bluuebunny/crossref_metadata_2025 huggingface dataset:
NCCN Guidelines Updates: Management of Patients With HER2-Negative Breast Cancer
Authors: Gradishar William J.
Published: June 2022

Treatment for metastatic HER2-negative breast cancer is becoming increasingly individualized as more of the tumor landscape is described and drugs are developed to target its pathways. Survival can be prolonged by CDK4/6 inhibitors in patients with hormone receptor–positive tumors and by immunotherapy in those with triple-negative disease. In patients with BRCA1/2 mutations, PARP inhibitors delay disease progression. Antibody–drug conjugates are expected to become critical components of the treatment landscape, and targeted drugs are proving to benefit small subsets of patients.
Locoregional Management of Early-Stage Breast Cancer
Authors: Moran Meena S. , Leitch A. Marilyn
Published: June 2022

The latest version of NCCN Guidelines for Breast Cancer on locoregional management of early-stage breast cancer contains numerous updated recommendations, particularly focusing on management of the axilla, locoregional management after neoadjuvant therapy, and radiation delivery. Recommendations for axillary staging have been separated for patients who have undergone breast-conserving surgery and those who have had a mastectomy, creating 2 individual pathways. The section on locoregional treatment after neoadjuvant therapy has been reformatted; optimal management of this patient group continues to evolve. Lastly, specifics regarding the delivery and sequencing of radiotherapy have been updated.
New Treatment Options for Patients With Bladder Cancer
Authors: Flaig Thomas W.
Published: June 2022

Bladder cancer is not rare—in men, it is the fourth most common cancer and the eighth leading cause of cancer-related death. The emergence of new systemic therapies, approval of PD-1 and PD-L1 inhibitors, and progress in the development of biomarkers have revolutionized the treatment of this urologic malignancy. The current NCCN Guidelines, which reflect the most up-to-date, evidence-based data relating to the evaluation and management of bladder cancer, support the incorporation of some of these novel therapeutics into clinical practice.
Justicia para los vasallos de su majestad. Administración de justicia en la villa de San Gil, siglo XVIII
Authors: Velasco Pedraza Julián Andrei
Published: June 2022

Para la monarquía hispánica gobernar era hacer justicia. Bajo este fundamento, la corona de Castilla construyó todo un complejo aparato de tribunales en sus dominios americanos. Esta obra analiza una parte de ese gobierno por medio de la administración de justicia de la villa de San Gil en el siglo XVIII. Desde una perspectiva histórico-jurídica, fundamentada en nuevas visiones sobre el derecho y las instituciones, se estudia cómo en un ámbito local funcionaban y se adaptaban criterios culturales y principios jurídicos generales de la tradición jurídica de Occidente. Mediante el estudio de las condiciones locales, las jurisdicciones y jueces que las ejercían, así como de otros elementos del gobierno, se traza un panorama de la lógica de funcionamiento de una parte de la monarquía. Un tema poco estudiado para el virreinato de Santa Fe y que puede ayudar al mejor entendimiento de las lógicas político-administrativas del siglo XVIII, además de comprender, de forma menos anacrónica, las fuentes judiciales que eran producto de una cultura jurídica distinta a la de nuestros días.
Reforma radical en el estado de Santander, 1850-1885
Authors: Zapata Giraldo Juan Gonzalo
Published: June 2022

A lo largo del siglo xix el país se vio obligado a definirse en favor o en contra de tres modelos políticos que tenían grandes diferencias entre sí. Por supuesto, uno de estos era el radical, que finalmente fue derrotado por uno mucho más fuerte, que logró imponerse durante un periodo muy largo. Sin embargo, durante los años radicales se vivieron una expansión económica y un progreso social importantes que poco se han valorado, pues a lo largo de casi treinta años del siglo xix el discurso y la política nacional yregional se movieron alrededor de las reformas radicales. Así, este extenso periodo de Gobierno conocido como la hegemonía radical permite mostrar en este libro cuáles fueron las políticas abanderadas por este grupo político y cuál fue su impacto tanto en el Gobierno Federal como en las regiones, pues su influencia en algunas fue permanente, pese al interés de los conservadores por anularlas. Un ejemplo de esta hegemonía es Santander, un estado que construirían los radicales, parte de una federación, laico, con vocación de estimular la actividad económica y donde s reconocía el papel que deberían desempeñar los empresarios y los comerciantes para lograr el anhelado progreso económico. Este libro permitirá conocer en detalle la puesta en marcha de las reformas en algunos sectores, analizar sus fuentes de financiamiento y los criterios para canalizar los recursos a algunos sectores del gasto público que consideraron prioritario y entender las novedosas herramientas administrativas utilizadas por los radicales, y con ello emitir un juicio final sobre sus políticas.
Multi-constraints based deep learning model for automated segmentation and diagnosis of coronary artery disease in X-ray angiographic images
Authors: Algarni Mona , Al-Rezqi Abdulkader , Saeed Faisal , Alsaeedi Abdullah , Ghabban Fahad
Published: June 2022

Background

The detection of coronary artery disease (CAD) from the X-ray coronary angiography is a crucial process which is hindered by various issues such as presence of noise, insufficient contrast of the input images along with the uncertainties caused by the motion due to respiration and variation of angles of vessels.

