bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic causes of non‐dermatologic chronic pruritus in the pediatric population and their management: An unexplored area
Authors: Gurnani Pooja , Miloh Tamir , Chandar Jayanthi , Landau Daniel A. , Hajjar Fouad , Yosipovitch Gil
Published: September 2021

Chronic pruritus associated with systemic diseases in the pediatric population has been infrequently addressed in the literature. This review focuses on chronic pruritus presenting without cutaneous manifestations. Common systemic etiologies include diseases with hepatic, renal, and hematologic origins. This encompasses several congenital liver disorders, end‐stage renal disease (ESRD), and lymphoproliferative disorders such as Hodgkin's lymphoma. In this paper, an expert panel describes the clinical characteristics, pathophysiology, and therapeutic treatment ladders for chronic pruritus associated with the aforementioned systemic etiologies. Novel therapies are also reviewed. Our aim is to shed light on this unexplored area of pediatric dermatology and instigate further research.
Analysis of over‐the‐counter products marketed to treat molluscum contagiosum
Authors: Ong Samantha K. , Hoft Isaac , Siegfried Elaine
Published: September 2021

Many over‐the‐counter (OTC) products are marketed to treat molluscum contagiosum, a common childhood viral infection with an estimated point prevalence of 5%‐11%. As optimal treatment has not been defined, a comprehensive internet search was performed to identify OTC products marketed for treating molluscum and to collect information on packaging, ingredients, application instructions, and dosing. Nine OTC products were identified and varied widely in cost, packaging size, and ingredients; six of the nine products contained Thuja occidentalis. Overall, the majority of OTC package labels do not include sufficient information about their plant‐based ingredients or appropriate dosing.
Successful treatment of a 3‐year‐old girl with generalized pustular psoriasis using secukinumab monotherapy
Authors: Zhu Huiying , Song Pingping , Du Donghong , Tian Hongqing
Published: September 2021

We report a case of a 3‐year‐old girl with generalized pustular psoriasis (GPP) and a compound heterozygous mutation within the IL36 receptor antagonist (IL36RN) gene at c.28C>T and c.115+6T>C, who was successfully treated using secukinumab monotherapy. The first dose of secukinumab (150 mg) was administered subcutaneously, followed by 75 mg of secukinumab subcutaneously once weekly for 4 weeks and then 75 mg every 4 weeks. The total course of treatment was 4 months, with a total of 8 doses. A PASI score of 75 and 100 was achieved at weeks 1 and 2, respectively, and maintained for 11 months of follow‐up, without disease recurrence or adverse events.
Analysis of the gut microbiome in dogs and cats
Authors: Suchodolski Jan S.
Published: September 2021

The gut microbiome is an important immune and metabolic organ. Intestinal bacteria produce various metabolites that influence the health of the intestine and other organ systems, including kidney, brain, and heart. Changes in the microbiome in diseased states are termed dysbiosis. The concept of dysbiosis is constantly evolving and includes changes in microbiome diversity and/or structure and functional changes (eg, altered production of bacterial metabolites). Molecular tools are now the standard for microbiome analysis. Sequencing of microbial genes provides information about the bacteria present and their functional potential but lacks standardization and analytical validation of methods and consistency in the reporting of results. This makes it difficult to compare results across studies or for individual clinical patients. The Dysbiosis Index (DI) is a validated quantitative PCR assay for canine fecal samples that measures the abundance of seven important bacterial taxa and summarizes the results as one single number. Reference intervals are established for dogs, and the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (eg, fecal microbiota transplantation). In situ hybridization or immunohistochemistry allows the identification of mucosa‐adherent and intracellular bacteria in animals with intestinal disease, especially granulomatous colitis. Future directions include the measurement of bacterial metabolites in feces or serum as markers for the appropriate function of the microbiome. This article summarizes different approaches to the analysis of gut microbiota and how they might be applicable to research studies and clinical practice in dogs and cats.
Self-Identification of Cable-Driven Exoskeleton Based on Asynchronous Iterative Method
Authors: Ji Yuhan , Chen Weihai , Zhang Jianbin , Li Zhongyi , Fang Zaojun , Yang Guilin
Published: September 2021

The upper limb rehabilitation exoskeleton with cable-driven parallel structure has the advantages of light weight and large payload, etc. However, due to the non-rigid nature of the actuating cables and the different body shape of the wearer, the geometric parameters of the exoskeleton have a large error. The parameter identification of cable-driven exoskeleton is of great significance. An asynchronous self-identification method for the upper limb seven degree-of-freedom (DOF) cable-driven exoskeleton was proposed and used in a wearable multi-redundant exoskeleton. Asynchronous iteration eliminates the accumulation of joint errors. High identification reliability is achieved by selecting proper identification parameters and optimizing error model.With the method, the geometric parameters of the exoskeleton can be identified by using exoskeleton joint angle and cable length data. The experiment verifies that the success rate of parameter identification for different wearers is in line with expectations, and the control precision and stability of the prototype are greatly improved after parameter identification.
Visually Quantifiable Test Piece for Five-Axis Machine Tools Thermal Effects
Authors: Huang Nuodi , Zhang Yang , Zhu Limin , Ibaraki Soichi
Published: September 2021

