bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives on plant flavonoid quercetin-based drugs for novel SARS-CoV-2
Authors: Saakre Manjesh , Mathew Deepu , Ravisankar V. 
Published: March 2021

Abstract
Background
The world pandemic COVID-19 caused by SARS-CoV-2 is currently claiming thousands of lives. Flavonoids abundantly present in the fruits and vegetables, especially quercetin, are shown to have antiviral activities.

Main text
This paper reviews the capability of the plant flavonoid quercetin to fight the novel coronavirus and the possibility for drug development based on this. The mode of action explaining the known pathways through which this molecule succeeds in the antiviral activity, action of quercetin on SARS-CoV-2 main protease 3CLpro, antiviral activities of its derivatives on human viruses, effect of combination of zinc co-factor along with quercetin in the COVID-19 treatment, and the regulation of miRNA genes involved in the viral pathogenesis are discussed. Proof for this concept is provided following the virtual screening using ten key enzymes of SARS-CoV-2 and assessing their interactions. Active residues in the 3D structures have been predicted using CASTp and were docked against quercetin. Key proteins 3CLpro, spike glycoprotein/ human ACE2-BOAT1 complex, RNA-dependent RNA polymerase, main peptidase, spike glycoprotein, RNA replicase, RNA binding protein, papain-like protease, SARS papain-like protease/ deubiquitinase, and complex of main peptidase with an additional Ala at the N-terminus of each protomer, have shown the binding energies ranging between − 6.71 and − 3.37 kcal/ Mol, showing that quercetin is a potential drug candidate inhibiting multiple SARS-CoV-2 enzymes.

Conclusion
The antiviral properties of flavonoid and the molecular mechanisms involved are reviewed. Further, proof for this concept is given by docking of key proteins from SARS-CoV-2 with quercetin.

Graphical abstract
Unequal effects of climate change and pre-existing inequalities on the mental health of global populations
Authors: Zhang Shuo , Braithwaite Isobel , Bhavsar Vishal , Das-Munshi Jayati 
Published: March 2021

SummaryClimate change is already having unequal effects on the mental health of individuals and communities and will increasingly compound pre-existing mental health inequalities globally. Psychiatrists have a vital part to play in improving both awareness and scientific understanding of structural mechanisms that perpetuate these inequalities, and in responding to global calls for action to promote climate justice and resilience, which are central foundations for good mental and physical health.
External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases
Authors: Elledge Christen R. , LaVigne Anna W. , Fiksel Jacob , Wright Jean L. , McNutt Todd , Kleinberg Lawrence R. , Hu Chen , Smith Thomas J. , Zeger Scott , DeWeese Theodore L. , Alcorn Sara R. 
Published: March 2021

PURPOSE The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown. PATIENTS AND METHODS Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set. RESULTS A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 v 62 years; P < .001), had more primary breast (27% v 19%; P = .03) and prostate cancer (20% v 12%; P = .01), and survived longer (median, 10.7 v 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained > 0.79. CONCLUSION BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.
Development and Evaluation of Perl-Based Algorithms to Classify Neoplasms From Pathology Records in Synoptic Report Format
Authors: Rossi Kristen R. , Echeverria Diana , Carroll Anna , Luse Tina , Rennix Christopher 
Published: March 2021

PURPOSE Synoptic reporting provides a mechanism for uniform and structured pathology diagnostics. This paper demonstrates the functionality of Perl alternation and grouping expressions to classify electronic pathology reports generated from military treatment facilities. Eight Perl-based algorithms are validated to classify malignant melanoma, Hodgkin lymphoma, non-Hodgkin lymphoma, leukemia, and malignant neoplasms of the breast, ovary, testis, and thyroid. METHODS Case finding cohorts were developed using diagnostic codes for neoplasm groups and matched by unique identifiers to obtain pathology records. Preprocessing techniques and Perl-based algorithms were applied to classify records as malignant, in situ, suspect, or nonapplicable, followed by a hand-review process to determine the accuracy of the algorithm classifications. Interrater reliability, sensitivity, specificity, positive predictive values, and negative predictive values were computed following abstractor adjudication. RESULTS The specificity of the Perl-based algorithms was consistently high, over 98%. Very few benign results were classified as malignant or in situ by the Perl-based algorithms; the leukemia algorithm classification was the only group to demonstrate a positive predictive value below 95%, at 91.9%. Three algorithm classification groups demonstrated a sensitivity of < 80%, including malignant neoplasm of the ovary (33.3%), leukemia (52.8%), and non-Hodgkin lymphoma (62.9%). The pathology records for these results included substantial linguistic variation. CONCLUSION This paper contextualizes the utility and value of an algorithm logic built around synoptic reporting to identify neoplasms from electronic pathology results. The major strength includes the application of Perl-based coding in SAS, an accessible software application, to develop highly specific algorithms across institutional variation in diagnostic documentation.
High Levels of Thyroid Hormone Impair Regulatory T Cell Function Via Reduced PD-1 Expression
Authors: Zhong Yi , Lu Ting-Ting , Liu Xiao-Mei , Liu Bing-Li , Hu Yun , Liu Shu , Wang Jie , Li Guo-Qing , Mao Xiao-Ming 
Published: March 2021

