bluuebunny/crossref_metadata_2025 huggingface dataset:
The Alignment of Real-World Evidence and Digital Health: Realising the Opportunity
Authors: Khosla Sajan , Tepie Maurille Feudjo , Nagy Mark J. , Kafatos George , Seewald Michael , Marchese Stephanie , Liwing Johan
Published: April 2021

In the new era of healthcare digitalization, there is a golden opportunity in the overlap between digital health and Real-World Evidence (RWE). In this commentary, we define RWE and digital health and investigate their intersection. We describe the stages in the RWE value chain critical to the evidence generation process, how these stages change with new digital technologies and the opportunities and challenges that arise from how these stages evolve—including their application for stakeholders such as patients, physicians and regulators. We also discuss the current published guidelines and frameworks regarding digital health. We categorise these publications in terms of their clarity as “Extensive”, “Intermediate” or “Basic” and according to whether they encompass all levels of digital health or are more focussed in their guidance. Finally, we provide recommendations to increase synergy between RWE and digital health.
Risk-Based Monitoring in Clinical Trials: Past, Present, and Future
Authors: Barnes Brian , Stansbury Nicole , Brown Debby , Garson Lauren , Gerard Geoff , Piccoli Nickolas , Jendrasek Debra , May Nick , Castillo Vanesa , Adelfio Anina , Ramirez Nycole , McSweeney Andrea , Berlien Ruth , Butler Paula Jo
Published: April 2021

Risk-based monitoring (RBM) is a powerful tool for efficiently ensuring patient safety and data integrity in a clinical trial, enhancing overall trial quality. To better understand the state of RBM implementation across the clinical trial industry, the Association of Clinical Research Organizations (ACRO) conducted a landscape survey among its member companies across 6,513 clinical trials ongoing at the end of 2019. Of these trials, 22% included at least 1 of the 5 RBM components: key risk indicators (KRIs), centralized monitoring, off-site/remote-site monitoring, reduced source data verification (SDV), and reduced source document review (SDR). The implementation rates for the individual RBM components ranged 8%–19%, with the most frequently implemented component being centralized monitoring and the least frequently implemented being reduced SDR. When the COVID-19 pandemic emerged in early 2020, additional data were collected to assess its impact on trial monitoring, focusing specifically on trials switching from on-site monitoring to off-site/remote-site monitoring. These mid-pandemic data show that the vast majority of monitoring visits were on-site in February 2020, but an even higher percentage were off-site in April, corresponding with the first peak of the pandemic. Despite this shift, similar numbers of non-COVID-related protocol deviations were detected from February through June, suggesting little or no reduction in monitoring effectiveness. The pre- and mid-pandemic data provide two very different snapshots of RBM implementation, but both support the need to promote adoption of this approach while also highlighting an opportunity to capitalize on the recent shift toward greater RBM uptake in a post-pandemic environment.
Understanding Development
Authors: Minelli Alessandro
Published: April 2021

Developmental biology is seemingly well understood, with development widely accepted as being a series of programmed changes through which an egg turns into an adult organism, or a seed matures into a plant. However, the picture is much more complex than that: is it all genetically controlled or does environment have an influence? Is the final adult stage the target of development and everything else just a build-up to that point? Are developmental strategies the same in plants as in animals? How do we consider development in single-celled organisms? In this concise, engaging volume, Alessandro Minelli, a leading developmental biologist, addresses these key questions. Using familiar examples and easy-to-follow arguments, he offers fresh alternatives to a number of preconceptions and stereotypes, awakening the reader to the disparity of developmental phenomena across all main branches of the tree of life.
THE MCKINSEY–TARSKI THEOREM FOR LOCALLY COMPACT ORDERED SPACES
Authors: BEZHANISHVILI GURAM , BEZHANISHVILI NICK , LUCERO-BRYAN JOEL , VAN MILL JAN
Published: April 2021

We prove that the modal logic of a crowded locally compact generalized ordered space is$\textsf {S4}$. This provides a version of the McKinsey–Tarski theorem for generalized ordered spaces. We then utilize this theorem to axiomatize the modal logic of an arbitrary locally compact generalized ordered space.
Ecohydrological controls on apparent rates of peat carbon accumulation in a boreal bog record from the Hudson Bay Lowlands, northern Ontario, Canada
Authors: Davies Marissa A. , Blewett Jerome , Naafs B. David A. , Finkelstein Sarah A.
Published: April 2021

A multiproxy Holocene record from a bog in the Hudson Bay Lowlands, northern Ontario, Canada, was used to evaluate how ecohydrology relates to carbon accumulation. The study site is located at a somewhat higher elevation and on coarser grained deposits than the surrounding peatlands. This promotes better drainage and thus a slower rate of carbon accumulation relative to sites with similar initiation age. The rate of peat vertical accretion was initially low as the site transitioned from a marsh to a rich fen. These lower rates took place during the warmer temperatures of the Holocene thermal maximum, confirming the importance of hydrological controls limiting peat accretion at the local scale. Testate amoebae, pollen, and plant macrofossils indicate a transition to a poor fen and then a bog during the late Holocene, as the carbon accumulation rate and reconstructed water table depth increased. The bacterial membrane lipid biomarker indices used to infer paleotemperature show a summer temperature bias and appear sensitive to changes in peat type. The bacterial membrane lipid biomarker pH proxy indicates a rich to a poor fen and a subsequent fen to bog transition, which are supported by pollen, macrofossil, and testate amoeba records.
Myo-inositol improves growth performance and regulates lipid metabolism of juvenile Chinese mitten crab (Eriocheir sinensis) fed different percentage of lipid
Authors: Bu Xianyong , Wang Xiaodan , Lin Zhideng , Wang Chunling , Li Lingyu , Liu Shubin , Shi Qingchao , Qin Jian G. , Chen Liqiao
Published: April 2021