Thermal deviation induced by ambient temperature changes and heat generated during machine operations influences the accuracy of machine tools. A thermal test is essential to evaluate the influence of thermal deviation. ISO 230-3 provides displacement sensor-based thermal tests for machine tools. This paper proposes a machining test that enables a user to visually, by the naked eye, observe the integrated thermal influence on the tool trajectory's displacement in the direction normal to the test piece surface from the length of the machined slots. The proposed test consists of the machining of the five surfaces to observe the thermal influence of the tool position with respect to the test piece in X, Y, and Z directions, as well as the position of two rotary axes with respect to the tool position. The advantages of the proposed test include that it requires no measuring instrument to quantitatively evaluate the thermal error in all directions. And since the thermal influence is evaluated by observing the position where the cutting tool leaves the test piece surface, where the cutting force is zero, the influence of the cutting force on the test results can be ignored. Thermal influences of a five-axis machine tool during the warm-up cycle are investigated by experiment to validate the feasibility of the proposed method. Results show that 150 min is needed for sufficient warm-up for the selected machine tool if permissible tolerance for thermal deviation is 2.5 µm for all the errors.
Reliability, Validity, and Performance Characteristics of Elite Adolescent Athletes at Different Stages of Maturity in the 10 to 5 Repeated Jump Test
Authors: Baker James , Shillabeer Barry , Brandner Christopher , Graham-Smith Philip , Mills Patrick , Read Paul
Published: September 2021

Purpose: To examine the reliability, validity, and performance characteristics of the 10 to 5 repeated jump test (10–5 RJT) in adolescent male athletes. The 10–5 RJT has been shown to be a valid and reliable test of reactive strength index (RSI) in older adolescents (age 17–19 y), but less is known in younger adolescent athletes at different stages of maturity. Methods: Athletes (age 11–17 y) completed the 10–5 RJT on 2 days, 1 week apart, to examine the reliability (n = 41), validity (n = 18) of the test. Athletes were classified as pre, circa, or post peak height velocity (PHV) height velocity using maturity offset to examine the effect of maturation status on RSI, flight time (FT), ground contact time (GCT), and jump height (JH) (n = 68) using a cross-sectional design. Results: Paired samples t tests showed no significant differences (P ≥ .05), and Bland–Altman analysis showed no bias and close limits of agreement for RSI, JH, FT, and GCT between the contact mat and force plate. Interday reliability was rated excellent for RSI (intraclass correlation coefficient = .91) and good for GCT, FT, and JH (intraclass correlation coefficient = .81–.85). All variables had a coefficient of variation ≤ 10%. RSI increased across maturation groups, with significant differences between pre-PHV and post-PHV groups (P = .014, d = 1.00). Conclusion: The 10–5 RJT is a valid and reliable test for adolescent male athletes. Greater RSI with advancing maturity was primarily due to increased FT and JH, with GCT remaining similar.
Lactococcus lactis Resistance to Aureocin A53- and Enterocin L50-Like Bacteriocins and Membrane-Targeting Peptide Antibiotics Relies on the YsaCB-KinG-LlrG Four-Component System
Authors: Tymoszewska Aleksandra , Ovchinnikov Kirill V. , Diep Dzung B. , Słodownik Małgorzata , Maron Edyta , Martínez Beatriz , Aleksandrzak-Piekarczyk Tamara
Published: September 2021

Resistance to nonribosomally synthesized peptide antibiotics affecting the cell envelope is well studied and mostly associated with the action of peptide-sensing and detoxification (PSD) modules, which consist of a two-component system (TCS) and an ATP-binding cassette (ABC) transporter. In contrast, the mechanisms of resistance to ribosomally synthesized bacterial toxic peptides (bacteriocins), which also affect the cell envelope, are studied to a lesser extent, and the possible cross-resistance between them and antibiotics is still poorly understood.
Development of Human Immunodeficiency Virus Type 1 Resistance to 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains
Authors: Cilento Maria E. , Reeve Aaron B. , Michailidis Eleftherios , Ilina Tatiana V. , Nagy Eva , Mitsuya Hiroaki , Parniak Michael A. , Tedbury Philip R. , Sarafianos Stefan G.
Published: September 2021

