bluuebunny/crossref_metadata_2025 huggingface dataset:
Printer source identification by feature modeling in the total variable printer space
Authors: Hamzehyan Roozbeh , Razzazi Farbod , Behrad Alireza
Published: August 2021

Advances in the digital world have attracted the attention of many researchers in terms of developing digital forensics. Using machine learning methods for print source identification is one of the developing areas in the field of digital forensics. In this paper, a new method is presented for printer source identification by modeling the primary Local Binary Pattern (LBP) features in the total variable printer space and extracting the secondary features based on the joint factor analysis. Only one low‐dimensional i‐vector feature is employed for each document image without using any optical character recognition (OCR) algorithm or similar processes. This property eliminates the requirement for the majority voting algorithm and reduces the computational cost of the classification process. Furthermore, the proposed algorithm is not limited to a specific language or character set. The capabilities of the proposed method in extracting useful discriminant information from the sparse print shadow texture are revealed through simulation. The simulation results showed that the proposed algorithm obtained the accuracy of 98.48% by refining the basic features of LBP, which is comparable to the results of the state‐of‐the‐art approaches in this field.
A novel multiplex assay system based on 10 methylation markers for forensic identification of body fluids
Authors: Huang Hongzhi , Liu Xiaozhao , Cheng Juanbo , Xu Linxia , He Ximiao , Xiao Chao , Huang Daixin , Yi Shaohua
Published: August 2021

Identifying the source of body fluids found at a crime scene is an essential forensic step. Some methods based on DNA methylation played significant role in body fluids identification. Since DNA methylation is related to multiple factors, such as race, age, and diseases, it is necessary to know the methylation profile of a given population. In this study, we tested 19 body fluid‐specific methylation markers in a Chinese Han population. A novel multiplex assay system based on the selected markers with smaller variation in methylation and stronger tissue‐specific methylation were developed for the identification of body fluids. The multiplex assay were tested in 265 body fluid samples. A random forest model was established to predict the tissue source based on the methylation data of the 10 markers. The multiplex assay was evaluated by testing the sensitivity, the mixtures, and old samples. For the result, the novel multiplex assay based on 10 selected methylation markers presented good methylation profiles in all tested samples. The random forest model worked extremely well in predicting the source of body fluids, with an accuracy of 100% and 97.5% in training data and test data, respectively. The multiplex assay could accurately predict the tissue source from 0.5 ng genomic DNA, six‐months‐old samples and distinguish the minor component from a mixture of two components. Our results indicated that the methylation multiplex assay and the random forest model could provide a convenient tool for forensic practitioners in body fluid identification.
Association of limited English proficiency and increased pediatric emergency department revisits
Authors: Portillo Elyse N. , Stack Anne M. , Monuteaux Michael C. , Curt Alexa , Perron Catherine , Lee Lois K.
Published: August 2021

Objective

Limited English proficiency (LEP) is a risk factor for health care inequity and an important focus for improving communication and care quality. This study examines the association between LEP and pediatric emergency department (ED) revisits.

Methods

This was a retrospective, cross‐sectional study of patients 0 to 21 years old discharged home after an initial visit from an academic, tertiary care pediatric ED from January 1, 2017, to June 30, 2018. We calculated rates of ED revisits within 72 h resulting in discharge or hospitalization and assessed rate differences between LEP and English‐proficient (EP) patients. Multivariable logistic regression models examined the association between revisits and LEP status controlling for age, race, ethnicity, triage acuity, clinical complexity, and ED arrival time. Sensitivity models including insurance were also conducted.

Results

There were 63,601 index visits in the study period; 12,986 (20%) were by patients with LEP. There were 2,387 (3.8%) revisits within 72 h of initial ED visit. Among LEP and EP patient visits, there were 4.53 and 3.55 revisits/100 initial ED visits, respectively (rate difference = 0.97, 95% confidence interval [CI] = 0.58 to 1.37). In the multivariable analyses, LEP was associated with increased odds of revisits resulting in discharge (odds ratio [OR] = 1.15, 95% CI = 1.01 to 1.30) and in hospitalization (OR = 1.28, 95% CI = 1.03 to 1.58). Sensitivity analyses additionally adjusting for insurance status attenuated these results.

