bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative whole genome sequencing analysis identified a candidate locus for lack of operculum in cultivated gilthead seabream (Sparus aurata)
Authors: Bertolini F. , Ribani A. , Capoccioni F. , Buttazzoni L. , Utzeri V. J. , Bovo S. , Schiavo G. , Caggiano M. , Rothschild M. F. , Fontanesi L.
Published: February 2021

The gilthead seabream (Sparus aurata, Sparidae family) is commonly used for aquaculture. Despite its great economic value, several problems in its cultivation remain. One of the major concerns is the high frequency of morphological abnormalities occurring during the early developmental stages. Partial and/or total lack of operculum is the most frequent anomaly affecting the fish cranial region. The existence of genetic factors that can at least partially determine this defect has been hypothesized. In this work, two DNA pools of highly related fry, one composed of normal‐looking (control) fish and the other lacking an operculum (case), were constructed and whole‐genome resequencing data produced from the two were compared. The analysis revealed a 1 Mb region on chromosome 2 with higher heterozygosity in the lack of operculum DNA pool than in the control DNA pool, consistent with the enrichment, in the first DNA pool, of one or more haplotypes causing or predisposing to the defect together with other normal haplotypes. A window‐based FST analysis between the two DNA pools indicated that the same region had the highest divergence score. This region contained 2921 SNVs, 10 of which, with predicted high impacts (three splice donor and seven stop‐gained variants), were detected in novel genes that are homologous to calcium‐sensing receptor‐like genes, probably involved in bone development. Other studies are needed to clarify the genetic mechanisms involved in predisposing fry to this deformity and then to identify associated markers that could be used in breeding programs to reduce the frequency of this defect in the broodstock.
Increased TOX expression concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with non‐Hodgkin lymphoma
Authors: Huang Shuxin , Liang Chaofeng , Zhao Yujie , Deng Tairan , Tan Jiaxiong , Lu Yuhong , Liu Sichu , Li Yangqiu , Chen Shaohua
Published: February 2021

Aim

To characterize immune suppression in lymphoma, thymocyte selection‐associated high mobility group box protein (TOX) expression and co‐expression with programmed cell death receptor‐1 (PD‐1), T cell immunoglobulin mucin‐domain‐containing‐3 (Tim‐3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed.

Methods

TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi‐color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals.

Results

An increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non‐Hodgkin's lymphoma (B‐NHL) in comparison with healthy controls. Moreover, TOX+PD‐1+ and TOX+Tim‐3+ double‐positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B‐NHL group. There was apparent heterogeneity in TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD‐1+ Treg cells also significantly increased in the B‐NHL group.

Conclusions

Higher expression of TOX concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with B‐NHL may contribute to T cell exhaustion and impair their special anti‐tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies.
Review of systemic chemotherapy in unresectable colorectal peritoneal carcinomatosis
Authors: Nindra Udit , Shahnam Adel , Mahon Kate L.
Published: February 2021

Colorectal cancer remains the third most common malignancy in Australia with the peritoneum being the second most common metastatic site. Colorectal peritoneal carcinomatosis (CPC) can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but this is only limited to a small subset of patients. Those with inoperable disease have a particularly poor prognosis. While the ideal systemic regimen has not been defined, 5‐fluorouracil‐based chemotherapy regimens appear to provide overall and progression free survival benefits. The role of targeted agents such as bevacizumab (vascular endothelial growth factor inhibitor) or cetuximab (epidermal growth factor inhibitor) in the setting of CPC is still evolving. Currently, retrospective analyses have shown promising results for the use of bevacizumab in addition to systemic chemotherapy but similar results have not been seen with cetuximab or panitumumab. However, there is significant heterogeneity in the trial data, lack of prospective randomized controlled trials and demonstrated treatment variability based on age and tumour characteristics. This review summarises the current literature in regard to treatment in the unresectable CPC setting as well as discussing issues with the current data and highlighting the need for further trials.
Psoriatic arthritis in patients with psoriasis: A clinical‐epidemiological study at a dermatology center in western Mexico
Authors: Barba‐Gómez José Fernando , Zolano‐Orozco Miroslava , Guevara‐Gutiérrez Elizabeth , Briseño‐Rodríguez Gabriela , Villanueva‐Quintero Guadalupe , Tlacuilo‐Parra Alberto , García‐Figueroa José Luis , Samano‐Tirado Gustavo , Terán‐Estrada Leobardo , Galván‐Villegas Federico , Gutiérrez‐Ureña Sergio
Published: February 2021

Background/Objective

Psoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical–epidemiological characteristics of PsA in psoriasis patients in western Mexico.

Methods

A cross‐sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used.

Results

Of 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001).

