bluuebunny/crossref_metadata_2025 huggingface dataset:
Sanity and Germination of Treated with Clove Extract Jurema-Preta and Faveleira Seeds
Authors: Silva Henrique Gilvanete , Dos Santos Gilvan José Campelo , De Souza Jaltiery Bezerra , Nicácio Luz Mellina , Cunha Lima Maria Alaine , De Moura Isadora Nayara Bandeira , Medeiros Silva Jailson
Published: October 2021

The Mimosa tenuiflora (jurema-preta) and Cnidoscolus quercifolius (faveleira) are quite common species in the Caatinga biome, being used from forage production to energy generation and in the recovery of degraded areas for reforestation purposes, among other uses. Considering the need and importance of studies related to forest seeds health, especially native seeds and taking into account the scarcity of studies in the literature regarding the association of pathogens to the seeds of the species studied, this work aimed to evaluate the efficiency of the hydroalcoholic extract of clove on germination and incidence of fungi associated with seeds of jurema-preta and faveleira. The experiment was conducted in the Laboratory of Forest Pathology, Center of Health and Rural Technology, Federal University of Campina Grande, Patos, Paraíba, Brasil. For the germination test we performed the dormancy breaking of seeds that were then treated with clove plant extract, and as substrate, washed and sterilized sand was used. Germination percentage and Twinning speed index (SVI) were evaluated. The sanity test was performed using the filter paper method "Blotter Test" for the development of microorganisms. The treatments consisted of: 0%, 25%, 50%, 75% and 100% of clove extract, with 4 repetitions of 25 seeds. The design used was entirely randomized and the means were compared using Tukey's test at 5% probability. The clove extract, in higher concentrations, provided an increase in germination and SVI of the species. It was identified in the seeds of jurema-preta, the fungi Aspergillus niger, Aspergillus flavus, Aspergillus glaucous, Rhizopus sp, the genus Phoma sp. In the seeds of C. quercifolius the microflorea was composed by fungi Aspergillus niger, Aspergillus flavus, Aspergillus glaucous, Rhizopus sp, Aspergillus alutaceous and Aspergillus candidus.
Comparison of Single Antibiotic Paste Nitrofurantoin and Calcium Hydroxide Paste as Intracanal Medicaments in Alleviating Post-Operative Pain in Patients with Symptomatic Irreversible Pulpitis -A Randomized Controlled Trial
Authors: Abbasi Hira , Lal Abhishek , Shamim Jaffrani Ammara
Published: October 2021

Aims: This study aims to compare the efficacy in alleviating pain between intracanal medicaments, namely Nitrofurantoin and Calcium Hydroxide Paste.

Study Design:  Randomized Controlled Trial.

Place and Duration of Study: Sample: Department of Operative Dentistry, Sir Syed College of Medical Sciences, Pakistan, between January 2021 and May 2021.

Methodology: 60 patients were randomly divided into 3 groups, each group having 20 patients as following: Group 1: Nitrofurantoin, Group 2: Calcium Hydroxide and Group 3: Control. Preoperative pain was recorded using a numerical pain scale. After access preparation, chemomechanical preparation was performed with subsequent placement of intracanal medicaments. Pre-operative pain score was initially recorded, followed by post-operative pain at 12, 24, 48, and 72 hours, respectively. Root canal treatment was performed in single rooted teeth with patients suffering from symptomatic irreversible pulpitis

Results: Majority of the patients in all 3 groups were initially presented with moderate to severe pre-operative pain. After 72 hours post-operatively, 50% patients in Group 1 reported no pain, while 5% patients in both Group 2 and 3 had no pain. Pain significantly subsided in Group 1 as compared to Group 2 and 3. Regarding age and gender, both had no significant relationship with the pain scores in all of the 3 groups

Conclusion: Nitrofurantoin has been proven to be an effective intracanal medicament in alleviating immediate post-operative pain in patients with symptomatic irreversible pulpitis as compared to calcium hydroxide. While the control group with no intracanal medicament showed little reduction in pain scores. So, nitrofurantoin can be used as a substitute to currently available standard intracanal medicaments.
Progress in Clinical Application of Positive End-Expiratory Pressure
Authors: Zhaoxia Wu , Xianjie Wen
Published: October 2021

In the surgery patient under general anesthesia doesn’t breathe spontaneously, and lung movement is completely dependent on the mechanical ventilation of the anesthesia machine. In order to achieve effective and safe mechanical ventilation of the patient’s lungs during the operation, the concept of lung protective ventilation strategy (LPVS) was proposed, that is, the use of a low tidal volume and an appropriate level of positive end expiratory pressure (PEEP) to reduce alveolar overexpansion and prevent alveolar collapse. In the past, PEEP was an important measure to treat acute lung injury(ALI) or acute respiratory distress syndrome(ARDS) by improving oxygenation and reducing pulmonary edema. Subsequent studies found that PEEP not only be used to treat patients with ALI or ARDS, but also can reduce the incidence of postoperative pulmonary complications(PPCs) in some thoracoabdominal operations. Moreover, PEEP can prevent atelectasis during and after surgery in patients undergoing thoracic and abdominal surgery under general anesthesia, and decrease the incidence of postoperative infection. However, PEEP can affect venous return by increasing intrathoracic pressure, thereby causing changes in heart function and hemodynamics, and indirectly affecting intracranial pressure and renal function. Therefore, with the widespread clinical application of PEEP, more and more people are starting to focus on how to choose the appropriate PEEP. This article reviews the research progress of PEEP selection method, the influence of PEEP on physiological function and the clinical application of PEEP during mechanical ventilation.
Combining liquid biopsy and functional imaging analysis in metastatic castration‐resistant prostate cancer helps predict treatment outcome
Authors: Conteduca Vincenza , Scarpi Emanuela , Caroli Paola , Lolli Cristian , Gurioli Giorgia , Brighi Nicole , Poti Giulia , Farolfi Alberto , Altavilla Amelia , Schepisi Giuseppe , Matteucci Federica , Paganelli Giovanni , De Giorgi Ugo
Published: October 2021