This study evaluated the effects of dietary myo-inositol (MI) on growth performance, antioxidant status and lipid metabolism of juvenile Chinese mitten crab (Eriocheir sinensis) fed different percentage of lipid. Crabs (4·58 (sem 0·05) g) were fed four diets including a normal lipid diet (N, containing 7 % lipid and 0 mg/kg MI), N with MI supplementation (N + MI, containing 7 % lipid and 1600 mg/kg MI), a high lipid diet (H, containing 13 % lipid and 0 mg/kg MI) and H with MI supplementation (H + MI, containing 13 % lipid and 1600 mg/kg MI) for 8 weeks. The H + MI group showed higher weight gain and specific growth rate than those in the H group. The dietary MI could improve the lipid accumulations in the whole body, hepatopancreas and muscle as a result of feeding on the high dietary lipid (13 %) in crabs. Besides, the crabs fed the H + MI diets increased the activities of antioxidant enzymes but reduced the malondialdehyde content in hepatopancreas compared with those fed the H diets. Moreover, dietary MI enhanced the expression of genes involved in lipid oxidation and exportation, yet reduced lipid absorption and synthesis genes expression in the hepatopancreas of crabs fed the H diet, which might be related to the activation of inositol 1,4,5-trisphosphate receptor (IP3R)/calmodulin-dependent protein kinase kinase-β (CaMKKβ)/adenosine 5’-monophosphate-activated protein kinase (AMPK) signalling pathway. This study demonstrates that MI could increase lipid utilisation and reduce lipid deposition in the hepatopancreas of E. sinensis fed a high lipid diet through IP3R/CaMKKβ/AMPK activation. This work provides new insights into the function of MI in the diet of crustaceans.
Genetic variability in cotton germplasm: predicting the agro physiological markers for high-temperature tolerance
Authors: Farooq Amjad , Shakeel Amir , Chattha Waqas Shafqat , Khan Tariq Manzoor , Azhar Muhammad Tehseen , Saeed Asif
Published: April 2021

High temperature negatively affects cotton production worldwide. In Pakistan, cotton crop faces high temperature at peak flowering during June–July, which is a major reason for yield losses. The present study was conducted to find some agro-physiological markers for high-temperature tolerance. Fifty cotton genotypes were raised under normal sown (high-temperature stress) and late sown (optimum temperature) conditions for 2 years. Data were recorded for relative cell injury percentage (RCI), chlorophyll content (CC), canopy temperature (CT), boll retention percentage (BR), bolls per plant (BP), boll weight (BW), hundred seed weight (HSW), sympodial branches per plant (SBP), plant height (PH) and seed cotton yield (SCY). A large amount of variability was found among cotton genotypes as proved by descriptive statistics. Stable genotypes were selected based on higher SCY and yield components (BP, BW, HSW, SBP, PH and SCY) performance along with less RCI%, high CC and low CT. The results of heatmap analysis showed that the six cotton genotypes viz., FH-Noor, FH-Lalazar, FH-458, FH-466, NIAB-545 and NIAB-878 performed better under high-temperature stress. These selected genotypes can be a source for breeding high-temperature tolerance. Furthermore, the results from correlation analysis confirmed that the traits such as RCI%, CC and CT can be considered as early selection criteria due to their positive association with SCY. Whilst some other parameters such as BP, BW, BR, SBP and PH might be used as direct selection indices for SCY under high-temperature stress.
Payton v. Abbott Laboratories: An Analysis of the Massachusetts
DES Class Action Suit
Authors: Silbersweig Susan E.
Published: April 2021

In Payton v. Abbott Laboratories, U.S.
District Court Judge Walter J. Skinner recently granted class certification
to an action brought by twentyseven Massachusetts women against major
manufacturers of DES. This is the first case in which a judge has
interpreted the requirements of Rule 23 of the Federal Rules of Civil
Procedure to allow women exposed in utero to DES
to sue as a class to determine liability for their injuries.

This Note reviews the Payton certification in
light of prior class action decisions involving DES and other types of
claims, and of legal commentary on Rule 23. This Note contends that Judge
Skinner’s application of the Rule 23 requirements in
Payton was procedurally correct, and
recommends the class action device as an effective method for litigating
such controversies. Finally, this Note analyzes the implications of this
landmark ruling for plaintiffs seeking class certification in DES suits and
in suits presenting analogous factual situations.
Tax Policy and Health Maintenance Organizations: The Case for a Section
501(c)(3) Tax Exemption
Authors: White Anne J.
Published: April 2021

The Internal Revenue Service typically grants health maintenance
organizations (HMOs) an I.R.C. section 501(c)(4) exemption from federal
income taxation. If these prepayment group medical providers were classified
as section 501 (c) (3) tax exempt organizations, however, they would receive
many additional advantages including increases in private funding and
decreases in material and operating costs.