Methods

In this article, an Automated Segmentation and Diagnosis of Coronary Artery Disease (ASCARIS) model is proposed in order to overcome the prevailing challenges in detection of CAD from the X-ray images. Initially, the preprocessing of the input images was carried out by using the modified wiener filter for the removal of both internal and external noise pixels from the images. Then, the enhancement of contrast was carried out by utilizing the optimized maximum principal curvature to preserve the edge information thereby contributing to increasing the segmentation accuracy. Further, the binarization of enhanced images was executed by the means of OTSU thresholding. The segmentation of coronary arteries was performed by implementing the Attention-based Nested U-Net, in which the attention estimator was incorporated to overcome the difficulties caused by intersections and overlapped arteries. The increased segmentation accuracy was achieved by performing angle estimation. Finally, the VGG-16 based architecture was implemented to extract threefold features from the segmented image to perform classification of X-ray images into normal and abnormal classes.

Results

The experimentation of the proposed ASCARIS model was carried out in the MATLAB R2020a simulation tool and the evaluation of the proposed model was compared with several existing approaches in terms of accuracy, sensitivity, specificity, revised contrast to noise ratio, mean square error, dice coefficient, Jaccard similarity, Hausdorff distance, Peak signal-to-noise ratio (PSNR), segmentation accuracy and ROC curve.

Discussion

The results obtained conclude that the proposed model outperforms the existing approaches in all the evaluation metrics thereby achieving optimized classification of CAD. The proposed method removes the large number of background artifacts and obtains a better vascular structure.
Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes in Elderly Patients. POPular AGE Hypothesis
Authors: Viruel Marcos , Muñoz Florencia , Garmendia Cristian , Parrilla Leandro , Ruano Carlos , Rivero Mirza , Zaidel Ezequiel , Lalor Nicolás , Pérez Gonzalo , Costabel Juan P.
Published: June 2022

Background: The POPular AGE study demonstrated that in patients over 70 years of age clopidogrel would be the P2Y12 receptor inhibitor (P2Y12i) of choice due to its association with lower bleeding incidence and no difference in ischemic events. Objective: We analyzed the safety and efficacy of different treatment regimens with P2Y12i, in patients ≥70 years with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) to test the “POPular AGE” hypothesis in the real world. Methods: This subanalysis of the prospective BUENOS AIRES I registry analyzed data corresponding to 1100 patients from 21 medical centers in Buenos Aires, Argentina, followed-up for 15 months. We considered the subgroup of patients ≥70 years, stratified according to the P2Y12i indicated at discharge. Results: This subgroup had a high burden of comorbidities, with 85.1% hypertension, 30.3% diabetes mellitus, and 43.2% chronic kidney disease. Patients treated with ticagrelor/prasugrel (n=54) presented with higher prevalence of active smoking, less atrial fibrillation and lower CRUSADE score, with no differences in the GRACE score, compared whit those treated with clopidogrel (n=286). At the 15-month follow-up, no significant differences were observed in the BARC ≥2 bleeding rate, with more events in the clopidogrel group, although without statistical significance, (25.4% vs. 18.2%; p=0.327) and a benefit in the incidence of major adverse cardiovascular events (MACE) in the ticagrelor/prasugrel treatment group (18.6% vs 36.3%, p= 0.023). Conclusions: In adequately selected patients with NSTE-ACS ≥70 years, treatment with Ticagrelor/prasugrel could be a safe and effective strategy.
Communication Behaviour of Groundnut Growers in Chittoor District of Andhra Pradesh
Authors: Charitha P. Sai , Jahanara .
Published: June 2022

This study was conducted in Chittoor District of Andhra Pradesh to measure communication behaviour among groundnut growers for agricultural technology. A total number of 120 respondents were selected purposively from 12 villages under Gudipala & Yadamari block to measure the level of communication behaviour among growers for agricultural technology. The data was recorded by personal interview method by using pre-structured interview schedule and latter appropriate statistical analysis was done to draw logical conclusion. The study revealed that 44.18 % of the Groundnut growers belonged to middle age category and 57.51 % belonged to middle and high school. 44.16 % of the groundnut growers belonged to medium (2.5 – 5) acre of land holding. The findings also revealed that that majority (41.66%) of the groundnut growers had medium level of communication behaviour among groundnut growers, (40.01%) and (18.33%) of the groundnut growers had high and low level of communication behaviour.
Classication of Units of Five Radical Zero Completely Primary Finite Rings with Variant Orders of Second Galois Ring Module Generators
Authors: Were Hezron Saka , Oduor Maurice Owino , Gichuki Moses Ndiritu
Published: June 2022

Let \(R\) be a commutative completely primary finite ring with a unique maximal ideal \(Z(R)\) such that \((Z(R))^{5}=(0) ;(Z(R))^{4} \neq(0)\). Then \(R / Z(R) \cong G F\left(p^{r}\right)\) is a finite field of order \(p^{r}\). Let \(R_{0}=G R\left(p^{k r}, p^{k}\right)\) be a Galois ring of order \(p^{k r}\) and of characteristic \(p^{k}\) for some prime number \(p\) and positive integers \(k, r\) so that \(R=R_{0} \oplus U \bigoplus V \bigoplus W \bigoplus Y\), where \(U, V, W\) and \(Y\) are \(R_{0} / p R_{0}\) - spaces considered as \(R_{0}\) modules generated by \(e, f, g\) and \(h\) elements respectively. Then \(R\) is of characteristic \(p^{k}\) where \(1 \leq k \leq 5\). In this paper, we investigate and determine the structures of the unit groups of some classes of commutative completely primary finite ring \(R\) with \(p u_{i}=p^{\xi} v_{j}=p w_{k}=p y_{l}=0\), where \(\xi=2,3 ; 1 \leq i \leq e, 1 \leq j \leq f, 1 \leq k \leq g\), and \(1 \leq l \leq h\).
A Review on Pharmacological and Therapeutic Potential of Aloe barbadensis Miller
Authors: Sharma Deepak , Purohit Naimish , Chaubey Shiwa , Tiwari Mohan , Bhadauriya Mradu , Mohit . , Bhasker Nilam , Kumar Dharmendra
Published: June 2022

