bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing theory-informed knowledge translation strategies to facilitate the use of patient-reported outcome measures in interdisciplinary low back pain clinical practices in Quebec: mixed methods study
Authors: Eilayyan Owis , Visca Regina , Zidarov Diana , Ware Patrick , Bussières André , Ahmed Sara
Published: August 2020

Background

There is a growing interest among healthcare providers (HCPs) to use Patient Reported Outcome Measures (PROMs) in clinical care. PROMs can help improve patient-care provider communication and may be used to inform the need for interdisciplinary care for Low Back Pain (LBP). However, PROM implementation to support clinical decision-making is complex and requires knowledge translation (KT) interventions that will overcome barriers to using PROMs in interdisciplinary clinical settings.

Objectives

to 1) identify potential barriers and enablers to using PROMs in primary care LBP clinical practice from the perspective of healthcare team members, and 2) develop a theory-based tailored KT intervention to facilitate the use of PROMs in interdisciplinary clinical practice.

Methods

We invited 25 HCPs working in an interdisciplinary team to complete a self-administered survey designed based on the Theoretical Domain Framework (TDF) to identify the barriers and enablers to using PROM scores in LBP clinical practice. The questionnaire consisted of 30 questions rated on a 5-point Likert scale (quantitative) and included open-ended questions (qualitative). Quantitative and qualitative data were analysed to estimate the frequency of barriers and enablers. Findings were then reviewed by a panel of four KT experts who mapped behaviour change techniques to barriers identified that informed the design of a KT intervention.

Results

Eighteen HCPs responded to the survey. Factors identified as likely to restrict the use of PROM scores includedknowledge, skills, social/professional role and identity, goals, decision processes, beliefs about consequences, environmental context and resources, behavioural regulation,andsocial influence. A multi-component evidence-based KT intervention was proposed by the panel of experts to address these barriers: a training workshop; educational materials; and use of PROM score reports to HCPs that were all delivered by an opinion leader.

Conclusion

The routine use of PROMs in clinical practice may optimize the quality of LBP care and improve patients’ outcomes. The proposed multi-component KT intervention is expected to be an effective strategy to increase HCPs’ ability to integrate PROMs into clinical decision-making and to engage patients in their care.
Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors
Authors: Yang Haomin , Holowko Natalie , Grassmann Felix , Eriksson Mikael , Hall Per , Czene Kamila
Published: August 2020

Background

Despite the biological link between thyroid hormones and breast cancer cell proliferation shown in experimental studies, little is known about the association between hyperthyroidism and breast cancer, as well as its association with the most common mammographic and genetic risk predictors for breast cancer.

Methods

This study estimates the incidence rate ratios (IRRs) of breast cancer among women diagnosed with hyperthyroidism, compared to those who are not, using two cohorts: a Swedish national cohort of the general female population (n = 3,793,492, 2002–2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 69,598, 2002–2017). We used logistic regression to estimate the odds ratios (ORs) of hyperthyroidism according to the mammographic and genetic risk predictors for breast cancer.

Results

An increased risk of breast cancer was observed in patients in the national cohort with hyperthyroidism (IRR = 1.23, 95% CI = 1.12–1.36), particularly for toxic nodular goiter (IRR = 1.38, 95% CI = 1.16–1.63). Hyperthyroidism was associated with higher body mass index, early age at first birth, and lower breastfeeding duration. Higher mammographic density was observed in women with toxic nodular goiter, compared to women without hyperthyroidism. Additionally, among genotyped women without breast cancer in the KARMA cohort (N = 11,991), hyperthyroidism was associated with a high polygenic risk score (PRS) for breast cancer overall (OR = 1.98, 95% CI = 1.09–3.60) and for estrogen receptor-positive specific PRS (OR = 1.90, 95% CI = 1.04–3.43).

Conclusion

Hyperthyroidism is associated with an increased risk of breast cancer, particularly for patients with toxic nodular goiter. The association could be explained by higher mammographic density among these women, as well as pleiotropic genetic variants determining shared hormonal/endocrine factors leading to the pathology of both diseases.
A TaqMan-based real-time PCR assay for specific detection of novel duck reovirus in China
Authors: Zhang Shuai , Li Weihua , Liu Xiaodong , Li Xudong , Gao Bin , Diao Youxiang , Tang Yi
Published: August 2020

Background

In China, Newly emerging duck reovirus (NDRV) variants have been causing major disease problems in cherry valley ducks. NDRV has the potential to cause high morbidity and 5–50% mortality rates. Severe hemorrhagic-necrosis in the liver and spleen were commonly seen in NDRV affected ducks. The availability of upgraded methods for rapid diagnosis of newly emerging DRV variants is crucial for successful DRV infection control and prevention.