Plasma tumour DNA (ptDNA) is a potential early noninvasive biomarker of treatment outcome in metastatic castration‐resistant prostate cancer (mCRPC). Herein, we investigated whether pretreatment ptDNA levels reflect metabolic tumour burden in mCRPC and better predict treatment outcome in combination with functional imaging. Targeted next‐generation sequencing was performed to estimate the ptDNA fraction from 102 mCRPC patients receiving abiraterone or enzalutamide. The maximum standardized uptake value (SUVmax), total lesion activity (TLA) and metabolic tumour volume (MTV) were evaluated on 18F‐fluorocholine positron emission tomography/computed tomography. We assessed a Weibull multiple regression model to determine the combined impact of clinical, molecular and imaging characteristics on overall survival (OS) and progression‐free survival (PFS), and to obtain prognostic scores. A significant association was seen between ptDNA and SUVmax, MTV and TLA. For survival analysis, patients were randomly allocated into a training (n = 68) and a validation (n = 34) set. In the training set, multivariable analyses showed that ptDNA, MTV and serum lactate dehydrogenase together with visceral metastasis were independent predictors of both OS and PFS. Prognostic scores were generated, with the identification of three groups of patients with significantly different median OS (29.2, 15.9 and 8.7 months) and PFS (13.3, 7.7 and 3.2 months) probabilities. The differences in median survival between risk groups were confirmed in the validation cohort for both OS and PFS. In our study, we showed that integrating plasma DNA analysis with functional imaging may improve prognostic risk stratification and treatment selection in mCRPC.
Ternary Transition Metal Chalcogenide Nb2Pd3Se8: A New Candidate of 1D Van der Waals Materials for Field‐Effect Transistors
Authors: Jeong Byung Joo , Choi Kyung Hwan , Jeon Jiho , Yoon Sang Ok , Chung You Kyoung , Sung Dongchul , Chae Sudong , Kim Bum Jun , Oh Seungbae , Lee Sang Hoon , Woo Chaeheon , Kim Tae Yeong , Ahn Jungyoon , Lee Jae‐Hyun , Huh Joonsuk , Yu Hak Ki , Choi Jae‐Young
Published: October 2021

In this work, high‐quality 1D van der Waals (vdW) Nb2Pd3Se8 is synthesized, showing an excellent scalability from bulk to single‐ribbon due to weakly bonded repeating unit ribbons. The calculation of electronic band structures confirmed that this novel Nb2Pd3Se8 is a semiconducting material, displaying indirect‐to‐direct bandgap transition with decreasing the number of unit‐ribbons from bulk to single. Field effect transistors (FETs) fabricated on the mechanically exfoliated Nb2Pd3Se8 nanowires exhibit n‐type transport characteristics at room temperature, resulting in the values for the electron mobility and Ion/Ioff ratio of 31 cm2 V−1 s−1 and ≈104, respectively. Through transport measurements at various temperatures from room temperature down to 90 K, it is confirmed that Nb2Pd3Se8 FETs can achieve negligible Schottky barrier height (SBH) for the Au contacts at the temperature range, displaying clear ohmic contact characteristics. Furthermore, top‐gated FETs fabricated with the Al2O3 dielectric layer are studied simultaneously with back‐gated FETs.
Amorphous VO2: A Pseudocapacitive Platform for High‐Rate Symmetric Batteries
Authors: Chao Dongliang , DeBlock Ryan , Lai Chun‐Han , Wei Qiulong , Dunn Bruce , Fan Hong Jin
Published: October 2021

Among the various VO2 polymorphs, the layered compound, VO2(B), has been the most widely investigated lithium‐ion battery electrode material. For sodium‐ion electrodes, however, an amorphous solid may be more advantageous as a result of the open framework to facilitate ion insertion and the ability to tolerate volumetric changes. Herein, it is shown that the Na+ insertion properties of amorphous VO2 (a‐VO2) are superior to those of crystalline VO2(B). Amorphous VO2 exhibits a linear voltage characteristic over a 3 V range (4.0 to 1.0 V vs Na/Na+) leading to a reversible capacity as high as 400 mAh g−1 and rapid redox kinetics, which is attributed to its pseudocapacitive nature. The linear voltage characteristic over 3 V affords the opportunity of fabricating a symmetric Na‐ion battery in which the a‐VO2 material serves as both the positive electrode and the negative electrode. Such a symmetric battery offers safer operation in terms of overcharging, overdischarging, polarity reversal, high charge/discharge current abuse, and long‐term usage. The results suggest that amorphous transition metal oxides may offer advantageous attributes for rapid, safe, and energy‐dense storage.
Anti‐Friction MSCs Delivery System Improves the Therapy for Severe Osteoarthritis
Authors: Yan Xin , Yang Bo , Chen Yourong , Song Yifan , Ye Jing , Pan Yufan , Zhou Bini , Wang Yuqing , Mao Fengbiao , Dong Yuanchen , Liu Dongsheng , Yu Jiakuo
Published: October 2021

