bluuebunny/crossref_metadata_2025 huggingface dataset:
Health technology assessment for digital technologies that manage chronic disease: a systematic review
Authors: von Huben Amy , Howell Martin , Howard Kirsten , Carrello Joseph , Norris Sarah
Published: May 2021

Objective

A growing number of evaluation frameworks have emerged over recent years addressing the unique benefits and risk profiles of new classes of digital health technologies (DHTs). This systematic review aims to identify relevant frameworks and synthesize their recommendations into DHT-specific content to be considered when performing Health Technology Assessments (HTAs) for DHTs that manage chronic noncommunicable disease at home.

Methods

Searches were undertaken of Medline, Embase, Econlit, CINAHL, and The Cochrane Library (January 2015 to March 2020), and relevant gray literature (January 2015 to August 2020) using keywords related to HTA, evaluation frameworks, and DHTs. Included framework reference lists were searched from 2010 until 2015. The EUNetHTA HTA Core Model version 3.0 was selected as a scaffold for content evaluation.

Results

Forty-four frameworks were identified, mainly covering clinical effectiveness (n = 30) and safety (n = 23) issues. DHT-specific content recommended by framework authors fell within 28 of the 145 HTA Core Model issues. A further twenty-two DHT-specific issues not currently in the HTA Core Model were recommended.

Conclusions

Current HTA frameworks are unlikely to be sufficient for assessing DHTs. The development of DHT-specific content for HTA frameworks is hampered by DHTs having varied benefit and risk profiles. By focusing on DHTs that actively monitor/treat chronic noncommunicable diseases at home, we have extended DHT-specific content to all nine HTA Core Model domains. We plan to develop a supplementary evaluation framework for designing research studies, undertaking HTAs, and appraising the completeness of HTAs for DHTs.
Sources of variation at the onset of bilingualism: The differential effect of input factors, AOA, and cognitive skills on HL Arabic and L2 English syntax
Authors: SOTO-COROMINAS Adriana , DASKALAKI Evangelia , PARADIS Johanne , WINTERS-DIFANI Magdalena , JANAIDEH Redab AL
Published: May 2021

Despite growing research on individual differences in child bilinguals, few studies have focused on the development of syntax, included both languages, and studied newly arrived school-age migrant children. Accordingly, this study investigated the syntactic development of heritage language (HL) Syrian Arabic and L2 English by Syrian refugee children (N = 119) recently arrived in Canada using a sentence repetition task. Regression analyses showed that a partially overlapping set of child-level (input and cognitive skills) and language-level (syntactic structure) factors accounted for performance in each language. HL performance was particularly sensitive to language, cognitive, and input variables indexing cumulative HL exposure. L2 performance, however, was sensitive to cognitive and environmental variables indexing current and cumulative L2 use. Finally, despite stronger performance in Arabic than in English, results revealed interdependence between the two languages, indicating that participants with stronger syntactic abilities in their HL tended to have stronger syntactic abilities in their emerging L2.
Prehistoric Pendants as Instigators of Sound and Body Movements: A Traceological Case Study from Northeast Europe, c. 8200 cal. bp
Authors: Rainio Riitta , Gerasimov Dmitry V. , Girya Evgeny Yu. , Mannermaa Kristiina
Published: May 2021

In the Late Mesolithic graves of Yuzhniy Oleniy Ostrov, northwest Russia, large numbers of Eurasian elk (Alces alces) incisors have been found. These teeth, for the most part fashioned into portable pendants, seem to have formed decorative sets for the garments or accessories of the deceased. This article examines both the technologies associated with these artefacts and their uses, as well as reflecting on the sensorial experiences generated by them. Osteological analysis of a sample of 100 specimens indicates that all types of incisors were used for making the pendants. Traceological analysis indicates that the teeth were modified by scraping, grooving, grinding and retouching. Traces of wear consist of general wear and distinctive pits or pecks on the perimeters of the crowns. These traces indicate that the pendants were worn before their deposition in the graves, in such a way that they were in contact with both soft and solid materials. This pattern of pits or pecks has until now been unreported in the traceological literature. In experiments, a similar pattern emerged when pendants of fresh elk incisors were hung in rows and bunches and struck against one another. These strokes created a rattling sound. Thus, the elk incisors of Yuzhniy Oleniy Ostrov appear to provide insight into previously unattainable sonic experiences and activities of Mesolithic hunter-gatherers, as well as the early history of the instrument category of rattles.
Sperm DNA fragmentation measured by sperm chromatin dispersion impacts morphokinetic parameters, fertilization rate and blastocyst quality in ICSI treatments
Authors: Wang Shikai , Tan Weihong , Huang Yueyue , Mao Xianbao , Li Zhengda , Zhang Xiaohui , Wei Pingpin , Xue Lintao
Published: May 2021