Results

In this study, we present a TaqMan-based real-time PCR assay (RT-qPCR) for the detection of NDRV infection. Using the conserved regions within the NDRV genome, we designed the specific primers and probe. The lower limit of detection for NDRV infection was 10 copies/μL (Ct values: 38.3) after the optimization of the RT-qPCR conditions. By cross-checking with other duck viral pathogens, no cross-reactivity was observed confirming the assay was highly specific for the detection of NDRV. Reproducibility of the RT-qPCR was confirmed by intra- and inter-assay variability was less than 2.91%(Intra-assay variability of Ct values: 0.07–1.48%; Interassay variability of Ct values: 0.49–2.91%). This RT-qPCR and conventional PCR (cPCR) detected one hundred and twenty samples of NDRV infection from different regions. The result shows that the positive rates were 94.17 and 84.17% respectively. The detection rate of RT-qPCR rapid detection assay was 10% higher than that of the cPCR method.

Conclusion

This research developed a highly sensitive, specific, reproducible and versatile of RT-qPCR for quantitatively detecting NDRV. It can be used to study the pathogenesis and epidemiology investigation of NDRV.
Upregulation of METTL14 mediates the elevation of PERP mRNA N6 adenosine methylation promoting the growth and metastasis of pancreatic cancer
Authors: Wang Min , Liu Jun , Zhao Yan , He Ruizhi , Xu Xiaodong , Guo Xingjun , Li Xu , Xu Simiao , Miao Ji , Guo Jianpin , Zhang Hang , Gong Jun , Zhu Feng , Tian Rui , Shi Chengjian , Peng Feng , Feng Yechen , Yu Shuo , Xie Yu , Jiang Jianxin , Li Min , Wei Wenyi , He Chuan , Qin Renyi
Published: August 2020

Background

Pancreatic cancer is one of the most lethal human cancers.N6-methyladenosine (m6A), a common eukaryotic mRNA modification, plays critical roles in both physiological and pathological processes. However, its role in pancreatic cancer remains elusive.

Methods

LC/MS was used to profile m6A levels in pancreatic cancer and normal tissues. Bioinformatics analysis, real-time PCR, immunohistochemistry, and western blotting were used to identify the role of m6A regulators in pancreatic cancer. The biological effects of methyltransferase-like 14 (METTL14), an mRNA methylase, were investigated using in vitro and in vivo models. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of METTL14.

Results

We found that the m6A levels were elevated in approximately 70% of the pancreatic cancer samples. Furthermore, we demonstrated that METTL14 is the major enzyme that modulates m6A methylation (frequency and site of methylation). METTL14 overexpression markedly promoted pancreatic cancer cell proliferation and migration both in vitro and in vivo,via direct targeting of the downstreamPERPmRNA (p53 effector related to PMP-22) in an m6A-dependent manner. Methylation of the target adenosine lead to increasedPERPmRNA turnover, thus decreasing PERP (mRNA and protein) levels in pancreatic cancer cells.

Conclusions

Our data suggest that the upregulation of METTL14 leads to the decrease of PERP levels via m6A modification, promoting the growth and metastasis of pancreatic cancer; therefore METTL14 is a potential therapeutic target for its treatment.
IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice
Authors: Liang Yuejin , Yi Panpan , Ru Wenjuan , Jie Zuliang , Wang Hui , Ghanayem Tamer , Wang Xiaofang , Alamer Edrous , Liu Jinjun , Hu Haitao , Soong Lynn , Cai Jiyang , Sun Jiaren
Published: August 2020

Background

The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown.

Methods

The cellular source of IL-22 was identified in IFNAR-/- mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22-/- mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads.

Results

We found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16–19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22-/- mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain.

Conclusions

Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.
Exploring augmented grasping capabilities in a multi-synergistic soft bionic hand
Authors: Piazza Cristina , Simon Ann M. , Turner Kristi L. , Miller Laura A. , Catalano Manuel G. , Bicchi Antonio , Hargrove Levi J.
Published: August 2020

Background

State-of-the-art bionic hands incorporate hi-tech devices which try to overcome limitations of conventional single grip systems. Unfortunately, their complexity often limits mechanical robustness and intuitive prosthesis control. Recently, the translation of neuroscientific theories (i.e. postural synergies) in software and hardware architecture of artificial devices is opening new approaches for the design and control of upper-limb prostheses.

Methods

Following these emerging principles, previous research on the SoftHand Pro, which embeds one physical synergy, showed promising results in terms of intuitiveness, robustness, and grasping performance. To explore these principles also in hands with augmented capabilities, this paper describes the SoftHand 2 Pro, a second generation of the device with 19 degrees-of-freedom and a second synergistic layer. After a description of the proposed device, the work explores a continuous switching control method based on a myoelectric pattern recognition classifier.

Results

The combined system was validated using standardized assessments with able-bodied and, for the first time, amputee subjects. Results show an average improvement of more than 30% of fine grasp capabilities and about 10% of hand function compared with the first generation SoftHand Pro.

