bluuebunny/crossref_metadata_2025 huggingface dataset:
role of laughter in establishing solidarity and status
Authors: McLachlan Angus James
Published: August 2022

Drawing on a range of American, Australian, British and Scandinavian research into laughter, the current paper will use the form of pragmatic analysis typically found in qualitative research and apply it to data produced by the quantitative methodology common in the author’s own discipline of psychology. Laughter will be examined as an indexical that serves both a discourse deictic function, designating the utterance in which it occurs as non-serious, and a social deictic function, marking the laughing person’s preference for social proximity with fellow interlocutors. The paper will then analyse examples and data pertaining to three types of laughter bout derived from taking laughter as an indexical. First, solitary listener laughter will be argued to signify a deferential acknowledgement of continued solidarity with the speaker. Second, solitary speaker laughter will be suggested to mark a simple preference for solidarity. Third, joint laughter will be accepted as a signifier of actual solidarity that may also be used to mark status depending on which party typically initiates the joint laughter. Joint laughter thus acts in a manner closely analogous to the exchange of another set of indexicals, the T and V versions of second person pronouns in European languages. Finally, the paper will conclude by examining the problematic case of laughing at another interlocutor, before briefly considering the implications of this pragmatic perspective for traditional accounts of laughter as well as for future research.
On the Effect of Seasonal Averages and Standard Deviations on Buys-Ballot Estimates of Time Series Components in the Presence of Missing Values
Authors: Dozie Kelechukwu C. N. , Ihekuna Stephen O.
Published: August 2022

In this study, we consider the effect of seasonal averages and seasonal standard deviations on Buys-Ballot estimates of time series components in the presence of missing values. The emphasis is to compare seasonal averages with seasonal standard deviations in the presence and absence of missing values using real life example. The methods adopted are Mean Imputation (MI), Regression Imputations (RI) and Buys-Ballot Procedure (BBP) for estimating missing values in time series data. Result of this analysis shows that, the differences between Seasonal averages and seasonal standard deviations with and without missing values have insignificant effect on the Buys-Ballot estimates of time series components.
Delineation and Mapping of Groundwater Quality in Chengalpattu District of Tamil Nadu, India
Authors: Hemavarshini M. P. , Janaki D. , Baskar M. , Radhika S. , Jagadeeswaran R.
Published: August 2022

Groundwater is a major natural source of water supply all around the world. It's utilised for irrigation, industry, and even household purposes. The quality of groundwater is important for irrigation. Irrigation water quality plays a critical role in long-term soil productivity. To assess the quality of the groundwater, 149 samples were taken in May 2022 from the coastal blocks of the Chengalpattu district: Chithamur (42), Lathur (37), Thirukalukundram (31), and Thiruporur (39). The samples were analysed in accordance with the appropriate protocol. The study revealed that the coastline blocks pH ranges from 8.92 to 7.52 and their EC ranges from 11.50 to 0.13 dS m-1. The Sodium Absorption Ratio (SAR) ranges from 20.00 to -6.80, while the Residual Sodium Carbonate (RSC) ranges from 14.77 to 0.26 meq/L. The Chengalpattu district has a high concentration of alkali water, according to CSSRI, Karnal classification. Among the coastal blocks, the Thiruporur block contains more alkali water compared to other coastal blocks (46%).
Effect of Laparoscopic Ovarian Cystectomy of Endometriotic and Non-Endometriotic Cysts on Ovarian Volume, Ovarian Reserve and Ovarian Doppler Velocimetry
Authors: Elagha Ahmed Salah Abo , Dawood Aymn Shehata , Elshorbagy Shahenaz Hamdy , Ghareeb Ashraf Elmohamady
Published: August 2022

Background: Laparoscopic ovarian cystectomy (LOC) is one of the most often performed and simplest gynaecological procedures. The aim of this study was to evaluate the change in ovarian reserve, ovarian volume and ovarian Doppler velocimetry after LOC, between endometrioma patients and other benign ovarian cysts.

Methods: Eighty participants were enrolled in this prospective cohort research. Aged 18-40 years suffering from unilateral ovarian cysts. Patients were classified into two equal groups: group I: unilateral (endometriotic cyst), and group II: unilateral (non-endometriotic cyst) each group was subdivided into 2 equal subgroups. Group I: subgroup A: stripping and subgroup B: cauterization. Group II: subgroup A: dermoid cysts and subgroup B: simple serous cyst.

Results: AMH (antimullerian hormone) post operation and after 3 months were significantly higher in stripping than cauterization subgroups. AMH post operation and after 3 months, AFC (unilateral antral follicle counts) after operation and reduction in AFC were significantly lower in stripping subgroup in endometrioma than dermoid subgroup in non-endometrioma. AFC before operation, reduction in AMH post 3 months, reduction in AFC and reduction in ovarian volume were significantly lower in dermoid than simple cyst subgroups in non- endometrioma group. AFC after operation was significantly higher in dermoid than simple cyst subgroups in non- endometrioma group.

Conclusions: AMH was higher in stripping subgroup than cauterization subgroup in endometrioma group post-operatively. AFC was higher in simple subgroup than dermoid subgroup in non-endometrioma group before operation, but no significant difference was noted after operation.
Evaluation of YKL-40 as a Biomarker of Inflammation and Atherosclerosis in Chronic Kidney Disease Patients
Authors: El-Ghorab Omar Ali Abdel Naby , Elshafey Mohamed Hassan Rashad , Negm Manal Saad Ahmed , Elkhateeb Mervat Abdel-Hameed Taha
Published: August 2022

Background: Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. In Egypt, CKD approximately affects 13% of the adult population, resulting in significant morbidity, mortality, and health care costs. Patients with advanced CKD (stage 3 or more) experience a high rate of cardiovascular complications compared to earlier stages of CKD.