Conclusions

These results suggest that LEP was associated with increased pediatric ED revisits. Improved understanding of language barrier effects on clinical care is important for decreasing health care disparities in the ED.
FGF5 missense mutation is associated with dromedary hair length variation
Authors: Maraqa T. , Alhajeri B. H. , Alhaddad H.
Published: August 2021

Several FGF5 mutations are associated with hair length variation in many domestic animals, including New World camelids. The dromedary was investigated in the present study with breeds exhibiting marked variations in hair length. This study aimed to: (1) identify the molecular variation(s) in the three exons of FGF5 of a diverse group of breeds (Mejaheem, Shaele, Sofor, Waddah and Omani; n = 28); (2) examine the association of the identified variants with hair length; (3) validate the association via genotyping the polymorphism in a large population of diverse camels (n = 113); and (4) test the segregation of the identified variant with hair length in a pedigree. A non‐synonymous mutation (c.779 C > T) was identified that changes the amino acid from proline to leucine and was found to be associated with different hair length in dromedaries. The variants at c.779 displayed a co‐dominance mode of inheritance and three hair length phenotypes: short (C/C), intermediate (C/T) and long (T/T). Across the examined dromedary breeds, both alleles were present, which is probably due to the breeders’ preference for an intermediate hair length. When compared with other camelids, the identified variant was found exclusively in dromedaries with the ancestral allele at c.779 being ‘C’. This study constitutes the first thorough exploration of the FGF5 gene in dromedaries.
Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry
Authors: Runhart Esmee H. , Dhooge Patty , Meester‐Smoor Magda , Pas Jeroen , Pott Jan Willem R. , van Leeuwen Redmer , Kroes Hester Y. , Bergen Arthur A. , de Jong‐Hesse Yvonne , Thiadens Alberta A. , van Schooneveld Mary J. , van Genderen Maria , Boon Camiel , Klaver Caroline , van den Born L. Ingeborg , Cremers Frans P. M. , Hoyng Carel B.
Published: August 2021

Purpose

To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases.

Methods

For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014‐2018) and point prevalence (2018) were assessed on the basis of this registry.

Results

A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67‐1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000‐1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher’s exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age‐at‐onset categories approximated one. Late‐onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014‐2018 compared to 19% in 2004‐2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann–Whitney). Misdiagnosis for age‐related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late‐onset STGD1.

Conclusion

The observed prevalence of STGD1 in real‐world data was lower than expected on the basis of population ABCA4 allele frequencies. Late‐onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis‐ and underdiagnosis of especially late‐onset STGD1 and the role of sex in STGD1 should receive special attention.
Global estimates of the implications of COVID‐19‐related preprimary school closures for children’s instructional access, development, learning, and economic wellbeing
Authors: McCoy Dana C. , Cuartas Jorge , Behrman Jere , Cappa Claudia , Heymann Jody , López Bóo Florencia , Lu Chunling , Raikes Abbie , Richter Linda , Stein Alan , Fink Günther
Published: August 2021

Observational data collected prior to the pandemic (between 2004 and 2019) were used to simulate the potential consequences of early childhood care and education (ECCE) service closures on the estimated 167 million preprimary‐age children in 196 countries who lost ECCE access between March 2020 and February 2021. COVID‐19‐related ECCE disruptions were estimated to result in 19.01 billion person‐days of ECCE instruction lost, 10.75 million additional children falling “off track” in their early development, 14.18 million grades of learning lost by adolescence, and a present discounted value of USD 308.02 billion of earnings lost in adulthood. Further burdens associated with ongoing closures were also forecasted. Projected developmental and learning losses were concentrated in low‐ and lower middle‐income countries, likely exacerbating long‐standing global inequities.
A larger low‐flow‐mediated constrictor response is associated with augmented flow‐mediated dilation in the popliteal artery
Authors: O'Brien Myles W. , Petterson Jennifer L. , Johns Jarrett A. , Mekary Said , Kimmerly Derek S.
Published: August 2021

In the brachial artery, conflicting evidence exists regarding the relationship between the low‐flow–mediated constriction (L‐FMC) and subsequent flow‐mediated dilation (FMD) responses, which may confound interpretation of the latter. The popliteal artery is a common site for atherosclerotic development, which is preceded by endothelial dysfunction. We aimed to determine whether the magnitude of popliteal L‐FMC impacted FMD responses, which is currently unknown. L‐FMC and FMD were assessed in the popliteal artery via high‐resolution duplex ultrasonography and quantified as the percent change in diameter (from baseline) during ischaemia and in response to hyperaemia, respectively. Using partial correlations and multiple regression analyses, we evaluated the association between popliteal L‐FMC on FMD in 110 healthy participants (60 females; 42 ± 22 [19–77] years). All variables univariately associated (p < 0.05) with popliteal relative FMD (relative L‐FMC, log‐SRAUC, age, systolic blood pressure, diastolic blood pressure, resting shear rate) were inputted into a model that explained 35% of the variance. The reactive hyperaemia stimulus (log‐SRAUC: β = 1.10) and relative L‐FMC (β = −0.39) were the only independent predictors of FMD (both, p < 0.01). Relative L‐FMC was negatively correlated to relative FMD, after controlling for the significant univariate predictor variables listed above (R = −0.30; p = 0.002). An augmented (ie healthier) L‐FMC response was linked with a larger FMD response as determined by the independent inverse association observed between these shear‐stress–mediated measures of vasoreactivity.
Novel Bruton’s Tyrosine Kinase inhibitor remibrutinib: Drug‐drug interaction potential as a victim of CYP3A4 inhibitors based on clinical data and PBPK modeling
Authors: Huth Felix , Schiller Hilmar , Jin Yi , Poller Birk , Schuhler Carole , Weis Wendy , Woessner Ralph , Drollmann Anton , End Peter
Published: August 2021