Osteoarthritis (OA) is a musculoskeletal disorder disease affecting about 500 million people worldwide and mesenchymal sem cells (MSCs) therapy has been demonstrated as a potential strategy to treat OA. However, the shear forces during direct injection and the harsher shear condition of OA environments would lead to significant cell damage and inhibit the therapeutic efficacy. Herein, DNA supramolecular hydrogel has been applied as delivering material for MSCs to treat severe OA model, which perform extraordinary protection in MSCs against the shear force both in vitro and in vivo. It is demonstrated that the DNA supramolecular hydrogel can promote formation of quality cartilage, reduce osteophyte, and normalize subchondral bone under the high friction condition of OA, whose molecular mechanisms underlying therapeutic effects are also investigated. It can be anticipated that DNA supramolecular hydrogel would be a promising cell delivery system for multiple potential MSCs therapy.
Contribution of Alzheimer's biomarkers and risk factors to cognitive impairment and decline across the Alzheimer's disease continuum
Authors: Tosun Duygu , Demir Zeynep , Veitch Dallas P. , Weintraub Daniel , Aisen Paul , Jack Clifford R. , Jagust William J. , Petersen Ronald C. , Saykin Andrew J. , Shaw Leslie M. , Trojanowski John Q. , Weiner Michael W. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2021

Introduction

Amyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer's disease (AD) risk factors affect the severity of clinical symptoms and disease progression.

Methods

Within 248 Aβ‐positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ‐positron emission tomography [PET] uptake, regional tau‐PET uptake, and regional magnetic resonance imaging–based atrophy) and risk‐factors (age, sex, education, apolipoprotein E [APOE], and white‐matter lesions) on cross‐sectional cognitive impairment and longitudinal cognitive decline.

Results

Sixteen percent of variance in cross‐sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ–tau–atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively.

Discussion

These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.
A review on the latest progress of C‐S cross‐coupling in diaryl sulfide synthesis: Update from 2012 to 2021
Authors: Abedinifar Fahimeh , Bahadorikhalili Saeed , Larijani Bagher , Mahdavi Mohammad , Verpoort Francis
Published: October 2021

Diaryl sulfides are a highly valuable class of sulfur‐containing compounds presented in numerous drugs with a broad range of therapeutic activities and are also employed as precursors to other higher oxidation state sulfur‐containing compounds with important bioactivities. Thus, the development of efficient approaches for C−S bond formation is essential in synthetic and medicinal chemistry. Many efforts have been made in constructing C−S bonds via various protocols. This review highlights the current strategies emphasizing metal‐catalyzed reactions (MRC), metal‐free approaches, photocatalysis reactions, and MCR's from 2012 onwards.
Transition‐Metal‐Free Catalyzed Dehydrative Coupling of Quinoline and Isoquinoline N‐Oxides with Propargylic Alcohols
Authors: Cai Zhao‐Nan , Feng Xiang‐Xuan , Zhang Yuecheng , Lu Cong‐Cong , Han Ya‐Ping , Zhao Jiquan
Published: October 2021

Comprehensive Summary

A novel, green, and transition‐metal‐free protocol for the facile modification of quinoline and isoquinoline derivatives is introduced, starting from readily available and environmentally benign quinoline and isoquinoline N‐oxides with propargylic alcohols in the presence of Na2S2O8 or K2S2O8 at 100 °C. The one‐pot transformation features the advantages of good functional group compatibility, short reaction time, operational simplicity, and highly efficient reaction system. This protocol, which produces water as the only byproduct, provides efficient and atom‐economical access to a class of fascinating quinoline and isoquinoline products in satisfactory yields. The method is effective on the gram scale, thus highlighting the inherent practicality of this methodology.
Risk‐Based Pharmacokinetic and Drug–Drug Interaction Characterization of Antibody–Drug Conjugates in Oncology Clinical Development: An International Consortium for Innovation and Quality in Pharmaceutical Development Perspective
Authors: Li Chunze , Menon Rajeev , Walles Markus , Singh Renu , Upreti Vijay V. , Brackman Deanna , Lee Anthony J. , Endres Christopher J. , Kumar Seema , Zhang Donglu , Barletta Frank , Suri Ajit , Hainzl Dominik , Liao Kai H. , Lalovic Bojan , Beaumont Maribel , Zuo Peiying , Mayer Andrew P. , Wei Dong
Published: October 2021

