bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality or Quantity of Proteins in the Diet for CKD Patients: Does “Junk Food” Make a Difference? Lessons from a High-Risk Pregnancy
Authors: Orozco-Guillien Alejandra Oralia , Muñoz-Manrique Cinthya , Reyes-López Maria Angelica , Perichat-Perera Otilia , Miranda-Araujo Osvaldo , D’Alessandro Claudia , Piccoli Giorgina B.
Published: February 2021

Background: How to manage patients with severe kidney disease in pregnancy is still a matter of discussion, and deciding if and when to start dialysis is based on the specialist’s experience and dialysis availability. The effect of toxic substances usually cleared by the kidney may be more severe and readily evident. The review, and related case, underlines the importance of considering the presence of additives in food in delicate conditions, such as CKD pregnancy. The Case: A 39-year-old indigenous woman from a low-resourced area in Mexico was referred to the obstetric nephrology at 25 gestational weeks because of serum creatinine at 3.6 mg/dL, hypertension on low-dose alpha-methyl-dopa, and nephrotic-range proteinuria. Kidney ultrasounds showed small poorly differentiated kidneys; foetal ultrasounds detected a female foetus, normal for gestational age. The patient’s baseline protein intake, which was estimated at 1.2–1.3 g/kg/day, was mostly of animal-origin (>70%) poor-quality food (“junk food”). In the proposed diet, protein intake was only slightly reduced (1.0–1.2 g/kg/day), but the source of proteins was changed (only 30% of animal origin) with attention to food quality. A remarkable decrease in BUN was observed, in concomitance with adequate dietary follow-up, with rapid rise of BUN when the patient switched temporarily back to previous habits. A healthy female baby weighing 2,460 g (11th centile for gestational age) was delivered at 37 gestational weeks. Discussion and Literature Review: While data on patients with chronic kidney disease are scant, the long list of contaminants present in food, especially if of low quality, should lead us to reflect on their potential negative effect on kidney function and make us realize that eating healthy, unprocessed “organic” food should be encouraged, in delicate conditions such as pregnancy and breastfeeding and for young children, in particular when kidney function is failing. The case herein described gave us the opportunity to reflect on the importance of diet quality and on the potential risks linked to food additives, many of which, including phosphates and potassium, are not declared on food labels, while others, including dyes, antioxidants, thickeners, emulsifiers, and preservatives, are qualitatively, but not quantitatively, reported.
Accuracy of Subclassification and Grading of Renal Tumors on Fine Needle Aspiration Cytology Alone
Authors: Chen Heather I.-Hsuan , Lapadat Razvan , Lastra Ricardo R. , Biernacka Anna , Reeves Ward , Mueller Jeffrey , Pambuccian Stefan E. , Barkan Güliz A. , Wojcik Eva M. , Antic Tatjana
Published: February 2021

Background: Fine needle aspiration (FNA) of renal masses can distinguish between benign and malignant neoplasms in 73–94% of cases. Previous studies suggested the correct subclassification of renal cell carcinomas (RCCs) by cytomorphology can be achieved in up to 80% of cases. However, as RCCs become increasingly subclassified by molecular signatures, correct subclassification based on cytology alone is increasingly difficult. Design: Two FNA passes (2 stained with Diff-Quik® and 2 with the Papanicolaou method) were performed on all fresh nephrectomy specimens for a 1-year period. There were 30 cases in this study, with 29 primary renal tumors and 1 case of metastatic lung adenocarcinoma. Each case was assigned a random number and came with 2 slides (1 from each staining method). Eight cytopathologists were asked to provide a diagnosis and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading if applicable. Fleiss’ Kappa and Cohen’s Kappa equations were used to look at inter-rater variability. Results: When compared to the surgical pathology diagnosis, the average percent correct diagnosis for all cytopathologist was 35%. Chromophobe RCCs had the best average percent accuracy at 72% followed by clearcell RCC at 48%. Average accuracy for grading RCCs was 40%. Inter-rater variability among the cytopathologists for all RCC diagnoses was fair with a Fleiss’ Kappa coefficient of 0.28. For the WHO/ISUP grade, the weighted coefficient for each pathologist ranged from 0.11 to 0.45, ranging from fair to moderate, respectively. Conclusions: Renal tumors are difficult to classify on cytopathology alone. Core needle biopsy and ancillary studies are necessary if diagnosis will change management.
Association between the Frequency of Daily Toothbrushing and Development of Nonalcoholic Fatty Liver Disease
Authors: Yamamoto Kazuki , Ikeya Takashi , Okuyama Shuhei , Fukuda Katsuyuki , Kobayashi Daiki
Published: February 2021

