bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of sleep with food cravings and loss‐of‐control eating in youth: An ecological momentary assessment study
Authors: Parker Megan N. , LeMay‐Russell Sarah , Schvey Natasha A. , Crosby Ross D. , Ramirez Eliana , Kelly Nichole R. , Shank Lisa M. , Byrne Meghan E. , Engel Scott G. , Swanson Taylor N. , Djan Kweku G. , Kwarteng Esther A. , Faulkner Loie M. , Zenno Anna , Brady Sheila M. , Yanovski Susan Z. , Tanofsky‐Kraff Marian , Yanovski Jack A.
Published: September 2021

Background

Inconsistent sleep patterns may promote excess weight gain by increasing food cravings and loss‐of‐control (LOC)‐eating; however, these relationships have not been elucidated in youth.

Objective

We tested whether sleep duration and timing were associated with food cravings and LOC‐eating.

Method

For 14 days, youths wore actigraphy monitors to assess sleep and reported severity of food cravings and LOC‐eating using ecological momentary assessment. Generalized linear mixed models tested the associations between weekly and nightly shifts in facets of sleep (i.e., duration, onset, midpoint, and waketime) and next‐day food cravings and LOC‐eating. Models were re‐run adjusting for relevant covariates (e.g., age, sex, adiposity).

Results

Among 48 youths (12.88 ± 2.69 years, 68.8% female, 33.3% with overweight/obesity), neither weekly nor nightly facets of sleep were significantly associated with food cravings (ps = 0.08–0.93). Youths with shorter weekly sleep duration (est. ß = −0.31, p = 0.004), earlier weekly midpoints (est. ß = −0.47, p = 0.010) and later weekly waketimes (est. ß = 0.49, p = 0.010) reported greater LOC‐eating severity; findings persisted in adjusted models.

Conclusions

In youth, weekly, but not nightly, shifts in multiple facets of sleep were associated with LOC‐eating severity; associations were not significant for food cravings. Sleep should be assessed as a potentially modifiable target in paediatric LOC‐eating and obesity prevention programs.
Patterns and rates of confirmed transfer of care of patients with juvenile idiopathic arthritis at a tertiary paediatric rheumatology centre
Authors: Tan Joachim , Tiller Georgina , Gowdie Peter , Cox Angela , Munro Jane , Allen Roger , Akikusa Jonathan
Published: September 2021

Background

Disease activity in juvenile idiopathic arthritis (JIA) commonly persists into adulthood. Transfer of JIA patients to adult healthcare services can be challenging, with prior studies showing poor rates of success.

Aims

This audit sought to examine characteristics of patients undergoing transfer of care within the rheumatology unit at the Royal Children's Hospital in Melbourne, with the aim of identifying areas for improvement. Specifically, we sought to determine the rate at which confirmation of established care with an adult service (confirmed transfer of care) was documented in the patient chart.

Methods

Patients with a diagnosis of JIA who turned 18 years of age between 2012 and 2019 were identified. A chart review was undertaken to collect relevant data.

Results

One hundred and seventy‐seven patients were identified. In all, 64% (114/177) were referred for adult care. The commonest JIA subtypes referred were seronegative polyarticular (35/114; 30.7%) and oligoarticular JIA (22/114; 19.3%). Documentation of confirmed transfer of care occurred in 62.3% (71/114), with correspondence received from adult services in 49.1% (56/114). There was no difference in rate of return correspondence from public versus private providers (45% vs 53.8%; P = 0.38). The use of ‘backstop appointments’ was more likely in those with confirmed transfer of care (66% vs 30%; P = 0.0002).

Conclusions

Lack of confirmed transfer of care for JIA patients is common and carries a risk of suboptimal outcomes. Strategies to improve communication with adult services, the routine use of ‘backstop’ appointments and vigilance regarding potential loss to follow up at the time of transfer would minimise this risk.
An efficient far‐red emission Sr2InSbO6:Mn4+, M (M = Li+, Na+, and K+) phosphors for plant cultivation LEDs
Authors: Xie Yan , Geng Xue , Wang Yuan , Guo Jiang , Lu Yuhui , Lv Qiuyi , Ma Zhijiang , zhang Dan , Zhao Jin , Deng Bin , Yu Ruijin
Published: September 2021