Conclusions

Patients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed.
(Almost) Everything in Moderation: New Evidence on Americans' Online Media Diets
Authors: Guess Andrew M.
Published: February 2021

Does the internet facilitate selective exposure to politically congenial content? To answer this question, I introduce and validate large‐N behavioral data on Americans' online media consumption in both 2015 and 2016. I then construct a simple measure of media diet slant and use machine classification to identify individual articles related to news about politics. I find that most people across the political spectrum have relatively moderate media diets, about a quarter of which consist of mainstream news websites and portals. Quantifying the similarity of Democrats' and Republicans' media diets, I find nearly 65% overlap in the two groups' distributions in 2015 and roughly 50% in 2016. An exception to this picture is a small group of partisans who drive a disproportionate amount of traffic to ideologically slanted websites. If online “echo chambers” exist, they are a reality for relatively few people who may nonetheless exert disproportionate influence and visibility.
Effects of containment and closure policies on controlling the COVID‐19 pandemic in East Asia
Authors: Chen Sylvia Xiaohua , Lam Ben C.P. , Liu James H. , Choi Hoon‐Seok , Kashima Emiko , Bernardo Allan B.I.
Published: February 2021

Growing efforts have been made to pool coronavirus data and control measures from countries and regions to compare the effectiveness of government policies. We examine whether these strategies can explain East Asia’s effective control of the COVID‐19 pandemic based on time‐series data with cross‐correlations between the Stringency Index and number of confirmed cases during the early period of outbreaks. We suggest that multidisciplinary empirical research in healthcare and social sciences, personality, and social psychology is needed for a clear understanding of how cultural values, social norms, and individual predispositions interact with policy to affect life‐saving behavioural changes in different societies.
Thyroid‐stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum: A prospective cohort study
Authors: Nijsten Kelly , Koot Marjette H. , van der Post Joris A. M. , Bais Joke M. J. , Ris‐Stalpers Carrie , Naaktgeboren Christiana , Bremer Henk A. , van der Ham David P. , Heidema Wieteke M. , Huisjes Anjoke , Kleiverda Gunilla , Kuppens Simone M. , van Laar Judith O. E. H. , Langenveld Josje , van der Made Flip , Papatsonis Dimitri , Pelinck Marie‐José , Pernet Paula J. , van Rheenen‐Flach Leonie , Rijnders Robbert J. , Scheepers Hubertina C. J. , Siegelaar Sarah E. , Vogelvang Tatjana , Mol Ben W. , Roseboom Tessa J. , Grooten Iris J. , Painter Rebecca C.
Published: February 2021

Introduction

Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG.

Material and methods

We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4.

Results

Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47‐3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36‐3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty‐one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03).

Conclusions

Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.
Pregnancy‐induced hypertension and retinopathy of prematurity: a meta‐analysis
Authors: Ge Ge , Zhang Yun , Zhang Meixia
Published: February 2021

Purpose

Retinopathy of prematurity (ROP), one of the leading causes of childhood blindness, is a complex condition in which various antenatal and neonatal factors participate at different stages of the disease. This meta‐analysis was conducted to investigate whether pregnancy‐induced hypertension (PIH) was associated with ROP by summarizing all available evidence.

Methods

PubMed, EMBASE, Web of Science, EBSCO and SCOPUS databases were searched for all relevant studies published from inception to April 2020. Studies investigating the association between PIH and ROP were included.

Results

A total of 29 studies were finally included for the meta‐analysis after study selection. The results showed there are both no significant association between PIH and the occurrence of ROP in case–control studies (OR 0.91, 95%CI 0.59 to 1.40, I2 = 81%, p = 0.67) and cohort studies (OR 1.32, 95%CI 0.89 to 1.98, I2 = 93%, p = 0.17). The conclusion was same between pre‐eclampsia and ROP (OR 0.82, 95%CI: 0.50 to 1.35, I2 = 83%, p = 0.43 in case–control studies and OR 1.70, 95%CI: 0.82 to 3.50, I2 = 95%, p = 0.15 in cohort studies).

Conclusion

In summary, this meta‐analysis did not reveal a consistent result, the conclusion remains inconclusive, and further studies will be needed to come to a conclusion for the effect of maternal PIH on ROP and foster a better understanding of the prevention of ROP.
Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study
Authors: Stilgenbauer Stephan , Bosch Francesc , Ilhan Osman , Kisro Jens , Mahé Béatrice , Mikuskova Eva , Osmanov Dzhelil , Reda Gianluigi , Robinson Sue , Tausch Eugen , Turgut Mehmet , Wójtowicz Marcin , Böttcher Sebastian , Perretti Thomas , Trask Peter , Van Hoef Marlies , Leblond Véronique , Foà Robin
Published: February 2021