Background & Aim: This study aimed to evaluate the association between the frequency of daily toothbrushing and the development of nonalcoholic fatty liver disease (NAFLD). Methods: A retrospective longitudinal study was conducted from 2005 to 2012 at the Center for Preventive Medicine at St. Luke’s International Hospital, Japan. Data on all participants who underwent a health checkup during the study period were collected. NAFLD was diagnosed by abdominal ultrasonography, and all participants who were diagnosed with NAFLD at the time of their initial visit, consumed alcohol in any amount, or had received only one health checkup were excluded. The questionnaire for the frequency of daily toothbrushing was conducted as part of health checkups. The primary outcome was the risk of developing NAFLD according to the frequency of daily toothbrushing (1–2 times a day or 3 times a day) compared to those who brush teeth once or less than once a day. Results: Data were collected from 25,804 people. A total of 3,289 (12.7%) participants developed NAFLD. The mean age was 45.2 years, and 6,901 (26.7%) of the participants were male. The risk of developing NAFLD significantly decreased with increased frequency of daily toothbrushing. Adjusted odds ratios (ORs) are as follows: brushing teeth 1–2 times a day (OR: 0.85, 95% confidence interval [CI]: 0.77–0.95) and 3 times a day (OR: 0.74, 95% CI: 0.67–0.82). Conclusion: Frequent toothbrushing was shown to significantly reduce the risk of developing NAFLD.
BCL11B Regulates Arterial Stiffness and Related Target Organ Damage
Authors: Valisno Jeff Arni C. , May Joel , Singh Kuldeep , Helm Eric Y. , Venegas Lisia , Budbazar Enkhjargal , Goodman Jena B. , Nicholson Christopher J. , Avram Dorina , Cohen Richard A. , Mitchell Gary F. , Morgan Kathleen G. , Seta Francesca
Published: February 2021

Rationale:

BCL11B (B-cell leukemia 11b) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study showed that a gene desert region downstream of
BCL11B
, known to function as a
BCL11B
enhancer, harbors single nucleotide polymorphisms associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown.

Objective:

Based on these human findings, we sought to examine the relation between BCL11B and arterial function.

Methods and Results:

Here we report that BCL11B is expressed in the vascular smooth muscle where it regulates vascular stiffness. RNA sequencing of aortas from wild-type and
Bcl11b
null mice (BSMKO) identified the cGMP (cyclic guanosine monophosphate)-cGMP-dependent protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared with wild-type mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca
++
-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and decreased levels of their common phosphorylation target, phosphorylated vasodilator-stimulated phosphoprotein (pVASP
S239
), a regulator of cytoskelatal actin rearrangements. Decreased pVASP
S239
in BSMKO aortas was associated with increased actin polymerization (filamentous/globular actin ratio). Functionally, aortic force, stress, wall tension, and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared with age-matched wild-type littermates.

Conclusions:

We have identified vascular smooth muscle BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
Rurality, Death, and Healthcare Utilization in Heart Failure in the Community
Authors: Manemann Sheila M. , St. Sauver Jennifer , Henning‐Smith Carrie , Finney Rutten Lila J. , Chamberlain Alanna M. , Fabbri Matteo , Weston Susan A. , Jiang Ruoxiang , Roger Véronique L.
Published: February 2021

Background

Prior reports indicate that living in a rural area may be associated with worse health outcomes. However, data on rurality and heart failure (HF) outcomes are scarce.

Methods and Results

Residents from 6 southeastern Minnesota counties with a first‐ever code for HF (
International Classification of Diseases, Ninth Revision
[
ICD‐9
], code 428, and
International Classification of Diseases, Tenth Revision
[
ICD‐10
] code I50) between January 1, 2013 and December 31, 2016, were identified. Resident address was classified according to the rural‐urban commuting area codes. Rurality was defined as living in a nonmetropolitan area. Cox regression was used to analyze the association between living in a rural versus urban area and death; Andersen‐Gill models were used for hospitalization and emergency department visits. Among 6003 patients with HF (mean age 74 years, 48% women), 43% lived in a rural area. Rural patients were older and had a lower educational attainment and less comorbidity compared with patients living in urban areas (
P
<0.001). After a mean (SD) follow‐up of 2.8 (1.7) years, 2440 deaths, 20 506 emergency department visits, and 11 311 hospitalizations occurred. After adjustment, rurality was independently associated with an increased risk of death (hazard ratio [HR], 1.18; 95% CI, 1.09–1.29) and a reduced risk of emergency department visits (HR, 0.89; 95% CI, 0.82–0.97) and hospitalizations (HR, 0.78; 95% CI, 0.73–0.84).