Abstract

Context
Regulatory T cell (Treg) dysfunction plays an important role in the development and progression of Graves’ disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Treg expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined.

Objective
To evaluate the role of PD-1 in Treg function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3.

Methods
We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Treg function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo.

Results
PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Treg function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3.

Conclusion
Treg dysfunction in GD patients might be due to downregulation of PD-1 expression in Tregs induced by high levels of serum T3.
Indios, Sambos, Mestizos, and the Social Construction of Racial Identity in Colonial Central America
Authors: Billing Samantha R. 
Published: March 2021

AbstractThe Miskitu, a group indigenous to the Caribbean Coast of Central America, have long been recognized for their racial diversity. In the mid-seventeenth century, a ship of African slaves wrecked on the Mosquito Coast and subsequently intermarried with the Miskitu population. Since then, there have been two groups of Miskitu: the “pure” indios and the racially mixed sambos. This article argues against this neat divide. Race during the colonial period was not fixed and could be influenced by a number of factors that included not only one’s ancestry but also their behavior. When Spanish writers assigned a racial category to the Miskitu, the context of the encounter often shaped perceived racial origin. When Miskitu-Spanish relations were hostile, Spaniards more often chose the racial label sambo. During times of peace, indio was more common, and mestizo was sometimes used to refer to Miskitu rulers. By focusing on the complexity and malleability of colonial racial rhetoric, this article argues that Spanish officials strategically selected racial labels for the Miskitu depending on the colonial policy they were trying to promote.
Diasporic Convergences: Tracing Knowledge Production and Transmission among Enslaved Chinos in New Spain
Authors: Luis Diego Javier 
Published: March 2021

Abstract
During the seventeenth century, transatlantic and transpacific diasporas created one of the world’s most globalized early modern societies in New Spain. As the slave trades to the colonial centers of central Mexico reached frenetic levels after the turn of the seventeenth century, processes of encounter, exchange, and transmission began to characterize these diverse communities. For “chinos” arriving in Acapulco, careful observation and experience coalesced into mobile bodies of knowledge ranging from the social practice of blasphemy to spiritual ritual. These varied modes of cultural production facilitated negotiation of enslaver/enslaved relations and represented a kaleidoscope of responses to power relations in colonial society. Through these forms of contestation, knowledge production in enslaved communities became central to the rhythms of daily life in New Spain.
DACA's Association With Birth Outcomes Among Mexican-Origin Mothers in the United States
Authors: Hamilton Erin R. , Langer Paola D. , Patler Caitlin 
Published: March 2021

Abstract
The 2012 Deferred Action for Childhood Arrivals (DACA) program granted work authorization and protection from deportation to more than 800,000 young undocumented immigrants who arrived to the United States as minors. We estimate the association between this expansion of legal rights and birth outcomes among 72,613 singleton births to high school–educated Mexican immigrant women in the United States from June 2010 to May 2014, using birth records data from the National Center for Health Statistics. Exploiting the arbitrariness of the upper age cutoff for DACA eligibility and using a difference-in-differences design, we find that DACA was associated with improvements in the rates of low birth weight and very low birth weight, birth weight in grams, and gestational age among Mexican immigrant mothers.
Model systems for regeneration:Arabidopsis
Authors: Mathew Mabel Maria , Prasad Kalika 
Published: March 2021