Remibrutinib, a novel oral Bruton’s Tyrosine Kinase inhibitor (BTKi) is highly selective for BTK, potentially mitigating the side effects of other BTKis. Enzyme phenotyping identified CYP3A4 to be the predominant elimination pathway of remibrutinib. The impact of concomitant treatment with CYP3A4 inhibitors, grapefruit juice and ritonavir (RTV), was investigated in this study in combination with an intravenous microtracer approach. Pharmacokinetic (PK) parameters, including the fraction absorbed, the fractions escaping intestinal and hepatic first‐pass metabolism, the absolute bioavailability, systemic clearance, volume of distribution at steady‐state, and the fraction metabolized via CYP3A4 were evaluated. Oral remibrutinib exposure increased in the presence of RTV 4.27‐fold, suggesting that remibrutinib is not a sensitive CYP3A4 substrate. The rich PK dataset supported the building of a robust physiologically‐based pharmacokinetic (PBPK) model, which well‐described the therapeutic dose range of 25–100 mg. Simulations of untested scenarios revealed an absence of drug‐drug interaction (DDI) risk between remibrutinib and the weak CYP3A4 inhibitor fluvoxamine (area under the concentration‐time curve ratio [AUCR] <1.25), and a moderate effect with the CYP3A4 inhibitor erythromycin (AUCR: 2.71). Predictions with the moderate and strong CYP3A4 inducers efavirenz and rifampicin, suggested a distinct remibrutinib exposure decrease of 64% and 89%. Oral bioavailability of remibrutinib was 34%. The inclusion of an intravenous microtracer allowed the determination of all relevant remibrutinib PK parameters, which facilitated construction of the PBPK model. This will provide guidance on the selection or restriction of comedications and prediction of DDI risks.
Evaluation of atezolizumab immunogenicity: Clinical pharmacology (part 1)
Authors: Wu Benjamin , Sternheim Nitzan , Agarwal Priya , Suchomel Julia , Vadhavkar Shweta , Bruno Rene , Ballinger Marcus , Bernaards Coen A. , Chan Phyllis , Ruppel Jane , Jin Jin , Girish Sandhya , Joshi Amita , Quarmby Valerie
Published: August 2021

Baseline patient characteristics and prognostic factors are important considerations in oncology when evaluating the impact of immunogenicity on pharmacokinetics (PK) and efficacy. Here, we assessed the impact of anti‐drug antibodies (ADA) on the PK of the immune checkpoint inhibitor atezolizumab (an anti–PD‐L1 monoclonal antibody). We evaluated data from ≈ 4500 patients from 12 clinical trials across different tumor types, treatment settings, and dosing regimens. In our dataset, ~ 30% of patients (range, 13–54%) developed treatment‐emergent ADA, and in vitro neutralizing antibodies (NAb) were seen in ~ 50% of ADA‐positive (+) patients. Pooled time course data showed a trend toward lower atezolizumab exposure in ADA+ patients, which was more pronounced in ADA+/NAb+ patients. However, the atezolizumab concentration distributions overlapped, and drug concentrations exceeded 6 µg/ml, the target concentration required for receptor saturation, in greater than 95% of patients. Patients had sufficient exposure regardless of ADA status. The dose selected to allow for dosing over effects from ADA resulted in a flat exposure‐response relationship. Analysis of study results by ADA titer showed that exposure and overall survival were not affected in a clinically meaningful way. High tumor burden, low albumin, and high CRP at baseline showed the greatest association with ADA development but not with subsequent NAb development. These imbalanced factors at baseline can confound analysis of ADA impact. ADA increases atezolizumab clearance minimally (9%), and its impact on exposure based on the totality of the clinical pharmacology assessment does not appear to be clinically meaningful.
Effect of sex chromosome number variation on attention‐deficit/hyperactivity disorder symptoms, executive function, and processing speed
Authors: Green Tamar , Flash Shira , Shankar Geeta , Bade Shrestha Sharon , Jo Booil , Klabunde Megan , Hong David S , Reiss Allan L
Published: August 2021

Aim

To study sex differences in attention‐deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed.

Method

We assessed 116 children (ages 3y 10mo–11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY).

Results

X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using non‐parametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in‐laboratory as well as parent‐reported working memory (all r>0.4).