Conclusions

Among patients with HF, living in a rural area is associated with an increased risk of death and fewer emergency department visits and hospitalizations. Further study to identify and address the mechanisms through which rural residence influences mortality and healthcare utilization in HF is needed in order to reduce disparities in rural health.
Sociosexual behaviour in wild chimpanzees occurs in variable contexts and is frequent between same-sex partners
Authors: Sandel Aaron A. , Reddy Rachna B.
Published: February 2021

Many animals engage in sociosexual behaviour, including that between same-sex pairs. Bonobos (Pan paniscus) are famous for their sociosexual behaviour, but chimpanzees (Pan troglodytes) apparently do not engage in sociosexual behaviour frequently. However, sociosexual behaviour in chimpanzees may have been overlooked. We observed 584 instances of sociosexual behaviour in chimpanzees at Ngogo, Kibale National Park, Uganda during three years of study. All ages and sexes engaged in sociosexual behaviour, which included mounting, touching of genitals, and pressing genitals together. Most sociosexual behaviour was between adult males. Sociosexual behaviour was often during tense contexts, such as subgroup reunions and during territorial behaviour. Among males, grooming and dominance rank relationships do not explain patterns of sociosexual behaviour. Although sociosexual behaviour may be less frequent in chimpanzees than in bonobos, and bonobos remain distinct in their genito-genital rubbing, our findings suggest that sociosexual behaviour is a regular part of chimpanzee behaviour.
Female Asceticism in Late Antique Georgian Literature
Authors: Matitashvili Shota
Published: February 2021

This article examines the forms of female asceticism preserved in the so-called extended recension of the Life of St. Nino – a young Christian Virgin who converted the eastern Georgian kingdom of Iberia in the beginning of the fourth century. This study attempts to reinterpret the traditionally-established point of view about the origins of this composition and investigates several aspects of early Georgian Christianity. According to traditional scholarly opinion, the Vita of St. Nino was composed during the eighth and ninth centuries in order to reinforce the cult of the holy virgin who converted Iberia but the contextualization of the vita into the literary realm of late antiquity reveals more ancient origins of various episodes and layers of the vita. We see martyrs, missionaries, miracle workers, prophets and apostles in the images of Nino and her fellow women. Nino is a typical representative of the female ascetic community formed in early Christendom. Apparently, after the invention of the Georgian alphabet, the literary interactions between Georgians and other eastern Christian peoples intensified. As the Martyrdom of the holy Queen Šušanik reveals, already in the fifth century Georgians had translated the acts of martyrs which certainly influenced the subsequent development of Georgian literature. Of course, the Life has an overwhelmingly legendary and fictional character but its ‘sacred fictions’ originated much earlier than has generally been thought in scholarship.
Barberry (Berberis vulgaris), a medicinal fruit and food with traditional and modern pharmaceutical uses
Authors: Sun Wenli , Shahrajabian Mohamad Hesam , Cheng Qi
Published: February 2021

Barberry is a resistant shrub which is able to grow up in semi-arid region with low-water or salty fields. Its red fruit widely used in Iranian foods because of its color and delicious taste. Berberis known as Zereshk in Persian has been consumed as both a remedy and traditional food additive. Its fruits are used mainly in Persian food in preparing juices, jam, chocolates, sauces and also a garniture. In both traditional and folkore medicine, it has been applied for its many biological and pharmacological activities. The most important compounds of B. Vulgaris are lupeol, oleanolic acid, stigmasterol, stigmasterolglucoside, berberamine, palmatine, berberine, oxyberberine, columbamine, isocorydie, lambertine, magniflorine, and oxycanthine. Barberry which are high in nutrients, contain beneficial plant compounds, which may help to manage diabetes, treat diarrhea, protect against metabolic syndrome, maintain dental health, and help fight acne. It also has anti-cancer effects, and it is appropriate to add to the diet. This review summarizes the beneficial effects of Barberry which is recommended for consumption.
Ophiocordyceps furcatosubulata, a new entomopathogenic fungus parasitizing beetle larvae (Coleoptera: Elateridae)
Authors: WANG YAO , WU HUI-JUAN , TRAN NGOC LAN , ZHANG GUO-DONG , SOUVANHNACHIT SISOMMAY , WANG YUAN-BING , YU HONG
Published: February 2021

