bluuebunny/crossref_metadata_2025 huggingface dataset:
NOVA: Rendering Virtual Worlds with Humans for Computer Vision Tasks
Authors: Kerim Abdulrahman , Aslan Cem , Celikcan Ufuk , Erdem Erkut , Erdem Aykut
Published: May 2021

Today, the cutting edge of computer vision research greatly depends on the availability of large datasets, which are critical for effectively training and testing new methods. Manually annotating visual data, however, is not only a labor‐intensive process but also prone to errors. In this study, we present NOVA, a versatile framework to create realistic‐looking 3D rendered worlds containing procedurally generated humans with rich pixel‐level ground truth annotations. NOVA can simulate various environmental factors such as weather conditions or different times of day, and bring an exceptionally diverse set of humans to life, each having a distinct body shape, gender and age. To demonstrate NOVA's capabilities, we generate two synthetic datasets for person tracking. The first one includes 108 sequences, each with different levels of difficulty like tracking in crowded scenes or at nighttime and aims for testing the limits of current state‐of‐the‐art trackers. A second dataset of 97 sequences with normal weather conditions is used to show how our synthetic sequences can be utilized to train and boost the performance of deep‐learning based trackers. Our results indicate that the synthetic data generated by NOVA represents a good proxy of the real‐world and can be exploited for computer vision tasks.
Plastid phylogenomics provides novel insights into the infrafamilial relationship of Polypodiaceae
Authors: Wei Ran , Yang Jie , He Li‐Juan , Liu Hong‐Mei , Hu Jia‐Yu , Liang Si‐Qi , Wei Xue‐Ping , Zhao Cun‐Feng , Zhang Xian‐Chun
Published: May 2021

The polygrammoids (Polypodiaceae) are the most species‐rich and diversified epiphytic fern lineages, and hold an important role to understand the deep diverging events and rapid adaptation to changing environments in the plant tree of life. Despite progress in the phylogeny of this group of ferns in previous multilocus phylogenetic studies, uncertainty remains especially in backbone relationships among closely related clades, and the phylogenetic placement of recalcitrant species or lineages. Here, we investigated the deep phylogenetic relationships within Polypodiaceae by sampling all major lineages and using 81 plastid genomes (plastomes), of which 70 plastomes were newly sequenced with high‐throughput sequencing technology. Based on parsimony, maximum‐likelihood, Bayesian and multispecies coalescent analyses of genome skimming data, we achieved a better resolution of the backbone phylogeny of Polypodiaceae. Using simulated data matrices, we detected that potential phylogenetic artefacts, such as long‐branch attraction and insufficient taxonomic sampling, may have a confounding impact on the incongruence of phylogenetic inferences. Furthermore, our phylogenetic analyses offer greater resolution than previous multilocus studies, providing a robust framework for future phylogenetic implications on the subfamilial taxonomy of Polypodiaceae. Our phylogenomic study not only demonstrates the advantage of a character‐rich plastome dataset for resolving the recalcitrant lineages that have undergone rapid radiation, but also sheds new light on integrative explorations understanding the evolutionary history of large fern groups in the genomic era.
Treatment with alitretinoin in patients taking part in a tertiary individual prevention program for work‐related skin diseases
Authors: Obermeyer Lara , Skudlik Christoph , John Swen M. , Brans Richard
Published: May 2021

Background

Patients taking part in a tertiary individual prevention program (TIP) for work‐related skin diseases frequently have chronic hand eczema (HE) for which alitretinoin is a treatment option.

Objective

To investigate treatment with alitretinoin before and during the TIP and related factors.

Methods

Data of 1614 patients taking part in the TIP between January 2015 and December 2019 were analyzed retrospectively.

Results

Three hundred forty‐eight patients (21.6%) reported treatment with alitretinoin prior to the TIP showing an increase over time, particularly in men. In 45 patients (2.8%), alitretinoin treatment was initiated during the TIP. Treatment with alitretinoin was significantly less common among female than male patients, both prior to (P < .001) and during the TIP (P = .015). Female patients who had received alitretinoin in the past were significantly older than the other female patients (P < .001). Among patients treated with alitretinoin prior to the TIP, women had a significantly higher disease severity at admission than men (P = .007).

Conclusions

About twenty percent of patients reported treatment with alitretinoin prior to the TIP. The data indicate that treatment of female TIP patients with alitretinoin is less frequent than among male patients and depends on age and disease severity.
Rhabdomyomatous mesenchymal hamartoma presenting as telangiectasia in a 57‐year‐old man
Authors: Zargari Omid , Asadi Masih , Azimi Seyyede Zeinab , Mesbah Alireza
Published: May 2021

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation of the dermis and subcutaneous tissue. Usually, RMH occurs in the midline of the face and neck region. We described a case of RMH presenting as telangiectasia in a 57‐year‐old man with a history of pityriasis lichenoides chronicus. Histopathological examination revealed a subepidermal haphazard proliferation of striated muscular tissue perpendicular to the epidermis. These bundles of striated muscular tissue were admixed with adnexal structures. The diagnosis was consistent with RMH. RMH is more common in the neonatal period or in young children, but we should consider it as part of a differential diagnosis in older adults as well.
Dermatophyte infections in children compared to adults in Germany: a retrospective multicenter study in Germany
Authors: Kromer Christian , Celis Daniel , Hipler Uta‐Christina , Zampeli Vasiliki A. , Mößner Rotraut , Lippert Undine
Published: May 2021

Background and objective

Dermatophyte infections of the skin and nails are common worldwide and vary between geographical areas and over time. The aim of this study was to determine the epidemiological profile of dermatophytes in Germany with a focus on comparing children with adults.