Antibody–drug conjugates (ADCs) represent a rapidly evolving area of drug development and hold significant promise. To date, nine ADCs have been approved by the US Food and Drug Administration (FDA). These conjugates combine the target specificity of monoclonal antibodies with the anticancer activity of small‐molecule therapeutics (also referred to as payload). Due to the complex structure, three analytes, namely ADC conjugate, total antibody, and unconjugated payload, are typically quantified during drug development; however, the benefits of measuring all three analytes at later stages of clinical development are not clear. The cytotoxic payloads, upon release from the ADC, are considered to behave like small molecules. Given the relatively high potency and low systemic exposure of cytotoxic payloads, drug–drug interaction (DDI) considerations for ADCs might be different from traditional small molecule therapeutics. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) convened an ADC working group to create an IQ ADC database that includes 26 ADCs with six unique payloads. The analysis of the ADC data in the IQ database, as well as nine approved ADCs, supports the strategy of pharmacokinetic characterization of all three analytes in early‐phase development and progressively minimizing the number of analytes to be measured in the late‐phase studies. The systemic concentrations of unconjugated payload are usually too low to serve as a DDI perpetrator; however, the potential for unconjugated payloads as a victim still exists. A data‐driven and risk‐based decision tree was developed to guide the assessment of a circulating payload as a victim of DDI.
Decidual CXCR4+CD56brightNK cells as a novel NK subset in maternal–foetal immune tolerance to alleviate early pregnancy failure
Authors: Tao Yu , Li Yan‐Hong , Zhang Di , Xu Ling , Chen Jia‐Jia , Sang Yi‐Fei , Piao Hai‐Lan , Jing Xue‐Ling , Yu Min , Fu Qiang , Zhou Sheng‐Tao , Li Da‐Jin , Du Mei‐Rong
Published: October 2021

Natural killer (NK) cells preferentially accumulate at maternal–foetal interface and are believed to play vital immune‐modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal–foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4+CD56brightdNK and investigated its origin and phenotypic and functional characteristics. CXCR4+CD56brightdNK displayed a less activated and cytotoxic phenotype but an enhanced immunomodulatory potential relative to the CXCR4 negative subset. CXCR4+CD56brightdNK promote Th2 shift in an IL‐4‐dependent manner and can be recruited from peripheral blood and reprogramed by trophoblasts, as an active participant in the establishment of immune‐tolerance during early pregnancy. Diminished CXCR4+ dNK cells and their impaired ability to induce Th2 differentiation were found in RM patients and mouse models of spontaneous abortion. Moreover, adoptive transfer of CXCR4+ dNK cells to NK‐deficient (Nfil3–/–) mice showed great therapeutic potential of CXCR4+ dNK via recovering the Th2/Th1 bias and reducing embryo resorption rates. The identification of this new dNK cell subset may lay the foundation for understanding NK cell mechanisms in early pregnancy and provide potential prognostic factors for the diagnosis and therapy of RM.
Can the impact of canopy trees on soil and understory be altered using litter additions?
Authors: Yelenik Stephanie G. , Rehm Evan M. , D'Antonio Carla M.
Published: October 2021

Trees can have large effects on soil nutrients in ways that alter succession, particularly in the case of nitrogen‐(N)‐fixing trees. In Hawaiʻi, forest restoration relies heavily on use of a native N‐fixing tree, Acacia koa (koa), but this species increases soil‐available N and likely facilitates competitive dominance of exotic pasture grasses. In contrast, Metrosideros polymorpha (‘ōhi‘a), the dominant native tree in Hawaiʻi, is less often planted because it is slow growing; yet it is typically associated with lower soil N and grass biomass, and greater native understory recruitment. We experimentally tested whether it is possible to reverse high soil N under koa by adding ‘ōhi‘a litter, using additions of koa litter or no litter as controls, over 2.5 yr. We then quantified natural litterfall and decomposition rates of ‘ōhi‘a and koa litter to place litter additions in perspective. Finally, we quantified whether litter additions altered grass biomass and if this had effects on native outplants. Adding ‘ōhi‘a litter increased soil carbon, but increased rather than decreased inorganic soil N pools. Contrary to expectations, koa litter decomposed more slowly than ‘ōhi‘a, although it released more N per unit of litter. We saw no reduction in grass biomass due to ‘ōhi‘a litter addition, and no change in native outplanted understory survival or growth. We conclude that the high N soil conditions under koa are difficult to reverse. However, we also found that outplanted native woody species were able to decrease exotic grass biomass over time, regardless of the litter environment, making this a better strategy for lowering exotic species impacts.
Tumor DNA‐methylome derived epigenetic fingerprint identifies HPV‐negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy
Authors: Tawk Bouchra , Wirkner Ute , Schwager Christian , Rein Katrin , Zaoui Karim , Federspil Philippe A. , Adeberg Sebastian , Linge Annett , Ganswindt Ute , Hess Julia , Unger Kristian , Tinhofer Ingeborg , Budach Volker , Lohaus Fabian , Krause Mechthild , Guberina Maja , Stuschke Martin , Balermpas Panagiotis , Rödel Claus , Grosu Anca L. , Schäfer Henning , Zips Daniel , Combs Stephanie E. , Pigorsch Steffi , Zitzelsberger Horst , Baumeister Philipp , Kirchner Thomas , Bewerunge‐Hudler Melanie , Weichert Wilko , Hess Jochen , Herpel Esther , Belka Claus , Baumann Michael , Debus Jürgen , Abdollahi Amir ,   For the DKTK‐ROG
Published: October 2021