This Note contends that most nonprofit HMOs—whether or not they have
qualified under the federal HMO Act—should be granted 501(c)(3) status
because they conform with all the specific requisites and general
theoretical justifications of a “charitable purpose” tax exempt
organization. Specifically, HMOs serve a tax exempt purpose by providing
health care, by benefiting the community as a whole, and relieving the
government of some of its public health burdens. HMOs comply with further
requirements of section 501 (c)(3) and its accompanying I.R.C. regulations
by serving a broad membership while avoiding insider control or commercial
dealings. Therefore, if an organization is a nonprofit prepayment group
practice health provider that serves a broad community and provides health
benefits without insider control, it should receive a 501 (c)(3) tax
exemption.
Vitek v. Jones: Transfer of Prisoners to Mental Institutions
Authors: Gottlieb Nancy R.
Published: April 2021

In Vitek v. Jones, the United States Supreme Court interpreted the due process clause as requiring that certain procedures be followed before transferring prisoners to mental institutions. This Note analyzes the Court's reasons for concluding that the existing transfer procedures embodied in the state's commitment statutes infringed on the prisoner's liberty interests and, therefore, were constitutionally inadequate. It finds that not only was one of the grounds used by the Court to find a constitutionally protected liberty inappropriate, but the calculus that the Court employed in mandating additional procedures was incorrect. This Note suggests alternative methods of holding the statutes unconstitutional, methods that would not lead to markedly different procedures for committing prisoners and civilians. Finally, die Note examines the procedures that the Court actually prescribed and discusses their implementation.
“Reasonable Cost” Reimbursement for Inpatient Hospital Services Under Medicare and Medicaid: The Emergence of Public Control
Authors: Weiner Stephen M.
Published: April 2021

In 1965 Congress, through amendments to the Social Security Act, established the Medicare and Medicaid programs and mandated that hospitals participating in those programs be reimbursed for the “reasonable cost” of providing inpatient services to Medicare and Medicaid patients. In this Article, the Chairman of the Massachusetts Rate Setting Commission contends that HEW—which, like Congress, was anxious to stimulate the voluntary participation of hospitals in the Medicare and Medicaid programs—interpreted “reasonable cost” with excessive liberality toward participating hospitals and created a fiscally burdensome and inflationary reimbursement system lacking principles of efficiency and planning. The author then describes a series of attempts—varying in scope and success—to reformulate “reasonable cost,” as applied to Medicare and Medicaid reimbursement, in a manner more consistent with the author's concept of sound public policy. The culmination of these attempts to date, he states, was Public Law 92-603 (Social Security Amendments of 1972), which introduced to the reimbursement system the concepts of (1) tough evaluation of the reasonableness of hospital costs, with emphasis on efficiency, utilization, and planning; (2) shifting de facto power over reimbursement rates away from the hospitals and into the hands of the agencies that purchase their services; and (3) increased public scrutiny of hospital operations. The author contends that this law, and the philosophy which underlies it, represents a healthy balancing of the needs of hospitals and the needs of the public; that the trend toward cost control and public control which the law embodies has been substantially furthered in those states which have statutorily established hospital budget or charge review programs; and that such trend will continue and profoundly affect any national health insurance plan enacted in the future.
The “Brave New Baby” and the Law: Fashioning Remedies for the Victims of In Vitro Fertilization
Authors: Cohen Mark E.
Published: April 2021

The birth of the world's first “test-tube baby,” a child conceived by in vitro fertilization (IVF), raises serious medical, ethical, and legal problems. This Note explores the present controversy over the use of IVF and advocates federal regulation of the technique. Furthermore, this Note argues that, in order to deter unduly hazardous use of IVF and to compensate its victims, an experimenter should be subject to civil liability for either negligent, or willful and nonconsensual, destruction of an IVF conceptus, and held strictly liable when an IVF child is born with severe defects that are attributable to the use of the technique.
Age Discrimination in Retirement: In Search of an Alternative
Authors: Rowland Adam Bruce
Published: April 2021

American employers have traditionally relied on age as the criterion for mandatory retirement. Yet advances in medicine indicate the inadequacy of age as a measure of job competence and suggest the potential for a more reliable measure. With current social and economic conditions pressing many employees to seek to work beyond mandatory retirement ages set by their employers, transition to more reliable measures has become a vital matter.

