bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis reveals potential function of long non-coding RNAs in 20-hydroxyecdysone regulated autophagy in Bombyx mori
Authors: Qiao Huili , Wang Jingya , Wang Yuanzhuo , Yang Juanjuan , Wei Bofan , Li Miaomiao , Wang Bo , Li Xiaozhe , Cao Yang , Tian Ling , Li Dandan , Yao Lunguang , Kan Yunchao
Published: May 2021

Background

20-hydroxyecdysone (20E) plays important roles in insect molting and metamorphosis. 20E-induced autophagy has been detected during the larval–pupal transition in different insects. In Bombyx mori, autophagy is induced by 20E in the larval fat body. Long non-coding RNAs (lncRNAs) function in various biological processes in many organisms, including insects. Many lncRNAs have been reported to be potential for autophagy occurrence in mammals, but it has not been investigated in insects.

Results

RNA libraries from the fat body of B. mori dissected at 2 and 6 h post-injection with 20E were constructed and sequenced, and comprehensive analysis of lncRNAs and mRNAs was performed. A total of 1035 lncRNAs were identified, including 905 lincRNAs and 130 antisense lncRNAs. Compared with mRNAs, lncRNAs had longer transcript length and fewer exons. 132 lncRNAs were found differentially expressed at 2 h post injection, compared with 64 lncRNAs at 6 h post injection. Thirty differentially expressed lncRNAs were common at 2 and 6 h post-injection, and were hypothesized to be associated with the 20E response. Target gene analysis predicted 6493 lncRNA-mRNA cis pairs and 42,797 lncRNA-mRNA trans pairs. The expression profiles of LNC_000560 were highly consistent with its potential target genes, Atg4B, and RNAi of LNC_000560 significantly decreased the expression of LNC_000560 and Atg4B. These results indicated that LNC_000560 was potentially involved in the 20E-induced autophagy of the fat body by regulating Atg4B.

Conclusions

This study provides the genome-wide identification and functional characterization of lncRNAs associated with 20E-induced autophagy in the fat body of B. mori. LNC_000560 and its potential target gene were identified to be related to 20-regulated autophagy in B. mori. These results will be helpful for further studying the regulatory mechanisms of lncRNAs in autophagy and other biological processes in this insect model.
Genome-wide identification and expression analysis of the WRKY transcription factor family in flax (Linum usitatissimum L.)
Authors: Yuan Hongmei , Guo Wendong , Zhao Lijuan , Yu Ying , Chen Si , Tao Lei , Cheng Lili , Kang Qinghua , Song Xixia , Wu Jianzhong , Yao Yubo , Huang Wengong , Wu Ying , Liu Yan , Yang Xue , Wu Guangwen
Published: May 2021

Background

Members of the WRKY protein family, one of the largest transcription factor families in plants, are involved in plant growth and development, signal transduction, senescence, and stress resistance. However, little information is available about WRKY transcription factors in flax (Linum usitatissimum L.).

Results

In this study, comprehensive genome-wide characterization of the flax WRKY gene family was conducted that led to prediction of 102 LuWRKY genes. Based on bioinformatics-based predictions of structural and phylogenetic features of encoded LuWRKY proteins, 95 LuWRKYs were classified into three main groups (Group I, II, and III); Group II LuWRKYs were further assigned to five subgroups (IIa-e), while seven unique LuWRKYs (LuWRKYs 96–102) could not be assigned to any group. Most LuWRKY proteins within a given subgroup shared similar motif compositions, while a high degree of motif composition variability was apparent between subgroups. Using RNA-seq data, expression patterns of the 102 predicted LuWRKY genes were also investigated. Expression profiling data demonstrated that most genes associated with cellulose, hemicellulose, or lignin content were predominantly expressed in stems, roots, and less in leaves. However, most genes associated with stress responses were predominantly expressed in leaves and exhibited distinctly higher expression levels in developmental stages 1 and 8 than during other stages.