Objective: To evaluate serum YKL-40 levels in patients with CKD to assess its value as a biomarker of inflammation and its correlation with carotid intima-media thickness (CIMT) as a predictor for early atherosclerosis.

Patients and Methods:  The present study was conducted on fifty subjects divided into 2 groups: group I includes 25 patients with CKD (from stage 1 to stage 5 "pre-dialysis") and group II (control group) includes 25 healthy volunteers. The patients were recruited from Internal Medicine Department and Nephrology Unit, Tanta university hospitals in the period between," August 2020 to September 2021 ".

Results: In our study, YKL-40 levels were significantly high in CKD patients(P=0.001). As regards CIMT measurements for the studied cases its median value was 0.90 and1 mm for the right and left carotid respectively. On the other hand, CIMT measurements for the studied volunteers were within the normal range with statistically significant differences between both groups (p=0.001). There is a positive significant correlation between the serum YKL-40 level from the studied cases with each of triglycerides, serum urea, serum creatinine, CRP, ESR, R CIMT, and L CIMT. Systolic blood pressure, triglyceride, cholesterol, LDL, serum urea, serum creatine, e-GFR, ESR, CRP, and YKL-40 were found to be independent predictors for CIMT (P<0.05). Serum YKL-40 is a highly sensitive predictor of atherosclerosis in CKD and its specificity is 74% in CKD cases.

Conclusion: Serum YKL-40 was significantly high in CKD patients. YKL-40 could be used as a biomarker for inflammation and early detection of atherosclerosis in patients with CKD, but further studies are needed. YKL-40 is an independent predictor of increased CIMT and early atherosclerosis.  YKL-40 is highly sensitive to increased CIMT.
Nonlinear Radial Consolidation Analysis of Vertical Drains Foundation under Cyclic Loadings
Authors: Yan Si , Miao Yong-hong , Yin Jie
Published: August 2022

Aiming at the stability of storage facilities built in soft soil areas, this paper analyzes the influence of cyclic loading on consolidation during used stage. Firstly, the nonlinear compressibility and permeability of soil are introduced, the well resistance and three kinds of radial permeability coefficient modes are considered, the corresponding governing equations are obtained, and the corresponding analytical solution is obtained by the separate variables method. Then, the corresponding solution under the action of trapezoidal and triangular cyclic loading is obtained. The rationality of the solution in this paper is verified by the degradation method. Finally, the settlement of storage facilities during the using period is predicted by case analysis. The results show that the ratio of soil compression index to permeability index (Cc/Ck) and the radial permeability coefficient mode have no significant influence on the average consolidation degree. The load-related intermittent parameter β, the loading parameter α, and the parameter Nσ have a great influence on the average consolidation degree. The smaller the three parameters are, the more energy the load generates at the same time, and the greater the corresponding average degree of consolidation. The solution can be effectively applied to nonlinear radial consolidation analysis under trapezoidal and triangular cyclic loadings.
DINÂMICAS DA AÇÃO COLETIVA NO BRASIL CONTEMPORÂNEO: encontros e desencontros entre o sindicalismo e a juventude trabalhadora
Authors: Braga Ruy , Aurélio Santana Marco
Published: August 2022

Tendo em vista o lugar tradicional dos sindicatos como canal de organização e condução de conflitividade na sociedade brasileira, o artigo se propõe articular a reconfiguração das classes sociais no Brasil contemporâneo, as manifestações atuais da inquietação social e a situação dos sindicatos frente a essa nova configuração. A especial ênfase ao papel dos sindicatos nesta nova conjuntura global parte da premissa de que as diferentes respostas dos sindicatos nacionais ao advento do protagonismo político da juventude trabalhadora em condições precárias de vida e de trabalho representam uma oportunidade privilegiada de observação das atuais reconfigurações classistas em contextos de crise. Palavras-chave: Trabalho. Trabalhadores. Juventude. Sindicatos. Ação Coletiva. DYNAMICS OF COLLECTIVE ACTIONS IN CONTEMPORARY BRAZIL: agreements and disagreements between unionism and the youth worker force Ruy Braga Marco Aurélio Santana Taking into account the traditional Unions’ role in the conflict organization and mobilization in the Brazilian society, the article associates the social classes reconfiguration, contemporary social uneasiness and their impacts upon Brazilian Unionism. The main emphasis on Unions’ role is related to the hypothesis that the different responses from Unions to this new scenario is a privileged opportunity to observe the current social classes reconfiguration during a crisis period and the resulting dynamics of collective action. Keywords: Work. Workers. Youth. Unions. Collective Action DYNAMIQUES DE L’ACTION COLLECTIVE AU SEIN DU BRÉSIL CONTEMPORAIN: Convergences et divergences entre le syndicalisme et les jeunes travailleurs Ruy Braga Marco Aurélio Santana Compte tenu de la place traditionnelle occupée par les syndicats en tant que moyen d’organisation et de résolution des conflits dans la société brésilienne, cet article se propose d’articuler la reconfiguration des classes sociales au sein du Brésil contemporain, ainsi que les manifestations actuelles de l’inquiétude sociale et la situation des syndicats face à cette nouvelle configuration. L’accent mis tout particulièrement sur le rôle des syndicats dans cette nouvelle conjoncture mondiale part du principe que les différentes réponses des syndicats nationaux face à l’avènement du rôle politique de la jeunesse travaillant dans des conditions précaires de vie et de travail sont une excellente occasion pour observer les reconfigurations actuelles des paramètres de classe dans le contexte d’une crise. Mots-clés: Travail. Travailleurs. Jeunesse. Syndicats. L’action collective. Publicação Online do Caderno CRH no Scielo: http://www.scielo.br/ccrh Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.br
A CAUSA E AS POLÍTICAS DE DIREITOS HUMANOS NO BRASIL
Authors: Engelmann Fabiano , Mori Madeira Lígia
Published: August 2022