This Note explores the potential for implementing medically-based alternatives to the age proxy. It initially addresses problems of medical feasibility and economic practicality, and considers how the divergent interests of employees and employers can be accomodated. The balance of the Note examines the present roles of Congress, agencies, and courts in facilitating age-blind mandatory retirement policy. It suggests the need for reform of the federal Age Discrimination in Employment Act and recommends a more effective distribution of roles among governmental institutions.
The Massachusetts Malpractice Plaintiff's New Hurdles: The Expanding Role of the Medical Malpractice Screening Tribunal
Authors: Ossyra James D.
Published: April 2021

The medical malpractice crisis of the early and mid-1970s prompted many states to enact legislation creating medical malpractice screening tribunals. This legislation often failed to define clearly the role and jurisdiction of the tribunals. The lack of statutory definition is particularly apparent where a claim before a tribunal raises primarily nonmedical issues. The changing doctrines of hospital liability, involving both medical and nonmedical determinations, illuminate this jurisdictional difficulty.

This Note examines the Massachusetts courts' attempts to define the tribunal's role when the tribunal is confronted with issues of hospital liability and other unsettled areas of the substantive law of medical malpractice. The Note suggests that tribunals should be limited to deciding issues concerning medical treatment and the professional conduct of physicians and hospitals.
Pests and People in Stef Smith’s Human Animals
Authors: Cowan Isla
Published: April 2021

Throughout the history of western theatre, animals onstage have invariably been read in relation to human concerns. The reviews of Stef Smith’s Human Animals (2016) at the Royal Court followed in this tradition, interpreting the play’s central animal players as symbolic stand-ins for humans. By examining the particularity of the non-human animals at the centre of Human Animals’ urban eco-crisis, this article aims to rectify previous anthropocentric readings and acknowledge the agency and autonomy of the play’s non-human animals, namely pigeons and foxes. Building on Una Chaudhuri’s ‘Theatre of Species’, this article demonstrates Human Animals’ deep engagement with animal alterity, subverting conventional socio-zoological classifications of ‘pest’ animals and popular preconceptions of pigeons and foxes in British culture. While Smith’s play uses the dystopian mode to dramatize a small-scale, localized eco-crisis, this article highlights how its focus on urban animal encounters and zoonotic disease holds broader implications for re-imagining inter-species relations and planetary health. An award-winning playwright, Isla Cowan is also a PhD student at the University of Glasgow. Her current research investigates ideas of ecological consciousness in contemporary Scottish theatre and is funded by the Arts and Humanities Research Council (SGSAH).
Performing National Identity in the Interwar Period: The Sarrasani Circus in Germany and Latin America
Authors: Hanke Sabine
Published: April 2021

This article examines the production and promotion of popular entertainments by the German Sarrasani Circus during the interwar period and how they were used to establish specific national narratives in Germany and Latin America. Focusing particularly on its engagement of Lakota performers, it argues that the Circus acted as an active negotiator of national concerns within and beyond Germany’s borders, and presented the group as ‘familiar natives’ in order to appeal to local and national ideas of Germanness. At the same time, it shows that the performers pursued their own interests in becoming international and cosmopolitan performers, thereby challenging the assimilation forced upon their traditions and culture by institutions in the United States. Finally, it demonstrates how foreign propaganda built on the Circus’s national image in Latin America to restore Germany’s international relations after the First World War. Sabine Hanke is a lecturer in Modern History at the University of Duisberg-Essen. Her research examines the German and British interwar circus. She was recently awarded her PhD in cultural history, from which this article has evolved, at the University of Sheffield. A chapter based on her research is scheduled for publication in Circus Histories and Theories, ed. Nisha P.R. and Melon Dilip (Oxford University Press).
Does the lag time between radicle and epicotyl emergences in acorns of pedunculate oak (Quercus roburL.) depend on the duration of cold stratification and post-stratification temperatures? Modelling with the sigmoidal growth curves approach
Authors: Jastrzębowski Szymon , Ukalska Joanna , Walck Jeffrey L.
Published: April 2021

The objective of this study was to determine how the current (10–16 weeks) and predicted future (2–8 weeks) length of cold stratification and current and predicted future post-stratification temperatures influence radicle and epicotyl emergence in acorns ofQuercus robur. We tested radicle and epicotyl emergence at two temperatures corresponding to the current (15/6°C) and predicted future early autumn and spring temperatures (25/15°C) in Poland. We fitted models to describe and derive parameters for radicle and epicotyl emergences over time. The parameters included maximum percentage, rate of emergences, time to achieve the maximum emergence rate, emergence delay and time to 50% emergence. In most cases, the Gompertz model was the best fit, but in a few cases, the logistic model was the best. Richard's model for most of the cases did not converge. This model, according to both information criteria values, was the best fit for epicotyl emergence at 15/6°C following 8 weeks of cold stratification. Richard's model was also the best fit for epicotyl emergence at 25/15°C following 14 weeks of stratification.. Our results indicate that at temperatures typical for early autumn (15/6°C), the time necessary for radicle emergence from 50% of acorns was longer than that from acorns placed at 25/15°C. Four weeks of cold stratification extended 50% radicle emergence at 15/6°C to 70 d, whereas 12 weeks of stratification shortened the time to 11 d. When the acorns were incubated at 25/15°C, radicle emergence occurred faster than at 15/6°C and the time lag between radicle and epicotyl was shorter.
The nutritive value of banana (Musa acuminata L.) by-products for
maintaining goats
Authors: Pieltain M. C. , Castan J. I. R. , Ventura M. R. , Flores M. P.
Published: April 2021