Conclusions

Encouraging results suggest how this approach could be a viable way towards the design of more natural, reliable, and intuitive dexterous hands.
MMPphg from the thermophilic Meiothermus bacteriophage MMP17 as a potential antimicrobial agent against both Gram-negative and Gram-positive bacteria
Authors: Wang Feng , Xiong Yan , Xiao Yao , Han Jian , Deng Xianyu , Lin Lianbing
Published: August 2020

Background

New strategies are urgently needed to deal with the growing problem of multidrug-resistant bacterial pathogens. As the natural viruses against bacteria, recently, bacteriophages have received particular attention. Here, we identified and characterized a novel peptidoglycan hydrolase named MMPphg by decoding the complete genome sequence of Meiothermus bacteriophage MMP17, which was isolated in Tengchong hot spring in China and contains a circular genome of 33,172 bp in size and a GC content of 63.4%.

Findings

We cloned the MMPphg gene, overproduced and purified the phage lytic protein, which contains a highly conserved M23 metallopeptidase domain and can be activated by Mg2+ and Zn2+. MMPphg is capable of withstanding temperatures up to 70 °C, and preserved more than 80% of its activity after a 30 min treatment between 35 and 65 °C. More interestingly, by disrupting bacterial cells, MMPphg exhibits surprising antimicrobial activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains such as Escherichia coli O157, Staphylococcus aureus and Klebsiella pneumonia.

Conclusions

In the current age of mounting antibiotic resistance, these results suggest the great potential of MMPphg, the gene product of bacteriophage MMP17, in combating bacterial infections and shed light on bacteriophage-based strategies to develop alternatives to conventional antibiotics for human or veterinary applications.
Metallothionein-3 as a multifunctional player in the control of cellular processes and diseases
Authors: Koh Jae-Young , Lee Sook-Jeong
Published: August 2020

Transition metals, such as iron, copper, and zinc, play a very important role in life as the regulators of various physiochemical reactions in cells. Abnormal distribution and concentration of these metals in the body are closely associated with various diseases including ischemic seizure, Alzheimer’s disease, diabetes, and cancer. Iron and copper are known to be mainly involved in in vivo redox reaction. Zinc controls a variety of intracellular metabolism via binding to lots of proteins in cells and altering their structure and function. Metallothionein-3 (MT3) is a representative zinc binding protein predominant in the brain. Although the role of MT3 in other organs still needs to be elucidated, many reports have suggested critical roles for the protein in the control of a variety of cellular homeostasis. Here, we review various biological functions of MT3, focusing on different cellular molecules and diseases involving MT3 in the body.
Residents working with Médecins Sans Frontières: training and pilot evaluation
Authors: Ripoll-Gallardo Alba , Ragazzoni Luca , Mazzanti Ettore , Meneghetti Grazia , Franc Jeffrey Michael , Costa Alessandro , della Corte Francesco
Published: August 2020

Background

Well-prepared humanitarian workers are now more necessary than ever. Essential to the preparation process are: clearly defined learning objectives, curricula tailored to the nuances of humanitarian settings, simulation-based training, and evaluation. This manuscript describes a training program designed to prepare medical residents for their first field deployment with Médecins Sans Frontières and presents the results of a pilot assessment of its effectiveness.

Methods

The training was jointly developed by the Research Center in Emergency and Disaster Medicine- CRIMEDIM of the Università del Piemonte Orientale, Novara, Italy, and the humanitarian aid organization Médecins Sans Frontières- Italy (MSF-Italy); the following topics were covered: disaster medicine, public health, safety and security, infectious diseases, psychological support, communication, humanitarian law, leadership, and job-specific skills. It used a blended-learning approach consisting of a 3-month distance learning module; 1-week instructor-led coaching; and a field placement with MSF. We assessed its effectiveness using the first three levels of Kirkpatrick’s training evaluation model.

Results

Eight residents took part in the evaluation. Four were residents in emergency medicine, 3 in anesthesia, and 1 in pediatrics; 3 of them were female and the median age was 31 years. Two residents were deployed in Pakistan, 1 in Afghanistan, 1 in the Democratic Republic of Congo, 1 in Iraq, 2 in Haiti and 1 on board of the MSF Mediterranean search & rescue ship. Mean deployment time was 3 months. The average median score for the overall course was 5 (excellent). There was a significant improvement in post-test multiple choice scores (p = 0.001) and in residents’ overall performance scores (P = 0.000001).

Conclusion

Residents were highly satisfied with the training program and their knowledge and skills improved as a result of participation.

Trial registration

This study was approved by the Institutional Ethics Committee (date 24-02-2016, study code UPO.2015.4.10).
Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial
Authors: Liu Liu , Lu Yi , Yan Xiao-ning , Yang Su-qing , Gong Li-ping , Li Ling-e , Zhao Yi-ding , Yin Qing-feng , Wang Rui-ping , An Yue-peng , Huang Gang , Zhang Jin-fang , Sun Xiao-ying , Li Xin , Li Bin
Published: August 2020

Background

Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis.

Methods

Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd.

Discussion

It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis.

