bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Spatiotemporal Gait Parameters Following Operative Treatment of Trimalleolar Ankle Fractures vs Healthy Controls
Authors: Tyler Andrew F. , Rose Thomas , Day Scott , Kenia Jessica , Horan Annamarie D. , Mehta Samir , Donegan Derek J.
Published: July 2020

Background:

Controversy continues regarding appropriate indications for posterior malleolus fracture fixation in unstable rotational trimalleolar ankle injuries, with limited data comparing gait in operatively treated trimalleolar ankle fractures vs control populations. The purpose of this study was to evaluate the effect of trimalleolar ankle fracture fixation on gait parameters in the early postoperative period as compared to a healthy control population.

Methods:

Adult patients having undergone operative treatment of isolated trimalleolar ankle fractures were eligible for inclusion. A total of 10 patients met the inclusion criteria and participated in the analysis. Patients were evaluated using standard parameters of human gait 6 months after their index procedures, with gait values compared to a population of 17 non–age-matched healthy control subjects in addition to literature values of healthy populations of younger and older subjects.

Results:

Significant differences were noted between the spatiotemporal gait parameters of healthy control subjects and patients who had undergone operative treatment of trimalleolar ankle fractures. However, within the fracture group itself, no differences were found between patients with or without posterior malleolar fixation for any of the tested gait parameters. When patients were compared to literature values of younger and older healthy control populations, they were found to have gait patterns more similar to older rather than younger individuals.

Conclusion:

Operative fixation of trimalleolar ankle fracture does not restore normal gait function in the early postoperative period. Fixation of the posterior malleolus in particular also does not appear to improve gait characteristics. Patients who undergo surgery for these injuries demonstrate gait patterns similar to those of healthy older adults.

Level of Evidence:

Level II, Therapeutic (prospective cohort study).
Effect of Periosteal Flap Augmentation on Outcomes of Modified Broström-Gould Procedure for Chronic Lateral Ankle Instability
Authors: Tay Kae Sian , Chew Chee Ping , Lie Denny Tjiauw Tjoen
Published: July 2020

Background:

Chronic lateral ankle instability is relatively common after ankle sprains. The modified Broström-Gould procedure (MBG) is the gold standard operative treatment but has a known failure rate of up to 10%, or even more in high-risk groups. Periosteal flap augmentation (PFA) has been proposed to strengthen the repair. This study aimed to compare the outcomes of MBG with and without PFA.

Methods:

A matched-pair study was performed based on prospectively collected registry data for all patients undergoing lateral ankle ligament reconstruction in a tertiary institution. Patients who underwent the MBG with PFA were matched in a 1:1 ratio with patients undergoing MBG alone, based on age, gender, and body mass index (BMI). Patients with generalized ligamentous laxity or obesity were excluded. Clinical outcome scores were compared preoperatively and 2 years postoperatively. A total of 48 patients were included in the study (24 in each group). The mean age was 24.1 years, mean BMI was 23.1, and all patients were male. The baseline demographics and clinical scores in both groups were similar.

Results:

At 2 years postoperatively, both groups demonstrated significantly improved AOFAS Ankle-Hindfoot scores ( P < .001), but there were no between-group differences in total AOFAS scores (PFA score 90, MBG score 88, P = .79). There were no recurrences of instability or revision surgeries.

Conclusion:

Routine PFA did not improve the outcomes of MBG for chronic lateral ankle instability in the absence of risk factors for failure. Further studies are warranted to determine if there is a long-term benefit for augmentation in this population.

Level of Evidence:

Level III, retrospective comparative study.
Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance
Authors: Bengtson Charles D. , Kim Michael D. , Anabtawi Abeer , He Jianghua , Dennis John S. , Miller Sara , Yoshida Makoto , Baumlin Nathalie , Salathe Matthias
Published: July 2020

Large-conductance, Ca2+-activated, voltage-dependent K+(BK) channel function is critical for adequate airway hydration and mucociliary function. In airway epithelia, BK function is regulated by its γ-subunit, leucine-rich repeat-containing protein 26 (LRRC26). Since patients with cystic fibrosis (CF)-related diabetes mellitus (CFRD) have worse lung function outcomes, this study determined the effects of hyperglycaemia on BK function in CF bronchial epithelial (CFBE) cellsin vitroand evaluated the correlation between glycaemic excursions and mRNA expression ofLRRC26in the upper airways of CF and CFRD patients.

CFBE cells were redifferentiated at the air–liquid interface (ALI) in media containing either 5.5 mM or 12.5 mM glucose. BK activity was measured in an Ussing chamber. Airway surface liquid (ASL) volume was estimated by meniscus scanning and inflammatory marker expression was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). CF patients were assessed by 7 days of continuous glucose monitoring (CGM).LRRC26mRNA expression was measured by quantitative real-time PCR from nasal cells obtained at the end of glucose monitoring.