The nutritive value of banana by-products (leaves, pseudostems and raceme
stems) for goats was studied by rumen degradability and in vitro digestibility
techniques, voluntary intake and maintenance trials. Banana by-products had both a
relatively low degradability and digestibility, with derived metabolizable energy
content (MJ ME per kg dry matter (DM)) of 6·54 for leaves, 6·66 for pseudostems
and 8·24 for raceme stems. Daily voluntary intake (g DM per kg
M0·75) was 66·4 for leaves, 19·3 for pseudostems, and 15·3
for raceme stems. On these results, pseudostems and raceme stems would provide
less than 0·30 of maintenance ME needs of goats. However, rations based only on
banana leaves should meet more than 0·85 of the maintenance energy needs.
Timeline of Palmer amaranth (Amaranthus palmeri) invasion and eradication in Minnesota
Authors: Yu Eric , Blair Shane , Hardel Mari , Chandler Monika , Thiede Denise , Cortilet Anthony , Gunsolus Jeffrey , Becker Roger
Published: April 2021

Palmer amaranth–a fast-growing, challenging-to-control noxious weed that significantly reduces crop yields—was first found in Minnesota in September 2016 in conservation plantings sown with Palmer amaranth contaminated seed mixes. Minnesota Department of Agriculture (MDA) designated Palmer amaranth as a Prohibited Noxious Weed in 2015 and listed it as a Noxious Weed Seed in 2016 by emergency order. A genetic test to identify Palmer amaranth was simultaneously developed by multiple laboratories, providing a tool to limit its spread as a contaminant in seed. Seed companies adopted genetic testing methods for labeling seed for sale, thus reducing introductions via the seed pathway. Additionally, MDA determined that manure spread on crop fields from contaminated screenings fed to livestock resulted in new infestations. Limiting spread via these and other potential pathways was critical to successfully reducing the impact of Palmer amaranth. MDA, University of Minnesota (UMN) Extension, Conservation Corps Minnesota and Iowa (CCMI), farmers, and other partners are working to eradicate these infestations before they can spread. In 2016, 35 sites were sown with Palmer amaranth–contaminated seed mixes. Palmer amaranth was found at eight (23%) of these sites. Management with intensive scouting, torching, prescribed burning, and herbicide application was implemented in 2016 and 2017. By 2018, no Palmer amaranth was found at any of these sites. Similar success to newer infestations in 2018, 2019, and 2020 was achieved using the same methods. MDA recorded management activities and documented a comprehensive timeline of Palmer amaranth in Minnesota. This timeline provides a story of success and challenges in combating and eradicating Palmer amaranth.
Justice for Families
Authors: Cleveland Kyndra C.
Published: April 2021

Abstract. When a substantiated allegation of child maltreatment occurs, a family may be referred to the child welfare court. This court may temporarily remove children from their homes, making them dependents of the state. Over the course of a case, the judge assesses the child's needs and safety, and orders services for the family to help them reunify. Internationally, the child welfare court process is complex and lengthy, with a number of hearings that parents are required to attend, and a host of legal decisions rendered. One major decision that may arise from these proceedings is a permanent legal separation of children from their parents, referred to as a termination of parental rights. A decision to terminate parental rights can be life-altering for the entire family. Yet, very little is known about parents' experiences during child welfare court cases, particularly about their legal understanding. A lack of parent understanding may contribute to difficulties with navigating cases and complying with court mandates. Recent mixed-methods research conducted with parents in child welfare proceedings in the United States systematically examined parents' understanding. Findings revealed that parents had a limited understanding of common court terms, professionals' roles, and key processes. Furthermore, 12% of parents could not describe the judge's most recent decision in their case. Qualitative research in the United Kingdom and Canada demonstrates that parents in these countries may also experience challenges with understanding child welfare proceedings. Policy recommendations are offered to underscore the importance of assessing and promoting parents' legal understanding, globally.
Dynamical Differences Between Short and Long Blocks in the Northern Hemisphere
Authors: Drouard Marie , Woollings Tim , Sexton David M. H. , McSweeney Carol F.
Published: April 2021

Blocking events are persistent weather systems that strongly impact daily weather and more importantly our societies. One reason behind their strong impact is their potential long duration, as blocking events can last from 5 days up to four‐five weeks. However, the mechanisms explaining this difference of duration have not been properly studied yet. Here, we investigate the differences between short blocks, which last 5 days, and long blocks, which last at least 10 days. We take a broad hemispheric and annual approach to this question, while recognizing that other specific factors may play a role in particular region and seasons. We show that long blocks often involve cyclonic Rossby wave breaking, while short blocks are equally associated with cyclonic and anticyclonic wave breaking. This main result is reproduced in a coupled climate model ensemble. The lower number of long anticyclonic blocks might be due to three main reasons: One/the anticyclone is reinforced on the downstream side during anticyclonic blocks which is less conducive to persistence; two/positive synoptic eddy feedback tends to force the mean zonal wind toward a more northward position during anticyclonic blocks, whereas it forces the mean zonal wind to the south of the block during cyclonic blocks, which has been previously shown to be associated with more persistent weather patterns; three/particularly sustained eddy feedback is needed to maintain long anticyclonic blocks.
The Rain Forest Can Recover After Fire, but It’s Not the Same
Authors: Wheeling Kate
Published: April 2021