Aloe vera, a popular succulent perennial medicinal plant with a wide range of phytochemicals that have shown various pharmacological activities including anti-oxidant, antimicrobial, antidiabetic, wound healing promotion and so on. Acemannan, aloe-emodin, aloin, aloesin, and emodin are widely investigated active constituents that show various pharmacological activities. Thus, the purpose of this review is to highlight previous pharmacological studied conducted in vivo, in vitro and human assays over the past decades. As current pharmacological research is focused on anticancer and neurological action, it would be interesting and important to study the main compounds present in Aloe vera for therapeutic purposes.
The Effects of Methanolic Plant Extract on the Haematological Indices of Induced Preeclamptic Wistar Rats
Authors: Atoe Kenneth , Idu Macdonald
Published: June 2022

Aims: Preeclampsia can have a deleterious impact on   hematological parameters of pregnant women. Management of this medical condition is critical for improving mother and fetal outcomes. Alternative phytomedicinal intervention is becoming more popular in prenatal care. The current study looked into the effects of methanolic extracts of Jatropha curcas, Alchonnea cordifolia, and Secamone afzelii on haematological markers in preeclamptic Wistar rats.

Study Design:  The study was a trial using an animal model.

Place and Duration of Study: The study was conducted in the University of Benin, Nigeria in July 2019.

Methodology: Age-matched (3 days) female Wistar rats weighing 220 to 256 g were used in the study (mean, 237 g). The Adriamycin Model was utilized in Wistar rats to induce preeclampsia. Methanolic extracts of Jatropha curcas, Alchonnea cordifolia, and Secamone afzelii were given to the rats in doses of 50, 100, and 200 mg/kg. The animals were anaesthetized with chloroform and humanely slaughtered (use ‘sacrificed’ instead) twenty-four (24) hours after the last dosage of the standard medicine and various treatment extracts were administered to the relevant groups. Blood samples were drawn from the aorta and transferred to tubes containing the anticoagulant EDTA before being evaluated for the various parameters on an Auto Haematology Analyzer Model XrHA640.

Results: White cell count was 6.77x103 in the control group, but when preeclampsia was developed, WBC plummeted to 5.8x103. However, when preeclamptic rats were given 100mg/kg of Secamone afzeli extracts, their WBC increased to 9.75x103. A similar increase in hematological differentials was observed in lymphocytes when preeclampsia dramatically reduced lymphocyte volume to 1.1% against 1.17 % in the control. The mean corpuscular volume in the control group was 71.6fL, but when preeclampsia was induced, it dropped to 67.0fL. This improved to 78.6fL when the normal medication was supplied, and 81.6fL when 50mg of Alchonnea cordifolia extracts were administered.

Conclusion: According to the findings, extracts of several plants (be specific and mention the plants used in the study) generated increases in PCV to varying degrees, and hence might be utilized to treat anemia. Their ability to improve platelet counts at various levels showed that they could be used in the treatment of thrombocytopenia. The extracts can help improve immune responses by increasing white cell numbers.
Stock Price Behaviour around the Announcement Date of Cash Dividend on the Indonesia Stock Exchange
Authors: Mujilan Mujilan
Published: June 2022

This study aims to explain the stock prices behavior around the announcement date of cash dividends. The study compares the stock prices a week before the cumulative date, cumulative date, record date, a week after the record date, and two weeks after the record date. The stock prices are also compared to the cash dividends nominals in 2017 and cash dividends in 2018. The researcher obtains the research data from LQ45 companies in 2018. The data is tested using the Wilcoxon Signed-Ranks Test. The results show that the date of announcement and recording of dividends do not have an impact on the increase in stock prices, but the result shows a decline in stock prices. The results of this study imply that the announcement of cash dividends does not trigger stock buying action around the announcement date for the companies who distribute cash dividends.
Hypoxia‐induced miR‐210‐3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2 mediated monocyte infiltration
Authors: Arora Leena , Patra Debarun , Roy Soumyajit , Nanda Sidhanta , Singh Navneet , Verma Anita K. , Chakraborti Anuradha , Dasgupta Suman , Pal Durba
Published: June 2022

