bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Automatic Speech Recognition Approaches
Authors: Pires Magalhães Regis , Rodrigues Vasconcelos Daniel Jean , Sales Fernandes Guilherme , Almada Cruz Lívia , Xavier Sampaio Matheus , Fernandes de Macêdo José Antônio , Linhares Coelho da Silva Ticiana
Published: October 2022

Automatic Speech Recognition (ASR) is essential for many applications like automatic caption generation for videos, voice search, voice commands for smart homes, and chatbots. Due to the increasing popularity of these applications and the advances in deep learning models for transcribing speech into text, this work aims to evaluate the performance of commercial solutions for ASR that use deep learning models, such as Facebook Wit.ai, Microsoft Azure Speech, Google Cloud Speech-to-Text, Wav2Vec, and AWS Transcribe. We performed the experiments with two real and public datasets, the Mozilla Common Voice and the Voxforge. The results demonstrate that the evaluated solutions slightly differ. However, Facebook Wit.ai outperforms the other analyzed approaches for the quality metrics collected like WER, BLEU, and METEOR. We also experiment to fine-tune Jasper Neural Network for ASR with four datasets different with no intersection to the ones we collect the quality metrics. We study the performance of the Jasper model for the two public datasets, comparing its results with the other pre-trained models.
Analysis of the Influence of Modeling, Data Format and Processing Tool on the Performance of Hadoop-Hive Based Data Warehouse
Authors: P. de Oliveira Beatriz F. , O. Valente Aline S. , Victorino Marcio , Ribeiro Edward , Holanda Maristela
Published: October 2022

With the emergence of Big Data and the continuous growth of massive data produced by web applications, smartphones, social networks, and others, organizations began to invest in alternative solutions that would derive value from this amount of data. In this context, this article evaluates three factors that can significantly influence the performance of Big Data Hive queries: data modeling, data format and processing tool. The objective is to present a comparative analysis of the Hive platform performance with the snowflake model and the fully denormalized one. Moreover, the influence of two types of table storage file types (CSV and Parquet) and two types of data processing tools, Hadoop and Spark, were also comparatively analyzed. The data used for analysis is the open data of the Brazilian Army in the Google Cloud environment. Analysis was performed for different data volumes in Hive and cluster configuration scenarios. The results yielded that the Parquet storage format always performed better than when CSV storage formats were used, regardless of the model and processing tool selected for the test scenario.
NaV1.1 is essential for proprioceptive signaling and motor behaviors
Authors: Espino Cyrrus M , Lewis Cheyanne M , Ortiz Serena , Dalal Miloni S , Garlapalli Snigdha , Wells Kaylee M , O'Neil Darik A , Wilkinson Katherine A , Griffith Theanne N
Published: October 2022

The voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch-clamp recordings in genetically identified mouse proprioceptors show ubiquitous channel expression and significant contributions to intrinsic excitability. Notably, genetic deletion of NaV1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting that this channel is a major contributor to sensory proprioceptive transmission. Ex vivo muscle afferent recordings from conditional knockout mice found that loss of NaV1.1 leads to inconsistent and unreliable proprioceptor firing characterized by action potential failures during static muscle stretch; conversely, afferent responses to dynamic vibrations were unaffected. This suggests that while a combination of Piezo2 and other NaV isoforms is sufficient to elicit activity in response to transient stimuli, NaV1.1 is required for transmission of receptor potentials generated during sustained muscle stretch. Impressively, recordings from afferents of heterozygous conditional knockout animals were similarly impaired, and heterozygous conditional knockout mice also exhibited motor behavioral deficits. Thus, NaV1.1 haploinsufficiency in sensory neurons impairs both proprioceptor function and motor behaviors. Importantly, human patients harboring NaV1.1 loss-of-function mutations often present with motor delays and ataxia; therefore, our data suggest that sensory neuron dysfunction contributes to the clinical manifestations of neurological disorders in which NaV1.1 function is compromised. Collectively, we present the first evidence that NaV1.1 is essential for mammalian proprioceptive signaling and behaviors.
Benefits of Streamlined Point-of-Care Trial Designs
Authors: Califf Robert M. , Cavazzoni Patrizia , Woodcock Janet
Published: October 2022

This Viewpoint discusses the benefits of streamlined point-of-care trial designs in clinical research, using lessons learned from the UK RECOVERY study of dexamethasone dosing for patients with COVID-19 and hypoxia.
Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer
Authors: Moretz Chad , Byfield Stacey DaCosta , Hatchell Kathryn E. , Dalton Joline , Onglao Peter Nicholas , Hang Lillian , Hansen Pamela , Radford Cristi , Nielsen Sarah M. , Heald Brandie , Munro Sandra B. , Nussbaum Robert L. , Esplin Edward D.
Published: October 2022

Importance

In 2020, some health insurance plans updated their medical policy to cover germline genetic testing for all patients diagnosed with colorectal cancer (CRC). Guidelines for universal tumor screening via microsatellite instability and/or immunohistochemistry (MSI/IHC) for mismatch repair protein expression for patients with CRC have been in place since 2009.