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA, MK-8591, islatravir) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with exceptional potency against wild-type (WT) and drug-resistant HIV-1 in phase III clinical trials. EFdA resistance is not well characterized.
Reexamining the Association of AmpC Variants with Enterobacter Species in the Context of Updated Taxonomy
Authors: Feng Yu , Hu Ya , Zong Zhiyong
Published: September 2021

We performed whole-genome sequencing for 17
Enterobacter
clinical strains and analyzed all available
Enterobacter
genomes and those of its closely related genera (
n
 = 3,389) from NCBI. The exact origins of plasmid-borne
bla
CMH
and
bla
MIR
genes are
Enterobacter cloacae
and
Enterobacter roggenkampii
, respectively, while plasmid-borne
bla
ACT
genes originated from multiple other
Enterobacter
species, including
Enterobacter xiangfangensis
,
Enterobacter hoffmannii
,
Enterobacter asburiae
,
Enterobacter ludwigii
, and
Enterobacter kobei
.
Distinct Assembly Processes and Determinants of Soil Microbial Communities between Farmland and Grassland in Arid and Semiarid Areas
Authors: Xu Aiai , Liu Jie , Guo Zhiying , Wang Changkun , Pan Kai , Zhang Fangfang , Pan Xianzhang
Published: September 2021

As one of the most diverse organisms, soil microbes play indispensable roles in many ecological processes in arid and semiarid areas with limited macrofaunal and plant diversity, yet the mechanisms underpinning soil microbial community are not fully understood. In this study, soil microbial communities were investigated along a 500-km transect covering a steep environmental gradient across farmland and grassland in the areas.
Cell Culture Evolution of a Herpes Simplex Virus 1 (HSV-1)/Varicella-Zoster Virus (VZV) UL34/ORF24 Chimeric Virus Reveals Novel Functions for HSV Genes in Capsid Nuclear Egress
Authors: Roller Richard J. , Hassman Tineke , Haugo-Crooks Alison
Published: September 2021

Interactions among virus proteins are critical for assembly and egress of virus particles, and such interactions are attractive targets for antiviral therapy. Identification of critical functional interactions can be slow and tedious.
Rapid-onset clozapine-induced hyperglycaemia: pathways of glycaemic dysregulation
Authors: Barbosa Mariana , Fernandes Vera
Published: September 2021

Clozapine is an atypical antipsychotic used in refractory schizophrenia, also efficient in alleviating dyskinesia in Parkinson’s disease. Despite its potency, this drug is associated with severe metabolic side effects, including increased risk for diabetes. We report the case of a 45-year-old overweight woman with Parkinson’s disease who presented with rapid-onset hyperglycaemia within 2 months after starting clozapine for refractory dyskinaesia. She had a history of gestational diabetes. At presentation, her blood glucose level was 505 mg/dL and glycated haemoglobin 12.4%, with no catabolic symptoms. Clozapine was suspended and metformin was started, but adequate glycaemic control was achieved only with insulin therapy, along with exenatide and empagliflozin afterwards. We assume that clozapine acted as a trigger for rapid deterioration of glycaemic control through direct pathophysiological mechanisms, rather than an indirect slowly evolving weight gain-related metabolic syndrome pathway. Clinicians should be aware of this complication, enabling timely diagnosis and proper treatment.
Left anterior descending artery myocardial bridge manifesting as episodic, symptomatic exertional non-sustained ventricular tachycardia
Authors: Aedma Surya Kiran , Khalil Muhammad Hasib , Abigail Adams , Martin Randolph S
Published: September 2021

A 48-year-old man presented to the emergency department (ED) with exertional chest pressure associated with palpitations and lightheadedness. He was found to have non-sustained ventricular tachycardia (NSVT) in the ED, which resolved spontaneously. Given his history of hyperlipidaemia, unknown family history due to being adopted and episode of NSVT in the ED, he underwent cardiac catheterisation, which showed non-obstructive coronary artery disease and distal left anterior descending artery myocardial bridge (MB). The patient subsequently underwent ECG treadmill stress test with reproduction of chest pressure and NSVT. The patient was referred to cardiac surgery for definitive management of symptomatic MB and underwent resection of MB.
Determinants of losses in the latent tuberculosis infection cascade of care in Brazil
Authors: Souza Alexandra Brito , Arriaga María B , Amorim Gustavo , Araújo-Pereira Mariana , Nogueira Betânia M F , Queiroz Artur T L , Figueiredo Marina C , Rocha Michael S , Benjamin Aline , Moreira Adriana S R , Oliveira Jamile G , Rolla Valeria , Durovni Betina , Lapa e Silva José R , Kritski Afrânio L , Cavalcante Solange , Sterling Timothy , Andrade Bruno B , Cordeiro-Santos Marcelo
Published: September 2021

Introduction

Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil.

Methods

Close contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6–24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Multivariable regressions were used to identify determinants of losses in the LTBI cascade.