In most cancers, tumor hypoxia downregulates the expression of C‐C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is not yet clear. We compared noncancerous and lung‐adenocarcinoma human samples for hypoxia‐inducible factor 1‐alpha (HIF‐1A), microRNA‐210‐3p (mir‐210‐3p), and CCL2 levels. Mechanistic studies were performed on lung adenocarcinoma cell lines and 3D tumor spheroids to understand the role of hypoxia‐induced miR‐210‐3p in the regulation of CCL2 expression and macrophage polarization. HIF‐1Α stabilization increases miR‐210‐3p levels in lung adenocarcinoma and impairs monocyte infiltration by inhibiting CCL2 expression. Mechanistically, miR‐210‐3p directly binds to the 3′untranslated region (UTR) of CCL2 mRNA and silences it. Suppressing miR‐210‐3p substantially downregulates the effect of hypoxia on CCL2 expression. Monocyte migration is significantly hampered in miR‐210‐3p mimic‐transfected HIF‐1A silenced cancer cells. In contrast, inhibition of miR‐210‐3p in HIF‐1A‐overexpressed cells markedly restored monocyte migration, highlighting a direct link between the miR‐210‐3p level and tumor monocyte burden. Moreover, miR‐210‐3p inhibition in 3D tumor spheroids promotes monocyte recruitment and skewing towards an antitumor M1 phenotype. Anti‐hsa‐miR‐210‐3p‐locked nucleic acid (LNA) delivery in a lung tumor xenograft zebrafish model caused tumor regression, suggesting that miR‐210‐3p could be a promising target for immunomodulatory therapeutic strategies against lung adenocarcinoma.
Elastic Lattice Enabling Reversible Tetrahedral Li Storage Sites in a High‐Capacity Manganese Oxide Cathode
Authors: Huang Weiyuan , Yang Luyi , Chen Zhefeng , Liu Tongchao , Ren Guoxi , Shan Peizhao , Zhang Bin‐Wei , Chen Shiming , Li Shunning , Li Jianyuan , Lin Cong , Zhao Wenguang , Qiu Jimin , Fang Jianjun , Zhang Mingjian , Dong Cheng , Li Fan , Yang Yong , Sun Cheng‐Jun , Ren Yang , Huang Qingzhen , Hou Guangjin , Dou Shi‐Xue , Lu Jun , Amine Khalil , Pan Feng
Published: June 2022

The key to breaking through the capacity limitation imposed by intercalation chemistry lies in the ability to harness more active sites that can reversibly accommodate more ions (e.g., Li+) and electrons within a finite space. However, excessive Li‐ion insertion into the Li layer of layered cathodes results in fast performance decay due to the huge lattice change and irreversible phase transformation. In this study, an ultrahigh reversible capacity is demonstrated by a layered oxide cathode purely based on manganese. Through a wealth of characterizations, it is clarified that the presence of low‐content Li2MnO3 domains not only reduces the amount of irreversible O loss; but also regulates Mn migration in LiMnO2 domains, enabling elastic lattice with high reversibility for tetrahedral sites Li‐ion storage in Li layers. This work utilizes bulk cation disorder to create stable Li‐ion‐storage tetrahedral sites and an elastic lattice for layered materials, with a reversible capacity of 600 mA h g−1, demonstrated in th range 0.6–4.9 V versus Li/Li+ at 10 mA g−1. Admittedly, discharging to 0.6 V might be too low for practical use, but this exploration is still of great importance as it conceptually demonstrates the limit of Li‐ions insertion into layered oxide materials.
Stereocomplementary Synthesis of a Key Intermediate for Tofacitinib via Enzymatic Dynamic Kinetic Resolution‐Reductive Amination
Authors: Zhan Zhuangzhuang , Xu Zefei , Yu Shanshan , Feng Jinhui , Liu Fufeng , Yao Peiyuan , Wu Qiaqing , Zhu Dunming
Published: June 2022

Tofacitinib is an oral protein tyrosine kinase inhibitor approved for the treatment of rheumatoid arthritis, active psoriatic arthritis and ulcerative colitis. Its efficient production remains a challenge due to the two consecutive stereogenic centers associated to the piperidine ring. In this study, an enzymatic dynamic kinetic resolution‐asymmetric reductive amination was developed to prepare enantiomerically complementary cis‐1‐benzyl‐N,4‐ dimethylpiperidin‐3‐amine and its analogues. Two enantiocomplementary imine reductases (IREDs) were identified for the synthesis of (3R,4R)‐ and (3S,4S)‐1‐benzyl‐N,4‐dimethylpiperidin‐3‐amine in high isolated yields (83% and 91%) with excellent stereoselectivity (97% and >99% ee values) and diastereoselectivity (>99:1 dr), providing a green methodology for the production of the key intermediate of tofacitinib.

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Copper‐Catalysed Synthesis of Propargyl Alcohol and Derivatives from Acetylene and other Terminal Alkynes
Authors: Sitte Nikolai A. , Ghiringhelli Francesca , Shevchenko Grigory A. , Rominger Frank , Hashmi A. Stephen K. , Schaub Thomas
Published: June 2022

A copper(I)/phosphine system that homogeneously catalyses the alkynylation of formaldehyde with acetylene or terminal alkynes is reported. Using acetylene at atmospheric pressure, the catalyst consisting of <1 mol% copper(I) phenylacetylide and a trialkyl bisphosphine ligand shows a high selectivity towards the formation of propargyl alcohol rather than 1,4‐butynediol, which is not reported for common heterogeneous copper acetylide catalysts. The biphasic water/toluene reaction mixture allows the separation of targeted products with the aqueous layer and catalyst recycling via the organic layer.