Trial registration

Clinicaltrials.govNCT03953885. Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome
Comparison of a flexible versus rigid bone cement injection system in unilateral percutaneous vertebroplasty
Authors: Li Yuwei , Cui Wei , Zhou Peng , Li Cheng , Wen Yan , Xiao Wei
Published: August 2020

Background

Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of acute osteoporotic vertebral fracture (AOVF). However, bilateral puncture takes more time to accept more X-ray irradiation; some scholars apply unilateral puncture PVP, but the cement cannot be symmetrically distributed in the vertebral body, so we use a flexible cement injector that undergoes PVP through the unilateral pedicle puncture. This research aims to compare the clinical results of PVP for AOVF with unilateral pedicle puncture using a straight bone cement injector and a bendable cement injector, determine the value of a bendable cement injector.

Methods

We undertook a retrospective analysis of patients with thoracic and lumbar compression fracture treated with unilateral pedicle puncture percutaneous vertebroplasty from our institution from June 2013 to July 2015. Operation time, radiation exposure, bone cement injection amount, and the incidence of bone cement leakage were recorded on presentation, the cement leakage was measured by X-ray and computed tomography scan. The patients were followed up postoperatively and were assessed mainly with regard to clinical and radiological outcomes.

Results

There was no significant difference in the operation time, radiation exposure time and incidence of bone cement leakage between the two groups. There was significant difference in the amount of bone cement injection and the difference between the two groups. There were no significant differences in VAS and the relative height of the vertebral body and local Cobb angle and QUALEFFO between the two groups at 1 week after PVP, significant difference was observed only 12 months after operation.

Conclusions

Application of flexible cement injector is safe and feasible, compared with the application of straight bone cement injector, without prolonging the operative time, radiation exposure time and the incidence of bone cement leakage; it has the advantages of good long-term effect and low incidence of vertebral fracture recurrence.
Risk factors and outcome of COVID-19 in patients with hematological malignancies
Authors: Piñana José Luis , Martino Rodrigo , García-García Irene , Parody Rocío , Morales María Dolores , Benzo Gonzalo , Gómez-Catalan Irene , Coll Rosa , De La Fuente Ignacio , Luna Alejandro , Merchán Beatriz , Chinea Anabelle , de Miguel Dunia , Serrano Ana , Pérez Carmen , Diaz Carola , Lopez José Luis , Saez Adolfo Jesús , Bailen Rebeca , Zudaire Teresa , Martínez Diana , Jurado Manuel , Calbacho María , Vázquez Lourdes , Garcia-Cadenas Irene , Fox Laura , Pimentel Ana I. , Bautista Guiomar , Nieto Agustin , Fernandez Pascual , Vallejo Juan Carlos , Solano Carlos , Valero Marta , Espigado Ildefonso , Saldaña Raquel , Sisinni Luisa , Ribera Josep Maria , Jimenez Maria Jose , Trabazo Maria , Gonzalez-Vicent Marta , Fernández Noemí , Talarn Carme , Montoya Maria Carmen , Cedillo Angel , Sureda Anna ,   Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
Published: August 2020

Background

Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined.

Patients and methods

This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020.

Results

We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1–93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2–3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6–5.2, p < 0.0001); ECOG 3–4 (OR, 2.56, 95% CI 1.4–4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3–6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7–6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2–0.89 and OR 0.31, 95% CI 0.11–0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37–1.1, P = 0.1).

Conclusions

In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.
Music performance anxiety from the challenge and threat perspective: psychophysiological and performance outcomes
Authors: Guyon Amélie J. A. A. , Studer Regina K. , Hildebrandt Horst , Horsch Antje , Nater Urs M. , Gomez Patrick
Published: August 2020

Background

Although many musicians perceive music performance anxiety (MPA) as a significant problem, studies about the psychobiological and performance-related concomitants of MPA are limited. Using the biopsychosocial model of challenge and threat as theoretical framework, we aim to investigate whether musicians’ changes in their psychobiological responses and performance quality from a private to a public performance are moderated by their general MPA level. According to the challenge and threat framework, individuals are in a threat state when the perceived demands of a performance situation outweigh the perceived resources, whereas they are in a challenge state when the perceived resources outweigh the perceived demands. The resources-demands differential (resources minus demands) and the cardiovascular challenge-threat index (sum of cardiac output and reverse scored total peripheral resistance) are the main indices of these states. We postulate that the relationship between general MPA level and performance quality is mediated by these challenge and threat measures.

Methods

We will test 100 university music students reporting general MPA levels ranging from low to high. They will perform privately (i.e., without audience) and publicly (i.e., with an audience) on two separate days in counterbalanced order. During each performance session, we will record their cardiovascular and respiratory activity and collect saliva samples and self-reported measures. Measures of primary interest are self-reported anxiety, the resources-demands differential, the cardiovascular challenge-threat index, sigh rate, total respiratory variability, partial pressure of end-tidal carbon dioxide and the salivary biomarkers cortisol, dehydroepiandrosterone, and alpha-amylase. Both, the participants and anonymous experts will evaluate the performance quality from audio recordings.