Results

Among 4145 TB contacts initially identified, 1901 were examined (54% loss). Among those examined, 933 were people living with HIV, ≤5 years old and/or had positive IGRA results, and therefore had a recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (54% of those initiating; 26% of those in whom treatment was recommended) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy and black/pardo(brown) race were independently associated with losses in the cascade.

Conclusion

There were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts of low socioeconomic status and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.
Trends in high deductible health plan enrolment and spending among commercially insured members with and without chronic conditions: a Natural Experiment for Translation in Diabetes (NEXT-D2) Study
Authors: Garabedian Laura F , Zhang Fang , LeCates Robert , Wallace Jamie , Ross-Degnan Dennis , Wharam James F
Published: September 2021

Objectives

To examine trends in high deductible health plan (HDHP) enrolment among members with diabetes and cardiovascular disease (CVD) compared with healthy members and compare out-of-pocket (OOP) and total spending for members with chronic conditions in HDHPs versus low deductible plans.

Design

Descriptive study with time trends.

Setting

A large national commercial insurance database.

Participants

1.2 million members with diabetes, 4.5 million members with CVD (without diabetes) and 18 million healthy members (defined by a low comorbidity score) under the age of 65 years and insured between 2005 and 2013.

Outcome measures

Percentage of members in an HDHP (ie, annual deductible ≥$1000) by year, annual mean OOP and total spending, adjusted for member sociodemographic and employer characteristics.

Results

Enrolment in HDHPs among members in all disease categories increased by 5 percentage points a year and was over 50% by 2013. On average, over the study period, HDHP enrolment among members with diabetes and CVD was 2.84 (95% CI: 2.78 to 2.90) and 2.02 (95% CI: 1.98 to 2.05) percentage points lower, respectively, than among healthy members. HDHP members with diabetes, CVD and low morbidity had higher annual OOP costs ($636 (95% CI: 630 to 642), $539 (95% CI: 537 to 542) and $113 (95% CI: 112 to 113)) and lower total costs (−$529 (95% CI: −597 to −461), −$364 (95% CI: −385 to −342) and −$79 (95% CI: −81 to −76)), respectively, than corresponding low deductible members when averaged over the study period. Members with chronic diseases had yearly OOP expenditures that were five to seven times higher than healthier members.

Conclusion

High HDHP enrolment coupled with the high OOP costs associated with HDHPs may be particularly detrimental to the financial well-being of people with diabetes and CVD, who have more healthcare needs than healthier populations.
Family refusal of eye tissue donation from potential solid organ donors: a retrospective analysis of summary and free-text data from the UK National Health Service Blood and Transplant Services (NHS-BT) National Referral Centre (1 April 2014 to 31 March 2017)
Authors: Bracher Mike , Madi-Segwagwe Banyana C , Winstanley Emma , Gillan Helen , Long-Sutehall Tracy
Published: September 2021

Objectives

Long-standing undersupply of eye tissue exists both in the UK and globally, and the UK National Health Service Blood and Transplant Service (NHSBT) has called for further research exploring barriers to eye donation. This study aims to: (1) describe reported reasons for non-donation of eye tissue from solid organ donors in the UK between 1 April 2014 and 31 March 2017 and (2) discuss these findings with respect to existing theories relating to non-donation of eyes by family members.

Design

Secondary analysis of a national primary data set of recorded reasons for non-donation of eyes from 2790 potential solid organ donors. Data analysis including descriptive statistics and qualitative content analysis of free-text data for 126 recorded cases of family decline of eye donation.

Setting

National data set covering solid organ donation (secondary care).

Participants

2790 potential organ donors were assessed for eye donation eligibility between 1 April 2014 and 31 March 2017.

Results

Reasons for non-retrieval of eyes were recorded as: family wishes (n=1339, 48% of total cases); medical reasons (n=841, 30%); deceased wishes (n=180, 7%). In >50% of recorded cases, reasons for non-donation were based on family’s knowledge of the deceased wishes, their perception of the deceased wishes and specific concerns regarding processes or effects of eye donation (for the deceased body). Findings are discussed with respect to the existing theoretical perspectives.

Conclusion

Eye donation involves distinct psychological and sociocultural factors for families and HCPs that have not been fully explored in research or integrated into service design. We propose areas for future research and service development including potential of only retrieving corneal discs as opposed to full eyes to reduce disfigurement concerns; public education regarding donation processes; exploration of how request processes potentially influence acceptance of eye donation; procedures for assessment of familial responses to information provided during consent conversations.
CARING FUTURES: a study protocol for transdisciplinary qualitative research on technology-mediated care practices and theory development for ethics of care
Authors: Ramvi Ellen , Gripsrud Birgitta Haga , Hellstrand Ingvil , Gjerstad Brita , Vagli Åse Elisabeth
Published: September 2021

Introduction

The world’s population is ageing. As older persons live longer and increase in number, society faces a greater disease burden and, in public welfare, a corresponding resource deficit. New technology is one solution to this deficit but there is scarce knowledge about ethical aspects of such innovations in care practices. In CARING FUTURES, we address this scarcity by interrogating how new technology in care can become ethically sound and, correspondingly, how ethics of care can become more technology aware. Our concern is to protect quality care for the future.