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Green Synthesis of Dimethyl Carbonate from CO2 and Methanol: New Strategies and Industrial Perspective
Authors: Raza Ali , Ikram Muhammad , Guo Song , Baiker Alfons , Li Gao
Published: June 2022

Dimethyl carbonate (DMC) is a commonly used and environmentally sustainable chemical compound and intermediate in a variety of industrial applications. To date, several large‐scale industrial DMC synthesis routes have been developed, including methanol phosgenation, transesterification, and oxidative carbonylation of methanol. However, these manufacturing routes have several disadvantages, such as the use of hypertoxic phosgene as raw material, costly processing, and explosion risks. The most encouraging and ecofriendly path is the green production of DMC from CO2 and methanol. Various catalytic materials have been examined concerning their suitability for DMC synthesis. The issues of low yield and difficulty in tests have not been resolved fundamentally, which is caused by the inherent problems of the synthetic pathway and limitations imposed by thermodynamics. The search for more efficient production routes has driven the activation of CO2 via electro‐assisted synthesis as well as membrane reactors, which can isolate products in real‐time to maximize DMC yield. The green synthesis of dimethyl carbonate catalyzed by different catalysts including Zr/Ce/Cu‐based nanocomposites, organometallic compounds, heteropoly acid, ionic liquid, metal‐organic frameworks, etc, is discussed in detail. Further, the structure–activity relationships and insights into molecular activation and catalytic mechanisms, as well as the identification of active sites on catalysts are addressed.
Stiffening Matrix Induces Age‐Mediated Microvascular Phenotype Through Increased Cell Contractility and Destabilization of Adherens Junctions
Authors: Schnellmann Rahel , Ntekoumes Dimitris , Choudhury Mohammad Ikbal , Sun Sean , Wei Zhao , Gerecht Sharon
Published: June 2022

Aging is a major risk factor in microvascular dysfunction and disease development, but the underlying mechanism remains largely unknown. As a result, age‐mediated changes in the mechanical properties of tissue collagen have gained interest as drivers of endothelial cell (EC) dysfunction. 3D culture models that mimic age‐mediated changes in the microvasculature can facilitate mechanistic understanding. A fibrillar hydrogel capable of changing its stiffness after forming microvascular networks is established. This hydrogel model is used to form vascular networks from induced pluripotent stem cells under soft conditions that mimic young tissue mechanics. Then matrix stiffness is gradually increased, thus exposing the vascular networks to the aging‐mimicry process in vitro. It is found that upon dynamic matrix stiffening, EC contractility is increased, resulting in the activation of focal adhesion kinase and subsequent dissociation of β‐catenin from VE‐Cadherin mediated adherens junctions, leading to the abruption of the vascular networks. Inhibiting cell contractility impedes the dissociation of β‐catenin, thereby preventing the deconstruction of adherens junctions, thus partially rescuing the age‐mediated vascular phenotype. The findings provide the first direct evidence of matrix's dynamic mechano‐changes in compromising microvasculature with aging and highlight the importance of hydrogel systems to study tissue‐level changes with aging in basic and translational studies.
Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co‐Culture Chip
Authors: Kim Hyunho , Sa Jason K. , Kim Jaehoon , Cho Hee Jin , Oh Hyun Jeong , Choi Dong‐Hee , Kang Seok‐Hyeon , Jeong Da Eun , Nam Do‐Hyun , Lee Hakho , Lee Hye Won , Chung Seok
Published: June 2022

Non‐small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti‐cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM‐NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri‐culture platform is proposed for recapitulating positive feedback from BM‐NSCLC and astrocytes and brain‐specific endothelial cells, two major players in bTME. Advanced imaging and quantitative functional assessment of the 3D tri‐culture model enable real‐time live imaging of cell viability and separate analyses of genomic/molecular/secretome from each subset. Susceptibility of multiple patient‐derived BM‐NSCLCs to representative targeted agents is altered and secretion of serpin E1, interleukin‐8, and secreted phosphoprotein 1, which are associated with tumor aggressiveness and poor clinical outcome, is increased in tri‐culture. Notably, multiple signaling pathways involved in inflammatory responses, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, and cancer metastasis are activated in BM‐NSCLC through interaction with two bTME cell types. This novel platform offers a tool to elucidate potential molecular targets and for effective anti‐cancer therapy targeting the crosstalk between metastatic cancer cells and adjacent components of bTME.
Superaerophobic Polyethyleneimine Hydrogels for Improving Electrochemical Hydrogen Production by Promoting Bubble Detachment
Authors: Bae Misol , Kang Yunseok , Lee Dong Woog , Jeon Dasom , Ryu Jungki
Published: June 2022

Removal of gas bubbles from the electrode surface is practically important to maintain the activity of electrochemical gas evolution reactions. Conventionally, most studies have focused on the development of electrocatalysts and paid less attention to the bubble removal issues. Recently, it has been reported that attached gas bubbles can be readily eliminated by imparting extremely gas‐repellent properties (so‐called superaerophobicity) to electrodes via controlling their nano/microstructure. However, this approach is material‐specific and requires harsh and expensive synthetic conditions, causing difficulties in scaling up to large‐area electrodes for commercialization. To address these issues, a universal method to impart superaerophobicity to various electrodes through simple coating with porous polymeric hydrogels without affecting the underlying target substrates is reported. The modification of electrodes with superaerophobic polymeric hydrogel substantially enhances the efficiency of the hydrogen evolution reaction because the hydrogel can facilitate the removal of as‐generated gas bubbles and thereby minimize ohmic and concentration overpotentials. Particularly, electrodes modified with the superaerophobic hydrogel outperform those modified with electrocatalysts at high current densities where more gas bubbles are generated and adhered to. The results provide insights into the design of various electrochemical devices that are based on gas‐involving reactions.
Application of an equation‐oriented framework to formulate and estimate parameters of chemical looping reaction models
Authors: Okoli Chinedu O. , Parker Robert , Chen Yu‐Yen , Ostace Anca , Lee Andrew , Bhattacharyya Debangsu , Tong Andrew , Biegler Lorenz T. , Burgard Anthony P. , Miller David C.
Published: June 2022