High‐efficiency and far‐red light phosphors based on Mn4+‐doped inorganic luminescence materials are beneficial to plant cultivation. However, Mn4+‐doped oxide phosphors have a common problem of low quantum efficiency. Alkali metal ion codoping can effectively improve the luminescence properties of Mn4+‐activated oxide phosphors. Herein, a series of Sr2InSbO6:Mn4+, M (SISO:Mn4+, M) (M = Li+, Na+, and K+) far‐red‐emitting phosphors codoped alkali metal ions were first synthesized. Density functional theory calculation indicated that SISO is a kind of indirect bandgap material with a bandgap of ∼1.60 eV. The SISO:Mn4+ samples showed a far‐red light at 698 nm upon 365 nm, which perfectly matched the absorption spectrum of the far‐red‐phytochrome (Pfr) of plants. The doping concentration of the SISO:Mn4+ samples was optimized to be 0.006 mol. The concentration quenching mechanism was defined as dipole–dipole interaction by combining the Dexter theory and the Inokuti–Hirayama model. Optimizing the sintering temperature and codoped with alkali metal ions (Li+, Na+, and K+) could improve the luminescent intensity of SISO:Mn4+. The optimum sintering temperature was 1300°C. The internal quantum efficiencies of SISO:0.006Mn4+ and SISO:0.006Mn4+, 0.006Li+ phosphors are 22.67% and 60.56%, respectively. SISO:Mn4+, Li+ phosphors‐based plant growth light‐emitting diodes (LEDs) demonstrate excellent optical stability and long lifetime. Thus, these phosphors are promising candidates for plant cultivation LEDs.
Capital Allocation and Corporate Strategy: An Examination of the Oil & Gas Majors
Authors: Inkpen Andrew , Moffett Michael H. , Ramaswamy Kannan
Published: September 2021

The authors present the findings of their study of the capital spending and cash distributions of the five largest publicly traded integrated oil and gas companies (ExxonMobil, Chevron, BP, Shell, and Total) over the past two decades. Deploying capital in the execution of strategy and achieving the proper balance between reinvesting in the business and returning capital to shareholders is particularly challenging in one of the world's most capital intensive industries. The practices of the five companies differed markedly despite similarities in business lines and international operations.

The study explores the different periods of industry growth and performance between 1998 and 2018, when the industry went through an extended period of stable growth (1998‐2008), followed by an extended period of stagnant growth in reserves and production despite extensive spending on capital expenditures. A key finding is that despite spending more than $1.8 trillion over the 20‐year period, the five supermajors were unable to expand production. The authors found that what little growth did occur was the result of acquisitions.

Capital allocation decisions by the five majors differed markedly in their cash returns to shareholders. Although all five firms maintained their commitments to shareholder dividends, ExxonMobil deployed massive and continued allocations of capital to share repurchases. Both dividends and share repurchases had mixed results in supporting corporate share prices.

The authors attribute the difficulty the majors had in generating profitable growth partly to the inherent challenges of a depleting industry and partly to the selection of capital investments—their timing and cycle length. The historical experience of the majors in dealing with large oil price cycles drove all five to maintain capital expenditures in the post‐2008 financial crisis period. Only when oil prices plunged in 2014 did the majors conclude that the decline was a transformative shift requiring a reconsideration of capital allocation and capital expenditures. The study notes that acquisitions, particularly ExxonMobil's acquisition of XTO, depressed market values despite some of the highest share repurchasing levels across U.S. industry.
Oestradiol promotes the intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via Notch signalling pathway
Authors: Dong Chen , Zhang Ben‐ping , Ying Yan‐Qin , Hou Ling , Wu Wei , Wei Hong , Luo Xiao‐ping
Published: September 2021

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway‐associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol‐mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.
Attention to online sales: The role of brand image concerns
Authors: Dertwinkel‐Kalt Markus , Köster Mats
Published: September 2021

We provide a novel intuition for why manufacturers restrict their retailers' ability to resell brand products online. Our approach builds on models of salience‐driven attention according to which price disparities across distribution channels guide a consumer's attention toward prices and lower her appreciation for quality. Absent vertical restraints, therefore, one of two salience distortions—a quality or a participation distortion—can arise in equilibrium. We show that, by ruling out both distortions, vertical restraints on online sales can be socially desirable but can also hurt consumers through higher retail prices. We thereby identify a novel trade‐off between efficiency and consumer surplus.
Genetic diversification of the Kanehira bitterling Acheilognathus rhombeus inferred from mitochondrial DNA, with comments on the phylogenetic relationship with its sister species Acheilognathus barbatulus
Authors: Miyake Takuya , Nakajima Jun , Umemura Keitaro , Onikura Norio , Ueda Takayoshi , Smith Carl , Kawamura Kouichi
Published: September 2021