New research finds that temperatures rise in the Amazon rain forest after a fire, even in areas that are not converted to agricultural land or pastures.
Avoiding transduction-induced heating in suspended microchannel resonators using piezoelectricity
Authors: Maillard Damien , De Pastina Annalisa , Abazari Amir Musa , Villanueva Luis Guillermo
Published: April 2021

Calorimetry of single biological entities remains elusive. Suspended microchannel resonators (SMRs) offer excellent performance for real-time detection of various analytes and could hold the key to unlocking pico-calorimetry experiments. However, the typical readout techniques for SMRs are optical-based, and significant heat is dissipated in the sensor, altering the measurement and worsening the frequency noise. In this manuscript, we demonstrate for the first time full on-chip piezoelectric transduction of SMRs on which we focus a laser Doppler vibrometer to analyze its effect. We demonstrate that suddenly applying the laser to a water-filled SMR causes a resonance frequency shift, which we attribute to a local increase in temperature. When the procedure is repeated at increasing flow rates, the resonance frequency shift diminishes, indicating that convection plays an important role in cooling down the device and dissipating the heat induced by the laser. We also show that the frequency stability of the device is degraded by the laser source. In comparison to an optical readout scheme, a low-dissipative transduction method such as piezoelectricity shows greater potential to capture the thermal properties of single entities.
Potential impact of celiac disease genetic risk factors on T cell receptor signaling in gluten-specific CD4+ T cells
Authors: Bakker Olivier B. , Ramírez-Sánchez Aarón D. , Borek Zuzanna A. , de Klein Niek , Li Yang , Modderman Rutger , Kooy-Winkelaar Yvonne , Johannesen Marie K. , Matarese Filomena , Martens Joost H. A. , Kumar Vinod , van Bergen Jeroen , Qiao Shuo-Wang , Lundin Knut E. A. , Sollid Ludvig M. , Koning Frits , Wijmenga Cisca , Withoff Sebo , Jonkers Iris H.
Published: April 2021

Celiac disease is an auto-immune disease in which an immune response to dietary gluten leads to inflammation and subsequent atrophy of small intestinal villi, causing severe bowel discomfort and malabsorption of nutrients. The major instigating factor for the immune response in celiac disease is the activation of gluten-specific CD4+ T cells expressing T cell receptors that recognize gluten peptides presented in the context of HLA-DQ2 and DQ8. Here we provide an in-depth characterization of 28 gluten-specific T cell clones. We assess their transcriptional and epigenetic response to T cell receptor stimulation and link this to genetic factors associated with celiac disease. Gluten-specific T cells have a distinct transcriptional profile that mostly resembles that of Th1 cells but also express cytokines characteristic of other types of T-helper cells. This transcriptional response appears not to be regulated by changes in chromatin state, but rather by early upregulation of transcription factors and non-coding RNAs that likely orchestrate the subsequent activation of genes that play a role in immune pathways. Finally, integration of chromatin and transcription factor binding profiles suggest that genes activated by T cell receptor stimulation of gluten‑specific T cells may be impacted by genetic variation at several genetic loci associated with celiac disease.
Interactive effects of incentive value and valence on the performance of discrete action sequences
Authors: Adkins Tyler J. , Gary Bradley S. , Lee Taraz G.
Published: April 2021

Incentives can be used to increase motivation, leading to better learning and performance on skilled motor tasks. Prior work has shown that monetary punishments enhance on-line performance while equivalent monetary rewards enhance off-line skill retention. However, a large body of literature on loss aversion has shown that losses are treated as larger than equivalent gains. The divergence between the effects of punishments and reward on motor learning could be due to perceived differences in incentive value rather than valence per se. We test this hypothesis by manipulating incentive value and valence while participants trained to perform motor sequences. Consistent with our hypothesis, we found that large reward enhanced on-line performance but impaired the ability to retain the level of performance achieved during training. However, we also found that on-line performance was better with reward than punishment and that the effect of increasing incentive value was more linear with reward (small, medium, large) while the effect of value was more binary with punishment (large vs not large). These results suggest that there are differential effects of punishment and reward on motor learning and that these effects of valence are unlikely to be driven by differences in the subjective magnitude of gains and losses.
Agreement between dried blood spots and HemoCue in Tamil Nadu, India
Authors: Roshania Reshma P. , Mehta Rukshan V. , Shete Ashwini , Bingewar Rohini , Kulkarni Sangeeta , Mahajan Aprajit , Miller Grant , Tarozzi Alessandro , Martorell Reynaldo
Published: April 2021