Interpretation

Our observations provide compelling evidence that the absence or excess of an X chromosome distinctly affects cognition and behaviors associated with ADHD.
From insulin injections to islet transplantation: An overview of the journey
Authors: Paget Michelle B. , Murray Hilary E. , Bailey Clifford J. , Downing Richard
Published: August 2021

When, in 1869, Paul Langerhans detected the “islands of tissue” in the pancreas, he took the first step on a journey towards islet transplantation as a treatment for type 1 diabetes. The route has embraced developments across biosciences, surgery, gene therapy and clinical research. This review highlights major milestones along that journey involving whole pancreas transplantation, islet transplantation, the creation of surrogate insulin‐secreting cells and novel islet‐like structures using genetic and bio‐engineering technologies. To obviate the paucity of human tissue, pluripotent stem cells and non‐β‐cells within the pancreas have been modified to create physiologically responsive insulin‐secreting cells. Before implantation, these can be co‐cultured with endothelial cells to promote vascularisation and with immune defence cells such as placental amnion cells to reduce immune rejection. Scaffolds to contain grafts and facilitate surgical placement provide further opportunities to achieve physiological insulin delivery. Alternatively, xenotransplants such as porcine islets might be reconsidered as opportunities exist to circumvent safety concerns and immune rejection. Thus, despite a long and arduous journey, the prospects for increased use of tissue transplantation to provide physiological insulin replacement are drawing ever closer.
Responses of a pair‐living, sexually monogamous primate to the simulated presence of solitary individuals: A field playback experiment
Authors: Garcia de la Chica Alba , Wood David Bechtel , Rotundo Marcelo , Fernandez‐Duque Eduardo
Published: August 2021

Loud calls play an important function in regulating the use of space and structuring social groups and mating systems in a wide range of taxa. In pair‐living territorial animals, where encounters with neighbors and solitary conspecifics are common, these calls are mainly associated with resource defense or mate guarding behaviors. Owl monkeys (Aotus azarae) live in groups of one pair of reproducing adults and 1–4 younger, non‐reproducing individuals. Both sexes disperse when they are around 3 years of age; they become solitary floaters who compete to replace same‐sex adults from other groups. Here, we examined the behavioral responses of Azara's owl monkey pairs toward calls of unpaired and unfamiliar males and females to better understand if the competition between floaters and groups is in relationship to the defense of their territory, their mates, or both. We collected behavioral data from six groups, before, during, and after the playing back of unfamiliar male and female loud calls and of a control stimulus at the center and border of their home ranges. Overall, our results showed that the playback location did not elicit differential responses in the monkeys and that both sexes were more reactive to male than female unfamiliar calls, as evidenced by higher rates of sociosexual and vocal responses, movement toward the playback, and intergroup encounters during and after the experiments. Our study indicates that paired male and female owl monkeys mainly defend their partners toward intruders and emphasizes the need of including the role of sexual competition on both sexes in models about the evolution of pair‐living social organizations and sexual monogamy mating systems.
Takeover duration and negotiation process
Authors: Calcagno Riccardo , de Bodt Eric , Demidova Irina
Published: August 2021

We study the relations between takeover negotiations duration, competition and learning, focusing on the private phase of bidder‐initiated transactions. While the negotiation goes on, both parties learn about true deal synergies. At any moment, rival bidders can show up and compete for the target. Using a discrete‐time finite‐horizon dynamic programming approach, we derive the equilibrium relations between the negotiation duration, the pressure of potential competition and the learning process. Next, we perform a calibration exercise on a large sample of merger negotiations with hand‐collected data from the Securities and Exchange Commission filings. Our results provide evidence of a very competitive M&A (Mergers and acquisitions) market.
TNF‐α blockade may lead to improvement of vascular function in psoriasis patients
Authors: Wegner Joanna , Karbach Susanne , Drosos Ioannis , Schnorbus Boris , Muxel Selina , Schmidt Frank , Wenzel Philip , Waisman Ari , Münzel Thomas , Gori Tommaso , von Stebut Esther
Published: August 2021

Psoriasis is one of the most common chronic inflammatory skin diseases and at the same time a risk factor for cardiovascular disease. Interleukin‐17A (IL‐17A)–mediated inflammation in psoriasis may lead to vascular dysfunction. This study aimed at investigating whether anti‐inflammatory treatment by tumor necrosis factor (TNF)‐α blockade alters vascular function in psoriasis patients. A total of 11 patients with psoriasis who underwent treatment with either adalimumab (n = 8) or etanercept (n = 3), 10 healthy control individuals and 14 patients with coronary artery disease (CAD) were included in this study. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI) score. Endothelial reactivity and resting endothelium‐dependent vascular tone were assessed by ultrasound measurement of flow‐mediated dilation (FMD) and low‐flow–mediated constriction (l‐FMC), respectively. FMD was slightly impaired in psoriasis patients compared to healthy controls. Anti‐TNF‐α treatment did not significantly change FMD levels. Psoriasis patients showed a trend towards increased baseline vascular activity compared to healthy controls. Anti‐TNF‐α treatment significantly improved l‐FMC in psoriasis patients. Noteworthy, both FMD and l‐FMC in psoriasis patients were comparable to those in patients with CAD; however, an important influence of age differences between the groups or co‐existent classical cardiovascular risk factors on FMD and l‐FMC cannot be ruled out by our small study. The results suggest that anti‐inflammatory treatment with TNF‐α blockade improves vascular function in patients with psoriasis, mainly by altering baseline vascular tone. Further studies will be necessary to establish the potentially protective impact of anti‐inflammatory therapy on vascular function in patients with chronic inflammatory diseases.
An investigation on fracture toughness of the heat‐affected zone in the welded joints of 13% Cr‐4% Ni martensitic stainless steels
Authors: Foroozmehr Fayaz , Bocher Philippe
Published: August 2021