Biomarkers with relevance for loco‐regional therapy are needed in human papillomavirus negative aka HPV(−) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome‐based classifier identifying HPV(−) HNSCC patients at risk for loco‐regional recurrence (LR) and all‐event progression after postoperative radiochemotherapy (PORT‐C). The training cohort consisted of HPV‐DNA negative HNSCC patients (n = 128) homogeneously treated with PORT‐C in frame of the German Cancer Consortium—Radiation Oncology Group (DKTK‐ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K‐EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia‐, 5‐microRNA (5‐miR), stem‐cell gene‐expression signatures and immunohistochemistry (IHC)‐based immunological characterization of tumors (CD3/CD8/PD‐L1/PD1). Validation occurred in an independent cohort of HPV(−) HNSCC patients, pooled from two German centers (n = 125). We identified a 38‐methylation probe‐based HPV(−) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10−9). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T‐stage). HICR high‐risk tumors were enriched for younger patients with hypoxic tumors (15‐gene signature) and elevated 5‐miR score. After adjustment for hypoxia and 5‐miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(−) HNSCC patients treated with PORT‐C and opens a new opportunity for biomarker‐assisted stratification and therapy adaptation in these patients.
Liver tumor segmentation using a new asymmetrical dilated convolutional semantic segmentation network in CT images
Authors: Arulappan Anisha , Thankaraj Ajith Bosco Raj
Published: October 2021

Liver cancer has become one of the commonly occurring cancers in men and women. The segmented computed tomography (CT) image of the tumor is the major source for a doctor to diagnose liver diseases. This article proposes a fully automatic system based on an asymmetric dilated convolutional encoder–decoder neural (ADCEDN) network for the problem of accurately extracting the liver and tumor from abdominal CT slices. Specifically, two ADCEDN networks are used in a cascaded form to perform both liver and liver abnormality segmentation. We enrich the encoder module by incorporating the multiscale contextual information through dilated convolutions that enhance the capacity and efficiency of the network. Hybrid dilated convolution across depths perform depth‐wise separable convolution by providing a less steep increase in dilation rate and thus denser sampling that can reduce the computation cost and several metrics while maintaining better performance. Also, the encoder–decoder network is made asymmetric, thereby making the network less complex and more generalizable. The suggested method produced an average dice similarity coefficient score of 96.54% and 76.16% for liver segmentation and liver abnormality segmentation on the 3D Image Reconstruction for Comparison of Algorithm Database data set and 96.42% and 75.7% on the Liver Tumor Segmentation data set. The test outcomes show that the proposed ADCEDN attains state‐of‐the‐art performance in both segmentation of liver and tumors.
An overview of current alternative models in the context of ocular surface toxicity
Authors: Bonneau Noémie , Baudouin Christophe , Réaux‐Le Goazigo Annabelle , Brignole‐Baudouin Françoise
Published: October 2021

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs.
Enhanced neural differentiation of human‐induced pluripotent stem cells on aligned laminin‐functionalized polyethersulfone nanofibers; a comparison between aligned and random fibers on neurogenesis
Authors: Ghollasi Marzieh , Poormoghadam Delaram
Published: October 2021

Despite the numerous attempts in nerve tissue engineering, no ideal strategy has been translated into effective therapy for neuronal regeneration yet. Here, we designed a novel nerve regeneration scaffold combining aligned laminin‐immobilized polyethersulfone (PES) nanofibers and human‐induced pluripotent stem cells (hiPSCs) for transplantation strategies. Aligned and random PES nanofibers were fabricated by electrospinning method with a diameter of 95–500 nm and were then modified with covalent laminin bounding subsequent to O2 plasma treatment. PES‐functionalized fibers found to induce a remarkable higher rate of neuronal genes expression as compared to nontreated group. In addition, hiPSCs cultured on aligned pure fibers exhibited the extension of neurites along with fibers direction and an exponentially elevated expression of neuron specific enolase (early neuroectoderm marker), Tuj‐1 (axonal marker), and microtubule‐associated protein 2 (dendritic marker) in comparison with random pure fibers. The concomitant of increased hydrophilicity and biocompatibility along with exploiting topographical cues and directional guidance make aligned PES‐plasma‐laminin a versatile scaffold for adhesion, proliferation, spreading, and differentiation of hiPSCs into nerve cells.
Oriented homo‐epitaxial crystallization of polylactic acid displaying a biomimetic structure and improved blood compatibility
Authors: Li Zhengqiu , Wu Ting , Chen Yueling , Gao Xiaoyan , Ye Jingbiao , Jin Ying , Chen Baoshu
Published: October 2021

Epitaxial crystallization and solid hot‐drawing technology were employed to fabricate oriented homo‐epitaxial crystallization of polylactic acid (PLA) with nano‐topography to enhance its blood compatibility and mechanical characteristics as blood‐contacting medical devices. The process involved solid hot stretching the PLA plates. A PLA nutrient solution was then used to immerse the oriented plates to dissolve some of the PLA solutes, ensuring plate integrity. Consequently, the drawing process exponentially enhanced the modulus and tensile strength of the PLA. Orientation and epitaxial crystallization could substantially enhance blood compatibility of PLA by prolonging clotting time and decreasing hemolysis rate, protein adsorption, and platelet activation. The oriented homo‐epitaxial crystallization of PLA exhibited a nano‐topography and fibrous structure similar to the intimal layer of a blood vessel, and this biomimetic structure was advantageous in decreasing the activation and/or adhesion of platelets.
Hemispheric cortical atrophy and chronic microglial activation following mild focal ischemic stroke in adult male rats
Authors: Ermine Charlotte M. , Nithianantharajah Jess , O’Brien Katrina , Kauhausen Jessica A. , Frausin Stefano , Oman Alexander , Parsons Mark W. , Brait Vanessa H. , Brodtmann Amy , Thompson Lachlan H.
Published: October 2021