The manageable toxicity profile of obinutuzumab (GA101; G) alone or with chemotherapy in first‐line (1L; fit and non‐fit) and relapsed/refractory (R/R) patients with chronic lymphocytic leukaemia (CLL) was established in the primary analysis of the Phase IIIb GREEN trial (Clinicaltrials.gov: NCT01905943). The final analysis (cut‐off, 31 January 2019) is reported here. Patients received G (1000 mg) alone (G‐mono; fit and non‐fit patients) or with chemotherapy [fludarabine and cyclophosphamide (FC; fit patients); chlorambucil (non‐fit patients); bendamustine (any patient)]. Study endpoints were safety (primary) and efficacy (secondary). Subgroup analyses were performed on prognostic biomarkers in 1L CLL. Overall, 630 patients received 1L and 341 received R/R CLL treatment. At the final analysis, no new safety signals were observed [Grade ≥ 3 adverse events (AEs): 1L 82·7%, R/R 84·5%; serious AEs: 1L 58·1%, R/R 62·5%]. Neutropenia (1L 50·5%, R/R 53·4%) and thrombocytopenia (1L 14·6%, R/R 19·1%) were the most common Grade 3–5 AEs. G‐mono‐, G‐bendamustine and G‐FC‐treated patients with unmutated immunoglobulin heavy chain trended towards shorter progression‐free survival. Achievement of minimal residual disease negativity was greatest in 1L patients treated with G‐FC. In this final analysis of the GREEN trial, the safety profile of G was consistent with current risk management strategies. Biomarker analyses supported efficacy in the specific subgroups.
Targeting self‐criticism in the treatment of nonsuicidal self‐injury in dialectical behavior therapy for adolescents: a randomized clinical trial
Authors: Ramsey William A. , Berlin Kristoffer S. , Del Conte Garry , Lightsey Owen R. , Schimmel‐Bristow Allison , Marks Laura R. , Strohmer Douglas C.
Published: February 2021

Background

The Benefits and Barriers Model proposes both benefits and barriers associated with nonsuicidal self‐injury (NSSI) and that a negative association with the self plays a key role in the initial selection of and acute motivation for NSSI. The current investigation builds upon previous findings by assessing the added benefit of targeting self‐criticism in the treatment of NSSI.

Methods

Sample included 40 participants (30 females; Mage = 14.92) enrolled in dialectical behavior therapy for adolescents within a partial hospitalization program. All study participants received dialectical behavior therapy for adolescents, and those randomized to the experimental condition received an additional brief cognitive intervention developed to decrease self‐criticism.

Results

There was no evidence of an indirect effect of targeting self‐criticism upon NSSI at post‐treatment via post‐treatment self‐criticism (b = −0.98, p = .543); however, there was evidence of a significant interaction between treatment condition and self‐criticism at pretreatment in the prediction of NSSI at post‐treatment (b = 0.33, p = .030). Analyses of simple slopes indicated the conditional direct effect of targeting self‐criticism varied as a function of patient’s level of self‐criticism at the onset of treatment, such that individuals −1 SD below the mean (b = −5.76, p = .037) and at average pretreatment levels of self‐criticism (b = −4.09, p = .042), but not + 1 SD above the mean (b = −2.42, p = .056), experienced fewer incidents of NSSI at post‐treatment.

Conclusions

The results of this investigation support the added benefit of targeting self‐criticism in the treatment of NSSI for adolescents.
Dysregulation of Wnt/β‐catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application
Authors: Li Qian , Sun Mengqing , Wang Menglan , Feng Mengqing , Yang Fan , Li Lina , Zhao Jianbo , Chang Cunjie , Dong Heng , Xie Tian , Chen Jianxiang
Published: February 2021

Wnt/β‐catenin signaling is indispensable for many biological processes, including embryonic development, cell cycle, inflammation, and carcinogenesis. Aberrant activation of the Wnt/β‐catenin signaling can promote tumorigenicity and enhance metastatic potential in hepatocellular carcinoma (HCC). Targeting this pathway is a new opportunity for precise medicine for HCC. However, inhibiting Wnt/β‐catenin signaling alone is unlikely to significantly improve HCC patient outcome due to the lack of specific inhibitors and the complexity of this pathway. Combination with other therapies will be an important next step in improving the efficacy of Wnt/β‐catenin signaling inhibitors. Protein kinases play a key and evolutionarily conserved role in the Wnt/β‐catenin signaling and have become one of the most important drug targets in cancer. Targeting Wnt/β‐catenin signaling and its regulatory kinase together will be a promising HCC management strategy. In this review, we summarize the kinases that modulate the Wnt/β‐catenin signaling in HCC and briefly discuss their molecular mechanisms. Furthermore, we list some small molecules that target the kinases and may inhibit Wnt/β‐catenin signaling, to offer new perspectives for preclinical and clinical HCC studies.
Development of Math Attitudes and Math Self‐Concepts: Gender Differences, Implicit–Explicit Dissociations, and Relations to Math Achievement
Authors: Cvencek Dario , Brečić Ružica , Gaćeša Dora , Meltzoff Andrew N.
Published: February 2021