Accurate, predictive reaction models are critical for the design and optimization of chemical looping combustion (CLC) reactors. The formulation and estimation of kinetic parameters for these reaction models using a first‐principles equation‐oriented (EO) approach is particularly beneficial as large amounts of experimental data spanning process‐relevant conditions can be used to estimate parameters in a computationally tractable way. This work demonstrates the application of a novel EO framework to develop reduction reaction kinetic models of an iron‐based CLC oxygen carrier (OC). An optimization problem is formulated to estimate kinetic parameters that provide the best fit to the experimental data. The model predicts the state of the OC with mean square error values of 2.5%–4.4% across the full range of validation data, including multiple reduction cycles.
Recent Advances in Cobalt‐catalyzed Functionalization of Unactivated Olefins
Authors: Patel Monak , Ajay Uppuluru , Padala Kishor , Naveen Togati
Published: June 2022

Olefins are low‐cost starting materials that may be obtained in bulk quantities from petrochemical feedstocks and renewable resources. The transition metal‐catalyzed unactivated olefin functionalization is well explored and received an extensive interest from synthetic chemists. In recent times, chemists have successfully employed different transition metals for the functionalization of unactivated olefins. Among the different transition metals that have been used, cobalt catalysts have received great attention from synthetic chemists for C−H functionalization reactions, owing to their ready availability and high reactivity. Herein, we discuss the most recent reports in the field of cobalt‐catalyzed functionalization of unactivated olefins that enable C−C, C−X and C−hetero bond formation and covers the literature from 2016 to 2021.
Lipids, Apolipoproteins, Statins, and Intracerebral Hemorrhage: A Mendelian Randomization Study
Authors: Yu Zhou , Zhang Linjing , Zhang Gan , Xia Kailin , Yang Qiong , Huang Tao , Fan Dongsheng
Published: June 2022

Objective

To investigate the causal role of lipid or apolipoprotein traits in intracerebral hemorrhage (ICH) and determine the effect of lipid‐lowering interventions on the disease.

Methods

Two‐sample Mendelian randomization (MR) analyses were conducted to evaluate the associations of high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), apolipoprotein (Apo)B and ApoA1 levels with risks for ICH, and those of LDL‐C‐ (HMGCR, PCSK9, and NPC1L1) and TG‐lowering targets (LPL and APOC3) with ICH.

Results

Increased levels of ApoB was associated with a decreased risk of overall ICH (OR 0.623, 95% CI 0.413–0.940; p = 0.024) and lobar ICH (OR 0.579, 95% CI 0.342–0.979; p = 0.042). The inverse relationship remained stable in multivariable MR. In addition, elevated TGs showed a causal effect on lobar ICH in multivariable MR (OR 1.600, 95% CI 1.009–2.537; p = 0.046). The LDL‐C‐reducing genetic variation alleles at or near the HMGCR gene (mimicking the effect of statins) were predicted to increase the overall and deep ICH risk. Additionally, genetic variation at or near the APOC3 gene suggested that genetically reducing the activity of APOC3 (mimicking antisense anti‐apoC3 agents) was predicted to decrease lobar ICH.

Interpretation

Genetically predicted elevated ApoB may have a protective effect on overall ICH and lobar ICH, whereas elevated TG was associated with a higher risk of lobar ICH conditional on LDL‐C and ApoB. MR analysis supports the conclusion that statins may increase the risk of overall and deep ICH independent of their lipid‐lowering effect. More specific lipid‐lowering targets may end up being the future. ANN NEUROL 2022;92:390–399
Recent advances on food‐based applications of monoglyceride oleogels
Authors: Palla Camila A. , Dominguez Martina , Carrín María Elena
Published: June 2022

Monoglyceride (MG) oleogels are soft matter structures designed to mimic the functionality of fats while maintaining a lipid profile comparable to that of edible oils. These novel fat materials have been mainly investigated as ingredients to reduce saturated fats and eliminate trans fats in the production of several foods, such as spreadables, bakeries, confectioneries, and meat products among others. Due to the versatility that oleogels offer, other relevant technological functionalities as well as the development of health‐promoting systems have been the subject of extensive research. MG oleogels have been explored as oil migration inhibitors, emulsion stabilizers, lipid oxidation stability enhancers, and even as 3D printing materials. Among the most recent applications are the use of MG oleogels as carriers of bioactive compounds as well as the development of systems able to modulate lipid digestion. This review exclusively focuses on the advances over the last decade in technological and nutritional applications of MG oleogels and MG oleogel‐based systems, outlining the most significant findings and conclusions from the literature, as well as challenges and trends for future studies.
Reutilization of crystalline waste plastics for modified asphalt using twin‐screw extrusion: Polyethylene and polypropylene as typical subjects
Authors: Li Junwei , Jia Shoubo , Yang Dan , Li Xin , Li Dongdong , Ye Xia , Guan Pengbing , Zhao Yongke
Published: June 2022

The key technologies for waste plastic modified asphalt were storage stability and low temperature performance. In order to reutilize waste plastics for modified asphalt, a simple strategy, which based on recrystallization of the waste plastics, was proposed in this article. It was found that the pretreated waste plastics had higher crystallinity and smaller crystal size. Moreover, the deformation resistance and stability of the modified asphalt were improved. In addition, a rational mechanism called “polymer crystals confinement effect” was proposed to reveal the intrinsic correlation between the properties of crystalline waste plastics and modified asphalt.
In vitro‐studies of adenosine‐ β‐cyclodextrin inclusion complexes loaded into chitosan, sodium alginate and bentonite‐based nanocomposite optimized by RSM as a sustained release system
Authors: Khushbu  , Jindal Rajeev
Published: June 2022