Objectives

To examine whether uptake of MSI/IHC screening and germline genetic testing in patients with CRC has improved under these policies and to identify actionable findings and management implications for patients referred for germline genetic testing.

Design, Setting, and Participants

The multicenter, retrospective cohort study comprised 2 analyses of patients 18 years or older who were diagnosed with CRC between January 1, 2017, and December 31, 2020. The first analysis used an insurance claims data set to examine use of MSI/IHC screening and germline genetic testing for patients diagnosed with CRC between 2017 and 2020 and treated with systemic therapy. The second comprised patients with CRC who had germline genetic testing performed in 2020 that was billed under a universal testing policy.

Main Outcomes and Measures

Patient demographic characteristics, clinical information, and use of MSI/IHC screening and germline genetic testing were analyzed.

Results

For 9066 patients with newly diagnosed CRC (mean [SD] age, 64.2 [12.7] years; 4964 [54.8%] male), administrative claims data indicated that MSI/IHC was performed in 6645 eligible patients (73.3%) during the study period, with 2288 (25.2%) not receiving MSI/IHC despite being eligible for coverage. Analysis of a second cohort of 55 595 patients with CRC diagnosed in 2020 and covered by insurance found that only 1675 (3.0%) received germline genetic testing. In a subset of patients for whom germline genetic testing results were available, 1 in 6 patients had pathogenic or likely pathogenic variants, with most of these patients having variants with established clinical actionability.

Conclusions and Relevance

This nationwide cohort study found suboptimal rates of MSI/IHC screening and germline genetic testing uptake, resulting in clinically actionable genetic data being unavailable to patients diagnosed with CRC, despite universal eligibility. Effective strategies are required to address barriers to implementation of evidence-based universal testing policies that support precision treatment and optimal care management for patients with CRC.
Reimagining Children’s Rights in the US
Authors: Barnert Elizabeth , Wright Joseph , Choi Charlene , Todres Jonathan , Halfon Neal ,   Reimagining Children’s Rights Steering Committee, Advisory Committee, and Project Team, Abaya Miriam A , Adedokun Lola A , Akl Abdullah , Alexander David T , Alvarez Mayra E , Aron Laudan Y , Auerswald Colette L , Barbosa Gabriella , Battle Gabrielle C , Bunnett Dana M , Chow Giselle , Christakis Dimitri A , Counts Nathaniel Z , El-Amin Champion Tezzaree S , Engman Mark G , Ewing Toby J , Gentile-Montgomery Chloe R , Godoy Blanca , Goldhagen Jeffrey L , Gran Brian , Hernandez Giovanni , Iyer Puja , Jones-Taylor Myra , Kemp Jasmin M , Kirsch Kayla A , Lansdown Gerison , Lazarus Wendy , Lesley Bruce , Lombardi Joan , López Hernández Guadalupe , Mejia-Garzaro Brianna N , Michael Brown Keaun , Morales Xavier , Moulton Melissa K , Peiffer Matthew B , Peńa Andrea R , Pitre Nikki , Porayouw William F , Poterek Lauren A , Santana Sandy , Sayed Rimsha S , Schotland Marieka S , Thomas III Bernard L , Togi Dashuri (Dash) L , Woodhouse Barbara , Zhang Adrianna
Published: October 2022

Importance

The US faces a pivotal moment of opportunity and risk regarding issues affecting children (aged 0-17 years). Although the US remains the only United Nations member state to not have ratified the Convention on the Rights of the Child (CRC), a child rights framework is essential for child health professionals seeking to advance many issues affecting children in the US. The Reimagining Children’s Rights project (2020-2021) conducted an in-depth environmental scan of relevant literature and policy analysis using the Three Horizons design process to assess strategies that could advance the rights and well-being of children in the US. The project was overseen by a steering committee and informed by an advisory committee composed of youth leaders and experts in children’s rights, advocacy, health, law, and a range of child-specific issues (eg, youth justice, early childhood development), who provided expert input on strategic considerations for advancing children’s rights.

Observations

Seven findings about advancing children’s rights in the US are notable, all reflecting current gaps and opportunities for using a whole-child rights framework in the US, even without formal adoption of the CRC. Actionable strategies, tactics, and tools to leverage sustainable change in the multitude of issue areas can advance the current state of children’s rights. High-potential strategies for catalyzing advancement of children’s rights include youth activism, innovations in governance and accountability, legislative action, impact litigation, place-based initiatives, education and public awareness, alignment with other children’s movements, and research. The child rights framework is unifying and adaptive to future unforeseen challenges.

