 in immunohistochemistry. However, the key diagnostic markers, desmin and CD34, were both negative. Finally, the diagnosis of myofibroblastoma was confirmed by detecting RB1 loss in immunohistochemistry and monoallelic 13q14 deletion (RB1 and FOXO1 loss) by fluorescence in situ hybridization assay. For the correct diagnosis of myofibroblastoma, it is important for pathologists to recognize the wide morphological spectrum, including a palisaded morphology, and the immunophenotypical variations, including desmin‐ and CD34‐negative immunophenotypes, and to employ a comprehensive diagnostic analysis through combined histological, immunohistochemical and molecular evaluations.
Implications of exchange rate volatility for trade: Volatility measurement matters
Authors: Roehling Allison
Published: May 2021

The relationship between exchange rate volatility and trade is inconclusive in the current literature. I find evidence this is due to variation in definitions of exchange rate volatility. My results suggest common volatility measures weigh variation differently over time and economic conditions. Using an autoregressive distributed lag model, I demonstrate the importance of volatility measurement to the estimated relationship of volatility and exports. I find substantial variation across volatility measures, trading partners, and pre‐/post‐2008. When significant, the relationship is almost always negative, albeit unsubstantial. In order to overcome the literature's mixed results, the definition of volatility needs to be standardized.
Vibration Characteristics Diagnosis and Estimation of Fault Sizes in Rolling Contact Bearings: A Model-Based Approach
Authors: Jamadar I. M.
Published: May 2021

A novel model-based technique is presented in this paper for the estimation of the fault size in different components of rolling contact bearings. A detailed dimensional analysis of the problem is carried out and an experimental methodology using the Box–Behnken design is applied to generate the experimental data set. First, the analysis of the vibration acceleration amplitude at fault frequency, its dependence on the bearing operating, and fault parameters using the obtained vibration data set are carried out by statistical analysis of variance. Numerical equations are developed then using the experimental data set for the correlation of the vibration acceleration amplitude in the frequency domain with the fault sizes based on the developed dimensionless terms. A hybrid backpropagation neural network integrating genetic algorithm is also developed to check the computational performance of the developed model equations. Validation of the proposed method is carried experimentally also for three seeded defect sizes on the outer race, inner race, and rolling element. The maximum model accuracy observed is for the inner race defect case with a predictive accuracy of 99.44% and for the roller defect case, it is 98.77%. The deviance observed for the model predictive performance is maximum for the outer race defect case with the least accuracy of 90.47% amongst all.
Thickness-dependent optical properties of aluminum nitride films for mid-infrared wavelengths
Authors: Beliaev Leonid Yu. , Shkondin Evgeniy , Lavrinenko Andrei V. , Takayama Osamu
Published: May 2021

We present a comparative study of optical properties of aluminum nitride (AlN) thin films with different thicknesses. The films with thicknesses ranging from 66 to 303 nm were deposited by reactive sputtering and plasma enhanced atomic layer deposition (PEALD). Permittivity was extracted from an ellipsometry and Fourier-transform infrared (FTIR) spectroscopy reflection measurements. Our particular focus is on the influence of the deposition method and the film thickness on the AlN dielectric function. Here, we show that both PEALD-deposited and sputtered AlN films exhibit a monotonic dependence of negative permittivity on their thickness for vast mid-IR wavelengths including the reststrahlen band around 11.5–15 μm (∼870–667cm−1). By structural analysis, it was shown that PEALD-deposited layers contain a lower amount of oxygen and have smoother surfaces than deposited by the sputtering technique. On the other hand, sputtered films have higher densities and crystallinity, which results in the higher background permittivity (ε∞). In FTIR spectra of the PEALD-deposited layers, two specific features are observed, which can be explained by a higher concentration of nitrogen due to nitrogen-rich plasma in the ALD process. Such peculiarities of the optical properties of AlN films should be taken into account in potential applications of this material for metamaterials and nanostructured systems.
Development of an 80-word clinical version of the modified rhyme test (MRT80)
Authors: Brungart Douglas S. , Makashay Matthew J. , Sheffield Benjamin M.
Published: May 2021