Conclusions

Ultimately, the present study provides a comprehensive analysis of predicted flax WRKY family genes to guide future investigations to reveal functions of LuWRKY proteins during plant growth, development, and stress responses.
The Rhododendron Plant Genome Database (RPGD): a comprehensive online omics database for Rhododendron
Authors: Liu Ningyawen , Zhang Lu , Zhou Yanli , Tu Mengling , Wu Zhenzhen , Gui Daping , Ma Yongpeng , Wang Jihua , Zhang Chengjun
Published: May 2021

Background

The genus Rhododendron L. has been widely cultivated for hundreds of years around the world. Members of this genus are known for great ornamental and medicinal value. Owing to advances in sequencing technology, genomes and transcriptomes of members of the Rhododendron genus have been sequenced and published by various laboratories. With increasing amounts of omics data available, a centralized platform is necessary for effective storage, analysis, and integration of these large-scale datasets to ensure consistency, independence, and maintainability.

Results

Here, we report our development of the Rhododendron Plant Genome Database (RPGD; http://bioinfor.kib.ac.cn/RPGD/), which represents the first comprehensive database of Rhododendron genomics information. It includes large amounts of omics data, including genome sequence assemblies for R. delavayi, R. williamsianum, and R. simsii, gene expression profiles derived from public RNA-Seq data, functional annotations, gene families, transcription factor identification, gene homology, simple sequence repeats, and chloroplast genome. Additionally, many useful tools, including BLAST, JBrowse, Orthologous Groups, Genome Synteny Browser, Flanking Sequence Finder, Expression Heatmap, and Batch Download were integrated into the platform.

Conclusions

RPGD is designed to be a comprehensive and helpful platform for all Rhododendron researchers. Believe that RPGD will be an indispensable hub for Rhododendron studies.
Integrative analysis of transcriptome and proteome revealed nectary and nectar traits in the plant-pollinator interaction of Nitraria tangutorum Bobrov
Authors: Chen Tingting , Zhou Yanwei , Zhang Jingbo , Peng Ye , Yang Xiuyan , Hao Zhaodong , Lu Ye , Wu Weihuang , Cheng Tielong , Shi Jisen , Chen Jinhui
Published: May 2021

Background

Nitraria tangutorum is an important desert shrub that shows resistance to drought, salt and wind erosion stresses. It is a central ecological species in its area. Here, we have studied how N. tangutorum has adapted to achieve a successful reproduction strategy.

Results

We found that N. tangutorum is mainly pollinated by insects of the Hymenoptera, Diptera and Coleoptera orders. Nitraria tangutorum has very small flowers, with the nectary composed of secretive epidermal cells from which nectar is secreted, located within the inner petals. In addition, analyzing the transcriptome of four successive flower developmental stages revealed that mainly differentially expressed genes associated with flower and nectary development, nectar biosynthesis and secretion, flavonoid biosynthesis, plant hormone signal transduction and plant-pathogen interaction show dynamic expression. From the nectar, we could identify seven important proteins, of which the L-ascorbate oxidase protein was first found in plant nectar. Based on the physiological functions of these proteins, we predict that floral nectar proteins of N. tangutorum play an important role in defending against microbial infestation and scavenging active oxygen.

Conclusions

This study revealed that N. tangutorum is an insect-pollinated plant and its nectary is composed of secretive epidermal cells that specialized into secretive trichomes. We identified a large number of differentially expressed genes controlling flower and nectary development, nectar biosynthesis and secretion, flavonoid biosynthesis, plant hormone signal transduction and plant-pathogen interaction. We suggest that proteins present in N. tangutorum nectar may have both an antibacterial and oxygen scavenging effect. These results provide a scientific basis for exploring how the reproductive system of N. tangutorum and other arid-desert plants functions.
High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial
Authors: Ingabire Prossie Merab , Ojji Dike B. , Rayner Brian , Ogola Elijah , Damasceno Albertino , Jones Erika , Dzudie Anastase , Ogah Okechukwu S. , Poulter Neil , Sani Mahmoud U. , Barasa Felix Ayub , Shedul Grace , Mukisa John , Mukunya David , Wandera Bonnie , Batte Charles , Kayima James , Pandie Shahiemah , Mondo Charles Kiiza ,   CREOLE Study Investigators
Published: May 2021

Background

Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction.