Conclusions and Relevance

Children’s rights provide a powerful, synergistic framework for child health professionals—in partnership with youth and other leaders—to increase equity and protect the rights and well-being of all children in the US.
Flowsheet generation through hierarchical reinforcement learning and graph neural networks
Authors: Stops Laura , Leenhouts Roel , Gao Qinghe , Schweidtmann Artur M.
Published: October 2022

Process synthesis experiences a disruptive transformation accelerated by artificial intelligence. We propose a reinforcement learning algorithm for chemical process design based on a state‐of‐the‐art actor‐critic logic. Our proposed algorithm represents chemical processes as graphs and uses graph convolutional neural networks to learn from process graphs. In particular, the graph neural networks are implemented within the agent architecture to process the states and make decisions. We implement a hierarchical and hybrid decision‐making process to generate flowsheets, where unit operations are placed iteratively as discrete decisions and corresponding design variables are selected as continuous decisions. We demonstrate the potential of our method to design economically viable flowsheets in an illustrative case study comprising equilibrium reactions, azeotropic separation, and recycles. The results show quick learning in discrete, continuous, and hybrid action spaces. The method is predestined to include large action‐state spaces and an interface to process simulators in future research.
[3+2] Cycloaddition Reactions of 2‐Ylidene Acenaphthylenones with 3‐Benzylidene Succinimides and 1,4‐Benzoxazinone Derivatives
Authors: Dahiya Pooja , Yadav Anoop , Rawat Megha , Peddinti Rama Krishna
Published: October 2022

A base‐catalyzed novel [3+2] cycloaddition reaction between arylidene‐1‐phenyl succinimides and alkylidene acenaphthylenones is carried out to access succinimide substituted spiro[acenaphthylenone‐cyclopentane]fused scaffolds with high regio‐ and stereo‐selectivity under mild conditions. The reaction of alkylidene acenaphthylenones with 1,4‐benzoxazinone derivatives under the influence of environmentally benign iodine afforded polyheterocyclic compounds embedded with pyrrole moiety. This metal‐free synthesis is highly efficient and atom economic and the protocol obviates column chromatography. The products are isolated by simple decantation followed by washing with solvent.
Reflections of manual labor in the hand entheses of early industrial women workers with extensively documented life histories
Authors: Karakostis Fotios Alexandros , Hotz Gerhard
Published: October 2022

Objectives

Sex‐based occupational variability constitutes a fundamental component of human behavior and a major focus of research focusing on biocultural evolution. However, the reliability of reconstructing physical activity in past women is often compromised by the lack of female skeletal collections with adequately documented lifetime occupations, domestic living conditions, medical records, and socioeconomic status. Here, we attempt to reconstruct habitual manual activity in a skeletal sample of early industrial women with uniquely archived life histories.

Materials and Methods

We rely on the application of our “Validated Entheses‐based Reconstruction of Activity” method on the hand skeletons of 38 extensively documented individuals from the Basel‐Spitalfriedhof collection. Our comparisons also include 40 documented males from the same collection.

Results

As expected, we found evidence of increased entheseal variability among women sharing the same unspecialized occupation (maids and factory workers). Moreover, certain entheseal patterns were almost exclusive to the men involved in occupations not associated with the female sex (mainly construction workers). Importantly, all six women known to have practiced more specific occupational activities (e.g., seamstresses) showed distinctive entheseal patterns, seemingly associated with more demanding physical practices. This within‐sex variation was not correlated with differences in biological age, estimated body size, socioeconomic status, relatedness, or the presence of reported children.

Discussion

Our findings directly reflect the rich historical sources on the working lives of low‐status women in early industrial Basel. These results highlight the high potential value of our documented sample as a reference basis for reconstructing the division of labor in bioarchaeological contexts.
Was there a need for high carbohydrate content in Neanderthal diets?
Authors: Klement Rainer J.
Published: October 2022

Objectives

In a recent paper, Hardy et al. (2022, Journal of Human Evolution 162: 103105) claim that the physiological Neanderthal requirement for plant carbohydrates may have reached 50%–60% of caloric intake, inferred from modern dietary guidelines and a putative need for high carbohydrate intake in pregnant/breastfeeding women and athletes. The aim of this article is to critically re‐examine these arguments under the premise that hominins could adapt to hypercarnivorous diets and low carbohydrate consumption.

Materials and Methods

Literature on ketogenic and carnivore diets was retrieved. A case report of a male rugby player voluntarily undertaking a carnivore diet under medical supervision is presented.

Results

Human metabolism is highly flexible towards adapting to long‐term low carbohydrate intakes by producing and utilizing ketone bodies. The evidence base of dietary guidelines is weak, and carbohydrate intake recommendations for athletes and during pregnancy/lactation are uncertain, making a translation to Neanderthal diets questionable. The studied rugby player maintained his sports performance and health over a 4‐months period despite minimal carbohydrate intake.