To determine the effects of sperm DNA fragmentation (SDF) on embryo morphokinetic parameters, cleavage patterns and embryo quality, this retrospective study analyzed 151 intracytoplasmic sperm injection (ICSI) cycles (1152 embryos collected) between November 2016 and June 2019. SDF was assessed using sperm chromatin dispersion. The cycles were divided into two groups based on the SDF rate: SDF < 15% (n = 114) and SDF ≥ 15% (n = 37). The embryo morphokinetic parameters, cleavage patterns, and embryo quality were compared between the two groups. The morphokinetic parameters tPNf, t2, t3, t4, t5, t6, and t8 were achieved significantly earlier in the SDF < 15% group compared with in the SDF ≥ 15% group. The fertilization and 2PN rates seemed to be significantly higher in the SDF < 15% group compared with in the SDF ≥ 15% group, while the abnormal cleavage rates were similar. However, a significantly higher rate of chaotic cleavage (CC) was observed in the SDF ≥ 15% group. The D3 high-quality embryo and available embryo rates were similar between the two groups. The blastocyst formation, high-quality blastocyst, and available blastocyst rates in the SDF < 15% group were significantly higher than those in the SDF ≥ 15% group. With an increase in SDF level, the chemical pregnancy, clinical pregnancy and implantation rates tended to decrease, while the miscarriage rate increased. This study demonstrated that SDF ≥ 15% reduces the fertilization rate of ICSI cycles and affects certain morphokinetic parameters. A higher SDF level can also induce a higher rate of CC, with subsequent decreases in the blastocyst formation rate and blastocyst quality.
Molecular analysis of dilated and left ventricular noncompaction cardiomyopathies in Egyptian children
Authors: Mehaney Dina A. , Haghighi Alireza , Embaby Amira K. , Zeyada Reham A. , Darwish Rania K. , Elfeel Nesrine S. , Abouelhoda Mohamed , El-Saiedi Sonia A. , Gohar Nadida A. , Seliem Zeinab S.
Published: May 2021

Background:

Paediatric cardiomyopathy is a progressive, often lethal disorder and the most common cause of heart failure in children. Despite its severe outcomes, the genetic aetiology is still poorly characterised. High-throughput sequencing offers a great opportunity for a better understanding of the genetic causes of cardiomyopathy.

Aim:

The current study aimed to elucidate the genetic background of cardiomyopathy in Egyptian children.

Methods:

This hospital-based study involved 68 patients; 58 idiopathic primary dilated cardiomyopathy and 10 left ventricular noncompaction cardiomyopathy. Cardiomyopathy-associated genes were investigated using targeted next-generation sequencing.

Results:

Consanguinity was positive in 53 and 70% of dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy patients, respectively. Positive family history of cardiomyopathy was present in 28% of dilated cardiomyopathy and 10% of the left ventricular noncompaction cardiomyopathy patients. In 25 patients, 29 rare variants were detected; 2 likely pathogenic variants inTNNI3andTTNand 27 variants of uncertain significance explaining 2.9% of patients.

Conclusions:

The low genetic detection rate suggests that novel genes or variants might underlie paediatric cardiomyopathy in Egypt, especially with the high burden of consanguinity. Being the first national and regional report, our study could be a reference for future genetic testing in Egyptian cardiomyopathy children. Genome-wide tests (whole exome/genome sequencing) might be more suitable than the targeted sequencing to investigate the primary cardiomyopathy patients. Molecular characterisation of cardiomyopathies in different ethnicities will allow for global comparative studies that could result in understanding the pathophysiology and heterogeneity of cardiomyopathies.
Differential educational patterning of cardiometabolic risks between women and men among community-dwelling Chinese adults in Hong Kong: the mediating role of obesity
Authors: Chung Gary KK , Lai Francisco TT , Hung Heidi , Yeoh Eng-Kiong , Chung Roger Y
Published: May 2021

Objectives:

Educational inequalities in cardiometabolic diseases (CMD) are globally recognised; nonetheless, the evidence on potential explanatory mechanisms and effective strategies for CMD prevention and inequality reduction is relatively scarce in Asia. Therefore, the current study examined the extent and potential mediators of the association of education level with CMD conditions (i.e., hypertension and diabetes) in an advanced economy in Asia.

Design:

A cross-sectional study.

Setting:

This territory-wide cross-sectional Population Health Survey in 2014–2015 was performed in Hong Kong. Demographic, socio-economic and lifestyle factors were collected via questionnaire, while clinical data on blood pressure and glucose levels, lipid profiles and anthropometric measures were obtained during health examination. Hypertension and diabetes statuses were objectively defined by both clinical data and the use of relevant medications.