Drugs with less aqueous solubility and permeability acquire significant hurdles in designing safe and effective formulations. The purpose of this study was to prepare an adenosine (ADS): β‐cyclodextrin (β‐CD) inclusion complex that could be consistently incorporated into a nanocomposite system for topical administration. Several procedures, including kneading, microwave irradiation, and co‐precipitation, were used to develop an adenosine: β‐CD inclusion complex. ROESY, DSC, XRD, and 1H NMR spectroscopy were used to analyze the adenosine‐β‐CD inclusion complex. Then bentonite (BN) incorporated chitosan (CH) and sodium alginate (ALG) nanocomposite were synthesized by microwave irradiation method. Response Surface Methodology (RSM) design was executed to optimize the reaction parameters. The Minimum Resolution V design was implemented to find significant variables to get maximum percentage swelling. The inclusion complexes of ADS: β‐CD were directly loaded into the CH/ALG/BN nanocomposite and the adenosine release was analyzed in simulated intestinal fluids (SIF) and simulated gastric fluids (SGF). Five kinetic models were investigated to know about the drug release mechanism. After a 24‐h interval, the ADS final release was 86 ppm at pH 2, 96 ppm at pH 7, and 85 ppm at pH 7.4. Bentonite has a layered structure that allows it to introduce the drug molecule into its cavity, resulting in sustainable adenosine release. The exploratory kinetic analysis demonstrated that β‐CD influences polymer relaxation, resulting in slow release.
A new pan‐kinosternid, Leiochelys tokaryki, gen. et sp. nov., from the late Maastrichtian Frenchman formation, Saskatchewan Canada
Authors: Brinkman Donald B. , Libke Caelan , McKellar Ryan C. , Gasilov Sergei , Somers Christopher M.
Published: June 2022

Previously, only a single member of Pan‐Kinosternidae (Yelmochelys rosarioae) had been documented from the Late Cretaceous epoch. In this report we describe a new pan‐kinosternid genus and species, herein named Leiochelys tokaryki, based on a nearly complete, articulated skeleton from the Late Cretaceous (Maastrichtian) Frenchman Formation of Saskatchewan, Canada. L. tokaryki differs most notably from the previously described Y. rosarioae in having triangular plastral lobes, and in that the suture between the hyo‐ and hypoplastron is in line with the suture between the fifth and sixth peripherals. A maximum parsimony analysis suggests that L. tokaryki is intermediate between Y. rosarioae and crown‐group kinosternids. Kinosternid features present in L. tokaryki include the presence of a reduced plastral bridge that extends from the posterior tip of peripheral 4 to the anterior tip of peripheral 7, two inframarginals that contact one another, a smooth triturating surface, and participation of the palatine in the triturating surface. An unexpected feature of the skull is the presence of a large stapedial canal, suggesting that the decrease in size of the stapedial canal and increase in the canalis caroticus cerebralis occurred independently in Dermatemydidae and Kinosternidae. The character‐states of the skull and skeleton of L. tokaryki indicate that morphological changes occurring during the diversification of Kinosternoidea were more complex than expected based on data from derived members of the group.
Morphologies in‐between: The impact of the first steps on the human talus
Authors: Figus Carla , Stephens Nicholas B. , Sorrentino Rita , Bortolini Eugenio , Arrighi Simona , Higgins Owen A. , Lugli Federico , Marciani Giulia , Oxilia Gregorio , Romandini Matteo , Silvestrini Sara , Baruffaldi Fabio , Belcastro Maria Giovanna , Bernardini Federico , Festa Anna , Hajdu Tamás , Mateovics‐László Orsolya , Pap Ildiko , Szeniczey Tamás , Tuniz Claudio , Ryan Timothy M. , Benazzi Stefano
Published: June 2022

Objective

The development of bipedalism is a very complex activity that contributes to shaping the anatomy of the foot. The talus, which starts ossifying in utero, may account for the developing stages from the late gestational phase onwards. Here, we explore the early development of the talus in both its internal and external morphology to broaden the knowledge of the anatomical changes that occur during early development.

Materials and Methods

The sample consists of high‐resolution microCT scans of 28 modern juvenile tali (from 36 prenatal weeks to 2 years), from a broad chronological range from the Late Roman period to the 20th century. We applied geometric morphometric and whole‐bone trabecular analysis to investigate the early talar morphological changes.

Results

In the youngest group (<6 postnatal months), the immature external shell is accompanied by an isotropic internal structure, with thin and densely packed trabeculae. After the initial attempts of locomotion, bone volume fraction decreases, while anisotropy and trabecular thickness increase. These internal changes correspond to the maturation of the external shell, which is now more defined and shows the development of the articular surfaces.