Animal modeling has played an important role in our understanding of the pathobiology of stroke. The vast majority of this research has focused on the acute phase following severe forms of stroke that result in clear behavioral deficits. Human stroke, however, can vary widely in severity and clinical outcome. There is a rapidly building body of work suggesting that milder ischemic insults can precipitate functional impairment, including cognitive decline, that continues through the chronic phase after injury. Here we show that a small infarction localized to the frontal motor cortex of rats following injection of endothelin‐1 results in an essentially asymptomatic state based on motor and cognitive testing, and yet produces significant histopathological change including remote atrophy and inflammation that persists up to 1 year. While there is understandably a major focus in stroke research on mitigating the acute consequences of primary infarction, these results point to progressive atrophy and chronic inflammation as additional targets for intervention in the chronic phase after injury. The present rodent model provides an important platform for further work in this area.
Expression of degQ gene and its effect on lipopeptide production as well as formation of secretory proteases in Bacillus subtilis strains
Authors: Lilge Lars , Vahidinasab Maliheh , Adiek Isabel , Becker Philipp , Kuppusamy Nesamani Chanthiya , Treinen Chantal , Hoffmann Mareen , Morabbi Heravi Kambiz , Henkel Marius , Hausmann Rudolf
Published: October 2021

Bacillus subtilis is described as a promising production strain for lipopeptides. In the case of B. subtilis strains JABs24 and DSM10T, surfactin and plipastatin are produced. Lipopeptide formation is controlled, among others, by the DegU response regulator. The activating phospho‐transfer by the DegS sensor kinase is stimulated by the pleiotropic regulator DegQ, resulting in enhanced DegU activation. In B. subtilis 168, a point mutation in the degQ promoter region leads to a reduction in gene expression. Corresponding reporter strains showed a 14‐fold reduced expression. This effect on degQ expression and the associated impact on lipopeptide formation was examined for B. subtilis JABs24, a lipopeptide‐producing derivative of strain 168, and B. subtilis wild‐type strain DSM10T, which has a native degQ expression. Based on the stimulatory effects of the DegU regulator on secretory protease formation, the impact of degQ expression on extracellular protease activity was additionally investigated. To follow the impact of degQ, a deletion mutant was constructed for DSM10T, while a natively expressed degQ version was integrated into strain JABs24. This allowed strain‐specific quantification of the stimulatory effect of degQ expression on plipastatin and the negative effect on surfactin production in strains JABs24 and DSM10T. While an unaffected degQ expression reduced surfactin production in JABs24 by about 25%, a sixfold increase in plipastatin was observed. In contrast, degQ deletion in DSM10T increased surfactin titer by threefold but decreased plipastatin production by fivefold. In addition, although significant differences in extracellular protease activity were detected, no decrease in plipastatin and surfactin produced during cultivation was observed.
On a weakly L‐stable time integration formula coupled with nonstandard finite difference scheme with application to nonlinear parabolic partial differential equations
Authors: Rawani Mukesh Kumar , Verma Lajja , Verma Amit Kumar , Agarwal Ravi P.
Published: October 2021

In the present paper, we establish an efficient numerical scheme based on weakly L‐stable time integration convergent formula and nonstandard finite difference (NSFD) scheme. We solve Burgers' equation with Dirichlet boundary conditions as well as Neumann boundary conditions. We also solve the Fisher equation. We use Hermite approximation polynomial of order five and backward explicit Taylor's series approximation of order six to derive the numerical integration formula for the initial value problem (IVP)
. We combine this method with the NSFD scheme and convert the problem into the system of algebraic equations. We discuss the convergence, truncation error, and stability of the developed method. To demonstrate the efficiency of the developed method, we compare the numerical results with some existing numerical results and exact solutions.
Intergenerational polygenic obesity risk throughout adolescence in a cross‐sectional study design: The HUNT study, Norway
Authors: Næss Marit , Sund Erik R. , Vie Gunnhild Å. , Bjørngaard Johan H. , Åsvold Bjørn Olav , Holmen Turid Lingaas , Kvaløy Kirsti
Published: October 2021

Objective

This study examined the relationship between parental obesity polygenic risk and children’s BMI throughout adolescence. Additionally, from a smaller subsample, the objective was to assess whether parental polygenic risk score (PRS) may act as a proxy for offspring PRS in studies lacking offspring genetic data.

Methods

A total of 8,561 parent‐offspring (age 13‐19 years) trios from the Trøndelag Health Study (the HUNT Study) were included, of which, 1,286 adolescents had available genetic data. Weighted parental PRSs from 900 single‐nucleotide polymorphisms robustly associated with adult BMI were constructed and applied in linear mixed‐effects models.

Results

A positive association between parental PRS and offspring sex‐ and age‐adjusted BMI (iso‐BMI) throughout adolescence was identified. The estimated marginal effects per standard deviation increase in parental PRS were 0.26 (95% CI: 0.18‐0.33), 0.36 (95% CI: 0.29‐0.43), and 0.62 kg/m2 (95% CI: 0.51‐0.72) for maternal, paternal, and combined parental PRS, respectively. In subsample analyses, the magnitude of association of the parental PRS versus offspring PRS with iso‐BMI in adolescents was similar.