Participants:

2297 community-dwelling adults aged between 15–84 years recruited via systematic replicated sampling of living quarters.

Results:

Multivariable binary logistic regression analysis showed that lower education level was significantly associated with hypertension among women but not men, whereas similar pattern was also observed for diabetes and other related clinical risk factors. Also, general and abdominal obesity were independently associated with hypertension and diabetes among both women and men, and substantially mediated the observed inequalities across education levels among women. Specifically, abdominal obesity was a particularly strong risk factor and mediator for diabetes.

Conclusion:

Educational patterning of CMD was more apparent among women in Hong Kong. Obesity control appears to be important for both overall CMD prevention and reduction of educational inequalities in CMD among women.
Consumption of ultra-processed foods and nutritional profile in a health promotion service of primary care
Authors: Campos Suellen F , dos Santos Luana Caroline , Lopes Mariana S , de Freitas Patrícia P , Lopes Aline CS
Published: May 2021

Objective:

Describing the consumption of ultra-processed foods (UPF) and their association with the nutritional profiles among users of a health promotion service in a Brazilian city.

Design:

Cross-sectional study.

Setting:

Public health promotion service of Primary Health Care in Belo Horizonte, Minas Gerais, Brazil.

Participants:

Totally, 3372 participants.

Results:

UPF were found to contribute to 27·7 % of the diet’s total energy. The highest consumption was associated with higher values for energy intake (1561·8v. 1331·8 kcal/d;P< 0·01), energy density (1·7v. 1·4 kcal/g;P< 0·01), total (32·5v. 27·3 %;P< 0·01) and trans-fats (2·1v. 1·2 %;P< 0·01) and Na (1001·6v. 758·9 mg/1000 kcal;P< 0·01) and with lower values for proteins (14·9v. 19·6 %;P< 0·01), mono-unsaturated fats (16·1v. 20·1 %;P= 0·02),n-3 (0·9v. 1·1 %;P< 0·01) and some vitamins and minerals when comparing individuals in the last quintile of energy contribution from UPF in relation to the first one. The prevalence rate of nutrient inadequacy aimed at preventing non-communicable diseases increased between 30 % and 100 % when compared with the values of the fifth to the first quintile of UPF consumption (P< 0·001). However, the participants had lower energy intake, energy density and Na and higher fibre consumption when compared to Brazilian population.

Conclusions:

Participants showed a high consumption of UPF, but also positive diet characteristics when compared with the national data. The results suggest the importance of health promotion services to promote healthy food and the need to include approaches to reduce UPF consumption.
Uncovering survivorship bias in longitudinal mental health surveys during the COVID-19 pandemic
Authors: Czeisler Mark É. , Wiley Joshua F. , Czeisler Charles A. , Rajaratnam Shantha M.W. , Howard Mark E.
Published: May 2021

Aims

Markedly elevated adverse mental health symptoms were widely observed early in the coronavirus disease-2019 (COVID-19) pandemic. Unlike the U.S., where cross-sectional data indicate anxiety and depression symptoms have remained elevated, such symptoms reportedly declined in the U.K., according to analysis of repeated measures from a large-scale longitudinal study. However, nearly 40% of U.K. respondents (those who did not complete multiple follow-up surveys) were excluded from analysis, suggesting that survivorship bias might partially explain this discrepancy. We therefore sought to assess survivorship bias among participants in our longitudinal survey study as part of The COVID-19 Outbreak Public Evaluation (COPE) Initiative.

Methods

Survivorship bias was assessed in 4039 U.S. respondents who completed surveys including the assessment of mental health as part of The COPE Initiative in April 2020 and were invited to complete follow-up surveys. Participants completed validated screening instruments for symptoms of anxiety, depression and insomnia. Survivorship bias was assessed for (1) demographic differences in follow-up survey participation, (2) differences in initial adverse mental health symptom prevalence adjusted for demographic factors and (3) differences in follow-up survey participation based on mental health experiences adjusted for demographic factors.

Results

Adjusting for demographics, individuals who completed only one or two out of four surveys had significantly higher prevalence of anxiety and depression symptoms in April 2020 (e.g. one-survey v. four-survey, anxiety symptoms, adjusted prevalence ratio [aPR]: 1.30, 95% confidence interval [CI]: 1.08–1.55, p = 0.0045; depression symptoms, aPR: 1.43, 95% CI: 1.17–1.75, p = 0.00052). Moreover, individuals who experienced incident anxiety or depression symptoms had significantly higher adjusted odds of not completing follow-up surveys (adjusted odds ratio [aOR]: 1.68, 95% CI: 1.22–2.31, p = 0.0015, aOR: 1.56, 95% CI: 1.15–2.12, p = 0.0046, respectively).