Fracture behavior of the welded joints of 13% Cr‐4% Ni stainless steels deposited using multipass flux‐cored arc welding process was examined in both as‐welded and heat‐treated conditions, and JIc tests were performed. A crack starter notch was placed one millimeter far from the fusion line to evaluate the heat‐affected zone (HAZ). Unstable crack propagations toward the weld metal occurred during stable tearing for both as‐welded and heat‐treated HAZ. Only single‐point fracture toughness Ju values could be determined before fracture instability. The fracture toughness of the as‐welded HAZ was about 60% lower than that of the substrate steel but get significantly improved by heat‐treatment, reaching a value even slightly higher than that of the substrate steel. The fracture mode of the stable tearing was transformed from a mix of cleavage and dimpled rupture occurring by micro‐void coalescence mechanism for the as‐welded condition to a totally dimpled rupture in the case of the heat‐treated material.
Late to bed, late to rise—Warmer autumn temperatures delay spring phenology by delaying dormancy
Authors: Beil Ilka , Kreyling Jürgen , Meyer Claudia , Lemcke Nele , Malyshev Andrey V.
Published: August 2021

Spring phenology of temperate forest trees has advanced substantially over the last decades due to climate warming, but this advancement is slowing down despite continuous temperature rise. The decline in spring advancement is often attributed to winter warming, which could reduce chilling and thus delay dormancy release. However, mechanistic evidence of a phenological response to warmer winter temperatures is missing. We aimed to understand the contrasting effects of warming on plants leaf phenology and to disentangle temperature effects during different seasons. With a series of monthly experimental warming by ca. 2.4°C from late summer until spring, we quantified phenological responses of forest tree to warming for each month separately, using seedlings of four common European tree species. To reveal the underlying mechanism, we tracked the development of dormancy depth under ambient conditions as well as directly after each experimental warming. In addition, we quantified the temperature response of leaf senescence. As expected, warmer spring temperatures led to earlier leaf‐out. The advancing effect of warming started already in January and increased towards the time of flushing, reaching 2.5 days/°C. Most interestingly, however, warming in October had the opposite effect and delayed spring phenology by 2.4 days/°C on average; despite six months between the warming and the flushing. The switch between the delaying and advancing effect occurred already in December. We conclude that not warmer winters but rather the shortening of winter, i.e., warming in autumn, is a major reason for the decline in spring phenology.
Enacting a just and sustainable blue economy through transdisciplinary action research
Authors: Heidkamp C. Patrick , Garland Michaela , Krak Louie
Published: August 2021

To enact a just and sustainable blue economy, one must consider all the actors involved in its shaping. This paper argues that a quintuple helix approach to stakeholder engagement – involving government, academia, the business community, and civil society – and an inclusive transdisciplinary action research (TAR) methodology are promising avenues with which to do so. Embracing critical pragmatism as a foundational framework, key ideas from three strands of research are consolidated: (1) the recent work on the geographical dimension of socio‐technical sustainability transitions; (2) the literature on just sustainabilities and just transition; and (3) action research and transdisciplinary approaches to problem solving. This allows for the reimagination of a common future for the blue economy that is developed through a different kind of democratic process driven and informed by co‐learning, and shared experiences. By adopting a transdisciplinary action research approach, actors from different disciplines and spheres of experience can gain a better mutual understanding and find commonality through the open door of collaboration. The theoretical argument presented in this paper is illustrated by a vignette of an ongoing TAR project at Southern Connecticut State University, which outlines the challenges and opportunities inherent to implementing a TAR approach.
Seasonal changes in carbon and nitrogen metabolism of Brachiaria decumbens in a long‐term silvopastoral system
Authors: Lima Marina A. , Lelis Daiana L. , Martins Auxiliadora O. , Paciullo Domingos S. C. , Nunes‐Nesi Adriano , Araújo Wagner L. , Morenz Mirton J. F. , Silva Fabyano F. , Gomide Carlos A. M. , Rodrigues Renato A. R. , Chizzotti Fernanda H. M.
Published: August 2021