Three hundred and ninety‐one children (195 girls; Mage = 9.56 years) attending Grades 1 and 5 completed implicit and explicit measures of math attitudes and math self‐concepts. Math grades were obtained. Multilevel analyses showed that first‐grade girls held a strong negative implicit attitude about math, despite no gender differences in math grades or self‐reported (explicit) positivity about math. The explicit measures significantly predicted math grades, and implicit attitudes accounted for additional variance in boys. The contrast between the implicit (negativity for girls) and explicit (positivity for girls and boys) effects suggest implicit–explicit dissociations in children, which have also been observed in adults. Early‐emerging implicit attitudes may be a foundation for the later development of explicit attitudes and beliefs about math.
Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women
Authors: Li Chun‐Wei , Yu Kang , Shyh‐Chang Ng , Li Guo‐Xun , Yu Song‐Lin , Liu Hui‐Jun , Yang Bo , Li Zi‐Yao , Zhao Yong‐Jie , Xu Long‐Yu , Xu Jing , Jiang Ling‐Juan , Liu Rong‐Ji , Zhang Xin‐Yuan , Li Shao‐Fei , Zhang Xiao‐Wei , Xie Hai‐Yan , Li Kang , Zhan Yi‐Xiang , Cui Min , Tao Hang‐Bo , Li Yao , Liu Gao‐Shan , Ni Ke‐Min , Li Dong‐Jing
Published: February 2021

Objectives

Our aim was to investigate the prevalence and predictive variables of sarcopenia.

Methods

We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables.

Results

The prevalence of sarcopenia and sarcopenic obesity was 9.2%‐16.2% and 0.26%‐9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut‐off value for age was 71 years, which departs from the commonly accepted cut‐off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25‐hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia.

Conclusions

Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.
Conservation science and the ethos of restraint
Authors: Brister Evelyn , Holbrook J. Britt , Palmer Megan J.
Published: February 2021

Despite aiming to make conservation science and practice more effective, many conservationists default to excessive precaution, advocating conservative actions—or even inaction. The field suffers from an understandable aversion to unintended consequences, especially for approaches involving biotechnology and “next‐generation” interventions. We call this default precautionary attitude among conservationists the ethos of restraint and argue for replacing it with an ethos of responsible conservation action. Loosening the ethos of restraint will require (a) more holistically accounting for comparative risks, benefits, and costs of novel approaches; (b) gathering more data on their consequences; (c) engaging in dialogue about intended consequences and conservation values; and (d) pursuing adaptive implementation strategies. Adopting an ethos of responsible conservation action requires grasping that precaution and proaction are not diametrically opposed attitudes. Instead, we must decide what level of precaution or proaction is warranted, and what to do, on a case‐by‐case basis.
Constraint‐induced movement therapy for children with neonatal brachial plexus palsy
Authors: Van der Looven Ruth , Coupe Anna Maria
Published: February 2021

This commentary is on the original article by Werner et al. on pages 545–551 of this issue.
Dapagliflozin effects on lung fluid volumes in patients with heart failure and reduced ejection fraction: Results from the DEFINE‐HF trial
Authors: Nassif Michael E. , Windsor Sheryl L. , Tang Fengming , Husain Mansoor , Inzucchi Silvio E. , McGuire Darren K. , Pitt Bertram , Scirica Benjamin M. , Austin Bethany , Fong Michael W. , LaRue Shane J. , Umpierrez Guillermo , Hartupee Justin , Khariton Yevgeniy , Malik Ali O. , Ogunniyi Modele O. , Wenger Nanette K. , Kosiborod Mikhail N.
Published: February 2021

Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular death or worsening heart failure (HF), and improve symptom burden, physical function and quality of life in patients with HF and reduced ejection fraction. The mechanisms of the HF benefits of SGLT2 inhibitors, however, remain unclear. In this substudy of the DEFINE‐HF trial, patients randomized to dapagliflozin or placebo had lung fluid volumes (LFVs) measured by remote dieletric sensing at baseline and after 12 weeks of therapy. A significantly greater proportion of dapagliflozin‐treated patients (as compared with placebo) experienced improvement in LFVs and fewer dapagliflozin‐treated patients had no change or deterioration in LFVs after 12 weeks of treatment. To our knowledge, this is the first study to suggest a direct effect of dapagliflozin (or any SGLT2 inhibitor) on more effective “decongestion”, contributing in a meaningful way to the ongoing debate regarding the mechanisms of SGLT2 inhibitor HF benefits.
Imaging a unicuspid aortic valve with transillumination
Authors: Malagoli Alessandro , Albini Alessandro , Baldini Luca , Grassi Laura , Tondi Stefano
Published: February 2021