A new invertebrate-associated fungus, Ophiocordyceps furcatosubulata, is reported from China, Vietnam and Laos. It is characterized by solitary stromata, clavate and slender stipes, cylindrical fertile parts, furcate and subulate sterile apices, immersed perithecia, short asci, filiform ascospores with multi-septa, short secondary ascospores, hirsutella-like asexual morph with polyphialidic conidiogenous cells, broadly ellipsoid or ellipsoid conidia, and on larvae of elaterid beetles buried in soil. Both morphological observation and phylogenetic analyses of combined nrSSU, nrLSU, tef-1α, rpb1 and rpb2 sequence data support that this fungus is a distinctive species in the genus Ophiocordyceps.
Three new species and one newly recorded species of genus Frisilia Walker (Lepidoptera, Lecithoceridae) from China, with a checklist of the world
Authors: YU SHUAI , WANG SHUXIA
Published: February 2021

Three species of the genus Frisilia Walker, 1864 are described as new: Frisilia basistricta sp. nov., F. motuoensis sp. nov. and F. trisigna sp. nov.; F. sulcata is newly recorded in China. Images of adults and genitalia for all newly described species, a key to the Chinese species, a checklist of the worldwide Frisilia species and a distribution map showing the locality of the Chinese Frisilia species are given.
A new charismatic Caenis Stephens, 1835 (Ephemeroptera: Caenidae) from Southern India
Authors: SRINIVASAN PANDIARAJAN , SIVARUBAN T. , BARATHY S. , MALZACHER PETER , ISACK RAJASEKARAN
Published: February 2021

Caenis americani sp. nov. is described based on larvae and female imagoes from the Mangalamkombu stream of Southern India. Caenis americani is most likely a parthenogenetic species, in the light of the fact that only females have been collected. The larva can be distinguished from other species of Caenis by the i) shape of the sternum IX and its shagreen field, ii) shape and denticulation of hind claws and iii) lateral lobes of mesonotum distinctly bulged. The phylogenetic relationships of the new species remain unknown, as molecular records of Caenis throughout the Oriental region are largely unknown, and the taxonomically important males are absent.
Contrasting Cloud Regimes and Associated Rainfall over the South Asian and East Asian Monsoon Regions
Authors: Wu Ruoting , Chen Guixing
Published: February 2021

The Asian monsoon has large spatial and temporal variabilities in winds and precipitation. This study reveals that the Asian monsoon also exhibits pronounced regional differences in cloud regimes and cloud–rainfall relationship at a wide range of time scales from diurnal to seasonal to interannual. Over South (East) Asia, the convectively active regime of deep convection (CD) occurs frequently in June–September (March–September) with a late-afternoon peak (morning feature). The intermediate mixture (IM) regime over South Asia mainly occurs in summer and maximizes near noon. It develops as CD at late afternoon and dissipates as convective cirrus (CC) after midnight, showing a life cycle of thermal convection in response to solar radiation. Over East Asia, IM is dominant in cold seasons with a small diurnal cycle, indicating a prevalence of midlevel stratiform clouds. Further analyses show that CD and CC contribute 80%–90% of the rainfall amount and most of the intense rainfall in the two key regions. The CD-related rainfall also accounts for the pronounced diurnal cycles of summer rainfall with a late-afternoon peak (morning feature) over northern India (Southeast China). The afternoon CD-related rainfall mainly results from thermal convection under the moderate humidity but warm conditions particularly over northern India, while the morning CD-related rainfall over Southeast China is more related to the processes with high humidity. The CD/CC-related rainfall also exhibits large interannual variations that explain ~90% of the interannual variance of summer rainfall. The interannual variations of CD/CC occurrence are positively correlated with the moist southerlies and induced convergence, especially over Southeast China, suggesting a close relationship between cloud regimes and monsoon activities.
Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis
Authors: Kohli Mikashmi , MacLean Emily , Pai Madhukar , Schumacher Samuel G. , Denkinger Claudia M.
Published: February 2021

Various diagnostic companies have developed high throughput molecular assays for tuberculosis (TB) and resistance detection for rifampicin and isoniazid. We performed a systematic review and meta-analyses to assess the diagnostic accuracy of five of these tests for pulmonary specimens. The tests included were Abbott RealTime MTB, Abbott RealTime RIF/INH, FluoroType MTB, FluoroType MTDBR and BD Max MDR-TB assay.

A comprehensive search of six databases for relevant citations was performed. Cross-sectional, case-control, cohort studies, and randomised controlled trials of any of the index tests were included. Respiratory specimens (such as sputum, bronchoalveolar lavage, tracheal aspirate,etc.) or their culture isolates.

A total of 21 included studies contributed 26 datasets. We could only meta-analyse data for three of the five assays identified, as data were limited for the remaining two. For TB detection, the included assays had a sensitivity of 91% or more and the specificity ranged from 97% to 100%. For rifampicin resistance detection, all the included assays had a sensitivity of more than 92%, with a specificity of 99–100%. Sensitivity for isoniazid resistance detection varied from 70 to 91%, with higher specificity of 99–100% across all index tests. Studies that included head-to-head comparisons of these assays with Xpert MTB/RIF for detection of TB and rifampicin resistance suggested comparable diagnostic accuracy.