Objectives

To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients.

Methods

This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures.

Results

The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17–2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar’s Chi2 0.71, p-value 0.40).

Conclusion

There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes.

Trial registration ClinicalTrials.gov (NCT02742467).
Classifying information-sharing methods
Authors: Nikolaidis Georgios F. , Woods Beth , Palmer Stephen , Soares Marta O.
Published: May 2021

Background

Sparse relative effectiveness evidence is a frequent problem in Health Technology Assessment (HTA). Where evidence directly pertaining to the decision problem is sparse, it may be feasible to expand the evidence-base to include studies that relate to the decision problem only indirectly: for instance, when there is no evidence on a comparator, evidence on other treatments of the same molecular class could be used; similarly, a decision on children may borrow-strength from evidence on adults. Usually, in HTA, such indirect evidence is either included by ignoring any differences (‘lumping’) or not included at all (‘splitting’). However, a range of more sophisticated methods exists, primarily in the biostatistics literature. The objective of this study is to identify and classify the breadth of the available information-sharing methods.

Methods

Forwards and backwards citation-mining techniques were used on a set of seminal papers on the topic of information-sharing. Papers were included if they specified (network) meta-analytic methods for combining information from distinct populations, interventions, outcomes or study-designs.

Results

Overall, 89 papers were included. A plethora of evidence synthesis methods have been used for information-sharing. Most papers (n=79) described methods that shared information on relative treatment effects. Amongst these, there was a strong emphasis on methods for information-sharing across multiple outcomes (n=42) and treatments (n=25), with fewer papers focusing on study-designs (n=23) or populations (n=8). We categorise and discuss the methods under four ’core’ relationships of information-sharing: functional, exchangeability-based, prior-based and multivariate relationships, and explain the assumptions made within each of these core approaches.

Conclusions

This study highlights the range of information-sharing methods available. These methods often impose more moderate assumptions than lumping or splitting. Hence, the degree of information-sharing that they impose could potentially be considered more appropriate. Our identification of four ‘core’ methods of information-sharing allows for an improved understanding of the assumptions underpinning the different methods. Further research is required to understand how the methods differ in terms of the strength of sharing they impose and the implications of this for health care decisions.
Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores
Authors: Hu Taobo , Chen Yan , Liu Yiqiang , Zhang Danhua , Pan Jiankang , Long Mengping
Published: May 2021

Purpose

PR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed.

Methods

In this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression.

Results

ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER+/PR+/HER2- and ER+/PR-/HER2- groups.

Conclusions

In conclusion, this study indicated in ER+/HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation.
Self-help guided by trained lay providers for generalized anxiety disorder in older adults: study protocol for a randomized controlled trial
Authors: Landreville Philippe , Gosselin Patrick , Grenier Sébastien , Carmichael Pierre-Hugues
Published: May 2021

Background

Only a small proportion of older patients with generalized anxiety disorder (GAD) seek professional help. Difficulties in accessing treatment may contribute to this problem. Guided self-help based on the principles of cognitive-behavioral therapy (GSH-CBT) is one way of promoting access to psychological treatment. Moreover, because the therapist’s role in GSH-CBT is limited to supporting the patient, this role could be assumed by trained and supervised lay providers (LPs) instead of licensed providers. The main goal of this study is to evaluate the efficacy of GSH-CBT guided by LPs for primary threshold or subthreshold GAD in older adults.

Methods

We will conduct a multisite randomized controlled trial comparing an experimental group receiving GSH-CBT guided by LPs (n = 45) to a wait-list control group (n = 45). Treatment will last 15 weeks and will be based on a participant’s manual. Weekly telephone sessions with LPs (30 min maximum) will be limited to providing support. Data will be obtained through clinician evaluations and self-assessment questionnaires. Primary outcomes will be the tendency to worry and severity of GAD symptoms. Secondary outcomes will be anxiety symptoms, sleep difficulties, functional deficit, diagnosis of GAD, and cognitive difficulties. For the experimental group, measurements will take place at pre- and post-treatment and at 6 and 12 months post-treatment. For the control group, three evaluations are planned: two pre-treatment evaluations (before and after the waiting period) and after receiving treatment (post-treatment). The efficacy of GSH-CBT will be established by comparing the change in the two groups on the primary outcomes.