Unicuspid aortic valve (UAV) is a rare congenital malformation which portends an augmented risk of early valve degeneration. Timely detection of this cardiac valvular anomaly is crucial because a strict follow‐up is warranted. Currently, the best morphological information is provided by two‐dimensional echocardiography; however, its diagnostic performance has been found to be suboptimal by some anatomical features, making it tough to distinguish between UAV and bicuspid aortic valve. Transillumination is a photo‐realism technique that employs the use of a virtual light source that simulates the interaction of light on 3‐dimensional surfaces, improving the visualization of morphological characteristics. Our report highlights the incremental value of photo‐realistic rendering and lighting source technology to better define the aortic valve morphology.
The influence of time, soil moisture and exogenous factors on the survival potential of oospores and chlamydospores of Phytophthora cinnamomi
Authors: Gyeltshen Jamba , Dunstan William A. , Grigg Andrew H. , Burgess Treena I. , St. J. Hardy Giles E.
Published: February 2021

The mode of persistence of Phytophthora cinnamomi, a highly aggressive soil‐ and water‐borne pathogen, remains unclear. This study investigated the survival of viable oospores and chlamydospores of P. cinnamomi when present as free propagules in untreated soil, or in soil subject to four exogenous treatments: smoke water, fish emulsion and two fungicides (ridomil and furalaxyl). The exogenous treatments were applied under moist and dry soil conditions. Spore viability was determined by the thiazolyl blue tetrazolium bromide (MTT) staining technique, with a qPCR assay used to compare general patterns of decline. Over 96% of oospores lost viability over a period of 48 weeks irrespective of soil moisture conditions. The mean percentage viability for oospores decreased from 91% at time zero to 72, 35, 20 and 1% after 6, 12, 24 and 48 weeks, respectively. Reduction in viability of chlamydospores was more rapid than oospores, with viability declining from 92% to zero after 12 weeks. There was no significant difference between untreated soil and the exogenous treatments. The RNA‐based qPCR assay indicated a strong presence of viable oospores of P. cinnamomi up to week 12 for moist soil and week 3 for dry soil, but thereafter failed to detect RNA even though viable oospores could be detected by MTT staining. Based on the MTT staining, this study indicated that viability of P. cinnamomi oospores may be entirely lost within 1 year and that of chlamydospores within 3 months for the soil type tested. Therefore, oospores and chlamydospores when existing as free propagules in soil appear unlikely to be involved in the long‐term survival of P. cinnamomi.
Screening of Metrosideros polymorpha (‘ōhi‘a) varieties for resistance to Ceratocystis lukuohia
Authors: Luiz Blaine , Stacy Elizabeth A. , Keith Lisa M.
Published: February 2021

Stands of the landscape‐dominant tree, Metrosideros polymorpha (‘ōhi‘a) on the Island of Hawai‘i, HI., USA, are dying from a phenomenon known as rapid ‘ōhi‘a death (ROD). Approximately 180,000 acres of forest have already been impacted by the disease, the majority of which is attributed to C. lukuohia, the more aggressive of the two Ceratocystis species responsible for ROD. Three isolates of C. lukuohia were compared for differences in aggressiveness. Mean disease severity and mean number of days to death did not differ among the three isolates of C. lukuohia. A single isolate was selected for use in a resistance screening of 128 plants across four varieties of M. polymorpha occurring on Hawai‘i Island: incana, glaberrima, polymorpha and newellii. Disease severity was lower in early‐successional var. incana (38.84%) and riparian var. newellii (36.11%) compared to late‐successional var. glaberrima (61.27%) and high‐elevation var. polymorpha (70.27%). Var. incana and var. newellii also had the lowest mortality (63% and 77%, respectively) while var. glaberrima (86%) and var. polymorpha (100%) had the highest mortality. Eighty‐five per cent of the plants that died did so within 49 days post‐inoculation and mean number of days to death was significantly higher for var. glaberrima (46) compared to var. polymorpha (31). The results of this preliminary study suggest that some form of resistance might be present in natural populations of at least one variety of M. polymorpha on Hawai‘i Island and should be investigated more intensively.
Botryosphaeriaceae species causing canker and dieback of English walnut (Juglans regia) in Italy
Authors: Gusella Giorgio , Giambra Selene , Conigliaro Gaetano , Burruano Santella , Polizzi Giancarlo
Published: February 2021