Conclusions

Our findings reveal significant survivorship bias among longitudinal survey respondents, indicating that restricting analytic samples to only respondents who provide repeated assessments in longitudinal survey studies could lead to overly optimistic interpretations of mental health trends over time. Cross-sectional or planned missing data designs may provide more accurate estimates of population-level adverse mental health symptom prevalence than longitudinal surveys.
Tidally Induced Temporal Variations in Growth of Young‐of‐the‐Year Pacific Cod in the Yellow Sea
Authors: Li Jianchao , Jiang Feng , Wu Rui , Zhang Chi , Tian Yongjun , Sun Peng , Yu Haiqing , Liu Yang , Ye Zhenjiang , Ma Shuyang , Liu Shude , Dong Xiuqiang
Published: May 2021

The Yellow Sea is the southern limit of the distribution of Pacific cod (Gadus microcephalus), and the Yellow Sea Cold Water Mass (YSCWM) provides an appropriate over‐summering habitat for this species. Tidal current is the major component of the Yellow Sea hydrodynamic system, and its periodic variations influence the local ecological conditions and related ecosystems, particularly in the YSCWM, which is stratified in summer. To investigate the influence of tidal currents on Pacific cod growth, otolith daily increment in young‐of‐the‐year (YOY) Pacific cod in the Yellow Sea was analyzed in 2017. These data were integrated with a simulated tidal current using a multi‐scenario time‐delay analysis. This showed that: (1) the otolith daily increment exhibited a strong signal similar to the fortnightly tidal variation; (2) there was a lag of ∼8 days between the highest growth rate induced by the tidal current variation and monthly spring tide; and (3) the influence of the tidal current on otolith daily growth was stronger after migration of the cod into the YSCWM, particularly during the settlement stage. Given the stratified ocean structure during the over‐summering period, enhanced tidal mixing during the fortnightly spring tide would improve the exchange of nutrients and oxygen within the YSCWM, and lead to a delayed response of otolith growth due to feeding/digestion and subsequent growth. Therefore, variations in the tidal current have a marked positive ecological effect on the growth of YOY Pacific cod, and ultimately on the YSCWM ecosystem.
An ERA‐5 Derived CONUS‐Wide High‐Resolution Precipitation Dataset Based on a Refined Parametric Statistical Downscaling Framework
Authors: Emmanouil Stergios , Langousis Andreas , Nikolopoulos Efthymios I. , Anagnostou Emmanouil N.
Published: May 2021

The spatiotemporal character of rainfall is particularly important for hydrologic modeling, as well as hydroclimatic risk estimation and impact assessment. Existing atmospheric reanalysis datasets offer extensive record lengths and global coverage, but usually their spatial resolution is coarse for distributed hydrologic simulations at small spatial scales. On the other hand, the temporal coverage of high‐resolution radar‐based rainfall estimates can be rather short for risk applications. To address these shortcomings, we simultaneously bias‐correct and downscale a state‐of‐the‐art atmospheric reanalysis (ERA5) rainfall dataset, using the radar‐based Stage IV precipitation product as fine resolution reference, to develop an hourly CONUS‐wide precipitation product over a 4‐km grid, which extends back to 1979. In this regard, we refine an existing parametric quantile mapping framework based on a two‐component theoretical distribution model, where we impose continuity of the parametric forms via optimal threshold selection to transition between higher and lower rain rates. An evaluation over the probability frequency and time domains, using NOAA’s raingauge measurements as benchmark, reveals that the developed product benefits from the strengths of the calibration datasets, demonstrating good performance and robust behavior over all studied time periods and Köppen climate classification zones, including snow‐prone regions or areas where mesoscale convective systems become dominant. The accuracy of the yielded high spatial‐resolution rain rates, especially in low probability events, shows that the developed product can be effectively used for hydroclimatic risk applications and frequency analysis, while its high temporal and spatial resolution makes it particularly useful for distributed hydrologic modeling.
Revealing a High Water Abundance in the Upper Mesosphere of Mars With ACS Onboard TGO
Authors: Belyaev Denis A. , Fedorova Anna A. , Trokhimovskiy Alexander , Alday Juan , Montmessin Franck , Korablev Oleg I. , Lefèvre Franck , Patrakeev Andrey S. , Olsen Kevin S. , Shakun Alexey V.
Published: May 2021