Methods and analysis

CARING FUTURES advances transdisciplinarity through knowledge exchange around technology-mediated care and ethics of care, involving key stakeholders. We rely on established and innovative methods to generate experience-near and practice-near knowledge. Through this empirical research, we seek to expand understanding of technology-mediated care and to enrich ethics of care theory.

Ethics and dissemination

Empirical studies have been approved or await approval by national ethics committees. CARING FUTURES is designed to create societal impact throughKnowledge Transfer Eventstargeting stakeholders in health, care and welfare, andEducational Packagesfor students of care—providing knowledge-exchange forums for future academics and practitioners of care. The project’s societal impact is also ensured in that participating researchers are also practitioners and/or educators of care personnel for the future. Project findings will be disseminated through scientific publications and conference presentations. Through communication in both traditional and digital media platforms, we engage in dialogues between researchers, user groups, policy makers and the wider public.
Living with heritable retinoblastoma and the perceived role of regular follow-up at a retinoblastoma survivorship clinic: ‘That is exactly what I have been missing’
Authors: Gregersen Pernille Axel , Funding Mikkel , Alsner Jan , Olsen Maja H , Overgaard Jens , Urbak Steen F , Staffieri Sandra E , Lou Stina
Published: September 2021

Objective

To explore living with heritable retinoblastoma, specifically survivors’ perceived role of regular follow-up at a retinoblastoma survivorship clinic.

Methods and analysis

Adult survivors of heritable retinoblastoma were recruited from the Retinoblastoma Survivorship Clinic, Aarhus University Hospital. Ten survivors participated in individual explorative, semistructured interviews. Thematic data analysis was conducted.

Results

Five key themes relating to vision, social life, family, second cancer risk and the healthcare system were identified. Subthemes relating to the Retinoblastoma Survivorship Clinic included the retinoblastoma coordinator, cancer risk, psychosocial support and genetic knowledge. The retinoblastoma-related physical and psychosocial issues influenced survivors’ everyday living; however, the opportunity to live a normal life varied considerably, with the majority experiencing no major limitations. The need for specialised management and a coordinator was emphasised to be the main value of the Retinoblastoma Survivorship Clinic.

Conclusion

Despite reporting an overall normal life and no major limitations in daily living activities, our data confirm that heritable retinoblastoma impacts several aspects of daily living. Uniquely, this study demonstrates that the main value of the Retinoblastoma Survivorship Clinic was a specialised contact person and coordinator in the healthcare system, providing continuous and necessary management and guidance after retinoblastoma treatment, and for all aspects of health related to heritable retinoblastoma. The needs of heritable retinoblastoma survivors are complex and extensive, and the specific role of the healthcare system to support survivorship should be prioritised, specialised and multidisciplinary.
Mass production methods for mass vaccination: improving flow and operational performance in a COVID-19 mass vaccination centre using Lean
Authors: Smith Iain M , Smith David T L
Published: September 2021

The COVID-19 pandemic has infected tens of millions of people worldwide causing many deaths. Healthcare systems have been stretched caring for the most seriously ill and lockdown measures to interrupt COVID-19 transmission have had adverse economic and societal impacts. Large-scale population vaccination is seen as the solution.

In the UK, a network of sites to deploy vaccines comprised National Health Service hospitals, primary care and new mass vaccination centres. Due to the pace at which mass vaccination centres were established and the scale of vaccine deployment, some sites experienced problems with queues and waiting times. To address this, one site used the Lean systematic improvement approach to make rapid operational improvements to reduce process times and improve flow.

The case example identifies obstacles to flow experienced by a mass vaccination centre and how they were addressed using Lean concepts and techniques. Process cycle times were used as a proxy metric for efficiency and flow. Based on daily demand volume and open hours, takt time was calculated to give a process completion rate to achieve flow through the vaccination centre.

The mass vaccination centre achieved its aim of reducing process times and improving flow. Administrative and clinical cycle times were reduced sufficiently to increase throughput and the number of queues and queueing time were reduced improving client experience.