Pretende-se analisar a emergência e consolidação da causa dos direitos humanos no Brasil nas últimas dé- cadas. O argumento principal é que o movimento dos direitos humanos emerge, como em outros contextos da América latina, a partir da contestação do regime militar-autoritário e consolida-se a partir de marcos institucionais após a redemocratização do país. A análise do perfil das causas e dos trajetos dos principais líderes do movimento no Brasil permite afirmar que os direitos humanos transformam-se, ao longo da dé- cada de 90, em uma “causa de Estado”. Um dos indicadores mais forte dessa transformação é a articulação entre os movimentos militantes e a burocracia governamental e a expansão de programas de direitos humanos principalmente nas regiões sul, sudeste e norte. Palavras-chave: Brasil. Direitos Humanos. Ativismo. Políticas Públicas. HUMAN RIGHTS CAUSES AND POLICIES IN BRAZIL Fabiano Engelmann Lígia Mori Madeira This study analyzes the emergence and consolidation of the human rights cause in Brazil over the last decades. The main argument is that the human rights movement emerged, as in other Latin American contexts, from the fight against totalitarian regimes, and was consolidated with institutional achievements after the re-democratization of the country. Analyzing the profile of the causes and trajectories of the main leaders of the movement in Brazil enables us to state that the human rights have become, over the 1990s, a “cause of the State”. One of the strongest indicators of this transformation is the articulation between militant movements and the government bureaucracy, and the expansion of human rights programs across Brazil, especially in the South, Southeast and North. Keywords: Brasil. Human Rights. Activism. Public Policies LA CAUSE ET LES POLITIQUES DES DROITS DE L’HOMME AU BRÉSIL Fabiano Engelmann Lígia Mori Madeira L’article se veut d’analyser l’apparition et la consolidation de la cause des droits de l’homme au Brésil au cours des dernières décennies. Le principal argument est que le mouvement des droits de l’homme surgit, comme dans d’autres contextes en Amérique latine, de la contestation du régime militaire autoritaire et qu’il s’est consolidé dans le cadre institutionnel après la re-démocratisation du pays. L’analyse du profil des causes et de la trajectoire des principaux leaders du mouvement au Brésil nous permet d’affirmer que les droits de l’homme se sont transformés au cours des années 90 en une “cause d’État”. L’un des indicateurs les plus forts de cette transformation est le rapport entre les mouvements militants et la bureaucratie gouvernementale ainsi que l’expansion de programmes de défense des droits de l’homme, surtout dans les régions sud, sud-est et nord du pays. Mots-clés: Brésil. Droits de l’Homme. Activisme. Politiques Publiques. Publicação Online do Caderno CRH no Scielo: http://www.scielo.br/ccrh Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.br
Neuron–Glial Interactions in Health and Brain Cancer
Authors: Pan Yuan , Monje Michelle
Published: August 2022

Brain tumors are devastating diseases of the central nervous system. Brain tumor pathogenesis depends on both tumor‐intrinsic oncogenic programs and extrinsic microenvironmental factors, including neurons and glial cells. Glial cells (oligodendrocytes, astrocytes, and microglia) make up half of the cells in the brain, and interact with neurons to modulate neurodevelopment and plasticity. Many brain tumor cells exhibit transcriptomic profiles similar to macroglial cells (oligodendrocytes and astrocytes) and their progenitors, making them likely to subvert existing neuron–glial interactions to support tumor pathogenesis. For example, oligodendrocyte precursor cells, a putative glioma cell of origin, can form bona fide synapses with neurons. Such synapses are recently identified in gliomas and drive glioma pathophysiology, underscoring how brain tumor cells can take advantage of neuron–glial interactions to support cancer progression. In this review, it is briefly summarized how neurons and their activity normally interact with glial cells and glial progenitors, and it is discussed how brain tumor cells utilize neuron–glial interactions to support tumor initiation and progression. Unresolved questions on these topics and potential avenues to therapeutically target neuron–glia–cancer interactions in the brain are also pointed out.
Quantitative System Modeling Bridges the Gap between Macro‐ and Microscopic Stomatal Model
Authors: Rui Mengmeng , Jing Yi , Jiang Hangjin , Wang Yizhou
Published: August 2022