Patients and methods

In this retrospective multicenter study, mycological dermatophyte culture results in the period 01/2014 to 12/2016 were analyzed according to identified pathogen, age and gender of patients, and type of disease.

Results

Of 1,136 infections (children: n = 88, adults: n = 1,048), 50.8 % were clinically classified as onychomycosis, followed by tinea pedis (34.6 %), tinea corporis (16.2 %), tinea manus (16.2 %), tinea capitis (2.5 %), and tinea faciei (1.2 %). The most frequent pathogen was Trichophyton (T.) rubrum (78.6 %), followed by T. interdigitale (14.3 %), T. benhamiae (3.2 %), T. mentagrophytes (2.1 %), and Microsporum canis (1.7 %). The fungal spectrum differed particularly in tinea corporis and tinea capitis between children and adults with a more diverse pathogen spectrum in children. Trichophyton tonsurans was rarely identified as cause for tinea corporis (2.7 %) or tinea capitis (3.3 %).

Conclusions

Differences in pathogens and frequency of fungal infections between age groups should be considered for optimal selection of the appropriate therapeutic regimen.
Neurodevelopmental outcomes in offspring of mothers with hypertensive disorders of pregnancy
Authors: Dachew Berihun Assefa , Alati Rosa
Published: May 2021

This commentary is on the original article by Chen et al. on pages 1107–1113 of this issue.
Development of Healthy Eating and Active Lifestyles for Diabetes, a culturally tailored diabetes self‐management education and support programme for Black‐British adults: A participatory research approach
Authors: Goff Louise M. , Moore Amanda P. , Harding Seeromanie , Rivas Carol
Published: May 2021

Aims

To develop an evidence‐based, culturally tailored, diabetes self‐management education and support programme for Black‐British adults, called Healthy Eating and Active Lifestyles for Diabetes (HEAL‐D), using participatory methods to engage key stakeholders in the intervention design process.

Methods

Black‐British adults living with type 2 diabetes, healthcare professionals and community leaders were engaged in an intervention development study. The intervention structure, format, content and delivery were developed through three phases of participatory research: Phase 1, formative research, involved focus groups and interviews; interactive co‐development workshops were conducted in Phase 2; and Phase 3 focused on materials development.

Results

In Phase 1, focus groups and interviews identified the importance of nurturing collectivism, a reliance on informal sources of information/advice, barriers to attending appointments associated with competing priorities of work, travel and carer commitments, and a preference for directness and simple, clear advice/messages. A priority for healthcare professionals was the intervention embedding within current primary care structures and aligning with incentivised targets/metrics. Phase 2 (workshops) highlighted key requirements: avoidance of medical settings, appropriately trained and culturally knowledgeable educators, flexible appointments, preference for verbal and visual information and avoidance of technical/medical terminology. In Phase 3 (materials development), culturally sensitive videos, short films and information booklets were developed to convey educational messages, and food photography was used to provide culturally relevant dietary advice.

Conclusions

Participatory methods provide a means to understand the needs of specific communities. This approach enables the development of healthcare interventions that are sensitive to the needs of service users and providers.
Fluid and electrolyte therapy in childhood diabetic ketoacidosis management: A rationale for new national guideline
Authors: Agwu Juliana Chizo , Ng Sze M.
Published: May 2021

Fluid and electrolyte therapy in childhood diabetic ketoacidosis (DKA) management has been controversial. Previous National Institute for Health and Care Excellence (NICE) 2015 guidance advocated a restricted fluid regimen while more recent guidelines have advocated a more liberal approach to fluid replacement in DKA. At the core of the debate is the need to avoid developing cerebral oedema as a complication. Although subtle asymptomatic cerebral oedema is common in children presenting in DKA, clinically apparent cerebral oedema is rare and has been reported in approximately 0.5%–1% of DKA cases in children. Recent research evidence has shown that there was no clear evidence of a difference in rates of clinically apparent cerebral injury in children in DKA managed with a range of fluid volumes and rates of rehydration. In view of this, NICE has updated its guideline. In this paper, we review literature evidence underpinning the current understanding of the pathophysiology of cerebral oedema in children and discuss the rationale for the new NICE guidance.
Temporal variations in maternal treatment requirements and early neonatal outcomes in patients with gestational diabetes
Authors: Fox Rachel A. , Patient Charlotte J. , Aiken Abigail R. , Meek Claire L. , Aiken Catherine E.
Published: May 2021

Aims

There is seasonal variation in the incidence of gestational diabetes (GDM) and delivery outcomes of affected patients. We assessed whether there was also evidence of temporal variation in maternal treatment requirements and early neonatal outcomes.