We present the first water vapor profiles encompassing the upper mesosphere of Mars, 100–120 km, far exceeding the maximum altitudes where remote sensing has been able to observe water to date. Our results are based on solar occultation measurements by Atmospheric Chemistry Suite (ACS) onboard the ExoMars Trace Gas Orbiter (TGO). The observed wavelength range around 2.7 μm possesses strong CO2 and H2O absorption lines allowing sensitive temperature and density retrievals. We report a maximum H2O mixing ratio varying from 10 to 50 ppmv at 100–120 km during the global dust storm (GDS) of Martian Year (MY) 34 and around southern summer solstice of MY 34 and 35. During other seasons water remains persistently below ∼2 ppmv. We claim that contributions of the MY34 GDS and perihelion periods into the projected hydrogen escape from Mars are nearly equivalent.
Mixing Efficiency for Breaking Internal Solitary Waves
Authors: la Forgia Giovanni , Cavaliere Davide , Adduce Claudia , Falcini Federico
Published: May 2021

We propose a semi‐analytic approach to estimate mixing induced by internal solitary waves (ISWs) breaking over a sloping boundary. The theoretical framework we develop describes the energetics of a stratified fluid flow during the interaction of ISWs with a slope. In particular, through both Ozmidov and Thorpe lengthscales we derive a heuristic expression for mixing efficiency, valid for plunging and plunging‐collapsing breakers. On the other hand, we perform laboratory experiments that also provide mixing efficiency by estimating both changes of the background potential energy and the incident and reflected ISWs energy. We then compare those results with the ones derived by our theoretical model, obtaining a power law that relates the two quantities. This function allows to estimate mixing efficiency when the change in the background potential energy due to the ISWs breaking is unknown. We finally successfully apply our model to estimate the mixing efficiency under real field conditions.
Barrier Breaching Versus Overwash Deposition: Predicting the Morphologic Impact of Storms on Coastal Barriers
Authors: Nienhuis Jaap H. , Heijkers Leoni G. H. , Ruessink Gerben
Published: May 2021

Waves and water level setup during storms can create overwashing flows across barrier islands. Overwashing flows can cause erosion, barrier breaching, and inlet formation, but their sediments can also be deposited and form washover fans. These widely different outcomes remain difficult to predict. Here we suggest that a breach develops when the sediment volume transported by overwashing flows exceeds the barrier subaerial volume. We form a simple analytical theory that estimates overwashing flows from storm characteristics, barrier morphology, and dune vegetation, and which can be used to assess washover deposition and breaching likelihood. Our theory suggests that barrier width and storm surge height are two important controls on barrier breaching. We test our theory with the hydrodynamic and morphodynamic model Delft3D as well as with field observations of 21 washover fans and 6 breaches that formed during Hurricane Sandy. There is reasonable correspondence for natural but not for developed barrier coasts, where traditional sediment transport equations do not readily apply. Our analytical formulations for breach formation and overwash deposition can be used to improve long‐term barrier island models.
Family environment and development in children adopted from institutionalized care
Authors: Keil Margaret F. , Leahu Adela , Rescigno Megan , Myles Jennifer , Stratakis Constantine A.
Published: May 2021

Background

After adoption, children exposed to institutionalized care show significant improvement, but incomplete recovery of growth and developmental milestones. There is a paucity of data regarding risk and protective factors in children adopted from institutionalized care. This prospective study followed children recently adopted from institutionalized care to investigate the relationship between family environment, executive function, and behavioral outcomes.

Methods

Anthropometric measurements, physical examination, endocrine and bone age evaluations, neurocognitive testing, and behavioral questionnaires were evaluated over a 2-year period with children adopted from institutionalized care and non-adopted controls.

Results

Adopted children had significant deficits in growth, cognitive, and developmental measurements compared to controls that improved; however, residual deficits remained. Family cohesiveness and expressiveness were protective influences, associated with less behavioral problems, while family conflict and greater emphasis on rules were associated with greater risk for executive dysfunction.

Conclusions

Our data suggest that a cohesive and expressive family environment moderated the effect of pre-adoption adversity on cognitive and behavioral development in toddlers, while family conflict and greater emphasis on rules were associated with greater risk for executive dysfunction. Early assessment of child temperament and parenting context may serve to optimize the fit between parenting style, family environment, and the child’s development.

Impact

Children who experience institutionalized care are at increased risk for significant deficits in developmental, cognitive, and social functioning associated with a disruption in the development of the prefrontal cortex. Aspects of the family caregiving environment moderate the effect of early life social deprivation in children.

Family cohesiveness and expressiveness were protective influences, while family conflict and greater emphasis on rules were associated with a greater risk for executive dysfunction problems.