Discussion

This project will provide evidence on the efficacy of a novel approach to treat GAD in older adults. If effective, it could be implemented on a larger scale and provide many older adults with much needed mental health treatment through an expanded workforce.

Trial registration

The trial was registered at ClinicalTrials.gov, number NCT03768544, on December 7, 2018.
Development of an 360-degree virtual reality video-based immersive cycle training system for physical enhancement in older adults: a feasibility study
Authors: Lee Namsu , Choi Wonjae , Lee Seungwon
Published: May 2021

Background

Recently, there is an increased number of studies that use 360° virtual reality (VR) video for medical and rehabilitative purposes. However, the 360° VR video experience for older adults has not yet been investigated. This study aimed to examine the validity of an 360° VR video-based immersive cycling training system (360° VRCTS) for older adults and to provide preliminary evidence of efficacy.

Methods

We developed a new virtual reality training system using an immersive environment 360° VRCTS. Five healthy older adults (2 males and 3 females) participated in this study. The system was tested in a single training session (biking for 20 min while viewing a 360° VR video scene through a large curved screen) to identify its strengths and weakness. The usability and acceptability of our system were measured using the system usability scale (SUS) and the simulator sickness questionnaire (SSQ).

Results

All participants successfully completed the session without any discomfort. The average score for the SUS was 94.60 (range, 90–100), indicating high usability of the technology. The average score for the SSQ was 2.24 (standard deviation = 2.05), indicating that the system is well tolerated and has few side effects.

Conclusions

The 360° VRCTS may be a useful indoor training system for older adults due to its easy manipulation, high usability, and limited cybersickness.

Trial registration number

Clinical Research Information Services (CRiS),
KCT0003555, Registered February 25, 2019, https://cris.nih.go.kr/cris/index/index.do.
Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis
Authors: Ledesma Jorge R. , Ma Jianing , Zheng Peng , Ross Jennifer M. , Vos Theo , Kyu Hmwe H.
Published: May 2021

Background

Identifying and treating individuals with high risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease is critical for eliminating the disease. We aimed to conduct a systematic review and meta-regression analysis to quantify the dose-response relationship between interferon-gamma release assay (IGRA) levels and the risk of progression to active TB.

Methods

We searched PubMed and Embase from 1 January 2001 to 10 May 2020 for longitudinal studies that reported the risk of progression from latent to active TB as a function of baseline IGRA values. We used a novel Bayesian meta-regression method to pool effect sizes from included studies and generate a continuous dose-response risk curve. Our modeling framework enabled us to incorporate random effects across studies, and include data with different IGRA ranges across studies. The quality of included studies were assessed using the Newcastle-Ottawa scale (NOS).

Results

We included 34 studies representing 581,956 person-years of follow-up with a total of 788 incident cases of TB in the meta-regression analysis. Higher levels of interferon-gamma were associated with increased risk of progression to active tuberculosis. In the dose-response curve, the risk increased sharply between interferon-gamma levels 0 and 5 IU/ml, after which the risk continued to increase moderately but at a slower pace until reaching about 15 IU/ml where the risk levels off. Compared to 0 IU/ml, the relative risk of progression to active TB among those with interferon-gamma levels of 0.35, 1, 5, 10, 15, and 20 IU/ml were: 1.64 (1.28–2.08), 2.90 (2.02–3.88), 11.38 (6.64–16.38), 19.00 (13.08–26.90), 21.82 (14.65–32.57), and 22.31 (15.43–33.00), respectively. The dose-response relationship remains consistent when limiting the analysis to studies that scored highest in the NOS.