The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn‐spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life‐history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55–0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (<0.10 Ma) was suggested in many of the lineages, which accords with other freshwater fishes. Biogeographically the ancestral A. rhombeus/A. barbatulus was likely to have repeatedly colonized Japan from the continent through land bridges in the late Pliocene and the early Pleistocene. However, the close genetic relationship between Japanese A. rhombeus and A. barbatulus suggests another possibility, with the second colonization occurring in reverse, from Japan to China. The small genetic distance between them indicates that the colonization occurred later than colonization events of other freshwater fishes, including other bitterling species.
Aortic valve replacement among patients with Alzheimer's disease and related dementias
Authors: Hollenbeck Brent K. , Dunn Rodney L. , Sukul Devraj , Modi Parth K. , Nallamothu Brahmajee K. , Sen Ananda , Bynum Julie P.
Published: September 2021

Background

Transcatheter aortic valve replacement (TAVR) has made palliation from aortic stenosis more broadly available to populations previously thought to be too high risk for surgery, such as those with Alzheimer's disease and related dementias (ADRD); however, its safety and effectiveness in this context are uncertain.

Methods

We performed a retrospective cohort study of national Medicare beneficiaries, aged 66 and older with Parts A and B, between 2010 and 2016. Patients undergoing AVR were identified, and follow‐up was available through 2017. Multivariable regression was used to measure the independent association between having a diagnosis of ADRD at the time of AVR, stratified by TAVR and surgery, and outcomes (mortality and Medicare institutional days at 1 year after AVR).

Results

The average rate of increase in AVR per year was 17.5 cases per 100,000 ADRD and 8.4 per 100,000 non‐ADRD beneficiaries, largely driven by more rapid adoption of TAVR. Adjusted mortality following AVR declined significantly between those treated in 2010 and 2016, from 13.5% (95% CI 10.2%–17.7%) to 6.3% (95% CI 5.2%–7.6%) and from 13.7% (95% CI 12.7%–14.7%) to 6.3% (95% CI 5.8%–6.9%) in those with and without ADRD, respectively. The sharpest decline was noted for patients undergoing TAVR between 2011 and 2016, with adjusted mortality declining from 19.9% (95% CI 11.2%–32.8%) to 5.2% (95% CI 4.1%–6.5%) and from 12.2% (95% CI 9.3%–15.8%) to 5.0% (95% CI 4.4%–5.6%) in patients with and without ADRD, respectively. Similar declines were evident for Medicare institutional days in the year after AVR in both patient groups.

Conclusions

Rates of AVR in those with ADRD increased during the past decade largely driven by the diffusion of TAVR. The use of TAVR in this vulnerable population did not come at the expense of increasing Medicare institutional days or mortality at 1‐year.
Is silence golden… In this context, not so much
Authors: Lyles Kenneth W. , Riska Kristal M. , Smith Sherri L.
Published: September 2021

This editorial comments on the article by Curhan et al
Outcomes using direct‐acting antiviral hepatitis‐C treatment in older versus younger Veterans
Authors: Blanquicett Carmelo J. , Raavi Tapasya , Mirk Anna , Johnson Theodore M. , Jaglal Michael , Cartwright Emily J.
Published: September 2021

Background

Historically, older adults have been excluded from trials evaluating hepatitis C virus (HCV) treatment, in part, due to the adverse effects associated with previous regimens. Veterans are at high risk of HCV infection. Ledipasvir/sofosbuvir (LED/SOF) is a once daily antiviral regimen with demonstrated efficacy and tolerability among the younger population. We examined the tolerability and effectiveness of LED/SOF in Veterans age ≥65 years versus those <65 years who were treated at the Atlanta VA Health Care System (AVAHCS).

Methods

Using the VA Clinical Case Registry, all persons who filled a LED/SOF prescription at the AVAHCS from January 1, 2015, through March 31, 2016, were identified. The electronic medical records were reviewed to identify basic demographic information: comorbidities; polypharmacy; and outcomes. Sustained virologic response (SVR) was defined as an undetectable HCV RNA, at least 12 weeks after completing treatment. Descriptive statistics were employed using SAS v9.2.

Results

We identified 345 Veterans who filled LED/SOF during the study period; 94 were excluded due to exposure to ribavirin and IFN containing regimens; 97 (38.6%) were ≥65 years. Veterans were predominantly black (57%) and male (97%). Cancer was more prevalent among older Veterans (p = 0.047) as was polypharmacy (p = 0.001). Treatment completion rates between older and younger Veterans were not significantly different (99 vs. 95%, respectively; p = 0.16), but significantly more older Veterans achieved SVR (98 vs. 91%; p = 0.03).