Conclusions

Parental PRS was consistently associated with offspring iso‐BMI throughout adolescence. Results from subsample analyses support the use of parental PRS of obesity as a proxy for adolescent PRS in the absence of offspring genetic data.
Synthesis, Characterization and Photocatalytic Behavior of SiO2@nitrized‐TiO2 Nanocomposites Obtained by a Straightforward Novel Approach
Authors: Gulino Antonino , Papanikolaou Georgia , Lanzafame Paola , Aaliti Abdellatif , Primerano Patrizia , Spitaleri Luca , Triolo Claudia , Dahrouch Zainab , Khaskhoussi Amani , Lo Schiavo Sandra
Published: October 2021

We report on the facile synthesis of SiO2@nitrized‐TiO2 nanocomposite (NST) by calcination of TiO2 xerogel with OctaAmmonium POSS® (N‐POSS; POSS=polyhedral oligomeric silsesquioxanes). The as‐obtained nanoporous mixed oxide is constituted by uniformly distributed SiO2 and nitrized‐TiO2, where the silica component is present in an amorphous state and TiO2 in an anatase/rutile mixed phase (92.1 % vs. 7.9 %, respectively) with very small anatase crystallites (3.7 nm). The TiO2 lattice is nitrized both at interstitial and substitutional positions. NST features a negatively charged surface with a remarkable surface area (406 m2 g−1), endowed with special adsorption capabilities towards cationic dyes. Its photocatalytic behavior was tested by following the degradation of standard aqueous methylene blue and methyl orange solutions under UV and visible light irradiation, according to ISO 10678:2010. For comparison, analogous investigations were carried out on a silica‐free N−TiO2, obtained by using NH4Cl as nitrogen source.
Efficacy and toxicity of high‐risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia
Authors: van Binsbergen Annelien L. , de Haas Valérie , van der Velden Vincent H.J. , de Groot‐Kruseman Hester A. , Fiocco Marta F. , Pieters Rob
Published: October 2021

Background

Children with acute lymphoblastic leukemia (ALL) and high‐risk (HR) features have a poor outcome and are treated with HR blocks, often followed by allogenic stem cell transplantation (SCT).

Procedure

This article analyses the outcomes of children treated with HR blocks between 2004 and 2017 according to DCOG ALL10/11 protocols. 1297 patients with newly diagnosed ALL were consecutively enrolled, of which 107 met the HR criteria (no complete remission; minimal residual disease (MRD) > 10–3 after consolidation; “MLL‐AF4” translocation and in ALL‐10 also poor prednisone response). Patients were treated with one induction and consolidation course followed by three HR chemotherapy blocks, after which they received either SCT or further chemotherapy. MRD levels were measured at end of induction, consolidation, and after each HR block.

Results

At five years, the event‐free survival was 72.8% (95% CI, 64.6‐82.0), and the cumulative incidence of relapse was 13.0% (95% CI, 6.3‐19.8). Patients with only negative or low‐positive MRD levels during HR blocks had a significantly lower five‐year cumulative incidence of relapse (CIR) of 2.2% (95% CI, 0‐6.6) compared with patients with one or more high‐positive MRD levels (CIR 15.4%; 95% CI, 3.9‐26.9). During the entire treatment protocol, 11.2% of patients died due to toxicity.

Conclusions

The high survival with HR blocks seems favorable compared with other studies. However, the limit of treatment intensification might have been reached as the number of patients dying from leukemia relapse is about equal as the number of patients dying from toxicity. Patients with negative or low MRD levels during HR blocks have lower relapse rates.
Bayesian inference and dynamic prediction of multivariate joint model with functional data: An application to Alzheimer's disease
Authors: Zou Haotian , Li Kan , Zeng Donglin , Luo Sheng ,   Alzheimer's Disease Neuroimaging Initiative
Published: October 2021

Alzheimer's disease (AD) is a severe neurodegenerative disorder impairing multiple domains, for example, cognition and behavior. Assessing the risk of AD progression and initiating timely interventions at early stages are critical to improve the quality of life for AD patients. Due to the heterogeneous nature and complex mechanisms of AD, one single longitudinal outcome is insufficient to assess AD severity and disease progression. Therefore, AD studies collect multiple longitudinal outcomes, including cognitive and behavioral measurements, as well as structural brain images such as magnetic resonance imaging (MRI). How to utilize the multivariate longitudinal outcomes and MRI data to make efficient statistical inference and prediction is an open question. In this article, we propose a multivariate joint model with functional data (MJM‐FD) framework that relates multiple correlated longitudinal outcomes to a survival outcome, and use the scalar‐on‐function regression method to include voxel‐based whole‐brain MRI data as functional predictors in both longitudinal and survival models. We adopt a Bayesian paradigm to make statistical inference and develop a dynamic prediction framework to predict an individual's future longitudinal outcomes and risk of a survival event. We validate the MJM‐FD framework through extensive simulation studies and apply it to the motivating Alzheimer's Disease Neuroimaging Initiative (ADNI) study.
Constructing a Cs3Sb2Br9/g‐C3N4 Hybrid for Photocatalytic Aromatic C(sp3)H Bond Activation
Authors: Zhang Hong-Hong , Zhou Zi-Chun , Dong Yu-Jie , Zhang Li , Chen Hong-Yan , Kuang Dai-Bin
Published: October 2021