India retains the world’s largest burden of anemia despite decades of economic growth and anemia prevention programming. Accurate screening and estimates of anemia prevalence are critical for successful anemia control. Evidence is mixed on the performance of HemoCue, a point-of-care testing device most widely used for large-scale surveys. The use of dried blood spots (DBS) to assess hemoglobin (Hb) concentration is a potential alternative, particularly in field settings. The objective of this study is to assess Hb measurement agreement between capillary HemoCue and DBS among two age groups, children 6–59 months and females age 12–40 years. We analyzed data from the baseline round of a cluster randomized rice fortification intervention in Cuddalore district of Tamil Nadu, India. Capillary blood was collected from a subset of participants for Hb assessment by HemoCue 301 and DBS methods. We calculated Lin’s concordance correlation coefficient, and tested bias by conducting paired t-tests of Hb concentration. Independence of the bias and Hb magnitude was examined visually using Bland–Altman plots and statistically tested by Pearson’s correlation. We assessed differences in anemia classification using McNemar’s test of marginal homogeneity. Concordance between HemoCue and DBS Hb measures was moderate for both children 6–59 months (ρc = 0.67; 95% CI 0.65, 0.71) and females 12–40 years (ρc = 0.67: 95% CI 0.64, 0.69). HemoCue measures were on average 0.06 g/dL higher than DBS for children (95% CI 0.002, 0.12; p = 0.043) and 0.29 g/dL lower than DBS for females (95% CI − 0.34, − 0.23; p < 0.0001). 50% and 56% of children were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). 55% and 47% of females were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). There is moderate statistical agreement of Hb concentration between HemoCue and DBS for both age groups. The choice of Hb assessment method has important implications for individual anemia diagnosis and population prevalence estimates. Further research is required to understand factors that influence the accuracy and reliability of DBS as a methodology for Hb assessment.
Multifaceted phase ordering kinetics of an antiferromagnetic spin-1 condensate
Authors: Pietraszewicz Joanna , Seweryn Aleksandra , Witkowska Emilia
Published: April 2021

We study phase domain coarsening in the long time limit after a quench of magnetic field in a quasi one-dimensional spin-1 antiferromagnetic condensate. We observe that the growth of correlation length obeys scaling laws predicted by the two different models of phase ordering kinetics, namely the binary mixture and vector field. We derive regimes of clear realization for both of them. We demonstrate appearance of atypical scaling laws, which emerge in intermediate regions.
A magnetically retrievable mixed-valent Fe3O4@SiO2/Pd0/PdII nanocomposite exhibiting facile tandem Suzuki coupling/transfer hydrogenation reaction
Authors: Singh Parminder , Mishra Saumyaranjan , Sahoo Anupam , Patra Srikanta
Published: April 2021

Herein, we report a magnetically retrievable mixed-valent Fe3O4@SiO2/Pd0/PdIINP (5) nanocomposite system for tandem Suzuki coupling/transfer hydrogenation reaction. The nanocomposite5was prepared first by making a layer of$$\hbox {SiO}_{2}$$SiO2on$$\hbox {Fe}_{3}\hbox {O}_{4}\hbox {NP}$$Fe3O4NPfollowed by deposition of$$\hbox {Pd}^{0}$$Pd0and sorption of$$\hbox {Pd}^{\mathrm{II}}$$PdIIions successively onto the surface of Fe3O4@SiO2NP. The nanocomposite was characterized by powder XRD, electron microscopy (SEM-EDS and TEM-EDS) and XPS spectroscopy techniques. The mixed-valent$$\hbox {Pd}^{0}/\hbox {Pd}^{\mathrm{II}}$$Pd0/PdIIpresent onto the surface of nanocomposite5was confirmed by XPS technique. Interestingly, the mixed-valent nanocomposite Fe3O4@SiO2/Pd0/PdIINP (5) exhibited tandem Suzuki coupling/transfer hydrogenation reaction during the reaction of aryl bromide with aryl boronic acid (90% ofC). The nanocomposite5displayed much better reactivity as compared to the monovalent Fe3O4@SiO2/Pd0NP (3) (25% ofC) and Fe3O4@SiO2/PdIINP (4) (15% ofC) nanocomposites. Further, because of the presence of magnetic$$\hbox {Fe}_{3}\hbox {O}_{4}$$Fe3O4, the nanocomposite displayed its facile separation from the reaction mixture and reused at least for five catalytic cycles.
Distinguishing retinal angiomatous proliferation from polypoidal choroidal vasculopathy with a deep neural network based on optical coherence tomography
Authors: Hwang Daniel Duck-Jin , Choi Seong , Ko Junseo , Yoon Jeewoo , Park Ji In , Hwang Joon Seo , Han Jeong Mo , Lee Hak Jun , Sohn Joonhong , Park Kyu Hyung , Han Jinyoung
Published: April 2021

This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model’s ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV.
Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice
Authors: Pádua-Reis Marina , Nôga Diana Aline , Tort Adriano B. L. , Blunder Martina
Published: April 2021