Discussion

The results of the planned project are expected to contribute to a more comprehensive understanding of the psychobiology of MPA and of the processes that influence musicians’ individual reactions to performance situations. We also anticipate the findings of this project to have important implications for the development and implementation of theory-based interventions aimed at managing musicians’ anxiety and improving performance quality. Thanks to the use of multimethod approaches incorporating psychobiology, it might be possible to better assess the progress and success of interventions and ultimately improve musicians’ chance to have a successful professional career.

Trial registration

Not applicable.
A recurrent mutation of GJB6 in a big Chinese family with Hidrotic ectodermal dysplasia
Authors: Zhan Yi , Luo Shuaihantian , Pi Zixin , Zhang Guiying
Published: August 2020

Hidrotic ectodermal dysplasia (HED) is a rare inherited syndrome characterised by nail dystrophy, palmoplantar hyperkeratosis and alopecia. Four mutations (p.G11R, p.A88V, p.V37E and p.D50N) in gap junction beta 6 (GJB6) gene, which codes connexin30 protein, have been found to cause HED in different populations. Here, we reported a big Chinese family in which 24 patients over five generations were suffered with HED. Sequence analysis identified all 24 patients carry a recurrent missense mutation c.263C > T (p.A88V) in GJB6. Our results reveal gene testing of GJB6 is important for diagnosis, prenatal diagnosis and future gene treatment of HED.
QTL and genetic analysis controlling fiber quality traits using paternal backcross population in upland cotton
Authors: MA LingLing , SU Ying , NIE Hushuai , CUI Yupeng , CHENG Cheng , IJAZ Babar , HUA Jinping
Published: August 2020

Background

Genetic improvement in fiber quality is one of the main challenges for cotton breeders. Quantitative trait loci (QTL) mapping provides a powerful approach to dissect the molecular mechanism in fiber quality traits. In present study, F14 recombinant inbred line (RIL) population was backcrossed to paternal parent for a paternal backcross (BC/P) population, deriving from one upland cotton hybrid. Three repetitive BC/P field trials and one maternal backcross (BC/M) field trial were performed including both two BC populations and the original RIL population.

Results

In total, 24 novel QTLs are detected for fiber quality traits and among which 13 QTLs validated previous results. Thirty-five QTLs in BC/P populations explain 5.01%–22.09% of phenotype variation (PV). Among the 35 QTLs, 23 QTLs are detected in BC/P population alone. Present study provides novel alleles of male parent for fiber quality traits with positive genetic effects. Particularly, qFS-Chr3–1 explains 22.09% of PV in BC/P population, which increaseds 0.48 cN·tex− 1 for fiber strength. A total of 7, 2, 8, 2 and 6 QTLs explain over 10.00% of PV for fiber length, fiber uniformity, fiber strength, fiber elongation and fiber micronaire, respectively. In RIL population, six common QTLs are detected in more than one environment: qFL-Chr1–2, qFS-Chr5–1, qFS-Chr9–1, qFS-Chr21–1, qFM-Chr9–1 and qFM-Chr9–2. Two common QTLs of qFE-Chr2–2 (TMB2386-SWU12343) and qFM-Chr9–1 (NAU2873-CGR6771) explain 22.42% and 21.91% of PV. The region between NAU4034 and TMB1296 harbor 30 genes (379 kb) in A05 and 42 genes (49 kb) in D05 for fiber length along the QTL qFL-Chr5–1 in BC/P population, respectively. In addition, a total of 142 and 46 epistatic QTLs and QTL × environments (E-QTLs and QQEs) are identified in recombinant inbred lines in paternal backcross (RIL-P) and paternal backcross (BC/P) populations, respectively.

Conclusions

The present studies provide informative basis for improving cotton fiber quality in different populations.
Facile preparation of hierarchical porous polydopamine microspheres for rapid removal of chromate from the wastewater
Authors: Xiang Lin , Lin Jiayou , Yang Qin , Lin Shaojian , Chen Sheng , Yan Bin
Published: August 2020

Cr(VI) containing industrial wastewaters are highly toxic and carcinogenic, and severely threats living creatures and the environment. Therefore, it is highly desired yet challenging to develop an available and economical adsorbent for simultaneously detoxifying Cr(VI) anions to Cr(III) ions and removing them from the wastewater. Here we propose a facile method for rapid removal of Cr(VI) ions from the wastewater by using a synthetic polydopamine microsphere (PPM) adsorbent with hierarchical porosity. The as-prepared PPM exhibits high Cr(VI) removal capacity of 307.7 mg/g and an outstanding removal efficiency. They can effectively decrease the Cr(VI) concentration to lower than 0.05 mg/L well below the limits for drinking water standard of WHO regulations in 60 s at pH 2. More importantly, PPMs can reduce the lethal Cr(VI) anions to Cr(III) ions with low toxicity, and simultaneously immobilize them on the matrices of PPMs.