Utilizing halide perovskites for photocatalytic aromatic C(sp3)H bond activation remains a great challenge due to the serious recombination of photogenerated charge carriers and slow reaction dynamics of the materials themselves. Herein, a lead‐free perovskite‐based hybrid of Cs3Sb2Br9/g‐C3N4 nanosheet is constructed and applied for photocatalytic aromatic C(sp3)H bond activation, which shows enhanced photocatalytic performance. By introducing ultrathin g‐C3N4 nanosheets as the heterogeneous nucleation sites, size‐reduced and well‐dispersed Cs3Sb2Br9 nanocrystals can be obtained. The as‐formed close contact and high‐quality heterointerface between Cs3Sb2Br9 and g‐C3N4 provides pathways for fast charge transfer which is beneficial to improve the separation efficiency of photogenerated electron−hole pairs. Under visible light irradiation, the Cs3Sb2Br9/g‐C3N4 hybrid photocatalyst can effectively oxidize toluene toward benzaldehyde and benzyl alcohol with a total conversion rate of 8346.8 μmol g−1 h−1, which is 26.6‐ and 6.0‐fold that of pure g‐C3N4 and Cs3Sb2Br9, respectively. This work demonstrates the potential of all‐inorganic lead‐free halide perovskite‐based heterostructures for photocatalytic organic reactions.
Application advances of deep learning methods for de novo drug design and molecular dynamics simulation
Authors: Bai Qifeng , Liu Shuo , Tian Yanan , Xu Tingyang , Banegas‐Luna Antonio Jesús , Pérez‐Sánchez Horacio , Huang Junzhou , Liu Huanxiang , Yao Xiaojun
Published: October 2021

De novo drug design is a stationary way to build novel ligands in the confined pocket of receptor by assembling the atoms or fragments, while molecular dynamics (MD) simulation is a dynamical way to study the interaction mechanism between the ligands and receptors based on the molecular force field. De novo drug design and MD simulation are effective tools for novel drug discovery. With the development of technology, deep learning methods, and interpretable machine learning (IML) have emerged in the research area of drug design. Deep learning methods and IML can be used further to improve the efficiency and accuracy of de novo drug design and MD simulations. The application summary of deep learning methods for de novo drug design, MD simulations, and IML can further promote the technical development of drug discovery. In this article, two major workflow methods and the related components of classical algorithm and deep learning are described for de novo drug design from a new perspective. The application progress of deep learning is also summarized for MD simulations. Furthermore, IML is introduced for the deep learning model interpretability of de novo drug design and MD simulations. Our paper deals with an interesting topic about deep learning applications of de novo drug design and MD simulations for the scientific community.

This article is categorized under:

Data Science > Chemoinformatics

Data Science > Artificial Intelligence/Machine Learning
Toward situational awareness in threat detection. A survey
Authors: Rendall Kieran , Mylonas Alexios , Vidalis Stilianos
Published: October 2021

The pervasiveness of the Internet did not come without security risk. The current threat landscape is characterized by the rise of sophisticated cyber attacks, which target user devices and corporate infrastructure. To tackle the risk of compromise, data‐driven detection strategies have become increasingly mainstream. The relevant literature includes many works that leverage open‐source datasets, supervised learning or, less commonly, unsupervised learning. However, advanced network attacks' spatial and temporal characteristics prove standalone threat detection systems inadequate, especially for detecting a multi‐stage attack and often stealthy techniques. Moreover, attackers have been demonstrating adversarial effects that are caused by deception and contaminating data‐driven methods with adversarial learning. For these reasons, recent research in threat detection is moving away from commonly, and often obsolete, datasets as well as adopting more multi‐layered decision strategies. As such, this article provides a comprehensive review of decision strategies. We also examine their ability to support cyber situational awareness (CSA), providing to security analysts CSA properties such as situation assessment and system refinement.

This article is categorized under:

Digital and Multimedia Science > Cyber Threat Intelligence
Inelastic dark matter, small scale problems, and the XENON1T excess
Authors: Baek Seungwon
Published: October 2021

Abstract

We study a generic model in which the dark sector is composed of a Majorana dark matter χ1, its excited state χ2, both at the electroweak scale, and a light dark photon Z′ with mz′ ∼ 10−4 eV. The light Z′ enhances the self-scattering elastic cross section χ1χ1 → χ1χ1 enough to solve the small scale problems in the N-body simulations with the cold dark matter. The dark matter communicates with the SM via kinetic mixing parameterized by ϵ. The inelastic scattering process χ1χ1 → χ2χ2 followed by the prompt decay χ2 → χ1Z′ generates energetic Z′. By setting δ ≡ mχ2− mχ1 ≃ 2.8 keV and ϵ ∼ 10−10 the excess in the electron-recoil data at the XENON1T experiment can be explained by the dark-photoelectric effect. The relic abundance of the dark matter can also be accommodated by the thermal freeze-out mechanism via the annihilation χ1χ1(χ2χ2) → Z′Z′ with the dark gauge coupling constant αX ∼ 10−3.