BK currents were significantly decreased in CFBE cells cultured under high glucose. These cells revealed significantly lower ASL volumes and increased inflammation, including the receptor for advanced glycation endproducts (RAGE), compared to cells cultured in normal glucose.In vivo, nasal cell expression ofLRRC26mRNA was inversely correlated with hyperglycaemic excursions, consistent with thein vitroresults.

Our findings demonstrate that hyperglycaemia induces inflammation and impairs BK channel function in CFBE cellsin vitro. These data suggest that declining lung function in CFRD patients may be related to BK channel dysfunction.
Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging
Authors: Sullivan Frank M. , Mair Frances S. , Anderson William , Armory Pauline , Briggs Andrew , Chew Cindy , Dorward Alistair , Haughney John , Hogarth Fiona , Kendrick Denise , Littleford Roberta , McConnachie Alex , McCowan Colin , Mcmeekin Nicola , Patel Manish , Rauchhaus Petra , Ritchie Lewis , Robertson Chris , Robertson John , Robles-Zurita Jose , Sarvesvaran Joseph , Sewell Herbert , Sproule Michael , Taylor Thomas , Tello Agnes , Treweek Shaun , Vedhara Kavita , Schembri Stuart ,   The Early Diagnosis of Lung Cancer Scotland (ECLS) Team
Published: July 2020

The EarlyCDT-Lung test is a high specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. Here we report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent CT scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/Unspecified lung cancer at diagnosis, compared with the standard clinical practice at the time the study began.

ECLS was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland. The intervention arm received the EarlyCDT-Lung test and, if test positive, low-dose CT scanning six-monthly for up to 2 years. EarlyCDT-Lung test negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.

At 2 years, 127 lung cancers were detected in the study population (1.0%).

In the intervention arm, 33/56 (58.9%) lung cancers were diagnosed at stage III/IV compared to 52/71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% confidence interval 0.41, 0.99). There were non-significant differences in lung cancer and all-cause mortality after 2 years.

ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation), and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage-shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of LDCT.
Characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who require hospitalisation
Authors: Beurnier Antoine , Jutant Etienne-Marie , Jevnikar Mitja , Boucly Athénaïs , Pichon Jérémie , Preda Mariana , Frank Marie , Laurent Jérémy , Richard Christian , Monnet Xavier , Duranteau Jacques , Harrois Anatole , Chaumais Marie-Camille , Bellin Marie-France , Noël Nicolas , Bulifon Sophie , Jaïs Xavier , Parent Florence , Seferian Andrei , Savale Laurent , Sitbon Olivier , Montani David , Humbert Marc
Published: July 2020

Background

Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France.

Methods

A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included.

Results

Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42–67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m−2. The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm−3(IQR 0–0 cells·mm−3). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities.

Conclusion

Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities.
Use of a whole genome sequencing-based approach forMycobacterium tuberculosissurveillance in Europe in 2017–2019: an ECDC pilot study
Authors: Tagliani Elisa , Anthony Richard , Kohl Thomas A. , de Neeling Albert , Nikolayevskyy Vlad , Ködmön Csaba , Maurer Florian P. , Niemann Stefan , van Soolingen Dick , van der Werf Marieke J. , Cirillo Daniela Maria
Published: July 2020

Whole genome sequencing (WGS) can be used for molecular typing and characterisation ofMycobacterium tuberculosiscomplex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learnt to be considered for the future development of a WGS-based surveillance system.

WGS and epidemiological data of patients with rifampicin-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) were collected from EU/EEA countries between January 2017 and December 2019. WGS-based genetic relatedness analysis was performed using a standardised approach including both core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP)-based calculation of distances on all WGS data that fulfilled minimum quality criteria to ensure data comparability.

A total of 2218 RR/MDR-MTBC isolates were collected from 25 countries. Among these, 56 cross-border clusters with increased likelihood of recent transmission (≤5 SNPs distance) comprising 316 RR/MDR-MTBC isolates were identified. The cross-border clusters included between two and 30 resistant isolates from two to six countries, demonstrating different RR/MDR-TB transmission patterns in Western and Eastern EU countries.

This pilot study shows that a WGS-based surveillance system is not only feasible but can efficiently elucidate the dynamics of in-country and cross-border RR/MDR-TB transmission across EU/EEA countries. Lessons learnt from this study highlight that the establishment of an EU/EEA centralised WGS-based surveillance system for TB will require strengthening of national integrated systems performing prospective WGS surveillance and the development of clear procedures to facilitate international collaboration for the investigation of cross-border clusters.
Reducing the consumption of personal protective equipment by setting up a multifunctional sampling station in the emergency department to screen for COVID-19 infection in Taiwan
Authors: Lin Po-Ting , Ni Ting-Yuan , Chen Tren-Yi , Su Chih-Pei , Sun Hsiao-Fen , Chen Mu-Kuan , Chou Chu-Chung , Wang Po-Yu , Lin Yan-Ren
Published: July 2020