The modified rhyme test [MRT; House, Williams, Hecker, and Kryter. (1965). J. Acoust. Soc. Am. 37, 158–166] is a widely used test for measuring the intelligibility of communication systems [ANSI (2009). S3.2 (American National Standards Institute, New York)] but has never gained widespread acceptance as a clinical test of speech intelligibility for listeners who are hearing impaired (HI). In this study, a clinical version of the MRT consisting of two 80-word lists was developed and tested on 2394 service members with varying levels of hearing loss. The test used a factorial design incorporating two speech levels [70 and 78 dB sound pressure level (SPL)], two signal-to-noise ratios (+4 and −4 dB), and two binaural conditions (diotic and binaural). High-frequency emphasis reduced the impact of audibility for HI listeners, focusing the test on the distortion component of hearing loss. The results show that listeners with normal hearing (NH) obtained an average score of 80% correct on the MRT80 test. Listeners with a moderate hearing impairment scored an average of 70% correct. The overall level had little impact on performance for either NH or HI listeners. The results demonstrate that the MRT80 test could be a useful test to assess the distortion effects of hearing loss on speech intelligibility, particularly in cases where it is desirable to use a closed-set test for automatic administration.
Chapter 2: Reversing Policy Neglect in U.S. Physical Education: A Policy-Focused Primer
Authors: van der Mars Hans , Lawson Hal A. , Mitchell Murray , Ward Phillip
Published: May 2021

Notwithstanding the contributions of a few policy experts, overall physical education is constrained by policy illiteracy and neglect. A brief historical perspective on physical education policy provides a foundation for “a policy primer” founded on three recurring needs: (a) antecedent and corequisite factors meriting attention in support of policy improvement, (b) field-wide capacity-building in support of policy advocacy and improvement, and (c) specialized policy courses and seminars in physical education teacher education and doctoral physical education teacher education programs. Recommendations for policy-focused research and development structure a new agenda that merits attention and action.
A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection
Authors: Humphries Fiachra , Shmuel-Galia Liraz , Jiang Zhaozhao , Wilson Ruth , Landis Philip , Ng Sze-Ling , Parsi Krishna Mohan , Maehr Rene , Cruz John , Morales Angel , Ramanjulu Joshi M. , Bertin John , Pesiridis G. Scott , Fitzgerald Katherine A.
Published: May 2021

Pharmacological activation of STING protects against SARS-CoV-2 infection.
Emergence of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Coharboring a
bla
NDM-1
-Carrying Virulent Plasmid and a
bla
KPC-2
-Carrying Plasmid in an Egyptian Hospital
Authors: Ahmed Mohamed Abd El-Gawad El-Sayed , Yang Yanxian , Yang Yongqiang , Yan Bin , Chen Guanping , Hassan Reem Mostafa , Zhong Lan-Lan , Chen Yuan , Roberts Adam P. , Wu Yiping , He Ruowen , Liang Xiaoxue , Qin Mingyang , Dai Min , Zhang Liyan , Li Hongyu , Yang Fan , Xu Lingqing , Tian Guo-Bao
Published: May 2021

CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment.
Supplemental Material: The impact of a tear in the subducted Indian plate on the Miocene geology of the Himalayan-Tibetan orogen
Authors: Wang Rui , al. et
Published: May 2021

Published ages and geochemical compositions of Cenozoic igneous rocks from the Gangdese belt and Himalayas.
Long-term outcome of cultivated oral mucosal epithelial transplantation for fornix reconstruction in chronic cicatrising diseases
Authors: Komai Seitaro , Inatomi Tsutomu , Nakamura Takahiro , Ueta Mayumi , Horiguchi Go , Teramukai Satoshi , Kimura Yasuko , Kagimura Tatsuo , Fukushima Masanori , Kinoshita Shigeru , Sotozono Chie
Published: May 2021

Background/aims

To investigate the long-term outcomes of cultivated oral mucosal epithelial transplantation (COMET) for fornix reconstruction in eyes with chronic cicatrising disease.

Methods

This retrospective cohort study involved 16 eyes of 15 patients who underwent COMET for symblepharon release and fornix reconstruction between June 2002 and December 2008. The mean postoperative follow-up period was 102.1±46.0 months (range: 32–183 months). The treated cicatrising disorders included ocular cicatricial pemphigoid (OCP, five eyes), thermal/chemical injury (three eyes) and other chronic diseases (seven eyes; including recurrent pterygium (two eyes), Stevens-Johnson syndrome (one eye) and graft-versus-host disease (one eye)). Ocular-surface appearance was evaluated before surgery, at 1, 4, 12 and 24 weeks postoperative, and then annually based on the previously reported scoring system. Main outcome measures included overall and disease-specific fornix-reconstruction success probabilities analysed by the Kaplan-Meier survival curve. Symblepharon/fornix-shortening recurrence at 24 weeks postoperative, and its relationship to long-term surgical success was also examined.

Results

At 5 years postoperative, the mean±SD overall fornix-reconstruction success probability was 79.6%±10.7%, and success probability for thermal/chemical injury and OCP was 100% and 53.3%±24.8%, respectively (p=0.53, log-rank test). The 3-year success probability was significantly higher in the no-disease-recurrence group at 24 weeks postoperative (13 eyes) than in the disease-recurrence group (three eyes) (100% and 33.3%±27.2%, respectively) (p=0.0073, log-rank test).