Conclusions

LED/SOF was a well‐tolerated and effective regimen in an older Veteran population despite their multiple comorbidities and polypharmacy presence.
Association between angiotensin‐converting enzyme gene insertion deletion polymorphism and androgenetic alopecia susceptibility among Egyptian patients: A preliminary case‐controlled study
Authors: Mustafa Amany Ibrahim , Ibrahim Samah Ezzat , Gohary Yasser Mostafa , Al‐Husseini Naglaa Fathy , Fawzy Eman , El‐Shimi Ola Samir
Published: September 2021

Background

Androgenetic alopecia (AGA) is a prevalent condition with a complex etiopathogenesis. Angiotensin‐converting enzyme (ACE) gene located on the chromosome 17q23 contains an insertion (I) and deletion (D) polymorphism in the intron 16. This gene polymorphism plays a role in multiple inflammatory disorders. However, there are no studies investigating its association with AGA susceptibility.

Objectives

In this work, we aimed at exploring the association of ACE gene I/D polymorphism in AGA susceptibility in a group of Egyptian patients.

Methods

This study included 100 AGA patients, and 100 apparently healthy controls. The ACE gene I/D polymorphism was analyzed by polymerase chain reaction.

Results

The DD, ID genotypes, and D allele showed higher frequent distribution among studied AGA patients than controls (p < 0.05 each). Positive family history and ACE gene I/D polymorphism were considered AGA susceptibility predictors in both uni‐ and multivariable analyses [p < 0.05 each (OR (95% CI)] on applying logistic regression analysis for risk factors prediction.

Conclusions

This study highlights the possible contribution of the suspected genetic polymorphism as a susceptibility indicator for AGA development in the examined group of patients.
Zinc and iron adequacy and relative importance of zinc/iron storage and intakes among breastfed infants
Authors: Dumrongwongsiri Oraporn , Winichagoon Pattanee , Chongviriyaphan Nalinee , Suthutvoravut Umaporn , Grote Veit , Koletzko Berthold
Published: September 2021

Neonatal nutrient storage and supplies from breast milk contribute to nutrient status and growth of infants during their early life. This study investigated the adequacy of zinc and iron intakes among breastfed infants during the first 4 months and determined the relative importance of zinc/iron storage versus nutrient intakes with infant's biochemical status and growth. A longitudinal study followed lactating women and their breastfed infants from birth to 4 months postpartum. Cord zinc and ferritin concentrations, as indicators of nutrient storages, were determined. Zinc and iron intakes from breast milk were determined by measurement of breast milk volume together with milk zinc and iron concentrations at 2 and 4 months postpartum. Inadequacy of nutrient intakes was determined using average requirement (AR) which were 1.6 and 0.24 mg/day for zinc and iron respectively. Infant's serum zinc and ferritin were determined at 4 months of age. The data were collected from 64 and 56 participants at 2 months and 4 months postpartum. Inadequate zinc intake was found in 14.5 and 40% of infants at 2 and 4 months old, respectively. The prevalence of biochemical zinc and iron deficiency in infants were 76 and 11%, respectively. Iron endowment was significantly associated with serum ferritin at 4 months. The cumulative zinc intake was positively associated with weight gain and weight‐for‐length Z‐score, but not length. This study provides quantitative data on zinc and iron intakes, and demonstrates the relative importance of nutrient storage versus intakes on biochemical status and growth of breastfed infants.
Integrating Praxis Through the Research Process: Caregivers for Older Americans During the COVID‐19 Pandemic
Authors: Freidus Andrea , Shenk Dena , Wolf Christin
Published: September 2021

While applied anthropological research is sometimes envisioned as a linear process, we present an alternative view based on our research with frontline workers providing long‐term care (LTC) for older adults during COVID‐19. We completed a rapid qualitative assessment in central North Carolina from May to November 2020. We conducted data analysis as we continued to collect data and implemented activities and interventions along the way. We report emerging findings that included the deleterious effects of isolation on older adults in both congregate and community‐based LTC, the value of creatively using technology as an avenue for communication and engagement, the importance of leadership and flexibility, as well as an abundance of mental health struggles LTC workers faced in caring for older adults during COVID‐19. We present how we were able to address these in a variety of ways during the inductive research process because of iterative analysis that occurred alongside continued data collection.
Strigolactones (SLs) modulate the plastochron by regulating KLUH (KLU) transcript abundance in Arabidopsis
Authors: Cornet Florent , Pillot Jean‐Paul , Le Bris Philippe , Pouvreau Jean‐Bernard , Arnaud Nicolas , de Saint Germain Alexandre , Rameau Catherine
Published: September 2021

The timing of leaf emergence at the shoot apical meristem, or plastochron, is highly regulated in plants. Among the genes known to regulate the plastochron in Arabidopsis (Arabidopsis thaliana), KLUH (KLU), orthologous to the rice (Oryza sativa) PLASTOCHRON1, encodes the cytochrome P450 CYP78A5, and is thought to act through generation of a still unknown mobile signal. As klu mutants display not only a short plastochron but also a branching phenotype reminiscent of strigolactone (SL) mutants, we investigated whether KLU/CYP78A5 is involved in SL biosynthesis.