The design and operational management of vaccination centre processes contribute to client experience, efficiency and throughput. Lean provides a systematic approach that can improve operational processes and facilitate client flow through mass vaccination centres.
Quantifying head acceleration exposure via instrumented mouthguards (iMG): a validity and feasibility study protocol to inform iMG suitability for the TaCKLE project
Authors: Tierney Gregory , Weaving Daniel , Tooby James , Al-Dawoud Marwan , Hendricks Sharief , Phillips Gemma , Stokes Keith A , Till Kevin , Jones Ben
Published: September 2021

Instrumented mouthguards (iMGs) have the potential to quantify head acceleration exposures in sport. The Rugby Football League is looking to deploy iMGs to quantify head acceleration exposures as part of the Tackle and Contact Kinematics, Loads and Exposure (TaCKLE) project. iMGs and associated software platforms are novel, thus limited validation studies exist. The aim of this paper is to describe the methods that will determine the validity (ie, laboratory validation of kinematic measures and on-field validity) and feasibility (ie, player comfort and wearability and practitioner considerations) of available iMGs for quantifying head acceleration events in rugby league. Phase 1 will determine the reliability and validity of iMG kinematic measures (peak linear acceleration, peak rotational velocity, peak rotational acceleration), based on laboratory criterion standards. Players will have three-dimensional dental scans and be provided with available iMGs for phase 2 and phase 3. Phase 2 will determine the on-field validity of iMGs (ie, identifying true positive head acceleration events during a match). Phase 3 will evaluate player perceptions of fit (too loose, too tight, bulky, small/thin, held mouth open, held teeth apart, pain in jaw muscles, uneven bite), comfort (on lips, gum, tongue, teeth) and function (speech, swallowing, dry mouth). Phase 4 will evaluate the practical feasibility of iMGs, as determined by practitioners using the system usability scale (preparing iMG system and managing iMG data). The outcome will provide a systematic and robust assessment of a range of iMGs, which will help inform the suitability of each iMG system for the TaCKLE project.
Update on the current opinion, status and future development of digital pathology in Switzerland in light of COVID-19
Authors: Koelzer Viktor Hendrik , Grobholz Rainer , Zlobec Inti , Janowczyk Andrew
Published: September 2021

Aims

The transition from analogue to digital pathology (DP) in Switzerland has coincided with the COVID-19 crisis. The Swiss Digital Pathology Consortium conducted a national survey to assess the experience of pathologists in dealing with the challenges of the pandemic and how this has influenced the outlook and adoption of DP.

Methods

A survey containing 20 questions relating to DP, personal experiences and challenges during the pandemic was addressed to Swiss pathologists at different experience stages in private practice, community and university hospitals.

Results

All 74 respondents were pathologists, with 81.1% reporting more than 5 years of diagnostic service experience. 32.5% reported having read 100 digital slides or more in a diagnostic context. 39.2% reported using whole slide imaging systems at their primary workplace. Key DP use cases before the COVID-19 lockdown were tumour boards (39.2%), education (60.8%) and research (44.6%), with DP used for primary diagnosis in 13.5%. During the COVID-19 crisis, the use of DP for primary diagnostics more than doubled (30% vs 13.5%), with internal consults as important drivers (22.5% vs 16.5%), while research use (25% vs 44.6%) and external consults (17.5% vs 41.9%) strongly decreased. Key challenges identified included a lack of established standard operating procedures and availability of specialised hardware and software.

Conclusions

This survey indicates that the crisis acted as a catalyst in promoting DP adoption in centres where basic workflows were already established while posing major technical and organisational challenges in institutions that were at an early stage of DP implementation.
Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells
Authors: Huckaby Justin T , Landoni Elisa , Jacobs Timothy M , Savoldo Barbara , Dotti Gianpietro , Lai Samuel K
Published: September 2021

Background

Chimeric antigen receptor (CAR) T cells have shown considerable promise as a personalized cellular immunotherapy against B cell malignancies. However, the complex and lengthy manufacturing processes involved in generating CAR T cell products ex vivo result in substantial production time delays and high costs. Furthermore, ex vivo expansion of T cells promotes cell differentiation that reduces their in vivo replicative capacity and longevity.

Methods

Here, to overcome these limitations, CAR-T cells are engineered directly in vivo by administering a lentivirus expressing a mutant Sindbis envelope, coupled with a bispecific antibody binder that redirects the virus to CD3+ human T cells.

Results

This redirected lentiviral system offers exceptional specificity and efficiency; a single dose of the virus delivered to immunodeficient mice engrafted with human peripheral blood mononuclear cells generates CD19-specific CAR-T cells that markedly control the growth of an aggressive pre-established xenograft B cell tumor.

