bluuebunny/crossref_metadata_2025 huggingface dataset:
Sur les traces d'Alain Robbe-Grillet: 1989. Une semaine Robbe-Grillet à l'Université de Salamanque
Authors: García Cela Carmen
Published: December 2022

In October 1989, French writer Alain Robbe-Grillet visited Salamanca Université after have been invited by Josette Borrás Dunand, professor at the Department of French Philology. The aim of this report is to broadcast the unpublished texts of Robbe-Grillet’s lectures at Salamanca University. Starting with a reflection upon formal aspects of literature – the renewal of the novel and autobiography, the enunciation, the differences and similarities between literature and cinema, or female representations – Robbe-Grillet undertakes a journey through authors such as Balzac, Camus or Flaubert, looking for the concomitances and divergences between Literature, Philosophy, Psychology or Psychoanalysis and Science.

Durante el mes de octubre de 1989, el escritor Alain Robbe-Grillet visitó la Universidad de Salamanca invitado por la profesora del Departamento de Filología Francesa, Josette Borrás Dunand. El objetivo del presente dossier es dar a conocer los textos inéditos de los seminarios que el escritor francés pronunció en la Universidad de Salamanca. Partiendo de una reflexión sobre aspectos formales de la literatura –la renovación de la novela y la autobiografía, la enunciación, las diferencias y similitudes entre la literatura y el cine o las representaciones femeninas–, Robbe-Grillet emprende un recorrido a través de autores como Balzac, Camus o Flaubert, buscando las concomitancias y las divergencias entre la literatura, la filosofía, la psicología o el psicoanálisis, y la ciencia.

En octobre 1989, l’écrivain Alain Robbe-Grillet a visité l’Université de Salamanque, invité par Josette Borrás Dunand, Maître de conférences au Département de Philologie française. Le présent dossier se donne pour but de diffuser les textes inédits des séminaires que l’écrivain français a réalisés à l’Université de Salamanque. En partant d’une réflexion concernant des aspects formels de la littérature –le renouveau du roman et de l’autobiographie, l’énonciation, les différences et similitudes entre la littérature et le cinéma ou bien les représentations féminines–, Robbe-Grillet entreprend un parcours à travers des auteurs comme Balzac, Camus ou Flaubert, en cherchant les concomitancese et les divergences entre la littérature, la philosophie, la psychologie ou la psychanalyse, et la science.
POTENTIALITY OF INDUSTRIAL TOURISM AND ITS CIVIL SOCIETY IN TWO CASES OF ANDEAN DESTINATIONS: EVOLUTIVE ANALYSIS OF SAMACÁ FACTORIES (COLOMBIA) AND SEWELL CAMP (CHILE)
Authors: Buitrago Jeffer , Cànoves Gemma
Published: December 2022

The objective of the research carried out was to analyze the influence exerted by two industrial tourism destinations on civil society in each of their territories. These destinations are called Samacá Factories (Colombia) and the Sewell Camp (Chile) and are located in South America. As industrial tourism destinations evolve, the greater the involvement of civil society organizations in this type of tourism, which stimulates its strengthening due to cooperation and the formation of alliances between various social actors.

El objetivo de la investigación realizada consistió en analizar la influencia que ejercen dos destinos de turismo industrial sobre la sociedad civil de cada uno de sus entornos. Estos destinos se denominan Fábricas de Samacá (Colombia) y Campamento Sewell (Chile) y se encuentran localizados en Suramérica. A medida que estos destinos evolucionan en el tiempo, mayor es el involucramiento de las organizaciones de la sociedad civil en este tipo de turismo, lo cual estimula su fortalecimiento gracias a la cooperación y a la conformación de alianzas entre diversos actores sociales.
Polarization of Stakeholder Orientation Towards Geotourism Development in the Mount Slamet and Serayu Mountainous Areas, Central Java Province
Authors:   1Graduate Program in Ecotourism Management and Environmental Services, Faculty of Forestry and Environment, IPB University, Academic Ring Road Campus IPB Dramaga, Bogor, Indonesia 16680, Munajat M , Avenzora R , Darusman D , Basuni S
Published: December 2022