Conclusion

COMET was found to be safe and effective for symblepharon release and long-term fornix reconstruction in eyes with chronic cicatrisation. Although the 5-year success probability differed depend on the underlying disease, ocular-surface appearance at 24 weeks postoperative is a factor for predicting long-term outcome.
Interpretation of change scores for the National Eye Institute Visual Function Questionnaire-25: the minimally important difference
Authors: Burr Jennifer M , Cooper David , Ramsay Craig R , Che Hamzah Jemaima , Azuara-Blanco Augusto
Published: May 2021

Aim

To estimate the minimally important difference (MID) in change in National Eye Institute Visual Function Questionnaire-25 (VFQ-25) composite score using methods aligned with patient perception.

Methods

Retrospective analysis of prospectively collected data from adults with primary angle closure or primary angle closure glaucoma enrolled in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction study. We included data from 335 participants with patient reported visual function (VFQ-25) and health status measured by the EQ-5D-3L over 36 months. We used the recommended anchor-based methods (receiver operating characteristic (ROC), predictive modelling and mean change) to determine the MID of the VFQ-25. EQ-5D-3L anchor change was defined as none (<0.065); minimal (0.065≤EQ-5D-3L change ≤0.075 points) and greater change (>0.075 points).

Results

Mean baseline VFQ-25 score was 87.6 (SD 11.8). Estimated MIDs in the change in VFQ-25 scores (95% CI) were 10.5 (1.9 to 19.2); 3.9 (−2.3 to 10.1); 5.8 (1.9 to 7.2) and 8.1 (1.7 to 14.8) for the ‘within-patient’, ‘between-patient’ change, ROC and predictive modelling anchor methods respectively. Excluding estimates from the methodologically weaker ‘within-patient’ method, the MID of a change in VFQ-25 composite score is 5.8 (median value).

Conclusions

Estimates of the MID using multiple methods assist in the interpretation of the VFQ scores. In the context of early glaucoma related visual disability, a change score of around six points on the VFQ-25 is likely to be important to patients. Further confirmatory research is required. Studies comparing changes in patient-reported outcome measure scores with a global measure of patients’ perceived change are required.
Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial
Authors: Reichel Felix Friedrich , Michalakis Stylianos , Wilhelm Barbara , Zobor Ditta , Muehlfriedel Regine , Kohl Susanne , Weisschuh Nicole , Sothilingam Vithiyanjali , Kuehlewein Laura , Kahle Nadine , Seitz Immanuel , Paquet-Durand Francois , Tsang Stephen H , Martus Peter , Peters Tobias , Seeliger Mathias , Bartz-Schmidt Karl Ulrich , Ueffing Marius , Zrenner Eberhard , Biel Martin , Wissinger Bernd , Fischer Dominik
Published: May 2021

Aims

To determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).

Methods

Details of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.

Results

No adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.

Conclusion

The results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.
Behavioral interventions to improve population health outreach for hepatitis C screening: randomized clinical trial
Authors: Mehta Shivan J , Day Susan C , Norris Anne H , Sung Jessica , Reitz Catherine , Wollack Colin , Snider Christopher K , Shaw Pamela A , Asch David A
Published: May 2021

Objective

To evaluate whether opt out framing, messaging incorporating behavioral science concepts, or electronic communication increases the uptake of hepatitis C virus (HCV) screening in patients born between 1945 and 1965.

Design

Pragmatic randomized controlled trial.

Setting

43 primary care practices from one academic health system (Philadelphia, PA, USA) between April 2019 and May 2020.

Participants

Patients born between 1945 and 1965 with no history of screening and at least two primary care visits in the two years before the enrollment period.

Interventions

This multilevel trial was divided into two studies. Substudy A included 1656 eligible patients of 17 primary care clinicians who were randomized in a 1:1 ratio to a mailed letter about HCV screening (letter only), or a similar letter with a laboratory order for HCV screening (letter+order). Substudy B included the remaining 19 837 eligible patients followed by 417 clinicians. Active electronic patient portal users were randomized 1:5 to receive a mailed letter about HCV screening (letter), or an electronic patient portal message with similar content (patient portal); inactive patient portal users were mailed a letter. In a factorial design, patients in substudy B were also randomized 1:1 to receive standard content (usual care), or content based on principles of social norming, anticipated regret, reciprocity, and commitment (behavioral content).

Main outcome measures

Proportion of patients who completed HCV testing within four months.