In people with symptoms of pulmonary TB, the centralised molecular assays demonstrate comparable diagnostic accuracy for detection of TB, rifampicin and isoniazid resistance to Xpert MTB/RIF assay, a WHO recommended molecular test.
Effect of asthma and asthma medication on the prognosis of patients with COVID-19
Authors: Choi Yong Jun , Park Ju-Young , Lee Hye Sun , Suh Jin , Song Jeung Yoon , Byun Min Kwang , Cho Jae Hwa , Kim Hyung Jung , Lee Jae-Hyun , Park Jung-Won , Park Hye Jung
Published: February 2021

Background

Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. However, the effects of asthma, asthma medication and asthma severity on the clinical outcomes of COVID-19 have not yet been established.

Methods

The study included 7590 de-identified patients, who were confirmed to have COVID-19 using the severe acute respiratory syndrome coronavirus 2 RNA-PCR tests conducted up to May 15, 2020; we used the linked-medical claims data provided by the Health Insurance Review and Assessment Service. Asthma and asthma severity (steps suggested by the Global Initiative for Asthma) were defined using the diagnostic code and history of asthma medication usage.

Results

Among 7590 COVID-19 patients, 218 (2.9%) had underlying asthma. The total medical cost associated with COVID-19 patients with underlying asthma was significantly higher than that of other patients. Mortality rate for COVID-19 patients with underlying asthma (7.8%) was significantly higher than that of other patients (2.8%; p<0.001). However, asthma was not an independent risk factor for the clinical outcomes of COVID-19 after adjustment, nor did asthma medication use and asthma severity affect the clinical outcomes of COVID-19. However, use of oral short-acting β2-agonists was an independent factor to increase the total medical cost burden. Patients with step 5 asthma showed significant prolonged duration of admission compared to those with step 1 asthma in both univariate and multivariate analysis.

Conclusions

Asthma led to poor outcomes of COVID-19; however, underlying asthma, use of asthma medication and asthma severity were not independent factors for poor clinical outcomes of COVID-19, generally.
Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease
Authors: Yokoyama Tadafumi , Gochuico Bernadette R.
Published: February 2021

Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.
Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol
Authors: Mathioudakis Alexander G. , Abroug Fekri , Agusti Alvar , Bakke Per , Bartziokas Konstantinos , Beghe Bianca , Bikov Andras , Bradbury Thomas , Brusselle Guy , Cadus Cordula , Coleman Courtney , Contoli Marco , Corlateanu Alexandru , Corlateanu Olga , Criner Gerard , Csoma Balazs , Emelyanov Alexander , Faner Rosa , Romero Gustavo Fernandez , Hammouda Zeineb , Horv�th Peter , Huerta Arturo Garcia , Jacobs Michael , Jenkins Christine , Joos Guy , Kharevich Olga , Kostikas Konstantinos , Lapteva Elena , Lazar Zsofia , Leuppi Joerg D. , Liddle Carol , L�pez-Giraldo Alejandra , McDonald Vanessa M. , Nielsen Rune , Papi Alberto , Saraiva Isabel , Sergeeva Galina , Sioutkou Agni , Sivapalan Pradeesh , Stovold Elizabeth , Wang Hao , Wen Fuqiang , Yorke Janelle , Williamson Paula R. , Vestbo J�rgen , Jensen Jens-Ulrik
Published: February 2021

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations.

For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus.

Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.
Study of Thermometry in Two-Dimensional Sb2Te3 from Temperature-Dependent Raman Spectroscopy
Authors: Singh Manavendra P. , Mandal Manab , Sethupathi K. , Rao M. S. Ramachandra , Nayak Pramoda K.
Published: February 2021

Discovery of two-dimensional (2D) topological insulators (TIs) demonstrates tremendous potential in the field of thermoelectric since the last decade. Here, we have synthesized 2D TI, Sb2Te3 of various thicknesses in the range 65–400 nm using mechanical exfoliation and studied temperature coefficient in the range 100–300 K using micro-Raman spectroscopy. The temperature dependence of the peak position and line width of phonon modes have been analyzed to determine the temperature coefficient, which is found to be in the order of 10–2 cm−1/K, and it decreases with a decrease in Sb2Te3 thickness. Such low-temperature coefficient would favor to achieve a high figure of merit (ZT) and pave the way to use this material as an excellent candidate for thermoelectric materials. We have estimated the thermal conductivity of Sb2Te3 flake with the thickness of 115 nm supported on 300-nm SiO2/Si substrate which is found to be ~ 10 W/m–K. The slightly higher thermal conductivity value suggests that the supporting substrate significantly affects the heat dissipation of the Sb2Te3 flake.
Inflexibility of the plasma miRNA response following a high-carbohydrate meal in overweight insulin-resistant women
Authors: Ramzan F. , D’Souza R. F. , Durainayagam B. R. , Milan A. M. , Roy N. C. , Kruger M. C. , Henry C. J. , Mitchell C. J. , Cameron-Smith D.
Published: February 2021

Context

Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs).