Graphical abstract
Chitin synthase localization in the diatom Thalassiosira pseudonana
Authors: Wustmann Martin , Poulsen Nicole , Kröger Nils , van Pée Karl-Heinz
Published: August 2020

Chitin constitutes an abundant component in many biologically formed minerals (biominerals). While the role of chitin for the formation and properties of calcium-based biominerals has been extensively studied, little is known about its role in silica-based biominerals. Furthermore, there is hardly any information about the enzyme machinery for chitin biosynthesis in biomineral-forming organisms. Here we have identified a chitin synthase, chs7305, in the diatomThalassiosira pseudonana. In stationary cells, chs7305 is located specifically in a ring pattern in the region of the silicified girdle bands. The expression pattern of the chs7305 gene and the co-localization of the encoded enzyme with chitin provides evidence for the importance of chitin synthesis for cell wall function under nutrient limited conditions. Chs7305 is the first chitin synthase that has been localized in a diatom.
An exploration of psychopathology for clinical practice
Authors: Sanati Abdi
Published: August 2020

Psychopathology is an integral part of the theory and practice of psychiatry. This commentary explores the importance of psychopathology, especially with regard to clinical practice. The concept of lifeworld is introduced as an important component of attributing meaning to a person's experience of mental disorder. It is also argued that the advance of neuroscience does not preclude the importance of psychopathology.
The importance of embedding psychopathology and phenomenology in clinical practice and training in psychiatry
Authors: Chakraborty Nandini
Published: August 2020

Psychiatrists live and work in complex, clinically challenging times. Their paperwork is geared increasingly towards defensive practice, key performance indicators and risk assessment forms. Somewhere in the process, detailed understanding of patient experience and clinical formulation based on key psychiatric expertise and skill in mental state examination have taken a backseat. I review the history behind the Present State Examination, the realisation in the 1980s of the need for a common psychiatric language internationally and the current position on phenomenology in psychiatry curricula in the UK. I conclude that it is time to think seriously about a return to basics in psychiatric phenomenology and psychopathology.
Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial
Authors: Meattini Icro , Marrazzo Livia , Saieva Calogero , Desideri Isacco , Scotti Vieri , Simontacchi Gabriele , Bonomo Pierluigi , Greto Daniela , Mangoni Monica , Scoccianti Silvia , Lucidi Sara , Paoletti Lisa , Fambrini Massimiliano , Bernini Marco , Sanchez Luis , Orzalesi Lorenzo , Nori Jacopo , Bianchi Simonetta , Pallotta Stefania , Livi Lorenzo
Published: August 2020

PURPOSE

To report the long-term results of external-beam accelerated partial-breast irradiation (APBI) intensity-modulated radiation therapy (IMRT) Florence phase III trial comparing whole-breast irradiation (WBI) to APBI in early-stage breast cancer.

PATIENTS AND METHODS

The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence (IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed boost (WBI arm) after breast-conserving surgery.

RESULTS

Five hundred twenty patients, more than 90% of whom had characteristics associated with low recurrence risk, were randomly assigned (WBI, n = 260; APBI, n = 260) between 2005 and 2013. Median follow-up was 10.7 years. The 10-year cumulative incidence of IBTR was 2.5% (n = 6) in the WBI and 3.7% (n = 9) in the APBI arm (hazard ratio [HR], 1.56; 95% CI, 0.55 to 4.37; P = .40). Overall survival at 10 years was 91.9% in both arms (HR, 0.95; 95% CI, 0.50 to 1.79; P = .86). Breast cancer–specific survival at 10 years was 96.7% in the WBI and 97.8% in the APBI arm (HR, 0.65; 95% CI, 0.21 to 1.99; P = .45). The APBI arm showed significantly less acute toxicity ( P = .0001) and late toxicity ( P = .0001) and improved cosmetic outcome as evaluated by both physician ( P = .0001) and patient ( P = .0001).

CONCLUSION

The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late treatment-related toxicity and cosmesis outcomes were significantly in favor of APBI.
Phase I trial and pharmacokinetic study of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with refractory solid tumors: A Children's Oncology Group Phase I Consortium study
Authors: Wagner L. M. , Perentesis J. P. , Reid J. M. , Ames M. M. , Safgren S. L. , Nelson M. D. , Ingle A. M. , Blaney S. M. , Adamson P. C.
Published: August 2020