ABSTRACTPlants encompass unparalleled multi-scale regenerative potential. Despite lacking specialized cells that are recruited to injured sites, and despite their cells being encased in rigid cell walls, plants exhibit a variety of regenerative responses ranging from the regeneration of specific cell types, tissues and organs, to the rebuilding of an entire organism. Over the years, extensive studies on embryo, shoot and root development in the model plant species Arabidopsis thaliana have provided insights into the mechanisms underlying plant regeneration. These studies highlight how Arabidopsis, with its wide array of refined molecular, genetic and cell biological tools, provides a perfect model to interrogate the cellular and molecular mechanisms of reprogramming during regeneration.
SARS-CoV-2 and the role of airborne transmission: a systematic review
Authors: Heneghan Carl J. , Spencer Elizabeth A. , Brassey Jon , Plüddemann Annette , Onakpoya Igho J. , Evans David H. , Conly John M. , Jefferson Tom 
Published: March 2021

Background: Airborne transmission is the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in the air. We carried out a systematic review to identify, appraise and summarise the evidence from studies of the role of airborne transmission of SARS-CoV-2. Methods: We searched LitCovid, MedRxiv, Google Scholar and the WHO Covid-19 database from 1 February to 20 December 2020 and included studies on airborne transmission. Data were dual extracted and we assessed quality using a modified QUADAS 2 risk of bias tool. Results: We included 67 primary studies and 22 reviews on airborne SARS-CoV-2. Of the 67 primary studies, 53 (79%) reported data on RT-PCR air samples, 12 report cycle threshold values and 18 copies per sample volume. All primary studies were observational and of low quality. The research often lacked standard methods, standard sampling sizes and reporting items. We found 36 descriptions of different air samplers deployed. Of the 42 studies conducted in-hospital that reported binary RT-PCR tests, 24 (57%) reported positive results for SARs-CoV-2 (142 positives out of 1,403 samples: average 10.1%, range 0% to 100%). There was no pattern between the type of hospital setting (ICU versus non-ICU) and RT-PCR positivity. Seventeen studies reported potential air transmission in the outdoors or in the community. Seven performed RT-PCR sampling, of which two studies report weak positive RNA samples for 2 or more genes (5 of 125 samples positive: average 4.0%). Ten studies attempted viral culture with no serial passage for viral culture. Conclusion: SARS-CoV-2 RNA is detected intermittently in the air in various settings. Standardized guidelines for conducting and reporting research on airborne transmission are needed. The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions over airborne transmission.
IoT Workload Emulation for Data Centers
Authors: Batz Thomas , Herzog Reinhard , Summers Jon , Watson Kym 
Published: March 2021

The Internet of Things (IoT) domain has been one of the fastest growing areas in the computer industry for the last few years. Consequently, IoT applications are becoming the dominant work load for many data centers. This has implications for the designers of data centers, as they need to meet their customers' requirements. Since it is not easy to use real applications for the design and test of data center setups, a tool is required to emulate real applications but is easy to configure, scale and deploy in a data center. This paper will introduce a simple but generic way to model the work load of typical IoT applications, in order to have a realistic and reproducible way to emulate IT loads for data centers. IoT application designers are in the process of harmonizing their approaches on how architectures should look, which building blocks are needed, and how they should interwork. While all IoT subdomains are diverse when it comes to the details, the architectural blueprints are becoming more and more aligned. These blueprints are called reference architectures and incorporate similar patterns for the underlying application primitives. This paper will introduce an approach to decompose IoT applications into such application primitives, and use them to emulate a workload as it would be created by the modeled application. The paper concludes with an example application of the IoT Workload Emulation in the BodenTypeDC experiment, where new cooling approaches for data centers have been tested under realistic work load conditions.
The parallels between particle induced lung overload and particle induced periprosthetic osteolysis (PPOL)
Authors: Borm Paul J.A. 
Published: March 2021