Results

21 303 patients were included in the intention-to-treat analysis. Among the 1642 patients in substudy A, 19.2% (95% confidence interval 16.5% to 21.9%) completed screening in the letter only arm and 43.1% (39.7% to 46.4%) in the letter+order arm (P<0.001). Among the 19 661 patients in substudy B, 14.6% (13.9% to 15.3%) completed screening with usual care content and 13.6% (13.0% to 14.3%) with behavioral science content (P=0.06). Among active patient portal users, 17.8% (16.0% to 19.5%) completed screening after receiving a letter and 13.8% (13.1% to 14.5%) after receiving a patient portal message (P<0.001).

Conclusions

Opt out framing and effort reduction by including a signed laboratory order with outreach increased screening for HCV. Behavioral science messaging content did not increase uptake, and mailed letters achieved a greater response rate than patient portal messages.

Trial registration

ClinicalTrials.gov
NCT03712553
.
Face-to-face physiotherapy compared with a supported home exercise programme for the management of musculoskeletal conditions: protocol of a multicentre, randomised controlled trial—the REFORM trial
Authors: Withers Hannah G , Glinsky Joanne V , Chu Jackie , Jennings Matthew D , Hayes Alison J , Starkey Ian J , Palmer Blake A , Szymanek Lukas , Cruwys Jackson J , Wong David , Duong Kitty , Barnett Anne , Tindall Matthew J , Lucas Barbara R , Lambert Tara E , Sherrington Catherine , Maher Christopher G , Ferreira Manuela L , Taylor Deborah A , Harvey Lisa A
Published: May 2021

Introduction

Exercise, support and advice are considered core components of management for most musculoskeletal conditions and are typically provided by physiotherapists through regular face-to-face treatments. However, exercise can be provided remotely as part of a home exercise programme, while support and advice can be provided over the telephone. There is initial evidence from trials and systematic reviews to suggest that remotely provided physiotherapy can be used to manage a variety of musculoskeletal conditions safely and effectively.

Methods and analysis

The aim of this single-blind randomised controlled non-inferiority trial is to determine whether a supported home exercise programme is as good as or better than face-to-face physiotherapy for the treatment of musculoskeletal conditions. Two hundred and ten participants will be recruited from five public hospitals in Sydney, Australia. Participants will be randomised to either the supported home exercise group or the face-to-face physiotherapy group. Participants allocated to the supported home exercise group will initially receive one face-to-face session with the trial physiotherapist and will then be managed remotely for the next 6 weeks. Participants allocated to the face-to-face physiotherapy group will receive a course of physiotherapy as typically provided in Sydney government hospitals. The primary outcome is function measured by the Patient Specific Functional Scale at 6 weeks. There will be nine secondary outcomes measured at 6 and 26 weeks. Separate analyses will be conducted on each outcome, and all analyses will be conducted on an intention-to-treat basis. A health economic evaluation will be conducted from a health funder plus patient perspective.

Ethics and dissemination

Ethical approval was obtained on the 17 March 2017 from the Northern Sydney Local Health District HREC, trial number HREC/16HAWKE/431-RESP/16/287. The results of this study will be submitted for publication to peer-reviewed journals and be presented at national and international conferences. Recruitment commenced in March 2019, and it is anticipated that the trial will be completed by December 2021. This trial will investigate two different models of physiotherapy care for people with musculoskeletal conditions.

Trial registration number

CPMP/ICH-135/95.

Protocol version

The most recent version of the protocol is V.1.2 dated November 2019.
Mortality attributable to fine particulate matter in Asia, 2000–2015: a cross-sectional cause-of-death analysis
Authors: Somboonsin Pattheera , Canudas-Romo Vladimir
Published: May 2021

Objectives

To investigate the effect that particulate matter with a diameter of 2.5 μg (PM2.5) had on mortality in Asian populations in years 2000–2015.

Setting

Mortality and level of PM2.5data from the United Nations, Global Burden of Disease and University of Chicago were used.

Outcome measures

Age pattern of mortality and the number of life-years lost (LYL) attributable to PM2.5in years 2000–2015. LYL were further separated into causes of death to quantify the contribution of each cause.

Results

Ischaemic heart disease (IHD) mortality increased to represent over 31% of the LYL attributable to PM2.5between 2005–2010 and 2010–2015 in Asia (females 31% and males 35%). However, great diversity in LYL attributable to PM2.5by causes-of-death were found across the region, with IHD proportions of LYL ranging from 25% to 63% for males from Eastern and Central Asia, respectively. Similar diversity was observed for mortality attributable to PM2.5for other causes of death across Asia: chronic obstructive pulmonary disease (LYL ranging from 6% to 28%), lung cancer (4% to 20%) and stroke (11% to 22%).