This study should be viewed as preliminary data to be referenced by larger studies investigating developmental and behavioral outcomes of children adopted from institutional care.
Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing
Authors: Gebauer Niklas , Künstner Axel , Ketzer Julius , Witte Hanno M. , Rausch Tobias , Benes Vladimir , Zimmermann Jürgen , Gebauer Judith , Merz Hartmut , Bernard Veronica , Harder Lana , Ratjen Katharina , Gesk Stefan , Peter Wolfgang , Busch Yannik , Trojok Peter , von Bubnoff Nikolas , Biersack Harald , Busch Hauke , Feller Alfred C.
Published: May 2021

Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease. Integrated WGS and tNGS analysis clearly distinguished this tumor type from EBV-negative DLBCL due to frequent mutations in ARID1A (45%), KMT2A/KMT2D (32/30%), ANKRD11 (32%), or NOTCH2 (32%). WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%), and YY1 (6%). Lastly, functional annotation of the mutational landscape by sequential gene set enrichment and network propagation predicted an effect on the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL6/JAK/STAT (SOCS1/3, STAT3), and WNT signaling (FRAT1, SFRP5) alongside aberrations in immunological processes, such as interferon response. This first comprehensive description of EBV + DLBCL (NOS) tumors substantiates the evidence of its pathobiological independence and helps stratify the molecular taxonomy of aggressive lymphomas in the effort for future therapeutic strategies.
Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM)
Authors: Lonial Sagar , Nooka Ajay K. , Thulasi Praneetha , Badros Ashraf Z. , Jeng Bennie H. , Callander Natalie S. , Potter Heather A. , Sborov Douglas , Zaugg Brian E. , Popat Rakesh , Degli Esposti Simona , Byrne Julie , Opalinska Joanna , Baron January , Piontek Trisha , Gupta Ira , Dana Reza , Farooq Asim V. , Colby Kathryn , Jakubowiak Andrzej
Published: May 2021

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.
Ethnicity and the tumour characteristics of invasive breast cancer in over 116,500 women in England
Authors: Gathani Toral , Reeves Gillian , Broggio John , Barnes Isobel
Published: May 2021

Background

Ethnic minority women are commonly reported to have more aggressive breast cancer than White women, but there is little contemporary national evidence available.

Methods

We analysed data from the National Cancer Registration and Analysis Service on women diagnosed with invasive breast cancer during 2013–2018. Multivariable logistic regression yielded adjusted odds ratios (and 95% confidence intervals) of less favourable tumour characteristics (high stage, high grade, ER negative, Her2 positive) by ethnicity (black African, black Caribbean, Indian, Pakistani and white) in younger (30–46 years) and older (53–70 years) women.

Results

In 24,022 women aged 30–46 at diagnosis, all ethnic minority groups apart from Indian women had a significantly greater odds of certain less favourable tumour characteristics compared to white women in fully adjusted models. In 92,555 women aged 53–70, all ethnic minorities had a significantly greater adjusted odds of several of the less favourable tumour characteristics. These differences were most marked in black African and black Caribbean women.

Conclusions

Ethnic minority women are at greater risk of breast cancers with less favourable characteristics, even after allowing for age and other potential confounders. These differences are greater in older than younger women, and in the Black rather than South Asian ethnic groups.
Tumor-derived exosomal components: the multifaceted roles and mechanisms in breast cancer metastasis
Authors: Tan Yufang , Luo Xiao , Lv Wenchang , Hu Weijie , Zhao Chongru , Xiong Mingchen , Yi Yi , Wang Dawei , Wang Yichen , Wang Haiping , Wu Yiping , Zhang Qi
Published: May 2021

Breast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.
Biodegradation of bio-sourced and synthetic organic electronic materials towards green organic electronics
Authors: Di Mauro Eduardo , Rho Denis , Santato Clara
Published: May 2021

Ubiquitous use of electronic devices has led to an unprecedented increase in related waste as well as the worldwide depletion of reserves of key chemical elements required in their manufacturing. The use of biodegradable and abundant organic (carbon-based) electronic materials can contribute to alleviate the environmental impact of the electronic industry. The pigment eumelanin is a bio-sourced candidate for environmentally benign (green) organic electronics. The biodegradation of eumelanin extracted from cuttlefish ink is studied both at 25 °C (mesophilic conditions) and 58 °C (thermophilic conditions) following ASTM D5338 and comparatively evaluated with the biodegradation of two synthetic organic electronic materials, namely copper (II) phthalocyanine (Cu–Pc) and polyphenylene sulfide (PPS). Eumelanin biodegradation reaches 4.1% (25 °C) in 97 days and 37% (58 °C) in 98 days, and residual material is found to be without phytotoxic effects. The two synthetic materials, Cu–Pc and PPS, do not biodegrade; Cu–Pc brings about the inhibition of microbial respiration in the compost. PPS appears to be potentially phytotoxic. Finally, some considerations regarding the biodegradation test as well as the disambiguation of “biodegradability” and “bioresorbability” are highlighted.
Interfacial piezoelectric polarization locking in printable Ti3C2Tx MXene-fluoropolymer composites
Authors: Shepelin Nick A. , Sherrell Peter C. , Skountzos Emmanuel N. , Goudeli Eirini , Zhang Jizhen , Lussini Vanessa C. , Imtiaz Beenish , Usman Ken Aldren S. , Dicinoski Greg W. , Shapter Joseph G. , Razal Joselito M. , Ellis Amanda V.
Published: May 2021