We combined a genetic approach, a parasitic plant seed germination bioassay to test klu root exudates, and analysis of transcript abundances of SL‐biosynthesis genes in the Arabidopsis klu mutants.

We demonstrate that KLU is not involved in the SL‐biosynthesis pathway. Moreover, this work allowed us to uncover a new role for SL during Arabidopsis development in modulating plastochron via a KLU‐dependent pathway.

Globally our data reveal that KLU is required for plastochron‐specific SL responses, a first indication of crosstalk between SL and the KLU‐derived signal.
Extending human healthspan and longevity: a symposium report
Authors: DeVito Loren M. , Barzilai Nir , Cuervo Ana Maria , Niedernhofer Laura J. , Milman Sofiya , Levine Morgan , Promislow Daniel , Ferrucci Luigi , Kuchel George A. , Mannick Joan , Justice Jamie , Gonzales Mitzi M. , Kirkland James L. , Cohen Pinchas , Campisi Judith
Published: September 2021

For many years, it was believed that the aging process was inevitable and that age‐related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age‐related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof‐of‐concept studies, as well as early‐stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.
Desert and redistribution: Justice as a remedy for, and cause of, economic inequality
Authors: Bower‐Bir Jacob S.
Published: September 2021

Post‐positivist scholars have shown that justice motivates personal behavior and policymaking, but they have not adequately explained how such normative concerns exert their influence. I argue that justice is the rewarding of desert, and desert is an emergent social institution. As a social institution, community members have built‐in incentives to enforce and perpetuate communal understandings of desert though external sanctions and inculcation. As an evolutionary phenomenon, what constitutes upright, moral behavior will vary across communities and contexts, constraining individuals and policymakers as they address community issues. In an empirical test of my theory, I find that an individual's support for redistributive policies is driven by her (a) belief in desert's reward and (b) definition of economic deservingness. People tolerate grave inequalities if they think those inequalities are deserved. Indeed, if outcomes appear deserved, altering them constitutes an unjust act. Moreover, people who assign a significant role to personal responsibility in their definitions of economic desert oppose large‐scale redistribution policies because government intervention makes it harder for people to (by their definition) deserve their economic station. In short, people must perceive inequality as undeserved to motivate a policy response, and the means of combating inequality must not undermine desert.
Cabinet ministers and the use of agenda‐setting power: Evidence from cabinet ministers in Israel
Authors: Shpaizman Ilana
Published: September 2021

Cabinet ministers in parliamentary democracies have significant agenda‐setting power. However, not all ministers use it equally. This paper examines what affects the ministers' use of their agenda‐setting power. It explores this question based on the case of Israel, using three measures of agenda change and in‐depth interviews with former ministers. The paper finds that limited agenda capacity constrains the ministers' agenda‐setting power. However, the ministers themselves do not see this as a significant constraint and point at motivation instead. Ministers holding a portfolio that is salient to their party are not likely to change the agenda more. Ministers from small parties change the agenda less, and so do ministers in ministries where a significant proportion of services are provided by street level bureaucrats. Ministers in ministries that are seen as more salient change the agenda more. These findings are consequential for understanding policy responsiveness and proportionality in policy response.
A novel competition ELISA for the rapid quantification of SARS‐CoV‐2 neutralizing antibodies in convalescent plasma
Authors: Wouters Elise , Verbrugghe Caro , Devloo Rosalie , Debruyne Isabelle , De Clippel Dorien , Van Heddegem Leen , Van Asch Kristin , Van Gaver Véronique , Vanbrabant Miek , Muylaert An , Compernolle Veerle , Feys Hendrik B.
Published: September 2021

Background

COVID‐19 convalescent plasma (CCP) ideally contains high titers of (neutralizing) anti‐SARS‐CoV‐2 antibodies. Several scalable immunoassays for CCP selection have been developed. We designed an enzyme‐linked immunosorbent assay (ELISA) that measures neutralizing antibodies (of all isotypes) in plasma by determining the level of competition between CCP and a mouse neutralizing antibody for binding to the receptor binding domain (RBD) of SARS‐CoV‐2.

Methods

Plasma was collected from 72 convalescent individuals and inhibition of viral infection was determined by plaque reduction neutralization (PRNT50). The level of neutralizing antibodies was measured in the novel competition ELISA and in a commercially available ELISA that measures inhibition of recombinant ACE2 binding to immobilized RBD. These results were compared with a high throughput chemiluminescent microparticle immunoassay (CMIA).