An understanding of stomatal function is vital for the carbon and water cycle in nature. In the past decades, various stomatal models with different functions have been established to investigate and predict stomatal behavior and its association with plants’ responses to the changing climate, but with limited biological information provided. On the other hand, many stomatal models at the molecular level focus on simulating and predicting molecular practices and ignore the dynamic quantitative information. As a result, stomatal models are often divided between the microscopic and macroscopic scales. Quantitative systems analysis offers an effective in silico approach to explore the link between microscopic gene function and macroscopic physiological traits. As a first step, a systems model, OnGuard, is developed for the investigation of guard cell ion homeostasis and its relevance to the dynamic stomatal movements. The system model has already yielded a series of important predictions to guide molecular physiological studies in stomata. It also exhibits great potential in breeding practice, which represents a key step toward “Breeding by design” of improving plant carbon–water use efficiency. Here, the development of stomatal models is reviewed, and the future perspectives on stomatal modeling for agricultural and ecological applications are discussed.
A DNA Aptamer Targeting Cellular Fibronectin Rather Than Plasma Fibronectin for Bioimaging and Targeted Chemotherapy of Tumors
Authors: Zou Yujian , Wang Yufei , Wen Xiaohong , Li Chihao , Lei Lei , Guo Qiuping , Sun Guoming , Yu Li , Nie Hemin
Published: August 2022

Fibronectin (FN) is a well‐established hallmark of epithelial‐to‐mesenchymal transition, and may serve as an omnipresent cancer biomarker regardless of the origins of tumor cells. An ssDNA aptamer (ZY‐1) with highly selective binding affinity to mesenchymal stromal cells is previously developed, but the binding target of ZY‐1 on the cells and the underlying mechanism is yet to be understood. Here, the identification of FN as the target protein of aptamer ZY‐1 is reported for the first time and the mechanism of ZY‐1 binding to cFN is explored. The data indicate that ZY‐1 solely recognizes cellular fibronectin (cFN) rather than plasma fibronectin (pFN). The ZY‐1 binding to cFN is explored through computational modeling and the competition of heparin in binding cFN owing to steric hindrance is confirmed. The in vitro assay and noninvasive in vivo fluorescence imaging results validate the specificity of ZY‐1 in targeting cFN and sensitivity in detecting tumors. The ZY‐1‐mediated targeted cancer therapy using a proof‐of‐concept study with a ZY‐1‐based complex loaded with doxorubicin (Dox) is further proved. This study would facilitate more comprehensive studies of anti‐FN aptamers in the imaging and treatment of tumors and other FN‐associated diseases.
Inorganic‐Rich and Flexible Solid‐Electrolyte Interphase Formed Over Dipole‐Dipole Interaction for Highly Stable Lithium‐Metal Anodes
Authors: Zhu Jinqi , Cui Zhe , He Shu‐Ang , Wang Hao , Gao Mengluan , Wang Wenqing , Yang Jianmao , Xu Xintong , Hu Junqing , Lu Aijiang , Zou Rujia
Published: August 2022

The uncontrollable lithium (Li) dendrite growth and unstable solid electrolyte interfaces (SEI) hinder the practical application of Li metal batteries (LMBs). Herein, a PAN/CNTs‐based SiO2‐modified vertical‐cavity film (PCS‐VCF) with a network structure is prepared by a simple spin‐coating process to address these challenges. This new current collector with a polar lithiophilic network stabilizes the Li metal anodes by regulating the chemical environment in carbonate electrolytes. The dipole interaction between the CN groups and the CO groups reduces the high reactivity of the carbonates in the electrolyte, forming an SEI layer with higher inorganic components and enhancing the stability of the electrode/electrolyte interface. The special vertical‐cavity network structure inside the current collector can decrease local current density and suppress the huge volume expansion of Li metal during the cycling process. Consequently, a high‐performance Li metal anode with dendrite‐free morphology is achieved (over 1500 cycles with low overpotential at 20 mA cm−2 in symmetric cells). Furthermore, full cell with the LiNi0.8Co0.1Mn0.1O2 cathode delivers a stable capacity of 164.5 mA h g−1 for 500 cycles at 5 C, with a capacity decay rate of 0.077% per cycle.
The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow
Authors: Mansouri Mehran , Ahmed Adeel , Ahmad S. Danial , McCloskey Molly C. , Joshi Indranil M. , Gaborski Thomas R. , Waugh Richard E. , McGrath James L. , Day Steven W. , Abhyankar Vinay V.
Published: August 2022

Microfluidic tissue barrier models have emerged to address the lack of physiological fluid flow in conventional “open‐well” Transwell‐like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the key advantages of both conventional open‐well and microfluidic systems. Here, a plug‐and‐play flow module is developed to introduce on‐demand microfluidic flow capabilities to an open‐well device that features a nanoporous membrane and live‐cell imaging capabilities. The magnetic latching assembly of this design enables bi‐directional reconfiguration and allows users to conduct an experiment in an open‐well format with established protocols and then add or remove microfluidic capabilities as desired. This work also provides an experimentally‐validated flow model to select flow conditions based on the experimental needs. As a proof‐of‐concept, flow‐induced alignment of endothelial cells and the expression of shear‐sensitive gene targets are demonstrated, and the different phases of neutrophil transmigration across a chemically stimulated endothelial monolayer under flow conditions are visualized. With these experimental capabilities, it is anticipated that both engineering and bioscience laboratories will adopt this reconfigurable design due to the compatibility with standard open‐well protocols.
Atomically Thin Synapse Networks on Van Der Waals Photo‐Memtransistors
Authors: Moon Gunho , Min Seok Young , Han Cheolhee , Lee Suk‐Ho , Ahn Heonsu , Seo Seung‐Young , Ding Feng , Kim Seyoung , Jo Moon‐Ho
Published: August 2022