Design

The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women.

Participants

Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women.

Methods

An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs).

Results

In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women.

Conclusions

The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs.

Trial registration

The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.
Natriuretic peptides and Forkhead O transcription factors act in a cooperative manner to promote cardiomyocyte cell cycle re-entry in the postnatal mouse heart
Authors: Ali Mir , Liccardo Daniela , Cao Tongtong , Tian Ying
Published: February 2021

Background

Cardiomyocytes proliferate rapidly during fetal life but lose their ability of proliferation soon after birth. However, before terminal withdrawal from the cell cycle, cardiomyocytes undergo another round of cell cycle during early postnatal life in mice. While a transient wave of increased DNA synthesis in cardiomyocyte has been observed in postnatal mouse hearts, the molecular mechanisms describing cardiomyocyte cell cycle re-entry remain poorly understood. Atrial and B-type natriuretic peptides (ANP and BNP) are abundantly expressed in embryonic heart ventricles. After birth, the expression of both genes is strongly reduced in the ventricular myocardium. Forkhead O (FOXO) transcription factors are expressed in both embryonic and postnatal heart ventricles. Their transcriptional activity negatively affects cardiomyocyte proliferation. Upon phosphorylation, FOXO is translocated to the cytoplasm and is transcriptionally inactive. Despite these important findings, it remains largely unknown whether natriuretic peptides and FOXO cooperatively play a role in regulating cardiomyocyte cell cycle activity during early postnatal life.

Results

We observed that the expression of ANP and BNP and the level of phosphorylated FOXO were transiently increased in the postnatal mouse heart ventricles, which coincided with the burst of cardiomyocyte cell cycle re-entry during early postnatal life in mice. Cell culture studies showed that ANP/BNP signaling and FOXO cooperatively promoted cell cycle activity in neonatal mouse cardiomyocytes. The enhanced cell cycle activity observed in combined treatment of ANP/BNP and dominant-negative FOXO (DN-FOXO), which can bind FOXO recognition sites on DNA but cannot activate transcription, was primarily mediated through natriuretic peptide receptor 3 (Npr3). In mice, simultaneous application of ANP and DN-FOXO in postnatal hearts reactivated cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction.

Conclusions

Our data demonstrate the cooperative effects of natriuretic peptide and DN-FOXO on promoting cardiomyocyte cell cycle activity and mouse cardiac repair and regeneration after injury.
The influence of QTL allelic diversity on QTL detection in multi-parent populations: a simulation study in sugar beet
Authors: Garin Vincent , Wimmer Valentin , Borchardt Dietrich , Malosetti Marcos , van Eeuwijk Fred
Published: February 2021

Background

Multi-parent populations (MPPs) are important resources for studying plant genetic architecture and detecting quantitative trait loci (QTLs). In MPPs, the QTL effects can show various levels of allelic diversity, which can be an important factor influencing the detection of QTLs. In MPPs, the allelic effects can be more or less specific. They can depend on an ancestor, a parent or the combination of parents in a cross. In this paper, we evaluated the effect of QTL allelic diversity on the QTL detection power in MPPs.

Results

We simulated: a) cross-specific QTLs; b) parental and ancestral QTLs; and c) bi-allelic QTLs. Inspired by a real application in sugar beet, we tested different MPP designs (diallel, chessboard, factorial, and NAM) derived from five or nine parents to explore the ability to sample genetic diversity and detect QTLs. Using a fixed total population size, the QTL detection power was larger in MPPs with fewer but larger crosses derived from a reduced number of parents. The use of a larger set of parents was useful to detect rare alleles with a large phenotypic effect. The benefit of using a larger set of parents was however conditioned on an increase of the total population size. We also determined empirical confidence intervals for QTL location to compare the resolution of different designs. For QTLs representing 6% of the phenotypic variation, using 1600F2offspring individuals, we found average 95% confidence intervals over different designs of 49 and 25 cM for cross-specific and bi-allelic QTLs, respectively.