Our objective was to quantify the metabolites involved in the carbon and nitrogen metabolism of leaf blades of Brachiaria decumbens grown under conditions of intense shade (69%) in the understory of a silvopastoral system (SPS) and compare them to B. decumbens leaf blades grown in an open pasture (OP) under full sunlight. Two treatments corresponding to the specific production system (SPS and OP) were evaluated over four seasons: Spring 2016, Summer 2017, Autumn 2017, and Winter 2017. In the SPS, we observed an increase in the levels of nitrogen‐related metabolites (chlorophyll, nitrate, amino acids and total soluble proteins) and a reduction in carbon‐related metabolites (total soluble carbohydrates, malate, fumarate, starch and sucrose) relative to those in the OP. This pattern of response was also influenced by the seasons, with higher levels of nitrogen‐related metabolites present during seasons with a greater availability of growth resources. In contrast, most carbon‐related metabolites were lower in the spring and summer and higher in the autumn and winter; only sucrose and starch were higher in the spring and winter. Our results demonstrated that intense light restriction in an SPS affects the productivity, longevity and nutritional value of the forage by reducing the levels of metabolites involved in carbon metabolism and increasing the metabolites involved in nitrogen metabolism.
Developing histories of Indian development
Authors: Menon Nikhil
Published: August 2021

This essay offers a tour of historical scholarship produced in the last two decades on economic development in early independent India. It is a sub‐field that for reasons of archival access and renewed interest is growing, like historical works on independent India more generally. Surveying this landscape, it appears that there are some analytical channels that seem to be exhausting themselves after having long pressed forward, and others that are mining rich seams and new terrain. Broadly speaking, these development histories of the early Indian republic cluster around three themes that spill into one another: interactions between the state and industrial capital, the centrality of food and water, and finally, interconnections with global development.
Study of natural product adverse events in adult HIV‐infected patients in Canada
Authors: Sparks Emma , Zorzela Liliane , Necyk Candace , Hughes Christine , Vohra Sunita
Published: August 2021

Introduction

Many individuals living with HIV use natural health products (NHPs) in an effort to decrease medication side effects and to enhance overall well‐being.

Methods

An active surveillance study of adult patients (≥ 18 years) with HIV was conducted between 2012 and 2014 to detect prescription drug and NHP use and associated adverse events (AEs) in the last month.

Results

Of the 167 participants, 85 (50.9%) took prescription medications only, three (1.8%) took NHPs only, 75 (44.9%) took NHPs and prescription medications concurrently, and four (2.4%) took neither. Patients who used both prescription drugs and NHPs concurrently were more than three times more likely to experience an AE compared with those who used prescription drugs only (OR, P = 0.003, 95% CI: 1.47–6.91).

Conclusions

Increased AEs are reported in patients with HIV who combine NHPs and prescription medications, and no serious AEs were reported. Active surveillance was found to be feasible in this clinical setting.
Electronic consultations (eConsults): a proof of concept trial in Australia
Authors: Russell Anthony W. , Adkins Peter , Hayes Lisa , Prior Erin , McCormack Christine , DiGregorio John
Published: August 2021

Background

Electronic consultations (eConsults) allow general practitioners (GP) to seek the advice of a specialist via secure asynchronous digital communication.

Aims

To report the outcomes of a proof of concept (POC) trial of eConsults for patients with diabetes and endocrine disorders.

Methods

A prospective observational study conducted from November 2020 to May 2021. eConsults were provided by endocrinologists from the Princess Alexandra Hospital, Brisbane. The requests for advice were from GP in Brisbane South. An online questionnaire was completed by the GP and endocrinologist after each eConsult.

Results

Forty eConsults were performed over 7 months. The majority were in relation to type 2 diabetes (30%) or thyroid conditions (30%). All eConsult responses were performed within the target of 72 h with 92.5% responses provided within 24 h. The average time taken for the endocrinologist to perform the eConsult was 14.2 ± 4.4 min. The GP rated the value of eConsults as excellent 97% of the time. The eConsult resulted in a new or additional course of action 68% (19/28) of the time and confirmed a course of action 32% (9/28) of the time. The eConsult avoided the need for referral of the patient for a face‐to‐face specialist review in 55% of the eConsults.

Conclusion

An eConsult service was able to be delivered by endocrinologists from a tertiary hospital to GP in Brisbane South. With an appropriate funding model, the broader implementation and adoption of eConsults has the potential to address specialist waiting lists and facilitate models of integrated care.
Antenatal FibroScan® assessment for metabolic‐associated fatty liver in pregnant women at risk of gestational diabetes from a multiethnic population: a pilot study
Authors: Deng Difei , George Jacob , Pasupathy Dharmintra , Cheung Ngai Wah
Published: August 2021

Background

Metabolic‐associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease with increasingly recognised associations with gestational diabetes (GDM), including within the antenatal period.

Aims

To assess the relationship between MAFLD in pregnancy and development of GDM.

Methods

Fifty pregnant women were enrolled before 24 weeks gestation from a multiethnic obstetrics service in Sydney, Australia. Two FibroScan® assessments were performed, one prior to 24 weeks and one after 30 weeks gestation, to assess hepatic steatosis and stiffness. A control attenuated parameter (CAP) score ≥ 233.5 dB/m signified MAFLD. GDM was determined by an antenatal 75‐g oral glucose tolerance testing.