A new type of atomically thin synaptic network on van der Waals (vdW) heterostructures is reported, where each ultrasmall cell (≈2 nm thick) built with trilayer WS2 semiconductor acts as a gate‐tunable photoactive synapse, i.e., a photo‐memtransistor. A train of UV pulses onto the WS2 memristor generates dopants in atomic‐level precision by direct light–lattice interactions, which, along with the gate tunability, leads to the accurate modulation of the channel conductance for potentiation and depression of the synaptic cells. Such synaptic dynamics can be explained by a parallel atomistic resistor network model. In addition, it is shown that such a device scheme can generally be realized in other 2D vdW semiconductors, such as MoS2, MoSe2, MoTe2, and WSe2. Demonstration of these atomically thin photo‐memtransistor arrays, where the synaptic weights can be tuned for the atomistic defect density, provides implications for a new type of artificial neural networks for parallel matrix computations with an ultrahigh integration density.
Preparation of Redox‐Active Metal–Organic Frameworks via Post‐Synthetic Modification of Organic Selenium for In Situ Confinement of Metal Nanoparticles
Authors: Fan Fuqiang , Feng Shiyi , Zhao Lin , Zhang Liying , Zhang Xuemin , Wang Tieqiang , Fu Yu
Published: August 2022

Redox‐active metal–organic frameworks (MOFs), with switchable physicochemical properties depending on their redox state, are widely used in catalysis, selective separation, and electrochemical sensing. However, the complex fabrication process limits the applications. Herein, a post‐synthetic modification strategy is proposed to prepare redox‐active MOFs by covalent grafting organic selenium compounds. The selenium moieties can reduce metal salt to in situ generate metal nanoparticles (MNPs) without an external reducing agent, and also act as anchors to stabilize the generated MNPs. As a proof of concept, two kinds of MOFs are selected to prepare redox‐active MOFs‐Se and further fabricate MNPs@MOFs composite materials. With controllable confinement of the MNPs, the MNPs@MOFs composite show noteworthy photocatalytic and electrocatalytic activity.
Pollinator research provides conservation management implications in North Dakota
Authors: Kral‐O'Brien Katherine C. , Adams Savannah , Antonsen Adrienne , Bendel Cayla , Keen Hailey , Pei C. K. , Roberton Bethany , Geaumont Benjamin , Limb Ryan , Hovick Torre , Harmon Jason
Published: August 2022

Pollinator declines have driven research and increased monitoring efforts. Within North Dakota, USA, our research group initiated research in 2015 on pollinator conservation and management. We synthesized results across five projects, producing 12 publications and providing baseline data on pollinator diversity and rangeland management to improve conservation efforts while land‐sharing with livestock. We detected 76 species of butterflies and ∼318 bee species. Butterfly diversity and relative abundance were driven by floral resources and less exotic plant invasions, with a positive relationship between flowers and pollinators. Invasive forbs were visited by pollinators, primarily honey bees. We also found management influenced vegetation characteristics within pastures, but landscape context was important for determining the specific outcome. Although pollinator abundance did not distinctly respond to management, diversity was affected by regime and grazer type. Using fire and grazing may benefit flowers to support pollinators. Our research will help guide rangeland management decisions that promote land sharing and benefit pollinator conservation efforts.

Core Ideas

We synthesized pollinator data from research conducted over six years in North Dakota.

Pollinator diversity correlated with more forb diversity and less invasive plant species cover.

Pollinator diversity, not abundance, has variable responses to management regime and grazer type.

Fire and grazing may benefit vegetation communities to conserve pollinators in some landscapes.
Peripheral Blood DNA Methylation–Based Machine Learning Models for Prediction of Knee Osteoarthritis Progression: Biologic Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project
Authors: Dunn Christopher M. , Sturdy Cassandra , Velasco Cassandra , Schlupp Leoni , Prinz Emmaline , Izda Vladislav , Arbeeva Liubov , Golightly Yvonne M. , Nelson Amanda E. , Jeffries Matlock A.
Published: August 2022

Objective

The lack of accurate biomarkers to predict knee osteoarthritis (OA) progression is a key unmet need in OA clinical research. The objective of this study was to develop baseline peripheral blood epigenetic biomarker models to predict knee OA progression.

Methods

Genome‐wide buffy coat DNA methylation patterns from 554 individuals from the Osteoarthritis Biomarkers Consortium (OABC) were determined using Illumina Infinium MethylationEPIC 850K arrays. Data were divided into model development and validation sets, and machine learning models were trained to classify future OA progression by knee pain, radiographic imaging, knee pain plus radiographic imaging, and any progression (pain, radiographic, or both). Parsimonious models using the top 13 CpG sites most frequently selected during development were tested on independent samples from participants in the Johnston County Osteoarthritis (JoCo OA) Project (n = 128) and a previously published Osteoarthritis Initiative (OAI) data set (n = 55).

Results

Full models accurately classified future radiographic‐only progression (mean ± SEM accuracy 87 ± 0.8%, area under the curve [AUC] 0.94 ± 0.004), pain‐only progression (accuracy 89 ± 0.9%, AUC 0.97 ± 0.004), pain plus radiographic progression (accuracy 72 ± 0.7%, AUC 0.79 ± 0.006), and any progression (accuracy 78 ± 0.4%, AUC 0.86 ± 0.004). Pain‐only and radiographic‐only progressors were not distinguishable (mean ± SEM accuracy 58 ± 1%, AUC 0.62 ± 0.001). Parsimonious models showed similar performance and accurately classified future radiographic progressors in the OABC cohort and in both validation cohorts (mean ± SEM accuracy 80 ± 0.3%, AUC 0.88 ± 0.003 [using JoCo OA Project data], accuracy 80 ± 0.8%, AUC 0.89 ± 0.002 [using previous OAI data]).