Conclusion

The current practice of dichotomizing IGRA test results simplifies the TB infection disease continuum. Evaluating IGRA test results over a continuous scale could enable the identification of individuals at greatest risk of progression to active TB.
Management of insecticides for use in disease vector control: a global survey
Authors: van den Berg Henk , da Silva Bezerra Haroldo Sergio , Chanda Emmanuel , Al-Eryani Samira , Nagpal Bhupender N. , Gasimov Elkhan , Velayudhan Raman , Yadav Rajpal S.
Published: May 2021

Background

Vector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the management practices of vector control insecticides at country level to identify gaps to inform future strategies on pesticide management, seeking to improve efficacy of interventions and reduce the side-effects of chemicals used on health and the environment.

Methods

A survey by questionnaire on the management practices of vector control insecticides was disseminated among all WHO Member States. Data were analysed using descriptive statistics in MS Excel.

Results

Responses were received from 94 countries, or a 48% response rate. Capacity for insecticide resistance monitoring was established in 68–80% of the countries in most regions, often with external support; however, this capacity was largely lacking from the European & Others Region (i.e. Western & Eastern Europe, North America, Australia and New Zealand). Procurement of vector control insecticides was in 50–75% of countries taking place by agencies other than the central-level procuring agency, over which the central authorities lacked control, for example, to select the product or assure its quality, highlighting the importance of post-market monitoring. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Large fractions (29–78%) of countries across regions showed shortcomings in worker safety, pesticide storage practices and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Region, which has long been relatively free from mosquito-borne diseases but has recently faced challenges of re-emerging vector-borne diseases.

Conclusions

Critical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country levels to address these challenges.
AIDS fighter health defense: protocol for a randomized controlled trial to test a game-based intervention to improve adolescents’ AIDS prevention ability
Authors: Tang Jian , Chen Yanhua , Yu Xingli , Ren Jianlan , Li Mei , Luo Yue , Xie Hong , Wen Jing
Published: May 2021

Background

Although great progress has been made in the prevention and treatment of AIDS, there are still a considerable number of new infections annually, especially in adolescents. With the advance of technology, game-based education has gradually become an important tool for changing healthy behaviors among youth.

Methods

A protocol for conducting a randomized controlled trial to evaluate the “AIDS Fighter · Health Defense”, a game-based AIDS education project aimed at improving the ability of adolescents to prevent AIDS. During the four-week intervention, participants will receive: 1) A virus combat game; 2) Goal setting to eliminate HIV; 3) Questions to be answered to be resurrected in the game; 4) Points ranking; 5) Recognition and Rewards. The primary outcomes include changes in participants’ knowledge, stigma attitude, and risk behaviors attitude related to AIDS after four weeks of intervention. The secondary outcomes are the participants’ AIDS-related risk behaviors three and six months after the intervention.

Discussion

AIDS Fighter· Health Defense may be an innovative approach to help adolescents improve AIDS prevention capabilities, fill the gap in game-based AIDS prevention education in China, and gain experience of AIDS management.

Trial registration

Chinese Clinical Trial Registry: ChiCTR2000040195. Registered 25 November 2020.
Whole brain 3D MR fingerprinting in multiple sclerosis: a pilot study
Authors: Mostardeiro Thomaz R. , Panda Ananya , Campeau Norbert G. , Witte Robert J. , Larson Nicholas B. , Sui Yi , Lu Aiming , McGee Kiaran P.
Published: May 2021

Background

MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis.

Methods

Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1 × 1 × 1 mm3) and a total acquisition time of 4 min 38 s. Data were collected on 18 subjects paired with 18 controls. Regions of interest were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms. Partial least squares discriminant analysis was performed to discriminate NAWM and Splenium in MS compared with controls.

Results

Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65 % (p = 0.21) and approached 90 % (p < 0.01) for the splenium. There was significant positive correlation between time since diagnosis and MS lesions mean T2 (p = 0.015), minimum T1 (p = 0.03) and negative correlation with splenium uniformity (p = 0.04). Perfect discrimination (AUC = 1) was achieved between selected features from MS lesions and F-NAWM.