Methods

We performed a retrospective analysis of women diagnosed with GDM (75 g oral glucose tolerance test, 0 h ≥ 5.1; 1 h ≥ 10.0; 2 h ≥ 8.5 mmol/L) in a UK tertiary obstetric centre (2015–2019) with a singleton infant. Data regarding demographic characteristics, total insulin requirements and neonatal outcomes were extracted from contemporaneous electronic medical records. Linear/logistic regression models using month of the year as a predictor of outcomes were used to assess annual variation.

Results

In all, 791 women (50.6% receiving pharmacological treatment) and 790 neonates were included. The likelihood of requiring insulin treatment was highest in November (p < 0.05). The average total daily insulin dose was higher at peak (January) compared to average by 19 units/day (p < 0.05). There was no temporal variation in neonatal intensive care admission, or neonatal capillary blood glucose. However, rates of neonatal hypoglycaemia (defined as <2.6 mmol/L) were highest in December (40% above average; p < 0.05).

Conclusions

Women with GDM diagnosed in winter are more likely to require insulin treatment and to require higher insulin doses. Neonates born to winter‐diagnosed mothers had a corresponding increased risk of neonatal hypoglycaemia. Maternal treatment requirements and neonatal outcomes of GDM vary significantly throughout the year, even in a relatively temperate climate.
Outcomes of a novel pharmacy screening intervention to address the burden of type 2 diabetes and cardiovascular disease in an Arabic‐speaking country
Authors: Alzubaidi Hamzah , Hasan Sanah , Saidawi Ward , Mc Namara Kevin , Chandir Subhash , Krass Ines
Published: May 2021

Aims

Aim of this study is to evaluate the capacity of a pharmacist‐delivered screening model for type 2 diabetes and cardiovascular disease (CVD) in identifying and referring individuals at risk.

Method

A screening programme was implemented in 12 community pharmacies in three cities in the United Arab Emirates. Trained pharmacists screened adults (≥40 years) without a previous diagnosis of diabetes or CVD. Most participants were recruited during their visits to the pharmacies; pharmacy‐based advertising and social media were also used. The screening included medical history, anthropometric measurements, point‐of‐care glycated haemoglobin (HbA1c) levels, and a lipid panel. High‐risk individuals (HbA1c ≥ 5.7% [39 mmol/mol], a high diabetes risk score, or a 10‐year CVD risk ≥7.5%) were given a referral letter and advised to visit their physician. Risk factors for elevated HbA1c were identified by logistic regression.

Results

Of the 568 screened participants, 332/568 (58%) were identified to be at risk: HbA1c levels were consistent with diabetes 67/560 (12%) or prediabetes 148/560 (26%), high diabetes risk score 243/566 (43%), CVD risk score > 7.5% 79/541 (15%). Obese people were more likely to have prediabetes or diabetes OR (95% CI): 3.2 (1.3, 7.5), as were those who spent more than 11 h/day sitting: 5.7 (1.8, 17.6). Of the 332 at‐risk participants, 206 (62%) responded to a telephone follow‐up at six weeks; one‐third had discussed screening results with their physician.

Conclusions

Community pharmacists detected and referred individuals at risk for diabetes or CVD, although participant follow‐up with their physician could be improved. Pharmacy screening is feasible and will potentially improve outcomes.
Insights into functional mitral regurgitation using transillumination rendering
Authors: Ramirez Roberto H. , Ro Richard , Lerakis Stamatios , Argulian Edgar
Published: May 2021

Secondary mitral regurgitation has been originally explained by tethering of the structurally normal mitral leaflets or by mitral annular dilation after atrial remodeling. Advances in echocardiography have provided more insights into functional anatomy of the mitral valve leaflets as active participants in this entity.
Persistence of abnormal global longitudinal strain in women with peripartum cardiomyopathy
Authors: Bortnick Anna E. , Lama von Buchwald Claudia , Hasani Aliaskar , Liu Christina , Berkowitz Julia L. , Vega Shayna , Mustehsan Mohammad Hashim , Wolfe Diana S. , Taub Cynthia
Published: May 2021

Objectives

Data regarding the longitudinal relationship of global longitudinal strain (GLS) and echocardiographic parameters are lacking in peripartum cardiomyopathy (PPCM). We evaluated GLS and its correlation with change (∆) in left ventricular ejection fraction (LVEF).

Methods

We retrospectively identified women age ≥16 years hospitalized at Montefiore Medical Center in Bronx, NY from 1999‐2015 with International Statistical Classification of Diseases and Related Health Problems, 9th revision codes for PPCM or an occurrence of unexplained heart failure during or up to 5 months postpartum. N = 195 charts were reviewed for inclusion/exclusion criteria, n = 53 patients met criteria for PPCM, and of those, n = 13 had a baseline and follow‐up echocardiogram suitable for GLS analysis.