Diazepam has been broadly accepted as an anxiolytic drug and is often used as a positive control in behavioral experiments with mice. However, as opposed to this general assumption, the effect of diazepam on mouse behavior can be considered rather controversial from an evidence point of view. Here we revisit this issue by studying the effect of diazepam on a benchmark task in the preclinical anxiety literature: the elevated plus maze. We evaluated the minute-by-minute time-course of the diazepam effect along the 10 min of the task at three different doses (0.5, 1 and 2 mg/kg i.p. 30 min before the task) in female and male C57BL/6J mice. Furthermore, we contrasted the effects of diazepam with those of a selective serotoninergic reuptake inhibitor (paroxetine, 10 mg/kg i.p. 1 h before the task). Diazepam had no anxiolytic effect at any of the tested doses, and, at the highest dose, it impaired locomotor activity, likely due to sedation. Noteworthy, our results held true when examining male and female mice separately, when only examining the first 5 min of the task, and when animals were subjected to one hour of restrain-induced stress prior to diazepam treatment. In contrast, paroxetine significantly reduced anxiety-like behavior without inducing sedative effects. Our results therefore suggest that preclinical studies for screening new anxiolytic drugs should be cautious with diazepam use as a potential positive control.
Spatial variation and mechanisms of leaf water content in grassland plants at the biome scale: evidence from three comparative transects
Authors: Wang Ruomeng , He Nianpeng , Li Shenggong , Xu Li , Li Mingxu
Published: April 2021

Leaf water content (LWC) has important physiological and ecological significance for plant growth. However, it is still unclear how LWC varies over large spatial scale and with plant adaptation strategies. Here, we measured the LWC of 1365 grassland plants, along three comparative precipitation transects from meadow to desert on the Mongolia Plateau (MP), Loess Plateau, and Tibetan Plateau, respectively, to explore its spatial variation and the underlying mechanisms that determine this variation. The LWC data were normally distributed with an average value of 0.66 g g−1. LWC was not significantly different among the three plateaus, but it differed significantly among different plant life forms. Spatially, LWC in the three plateaus all decreased and then increased from meadow to desert grassland along a precipitation gradient. Unexpectedly, climate and genetic evolution only explained a small proportion of the spatial variation of LWC in all plateaus, and LWC was only weakly correlated with precipitation in the water-limited MP. Overall, the lasso variation in LWC with precipitation in all plateaus represented an underlying trade-off between structural investment and water income in plants, for better survival in various environments. In brief, plants should invest less to thrive in a humid environment (meadow), increase more investment to keep a relatively stable LWC in a drying environment, and have high investment to hold higher LWC in a dry environment (desert). Combined, these results indicate that LWC should be an important variable in future studies of large-scale trait variations.
Calcium carbonate nanoparticles stimulate cancer cell reprogramming to suppress tumor growth and invasion in an organ-on-a-chip system
Authors: Lam Sandra F. , Bishop Kevin W. , Mintz Rachel , Fang Lei , Achilefu Samuel
Published: April 2021

The acidic microenvironment of solid tumors induces the propagation of highly invasive and metastatic phenotypes. However, simulating these conditions in animal models present challenges that confound the effects of pH modulators on tumor progression. To recapitulate the tumor microenvironment and isolate the effect of pH on tumor viability, we developed a bifurcated microfluidic device that supports two different cell environments for direct comparison. RFP-expressing breast cancer cells (MDA-MB-231) were cultured in treatment and control chambers surrounded by fibrin, which received acid-neutralizing CaCO3 nanoparticles (nanoCaCO3) and cell culture media, respectively. Data analysis revealed that nanoCaCO3 buffered the pH within the normal physiological range and inhibited tumor cell proliferation compared to the untreated control (p < 0.05). Co-incubation of cancer cells and fibroblasts, followed by nanoCaCO3 treatment showed that the nanoparticles selectively inhibited the growth of the MDA-MB-231 cells and reduced cellular migration of these cells with no impact on the fibroblasts. Sustainable decrease in the intracellular pH of cancer cells treated with nanoCaCO3 indicates that the extracellular pH induced cellular metabolic reprogramming. These results suggest that the nanoCaCO3 can restrict the aggressiveness of tumor cells without affecting the growth and behavior of the surrounding stromal cells.
Carbon stocks of homestead forests have a mitigation potential to climate change in Bangladesh
Authors: Baul Tarit Kumar , Peuly Tajkera Akhter , Nandi Rajasree , Schmidt Lars Holger , Karmakar Shyamal
Published: April 2021

A total of 176 homestead forests at three altitudes in the Chittagong Hill Tracts, Bangladesh were randomly surveyed to estimate carbon (C) stocks and how stand structure affects the biomass C. All woody vegetations were measured, and litter and soil (0–30 cm depth) were sampled. The tree biomass C stock in the top two altitude forests was up to 37–48% higher than in low altitude, owing to significantly higher tree density and species diversity. An increase in species diversity index by one unit increased the biomass stock by 23 Mg C ha−1. The C stock of litterfall in low altitude forests was 22–28% higher than in the top two altitude due to the deposition of litters downslope and deliberate use of mulch for soil improvement and conservation, resulting in up to 5% higher total soil C. The topsoil C was 10–25% higher than the deeper soil, depending on the altitude. The forest stored 89 Mg C ha−1, indicating a potential for C sequestration in trees outside forest. This study would help policymakers to strengthen the recognition of small-scale forests for mitigation in REDD + (reducing emissions from deforestation and forest degradation, the role of conservation, sustainable management of forests, and enhancement of forest carbon stocks) and support owners through C credits from sustainably managed forests.