Conclusions

These findings underscore in vivo engineering of CAR-T cells as a promising approach for personalized cancer immunotherapy.
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma
Authors: Greten Tim F , Abou-Alfa Ghassan K , Cheng Ann-Lii , Duffy Austin G , El-Khoueiry Anthony B. , Finn Richard S , Galle Peter R , Goyal Lipika , He Aiwu Ruth , Kaseb Ahmed O , Kelley Robin Kate , Lencioni Riccardo , Lujambio Amaia , Mabry Hrones Donna , Pinato David J , Sangro Bruno , Troisi Roberto I , Wilson Woods Andrea , Yau Thomas , Zhu Andrew X , Melero Ignacio
Published: September 2021

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
Authors: Brown Landon C. , Desai Kunal , Wei Wei , Kinsey Emily N. , Kao Chester , George Daniel J. , Rini Brian I. , Ornstein Moshe C. , Zhang Tian
Published: September 2021

The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher’s exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0–35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials.
Charcot-Marie-Tooth disease type 2CC due toNEFHvariants causes a progressive, non-length-dependent, motor-predominant phenotype
Authors: Pipis Menelaos , Cortese Andrea , Polke James M , Poh Roy , Vandrovcova Jana , Laura Matilde , Skorupinska Mariola , Jacquier Arnaud , Juntas-Morales Raul , Latour Philippe , Petiot Philippe , Sole Guilhem , Fromes Yves , Shah Sachit , Blake Julian , Choi Byung-Ok , Chung Ki Wha , Stojkovic Tanya , Rossor Alexander M , Reilly Mary M
Published: September 2021

Objective

Neurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants inNEFHhave recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC).

Methods

In this large observational study, we present phenotype–genotype correlations on 30 affected and 3 asymptomatic mutation carriers from eight families.

Results

The majority of patients presented in adulthood with motor-predominant and lower limb-predominant symptoms and the average age of onset was 31.0±15.1 years. A prominent feature was the development of proximal weakness early in the course of the disease. The disease progressed rapidly, unlike other Charcot-Marie-Tooth disease (CMT) subtypes, and half of the patients (53%) needed to use a wheelchair on average 24.1 years after symptom onset. Furthermore, 40% of patients had evidence of early ankle plantarflexion weakness, a feature which is observed in only a handful of CMT subtypes. Neurophysiological studies and MRI of the lower limbs confirmed the presence of a non-length-dependent neuropathy in the majority of patients.

All families harboured heterozygous frameshift variants in the last exon ofNEFH, resulting in a reading frameshift to an alternate open reading frame and the translation of approximately 42 additional amino acids from the 3' untranslated region (3′-UTR).

Conclusions

This phenotype–genotype study highlights the unusual phenotype of CMT2CC, which is more akin to spinal muscular atrophy rather than classic CMT. Furthermore, the study will enable more informative discussions on the natural history of the disease and will aid inNEFHvariant interpretation in the context of the disease’s unique molecular genetics.
De novo mutations in SOD1 are a cause of ALS
Authors: Müller Kathrin , Oh Ki-Wook , Nordin Angelica , Panthi Sudhan , Kim Seung Hyun , Nordin Frida , Freischmidt Axel , Ludolph Albert C , Ki Chang Seok , Forsberg Karin , Weishaupt Jochen , Kim Young-Eun , Andersen Peter Munch
Published: September 2021

Objective

The only identified cause of amyotrophic lateral sclerosis (ALS) are mutations in a number of genes found in familial cases but also in sporadic cases. De novo mutations occurring in a parental gonadal cell, in the zygote or postzygotic during embryonal development can result in an apparently sporadic/isolated case of ALS later in life. We searched for de novo mutations in SOD1 as a cause of ALS.

Methods

We analysed peripheral-blood exome, genome and Sanger sequencing to identify deleterious mutations in SOD1 in 4000 ALS patients from Germany, South Korea and Sweden. Parental kinship was confirmed using highly polymorphic microsatellite markers across the genome. Medical genealogical and clinical data were reviewed and compared with the literature.

Results

We identified four sporadic ALS cases with de novo mutations in SOD1. They aggregate in hot-spot codons earlier found mutated in familial cases. Their phenotypes match closely what has earlier been reported in familial cases with pathogenic mutations in SOD1. We also encountered familial cases where de novo mutational events in recent generations may have been involved.

Conclusions

De novo mutations are a cause of sporadic ALS and may also be underpinning smaller families with few affected ALS cases. It was not possible to ascertain if the origin of the de novo mutations was parental germline, zygotic or postzygotic during embryonal development. All ALS patients should be offered genetic counselling and genetic screening, the challenges of variant interpretation do not outweigh the potential benefits including earlier confirmed diagnosis and possible bespoken therapy.
Long-term outcomes after treatment of in-stent restenosis using the Absorb everolimus-eluting bioresorbable scaffold
Authors: Madanchi Mehdi , Cioffi Giacomo Maria , Attinger-Toller Adrian , Wolfrum Mathias , Moccetti Federico , Seiler Thomas , Vercelli Luca , Burkart Philipp , Toggweiler Stefan , Kobza Richard , Bossard Matthias , Cuculi Florim
Published: September 2021

Background

Early studies evaluating the performance of bioresorbable scaffold (BRS) Absorb in in-stent restenosis (ISR) lesions indicated promising short-term to mid-term outcomes.