Results

Of those eligible for strain analysis, the mean age was 30 ± 6 years, 46.2% identified as Black and 38.5% as Hispanic/Latina. Baseline LVEF was 30 (25, 35)%, GLS was −13.2 (−14, −7.6)%. At a mean follow‐up time of 1.2 ± 0.7 years, 11/13 had persistently mild −15.6 (−16.3, −12.7)%, and 2/13 severely abnormal GLS −7.05 (−7.1, −7.0)%. There was no correlation between baseline GLS and ∆LVEF (r = .014, P = .965).

Conclusions

Global longitudinal strain is a sensitive method to identify subclinical myocardial dysfunction. In this series of women with PPCM, GLS remained persistently abnormal over time, even if LVEF improved. Future studies should examine the implication of persistently abnormal GLS in PPCM.
Urinary biopyrrins and free immunoglobin light chains are biomarker candidates for screening at‐risk mental state in adolescents
Authors: Wake Rei , Araki Tomoko , Fukushima Michiyo , Matsuda Hiroyuki , Inagaki Takuji , Hayashida Maiko , Hashioka Sadayuki , Horiguchi Jun , Inagaki Masatoshi , Miyaoka Tsuyoshi , Oh‐Nishi Arata
Published: May 2021

Background

Early diagnosis of individuals' at‐risk mental state (ARMS) is important for preventing their pathogenesis or, at least, delaying onset of overt psychosis. Traditional diagnosis of ARMS subjects is mainly based on structured interviews, but future diagnosis would be carried out together with biomarkers.

Aim

In this study, we report urinary biopyrrins and free immunoglobin light chains κ and λ (κFLC and λFLC) as novel diagnostic biomarker candidates for screening ARMS subjects.

Methods

Nineteen ARMS subjects and 21 age‐ and sex‐matched healthy controls were enrolled in this study. Inclusion criteria of the ARMS subjects were based on a comprehensive assessment of Structured Interview for Prodromal Syndromes. We compared oxidative stress and immunological markers in the urine of ARMS subjects with those of healthy controls by ELISA protocol.

Results

Augmentation of biopyrrins and reduction of κFLC and λFLC were found in the ARMS samples, and their diagnostic performance was evaluated by receiver operating characteristic analysis, of which area under the curve was as large as 0.915 in combination.

Conclusion

Our findings suggest that the ARMS subjects were under higher oxidative stress but lower in B cell activation, and that the combined assay of urinary biopyrrins and free immunoglobulin light chains would be useful for the early detection and screening of ARMS subjects among adolescents.
Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma
Authors: Jonsdottir Gudbjorg , Björkholm Magnus , Turesson Ingemar , Hultcrantz Malin , Diamond Benjamin , Porwit Anna , Landgren Ola , Kristinsson Sigurdur Y.
Published: May 2021

Objectives

The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Methods

We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis.

Results

The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7‐5.2; P < .001) among cases (median 988 mg; IQR 644‐1640) compared with controls (median 578 mg; IQR 360‐967). Median time to AML/MDS development was 3.8 years (IQR 2.8‐5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy.

Conclusion

In this nationwide population‐based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long‐term risks.
Determining the types of descending waves from transcranial magnetic stimulation measured with conditioned H‐reflexes in humans
Authors: Leukel Christian , Kurz Alexander
Published: May 2021

Non‐invasive techniques are scarce with which human (motor) cortical mechanisms can be investigated. In a series of previous experiments, we have applied an advanced form of conditioning technique with transcranial magnetic stimulation (TMS) and peripheral nerve stimulation by which excitability changes at the laminar level in the primary motor cortex can be estimated. This method builds on the assumption that the first of subsequent corticospinal waves from TMS which is assessed with H‐reflexes (called early facilitation) results from indirect excitation of corticospinal neurons in motor cortex (I‐wave) and not direct excitation of corticospinal axons (D‐wave). So far, we have not provided strong experimental evidence that this is actually the case. In the present study, we therefore compared temporal differences of the early facilitation between transcranial magnetic and electrical stimulation (TES). TES is known to excite the axons of corticospinal neurons. TES in our study caused a temporal shift of the early facilitation of H‐reflexes in all subjects compared to TMS, which indicates that the early facilitation with TMS is indeed produced by an I‐wave. Additionally, we investigated temporal shifts of the early facilitation with different TMS intensities and two TMS coils. It has long been known that TMS with higher intensities can induce a D‐wave. Accordingly, we found that TMS with an intensity of 150% of resting motor threshold compared to 130%/110% results in a temporal shift of the early facilitation, indicating the presence of a D‐wave. This effect was dependent on the coil type.
Effects of size selection versus density dependence on life histories: A first experimental probe
Authors: Lyberger Kelsey , Schoener Thomas W. , Schreiber Sebastian J.
Published: May 2021