In Taiwan, high-risk patients have been identified and tested for preventing community spread of COVID-19. Most sample collection was performed in emergency departments (EDs). Traditional sample collection requires substantial personal protective equipment (PPE), healthcare professionals, sanitation workers, and isolation space. To solve this problem, we established a multifunctional sample collection station (MSCS) for COVID-19 testing in front of our ED. The station is composed of a thick and clear acrylic board (2 cm), which completely separates the patient and medical personnel. Three pairs of gloves (length, 45 cm) are attached and fixed on the outside wall of the MSCS. The gloves are used to conduct sampling of throat/nasal swabs, sputum, and blood from patients. The gap between the board and the building is only 0.2 cm (sealed with silicone sealant). ED personnel communicate with patients using a small two-way broadcast system. Medical waste is put in specific trashcans installed in the table outside the MSCS. With full physical protection, the personnel conducting the sampling procedure need to wear only their N95 mask and gloves. After we activated the station, our PPE, sampling time, and sanitization resources were considerably conserved during the 4-week observation period. The MSCS obviously saved time and PPE. It elevated the efficiency and capacity of the ED for handling potential community infections of COVID-19.
Alix and Syntenin-1 direct amyloid precursor protein trafficking into extracellular vesicles
Authors: Cone Allaura S. , Hurwitz Stephanie N. , Lee Gloria S. , Yuan Xuegang , Zhou Yi , Li Yan , Meckes David G.
Published: July 2020

Background

Endosomal trafficking and amyloidogenic cleavage of amyloid precursor protein (APP) is believed to play a role in the neurodegeneration observed in Alzheimer’s disease (AD). Recent evidence has suggested that packaging and secretion of APP and its amyloidogenic cleaved products into small extracellular vesicles (EVs) may facilitate uptake of these neurotoxic factors during disease progression. However, the molecular mechanisms underlying trafficking of APP into EVs are poorly understood.

Results

In this study, the mechanism and impact of APP trafficking into extracellular vesicles (EVs) were assessed by a series of inducible gene knockdowns. We demonstrate that vesicle-associated proteins Alix and Syntenin-1 are essential for proper subcellular localization and efficient EV secretion of APP via an endosomal sorting complexes required for transport (ESCRT)-independent pathway. The neurotoxic C-terminal fragment (CTFβ) of APP is similarly secreted in association with small vesicles. These mechanisms are conserved in terminally differentiated neuron-like cells. Furthermore, knockdown of Alix and Syntenin-1 alters the subcellular localization of APP, sequestering the precursor protein to endoplasmic reticulum and endolysosomal compartments, respectively. Finally, transfer of small EVs containing mutant APP confers an increase in reactive oxygen species production and neurotoxicity to human induced pluripotent stem cell-derived cortical neurons and naïve primary neurons, an effect that is ameliorated by Alix and Syntenin-1 depletion.

Conclusions

Altogether these findings elucidate a novel mechanism for understanding the intracellular trafficking of APP and CTFβ into secreted extracellular vesicles, and the resultant potential impact on neurotoxicity in the context of Alzheimer’s disease amyloidopathy.
Platelet counts are associated with arterial stiffness in Chinese Han population: a longitudinal study
Authors: Liu Kuo , Xu Junfeng , Tao Lixin , Yang Kun , Sun Yang , Guo Xiuhua
Published: July 2020

Background

Determining the risk factors for brachial-ankle pulse wave velocity (baPWV) may help to identify people susceptible to diabetic atherosclerosis and could prevent diabetic macrovascular complications in the early stages. We aim to comprehensively investigate risk factors contributing to arterial stiffness in patients with and without diabetes.

Methods

BaPWV was measured in 5651 individuals who attended health check-ups at baseline and follow-up. Lasso regression was used to screen for risk factors. Mixed models and multiple linear regressions were subsequently established to evaluate the effect size of the potential risk factors on baPWV and PWV change rates. All analyses were stratified by diabetes. Mediation analysis was also conducted to demonstrate the mechanisms of arterial stiffness in patients with diabetes.

Results

In lasso regression, postprandial 2-h glucose (P2hG), systolic blood pressure (SBP) and age were associated with baPWV regardless of diabetes. Platelet counts (PLT), mean corpuscular volume (MCV) and coronary heart disease (CHD) were associated with baPWV in patients with diabetes. In the mixed models, PLT were positively associated with baPWV in patients with diabetes (βplatelet, perSD = 25.80; 18.26–33.33). Elevated PLTs could also significantly increase the PWV change rate in patients with diabetes (βplatelet, perSD = 54.05; 10.00–107.10). In mediation analysis, diabetes had a significant average direct effect on baPWV. The average causal mediation effect (ACME) of PLTs was 1.76, with a range of 0.17 to 3.70.