Conclusion

PM2.5is a crucial component in the rising health effects in Asia. The diverse trends in cause-specific mortality attributable to PM2.5creates a further challenge for health systems in the region. These findings highlight that immediate interventions are needed to mitigate the increasing levels of air pollution and with that reduce its detrimental effect on the health and mortality of Asian populations.
Comparison of trauma management between two major trauma services in Riyadh, Kingdom of Saudi Arabia and Melbourne, Australia
Authors: Alsenani Mohammad , A Alaklobi Faisal , Ford Jane , Earnest Arul , Hashem Waleed , Chowdhury Sharfuddin , Alenezi Ahmed , Fitzgerald Mark , Cameron Peter
Published: May 2021

Introduction

The burden of injury in the Kingdom of Saudi Arabia (KSA) has increased in recent years, but the country has lacked a consistent methodology for collecting injury data. A trauma registry has been established at a large public hospital in Riyadh from which these data are now available.

Objectives

We aimed to provide an overview of trauma epidemiology by reviewing the first calendar year of data collection for the registry. Risk-adjusted analyses were performed to benchmark outcomes with a large Australian major trauma service in Melbourne. The findings are the first to report the trauma profile from a centre in the KSA and compare outcomes with an international level I trauma centre.

Methods

This was an observational study using records with injury dates in 2018 from the registries at both hospitals. Demographics, processes and outcomes were extracted, as were baseline characteristics. Risk-adjusted endpoints were inpatient mortality and length of stay. Binary logistic regression was used to measure the association between site and inpatient mortality.

Results

A total of 2436 and 4069 records were registered on the Riyadh and Melbourne databases, respectively. There were proportionally more men in the Saudi cohort than the Australian cohort (86% to 69%). The Saudi cohort was younger, the median age being 36 years compared with 50 years, with 51% of injuries caused by road traffic incidents. The risk-adjusted length of stay was 4.4 days less at the Melbourne hospital (95% CI 3.95 days to 4.86 days, p<0.001). The odds of in-hospital death were also less (OR 0.25; 95% CI 0.15 to 0.43, p<0.001).

Conclusions

This is the first hospital-based study of trauma in the kingdom that benchmarks with an individual international centre. There are limitations to interpreting the comparisons, however the findings have established a baseline for measuring continuous improvement in outcomes for KSA trauma services.
Tai Chi postural training for dyskinesia rehabilitation: a study protocol for a randomised controlled trial in convalescent ischaemic stroke patients
Authors: Jing Chengyang , Li Kuangshi , Li Zongheng , Sun Yiting , Wu Jiabao , Li Yingjie , Li Yuyue , Zhou Li , Zhang Zhe , Zhao Mingzhi , Zhang Yong
Published: May 2021

Introduction

Acute ischaemic stroke (AIS) is not only seriously damaging to the physical and mental health of patients, but also has become a major social public health problem. Effective dyskinesia rehabilitation treatment in convalescence is of great significance for AIS patients’ prognosis and quality of life. Tai Chi (TC) shows great potential in improving motor function. This trial aims to evaluate the clinical efficacy of modified TC postural training (TPT), and to explore the related central-peripheral neurotransmitter mechanisms.

Methods/design

The proposed study will be a multicentre randomised controlled trial. The trial will randomise 120 eligible AIS patients in a 1:1 ratio to receive TPT or Bobath rehabilitation training. Each training session will last 40 min and will be implemented once a day and five times per week (from Monday to Friday) in a duration of 4 weeks. After finishing the 4-week treatment, another 3-month follow-up period will be seen. Root mean square generated from the surface electromyogram (sEMG) will be the primary outcome. Other sEMG time-domain parameters and frequency-domain parameters and clinical scales assessment will be the secondary outcomes. Peripheral blood samples will be collected at baseline and at the end of 4-week treatment, which will be used to explore the related therapeutic mechanisms. Intention-to-treat analysis and per-protocol analysis will both be implemented in this trial.

Ethics and dissemination

The study has been approved by Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, being granted approval numbers DZMEC-KY-2020–22. The research results will be disseminated through (open access) peer-reviewed publications and presentations at conferences.

Trial registration number

ChiCTR2000032999.
Critical care work during COVID-19: a qualitative study of staff experiences in the UK
Authors: Montgomery Catherine M , Humphreys Sally , McCulloch Corrienne , Docherty Annemarie B , Sturdy Steve , Pattison Natalie
Published: May 2021

Objective

To understand National Health Service (NHS) staff experiences of working in critical care during the first wave of the COVID-19 pandemic in the UK.

Design

Qualitative study using semistructured telephone interviews and rapid analysis, interpreted using Baehr’s sociological lens of ‘communities of fate’.