When prey experience size‐based harvesting by predators, they are not only subject to selection due to larger individuals being preferentially harvested but also selection due to reductions in population density. Density‐dependent selection represents one of the most basic interactions between ecology and evolution. Yet, the reduction in density associated with exploitation has not been tested as a possible driving force of observed evolutionary changes in populations harvested size‐dependently. Using an artificial selection experiment with a mixture of Daphnia clones, we partition the evolutionary effects of size‐based harvesting into the effects of removing large individuals and the effects of lowering the population density. We show that both size selection and density‐dependent selection are significant drivers of life‐history evolution. Importantly, these drivers affected different life‐history traits with size‐selective harvesting selecting for slower juvenile growth rates and a larger size at maturity, and low‐density selecting for reduced reproductive output.
Current views on neuropeptides in atopic dermatitis
Authors: Zhang Yue , Zhang Hanyi , Jiang Boyue , Tong Xiaoliang , Yan Siyu , Lu Jianyun
Published: May 2021

Atopic dermatitis (AD) is a chronic inflammatory skin disease involving skin barrier dysfunction and immune imbalance. However, the mechanism of AD is not clear completely and may be related to heredity and environment. Neuropeptides are a class of peptides secreted by nerve endings, they may play roles in promoting vasodilation, plasma extravasation, chemotaxis of inflammatory cells and mediating pruritus. Since itching and immune cell infiltration are the main manifestations of atopic dermatitis, to further investigate the impact of neuropeptides on AD, our review summarized the mechanisms of several common neuropeptides in AD and hypothesized that neuropeptides may be the novel potential targets in AD treatment.
Effects of 27 CYP3A4 protein variants on saxagliptin metabolism in vitro
Authors: liu Qian , Ou‐Yang Qiu‐Geng , Lin Qian‐Meng , Lu Xiang‐Ran , Ma Ya‐Qing , Li Ying‐Hui , Xu Ren‐Ai , Lin Dong‐dong , Hu Guo‐Xin , Cai Jian‐Ping
Published: May 2021

Saxagliptin is a dipeptidyl peptidase 4 (DPP‐4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) can metabolize about 30%–40% of therapeutic drugs. Individual differences caused by CYP3A4 genetic polymorphisms can lead to treatment failure, unpredictable side effects, or severe drug toxicity. The aim of this study was to evaluate the catalytic activities of 27 CYP3A4 variants on saxagliptin metabolism in vitro, which were identified in human CYP alleles. We successfully constructed 27 kinds of wild‐type and variant vectors of pFast‐dual‐OR‐3A4 by overlap extension PCR and prepared 27 kinds of CYP3A4 highly expressed cell microsomes by baculovirus insect cell expression system. The ultra‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) was used to detect the concentrations of the metabolite of saxagliptin (5‐hydroxysaxagliptin) and the internal standard. Compared with the wild‐type CYP3A4.1, the intrinsic clearance values of most varieties decreased to 1.91%–77.08%. Most of these varieties showed a decrease in Vmax and an increase in Km values compared with wild type. We are the first to report the vitro metabolic data of 27 CYP3A4 variants of the metabolism of saxagliptin which can deepen our understanding of individualized drug use by combining previous studies about the effects of CYP3A4 variants of drug metabolism. With further in vivo studies, we hope it can guide individualized drug use in the clinic when the variants with low metabolic activity to saxagliptin were sequenced in the human body.
Membrane protein biogenesis at the ER: the highways and byways
Authors: O'Keefe Sarah , Pool Martin R. , High Stephen
Published: May 2021

The Sec61 complex is the major protein translocation channel of the endoplasmic reticulum (ER), where it plays a central role in the biogenesis of membrane and secretory proteins. Whilst Sec61‐mediated protein translocation is typically coupled to polypeptide synthesis, suggestive of significant complexity, an obvious characteristic of this core translocation machinery is its surprising simplicity. Over thirty years after its initial discovery, we now understand that the Sec61 complex is in fact the central piece of an elaborate jigsaw puzzle, which can be partly solved using new research findings. We propose that the Sec61 complex acts as a dynamic hub for co‐translational protein translocation at the ER, proactively recruiting a range of accessory complexes that enhance and regulate its function in response to different protein clients. It is now clear that the Sec61 complex does not have a monopoly on co‐translational insertion, with some transmembrane proteins preferentially utilising the ER membrane complex instead. We also have a better understanding of post‐insertion events, where at least one membrane‐embedded chaperone complex can capture the newly inserted transmembrane domains of multi‐span proteins and co‐ordinate their assembly into a native structure. Having discovered this array of Sec61‐associated components and competitors, our next challenge is to understand how they act together in order to expand the range and complexity of the membrane proteins that can be synthesised at the ER. Furthermore, this diversity of components and pathways may open up new opportunities for targeted therapeutic interventions designed to selectively modulate protein biogenesis at the ER.
Effect of initial crack‐depth ratio on fracture characteristics of FRP‐strengthened concrete
Authors: Liu Jueding , Fan Xiangqian , Shi Chenyu
Published: May 2021