Conclusions

Elevated PLT counts can increase baPWV in diabetes and are a potential mediator between diabetes and atherosclerosis.
Factors that facilitate recognition and management of domestic violence by primary care physicians in a Chinese context - a mixed methods study in Hong Kong
Authors: Lam Tai Pong , Chan Hoi Yan , Piterman Leon , Wong Mei Wa , Sun Kai Sing , Lam Kwok Fai , Chan Tak Hon , Dan Wu , Tiwari Agnes
Published: July 2020

Background

Domestic violence is common in the community. Many of its victims present to primary care physicians (PCPs) but are not being recognized and managed. The barriers, with specific reference to a Chinese cultural context, were investigated earlier. This paper explored the factors which facilitated the process of recognizing and managing suspected cases of domestic violence by PCPs in Hong Kong.

Methods

Four focus group interviews were conducted to explore in-depth the experiences of PCPs in recognition, management and referral of domestic violence cases from which facilitators were identified. The relevant themes were then investigated in a questionnaire survey with 504 PCPs working in public and private sectors.

Results

The focus group participants emphasized mood symptoms as useful indicators for probable abuse and continuity of care was important to unmask issues of domestic violence. The top facilitators perceived by the respondents of the survey included: a trusting doctor-patient relationship (99.8%), good communication skills (99.0%), patients’ unexplained bruises (96.3%), medical history (94.6%), and mood symptoms (94.4%). Further, the survey found that PCPs with longer years of practice, a medical degree obtained from Western countries, and postgraduate training in family counselling or psychological medicine perceived more facilitators in managing domestic violence.

Conclusions

Without a local screening policy and training protocol to manage domestic violence, PCPs regarded their skills in mental healthcare and good relationships with patients as the key facilitators. While training in mental health care helps PCPs manage domestic violence, a specific protocol emphasizing medical-social collaboration is anticipated to facilitate them to take a more proactive and effective stance from screening to management.
The Valued Life Activities Scale (VLAs): linguistic validation, cultural adaptation and psychometric testing in people with rheumatic and musculoskeletal diseases in the UK
Authors: Prior Y. , Tennant A. , Tyson S. , Hammond A.
Published: July 2020

Background

The Valued Life Activities Scale (VLAs) measures difficulty in daily activities and social participation. With various versions involving a different number of items, we have linguistically and culturally adopted the full VLAs (33-items) and psychometrically tested it in adults with rheumatic and musculoskeletal diseases in the United Kingdom.

Methods

Participants with Rheumatoid Arthritis, Ankylosing Spondylitis, Chronic Pain/ Fibromyalgia, Chronic Hand/ Upper Limb Conditions, Osteoarthritis, Systemic Lupus, Systemic Sclerosis and Primary Sjogren’s Syndrome were recruited from out-patient clinics in National Health Service Hospitals, General Practice and patient organisations in the UK. Phase1 involved linguistic and cultural adaptation: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews. In Phase2 participants completed postal questionnaires to assess internal construct validity using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model.

Results

Responders (n = 1544) had mean age of 59 years (SD13.3) and 77.2% women. A CFA failed to support a total score from the 33-items (Chi Square 3552:df 464: p < 0.0001). Mokken scaling indicated a strong non-parametric association between items. Fit to the Rasch model indicated that the VLAs was characterised by multidimensionality and item misfit, which may have been influenced by clusters of residual item correlations. An item banking approach resolved a 25-item calibrated set whose application could accommodate the ‘does not apply to me’ response option.

Conclusions

The UK version of the VLAs failed to satisfy classical and modern psychometric standards for complete item sets. However, as the scale is not usually applied in complete format, an item bank approach calibrated 25 items with fit to the Rasch model. Suitable Computer Adaptive Testing (CAT) software could implement the item set, giving patients the choice of whether an item applies to them, or not.
Prescription patterns and factors influencing the use of Chinese herbal medicine among pregnant women in Taiwan: a population-based retrospective study
Authors: Wen Shu-Hui , Chang Wei-Chuan , Shen Hsuan-Shu , Wu Hsien-Chang
Published: July 2020

Background

The use of Chinese herbal medicine (CHM) has been widely promoted as a natural and safe way to treat illness during pregnancy. However, prescription patterns and factors influencing its use are largely unknown. Therefore, we conducted a population-based study to address these questions.

Methods

Pregnant women aged 18–50 years were selected from Taiwan’s National Health Insurance Research Database between 2001 to 2011. CHM prescriptions and diagnostic records were collected. Demographic data and pre-existing diseases were compared between CHM users and non-users. A multivariate logistic regression analysis was performed to identify possible factors influencing the use of CHM during pregnancy.