Discussion

Human physiology appears to have an extraordinary ability to utilize ketone bodies as a fuel for the brain and skeletal muscle, in particular also during exercise. The translation of dietary guidelines to Neanderthals and interpretation of studies in subjects not adapted to ketosis may be biased by a “glucocentric” perspective supposing that high carbohydrate intake is necessary for maintaining health. Allowing for the possibility of keto‐adaption leads to a more coherent integration of archeological and physiological data.
Spectro‐Microscopic Techniques for Studying Nanoplastics in the Environment and in Organisms
Authors: Mandemaker Laurens D. B. , Meirer Florian
Published: October 2022

Nanoplastics (NPs), small (<1 μm) polymer particles formed from bulk plastics, are a potential threat to human health and the environment. Orders of magnitude smaller than microplastics (MPs), they might behave differently due to their larger surface area and small size, which allows them to diffuse through organic barriers. However, detecting NPs in the environment and organic matrices has proven to be difficult, as their chemical nature is similar to these matrices. Furthermore, as their size is smaller than the (spatial) detection limit of common analytical tools, they are hard to find and quantify. We highlight different micro‐spectroscopic techniques utilized for NP detection and argue that an analysis procedure should involve both particle imaging and correlative or direct chemical characterization of the same particles or samples. Finally, we highlight methods that can do both simultaneously, but with the downside that large particle numbers and statistics cannot be obtained.
An Electrochemical Method for Deborylative Hydroxylation of Arylboronic Acids under Metal‐free Conditions
Authors: Fu Zhengjiang , Yi Xuezheng , Fang Ziqi , Zhong Tingting , He Dongdong , Guo Shengmei , Cai Hu
Published: October 2022

An electrochemical method for the synthesis of (poly)phenols via deborylative hydroxylation of arylborons has been well established under metal‐free conditions, whose practicability and advantage has been highlighted by the preparation of drug molecules and preformation of scalable transformation. Mechanistic studies have demonstrated that superoxide anion radical was involved in the conversion followed by the reaction with arylboronic acid substrate.
Implementation of a method for a clinical biochemistry lesson plan based on the flowchart
Authors: Haeri Mohammad Reza
Published: October 2022

Biochemistry is believed to be a difficult subject to understand for most life science and medical students. This article explains an experience with a flowchart‐based teaching approach that is applicable to different kinds of biochemistry courses (basic, medical, and clinical) for undergraduate and postgraduate students. After preparing the flowcharts, they were given to the students at the beginning of the semester, and the flowchart‐based teaching was performed for a whole semester. At the end of the semester, they were asked about the effectiveness and facilitation of learning using flowchart‐based teaching. This survey was performed for several semesters. Approximately, 95% stated that it facilitates learning and understanding.
Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long‐term clinical outcomes and health‐related quality of life assessment
Authors: Yan Chen‐hua , Wang Yu , Sun Yu‐qian , Cheng Yi‐fei , Mo Xiao‐dong , Wang Feng‐rong , Chen Yu‐hong , Zhang Yuan‐yuan , Han Ting‐ting , Chen Huan , Xu Lan‐ping , Zhang Xiao‐hui , Liu Kai‐yan , Huang Xiao‐jun
Published: October 2022

Background

Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health‐related quality of life (HR‐QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft‐versus‐host disease (GvHD)‐guided DLIs.

Methods

Consecutive patients who had refractory or relapsed AML and had received non‐T‐cell‐depleted allo‐HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)‐matched related HSCT or at 45‐60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.

Results

A total of 105 patients were eligible. Eighty‐seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2‐4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%‐50.6%) and 73.3% (95% CI = 67.4%‐79.2%), respectively. The cumulative incidence of relapse (CIR), transplant‐related mortality (TRM), and leukemia‐free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%‐41.1%), 22.1% (95% CI = 11.3%‐32.9%), and 46.4% (95% CI = 36.8%‐56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%‐37.6%), 21.6% (95% CI = 11.2%‐32.0%), and 50.8% (95% CI = 40.0%‐61.6%), respectively. At the end of follow‐up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR‐QoL.

Conclusions

Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long‐term LFS, but also with satisfactory HR‐QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.
Chemical Variability of Hexane Extracts from Five Subspecies of Calendula suffruticosa from Spain
Authors: Ohse Silvana , Marques Mariza B. , Silveira Paulo C. , Válega Mónica S. G. A. , Silva Artur M. S. , Pinto Diana C. G. A.
Published: October 2022