Discussion

The internal and external morphology of the human talus reflects the diverse load on the foot during the initial phases of the bipedal locomotion, with the youngest group potentially reflecting the lack of readiness of the human talus to bear forces and perform bipedal walking. These results highlight the link between mechanical loading and bone development in the human talus during the acquisition of bipedalism, providing new insight into the early phases of talar development.
Design, synthesis, biological evaluation, and in silico studies of 2‐aminobenzothiazole derivatives as potent PI3Kα inhibitors
Authors: Haider Kashif , Ahmad Kamal , Najmi Abul Kalam , Das Subham , Joseph Alex , Shahar Yar M.
Published: June 2022

A new series of 2‐aminobenzothiazole derivatives was designed, synthesized and evaluated for their anticancer activity against the MCF7, MDAMB‐231, and HepG2 cancer cell lines. All synthesized derivatives (8a–8n) demonstrated moderate to high anticancer activity against the tested cell lines. As the most potent compound in the series, compound 8i displayed excellent inhibitory potency with an IC50 value of 6.34 μM and compound 8m displayed an IC50 value of 8.30 µM against the MCF7 cell line compared to the standard drug HS‐173 (IC50 = 10.25 μM). PI3K enzyme activity assays demonstrated that compound 8i is highly selective against PI3Kα, with an IC50 value of 1.03 nM. Wound healing assays and cell cycle analysis of compounds 8i and 8m revealed that both compounds suppressed the migration of MCF7 cells and induce cell cycle arrest in the S phase. In the cell death assay, compound 8i was revealed to induce apoptosis in a dose‐dependent pattern; further Western blot assays revealed that compound 8i obviously decreases the levels of the antiapoptotic proteins Bcl‐xL and Mcl‐1. Downregulation of the expression of p‐Akt confirmed the PI3K inhibitory activity of compound 8i. The molecular docking and molecular dynamics simulation studies performed were found in agreement with the PI3Kα inhibitory activity assessments performed experimentally.
Characterization of lignocellulosic crop residues for potential biogas production in Zimbabwe
Authors: Kamusoko Reckson , Jingura Raphael M. , Parawira Wilson , Chikwambi Zedias
Published: June 2022

Lignocellulosic biomass is considered to be an abundant and cheap resource for biogas plants. Efficient production of biogas from lignocelluloses depends upon its proximate composition. This short communication characterizes the proximate composition of locally available lignocellulosic crop residues (LCRs) – wheat straw, maize stover and soybean straw – as potential feedstocks for biogas production. Standard Methods for the Examination of Water and Wastewater were used to determine its physicochemical characteristics. Cellulose, lignocellulose and lignin content of the biomass were evaluated after Soxhlet ectraction. Results show that proximate composition varied widely amongst LCRs. Lignocellulosic crop residues were acidic in nature with high total nitrogen (TN) content, hence the need for some buffering in anaerobic digestion (AD). Soybean straw and wheat straw showed the highest pH and TN content, respectively. However, all LCRs contained more than 30% cellulose, suggesting their potential use in AD. Wheat straw reported the highest cellulose (37.8%) and hemicellulose (28.2%) content, and it was thus considered to be the most competitive feedstock for AD. Soybean straw had the lowest cellulose and hemicellulose content but it was found to have the highest lignin content (23.5%). The findings imply that soybean straw will have the lowest AD efficiency. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.
The Drama of Farm Hall: A Historian Ventures into Play Writing
Authors: Cassidy David C.
Published: June 2022

In this paper, the author, a historian, describes the challenges he encountered as he sought to turn the Farm Hall event and its surviving transcripts into a theatrical play. The play, Farm Hall, was produced in New York in 2014 and published in Cassidy 2017. This paper further discusses what the author learned about the nature and elements of a play, how he applied those lessons to his play, and the advantages and disadvantages of this genre for bringing historical events to the general public.
Guidance to trigger point injection for treating myofascial pain syndrome: Intramuscular neural distribution of the quadratus lumborum
Authors: Yi Kyu‐Ho , Lee Kyu‐Lim , Lee Ji‐Hyun , Hu Hye‐Won , Kim Hee‐Jin
Published: June 2022

Postural habits and repetitive motion contribute toward the progress of myofascial pain by affecting overload on specific muscles, the quadratus lumborum (QL) muscle being the most frequently involved. The therapy of myofascial pain syndrome includes the release of myofascial pain syndrome using injective agents such as botulinum neurotoxin, lidocaine, steroids, and normal saline. However, an optimal injection point has not been established for the QL muscle. This study aimed to propose an optimal injection point for this muscle by studying its intramuscular neural distribution using the whole mount staining method. A modified Sihler's procedure was completed on 15 QL muscles to visualize the intramuscular arborization areas in terms of the inferior border of the 12th rib, the transverse processes of L1–L4, and the iliac crest. The intramuscular neural distribution of the QL had the densely arborized areas in the three lateral portions of L3–L4 and L4–L5 and the medial portion between L4 and L5.
Malnutrition from anorexia nervosa triggers severe complications of hereditary spherocytosis in an adolescent girl: A case report
Authors: Trivedi Aditi M. , Dworsky Zephyr D. , Kim Jenny , Yu Jennifer C. , Kumar Maya M.
Published: June 2022

Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS who developed unexpected and life‐threatening complications of her inherited hemolytic anemia as a consequence of anorexia nervosa and severe malnutrition.
A solitary precaval right renal artery: A case report
Authors: Farahzadi Athena , Mahmoodzadeh Habibollah , Gopal Nikhil
Published: June 2022

Knowledge of aberrant renal vasculature is critical for preoperative planning of either open or minimally invasive renal surgery. A precaval right renal artery is a rare anatomical variant in which the artery passes anterior to the inferior vena cava(IVC), as opposed to coursing posteriorly. When encountered, this artery is mostly accessory and thus accompanied by renal vessels in orthotopic position. Here, we describe an unusual instance of a solitary, main precaval right renal artery. It can be diagnosed preoperatively by a cross‐sectional imaging study. Awareness of this anomaly is very important to prevent iatrogenic injury during surgical intervention.