Background: When particles deposit for instance in the lung after inhalation or in the hip joint after local release from a hip implant material they can initiate a defense response. Even though these particles originate from inert materials such as polyethylene (PE) or titanium, they may cause harm when reaching high local doses and overwhelming local defense mechanisms. Main body: This paper describes the parallels between adverse outcome pathways (AOP) and particle properties in lung overload and periprosthetic osteolysis (PPOL). It is noted that in both outcomes in different organs , the macrophage and cytokine orchestrated persistent inflammation is the common driver of events, in the bone leading to loss of bone density and structure, and in the lung leading to fibrosis and cancer. Most evidence on lung overload and its AOP is derived from chronic inhalation studies in rats, and the relevance to man is questioned. In PPOL, the paradigms and metrics are based on human clinical data, with additional insights generated from in vitro and animal studies. In both organ pathologies the total volume of particle deposition has been used to set threshold values for the onset of pathological alterations. The estimated clinical threshold for PPOL of 130 mg/ml is much higher than the amount to cause lung overload in the rat (10 mg/ml). Conclusions: The paradigms developed in two very different areas of particle response in the human body have major similarities in their AOP. Connecting the clinical evidence in PPOL to lung overload challenges current paradigms and the human relevance of rat inhalation studies.
Impact of Social Interactions on Duopoly Competition with Quality Considerations
Authors: Geng Xin , Guo Xiaomeng , Xiao Guang 
Published: March 2021

We study the impacts of social interactions on competing firms’ quality differentiation, pricing decisions, and profit performance. Two forms of social interactions are identified and analyzed: (1) market-expansion effect (MEE)—the total market expands as a result of both firms’ sales—and (2) value-enhancement effect (VEE)—a consumer gains additional utility of purchasing from one firm based on this firm’s previous and/or current sales volume. We consider a two-stage duopoly competition framework, in which both firms select quality levels in the first stage simultaneously and engage in a two-period price competition in the second stage. In the main model, we assume that each firm sets a single price and commits to it across two selling periods. We find that both forms of social interactions tend to lower prices and intensify price competition for given quality levels. However, MEE weakens the product-quality differentiation and is benign to both high-quality and low-quality firms. It also benefits consumers and improves social welfare. By contrast, VEE enlarges the quality differentiation and only benefits the high-quality firm, but is particularly malignant to the low-quality firm. It further reduces the consumers’ monetary surplus. Such impact is consistent, regardless of whether the VEE interactions involve previous or current consumers. We further discuss several model extensions, including dynamic pricing, combined social effects, and various cost structures, and verify that the aforementioned impacts of MEE and VEE are qualitatively robust to those extensions. Our results provide important managerial insights for firms in competitive markets and suggest that they need to not only be aware of the consumers’ social interactions, but also, more importantly, distinguish the predominant form of the interactions so as to apply proper marketing strategies. This paper was accepted by Matthew Shum, marketing.
Clinical outcomes in pediatric tibial lengthening and deformity correction: A comparison of the Taylor Spatial Frame with the Orthex Hexapod System
Authors: Messner Juergen , Chhina Harpreet , Davidson Sophia , Abad Jero , Cooper Anthony 
Published: March 2021

Purpose Comparison of two hexapod frame systems in paediatric tibial deformity correction; the Taylor Spatial Frame (TSF) and Orthex Hexapod System. Methods Paediatric patients with congenital and acquired tibial deformities treated with either TSF (between 2014 and 2016) or Orthex (between 2017 and 2019) frames were included in a retrospective comparative study. Outcome measures were healing index, pin infection rate, regenerate quality and density, software residual rate, deformity correction accuracy, strut exchanges and quality of life (QoL). Results The TSF group had 17 patients (18 frames) and the Orthex group had 21 patients (25 frames). The most common indications for tibial deformity correction were fibular hemimelia (14) and septic or traumatic growth arrest (8). The median time in frame was 230 days (TSF) versus 203 days (Orthex) (p= 0.06). The mean lengthening achieved was 54 mm (TSF) and 51 mm (Orthex) (p = 0.41). The healing index was 41 days/cm (TSF) versus 43 days/cm (Orthex) (p = 0.70). Pin site infections occurred more in the TSF cohort (40%) than in the Orthex cohort (18%) (p < 0.001). The regenerate in the Orthex group showed higher density at three months (p = 0.029) and was more homogenous (p = 0.023) at six months after frame application. Strut exchanges were less frequent with the Orthex system (p < 0.0001). QoL measures were similar in both cohorts (p = 0.92). Conclusions This is the first study to compare two hexapod designs in paediatric orthopaedics. The Orthex system showed superiority in regenerate quality and a significant reduction in pin site infection rates. Both systems delivered predictable and accurate limb deformity correction. Level of evidence III