English walnut (Juglans regia) is an important nut crop worldwide and is currently considered emerging in Italy. Botryosphaeriaceae fungi cause symptoms including cankers, discoloration and dieback, and several species are reported across the world on walnut. In this study, symptomatic trees from an orchard in Southern Italy showing branch dieback, cankers, wood discoloration and gummosis were surveyed. Three different fungi from the Botryosphaeriaceae were consistently isolated from symptomatic tissues. Representative isolates were characterized using morphological and molecular approaches based on conidial morphology, optimum growth temperature and the comparison of DNA sequence data from the ITS, tef1‐α and tub2 loci. Three species were identified: Botryosphaeria dothidea, Neofusicoccum mediterraneum and Neofusicoccum parvum. Pathogenicity tests on detached fruits and potted plants showed that all three species were pathogenic. To our knowledge, this is the first report of these Botryosphaeriaceae species causing canker and dieback on English walnut in Italy.
Phylogeography and host range of Armillaria gallica in riparian forests of the northern Great Plains, USA
Authors: Alveshere Brandon C. , McMurtrey Shawn , Bennett Patrick , Kim Mee‐Sook , Hanna John W. , Klopfenstein Ned B. , Blodgett James T. , LeBoldus Jared M.
Published: February 2021

Root disease pathogens, including Armillaria, are a leading cause of growth loss and tree mortality in forest ecosystems of North America. Armillaria spp. have a wide host range and can cause significant reductions in tree growth that may lead to mortality. DNA sequence comparisons and phylogenetic studies have allowed a better understanding of Armillaria spp. taxonomic diversity. Genetic sequencing has facilitated the mapping of species distributions and host associations, providing insights into Armillaria ecology. These studies can help to inform forest management and are essential in the development of disease risk maps, leading to more effective management strategies for Armillaria root disease. Armillaria surveys were conducted on publicly owned lands in North Dakota, South Dakota, and Nebraska, U.S.A. Surveyed stands consisted of riparian forests ≥0.4 hectares in area. Armillaria was found at 78 of 101 sites. A total of 57 Armillaria isolates—associated with 12 host tree species—were used for DNA sequencing of the translation elongation factor‐1 alpha (tef1) gene. Armillaria gallica was the only species identified within the study sites. Results suggest that A. gallica is a common root pathogen of hardwood trees in riparian forests of the northern Great Plains with a wider host range and geographic distribution than previously recognized.
Healthcare resource utilization in adult patients with relapsed/refractory FLT3 mutated acute myeloid leukemia: A retrospective chart review from Spain
Authors: Solana‐Altabella Antonio , Boluda Blanca , Rodríguez‐Veiga Rebeca , Cano Isabel , Acuña‐Cruz Evelyn , Blanco Albert , Marco‐Ayala Javier , de la Puerta Rosalía , Díaz‐González Álvaro , Piñana José L. , Sanz Jaime , Sempere Amparo , Cervera José , Barragán Eva , Sargas Claudia , Ballesta‐López Octavio , Megías‐Vericat Juan Eduardo , Martínez‐Cuadrón David , Sanz Miguel Á. , Montesinos Pau
Published: February 2021

Background

Information regarding impact on healthcare systems of relapsed or refractory (R/R) FLT3 mutated (FLT3mut) acute myeloid leukemia (AML) is scarce.

Objective

To assess the time and reimbursement associated with hospitalizations of patients with R/R FLT3mut AML in a tertiary Spanish hospital.

Methods

Retrospective review of medical charts identified patients aged ≥ 18 years with R/R FLT3mut AML between 1998 and 2018. Data were collected from the date of first diagnosis of R/R FLT3mut AML (index) until death or loss to follow‐up. The primary end point was duration and frequency of hospitalization, use of outpatient resources and transfusion burden. Reimbursement associated with hospitalizations (including associated chemotherapy) was also assessed.

Results

Thirty‐eight patients were eligible for inclusion. Their median age was 52 years, and 30 (79%) received intensive salvage chemotherapy; FLAG‐IDA‐based regimens were the most frequent (24 patients, 63%). Overall, there were 150 hospitalizations (mean 3.9/patient; mean duration 21 days). Patients spent a mean of 24% of the study period in hospital. Total mean reimbursement was €108 293 per patient; the majority (€89 834) attributable to inpatient stays (€22 576 /hospitalization). During chemotherapy period (prior to first alloHSCT), there were 73 hospitalizations (mean duration 22 days); mean reimbursement was €19 776 per hospitalization and €49 819 per patient. AlloHSCT (n = 16) involved 77 hospitalizations (mean duration 21 days), mean reimbursement €25 231/hospitalization and €131 515 per patient.