Conclusion

Our data suggest that pain and structural progression share similar early systemic immune epigenotypes. Further studies should focus on evaluating the pathophysiologic consequences of differential DNA methylation and peripheral blood cell epigenotypes in individuals with knee OA.

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The Role of Genetics in Clinically Suspect Arthralgia and Rheumatoid Arthritis Development: A Large Cross‐Sectional Study
Authors: Maurits Marc P. , Wouters Fenne , Niemantsverdriet Ellis , Huizinga Thomas W. J. , van den Akker Erik B. , Le Cessie Saskia , van der Helm‐van Mil Annette H. M. , Knevel Rachel
Published: August 2022

Objective

To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients.

Methods

Using analyses of variance, chi‐square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA‐SE) with all participant groups, both unstratified and stratified for anti–citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients). CSA patients were assessed for conversion to inflammatory arthritis over a period of 2 years, after which they were classified as either CSA converters (n = 84) or CSA nonconverters (n = 395).

Results

The PRS was increased in RA patients (mean ± SD PRS 1.31 ± 0.96) compared to the complete CSA group (1.07 ± 0.94) and compared to CSA converters (1.12 ± 0.94). In ACPA– strata, PRS distributions differed strongly when comparing the complete CSA group (mean ± SD PRS 1.05 ± 0.94) and CSA converters (0.97 ± 0.87) to RA patients (1.20 ± 0.94), while in the ACPA+ strata, the complete CSA group (1.25 ± 0.99) differed clearly from healthy controls (1.05 ± 0.94) and RA patients (1.41 ± 0.96). HLA‐SE was more prevalent in the RA group (prevalence 0.64) than the complete CSA group (0.45), with small differences between RA patients and CSA converters (0.64 versus 0.60) and larger differences between CSA converters and CSA nonconverters (0.60 versus 0.42). HLA‐SE prevalence differed more strongly within the ACPA+ strata as follows: healthy controls (prevalence 0.43), CSA nonconverters (0.48), complete CSA group (0.59), CSA converters (0.66), and RA patients (0.79).

Conclusion

We observed that genetic predisposition increased across pre‐RA participant groups. The RA PRS differed in early classified RA and inflammatory pre‐disease stages, regardless of ACPA stratification. HLA‐SE prevalence differed between arthritis patients, particularly ACPA+ patients, and healthy controls. Genetics seem to fulfill different etiologic roles.
Toughened Hydrogels for 3D Printing of Soft Auxetic Structures
Authors: Pruksawan Sirawit , Chee Heng Li , Wang Zizhen , Luo Ping , Chong Yi Ting , Thitsartarn Warintorn , Wang FuKe
Published: August 2022

Materials with negative Poisson's ratio have attracted considerable attention and offered high potential applications as biomedical devices due to their ability to expand in every direction when stretched. Although negative Poisson's ratio has been obtained in various base materials such as metals and polymers, there are very limited works on hydrogels due to their intrinsic brittleness. Herein, we report the use of methacrylated cellulose nanocrystals (CNCMAs) as a macro‐cross‐linking agent in poly(2‐hydroxyethyl methacrylate) (pHEMA) hydrogels for 3D printing of auxetic structures. Our developed CNCMA‐pHEMA hydrogels exhibit significant improvements in mechanical properties, which is attributed to the coexistence of multiple chemical and physical interactions between the pHEMA and CNCMAs. Structures printed by using CNCMA‐pHEMA hydrogels show auxetic behavior with greatly enhanced toughness and stretchability compared to the hydrogel with a traditional cross‐linking agent. Such strong and tough auxetic hydrogels would contribute toward establishing advanced flexible implantable devices such as biodegradable oesophageal self‐expandable stents.
Silver‐Catalyzed One‐Pot Three‐Component Synthesis of α‐Aminonitriles and Biologically Relevant α‐Amino‐phosphonates
Authors: Pandey Vipin K. , Tiwari Chandra Shekhar , Rit Arnab
Published: August 2022

A simple silver salt (AgSbF6)‐catalyzed aminophosphonylation and Strecker reaction have been developed and successfully applied to a wide range of substrates (>55 substrates). This solvent‐, ligand‐, and base‐free one‐pot three‐component protocol operates effectively at room temperature to provide diversified α‐aminophosphonates and α‐aminonitriles, which gave access to the respective α‐amino amides. Importantly, the present catalyst system is also capable to produce the rarely reported and biologically relevant aminophosphonates (having anti‐leishmanial activity). Further, mechanistic studies reveal that the present phosphonylation protocol follows a radical pathway.
Association between maternal prepregnancy diabetes mellitus and preconception folic acid supplement use by Hispanic ethnicity: Findings from Georgia, New York City, and Puerto Rico PRAMS 2016–2018
Authors: Guzman Iridian A. , Kramer Michael R. , Kancherla Vijaya
Published: August 2022

Background

Maternal ethnicity, prepregnancy diabetes, and preconception folic acid intake, are all associated with increased risk of neural tube defects in the United States. We assessed the association between prepregnancy diabetes and preconception folic acid use by Hispanic ethnicity.

Methods

We used population‐based, cross‐sectional survey data from New York City, Georgia and Puerto Rico's 2016–2018 Pregnancy Risk Assessment Monitoring System (PRAMS). Prepregnancy Type 1 or Type 2 diabetes was self‐reported. Adequate preconception folic acid intake was defined as intake of a multivitamin, a prenatal vitamin, or a folic acid vitamin 4–7 times/week during the month before pregnancy. Multivariable logistic regression was used to calculate adjusted prevalence odds ratio (aPORs) and 95% confidence intervals (CI), stratified by Hispanic ethnicity.