Conclusions

3D-MRF has the ability to differentiate between MS and controls based on relaxometry properties from the F-NAWM and splenium. Whole brain coverage allows the assessment of quantitative properties within lesions that provide chronological assessment of the time from MS diagnosis.
Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study
Authors: Sai Asuka , Tanaka Kentaro , Ohashi Yasushi , Kushiyama Akifumi , Tanaka Yoshihide , Motonishi Shuta , Sakai Ken , Hara Shigeko , Ozawa Takashi
Published: May 2021

Background

Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients.

Methods

Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient’s self-report during the one-year period.

Results

Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22–4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576–0.738), 0.625 (95% CI, 0.545–0.699), and 0.701 (95% CI, 0.617–0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients.

Conclusions

Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.
First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients
Authors: Mrevlje Maja , Oblak Manca , Mlinšek Gregor , Lindič Jelka , Jadranka-Buturović-Ponikvar  , Arnol Miha
Published: May 2021

Background

Quantification of proteinuria in kidney transplant recipients is important for diagnostic and prognostic purposes. Apart from correlation tests, there have been few evaluations of spot urine protein measurements in kidney transplantation.

Methods

In this cross-sectional study involving 151 transplanted patients, we investigated measures of agreement (bias and accuracy) between the estimated protein excretion rate (ePER), determined from the protein-to-creatinine ratio in the first and second morning urine, and 24-h proteinuria and studied their performance at different levels of proteinuria. Measures of agreement were reanalyzed in relation to allograft histology in 76 patients with kidney biopsies performed for cause before enrolment in the study.

Results

For ePER in the first morning urine, percent bias ranged from 1 to 28% and accuracy (within 30% of 24-h collection) ranged from 56 to 73%. For the second morning urine, percent bias ranged from 2 to 11%, and accuracy ranged from 71 to 78%. The accuracy of ePER (within 30%) in first and second morning urine progressively increased from 56 and 71% for low-grade proteinuria (150–299 mg/day) to 60 and 74% for moderate proteinuria (300–999 mg/day), and to 73 and 78% for high-grade proteinuria (≥1000 mg/day). Measures of agreement were similar across histologic phenotypes of allograft injury.

Conclusions

The ability of ePER to accurately predict 24-h proteinuria in kidney transplant recipients is modest. However, accuracy improves with an increase in proteinuria. Given the similar accuracy of ePER measurements in first and second morning urine, second morning urine can be used to monitor protein excretion.
Midterm prognosis and surgical implication for clival chordomas after extended transsphenoidal tumor removal and gamma knife radiosurgery
Authors: Ogawa Yoshikazu , Jokura Hidefumi , Tominaga Teiji
Published: May 2021

Background

Treating chordoma through surgery alone is often ineffective. Thus, surgery often performed with irradiation, with a reported 5-year survival rate of 60–75%. The clinical course varies, and disease rarity prevents larger number of clinical investigations.

Methods

In total, 19 patients with clival chordomas were retrospectively extracted from our institutional database. They were initially treated with maximal tumor removal using the extended transsphenoidal approach between March 2006 and January 2021. When total tumor removal was achieved, prophylactic irradiation was not performed. If tumor remnants or recurrence were confirmed, Gamma Knife (GK) radiosurgery was performed. The mean follow-up period was 106.7 months (ranged 27–224 months). The clinical course and prognostic factors were investigated.

Results

Total removal was achieved in 10 patients, whereas 4 patients suffered recurrence and required GK. GK was applied to 11 patients with a 50% isodose of 13–18 Gy (mean: 15.4 Gy), and eight patients remained progression free, whereas three patients suffered repeated local recurrence and died of tumor-related complications. The mean overall progression-free interval was 57.2 months (range: 6–169 months). One male patient died of tumor un-related lung cancer 36 months after the initial treatment, and other patients survived throughout the observational periods. The mean overall survival was 106.7 months (range: 27–224 months). Thus, the 5-year survival rate was 94.7%. Statistical analysis indicated that sex (men), > 15 Gy of 50% isodose by GK, and screening brain examinations as prophylactic medicine were significant favorable prognostic factors.