Conclusions

MPPs derived from less parents with few but large crosses generally increased the QTL detection power. Using a larger set of parents to cover a wider genetic diversity can be useful to detect QTLs with a reduced minor allele frequency when the QTL effect is large and when the total population size is increased.
Authoritative subspecies diagnosis tool for European honey bees based on ancestry informative SNPs
Authors: Momeni Jamal , Parejo Melanie , Nielsen Rasmus O. , Langa Jorge , Montes Iratxe , Papoutsis Laetitia , Farajzadeh Leila , Bendixen Christian , Căuia Eliza , Charrière Jean-Daniel , Coffey Mary F. , Costa Cecilia , Dall’Olio Raffaele , De la Rúa Pilar , Drazic M. Maja , Filipi Janja , Galea Thomas , Golubovski Miroljub , Gregorc Ales , Grigoryan Karina , Hatjina Fani , Ilyasov Rustem , Ivanova Evgeniya , Janashia Irakli , Kandemir Irfan , Karatasou Aikaterini , Kekecoglu Meral , Kezic Nikola , Matray Enikö Sz. , Mifsud David , Moosbeckhofer Rudolf , Nikolenko Alexei G. , Papachristoforou Alexandros , Petrov Plamen , Pinto M. Alice , Poskryakov Aleksandr V. , Sharipov Aglyam Y. , Siceanu Adrian , Soysal M. Ihsan , Uzunov Aleksandar , Zammit-Mangion Marion , Vingborg Rikke , Bouga Maria , Kryger Per , Meixner Marina D. , Estonba Andone
Published: February 2021

Background

With numerous endemic subspecies representing four of its five evolutionary lineages, Europe holds a large fraction of Apis mellifera genetic diversity. This diversity and the natural distribution range have been altered by anthropogenic factors. The conservation of this natural heritage relies on the availability of accurate tools for subspecies diagnosis. Based on pool-sequence data from 2145 worker bees representing 22 populations sampled across Europe, we employed two highly discriminative approaches (PCA and FST) to select the most informative SNPs for ancestry inference.

Results

Using a supervised machine learning (ML) approach and a set of 3896 genotyped individuals, we could show that the 4094 selected single nucleotide polymorphisms (SNPs) provide an accurate prediction of ancestry inference in European honey bees. The best ML model was Linear Support Vector Classifier (Linear SVC) which correctly assigned most individuals to one of the 14 subspecies or different genetic origins with a mean accuracy of 96.2% ± 0.8 SD. A total of 3.8% of test individuals were misclassified, most probably due to limited differentiation between the subspecies caused by close geographical proximity, or human interference of genetic integrity of reference subspecies, or a combination thereof.

Conclusions

The diagnostic tool presented here will contribute to a sustainable conservation and support breeding activities in order to preserve the genetic heritage of European honey bees.
Triple null mutations in starch synthase SSIIa gene homoeologs lead to high amylose and resistant starch in hexaploid wheat
Authors: Schoen Adam , Joshi Anupama , Tiwari Vijay , Gill Bikram S. , Rawat Nidhi
Published: February 2021

Background

Lack of nutritionally appropriate foods is one of the leading causes of obesity in the US and worldwide. Wheat (Triticum aestivum) provides 20% of the calories consumed daily across the globe. The nutrients in the wheat grain come primarily from the starch composed of amylose and amylopectin. Resistant starch content, which is known to have significant human health benefits, can be increased by modifying starch synthesis pathways. Starch synthase enzyme SSIIa, also known as starch granule protein isoform-1 (SGP-1), is integral to the biosynthesis of the branched and readily digestible glucose polymer amylopectin. The goal of this work was to develop a triple null mutant genotype for SSIIa locus in the elite hard red winter wheat variety ‘Jagger’ and evaluate the effect of the knock-out mutations on resistant starch content in grains with respect to wild type.

Results

Knock-out mutations in SSIIa in the three genomes of wheat variety ‘Jagger’ were identified using TILLING. Subsequently, these loss-of function mutations on A, B, and D genomes were combined by crossing to generate a triple knockout mutant genotype Jag-ssiia-∆ABD. The Jag-ssiia-∆ABD had an amylose content of 35.70% compared to 31.15% in Jagger, leading to ~ 118% increase in resistant starch in the Jag-ssiia-∆ABD genotype of Jagger wheat. The single individual genome mutations also had various effects on starch composition.