Results

Prepregnancy diabetes was reported by 2.9% of Hispanic and 3.6% of non‐Hispanic participants. Adequate preconception folic acid use was reported by 25.9% and 39.9% of Hispanics and non‐Hispanics, respectively. There was an inverse association between prepregnancy diabetes and preconception folic acid use among Hispanics (aPOR = 0.75; 95% CI = 0.31, 1.81), while the association was positive among non‐Hispanics (aPOR = 1.26; 95% CI = 0.70, 2.26); however, the 95% confidence intervals for both groups contained the null value.

Conclusions

The association between prepregnancy diabetes and folic acid intake varied by Hispanic ethnicity. Our hypothesis that reproductive‐aged women with prepregnancy diabetes may receive timely diabetic care, including health counseling to take preconception folic acid, was not supported by our study data. Future studies should examine the association in additional PRAMS sites. Preconception health screening, and folic acid intake among Hispanics, should be strengthened.
Shaping the “hot” immunogenic tumor microenvironment by nanoparticles co‐delivering oncolytic peptide and TGF‐β1 siRNA for boosting checkpoint blockade therapy
Authors: Phung Cao Dai , Nguyen Bao Loc , Jeong Jee‐Heon , Chang Jae‐Hoon , Jin Sung Giu , Choi Han‐Gon , Ku Sae Kwang , Kim Jong Oh
Published: August 2022

Induction of potent immune responses toward tumors remains challenging in cancer immunotherapy, in which it only showed benefits in a minority of patients with “hot” tumors, which possess pre‐existing effector immune cells within the tumor. In this study, we proposed a nanoparticle‐based strategy to fire up the “cold” tumor by upregulating the components associated with T and NK cell recruitment and activation and suppressing TGF‐β1 secretion by tumor cells. Specifically, LTX‐315, a first‐in‐class oncolytic cationic peptide, and TGF‐β1 siRNA were co‐entrapped in a polymer‐lipid hybrid nanoparticle comprising PLGA, DSPE‐mPEG, and DSPE‐PEG‐conjugated with cRGD peptide (LTX/siR‐NPs). The LTX/siR‐NPs showed significant inhibition of TGF‐β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting. The in vivo data showed that the LTX/siR‐NPs could effectively protect the LTX‐315 peptide from degradation in serum, which highly accumulated in tumor tissue. Consequently, the LTX/siR‐NPs robustly suppressed TGF‐β1 production by tumor cells and created an immunologically active tumor with high infiltration of antitumor effector immune cells. As a result, the combination of LTX/siR‐NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8+NKG2D+ and NK1.1+NKG2D+ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice. Taken together, this study suggests the potential of the LTX/siR‐NPs for inflaming the “cold” tumor for potentiating the efficacy of cancer immunotherapy.
Computing hydrodynamic eigenmodes of channel flow with slip—A highly accurate algorithm
Authors: Raju Suraj , Gründing Dirk , Marić Tomislav , Bothe Dieter , Fricke Mathis
Published: August 2022

The transient start‐up flow solution with slip is a useful tool to verify computational fluid dynamics (CFD) simulations. However, a highly accurate, open‐source black box solution does not seem to be available. Our method provides a fast, automated, and rigorously verified open‐source implementation that can compute the hydrodynamic eigenmodes of a two‐dimensional channel flow beyond the standard floating‐point precision. This allows for a very accurate computation of the corresponding Fourier series solution. We prove that all roots are found in all special cases for the general flow problem with different slip lengths on the channel walls. The numerical results confirm analytically derived asymptotic power laws for the leading hydrodynamic eigenmode and the characteristic timescale in the limiting cases of small and large slip. The code repository including test cases is publicly available (DOI: 10.5281/zenodo.6806351). The Navier slip boundary condition for numerical simulations in OpenFOAM is also publicly available (DOI: 10.5281/zenodo.7037712).
Amelioration of Leigh syndrome induced by mouse blastocyst complementation with a mutant human mitochondrial ATP synthase 6
Authors: Yuan Huijun , Webster Keith A. , Bhatti Muhammad Tariq , Hauswirth William W. , Lewin Alfred S. , Guy John
Published: August 2022

Background

Mutation of the m. 8993 T > G ATP6 subunit of ATP synthase causes a maternally inherited Leigh Syndrome (LS), a rapidly fatal encephalomyelopathy in childhood called and related Neuropathy, Ataxia and Retinitis Pigmentosa (NARP) in adults. There is no cure, and relevant animal models are few. Here we describe a novel ATP6 mouse model of LS and preclinical efficacy of a gene therapy approach to neutralize the ATP6 mutation by competition with a mitochondrial targeted adeno‐associated virus serotype 9 (AAV9) vector containing wild‐type ATP6.

Methods

LS transgenic mice with an ATP6 mutation were developed by microinjecting AAV2 modified by a COX8 mitochondrial targeting sequence (MTS) into mouse blastocysts to deliver the human ATP6 gene with a T > G mutation at position 8993 of the mitochondrial genome, responsible for clinical LS DNA, protein, and metabolic assays confirmed functional gene delivery and in depth physiological/clinical assessments supported germline transmission of an LS phenotype. Rescue of LS in this model was evaluated after intravenous injection of mito‐targeted AAV9 containing wild‐type ATP6 followed by reevaluation of phenotypes.