Conclusions

The favorable outcomes in this investigation suggest the importance of early detection and treatment. Surgery may enable better conditions for sufficient GK doses.
Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort
Authors: Pasutharnchat Nath , Taychargumpoo Chamaiporn , Vorasettakarnkij Yongkasem , Amornvit Jakkrit
Published: May 2021

Background

Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients.

Methods

The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed.

Results

Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10–92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3–9).

Conclusions

This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.
Identifying outcomes reported in exercise interventions in oesophagogastric cancer survivors: a systematic review
Authors: O’Connor Louise , Smyth Emily , Bennett Annemarie E. , Smith Valerie , O’Neill Linda , Reynolds John V. , Hussey Juliette , Guinan Emer
Published: May 2021

Background

Research investigating exercise interventions in oesophagogastric cancer survivors is sparse, and the outcomes are varied. The aim of this systematic review is to identify the domains and outcomes reported in exercise interventions in oesophagogastric cancer survivors to be included in a Delphi study, with a view to informing the development of a core outcome set (COS).

Methods

EMBASE, PubMed, CINHAL, Cochrane Library, SCOPUS, and PEDro were searched up to March 2020 using a predefined search strategy. The outcomes identified during data extraction were categorised using the core areas outlined in the OMERACT Filter 2.0.

Results

Fourteen domains and 63 outcomes were identified. The most frequently reported outcomes were in the domains of quality of life using the EORTC-QLQ-C30 questionnaire and the relevant disease-specific modules (100%), exercise capacity/fitness/physical function (100%), anthropometrics (83.33%), physical activity (66.67%), and biomarker analysis (50%).

Conclusion

This systematic review quantifies and describes the domains and outcomes examined in exercise interventions in oesophagogastric cancer survivors. Some inconsistency exists within the domains and outcomes used, and little attention was given to nutritional or economic endpoints. In order to develop a COS, a Delphi consensus process with key stakeholders is needed to identify the relevant domains and outcomes for inclusion.
Characterization of alternative splicing events and prognostic signatures in breast cancer
Authors: Han Pihua , Zhu Jingjun , Feng Guang , Wang Zizhang , Ding Yanni
Published: May 2021

Background

Breast cancer (BRCA) is one of the most common cancers worldwide. Abnormal alternative splicing (AS) frequently observed in cancers. This study aims to demonstrate AS events and signatures that might serve as prognostic indicators for BRCA.

Methods

Original data for all seven types of splice events were obtained from TCGA SpliceSeq database. RNA-seq and clinical data of BRCA cohorts were downloaded from TCGA database. Survival-associated AS events in BRCA were analyzed by univariate COX proportional hazards regression model. Prognostic signatures were constructed for prognosis prediction in patients with BRCA based on survival-associated AS events. Pearson correlation analysis was performed to measure the correlation between the expression of splicing factors (SFs) and the percent spliced in (PSI) values of AS events. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to demonstrate pathways in which survival-associated AS event is enriched.

Results

A total of 45,421 AS events in 21,232 genes were identified. Among them, 1121 AS events in 931 genes significantly correlated with survival for BRCA. The established AS prognostic signatures of seven types could accurately predict BRCA prognosis. The comprehensive AS signature could serve as independent prognostic factor for BRCA. A SF-AS regulatory network was therefore established based on the correlation between the expression levels of SFs and PSI values of AS events.

Conclusions

This study revealed survival-associated AS events and signatures that may help predict the survival outcomes of patients with BRCA. Additionally, the constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.
ALDH2 polymorphism rs671 is a predictor of PD-1/PD-L1 inhibitor efficacy against thoracic malignancies
Authors: Matsumoto Akiko , Nakashima Chiho , Kimura Shinya , Sueoka Eizaburo , Aragane Naoko
Published: May 2021

Background

Aldehyde dehydrogenase 2 (ALDH2) plays an important role in the endogenous aldehyde detoxification of various types of cells. ALDH2*2, a variant allele of the ALDH2 polymorphism rs671, leads to decreased enzymatic activity. ALDH2*2 may enhance tumor antigen presentation due to aldehyde-induced DNA damage while suppressing peripheral blood T cell counts and T cell activation.