The chemical profile of the hexane extracts of the subspecies carbonellii, greuteri, marginata, trialata, and vejerensis of Calendula suffruticosa growing in Spain, herein described for the first time, were studied to access their value as a chemo taxonomical tool and search for potentially useful compounds. The subsp. greuteri and carbonellii showed higher extract yields. Terpenoids were the most abundant chemical class in subsp. carbonellii, greuteri, trialata, and vejerensis, while alkanes were the most abundant in subsp. marginata. Differences in chemical constituents were identified among the subspecies of C. suffruticosa analysed, which the PCA can prove. The subsp. trialata and greuteri showed more significant phytochemical similarity, which might indicate genetic proximity between these two subspecies. C. suffruticosa subsp. marginata presented the fewest number of compounds and in the smallest quantities, and C. suffruticosa subsp. vejerensis presented the largest number, however, both showed no alcohols. Furthermore, some of the compounds found in significant amounts are known for their pharmacological and nutraceutical properties, denoting potential use.
The HD Reaction of Nitrogenase: a Detailed Mechanism
Authors: Dance Ian
Published: October 2022

Nitrogenase is the enzyme that converts N2 to NH3 under ambient conditions. The chemical mechanism of this catalysis at the active site FeMo‐co [Fe7S9CMo(homocitrate)] is unknown. An obligatory co‐product is H2, while exogenous H2 is a competitive inhibitor. Isotopic substitution using exogenous D2 revealed the N2‐dependent reaction D2+2H++2e−→2HD (the ‘HD reaction’), together with a collection of additional experimental characteristics and requirements. This paper describes a detailed mechanism for the HD reaction, developed and elaborated using density functional simulations with a 486‐atom model of the active site and surrounding protein. First D2 binds at one Fe atom (endo‐Fe6 coordination position), where it is flanked by H−Fe6 (exo position) and H−Fe2 (endo position). Then there is synchronous transfer of these two H atoms to bound D2, forming one HD bound to Fe2 and a second HD bound to Fe6. These two HD dissociate sequentially. The final phase is recovery of the two flanking H atoms. These H atoms are generated, sequentially, by translocation of a proton from the protein surface to S3B of FeMo‐co and combination with introduced electrons. The first H atom migrates from S3B to exo‐Fe6 and the second from S3B to endo‐Fe2. Reaction energies and kinetic barriers are reported for all steps. This mechanism accounts for the experimental data: (a) stoichiometry; (b) the N2‐dependence results from promotional N2 bound at exo‐Fe2; (c) different N2 binding Km for the HD reaction and the NH3 formation reaction results from involvement of two different sites; (d) inhibition by CO; (e) the non‐occurrence of 2HD→H2+D2 results from the synchronicity of the two transfers of H to D2; (f) inhibition of HD production at high pN2 is by competitive binding of N2 at endo‐Fe6; (g) the non‐leakage of D to solvent follows from the hydrophobic environment and irreversibility of proton introduction.
Optical Manipulation of Gb3 Enriched Lipid Domains: Impact of Isomerization on Gb3‐Shiga Toxin B Interaction
Authors: Socrier Larissa , Ahadi Somayeh , Bosse Mathias , Montag Cindy , Werz Daniel B. , Steinem Claudia
Published: October 2022

The plasma membrane is a complex assembly of proteins and lipids that can self‐assemble in submicroscopic domains commonly termed “lipid rafts”, which are implicated in membrane signaling and trafficking. Recently, photo‐sensitive lipids were introduced to study membrane domain organization, and photo‐isomerization was shown to trigger the mixing and de‐mixing of liquid‐ordered (lo) domains in artificial phase‐separated membranes. Here, we synthesized globotriaosylceramide (Gb3) glycosphingolipids that harbor an azobenzene moiety at different positions of the fatty acid to investigate light‐induced membrane domain reorganization, and that serve as specific receptors for the protein Shiga toxin (STx). Using phase‐separated supported lipid bilayers on mica surfaces doped with four different photo‐Gb3 molecules, we found by fluorescence microscopy and atomic force microscopy that liquid disordered (ld) domains were formed within lo domains upon trans‐cis photo‐isomerization. The fraction and size of these ld domains were largest for Gb3 molecules with the azobenzene group at the end of the fatty acid. We further investigated the impact of domain reorganization on the interaction of the B‐subunits of STx with the photo‐Gb3. Fluorescence and atomic force micrographs clearly demonstrated that STxB binds to the lo phase if Gb3 is in the trans‐configuration, whereas two STxB populations are formed if the photo‐Gb3 is switched to the cis‐configuration highlighting the idea of manipulating lipid‐protein interactions with a light stimulus.
A comprehensive assessment of four whole blood stabilizers for flow‐cytometric analysis of leukocyte populations
Authors: Nguyen Ngoc Anh , Huang Xiaobo , Cabrera Luz E. , Pekkarinen Pirkka T. , Nowlan Kirsten , Strandin Tomas , Kantele Anu , Vapalahti Olli , Heinonen Santtu , Kekäläinen Eliisa
Published: October 2022

Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head‐to‐head the performance of four commercial whole blood cryopreservation kits; (1) Cytodelics, (2) Stable‐Lyse V2 and Stable‐Store V2 (SLSS‐V2), (3) Proteomic stabilizer (PROT‐1), and (4) Transfix. We found that PROT‐1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets—granulocytes, T cells, natural killer cells, and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilizers also maintained the activated phenotypes of neutrophils upon stimulation with N‐formylmethionyl‐leucyl‐phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16), and granule proteins (CD66b), as well as the shedding of surface L‐selectin (CD62L), was conserved most efficiently in PROT‐1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilizers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID‐19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilizers should depend on cell type of interest, as well as antibody clones and experimental design of each study.
Highly Flexible Graphene‐Film‐Based Rectenna for Wireless Energy Harvesting
Authors: Zhang Jingwei , Wang Yuchao , Song Rongguo , Kou Zongkui , He Daping
Published: October 2022

Herein, we report the design, fabrication, and performance of two wireless energy harvesting devices based on highly flexible graphene macroscopic films (FGMFs). We first demonstrate that benefiting from the high conductivity of up to 1 × 106 S m−1 and good resistive stability of FGMFs even under extensive bending, the FGMFs‐based rectifying circuit (GRC) exhibits good flexibility and RF‐to‐DC efficiency of 53% at 2.1 GHz. Moreover, we further expand the application of FGMFs to a flexible wideband monopole rectenna and a 2.45 GHz wearable rectenna for harvesting wireless energy. The wideband rectenna at various bending conditions produces a maximum conversion efficiency of 52%, 46%, and 44% at the 5th Generation (5G) 2.1 GHz, Industrial Long‐Term Evolution (LTE) 2.3 GHz, and Scientific Medical (ISM) 2.45 GHz, respectively. A 2.45 GHz GRC is optimized and integrated with an AMC‐backed wearable antenna. The proposed 2.45 GHz wearable rectenna shows a maximum conversion efficiency of 55.7%. All the results indicate that the highly flexible graphene‐film‐based rectennas have great potential as a wireless power supplier for smart Internet of Things (IoT) applications.
Seismic vulnerability of reinforced concrete buildings with discontinuity in columns
Authors: Gwalani Payal , Singh Yogendra , Varum Humberto
Published: October 2022

Irregular reinforced concrete (RC) buildings constitute a significant portion of the existing housing stock. A common type of irregularity is in the form of discontinuity in the vertical framing elements, which can exacerbate their seismic vulnerability. The design guidelines available in seismic design codes essentially cater to only regular buildings, and the safety of such buildings, even when the other guidelines of the codes are followed, is doubtful. This article evaluates the vulnerability of RC frame buildings with discontinuity in columns designed for modern seismic codes, in the form of seismic collapse capacity, collapse resistance against maximum earthquake demand level, and failure mechanism. The adequacy and limitations of the provisions of the seismic design codes are evaluated for such buildings. Analysis results show that the sequential analysis of buildings considering the construction staged effects, considerably affects the design and hence the collapse failure mechanism of even low‐ and mid‐rise buildings. The results also underline the importance of strong column–weak beam design in the seismic performance of the floating column buildings. The vertical component of ground motion is also observed to be relatively more crucial in floating column buildings.
Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta‐analysis
Authors: Becerra‐Tomás Nerea , Balducci Katia , Abar Leila , Aune Dagfinn , Cariolou Margarita , Greenwood Darren C. , Markozannes Georgios , Nanu Neesha , Vieira Rita , Giovannucci Edward L. , Gunter Marc J. , Jackson Alan A. , Kampman Ellen , Lund Vivien , Allen Kate , Brockton Nigel T. , Croker Helen , Katsikioti Daphne , McGinley‐Gieser Deirdre , Mitrou Panagiota , Wiseman Martin , Cross Amanda J. , Riboli Elio , Clinton Steven K. , McTiernan Anne , Norat Teresa , Tsilidis Konstantinos K. , Chan Doris S. M.
Published: October 2022

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta‐analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random‐effects linear dose‐response meta‐analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta‐analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta‐analysis was only possible for all‐cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25‐hydroxyvitamin D (25(OH)D), and for breast cancer‐specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited‐suggestive evidence that predefined dietary patterns may reduce the risk of all‐cause and other causes of death; that isoflavone intake reduces the risk of all‐cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92‐1.02), breast cancer‐specific mortality (RR for high vs low: 0.83, 95% CI: 0.64‐1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61‐0.92); that dietary fibre intake decreases all‐cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80‐0.94); and that serum 25(OH)D is inversely associated with all‐cause and breast cancer‐specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89‐0.97 and 0.94, 95% CI: 0.90‐0.99, respectively). The remaining associations were graded as limited‐no conclusion.
American Academy of Periodontology best evidence consensus statement on the use of biologics in clinical practice
Authors: Avila‐Ortiz Gustavo , Ambruster Jeanne , Barootchi Shayan , Chambrone Leandro , Chen Chia‐Yu , Dixon Douglas R. , Geisinger Maria L. , Giannobile William V. , Goss Katie , Gunsolley John C. , Heard Rick H. , Kim David M. , Mandelaris George A. , Monje Alberto , Nevins Marc L. , Palaiologou‐Gallis Angela , Rosen Paul S. , Scheyer E. Todd , Suarez‐Lopez del Amo Fernando , Tavelli Lorenzo , Velasquez Diego , Wang Hom‐Lay , Mealey Brian L.
Published: October 2022