Results

A total of 81,873 eligible prescription records were identified, and 16,553 pregnant women were prescribed CHM during pregnancy, yielding a CHM prescription rate of 20.2%. The three most frequently used herbs were Scutellariae Radix (Huang Qin) (4.4%), Eucommiae cortex (Du Zhong) (2.5%), and Atractylodes Rhizome (Bai Zhu) (2.4%). The most frequently used herbal formulae were Dang-Guei-Shao-Yao-San (4.1%), Jia-Wei-Xiao-Yao-San (3.5%), and Xiang-Sha-Liu-Jun-Zi-Tang (2.6%). Multivariate logistic regression revealed that subjects with an older age, a university education, a pre-pregnancy history of CHM use, asthma, chronic renal disease, and cardiac valvular disease and living in a residential area other than northern Taiwan had an increase in adjusted odds ratio for CHM use during pregnancy.

Conclusions

In this population-based study, we found that demographic factors and pre-existing diseases were associated with the use of CHM among pregnant women. It is worth noting that Leonuri Herba (Yi Mu Cao) and Shao-Fu-Zhu-Yu-Tang should be used with caution in the first trimester. Further research is needed to explore the safety and effectiveness of the use of CHM in pregnant women.
Rare case of a giant thrombosed left anterior descending coronary artery aneurysm
Authors: Peng Yong , Li Yaxiong , Jiang Yu
Published: July 2020

Background

Coronary artery aneurysms (CAAs) are rare, and giant CAAs are even rarer. The pathophysiology of this phenomenon is still unknown.

Case presentation

Herein, we present the case of a 49-year-old male with a giant aneurysm in the left anterior descending artery.

Conclusions

The optimal treatment for CAAs is debatable, but surgical intervention is preferred for giant CAAs.
A pipeline for complete characterization of complex germline rearrangements from long DNA reads
Authors: Mitsuhashi Satomi , Ohori Sachiko , Katoh Kazutaka , Frith Martin C. , Matsumoto Naomichi
Published: July 2020

Background

Many genetic/genomic disorders are caused by genomic rearrangements. Standard methods can often characterize these variations only partly, e.g., copy number changes or breakpoints. It is important to fully understand the order and orientation of rearranged fragments, with precise breakpoints, to know the pathogenicity of the rearrangements.

Methods

We performed whole-genome-coverage nanopore sequencing of long DNA reads from four patients with chromosomal translocations. We identified rearrangements relative to a reference human genome, subtracted rearrangements shared by any of 33 control individuals, and determined the order and orientation of rearranged fragments, with our newly developed analysis pipeline.

Results

We describe the full characterization of complex chromosomal rearrangements, by filtering out genomic rearrangements seen in controls without the same disease, reducing the number of loci per patient from a few thousand to a few dozen. Breakpoint detection was very accurate; we usually see ~ 0 ± 1 base difference from Sanger sequencing-confirmed breakpoints. For one patient with two reciprocal chromosomal translocations, we find that the translocation points have complex rearrangements of multiple DNA fragments involving 5 chromosomes, which we could order and orient by an automatic algorithm, thereby fully reconstructing the rearrangement. A rearrangement is more than the sum of its parts: some properties, such as sequence loss, can be inferred only after reconstructing the whole rearrangement. In this patient, the rearrangements were evidently caused by shattering of the chromosomes into multiple fragments, which rejoined in a different order and orientation with loss of some fragments.

Conclusions

We developed an effective analytic pipeline to find chromosomal aberration in congenital diseases by filtering benign changes, only from long read sequencing. Our algorithm for reconstruction of complex rearrangements is useful to interpret rearrangements with many breakpoints, e.g., chromothripsis. Our approach promises to fully characterize many congenital germline rearrangements, provided they do not involve poorly understood loci such as centromeric repeats.
Heavy metal remediation in soil with chemical amendments and its impact on activity of antioxidant enzymes in Lettuce (Lactuca sativa) and soil enzymes
Authors: Hong Young Kyu , Kim Jin Wook , Lee Sang Phil , Yang Jae E. , Kim Sung Chul
Published: July 2020

Chemical amendments have been used to remediate soils contaminated with heavy metals. However, there is little understanding on the impacts of these amendments on the physiological and biochemical functions of plants and soil. This study used in situ microcosm experiment to understand the effect of chemical amendments on antioxidant and soil enzyme activity in plant and soil with respect to heavy metal reduction. Three chemical amendments—acid mine drainage sludge (AMDS), limestone (LS), and steel slag (SS)—were applied to soil at 3, 5, and 10% mixing ratios, and lettuce (Lactuca sativa) was cultivated in that soil for 30 days. The results showed that bioavailable Cd and Pb in soil was reduced by 9.8–40.5% and 4.2–92.5%, respectively. The most efficient amendment for heavy metal reduction was AMDS. The uptake of Cd and Pb also decreased by 0.5–66.1 and 21.6–79.5%, respectively, depending on the amendment type and application ratio. The activity of three antioxidants—catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR)—was generally higher than the control with no amendments. This result indicated that there was minimal inhibition of antioxidant activity due to the reduction of heavy metal uptake. Also, no significant difference was observed in chemical amendments applied soil compared to control in terms of soil enzyme activity. However, correlation analysis between heavy metal concentration in soil and two soil enzyme activities showed that significantly negative correlation (p < 0.01) was observed between bioavailable Pb in soil and acid-phosphatase activity. This result might indicate that impact of bioavailable Pb was much higher than Cd in terms of inhibition of soil enzyme activity. Overall, the application of chemical amendments to heavy metal polluted had a positive effect on plant physiological function and soil enzyme activity with a reduction in bioavailable heavy metals in soil and plants.
Six new species of Begonia from Guangxi, China
Authors: Liu Yan , Tseng Yu-Hsin , Yang Hsun-An , Hu Ai-Qun , Xu Wei-Bin , Lin Che-Wei , Kono Yoshiko , Chang Chiung-Chih , Peng Ching-I , Chung Kuo-Fang
Published: July 2020