Aims

To evaluate long-term outcomes (up to 5 years) of patients with ISR treated with the Absorb BRS.

Methods

We did an observational analysis of long-term outcomes of patients treated for ISR using the Absorb BRS (Abbott Vascular, Santa Clara, California, USA) between 2013 and 2016 at the Heart Centre Luzern. The main outcomes included a device-oriented composite endpoint (DOCE), defined as composite of cardiac death, target vessel (TV) myocardial infarction and TV revascularisation, target lesion revascularisation and scaffold thrombosis (ScT).

Results

Overall, 118 ISR lesions were treated using totally 131 BRS among 89 patients and 31 (35%) presented with an acute coronary syndrome. The median follow-up time was 66.3 (IQR 52.3–77) months. A DOCE had occurred in 17% at 1 year, 27% at 2 years and 40% at 5 years of all patients treated for ISR using Absorb. ScTs were observed in six (8.4%) of the cohort at 5 years.

Conclusions

Treatment of ISR using the everolimus-eluting BRS Absorb resulted in high rates of DOCE at 5 years. Interestingly, while event rates were low in the first year, there was a massive increase of DOCE between 1 and 5 years after scaffold implantation. With respect to its complexity, involving also a more unpredictable vascular healing process, current and future BRS should be used very restrictively for the treatment of ISR.
Traditional uses and beneficial effects of various species of berry-producing plants in eastern Canada
Authors: Weber John T.
Published: September 2021

There are many different types of berry-producing plants that grow throughout North America. These various species of plants produce berries, known by their common names, such as blueberry, lingonberry, cranberry, crowberry, blackberry, bunchberry, bearberry, and strawberry. The berry fruits are important food sources and can be eaten fresh or preserved. The leaves of several species can also be enjoyed in teas. Contemporary medicine has demonstrated many potential health benefits of berries due to their antioxidant and anti-inflammatory activity. Indigenous Peoples have not only utilized berries as food, likely over many centuries, but have also passed down knowledge on the medicinal uses of various parts of these plants including the fruits, leaves and roots. This short review provides a synopsis of some of the major species of berry-producing plants that are prevalent in Canada, particularly eastern Canada. Current knowledge and traditional uses of important species of berry-producing plants are discussed.
Analysis of persistent macroaggregates on the surface of agricultural soils
Authors: Tian Tian , Whalen Joann K. , Dutilleul Pierre
Published: September 2021

In humid regions, the number of macroaggregates on the soil surface could decline because of rainfall disturbance, or increase due to rainfall-activated chemical and biological stabilization. We took digital images of macroaggregates at the surface of clay and organic soils six times during a 68 d period with 264 mm natural rainfall. Based on the constant or increasing number of surface macroaggregates during the five time intervals, rainfall did not disturb macroaggregates. Macroaggregate persistence was positively correlated with cumulative rainfall (both soils) and soil moisture (organic soil), so we infer that rainfall promoted macroaggregate assemblage through chemical and biological processes.
Test of quantum nonlocality via vector meson decays to KSKS
Authors: Jiang Pei-Cheng , Wang Xuan , Wang Da-Yong
Published: September 2021

In the system of a pair of quantum-entangled neutral kaons from meson decays, when one kaon collapses into the [Formula: see text] state, the other will collapse instantaneously into the [Formula: see text] state, due to entanglement and nonlocality. However, if the alternative hypothesis is correct and there is a time window during which one kaon is unaware that the other has decayed, some quantum mechanically prohibited [Formula: see text] decays may occur. We calculate the branching ratios of [Formula: see text] in vector meson decays under locality hypothesis and compare them with experimental results. We show that the branching ratio of [Formula: see text] under locality assumption is already excluded by the BESIII experimental upper limit. Additional experimental results are proposed to perform this test in the future.
Synergistic effect between flake graphite and small-sized graphene in lithium storage
Authors: Li Hai , Lu Chunxiang
Published: September 2021

As anode material for lithium-ion batteries, graphite has the disadvantage of relatively low specific capacity. In this work, a simple yet effective strategy to overcome the disadvantages by using a composite of flake graphite (FG) and small-sized graphene (SG) has been developed. The FG/SG composite prepared by dispersing FG and SG (90:10 w/w) in ethanol and drying delivers much higher specific capacity than that of individual component except for improved rate capability. More surprisingly, FG/SG composite delivers higher reversible capacity than its theoretical value calculated according to the theoretical capacities of graphite and graphene. Therefore, a synergistic effect between FG and SG in lithium storage is clearly discovered. To explain it, we propose a model that abundant nanoscopic cavities were formed due to physical adhesion between FG and SG and could accommodate extra lithium.