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Background: In preclinical models, temozolomide (TMZ) and vincristine (VCR) are synergistic with irinotecan (IRN). We sought to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of orally administered IRN given on two different schedules together with TMZ and VCR in children with refractory solid tumors, using cefixime to reduce IRN-associated diarrhea. Methods: Schedule A: Oral IRN daily for 5 days for 2 weeks (dx5x2), with VCR 1.5 mg/m2 on days 1 and 8 and TMZ 100 mg/m2 on days 1 - 5. Schedule B: Oral IRN daily for 5 days for 1 week (dx5x1) with VCR 1.5 mg/m2 on day 1 and TMZ 100 - 150 mg/m2 on days 1 - 5. Courses were repeated every 3 weeks. A standard cohorts of 3 + 3 design was used. Results: On Schedule A, 18 evaluable patients (median age 15 yrs, range 3 - 21) received 55 courses. At IRN 50 mg/m2/day, 4/12 pts had DLT (hepatotoxicity, abdominal pain, anorexia, hypokalemia, and thrombocytopenia). The oral IRN MTD on this dx5x2 schedule was 35 mg/m2/d (1/6 pts with DLT of hypoalbuminemia). On Schedule B, 18 evaluable patients (median age 9 yrs, range 3–21) received 71 courses of oral IRN 70 - 90 mg/m2/d x 5 with TMZ 100 - 150 mg/m2/d x 5. At oral IRN 90 mg/m2/d with TMZ 150 mg/m2/d, 0/6 pts had DLT, and no Grade 4 toxicities were seen. No further doses were explored. First-course and cumulative toxicity appeared worse with Schedule A, including 3 patients with responding or stable tumors who withdrew due to fatigue, nausea, and weight loss. UGT1A1*28genotype did not correlate with DLT. At the oral IRN MTD of 90 mg/m2/d, the median SN-38 AUCinf was 72 ng/ml*h. One patient with osteosarcoma had a confirmed partial response. Unconfirmed complete and partial responses were seen in 2 Ewing sarcoma patients. Eight additional patients received > 6 courses, including 2 each with neuroblastoma and medulloblastoma. Conclusions: The dx5x1 schedule of VOIT was well tolerated, with SN-38 exposures similar to those achieved with intravenous IRN. Activity on this and prior studies suggests a potential role for VOIT in sarcoma patients.

No significant financial relationships to disclose.
Overall survival (OS) in contemporary randomized clinical trials (RCT) in advanced breast cancer (ABC)
Authors: Katz A. , Saad E. D. , Buyse M. E.
Published: August 2020

1002

Background: OS has been considered an elusive endpoint, while progression-free survival (PFS), time to tumor progression (TTP), and time to treatment failure (TTF) have been used frequently and often interchangeably as primary endpoints (PE) in ABC (Saad, Ann Oncol 2009). Methods: We searched PubMed using the medical subject headings “breast neoplasms” and “drug therapy,” limiting the search to phase III trials on systemic antineoplastic therapies published between 1/2000 and 12/2007 in 8 leading medical journals (Ann Oncol, BCRT, BJC, Cancer, EJC, JCO, Lancet Oncol, and NEJM). PE was the one stated explicitly, used for N calculation, or listed first. Significant PE (SigPE) was considered as P <0.05 for superiority trials (N=47), or proven non-inferiority/equivalence otherwise. Results: We retrieved 58 RTCs, with a median sample size of 329 evaluable patients. The table shows the breakdown of these trials by size and PE, and the number of trials that reached statistical significance on their PE and on OS. Overall, a statistically significant gain in OS was reported in 11 of 58 RCTs (19%). In 30 RCTs with gain in PE, 26 favored the experimental arm. Conclusions: While publication and journal selection biases may not be excluded, our review suggests that gain in OS, although seldom a primary study objective, is not infrequent in contemporary RCTs in ABC. However, the majority of RCTs are underpowered for OS, which remains a secondary or exploratory endpoint in most cases.

[Table: see text]

No significant financial relationships to disclose.
Pegfilgrastim in pediatric sarcoma patients undergoing dose-intensive chemotherapy: Phase II study results
Authors: Spunt S. L. , Irving H. , Frost J. , Sender L. , Yang B. , Santana V. M.
Published: August 2020

10024

Background: Children with cancer undergoing dose-intensive chemotherapy often require G-CSF support. Patients (pts) < 2 yrs have the highest risk of prolonged neutropenia due to imprecise dosing and immature drug clearance. Once-per-cycle pegfilgrastim may be beneficial due to neutrophil-mediated clearance that allows adequate serum levels throughout the neutropenic period. Young pts, who receive relatively more myeloablative chemotherapy, should have the highest pegfilgrastim exposure. Methods: Pts ≤21 yrs (age groups 0–5, 6–11, and ≥12 yrs) with sarcoma and scheduled to receive VAdriaC (cycles 1 & 3) and IE (cycles 2 & 4) were randomized 6:1 to receive pegfilgrastim 100 μg/kg or filgrastim (5 μg/kg/d until ANC ≥ 10×109/L) 24 hrs after chemotherapy administration. Post-nadir ANC recovery, incidence of ANC recovery by day 21 of cycles 1 & 3, pharmacokinetics (PK), and safety by age group were evaluated. Results: 43 pts (63% male) received pegfilgrastim (n=37) or filgrastim (n=6). Maximum pegfilgrastim concentration was achieved ∼24-hrs postdose and sustained until ANC nadir. Pegfilgrastim levels fell rapidly as ANC recovered. One child did not achieve ANC recovery by day 21 in cycle 1: an 8-mo-old 7.9-kg boy with non-metastatic undifferentiated sarcoma had 24 days of severe neutropenia in cycle 1. The youngest age group (including this child) had longer duration of severe neutropenia and, consequently, higher pegfilgrastim exposure ( Table ). Treatment-related adverse events were generally mild to moderate (pegfilgrastim 22%, filgrastim 33%); the only treatment-related event reported by >1 pt was bone pain (pegfilgrastim=11%, filgrastim=17%). Conclusions: ANC, PK, and safety profiles in pediatric patients were comparable with those in adults and support pegfilgrastim dosing across pediatric age groups. Consistent with neutrophil-mediated clearance, adequate exposure to pegfilgrastim was maintained in the youngest pts who received the most myelosuppressive chemotherapy.