Background

With currently 1980 described species, the mega-diverse Begonia is now perhaps the 5th largest flowering plant genus, expanding rapidly from ca. 900 species in 1997 to its current size in merely two decades. In continuation of our studies of Asian Begonia, we report six additional new species from Guangxi, the region/province harboring the second richest Begonia flora of China.

Results

Based on morphological and molecular data, the new species B. aurora belongs to Begonia sect. Platycentrum, while the other five new species (viz. B. larvata, B. longiornithophylla, B. lui, B. scabrifolia, and B. zhuoyuniae) are members of Sect. Coelocentrum. Somatic chromosome numbers of B. longiornithophylla and B. zhuoyuniae at metaphase were counted as 2n = 30, consistent with previously reports for Sect. Coelocentrum.

Conclusions

With the addition of the six new species, the total number of Begonia species in Guangxi increases from 86 to 92. Detailed description, line drawings, and color plates are provided to aid in identification.
Utilising the nasal aperture for template stabilisation for guided surgery in the atrophic maxilla
Authors: Onclin Pieter , Kraeima Joep , Merema Bram B. J. , Meijer Henny J. A. , Vissink Arjan , Raghoebar Gerry M.
Published: July 2020

Background

Templates aim to facilitate implant placement in the prosthetically preferred position. Mucosa-supported and bone-supported templates are commonly used in the edentulous maxilla. In the atrophic maxilla (Cawood V and VI), however, these templates can be easily displaced due to a lack of supportive tissues, even in cases where anterior sites offer sufficient bone for implant placement. To assist in positioning and stabilisation, we designed a template that utilises the nasal aperture as a fulcrum to create a forced and exclusive fit. The aim of this study was to assess the clinical usability of the developed template and the corresponding implant placement accuracy in patients with edentulous atrophic maxillae. Deviations between planned and placed implant positions were measured by aligning pre- and post-operative cone beam computed tomography scans.

Results

Twenty-four implants were placed in 11 patients. One template did not fit properly due to a slight undercut. All implants could be placed with good primary stability. The implants had high accuracy at the implant shoulder (global deviation 1.1 ± 0.5 mm, lateral deviation 0.8 ± 0.5 mm) and a mean angular deviation of 7.2 ± 3.4°.

Conclusions

The developed surgical template offers stabilised and secure template placement in the edentulous atrophic maxilla, resulting in satisfying implant placement accuracy when using a semi-guided approach.

Trial registration

Netherlands Trial Register, NL6561, registered 26 September 2017.
Brief Montreal-Toulouse Language Assessment Battery: adaptation and content validity
Authors: Altmann Raira Fernanda , Ortiz Karin Zazo , Benfica Tainá Rossato , de Oliveira Eduarda Pinheiro , Pagliarin Karina Carlesso
Published: July 2020

Background

Evaluating patients in the acute phase of brain damage allows for the early detection of cognitive and linguistic impairments and the implementation of more effective interventions. However, few cross-cultural instruments are available for the bedside assessment of language abilities. The aim of this study was to develop a brief assessment instrument and evaluate its content validity.

Methods

Stimuli for the new assessment instrument were selected from the M1-Alpha and MTL-BR batteries (Stage 1). Sixty-five images were redesigned and analyzed by non-expert judges (Stage 2). This was followed by the analysis of expert judges (Stage 3), where nine speech pathologists with doctoral training and experience in aphasiology and/or linguistics evaluated the images, words, nonwords, and phrases for inclusion in the instrument. Two pilot studies (Stage 4) were then conducted in order to identify any remaining errors in the instrument and scoring instructions.

Results

Sixty of the 65 figures examined by the judges achieved inter-rater agreement rates of at least 80%. Modifications were suggested to 22 images, which were therefore reanalyzed by the judges, who reached high levels of inter-rater agreement (AC1 = 0.98 [CI = 0.96–1]). New types of stimuli such as nonwords and irregular words were also inserted in the Brief Battery and favorably evaluated by the expert judges. Optional tasks were also developed for specific diagnostic situations. After the correction of errors detected in Stage 4, the final version of the instrument was obtained.