Participants

Forty NHS staff working in critical care, including 21 nurses, 10 doctors and advanced critical care practitioners, 4 allied health professionals, 3 operating department practitioners and 2 ward clerks. Participants were interviewed between August and October 2020; we purposefully sought the experiences of trained and experienced critical care staff and those who were redeployed.

Setting

Four hospitals in the UK.

Results

COVID-19 presented staff with a situation of extreme stress, duress and social emergency, leading to a shared set of experiences which we have characterised as a community of fate. This involved not only fear and dread of working in critical care, but also a collective sense of duty and vocation. Caring for patients and families involved changes to usual ways of working, revolving around: reorganisation of space and personnel, personal protective equipment, lack of evidence for treating COVID-19, inability for families to be physically present, and the trauma of witnessing extreme patient acuity and death on a large scale. The stress and isolation of working in critical care during COVID-19 was mitigated by strong teamwork, camaraderie, pride and fulfilment.

Conclusion

COVID-19 has changed working practices in critical care and profoundly affected staff physically, mentally and emotionally. Attention needs to be paid to the social and organisational conditions in which individuals work, addressing both practical resourcing and the interpersonal dynamics of critical care provision.
Positive psychological profiles based on perceived health clustering in patients with cardiovascular disease: a longitudinal study
Authors: Castillo-Mayén Rosario , Luque Bárbara , Rubio Sebastián Jesús , Cuadrado Esther , Gutiérrez-Domingo Tamara , Arenas Alicia , Delgado-Lista Javier , Pérez-Martínez Pablo , Tabernero Carmen
Published: May 2021

Objectives

Psychological well-being and sociodemographic factors have been associated with cardiovascular health. Positive psychological well-being research is limited in the literature; as such, this study aimed to investigate how patients with cardiovascular disease could be classified according to their perceived mental and physical health, and to identify positive psychological profiles based on this classification and test their stability over time.

Design and setting

Longitudinal study with patients from a public hospital located in Córdoba (Spain).

Participants

This study comprised 379 cardiovascular patients (87.3% men) tested at three measurement points.

Outcome measures

Participants reported their sociodemographic variables (age, sex, educational level, employment and socioeconomic status) at phase 1, while their perceived health and variables relating to positive psychological well-being were tested at this and two subsequent time points (average interval time: 9 months).

Results

The two-step cluster analysis classified participants into three groups according to their mental and physical health levels, p<0.001: high (n=76), moderate (n=113) and low (n=189) perceived health clusters. Low perceived health was the largest cluster, comprising almost half of patients. Clusters significantly differed according to sex, p=0.002, and socioeconomic level, p=0.004. The profile analysis indicated that participants in the high perceived health cluster showed high positive affect, positivity, life satisfaction, and self-efficacy in emotion regulation, and less negative affect and use of passive strategies over the three measurement points (95% CI, all ps<0.01). Moreover, psychological profile stability for each cluster was generally found over an 18-month period, all ps<0.05.

Conclusion

Cardiovascular patients may differ in terms of their perceived health and, accordingly, in terms of other relevant variables. Perceived health clusters generated varying and generally stable psychological profiles based on positive psychological well-being variables. Psychological interventions should be adapted to patients’ requirements.
Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy
Authors: Huang Jumin , Liu Di , Wang Yuwei , Liu Liang , Li Jian , Yuan Jing , Jiang Zhihong , Jiang Zebo , Hsiao WL Wendy , Liu Haizhou , Khan Imran , Xie Ying , Wu Jianlin , Xie Yajia , Zhang Yizhong , Fu Yu , Liao Junyi , Wang Wenjun , Lai Huanling , Shi Axi , Cai Jun , Luo Lianxiang , Li Runze , Yao Xiaojun , Fan Xingxing , Wu Qibiao , Liu Zhongqiu , Yan Peiyu , Lu Jingguang , Yang Mingrong , Wang Lin , Cao Yabing , Wei Hong , Leung Elaine Lai-Han
Published: May 2021

Objective

Programmed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and Panax ginseng has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota.

Design

Syngeneic mouse models were administered GPs and αPD-1 mAb, the sensitising antitumour effects of the combination therapy on gut microbiota were assessed by faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing. To assess the immune-related metabolites, metabolomics analysis of the plasma samples was performed.

Results

We found GPs increased the antitumour response to αPD-1 mAb by increasing the microbial metabolites valeric acid and decreasing L-kynurenine, as well as the ratio of Kyn/Trp, which contributed to the suppression of regulatory T cells and induction of Teff cells after combination treatment. Besides, the microbial analysis indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders in the clinic. Furthermore, the combination therapy sensitised the response to PD-1 inhibitor in the mice receiving microbes by FMT from six non-responders by reshaping the gut microbiota from non-responders towards that of responders.