Results

The results from both ELISAs were correlating, in particular for high titer CCP (PRNT50 ≥ 1:160) (Spearman r = .73, p < .001). Moderate correlation was found between the competition ELISA and CMIA (r = .57 for high titer and r = .62 for low titer CCP, p < .001). Receiver operator characteristic analysis showed that the competition ELISA selected CCP with a sensitivity and specificity of 61% and 100%, respectively. However, discrimination between low and high titer CCP had a lower resolution (sensitivity: 34% and specificity: 89%).

Conclusion

The competition ELISA screens for neutralizing antibodies in CCP by competition for just a single epitope. It exerts a sensitivity of 61% with no false identifications. These ELISA designs can be used for epitope mapping or for selection of CCP.
Validation of the Intuitive Exercise Scale in Patients With Eating Disorders
Authors: Voelker Dana K. , Galli Nick , Miyairi Maya , Reel Justine J. , James Karley
Published: September 2021

Unhealthy cognitive–emotional relationships with exercise can hinder positive treatment outcomes when left unaddressed. However, clinicians lack validated tools to monitor this aspect of treatment. This study examined the 14-item Intuitive Exercise Scale with 165 patients in the United States (Mage = 26.48 years) who were receiving treatment for an eating disorder. The original factor structure was inadequate for the current sample, and exploratory factor analysis generated three factors—emotional exercise, body intuition, and exercise variety. The three-factor solution yielded strong internal consistency and partial support for the scale’s validity. Furthermore, patients scored lowest in body intuition, confirming low awareness of bodily cues common in patients with eating disorders. This study informs how clinicians may integrate and monitor patients’ cognitive–emotional relationship with exercise as part of holistic and intuitive eating disorder treatment approaches.
The three-spin intermediate at the O–O cleavage and proton-pumping junction in heme–Cu oxidases
Authors: Jose Anex , Schaefer Andrew W. , Roveda Antonio C. , Transue Wesley J. , Choi Sylvia K. , Ding Ziqiao , Gennis Robert B. , Solomon Edward I.
Published: September 2021

Breaking down oxygen

Molecular oxygen (O
2
) is the terminal oxidant for respiration in mitochondria and many bacteria. Within membrane-bound heme–copper oxidases, a controlled, four-electron reduction of O
2
to water is coupled to pumping of protons across the membrane that can be used, among other outcomes, to generate adenosine triphosphate. Studying cytochrome
bo
3
ubiquinol oxidase, Jose
et al
. investigated the key P
M
intermediate, which forms after O–O bond cleavage and precedes proton pumping, using magnetic circular dichroism spectroscopy. The authors observed features demonstrating that P
M
is a three-spin system, which is consistent with a consensus model including an iron(IV)-oxo species, copper(II) ion, and tyrosyl radical. These results provide an important validation of the O–O cleavage mechanism and open the door to understanding the proton pumping step. —MAF
A P(V) platform for oligonucleotide synthesis
Authors: Huang Yazhong , Knouse Kyle W. , Qiu Shenjie , Hao Wei , Padial Natalia M. , Vantourout Julien C. , Zheng Bin , Mercer Stephen E. , Lopez-Ogalla Javier , Narayan Rohan , Olson Richard E. , Blackmond Donna G. , Eastgate Martin D. , Schmidt Michael A. , McDonald Ivar M. , Baran Phil S.
Published: September 2021

Platform for the synthesis of diverse oligos

DNA is primarily viewed as a carrier of information encoded in the sequence of bases, but the chemistry of the phosphodiester backbone is crucial to oligonucleotide stability and structure. Building on previous work in synthetic P(V) phosphorothioate coupling chemistry, Huang
et al
. developed two new reagents for making phosphorodithioate- and phosphate-based linkages (see the Perspective by Virta). The authors incorporated all of these reagents into a unified P(V)-based synthesis platform capable of running at high efficiency on a commercial automated solid-phase synthesizer. They demonstrate the flexibility of this system by producing oligonucleotides with all three linkage types in specific positions. Access to such precisely constructed molecules opens new approaches to therapeutic oligonucleotide design. —MAF
The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
Authors: Altae-Tran Han , Kannan Soumya , Demircioglu F. Esra , Oshiro Rachel , Nety Suchita P. , McKay Luke J. , Dlakić Mensur , Inskeep William P. , Makarova Kira S. , Macrae Rhiannon K. , Koonin Eugene V. , Zhang Feng
Published: September 2021