To investigate the fracture characteristics of FRP (fiber‐reinforced polymer)‐strengthened concrete, three‐point bending tests were carried out on concrete specimens with different initial crack‐depth ratios. The effects of the different crack‐depth ratios on the fracture parameters were analyzed, and the correlation between the crack‐depth ratio and the fracture parameters was verified quantitatively. The test results reveal that there are three critical points in the damage process: the crack initiation point, first peak point, and ultimate bearing capacity point. With the increase of the initial crack‐depth ratio, the crack initiation load decreased, but the first peak load and ultimate load first increased and then decreased. The stress intensity factors of the three points also first increased and then decreased. Additionally, the damage variable decreased with the initial crack‐depth ratio increased. The increment of the critical crack‐depth ratio and the flexibility coefficient are related to the initial crack‐depth ratio.
Fatigue life evaluation of Ti–6Al–4V welded joints manufactured by electron beam melting
Authors: Hu Yanan , Wu Shengchuan , Xie Cheng , Wu Wenwang , Zhang Jie
Published: May 2021

Electron beam melting (EBM) is a promising three‐dimensional printing technology for the fabrication of components with high complexity and freedom of structural design. However, the major limit for its wider industrial applications is to preclude manufacturing the large‐scale part in one piece. It is because the part size is largely limited by the enclosed vacuum chamber. An alternative option is the use of welding to join EBM‐processed subparts together. In this study, fatigue crack growth (FCG) rate and high‐cycle fatigue (HCF) performance were measured for both EBM‐processed Ti–6Al–4V alloy and its welded joints. An X‐parameter model was then proposed to correlate stress amplitude and geometric parameters (location, size, and shape) of the critical defects at the crack origins with fatigue life. Research framework and result from this work are expected to serve a reference for the defect‐based fatigue life evaluation of welded parts individually manufactured using additive manufacturing.
Cloudiness reduces the bleaching response of coral reefs exposed to heat stress
Authors: Gonzalez‐Espinosa Pedro C. , Donner Simon D.
Published: May 2021

Climate change and warming ocean temperatures are a threat to coral reef ecosystems. Since the 1980s, there has been an increase in mass coral bleaching and associated coral mortality due to more frequent and severe thermal stress. Although most research has focused on the role of temperature, coral bleaching is a product of the interacting effects of temperature and other environmental variables such as solar radiation. High light exacerbates the effects of thermal stress on corals, whereas reductions in light can reduce sensitivity to thermal stress. Here, we use an updated global dataset of coral bleaching observations (n = 35,769) from 1985 to 2017 and satellite‐derived datasets of SST and clouds to examine for the first time at a global scale the influence of cloudiness on the likelihood of bleaching from thermal stress. We find that among coral reefs exposed to severe bleaching‐level heat stress (Degree Heating Weeks >8°Cˑweek), bleaching severity is inversely correlated with the interaction of heat stress and cloud fraction anomalies (p < 0.05), such that higher cloudiness implies reduced bleaching response. A Random Forest model analysis employing different set of environmental variables shows that a model employing Degree Heating Weeks and the 30‐day cloud fraction anomaly most accurately predicts bleaching severity (Accuracy = 0.834; Cohen's Kappa = 0.769). Based on these results and global warm‐season cloudiness patterns, we develop a ‘cloudy refugia’ index which identifies the central equatorial Pacific and French Polynesia as regions where cloudiness is most likely to protect corals from bleaching. Our findings suggest that incorporating cloudiness into prediction models can help delineate bleaching responses and identify reefs which may be more resilient to climate change.
Applying a science‐based systems perspective to dispel misconceptions about climate effects of forest bioenergy
Authors: Cowie Annette L. , Berndes Göran , Bentsen Niclas Scott , Brandão Miguel , Cherubini Francesco , Egnell Gustaf , George Brendan , Gustavsson Leif , Hanewinkel Marc , Harris Zoe M. , Johnsson Filip , Junginger Martin , Kline Keith L. , Koponen Kati , Koppejan Jaap , Kraxner Florian , Lamers Patrick , Majer Stefan , Marland Eric , Nabuurs Gert‐Jan , Pelkmans Luc , Sathre Roger , Schaub Marcus , Smith Charles Tattersall , Soimakallio Sampo , Van Der Hilst Floor , Woods Jeremy , Ximenes Fabiano A.
Published: May 2021

The scientific literature contains contrasting findings about the climate effects of forest bioenergy, partly due to the wide diversity of bioenergy systems and associated contexts, but also due to differences in assessment methods. The climate effects of bioenergy must be accurately assessed to inform policy‐making, but the complexity of bioenergy systems and associated land, industry and energy systems raises challenges for assessment. We examine misconceptions about climate effects of forest bioenergy and discuss important considerations in assessing these effects and devising measures to incentivize sustainable bioenergy as a component of climate policy. The temporal and spatial system boundary and the reference (counterfactual) scenarios are key methodology choices that strongly influence results. Focussing on carbon balances of individual forest stands and comparing emissions at the point of combustion neglect system‐level interactions that influence the climate effects of forest bioenergy. We highlight the need for a systems approach, in assessing options and developing policy for forest bioenergy that: (1) considers the whole life cycle of bioenergy systems, including effects of the associated forest management and harvesting on landscape carbon balances; (2) identifies how forest bioenergy can best be deployed to support energy system transformation required to achieve climate goals; and (3) incentivizes those forest bioenergy systems that augment the mitigation value of the forest sector as a whole. Emphasis on short‐term emissions reduction targets can lead to decisions that make medium‐ to long‐term climate goals more difficult to achieve. The most important climate change mitigation measure is the transformation of energy, industry and transport systems so that fossil carbon remains underground. Narrow perspectives obscure the significant role that bioenergy can play by displacing fossil fuels now, and supporting energy system transition. Greater transparency and consistency is needed in greenhouse gas reporting and accounting related to bioenergy.
Phylogenetic relatedness drives protist assembly in marine and terrestrial environments
Authors: Lentendu Guillaume , Dunthorn Micah
Published: May 2021