Conclusions

Our full null Jag-ssiia-∆ABD mutant showed a significant increase in RS without the shriveled grain phenotype seen in other ssiia knockouts in elite wheat cultivars. Moreover, this study shows the potential for developing nutritionally improved foods in a non-GM approach. Since all the mutants have been developed in an elite wheat cultivar, their adoption in production and supply will be feasible in future.
Clinical characteristics of hospitalized mild/moderate COVID-19 patients with a prolonged negative conversion time of SARS-CoV-2 nucleic acid detection
Authors: Yang Ya , Hu Xiaogang , Xiong Lirong , Fu Peishu , Feng Wei , Li Wei , Zhang Liwen , Sun Fengjun
Published: February 2021

Background

The impact of COVID-19 has been devastating on a global scale. The negative conversion time (NCT) of SARS-CoV-2 RNA is closely related to clinical manifestation and disease progression in COVID-19 patients. Our study aimed to predict factors associated with prolonged NCT of SARS-CoV-2 RNA in mild/moderate COVID-19 patients.

Methods

The clinical features, laboratory data and treatment outcomes of COVID-19 patients were retrospectively analyzed. Then univariate and multivariate analysis were used to screen out risk factors of influencing prolonged NCT of SARS-CoV-2 RNA.

Results

Thirty-two hospitalized mild/moderate COVID-19 patients were enrolled. The general clinical symptoms were cough (78.1%), fever (75%), diarrhea (68.8%), expectoration (56.3%), and nausea (37.5%). More than 40% of the patients had decreased erythrocyte, hemoglobin and leucocyte and 93.8% patients were detected in abnormalities of chest CT. The median NCT of SARS-CoV-2 RNA was 19.5 days (IQR: 14.25–25). Univariate analysis found fever, nausea, diarrhea and abnormalities in chest CTs were positively associated with prolonged NCT of viral RNA (P< 0.05). The multivariate Cox proportional hazard model revealed that fever [Exp (B), 0.284; 95% CI, 0.114–0.707; P<0.05] and nausea [Exp (B), 0.257; 95%CI, 0.096–0.689; P<0.05] were two significant independent factors.

Conclusions

Fever and nausea were two significant independent factors in prolonged NCT of viral RNA in mild/moderate COVID-19 patients, which provided a useful references for disease progression and treatment of COVID-19.
Differentiation of Pseudoprogression from True Progressionin Glioblastoma Patients after Standard Treatment: A Machine Learning Strategy Combinedwith Radiomics Features from T1-weighted Contrast-enhanced Imaging
Authors: Sun Ying-Zhi , Yan Lin-Feng , Han Yu , Nan Hai-Yan , Xiao Gang , Tian Qiang , Pu Wen-Hui , Li Ze-Yang , Wei Xiao-Cheng , Wang Wen , Cui Guang-Bin
Published: February 2021

Background

Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T1-weighted contrast enhanced imaging(T1CE) in differentiating pseudoprogression from true progression after standard treatment for GBM.

Methods

Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T1CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T1CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity.

Results

No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists’ assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively.

Conclusion

T1CE–based radiomics showed better classification performance compared with radiologists’ assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.
Subcortical and brainstem hemiatrophy accompanied by iron deposition in a patient with hemiparkinsonism-hemiatrophy syndrome: a case report
Authors: Chung Su Jin
Published: February 2021

Background

There is no established pathogenesis of hemiparkinsonism-hemiatrophy syndrome (HPHA), and the varied clinical presentations have been reported in several case studies. To the best of our knowledge, the present report describes the first case of HPHA with unusual brain imaging findings.

Case presentation

A 20-year-old man presented with a 6-month history of weakness and clumsiness in his right limbs. He showed right-sided parkinsonism with dystonic hand posture; however, body asymmetry was not noted. Brain imaging revealed hemiatrophy of the left hemisphere subcortical structures and brainstem, and iron deposition in the left globus pallidus and substantia nigra. In addition, dopamine transporter imaging demonstrated normal presynaptic dopaminergic function. The patient was treated with levodopa, which had little to no effect.

Conclusions

This case demonstrates the unique imaging characteristics of HPHA associated with widespread brain hemiatrophy and iron deposition. Further studies are needed to elucidate the diagnostic criteria for this heterogeneous syndrome.
The aquaporin4-IgG status and how it affects the clinical features and treatment response in NMOSD patients in Egypt
Authors: Kishk Nirmeen A. , Abdelfattah Walaa , Shalaby Nevin M. , Shehata Hatem S. , Hassan Amr , Hegazy Mohamed I. , Abokrysha Noha T. , Abdellatif Doaa , Shawky Shereen M. , Abdo Sarah S. , Taha Noha , Fouad Amr M. , Elmazny Alaa , Ragab Amany H.
Published: February 2021

Background

In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking.

Objectives

To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients.

Methods

Retrospective analysis of 70 NMOSD patients’ records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018.

Results

Patients’ mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01).

Conclusion

Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.