Piezoelectric fluoropolymers convert mechanical energy to electricity and are ideal for sustainably providing power to electronic devices. To convert mechanical energy, a net polarization must be induced in the fluoropolymer, which is currently achieved via an energy-intensive electrical poling process. Eliminating this process will enable the low-energy production of efficient energy harvesters. Here, by combining molecular dynamics simulations, piezoresponse force microscopy, and electrodynamic measurements, we reveal a hitherto unseen polarization locking phenomena of poly(vinylidene fluoride–co–trifluoroethylene) (PVDF-TrFE) perpendicular to the basal plane of two-dimensional (2D) Ti3C2Tx MXene nanosheets. This polarization locking, driven by strong electrostatic interactions enabled exceptional energy harvesting performance, with a measured piezoelectric charge coefficient, d33, of −52.0 picocoulombs per newton, significantly higher than electrically poled PVDF-TrFE (approximately −38 picocoulombs per newton). This study provides a new fundamental and low-energy input mechanism of poling fluoropolymers, which enables new levels of performance in electromechanical technologies.
Live-cell imaging reveals the spatiotemporal organization of endogenous RNA polymerase II phosphorylation at a single gene
Authors: Forero-Quintero Linda S. , Raymond William , Handa Tetsuya , Saxton Matthew N. , Morisaki Tatsuya , Kimura Hiroshi , Bertrand Edouard , Munsky Brian , Stasevich Timothy J.
Published: May 2021

The carboxyl-terminal domain of RNA polymerase II (RNAP2) is phosphorylated during transcription in eukaryotic cells. While residue-specific phosphorylation has been mapped with exquisite spatial resolution along the 1D genome in a population of fixed cells using immunoprecipitation-based assays, the timing, kinetics, and spatial organization of phosphorylation along a single-copy gene have not yet been measured in living cells. Here, we achieve this by combining multi-color, single-molecule microscopy with fluorescent antibody-based probes that specifically bind to different phosphorylated forms of endogenous RNAP2 in living cells. Applying this methodology to a single-copy HIV-1 reporter gene provides live-cell evidence for heterogeneity in the distribution of RNAP2 along the length of the gene as well as Serine 5 phosphorylated RNAP2 clusters that remain separated in both space and time from nascent mRNA synthesis. Computational models determine that 5 to 40 RNAP2 cluster around the promoter during a typical transcriptional burst, with most phosphorylated at Serine 5 within 6 seconds of arrival and roughly half escaping the promoter in ~1.5 minutes. Taken together, our data provide live-cell support for the notion of efficient transcription clusters that transiently form around promoters and contain high concentrations of RNAP2 phosphorylated at Serine 5.
The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing
Authors: Goulielmaki Evi , Tsekrekou Maria , Batsiotos Nikos , Ascensão-Ferreira Mariana , Ledaki Eleftheria , Stratigi Kalliopi , Chatzinikolaou Georgia , Topalis Pantelis , Kosteas Theodore , Altmüller Janine , Demmers Jeroen A. , Barbosa-Morais Nuno L. , Garinis George A.
Published: May 2021

RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csbm/m developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for transcription-coupled DNA repair disorders.
A tighter constraint on Earth-system sensitivity from long-term temperature and carbon-cycle observations
Authors: Wong Tony E. , Cui Ying , Royer Dana L. , Keller Klaus
Published: May 2021