Aim

Assembly of protist communities is known to be driven mainly by environmental filtering, but the imprint of phylogenetic relatedness is unknown. In this study, we aimed to test the degree to which co‐occurrences and co‐exclusions of protists in different phylogenetic relatedness classes deviate from random expectation in two ecosystems, in order to link them to ecological processes.

Location

Global open oceans and Neotropical rain‐forest soils.

Major taxa

Protists.

Time period

2009–2013.

Methods

Protist metabarcoding data originated from two large‐scale studies. Co‐occurrence and co‐exclusion networks were constructed using a recent method combining a null distribution model with Spearman's rank correlation coefficients among pairs of operational taxonomic units. Phylogenetic relatedness was estimated using either global pairwise sequence distance or phylogenetic distance inferred from best maximum‐likelihood trees derived from multiple alignments of operational taxonomic unit representative sequences. The significance of observed patterns relating networks and phylogenies was evaluated by distance classes against two null models, in which either the tips of the phylogenetic trees or the network edges were randomized.

Results

Closely related protists co‐occurred more often than expected by chance in all datasets, but also co‐excluded less often than expected by chance in the marine dataset only. Concurrent excesses of co‐occurrences and co‐exclusions were observed at intermediate phylogenetic distances in the marine dataset.

Main conclusions

This suggests that environmental filtering and dispersal limitation are the dominant forces driving protist co‐occurrences in both environments, whereas a signal of competitive exclusion is detected only in the marine environment. Differences in co‐exclusion are potentially linked to the individual environments, in that marine waters are more homogeneous, whereas rain‐forest soils contain a myriad of nutrient‐rich microenvironments, reducing the strength of mutual exclusion.
Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis
Authors: Sato Sho , Amano Nozomi , Sato Shunsuke , Kita Yuji , Ikeda Yuji , Kabemura Daishi , Murata Ayato , Yatagai Noboru , Tsuzura Hironori , Shimada Yuji , Genda Takuya
Published: May 2021

Aim

Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis.

Methods

This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched‐chain amino acids (BCAAs) and tyrosine, as well as the BCAA‐to‐tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation.

Results

Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA‐to‐tyrosine ratio for 114 patients (72.2%). During a median follow‐up period of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person‐year. Multivariable analysis showed that transplant‐free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child–Turcotte–Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110 µmol/L was the optimal cut‐off value for predicting transplant‐free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15–3.11, p = 0.012). Kaplan–Meier analysis showed a significant difference in the 5‐year transplant‐free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p < 0.001).

Conclusions

Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA‐to‐tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.
Acceptability of risk‐stratified population screening across cancer types: Qualitative interviews with the Australian public
Authors: Dunlop Kate , Rankin Nicole M. , Smit Amelia K. , Salgado Zofia , Newson Ainsley J. , Keogh Louise , Cust Anne E.
Published: May 2021

Background

There is mounting evidence of the benefit of risk‐stratified (risk‐tailored) cancer population screening, when compared to standard approaches. However, shifting towards this approach involves changes to practice that may give rise to implementation challenges.

Objectives

To explore the public's potential acceptance of risk‐stratified screening across different cancer types, including reducing screening frequency if at low risk and the use of personal risk information, to inform implementation strategies.

Method

Semi‐structured interviews were conducted with 40 public participants; half had received personal genomic risk information and half had not. Participants were prompted to consider different cancers. Data were analysed thematically as one dataset.

Results

Themes included the following: (a) a sense of security; (b) tailored screening is common sense; (c) risk and the need to take action; (d) not every cancer is the same; and (e) trust and belief in health messages. Both groups expressed similar views. Participants were broadly supportive of risk‐stratified screening across different cancer types, with strong support for increased screening frequency for high‐risk groups. They were less supportive of reduced screening frequency or no screening for low‐risk groups. Findings suggest the public will be amenable to reducing screening when the test is invasive and uncomfortable; be less opposed to forgo screening if offered the opportunity to screen at some stage; and view visible cancers such as melanoma differently.