[Table: see text]

[Table: see text]
Exercise capacity in long-term survivors of pediatric cancer
Authors: Miller T. L. , Miller A. M. , Lopez-Mitnik G. , Somarriba G. , Lipsitz S. R. , Hinkle A. S. , Constine L. S. , Lipshultz S. E.
Published: August 2020

10026

Background: Childhood cancer survivors may have premature symptomatic cardiovascular and noncardiovascular diseases that contribute to reduced capacity for physical activity. Controlled assessments of exercise capacity and identification of risk factors for reduced capacity in survivors are lacking. Methods: We assessed maximal myocardial oxygen consumption (VO2max; measure of exercise capacity) in survivors at least 4 years after diagnosis and sibling controls. We evaluated associations between VO2max and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity. Results: Of 72 survivors (mean age, 22 y; range, 8.0 to 40 y) and 32 siblings (mean age, 20.2 y; range, 8 to 46 y), about half were male. The mean time since cancer diagnosis was 13.4 y (range, 4.5 to 31.6 y). In age- and sibling-pair adjusted analyses, VO2max was lower in survivors than siblings (males, 28.53 vs. 30.90 mL/kg/min, P = 0.08; females, 19.81 vs. 23.40 mL/kg/min, P = 0.03). In male survivors, older age (P = 0.01), higher percent body fat (P < 0.001) and high or low left ventricular (LV) mass Z-scores (P = 0.03) predicted lower VO2max. In females, older age (P < 0.001), methotrexate exposure (P = 0.01), and higher, but normal, LV load-dependent contractility (P = 0.02) predicted lower VO2max. Conclusions: Physical fitness for most participants in each group was poor, and was generally lower in survivors, particularly females. Older age, higher body fat, methotrexate exposure, and extremes of LV mass/function were associated with lower VO2max in survivors. Because physical activity can improve nutritional and cardiac conditions, survivors should be encouraged to engage in regular exercise with close medical monitoring.

No significant financial relationships to disclose.
A longitudinal study of processing speed among children treated for medulloblastoma (MB), supratentorial primitive neuroectodermal tumor (SPNET), or atypical teratoid rhabdoid tumor (ATRT)
Authors: Palmer S. , Wallace D. , Bonner M. , Raggl R. , Chapieski L. , Janzen L. , Knight S. , Boyle R. , Armstrong C. , Gajjar A.
Published: August 2020

10028

Background: Indicating a strong relationship to intelligence, processing speed parallels with the rate of knowledge acquisition. To further our understanding of the etiology of deficits in intellectual ability that continues to plague this group of children, the current study prospectively examined longitudinal changes in an underlying cognitive ability, processing speed. Methods: The study included 174 patients (median age at diagnosis = 9.0) enrolled on a multi-site protocol (SJMB03) for MB, SPNET or ATRT. Patients were treated with post-surgical risk-adapted craniospinal irradiation (CSI) followed by 4 cycles of high-dose chemotherapy (cyclophosphamide, cisplatin, vincristine) with stem cell support. High risk (HR, n = 55) patients received 36 - 39.6 Gy CSI and 3D conformal boost to the primary site to 55.8 –59.4 Gy. Average-risk (AR, n=119) patients received 23.4 Gy CSI, 3D conformal boost to the primary site to 55.8 Gy. Those who had posterior fossa syndrome were excluded (n = 26) resulting in 148 patients who completed 459 neuropsychological evaluations using the Woodcock Johnson Tests of Cognitive Abilities-III over a period of 0.03 –4.94 years postdiagnosis. Results: Multivariate modeling revealed a statistically significant decline in processing speed for those < 7 years of age at time of diagnosis (-3.83 points per year, p = 0.003). Those who were > 7 years at diagnosis did not experience a significant change (.86, NS). HR patients experienced greater declines (-.82) than those who were AR (-0.29), but neither slope was statistically significant. Interaction models revealed declines for those in the <7/AR group (-4.17, p = 0.003), and <7/HR group (-3.38, NS). Those >7/AR and >7/HR did not experience significant change (1.06 and 0.32, respectively). Conclusions: Young age at diagnosis is a prominent risk factor for processing speed impairment among survivors of pediatric embryonal tumors. Processing speed may also be among the first deficits to appear following treatment. This study represents the largest comparison of processing speed ability among patients treated for pediatric embryonal tumors with conventional or reduced dose CSI and adjuvant chemotherapy.

No significant financial relationships to disclose.