Results

Six (12%) women had evidence of FibroScan®‐detected MAFLD in early pregnancy, while none had abnormal hepatic stiffness. Sixteen (32%) women developed GDM. No significant difference was observed in GDM rates (50% vs 29.5%; P = 0.37) between those with MAFLD in early pregnancy and those without. At the second scan (completed by 34 women), those who developed GDM had a lower observed mean increase in CAP scores (11.1 ± 23.3 dB/m vs −14.9 ± 26.0 dB/m; P = 0.004) and lower maternal weight gain (0.6 ± 0.2 kg/week vs 0.4 ± 0.2 kg/week; P = 0.04).

Conclusions

There was no statistically significant association between FibroScan®‐detected MAFLD in early pregnancy and subsequent development of GDM in this pilot study. Maternal weight gain may be associated with changes in the CAP scores, which reflect steatosis, during pregnancy.
Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3+/CD141+) dendritic cells
Authors: Basit Farhan , van Oorschot Tom , van Buggenum Jessie , Derks Rico J. E. , Kostidis Sarantos , Giera Martin , de Vries I. Jolanda. M.
Published: August 2021

Dendritic cells (DCs) bridge the connection between innate and adaptive immunity. DCs present antigens to T cells and stimulate potent cytotoxic T‐cell responses. Metabolic reprogramming is critical for DC development and activation; however, metabolic adaptations and regulation in DC subsets remains largely uncharacterized. Here, we mapped metabolomic and lipidomic signatures associated with the activation phenotype of human conventional DC type 1, a DC subset specialized in cross‐presentation and therefore of major importance for the stimulation of CD8+ T cells. Our metabolomics and lipidomic analyses showed that Toll‐like receptor (TLR) stimulation altered glycerolipids and amino acids in cDC1. Poly I:C or pRNA stimulation reduced triglycerides and cholesterol esters, as well as various amino acids. Moreover, TLR stimulation reduced expression of glycolysis‐regulating genes and did not induce glycolysis. Conversely, cDC1 exhibited increased mitochondrial content and oxidative phosphorylation (OXPHOS) upon TLR3 or TLR7/8 stimulation. Our findings highlight the metabolic adaptations required for cDC1 maturation.
Incidence and seasonality of respiratory viruses among medically attended children with acute respiratory infections in an Ecuador birth cohort, 2011–2014
Authors: Azziz‐Baumgartner Eduardo , Bruno Alfredo , Daugherty Michael , Chico Martha E. , Lopez Andrea , Arriola Carmen Sofia , de Mora Domenica , Ropero Alba María , Davis William W. , McMorrow Meredith , Cooper Philip J.
Published: August 2021

Background

Ecuador annually has handwashing and respiratory hygiene campaigns and seasonal influenza vaccination to prevent respiratory virus illnesses but has yet to quantify disease burden and determine epidemic timing.

Methods

To identify respiratory virus burden and assess months with epidemic activity, we followed a birth cohort in northwest Ecuador during 2011–2014. Mothers brought children to the study clinic for routine checkups at ages 1, 2, 3, 5, and 8 years or if children experienced any acute respiratory illness symptoms (e.g., cough, fever, or difficulty breathing); clinical care was provided free of charge. Those with medically attended acute respiratory infections (MAARIs) were tested for common respiratory viruses via real‐time reverse‐transcription polymerase chain reaction (rRT‐PCR).

Results

In 2011, 2376 children aged 1–4 years (median 35 months) were enrolled in the respiratory cohort and monitored for 7017.5 child‐years (cy). The incidence of respiratory syncytial virus (RSV) was 23.9 (95% CI 17.3–30.5), influenza 10.6 (2.4–18.8), adenoviruses 6.7 (4.6–28.0), parainfluenzas 5.0 (2.3–10.5), and rhinoviruses, bocaviruses, human metapneumoviruses, seasonal coronaviruses, and enteroviruses <3/100 cy among children aged 12–23 months and declined with age. Most (75%) influenza detections occurred April–September.

Conclusion

Cohort children frequently had MAARIs, and while the incidence decreased rapidly among older children, more than one in five children aged 12–23 months tested positive for RSV, and one in 10 tested positive for influenza. Our findings suggest this substantial burden of influenza occurred more commonly during the winter Southern Hemisphere influenza season.
Position statement on classification of basal cell carcinomas. Part 1: unsupervised clustering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition
Authors: Grob J.J. , Guminski A. , Malvehy J. , Basset‐seguin N. , Bertrand B. , Fernandez‐Penas P. , Kaufmann R. , Zalaudek I. , Gaudy‐Marqueste C. , Fargnoli M.C. , Tagliaferri L. , Fertil B. , Del Marmol V. , Stratigos A. , Garbe C. , Peris K.
Published: August 2021

Background

No simple classification system has emerged for ‘advanced basal cell carcinomas’, and more generally for all difficult‐to‐treat BCCs (DTT‐BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists.