Conclusions

Approaching distinct cancer types differently, tailoring messages for different audiences and understanding reasons for participating in screening may assist with designing future implementation strategies for risk‐stratified cancer screening.
Patient and public involvement in care home research: Reflections on the how and why of involving patient and public involvement partners in qualitative data analysis and interpretation
Authors: Stocker Rachel , Brittain Katie , Spilsbury Karen , Hanratty Barbara
Published: May 2021

Background

There is limited evidence for the impact of involving patients and the public (PPI) in health research. Descriptions of the PPI process are seldom included in publications, particularly data analysis, yet an understanding of processes and impacts of PPI is essential if its contribution to research is to be evaluated.

Objective

To describe the ‘how’ of PPI in qualitative data analysis and critically reflect on potential impact.

Methods

We focus on the development and critical reflection of our step‐by‐step approach to collaborative qualitative data analysis (through a series of analysis workshops) in a specific care home study, and our long‐term engagement model with patients and the public (termed PPI partners).

Results

An open access PPI group, with multiple events over time, sustained broad interest in care home research. Recordings of interview clips, role‐play of interview excerpts and written theme summaries were used in workshops to facilitate PPI partner engagement with data analysis in a specific study. PPI resulted in changes to data interpretation and was perceived to make the research process accessible. We reflect on the challenge of judging the benefits of PPI and presenting PPI in research publications for critical commentary.

Conclusions

Patient and public involvement partners who are actively engaged with data analysis can positively influence research studies. However, guidance for researchers is needed on approaches to PPI, including appropriate levels and methods for evaluation. Without more systematic approaches, we argue that it is impossible to know whether PPI represents good use of resources and is generating a real impact.
Diagnostic concordance of phyllodes tumour of the breast
Authors: Rakha Emad , Mihai Raluca , Abbas Areeg , Bennett Rachel , Campora Michela , Morena Philippa , Toss Michael , Ellis Ian
Published: May 2021

Aims

Phyllodes tumours (PT) are rare and distinct breast tumours, which span a morphological continuum. Classification into benign, borderline and malignant categories reflects their biology and clinical behaviour and is essential to guide management. This study aims to assess the diagnostic agreement of PT using the UK National Health Service Breast Screening Programme (NHSBSP) breast pathology external quality assurance (EQA) scheme data.

Methods and results

Twenty‐six PTs were identified in the EQA scheme, which were diagnosed by an average of 607 participants/circulation. Data on diagnostic categories were collected and representative slides were reviewed. The level of concordance between reporting pathologists was assessed. There were 14 benign, six borderline and six malignant PT. The overall rate of diagnosis agreement was 86% when analysed as benign lesions, borderline PT and malignant lesions, which decreased to 79% when diagnosed as PT (irrespective of grade) and to 63% when the diagnosis was further refined to PT categories (benign, borderline and malignant PTs). The highest agreement rate was observed in malignant PT (86%) and the lowest in borderline PT (42%). Malignant heterologous elements, stromal overgrowth and leaf‐like architecture are features associated with higher concordance rates. Lower‐priority features were stromal expansion, clefting and multinodularity.

Conclusion

The concordance of PT diagnosis, as an entity, is high, but its classification into benign, borderline and malignant has variable agreement levels, with borderline tumours having the lowest concordance rate. More research to refine the diagnostic criteria for categorisation of PT is warranted to improve concordance between pathologists.
Expression of the C‐terminal region of the SSX protein is a useful diagnostic biomarker for spermatocytic tumour
Authors: Anderson William J , Maclean Fiona M , Acosta Andres M , Hirsch Michelle S
Published: May 2021

Aims

Spermatocytic tumour (ST) is a rare testicular germ cell neoplasm with few confirmatory biomarkers that can be challenging to diagnose. Like normal spermatogonia, STs are known to express SSX proteins. Recently, a novel SSX antibody directed against a conserved C‐terminal region of SSX1, SSX2 and SSX4 (SSX_CT) has emerged as a reliable biomarker for these SSX proteins and synovial sarcoma. However, SSX_CT immunostaining has not been demonstrated in ST. The aim of this study was to assess the diagnostic utility of SSX_CT immunohistochemistry in ST and other tumours in the differential diagnosis with ST.

Methods and results

SSX_CT, OCT3/4 and c‐KIT immunohistochemistry was performed on 15 STs, 38 seminomas, 13 embryonal carcinomas, 12 yolk sac tumours, six choriocarcinomas, four teratomas, seven Sertoli cell tumours, and six lymphomas. Staining was scored as negative, rare, focal, or diffuse. SSX_CT was positive in all (15/15) STs, and diffusely positive in 14 of 15 (93%). SSX_CT was positive in 22 of 38 (58%) seminomas; however, only two cases showed diffuse expression. SSX_CT was negative in all other tumours. OCT3/4 was negative in all STs, but positive in all seminomas and embryonal carcinomas. c‐KIT was frequently positive in both STs (12/15; 80%) and seminomas (33/38; 87%). OCT3/4 and c‐KIT were negative in all other tumours.

Conclusions

SSX_CT is a valuable and highly sensitive biomarker that supports the diagnosis of ST. Diffuse expression of SSX‐CT in STs is also highly specific for ST. Nevertheless, SSX_CT is best used in combination with OCT3/4 when ST is in the differential diagnosis.