Tracing the origin of CRISPR-Cas

CRISPR-Cas systems have transformed genome editing and other biotechnologies; however, the broader origins and diversity of RNA-guided nucleases have largely remained unexplored. Altae-Tran
et al
. show that three distinct transposon-encoded proteins, IscB, IsrB, and TnpB, are naturally occurring, reprogrammable RNA-guided DNA nucleases (see the Perspective by Rousset and Sorek). In addition to identifying diverse guide-encoding mechanisms, the authors elucidate the evolutionary relationship between IsrB, IscB, and CRISPR-Cas9. Overall, these newly characterized systems, called OMEGA (for obligate mobile element–guided activity) systems, are found in all domains of life and may be harnessed for biotechnology development. —DJ
The keepers of the seas
The Blue Age
Gregg Easterbrook
PublicAffairs, 2021. 304 pp.
Authors: Smith Jason W.
Published: September 2021

As oceans warm, an author reveals the centrality of maritime activities in the modern world
Increased serotonin prevents compulsion in addiction
Authors: Miyazaki Katsuhiko , Miyazaki Kayoko W.
Published: September 2021

Extracellular serotonin decreases cocaine taking in mice
Convective hydration of the stratosphere
Authors: Smith Jessica B.
Published: September 2021

Cirrus plumes above superstorm anvils are visible manifestations of a hydraulic jump
In Science Journals
Authors: Ferrarelli Leslie K. , Norton Melissa , Stajic Jelena , Funk Michael A. , Lavine Marc S. , Grocholski Brent , Osborne Ian S. , Vignieri Sacha , Alderton Gemma , Jiang Di , Stern Peter , Smith H. Jesse , Williams Ifor
Published: September 2021

Highlights from the
Science
family of journals
A pandemic prevention moonshot
Authors: Cohen Jon
Published: September 2021

Biden plan would deliver new vaccines in 100 days
U.S. ups coronavirus surveillance
Authors: Wadman Meredith
Published: September 2021

Country has fewer blind spots as variant Mu draws attention, but sequencing challenges remain
Vultures face new toxic threat
Authors: Stokstad Erik
Published: September 2021

Concern mounts over veterinary drugs used to treat cattle
Draft Genome Sequence of Pseudoalteromonas sp. Strain JC3
Authors: Rosario Margaret E. , Camm Jacqueline , Cavanagh Damian , Rowley David C. , Nelson David R.
Published: September 2021

We report the draft genome sequence for
Pseudoalteromonas
sp. strain JC3, an isolate obtained from an aquaculture facility for whiteleg shrimp (
Litopenaeus vannamei
). The JC3 genome suggests multiple mechanisms for microbial interactions, including a type VI secretion system and potential for antibiotic production.
Chromosome-Level Genome Sequence of Aspergillus puulaauensis MK2, a Fungus Isolated from a Dead Hard Tick
Authors: Futagami Taiki , Mori Kazuki , Kadooka Chihiro , Niihara Hiroko , Tashiro Kosuke , Tamaki Hisanori , Tanaka Tetsuya
Published: September 2021

Aspergillus puulaauensis
strain MK2 was isolated from a dead hard tick (
Haemaphysalis longicornis
). Here, we determined the chromosome-level genome sequence of
A. puulaauensis
MK2.
Origin of alkali olivine basalts and hawaiites in the western Mexican arc: Evidence of rapid phenocryst growth and magma mixing during ascent along fractures
Authors: Mesa Juliana , Lange Rebecca A.
Published: September 2021

A detailed petrological study is presented to constrain the origin of a suite of alkali olivine basalt and hawaiite (>5 wt% MgO) lavas that were erupted in a rift zone within the western Mexican arc (Trans-Mexican Volcanic Belt), adjacent to the Sangangüey andesitic stratovolcano, together with more evolved lavas (mugearites and benmoreites; <5 wt% MgO). As previously documented in the literature, the Sangangüey mafic lavas are devoid of any arc geochemical signature, despite their location within an arc. In this study, a new olivine-melt thermometer/hygrometer, based on the partitioning behavior of Ni2+ and Mg2+, was applied to the Sangangüey basalts (SB). The results show that the high-MgO (>9 wt%) SB crystallized at higher temperatures and lower melt-water contents (0–1.3 wt%) compared to high-MgO arc basalts (≤5.7 wt% H2O) erupted in the west-central Mexican arc. The Sangangüey lavas with 5–8 wt% MgO display evidence of mixing between high-MgO alkali olivine basalts and low-MgO mugearites. It is proposed that the unique composition of the mugearites (i.e., low SiO2 contents and elevated FeO and TiO2 contents) is the result of partial melting of mafic lower crust driven by the influx of high-MgO intraplate basalts under relatively hot, dry, and reduced conditions. On the basis of crystal textures and compositional zoning patterns, it is shown that both phenocryst growth and magma mixing occurred rapidly, most likely during ascent along fractures, and not slowly during prolonged storage in a crustal magma chamber.
Iatrogenic intrathoracic encapsulated siliconoma from a ruptured breast implant
Authors: Chopra Christina Shree , Thistlethwaite Patricia , Herrera Fernando , Suliman Ahmed
Published: September 2021