Results

LS transgenic mice expressed mutant ATP6 protein in multiple relevant tissues including brain, eye, liver. Mutant ATP6 incorporated into Complex V and conferred decreased ATP synthase efficiency. Mice exhibited hallmarks of the human disease with one or multiple systemic symptoms including early death, paralysis, hunching, vision loss and seizures over six generations. Necropsy revealed spongiform encephalopathy, retinal degeneration, and cardiomegaly. Rescue by mitochondrially directed AAV9 containing wild type ATP6 after disease onset conferred prolonged survival and reduced paralysis. When administered prior to disease onset all treated ATP6 mice survived with evidence of globally improved function.

Conclusions

The results are consistent with efficient delivery and expression of foreign genes in mitochondria by AAV vectors directed by MTS and support further development of such strategies via intravenous injection of mitochondrial targeted AAV9 to deliver corrective genes.
Exploring the intersection of multiple social determinants of health and disordered eating behaviors in a population‐based sample in the United States
Authors: Simone Melissa , Slaughter‐Acey Jaime , Hazzard Vivienne M. , Eisenberg Marla , Neumark‐Sztainer Dianne
Published: August 2022

Objective

Disordered eating behaviors (DEBs) have long‐term, deleterious effects on health and are more prevalent among socially marginalized groups, likely as a result of systemic inequities across social determinants of health (SDoH). This exploratory study aimed to identify subgroups of emerging adults characterized by main and interactive associations between SDoH and two forms of DEB (binge eating, extreme unhealthy weight control behaviors).

Method

Participants (n = 1568; age 22.2 ± 2.1 years) from the United States were drawn from the EAT 2010–2018 longitudinal study. Conditional inference tree (CIT) analyses derived main and intersecting SDoH related to DEB across 33 input variables collected during adolescence and emerging adulthood.

Results

The binge eating CIT revealed five subgroups (prevalence: 6.3–23.2%) shaped by variables collected during emerging adulthood: appearance‐based teasing (p < .001), financial difficulty (p = .003), gender (p < .001), and everyday discrimination (p = .008). The CIT results for extreme unhealthy weight control behaviors derived six subgroups (prevalence: 2.3–45.5%) shaped by weight teasing (p < .001) and gender (p < .001) during emerging adulthood and public assistance (p = .008) and neighborhood safety (p = .007) in adolescence.

Discussion

This exploratory study revealed distinct subgroups of emerging adults with varying DEB prevalence, suggesting that variability in DEB prevalence may be partially explained by intersecting SDoH during adolescence and emerging adulthood. Hypothesis‐driven research and replication studies are needed to further explore the associations between SDoH and DEB during emerging adulthood.

Public Significance Statement

Disordered eating behaviors are common among young people in the United States and have long‐term health consequences. This exploratory study identified subgroups of young people, characterized by combinations of social inequities (e.g., financial difficulties, teasing). Results highlight high‐risk subgroups of emerging adults that should be examined further in hypothesis‐driven research.
Porously Reduced 2‐Dimensional Bi2O2CO3 Petals for Strain‐Mediated Electrochemical CO2 Reduction to HCOOH
Authors: Cho Won Seok , Hong Dae Myung , Dong Wan Jae , Lee Tae Hyung , Yoo Chul Jong , Lee Donghwa , Jang Ho Won , Lee Jong‐Lam
Published: August 2022

Here we introduce bismuth‐based catalysts for the efficient electrochemical reduction of CO2 to formic acid (HCOOH), which are composed of petal‐shaped Bi2O2CO3 (BOC) that spontaneously formed from Bi thin film in aqueous carbonate solution at room temperature. During the electrochemical reduction process, the BOC petals transform to reduced BOC (R‐BOC) consisting of individual BOC and Bi domains. Lattice mismatch between both domains induces biaxial strain at the interfaces. Density functional theory calculations suggest that the tensile strain on the Bi domain stabilizes the *OCHO intermediate, reducing the thermodynamic barrier toward CO2 conversion to HCOOH. Together with the thermodynamic benefit and the unique nanoporous petal‐shaped morphology, R‐BOC petals have a superior Faradaic efficiency of 95.9% at −0.8 VRHE for the electrochemical conversion of CO2 to HCOOH. This work demonstrates that the spontaneously formed binary phases with desirable lattice strain can increase the activity of bismuth catalysts to the CO2 reduction reaction; such a strategy can be applicable in design of various electrocatalysts.
Solvation Effects on the Dielectric Constant of 1 M LiPF6 in Ethylene Carbonate: Ethyl Methyl Carbonate 3:7
Authors: Self Julian , Hahn Nathan T. , Persson Kristin A.
Published: August 2022

We report the dielectric constant of 1 M LiPF6 in EC:EMC 3:7 w/w (ethylene carbonate/ethyl methyl carbonate) in addition to neat EC:EMC 3:7 w/w. Using three Debye relaxations, the static permittivity value, or dielectric constant, is extrapolated to 18.5, which is compared to 18.7 for the neat solvent mixture. The EC solvent is found to strongly coordinate with the Li+ cations of the salt, which results in a loss of dielectric contribution to the electrolyte. However, the small amplitude and large uncertainty in relaxation frequency for EMC cloud definitive identification of the Li+ solvation shell. Importantly, the loss of the free EC permittivity contribution due to Li+ solvation is almost completely balanced by the positive contribution of the associated LiPF6 salt, demonstrating that a significant quantity of dipolar ion pairs exists in 1 M LiPF6 in EC:EMC 3:7.