The long-term temperature response to a given change in CO2 forcing, or Earth-system sensitivity (ESS), is a key parameter quantifying our understanding about the relationship between changes in Earth’s radiative forcing and the resulting long-term Earth-system response. Current ESS estimates are subject to sizable uncertainties. Long-term carbon cycle models can provide a useful avenue to constrain ESS, but previous efforts either use rather informal statistical approaches or focus on discrete paleoevents. Here, we improve on previous ESS estimates by using a Bayesian approach to fuse deep-time CO2 and temperature data over the last 420 Myrs with a long-term carbon cycle model. Our median ESS estimate of 3.4 °C (2.6-4.7 °C; 5-95% range) shows a narrower range than previous assessments. We show that weaker chemical weathering relative to the a priori model configuration via reduced weatherable land area yields better agreement with temperature records during the Cretaceous. Research into improving the understanding about these weathering mechanisms hence provides potentially powerful avenues to further constrain this fundamental Earth-system property.
Early constipation predicts faster dementia onset in Parkinson’s disease
Authors: Camacho M. , Macleod A. D. , Maple-Grødem J. , Evans J. R. , Breen D. P. , Cummins G. , Wijeyekoon R. S. , Greenland J. C. , Alves G. , Tysnes O. B. , Lawson R. A. , Barker R. A. , Williams-Gray C. H.
Published: May 2021

Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson’s Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan–Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.
Quantum enhanced measurement of an optical frequency comb
Authors: Cai Y. , Roslund J. , Thiel V. , Fabre C. , Treps N.
Published: May 2021

Measuring the spectral properties of an optical frequency comb is among the most fundamental tasks of precision metrology. In contrast to general single-parameter measurement schemes, we demonstrate here single shot multi-parameter estimation of an optical frequency comb at and beyond the standard quantum limit. The mean energy and the central frequency as well as the spectral bandwidth of ultrafast pulses are simultaneously determined with a multi-pixel spectrally resolved (MPSR) apparatus, without changing the photonics architecture. Moreover, using a quantum frequency comb that intrinsically consists of multiple squeezed states in a family of Hermite–Gaussian spectral/temporal modes, the signal-to-noise ratios of the multiple spectral parameters estimation can surpass the standard quantum limit. Combining our multi-pixel detection scheme and the multimode entangled resource could find applications in ultrafast quantum metrology and multimode quantum information processing.
Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2
Authors: Au Lewis , Fendler Annika , Shepherd Scott T. C. , Rzeniewicz Karolina , Cerrone Maddalena , Byrne Fiona , Carlyle Eleanor , Edmonds Kim , Del Rosario Lyra , Shon John , Haynes Winston A. , Ward Barry , Shum Ben , Gordon William , Gerard Camille L. , Xie Wenyi , Joharatnam-Hogan Nalinie , Young Kate , Pickering Lisa , Furness Andrew J. S. , Larkin James , Harvey Ruth , Kassiotis George , Gandhi Sonia ,   Crick COVID-19 Consortium, Kassiotis George , Gandhi Sonia , Swanton Charles , Swanton Charles , Fribbens Charlotte , Wilkinson Katalin A. , Wilkinson Robert J. , Lau David K. , Banerjee Susana , Starling Naureen , Chau Ian ,   CAPTURE Consortium, Au Lewis , Fendler Annika , Shepherd Scott T. C. , Byrne Fiona , Shum Ben , Gerard Camille , Young Kate , Pickering Lisa , Furness Andrew J. S. , Larkin James , Kassiotis George , Wilkinson Katalin A. , Wilkinson Robert J. , Banerjee Susana , Starling Naureen , Chau Ian , Turajlic Samra , Turajlic Samra
Published: May 2021

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population.
Temperature effect in physicochemical and bioactive behavior of biogenic hydroxyapatite obtained from porcine bones
Authors: Forero-Sossa P. A. , Salazar-Martínez J. D. , Giraldo-Betancur A. L. , Segura-Giraldo B. , Restrepo-Parra E.
Published: May 2021

Biogenic hydroxyapatite (BHAp) is a widely used material in the biomedical area due to its similarities with the bone tissue mineral phase. Several works have been spotlighted on the thermal behavior of bone. However, little research has focused on determining the influence of calcination temperature in the physicochemical and bioactive properties of BHAp. In this work, a study of the physicochemical properties’ changes and bioactive response of BHAp produced from porcine femur bones using calcination temperatures between 900 to 1200 °C was conducted. The samples’ structural, morphological, and compositional changes were determined using XRD, SEM, and FTIR techniques. XRD results identified three temperature ranges, in which there are structural changes in BHAp samples and the presence of additional phases. Moreover, FTIR results corroborated that B-type substitution is promoted by increasing the heat treatment temperature. Likewise, samples were immersed in a simulated biological fluid (SBF), following the methodology described by Kokubo and using ISO 23317:2014 standard, for 3 and 7 days. FTIR and SEM results determined that the highest reaction velocity was reached for samples above 1000 °C, due to intensity increasing of phosphate and carbonate bands and bone-like apatite morphologies, compared to other temperatures evaluated.