Conclusion

This study confirmed the content validity of the Brief MTL-BR Battery. The method used in this investigation was effective and can be used in future studies to develop brief instruments based on preexisting assessment batteries.
Room for improvement in non-pharmacological systemic sclerosis care? — a cross-sectional online survey of 650 patients
Authors: Stöcker Juliane K. , Vonk Madelon C. , van den Hoogen Frank H. J. , Nijhuis-van der Sanden Maria W. G. , Spierings Julia , Staal J. Bart , Satink Ton , van den Ende Cornelia H. M. ,   on behalf of the ARCH study group
Published: July 2020

Background/ objective

To gain insight in the use of current systemic sclerosis (SSc) care provided by health professionals from the patient perspective. We focused on referral reasons, treatment goals, the alignment with unmet care needs, and outcome satisfaction.

Methods

Dutch SSc patients from 13 participating rheumatology departments were invited to complete an online survey. Descriptive statistics were used to describe current use of non-pharmacological care and outcome satisfaction. Reasons for referral and treatment goals were encoded in International Classification of Function and Disability (ICF) terms.

Results

We included 650 patients (mean (standard deviation [SD]) age, 59.4 (11.4) years. 50% had contact with a health professional in the past year; 76.3% since disease onset. Physiotherapists were the most frequently visited in the past year (40.0%), followed by dental hygienists (11.4%) and podiatrists (9.2%). The three most common referral reasons were pain, joint mobility and cardiovascular functions. Fatigue, Raynaud’s phenomenon, physical limitations, reduced hand function and joint problems were mentioned by more than 25% of all respondents as unmet needs. The proportion of patients treated in the past year by a health professional who were satisfied with knowledge and expertise of their health professionals was 74.4%; 73% reported improved daily activities and better coping with complaints. However, 48.9% perceived that the collaboration between rheumatologist and health professional was never or only sometimes sufficient.

Conclusion

Despite the high outcome satisfaction and good accessibility of health professionals, there are obstacles in the access to non-pharmacological care and communication barriers between health professionals and rheumatologists.
Integrated single-molecule long-read sequencing and Illumina sequencing reveal the resistance mechanism of Psathyrostachys huashanica in response to barley yellow dwarf virus-GAV
Authors: Shen Chuan , Wei Caiyan , Li Jingyuan , Zhang Xudong , Wu Yunfeng
Published: July 2020

AlthoughPsathyrostachys huashanicahas excellent potential for resistance gene mining and molecular genetic breeding, no reference genome is available. To date, most studies ofP. huashanicahave been focused on the creation of translocation lines and additional lines, as well as the development of molecular markers. Therefore, research at the transcriptional level is lacking. In this study, the full-length transcriptome ofP. huashanicawas sequenced using PacBio isoform sequencing (Iso-Seq) of a pooled RNA sample to explore the potential full-length transcript isoforms. We obtained 112,596 unique transcript isoforms with a total length of 114,957,868 base pairs (bp). Subsequently, Illumina sequencing reads were used to correct and trim the PacBio isoforms. We annotated 103,875 unigenes in at least one functional database, and identified a plethora of differentially-expressed genes (DEGs) that are involved in the defense responses ofP. huashanicaagainst barley yellow dwarf virus-GAV (BYDV-GAV). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these DEGs were mostly involved in plant-pathogen interaction, plant hormone signal transduction, and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we selected twenty of the RNA-seq identified resistance-related up-regulated genes, including MAPKs, cysteine-rich receptor-like protein kinases (CRPKs), calcium-dependent protein kinases (CDPKs), pathogenesis-related protein (PR) proteins, WRKYs, and disease resistance proteins, and validated their up-regulation in response to BYDV-GAV by quantitative real-time PCR. Our results indicate that a series of defense-related genes were induced inP. huashanicaduring BYDV-GAV infection. The full-length transcriptome dataset will contribute to improved use of stress-resistance genes ofP. huashanica, and serves as a reference database for the analysis of transcript expression inP. huashanica.
Mapping quantitative trait loci for disease resistance to false smut of rice
Authors: Han Yanqing , Li Deqiang , Yang Jun , Huang Fu , Sheng Hongyan , Sun Wenxian
Published: July 2020

False smut of rice, an important emerging disease caused by Ustilaginoidea virens, greatly reduces grain yield and deteriorates grain quality in many rice-growing regions worldwide. Identification of quantitative trait loci (QTL) conferring false smut resistance will facilitate incorporation of false smut resistance into elite cultivars. In this study, a set of recombinant inbred lines (RILs) derived from a cross of a resistant rice landrace MR183–2 and a high susceptible line 08R2394 were evaluated to map resistance QTLs for false smut. A total of 179 simple sequence repeat (SSR) polymorphic markers were identified for constructing genetic linkage maps. Using a composite interval mapping method, five false smut resistance QTLs were detected on chromosomes 2, 4, 8 and 11 in the RIL population. Among these QTLs, qFsr8–1 within a small region on chromosome 8 represents a major quantitative locus explaining the greatest phenotypic variance. Gene annotation in this major QTL region provides a theoretical basis for cloning of resistance QTLs. The SSR markers genetically linked to qFsr8–1 are valuable for marker-assisted breeding for false smut resistance in rice. In addition, nine QTLs for heading date were detected in this population. Correlation analysis of disease resistance score and heading date indicates that false smut resistance negatively correlates with the growth period length in rice.
Provenance of upper Permian-lowermost Triassic sandstones, Wutonggou low-order cycle, Bogda Mountains, NW China: implications on the unroofing history of the Eastern North Tianshan Suture
Authors: Zheng Dong-Yu , Yang Wan
Published: July 2020