Conclusion

Our results demonstrate that GPs combined with αPD-1 mAb may be a new strategy to sensitise non-small cell lung cancer patients to anti-PD-1 immunotherapy. The gut microbiota can be used as a novel biomarker to predict the response to anti-PD-1 immunotherapy.
WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome
Authors: Hu Kun , Zatyka Malgorzata , Astuti Dewi , Beer Nicola , Dias Renuka P , Kulkarni Archana , Ainsworth John , Wright Benjamin , Majander Anna , Yu-Wai-Man Patrick , Williams Denise , Barrett Timothy
Published: May 2021

Background

Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in theWFS1gene. We undertook functional studies ofWFS1variants and correlated these with WFS1 protein expression and phenotype.

Methods

9 patients with a clinical diagnosis of WFS were studied with quantitative PCR for markers of endoplasmic reticulum (ER) stress and immunoblotting of fibroblast protein extracts for WFS1 protein expression. Luciferase reporter assay was used to assess ATF-6 dependent unfolded protein response (UPR) activation.

Results

6 patients with compound heterozygous nonsense mutations inWFS1had no detectable WFS1 protein expression; 3 patients with missense variants had 4%, 45% and 48% WFS1 protein expression. One of these also had anOPA1mutation and was reclassified as autosomal dominant optic atrophy-plus syndrome. There were no correlations between ER stress marker mRNA and WFS1 protein expression. ERSE-luciferase reporter indicated activation of the ATF6 branch of UPR in two patients tested. Patients with partial WFS1 expression showed milder visual acuity impairment (asymptomatic or colour blind only), compared with those with absent expression (registered severe vision impaired) (p=0.04). These differences remained after adjusting for duration of optic atrophy.

Conclusions

Patients with WFS who have partial WFS1 protein expression present with milder visual impairment. This suggests a protective effect of partial WFS1 protein expression on the severity and perhaps progression of vision impairment and that therapies to increase residual WFS1 protein expression may be beneficial.
Development and evaluation of an online, patient-driven, family outreach intervention to facilitate sharing of genetic risk information in families with Lynch syndrome
Authors: Pande Mala , Peterson Susan , Lynch Patrick M
Published: May 2021

Background

Identifying at-risk relatives of individuals with genetic conditions facilitates ‘cascade’ genetic testing and cancer prevention. Although current standards of care give mutation-positive (index) patients the responsibility of sharing genetic risk information with relatives, the communication is suboptimal, limited largely to close relatives. We developed FamilyCONNECT, a provider-mediated, patient-navigated online tool to facilitate family outreach, and assessed its feasibility, usability and acceptability.

Methods

(1) Development of the FamilyCONNECT prototype; (2) testing using online surveys of: (a) members of Lynch Syndrome (LS) International (LSI); (b) genetics service providers; and (3) hands-on testing with patients with LS.

Results

(1) FamilyCONNECT’s features include introductory email to elicit participation, informational website/video, identity authentication/account creation, informed consent, sharing of genetic test results, pedigree expansion and process to invite at-risk relatives. (2a) 33% of the 170 LSI participants completed the survey. FamilyCONNECT’s features received favourable responses from at least 79% of respondents. Unfavourable responses were for length of the consent document and mistrust of opening emailed links. (2b) Thirty-five genetics professionals responded to the providers’ survey. Key perceived barriers to FamilyCONNECT’s usage were privacy/confidentiality (83%), a lack of institutional resources (76%), a defined process (66%) and time (69%). (3) Ten patients navigated data collection fields and provided feedback for improvements.

Conclusion

FamilyCONNECT tool’s content and features were well received among patients with LS as well as providers. The tool could be a viable alternative to increase family outreach among patients with LS. Future efforts will focus on refining FamilyCONNECT and assessing its uptake and utilisation by patients with LS.
Machine learning in medicine: should the pursuit of enhanced interpretability be abandoned?
Authors: Yoon Chang Ho , Torrance Robert , Scheinerman Naomi
Published: May 2021

We argue why interpretability should have primacy alongside empiricism for several reasons: first, if machine learning (ML) models are beginning to render some of the high-risk healthcare decisions instead of clinicians, these models pose a novel medicolegal and ethical frontier that is incompletely addressed by current methods of appraising medical interventions like pharmacological therapies; second, a number of judicial precedents underpinning medical liability and negligence are compromised when ‘autonomous’ ML recommendations are considered to be en par with human instruction in specific contexts; third, explainable algorithms may be more amenable to the ascertainment and minimisation of biases, with repercussions for racial equity as well as scientific reproducibility and generalisability. We conclude with some reasons for the ineludible importance of interpretability, such as the establishment of trust, in overcoming perhaps the most difficult challenge ML will face in a high-stakes environment like healthcare: professional and public acceptance.
Framework for evaluation research on clinical ethical case interventions: the role of ethics consultants
Authors: Haltaufderheide Joschka , Nadolny Stephan , Vollmann Jochen , Schildmann Jan
Published: May 2021