Conclusion

Data from this study suggest that there is a substantial healthcare resource utilization and cost burden on R/R FLT3mut AML patients in Spain receiving active treatments.
Experimental manipulation of body size alters life history in hydra
Authors: Ngo Kha Sach , R‐Almási Berta , Barta Zoltán , Tökölyi Jácint
Published: February 2021

Body size has fundamental impacts on animal ecology and physiology but has been strongly influenced by recent climate change and human activities, such as size‐selective harvesting. Understanding the ecological and life history consequences of body size has proved difficult due to the inseparability of direct effects of body size from processes connected to it (such as growth rate and individual condition). Here, we used the cnidarian Hydra oligactis to directly manipulate body size and understand its causal effects on reproduction and senescence. We found that experimentally reducing size delayed sexual development and lowered fecundity, while post‐reproductive survival increased, implying that smaller individuals can physiologically detect their reduced size and adjust life history decisions to achieve higher survival. Our experiment suggests that ecological or human‐induced changes in body size will have immediate effects on life history and population dynamics through a growth‐independent link between body size, reproduction and senescence.
Menopause does not modify disability trajectories in a longitudinal cohort of women with clinically isolated syndrome and multiple sclerosis followed from disease onset
Authors: Otero‐Romero Susana , Midaglia Luciana , Carbonell‐Mirabent Pere , Zuluaga María , Galán Ingrid , Río Jordi , Arrambide Georgina , Rodríguez‐Barranco Marta , Vidal‐Jordana Angela , Castillo Joaquin , Rodríguez‐Acevedo Breogán , Zabalza Ana , Nos Carlos , Comabella‐Lopez Manuel , Mulero Patricia , Auger Cristina , Sastre‐Garriga Jaume , Pérez‐Hoyos Santiago , Rovira Alex , Montalban Xavier , Tintoré Mar
Published: February 2021

Background and purpose

To evaluate the effect of menopause on disability accumulation in women followed from their clinically isolated syndrome (CIS).

Methods

We examined the longitudinal changes in Expanded Disability Status Scale (EDSS) scores from CIS until the last follow‐up in women belonging to the Barcelona CIS prospective cohort, followed through their menopausal transition. The analysis is based on 13,718 EDSS measurements, with an average of 28 EDSS measurements per patient. Differences in EDSS trajectories between menopausal and nonmenopausal women, controlling for age and disease duration, were evaluated. We performed two sensitivity analyses in women with confirmed MS and in those experiencing early menopause.

Results

From 764 eligible women, 496 (65%) responded to the questionnaire, and 74 (14.9%) reached menopause over the follow‐up. We did not find a significant inflection point in EDSS trajectories around menopause (slope change −0.009; 95% CI −0.066; 0.046). The annual increase in EDSS over the complete course of the disease was significantly higher in menopausal women (0.049; 95% CI, 0.026–0.074) versus nonmenopausal (0.019; 95% CI, 0.008–0.031; interaction p value 0.025). This difference was lost when controlling for age and disease duration (EDSS annual increase of 0.059; 95% CI, 0.025–0.094 vs. 0.038; 95% CI, 0.021–0.057, respectively; interaction p value 0.321). No inflection point was detected when the analysis was restricted to women with confirmed MS or with earlier menopause.

Conclusions

Menopause is not associated with an increased risk of disability in a CIS population, considering EDSS trajectories throughout the course of the disease together with age and disease duration.
An attention‐driven videogame based on steady‐state motion visual evoked potentials
Authors: Perez‐Valero Eduardo , Lopez‐Gordo Miguel Angel , Vaquero‐Blasco Miguel A.
Published: February 2021

In Neuroscience, steady‐state visually evoked potentials (SSVEPs) have been generally used for the characterization of dynamic visual processes along the afferent pathway. In Neuroengineering, SSVEP‐based brain‐computer interfaces (SSVEP‐BCI) have been used in applications such as communications or entertainment for the detection of the overt attention to static‐flickering stimuli or other structured stimulation that involves motion (SSMVEP‐BCI). In this work, we propose an attention‐driven videogame controlled by an SSVEP‐BCI with mobile‐flickering stimuli. In this game, enemy avatars launch attacks that are presented as mobile ring‐shaped checkerboards that flicker at 15 Hz to the player, who must deflect them by exerting attention. We detected the attention of the participants based on the power spectral density of the elicited SSVEP and the adjacent electroencephalographic background noise. Twenty volunteers participated in this study. After completion, according to a game experience survey, the participants described the game as amusing and challenging. We also conducted a level survey that revealed a significant difference between the levels of attention exerted by the participants when they passed the levels with respect to when they missed (p‐value = 17 · 10−5). Additionally, the detection accuracy of the SSVEP‐BCI had a baseline level of 84%. The results suggest that mobile flickers can be robustly detected within few seconds by means of an SSVEP‐BCI. This principle could be used as a serious game to play or train the attention and the visual tracking capabilities to mobile target stimuli in special needs education schools or in centres dealing with attention disorders.
Medical imaging examination in psoriasis and early psoriatic arthritis patients: an updated systematic review and meta‐analysis
Authors: Qi Fei , Yao Amin , He Yanling
Published: February 2021