Objective

To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions.

Method

Non‐supervised independent and blinded clustering of real clinical cases of DTT‐BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered ‘difficult to treat’ into as many clusters they want (≤10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K‐mean approach, and average silhouette method.

Results

There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT‐BCCs into five clusters, easily recognizeda posteriorias five clear‐cut patterns of clinical situations. The concept of ‘locally advanced’ did not appear consistent between experts.

Conclusion

Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT‐BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology.
Immersion immunization of common carp with bacterial ghost‐based DNA vaccine inducing prophylactic protective immunity against spring viraemia of carp virus
Authors: Zheng Yu‐Ying , Zhang Chen , Li Yang , Zhang Peng‐Qi , Chen Guo , Wang Gao‐Xue , Zhu Bin
Published: August 2021

The interactive applications of immunization route, vaccine type and delivery vectors are emerging as a key area of research within the field of mass immunization in fishery production. In an effort to improve DNA vaccine's immune efficiency in large‐scale immunization, a promising bacterial ghost‐loaded DNA vaccine was constructed based on Escherichia coli DH5α. In common carp was investigated the immune response to immersion immunization via related indicator analysis, and the challenge test of spring viraemia of carp virus (SVCV) was carried out. The result indicated that BG‐loaded DNA vaccine induced higher serum antibody level than naked pEG‐G. Simultaneously, the immunophysiological indicators and genes change at the more advanced levels in the BG/pEG‐G immune group. At the treatment concentration of 20 mg/L of the BG/pEG‐G group, IgM and IgZ expressions in vivo were markedly increased by 21.62 times and 6.91 times, respectively, and the relative percentage survival reached the peak of 59.57%. This study paves the way for future aquatic animal vaccine research, which aimed to develop the highly effective immersion vaccine system by delivery vectors, with the ultimate aim to prevent and restrict SVCV in actual production.
Diagnostic performance of endoscopic ultrasound‐artificial intelligence using deep learning analysis of gallbladder polypoid lesions
Authors: Jang Sung Ill , Kim Young Jae , Kim Eui Joo , Kang Huapyong , Shon Seung Jin , Seol Yu Jin , Lee Dong Ki , Kim Kwang Gi , Cho Jae Hee
Published: August 2021

Background and Aim

Endoscopic ultrasound (EUS) is the most accurate diagnostic modality for polypoid lesions of the gallbladder (GB), but is limited by subjective interpretation. Deep learning‐based artificial intelligence (AI) algorithms are under development. We evaluated the diagnostic performance of AI in differentiating polypoid lesions using EUS images.

Methods

The diagnostic performance of the EUS‐AI system with ResNet50 architecture was evaluated via three processes: training, internal validation, and testing using an AI development cohort of 1039 EUS images (836 GB polyps and 203 gallstones). The diagnostic performance was verified using an external validation cohort of 83 patients and compared with the performance of EUS endoscopists.

Results

In the AI development cohort, we developed an EUS‐AI algorithm and evaluated the diagnostic performance of the EUS‐AI including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. For the differential diagnosis of neoplastic and non‐neoplastic GB polyps, these values for EUS‐AI were 57.9%, 96.5%, 77.8%, 91.6%, and 89.8%, respectively. In the external validation cohort, we compared diagnostic performances between EUS‐AI and endoscopists. For the differential diagnosis of neoplastic and non‐neoplastic GB polyps, the sensitivity and specificity were 33.3% and 96.1% for EUS‐AI; they were 74.2% and 44.9%, respectively, for the endoscopists. Besides, the accuracy of the EUS‐AI was between the accuracies of mid‐level (66.7%) and expert EUS endoscopists (77.5%).

Conclusions

This newly developed EUS‐AI system showed favorable performance for the diagnosis of neoplastic GB polyps, with a performance comparable to that of EUS endoscopists.
A generalized framework for analyzing car lifetime effects on stock, flow, and carbon footprint
Authors: Nakamoto Yuya , Kagawa Shigemi
Published: August 2021

This study proposes a new framework for estimating the effects of changes in the physical lifespan (PHL) of cars and the possession lifespan (POL) of new and used cars on stock, flow, and carbon footprint (CF). Applying this framework to all new and used cars registered in Japan from 1990 to 2016 showed that a 10% extension of the PHL of cars reduced the CF of cars by 30.7 Mt, while a 10% extension of the POL of new cars reduced the CF of cars by 26.4 Mt, and a 10% extension of the POL of used cars produced a 5.2 Mt CF reduction. On the other hand, a 10% lifetime reduction in the three cases increased CF by 42.2, 29.4, and 6.0 Mt, respectively. These results indicate that increasing the lifetime of new and used cars could contribute significantly to the mitigation of global warming. To achieve a large reduction in life cycle emissions, car designers should focus on ways to extend vehicle lifetimes.