Methods

On the basis of our hypothesis that rs671 affects the sensitivity of immune checkpoint inhibitors (ICIs), we evaluated the effects of rs671 on patients with thoracic malignancies who started ICI therapy in 2016–2019. The cohort consisted of 105 cases, including 64 cases with adenocarcinoma and 30 cases with squamous cell carcinoma, 49 of whom were ALDH2*2 carriers. The first ICI was PD-1/PD-L1 inhibitor (Nivolumab, Pembrolizumab, or Atezolizumab) in all cases.

Results

The best response to anti-PD-1/PD-L1 therapy (partial response/stable disease/progressive disease) was 36%/50%/14% in the rs671(−) cases; however, the response was relatively poor in the rs671(+) cases (27%/29%/45%, respectively) (p = 0.002). The hazard ratio (95% confidence interval) of disease progression within the observation period of 6 months for the rs671(+) cases was estimated to be 5.0 (2.5–10) after the adjustment for covariates, including sex, Brinkman index, treatment line, tumor tissue programmed death-ligand 1 positivity rate, tumor tissue EGFR mutation. This association was also maintained in a stratified analysis, suggesting that ALDH2*2 is an independent negative predictive factor for the short-term prognosis of anti-PD-1/PD-L1 therapy. Thus, the progression-free survival (PFS) ratio of the rs671(+) cases decreased rapidly after ICI initiation but was eventually higher than that of the rs671(−) cases (restricted mean survival time in 12 months from 2 to 3 years afterward was 1.3 times that of the rs671(−) cases). Moreover, the highest PFS ratio after 2 years among sub-groups was found in the first-line treatment sub-group of rs671(+) group (40%).

Conclusions

Our study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.
Effectiveness of self-help workbook intervention on quality of life in cancer patients receiving chemotherapy: results of a randomized controlled trial
Authors: Takano Toshimi , Matsuda Ayako , Ishizuka Noriko , Ozaki Yukinori , Suyama Koichi , Tanabe Yuko , Miura Yuji , Matsushima Eisuke
Published: May 2021

Background

A self-help workbook is expected to support cancer patients to cope with physical and psychosocial distress, to facilitate communication with medical staff, and to improve quality of life (QOL). We conducted a randomized controlled trial to evaluate the effectiveness of a self-help workbook intervention on QOL and survival.

Methods

From June 2014 to March 2015, patients with breast, colorectal, gastric, and lung cancer receiving outpatient chemotherapy were randomized into an intervention group (n = 100) or control group (n = 100). Intervention group participants received workbooks originally made for this study, read advice on how to cope with distress, and filled out questionnaires on the workbooks periodically. EORTC QLQ-C30 was evaluated at baseline, at 12 weeks, and at 24 weeks. The primary endpoint was Global Health Status / QOL scale (GQOL).

Results

No significant interaction was observed between the intervention and time in terms of GQOL or any of the functional scales. Among the 69 patients who continued cytotoxic chemotherapy at 24 weeks, the intervention was significantly associated with improved emotional functioning scores (P = 0.0007). Overall survival was not significantly different between the two groups.

Conclusions

Self-help workbook intervention was feasible in cancer patients receiving chemotherapy. Although the effect of the intervention was limited, a post-hoc subset analysis suggested that the intervention may improve emotional functioning among patients who receive long-term cytotoxic chemotherapy.

Trial registration

UMIN Clinical Trials Registry, UMIN000012842. Registered 14 January 2014.
Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors
Authors: Anwar Sumadi Lukman , Cahyono Roby , Prabowo Dayat , Avanti Widya Surya , Choridah Lina , Dwianingsih Ery Kus , Harahap Wirsma Arif , Aryandono Teguh
Published: May 2021

Background

Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes.

Methods

Non-metastatic breast cancer patients (N = 1081) treated in our department (2014–2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years.

Results

Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071–1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090–2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139–2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035–3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors.

Conclusion

Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients’ quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.