Psoriatic arthritis appears in one in four skin psoriasis patients. Early detection of the presence of joint involvement and early interception of its developments may minimize long‐term functional disability, and the radiological methods may be a perfect choice. To summarize and compare different imaging methods for diagnosing early‐stage psoriatic arthritis and determine the necessity of joint examination in all psoriasis patients, several electronic databases, including MEDLINE and EMBASE, were searched for English language studies. A specific selection criterion followed the retrieval of studies. Thirteen studies were finally enrolled in the meta‐analysis, eight of which compared the bone changes presentat on medical imaging examination between psoriasis patients without psoriatic arthritis and healthy people; three studies focused on differences between psoriatic arthritis patients and free joint involvement psoriasis patients shown on medical imaging tests. Medical imaging examination, including ultrasound (US), high‐resolution peripheral quantitative CT scans (HR‐pQCT), and magnetic resonance imaging (MRI), can be good choices for detecting the start of asymptomatic joint inflammation in psoriasis patients, which is essential to early detection and interception of joint damage to lower joint deformities and improve the future quality of life for patients. Additionally, the examination for psoriasis patients with arthralgia is also highly recommended.
Immunity against Mycobacterium ulcerans: The subversive role of mycolactone
Authors: Demangel Caroline
Published: February 2021

Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life‐long deformity and disability. Differently from other mycobacterial pathogens, M ulcerans produces mycolactone, a diffusible lipid factor with unique cytotoxic and immunomodulatory properties. Both traits result from mycolactone targeting Sec61, the entry point of the secretory pathway in eukaryotic cells. By inhibiting Sec61, mycolactone prevents the host cell's production of secreted proteins, and most of its transmembrane proteins. This molecular blockade dramatically alters the functions of immune cells, thereby the generation of protective immunity. Moreover, sustained inhibition of Sec61 triggers proteotoxic stress responses leading to apoptotic cell death, which can stimulate vigorous immune responses. The dynamics of bacterial production of mycolactone and elimination by infected hosts thus critically determine the balance between its immunostimulatory and immunosuppressive effects. Following an introduction summarizing the essential information on Buruli ulcer disease, this review focuses on the current state of knowledge regarding mycolactone's regulation and biodistribution. We then detail the consequences of mycolactone‐mediated Sec61 blockade on initiation and maintenance of innate and adaptive immune responses. Finally, we discuss the key questions to address in order to improve immunity to M ulcerans, and how increased knowledge of mycolactone biology may pave the way to innovative therapeutics.
Diagnostic performance of COVID‐19 serological assays during early infection: A systematic review and meta‐analysis of 11 516 samples
Authors: Zhang John J. Y. , Lee Keng Siang , Ong Chee Wui , Chan Mae Yee , Ang Li Wei , Leo Yee Sin , Chen Mark I‐Cheng , Lye David Chien Boon , Young Barnaby Edward
Published: February 2021

Objective

The use of coronavirus disease 2019 (COVID‐19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID‐19 by providing summary sensitivity and specificity estimates with time from symptom onset.

Methods

A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer‐reviewed publications reporting the diagnostic performance of serological testing vis‐à‐vis virologically confirmed SARS‐CoV‐2 infection were included.

Results

Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784‐0.928) and specificity 0.973 (95% CI: 0.938‐0.988), while IgG sensitivity was 0.913 (95% CI: 0.823‐0.959) and specificity 0.960 (95% CI: 0.919‐0.980). On meta‐regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme‐linked immunosorbent assay (ELISA) compared to other methods.

Conclusions

Serological assays offer imperfect sensitivity for the diagnosis of acute SARS‐CoV‐2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.
Three‐dimensional shape‐conformation performances of wound dressings tested in a robotic sacral pressure ulcer phantom
Authors: Lustig Adi , Gefen Amit
Published: February 2021

Effective exudate retention by dressings requires close and intimate dressing‐wound contact, immediately and continuously after the dressing application. Any dressing‐wound spaces may allow for build‐up of non‐retained fluids, causing exudate pooling which forms a favourable environment for pathogen growth. Maceration may follow if the pooled exudates spread to peri‐wound skin. Dressings with a claimed 3D‐shape‐conformation technology are commercially available; however, their effectiveness in minimising dressing‐wound gaps has never been scientifically investigated. We present a novel bioengineering methodology for testing the effectiveness of such 3D‐shape‐conformation dressings, using our recently reported robotic phantom system of a sacral pressure ulcer. By means of 3D laser scanning and bespoke software, we reconstructed dressing shapes after simulated use and calculated the goodness‐of‐fit between each dressing (swelled to near‐saturation) and the corresponding wound geometry. Two dressing sizes (10 × 10 cm and 12.5 × 12.5 cm) and two wound depths (2.5 or 2 cm) were considered. All the tested dressings were far from reaching good contact with the (simulated) wounds: Approximately one‐third of the wound volume and nearly half of the wound surface were not in contact with the swelled dressings. Our present findings question whether 3D‐shape‐conformation dressings are effective, by revealing their swelling behaviour which was previously unknown.