Evaluation of clinical ethical case consultations has been discussed as an important research task in recent decades. A rigid framework of evaluation is essential to improve quality of consultations and, thus, quality of patient care. Different approaches to evaluate those services appropriately and to determine adequate empirical endpoints have been proposed. A key challenge is to provide an answer to the question as to which empirical endpoints—and for what reasons—should be considered when evaluating the quality of a service. In this paper, we argue for an approach that adopts the role of ethics consultants as its point of departure. In a first step, we describe empirical and ethical characteristics of evaluating clinical ethical case. We show that the mode of action and the explicit normative character of the interventions constitute two characteristics which pose challenges to the selection of appropriate quality criteria and require special attention. In a second step, we outline the way in which an analysis of the role of ethics consultants in the context of a clinical ethical case consultation services can account for the existing challenges by linking empirically measurable endpoints with normative theory. Finally, we discuss practical implications of our model for evaluation research.
Wide-ranging clinical spectrum of paradoxical embolism
Authors: Jolobe Oscar
Published: May 2021

The purpose of this review is to raise the index of suspicion for paradoxical embolism among generalists. The review is based solely on anecdotal reports compiled from EMBASE, MEDLINE, Googlescholar and Pubmed. Search terms were ‘paradoxical embolism’, ‘pulmonary embolism’ and ‘pulmonary arteriovenous malformations’. What emerged was that right-to-left paradoxical embolism could occur with or without concurrent pulmonary embolism, and also with and without proof of the presence of an ‘embolus-in-transit’. Potential sites of single or multiple systemic involvement included the central nervous system, the coronary circulation, renal arterial circulation, splenic circulation, the mesenteric circulation and the limbs. In many cases, the deep veins of the lower limbs were the source of thromboembolism. In other cases, thrombi originated from an atrial septal aneurysm, from a central venous line, from a haemodialysis-related arterio-venous shunt, from a popliteal vein aneurysm, internal jugular vein, superior vena cava, from a pulmonary arteriovenous malformation, from tricuspid valve endocarditis (with and without pulmonary embolism) and from the right atrium, respectively. Stroke was by far the commonest systemic manifestation of paradoxical embolism. Some strokes were attributable to pulmonary arteriovenous malformations with or without coexistence of intracardiac shunts. Clinicians should have a high index of suspicion for paradoxical embolism because of its time-sensitive dimension when it occurs in the context of involvement of the intracranial circulation, coronary circulation, mesenteric circulation, and peripheral limb circulation.
Self-Adaptive Inertial Projection and Contraction Algorithm for Monotone Variational Inequality
Authors: Gao Xue , Cai Xingju , Wang Xueye
Published: May 2021

In this paper, we propose a self-adaptive inertial projection and contraction algorithm, by combining backtracking search with the inertial projection and contraction algorithm, for solving monotone variational inequality in Hilbert space. This algorithm not only circumvents the restrictive assumption of Lipschitz continuity of the operator, but also gives more suitable and feasible parameters. Under the assumption that the operator is continuous and monotone, we establish weak convergence for proposed algorithm. Finally, we report some preliminary computational results to show the efficiency and advantage of the algorithm.
Tensor Manifold with Tucker Rank Constraints
Authors: Chang Shih Yu , Luo Ziyan , Qi Liqun
Published: May 2021

Low-rank tensor approximation plays a crucial role in various tensor analysis tasks ranging from science to engineering applications. There are several important problems facing low-rank tensor approximation. First, the rank of an approximating tensor is given without checking feasibility. Second, even such approximating tensors exist, however, current proposed algorithms cannot provide global optimality guarantees. In this work, we define the low-rank tensor set (LRTS) for Tucker rank which is a union of manifolds of tensors with specific Tucker rank. We propose a procedure to describe LRTS semi-algebraically and characterize the properties of this LRTS, e.g., feasibility of tensors manifold, the equations/inequations size of LRTS, algebraic dimensions, etc. Furthermore, if the cost function for tensor approximation is polynomial type, e.g., Frobenius norm, we propose an algorithm to approximate a given tensor with Tucker rank constraints and prove the global optimality of the proposed algorithm through critical sets determined by the semi-algebraic characterization of LRTS.