A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenarios. Given their availability for routine clinical use and the existing amount of related evidence, the goal of this American Academy of Periodontology (AAP) best evidence consensus (BEC) was to provide a state‐of‐the‐art, evidence‐based perspective on the therapeutic application of autologous blood‐derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet‐derived growth factor BB (rhPDGF‐BB), and recombinant human bone morphogenetic protein 2 (rhBMP‐2). A panel of experts with extensive knowledge on the science and clinical application of biologics was convened. Three systematic reviews covering the areas of periodontal plastic surgery, treatment of infrabony defects, and alveolar ridge preservation/reconstruction and implant site development were conducted a priori and provided the foundation for the deliberations. The expert panel debated the merits of published data and exchanged experiential information to formulate evidence‐based consensus statements and recommendations for clinical practice and future research. Based on an analysis of the current evidence and expert opinion, the panel concluded that the appropriate use of biologics in periodontal practice is generally safe and provides added benefits to conventional treatment approaches. However, therapeutic benefits and risks range based on the specific biologics used as well as patient‐related local and systemic factors. Given the limited evidence available for some indications (e.g., gingival augmentation therapy, alveolar ridge preservation/reconstruction, and implant site development), future clinical studies that can expand the knowledge base on the clinical use of biologics in periodontal practice are warranted.
Fibrotic and inflammatory characteristics of epidural fat adjacent to the ossification area in patients with ossification of the ligament flavum
Authors: Dou Xinyu , Mao Tianli , Ma Yunlong , Jia Fei , Liu Yu , Liu Xiaoguang
Published: October 2022

Objectives

To observe histological and inflammatory characteristics of epidural fat (EF) adjacent to the ossification area in patients with ossification of the thoracic ligament flavum (TOLF) and provide a preliminary research basis for investigating the impact of the EF on OLF.

Methods

Samples of EF and autologous subcutaneous adipose tissue (SCAT) from TOLF patients (n = 26) and non‐TOLF patients (n = 23) were harvested during posterior thoracic spine surgery. Adipocyte size and fibrosis were measured by histology. Vascularization and inflammatory cell infiltration were evaluated by immunohistochemical staining. Adipogenesis‐related genes were assessed by real‐time quantitative PCR. Conditioned media from cultured EF were evaluated via enzyme‐linked immunosorbent assay to detect the secretion of inflammatory cytokines, including interleukin‐6 (IL‐6), tumor necrosis factor (TNF‐α), and leptin. The phosphorylated STAT3 protein level in ligament flavum (LF) was examined using Western blot.

Results

Adipocytes size in EF was similar between in the TOLF and non‐TOLF groups, but significantly smaller than that from autologous SCAT. Adipogenesis‐related mRNA expression in EF was lower than that in SCAT. More fibrosis and vascularization were found in TOLF than in non‐TOLF. EF in the TOLF group exhibited more macrophages and B lymphocytes infiltrated. The levels of cytokines such as IL‐6, TNF‐α, and leptin secreted by EF were significantly higher in the TOLF group than non‐TOLF. The level of phosphorylated STAT3 in LF was significantly upregulated in the TOLF group.

Conclusions

Morphologically, EF adjacent to the ossification area is smaller and more uniform than autologous SCAT, exhibiting a characteristic similarity to visceral fat. EF in the TOLF group shows a more fibrotic, vascularized, and inflammatory phenotype, which secretes multiple cytokines. The phosphorylated STAT3 protein was significantly upregulated in the TOLF group. Whether these properties of EF directly affect the process of OLF needs to be further explored.
5‐Aminolevulinic Acid‐Mediated Photodynamic Therapy Improves Vocal Fold Wound Healing in Rats
Authors: Zhang Chi , Pang Wenting , Gong Ting , Jiang Jack J. , Silverman Matthew , Li Gelin
Published: October 2022

Objective

Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo.

Study Design

In vivo.

Methods

Vocal fold stripping was performed in Sprague–Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5‐Aminolevulinic Acid (5‐ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm2. PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real‐time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin–eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III.

Results

PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFβ1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm2 PDT group.

Conclusion

PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring.