This study investigates the provenance of sedimentary rocks in Bogda Mountains, NW China, and reconstructs the lithology and unroofing history of the Eastern North Tianshan Suture. Petrographic point counting data of sandstones and compositions of conglomerates of upper Permian-lowermost Triassic Wutonggou low-order cycle from Zhaobishan, North Tarlong, Taodonggou, and Dalongkou sections in the southern and northern foothills of Bogda Mountains were used to interpret the temporal and spatial variations of lithology of the Eastern North Tianshan Suture, which is the sediment source area. Three compositional trends were identified. A trend of upward-increasing quartz content and granitic pebbles in Zhaobishan section suggests a change from the undissected volcanic arc, accretionary wedge and trench setting to predominantly transitional volcanic arc and subordinate accretionary wedge and trench, in the eastern part of the Eastern North Tianshan Suture. In North Tarlong and Taodonggou sections, however, the lithic content decreases and the contents of quartz and granitic pebbles increase up sections. These trends indicate that the western part of the Eastern North Tianshan Suture changed from an undissected volcanic arc to the transitional volcanic arc, accretionary wedge and trench. No clear trend in the lithic-rich sandstones of the Dalongkou section indicates that sediments were derived from the undissected volcanic arc in the Eastern North Tianshan Suture and local rift shoulders. Compositional variations of studied rocks suggest that the Eastern North Tianshan Suture was an amalgamated complex with great spatial and temporal heterogeneities in lithology and experienced persistent unroofing during late Permian-earliest Triassic. This study reconstructs a key element of the Chinese Tianshan Suture and serves as an example to understand the unroofing processes of ancient sutures.
Diagnostic and prognostic role of proton single-voxel spectroscopy (SVS) in non-lesional epilepsy pediatric patients: prospective controlled study
Authors: Faheem Mohamed H. , Dabour Ahmed S. , Abdelhaie Omima M.
Published: July 2020

Background

We aimed to verify the diagnostic and prognostic role of proton single-voxel spectroscopy (SVS) in children with non-lesional epilepsy and its add-on value to conventional MR. The prospective controlled study carried out on the epileptic patients who were regularly following in the pediatric neurology clinic in our university hospital, over the period from July 2017 to July 2018. It compared SVS findings (NAA/Cr, NAA/Cho, and NAA/Cho+Cr ratios) between the case (50 patients) and control group (20 children), between the cases with different seizures semiology and between the patients with intractable and non-intractable epilepsy.

Results

NAA/Cr ratio showed a significant difference between the patients with intractable and non-intractable epilepsy in the basal ganglia (P value 0.005) and white matter (P value 0.043) with cutoff values of 1.5 and 1.9 respectively. A significant difference of NAA/Cho ratio was found between generalized seizures cases and other seizures semiology in basal ganglia (P value 0.012) and cortex (P value <.001). There was no significant difference between the patient and control groups or between generalized seizures cases and the control group.

Conclusion

Proton SVS has limited diagnostic value in non-lesional epilepsy pediatric patients, in differentiation between generalized seizures and other seizure types, but, it has a good prognostic role in predicting patients who will develop intractable epilepsy.
Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)
Authors: Lugtenburg Pieternella Johanna , de Nully Brown Peter , van der Holt Bronno , D’Amore Francesco A. , Koene Harry R. , de Jongh Eva , Fijnheer Rob , van Esser Joost W. , Böhmer Lara H. , Pruijt Johannes F. , Verhoef Gregor E. , Hoogendoorn Mels , Bilgin Memis Y. , Nijland Marcel , van der Burg-de Graauw Nicole C. , Oosterveld Margreet , Jie Kon-Siong G. , Larsen Thomas Stauffer , van der Poel Marjolein W. , Leijs Maria B. , Silbermann Matthijs H. , van Marwijk Kooy Marinus , Beeker Aart , Kersten Marie J. , Doorduijn Jeanette K. , Tick Lidwine W. , Brouwer Rolf E. , Lam King H. , Burggraaff Coreline N. , de Keizer Bart , Arens Anne I. , de Jong Daphne , Hoekstra Otto S. , Zijlstra-Baalbergen Josée M.
Published: July 2020

PURPOSE

Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP.

PATIENTS AND METHODS

A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat.

RESULTS

CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections.

CONCLUSION

Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.