Our patient was a 57-year-old woman with a history of bilateral retropectoral silicone breast augmentation and axillary hyperhidrosis who underwent a bilateral thoracic sympathectomy via video-assisted thoracoscopic surgery by a surgeon at an outside hospital approximately 20 years ago. The left side required an open thoracotomy. Shortly after the surgery, she developed a left-sided Baker 4 capsular contracture and the left implant was noted to be ruptured. Both implants were exchanged. Several years later the patient began to experience progressive fatigue. Work-up revealed a left lung nodule and she underwent a biopsy that confirmed silicone granulomas. It was hypothesised that at the time of her initial thoracotomy the implant was violated resulting in silicone spillage into the thoracic cavity. The patient was referred to our institution for advanced management of her intrathoracic silicosis. The patient underwent bilateral removal of her silicone implants, total capsulectomy and needle-localised removal of her left thoracic silicone masses. She had an uneventful postoperative course with resolution of her fatigue.
Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study
Authors: Gyawali Bishal , Rome Benjamin N , Kesselheim Aaron S
Published: September 2021

Objectives

To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines.

Design

Retrospective observational study.

Setting

FDA and National Comprehensive Cancer Network (NCCN) reports.

Included drugs

Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials.

Main outcome measures

Regulatory outcomes, including withdrawal, conversion to regular approval, and no action.

Results

18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked.

Conclusion

Cancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval.
Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden
Authors: Nilsson Sommar Johan , Andersson Eva M , Andersson Niklas , Sallsten Gerd , Stockfelt Leonard , Ljungman Petter LS , Segersson David , Eneroth Kristina , Gidhagen Lars , Molnar Peter , Wennberg Patrik , Rosengren Annika , Rizzuto Debora , Leander Karin , Lager Anton , Magnusson Patrik KE , Johansson Christer , Barregard Lars , Bellander Tom , Pershagen Göran , Forsberg Bertil
Published: September 2021

Objectives

To estimate concentration–response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels.

Setting

Cohorts from Gothenburg, Stockholm and Umeå, Sweden.

Design

High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), and BC, at individual addresses during each year of follow-up, 1990–2011. Moving averages were calculated for the time windows 1–5 years (lag1–5) and 6–10 years (lag6–10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort.

Participants

During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up.

Results

Both PM10 (range: 6.3–41.9 µg/m3) and BC (range: 0.2–6.8 µg/m3) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 µg/m3and 1 µg/m3of lag1-5 exposure, respectively. For PM2.5 (range: 4.0–22.4 µg/m3), the estimated increase was 13% per 5 µg/m3, but less precise (95% CI −9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality.

Conclusion

The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.
External validation of the 4C Mortality Score for patients with COVID-19 and pre-existing cardiovascular diseases/risk factors
Authors: Kuroda Shunsuke , Matsumoto Shingo , Sano Takahide , Kitai Takeshi , Yonetsu Taishi , Kohsaka Shun , Torii Sho , Kishi Takuya , Komuro Issei , Hirata Ken-ichi , Node Koichi , Matsue Yuya
Published: September 2021

Objectives

Predictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data.

Design

Retrospective cohort study.

Setting and participants

Hospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan.

Main outcome measures

Two different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality.

Results

The risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome.

Conclusions

The 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources.

Trial registration numberUMIN000040598.
A varying dark energy effective speed of sound parameter in the phantom Universe
Authors: Albarran Imanol , Bouhmadi-López Mariam , Marto João
Published: September 2021

We analyse the phenomenological effects of a varying Dark Energy (DE) effective speed of sound parameter,$$c^{2}_{\text {sd}}$$csd2, on the cosmological perturbations of three phantom DE models. Each of these models induce a particular abrupt future event known as Big Rip (BR), Little Rip (LR), and Little Sibling of the Big Rip (LSBR). In this class of abrupt events, all the bound structures in the Universe would be ripped apart at a finite cosmic time. We compute the evolution of the perturbations,$$f\sigma _{8}$$fσ8growth rate and forecast the current matter power spectrum. We vary the$$c^{2}_{\text {sd}}$$csd2parameter in the interval [0, 1] and compute the relative deviation with respect$$c^{2}_{\text {sd}}=1$$csd2=1. In addition, we analyse the effect of gravitational potential sign flip that occurs at very large scale factors as compared with the current one.