Level of Evidence

N/A Laryngoscope, 133:1943–1951, 2023
SRv6‐based Time‐Sensitive Networks (TSN) with low‐overhead rerouting
Authors: Nandha Kumar Gagan , Katsalis Kostas , Papadimitriou Panagiotis , Pop Paul , Carle Georg
Published: October 2022

Time‐Sensitive Networks (TSN) aims at providing a solid underpinning for the support of application connectivity demands across a wide spectrum of use cases and operational environments, such as industrial automation and automotive networks. However, handling network updates in TSN entails additional challenges, stemming from the need to perform both flow rerouting and TSN schedule reconfiguration. To address this issue, we propose a software‐defined network (SDN)‐based approach for low‐overhead TSN network updates, exploiting segment routing over IPv6 (SRv6) for path control. To this end, we introduce the concept of TSN subgraphs in order to quickly reschedule the flows traversing the problematic area and propose a TSN‐aware routing heuristic to minimize the convergence time. We further describe the control plane implementation and its integration into Mininet, which empowers us to conduct a wide range of performance tests. Our evaluation results indicate that our approach yields faster recovery and reduces significantly the number of required reconfigurations upon failures, at the expense of a small SRv6 encoding/decoding overhead.
Ternary structure design based on hydrogen bonding for transparent and flame retardant PMMA with good mechanical properties
Authors: Xie Wang , Liu Yuan , Yu Mingming , Wang Qi
Published: October 2022

The synthesis of intrinsic flame retardant copolymer by copolymerization with reactive flame retardants is the most potential method to prepare transparent and flame retardant poly (methyl methacrylate) (PMMA) at present，but the main challenge of this method is that the copolymer usually has poor mechanical properties and heat resistance. In this work, the hydrogen bond enhancement strategy is adopted, and the flame retardant PMMA with excellent comprehensive properties is obtained by ternary copolymerization with methyl methacrylate (MMA) as matrix unit, diethyl (methacryloyloxymethyl) phosphonate (DEP) as flame retardant unit and methacrylamide (MAA) as hydrogen bond unit. Due to the formation of intermolecular hydrogen bond via MAA unit, the storage modulus, flexural strength and impact strength of the terpolymer containing 15 mol% MAA are 48%, 19%, and 24% higher than those of the copolymer of MMA and DEP, and its hardness, glass transition temperature and load thermal deformation temperature (increased by 7°C) are also superior. Moreover, owing to the gas‐phase dilution and charring flame retardancy of MAA unit, the terpolymer shows increased limiting oxygen index (24.3%) and UL94 rating (V‐1). This work not only provides a promising flame retardant PMMA for practical application, but also offers a new strategy to design flame retardant polymers with good mechanical properties.
Synthesis and chemoselective crosslinking of functionalized polyesters from bio‐based epoxides and cyclic anhydrides
Authors: Haslewood Marcell N. D. , Farmer Thomas J. , North Michael
Published: October 2022

Biomass derivable epichlorohydrin undergoes ring‐opening copolymerization with either succinic or itaconic anhydride (both biosourcable) under standard laboratory conditions using metal‐based or an entirely organic initiator to form highly functionalized, low molecular weight polyesters. The linear polyesters obtained from epichlorohydrin and itaconic anhydride contain both alkyl chlorides and α,β‐unsaturated esters and can be crosslinked to form insoluble resins by treatment with di‐ to tetra‐functional amines and thiols. Crosslinking with amines predominately occurs through the alkyl chlorides whilst crosslinking with thiols occurs through the α,β‐unsaturated esters allowing the synthesis of insoluble polyester derived resins with complementary and controllable functionalities.
Simultaneous fault‐tolerant control and disturbance rejection for systems with fault in polynomial form
Authors: Jiao Yu , Pang Guochen , Mou Xiaojian , Zhang Ancai , Qiu Jianlong , Cao Jinde
Published: October 2022

This article studies the simultaneous fault‐tolerant control and disturbance rejection for systems with fault in polynomial form. The unknown external disturbance is considered to be caused by the external source system, and the fault can be expressed as a polynomial function of time. Combining the fault observer and the disturbance observer, a controller is designed, which can not only diagnose the fault, but also improve the anti‐disturbance performance. Finally, a numerical example is given to verify the validity of the results.
Bet on innovation, not Environmental, Social and Governance metrics, to lead the Net Zero transition
Authors: Madden Bartley J.
Published: October 2022

The conventional Net Zero perspective with its emphasis on Environmental, Social and Governance (ESG) metrics represents linear cause‐and‐effect thinking. That is, implementation of the metrics will then change company behaviour with the eventual effect of a successful Net Zero transition. Different perspectives are presented, rooted in systems thinking. Numerous company examples explain why innovation, not ESG metrics, will be the prime mover in achieving Net Zero. The crux of the argument for systems thinking is that a company like Honeywell, currently given an ‘F’ ESG score, is delivering stellar innovations that will enable its customers to significantly reduce their greenhouse gas emissions. As to behaviour, boards of directors should demand new information from management with particular attention to returns on capital versus the cost of capital under scenarios that include a price (tax) on carbon. The integration of corporate finance principles with systems thinking will improve decision‐making and facilitate an efficient Net Zero transition.