The success of geotourism development is strongly influenced by the orientation (perceptions, motivations and preferences) of the stakeholders. An aim of the study was to analyze the polarization of stakeholder orientation towards geotourism development in the Mount Slamet and Serayu Mountainous areas, Central Java Province. Research instrument used a closed-ended questionnaire following the scoring pattern of "One Score One Indicator Scoring System”. The sample of respondents was 8 stakeholder groups with a total of 1,252 respondents. The characteristics of the stakeholder was analysed by quantitative descriptive, while the indication of the polarization of the stakeholder orientation was analyzed by using the one way Anova statistical test. Results indicated that the polarization of stakeholder orientation had a positive direction and scale of polarization was strong. This conditions showed that there is a gap in the value of stakeholder orientation which makes the performance of geotourism development less than optimal. It is necessary to improve the quality of collaboration and cooperation so that there is no polarization in the orientation between stakeholders to achieve the sustainable geotourism development.
¿Son necesarios unos premios sobre visualización de datos?
Authors: Cantón Javier
Published: December 2022

La visualización de datos es una disciplina que vive actualmente lo que muchos consideran una segunda edad dorada. Sobre la primera «Edad de Oro» ya tuvimos ocasión de hablar en otro artículo de esta misma revista, gracias a una exposición de obras del siglo XIX pioneras para la visualización de datos. En el siglo XXI, con la explosión de información propiciada por el volumen, variedad y velocidad del fenómeno que conocemos como big data, la visualización de datos se ha convertido en una disciplina fundamental que nos permite convertir la información generada en conocimiento útil.
Aizsarggāzes ietekme uz augstas stiprības tērauda metināšanas procesu un šuvi pusautomātiskā metināšanā
Authors: Avišāns Didzis
Published: December 2022

Piedevmateriāli, aizsarggāze un metināšanas parametri ietekmē augstas stiprības tērauda MAG metināšanas procesu, metināšanas šuvi un tās ķīmisko sastāvu un struktūru. Promocijas darba gaitā veikts pētījums par četru dažādu aizsarggāzu ietekmi uz augstas izturības mazleģēta tērauda (MPa 650) MAG metināšanas procesu strūklveida loka apstākļos. Palielinoties metināšanas parametriem un samazinoties CO2 saturam aizsarggāzē, plazmai metināšanas vannītē bija daudz lielāka ietekme nekā īssavienojumam. Skābekļa maisījums nav piemērots augstas stiprības tērauda metināšanai ar augstiem metināšanas parametriem.
Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis
Authors: Wang Zhongxiao , Yemanyi Felix , Blomfield Alexandra K , Bora Kiran , Huang Shuo , Liu Chi-Hsiu , Britton William R , Cho Steve S , Tomita Yohei , Fu Zhongjie , Ma Jian-xing , Li Wen-hong , Chen Jing
Published: December 2022

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5−/− and Ndpy/− mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.
Modularization in Belief-Desire-Intention agent programming and artifact-based environments
Authors: Ortiz-Hernández Gustavo , Guerra-Hernández Alejandro , Hübner Jomi F. , Luna-Ramírez Wulfrano Arturo
Published: December 2022

This article proposes an extension for the Agents and Artifacts meta-model to enable modularization. We adopt the Belief-Desire-Intention (BDI) model of agency to represent independent and reusable units of code by means of modules. The key idea behind our proposal is to take advantage of the syntactic notion of namespace, i.e., a unique symbol identifier to organize a set of programming elements. On this basis, agents can decide in BDI terms which beliefs, goals, events, percepts and actions will be independently handled by a particular module. The practical feasibility of this approach is demonstrated by developing an auction scenario, where source code enhances scores of coupling, cohesion and complexity metrics, when compared against a non-modular version of the scenario. Our solution allows to address the name-collision issue, provides a use interface for modules that follows the information hiding principle, and promotes software engineering principles related to modularization such as reusability, extensibility and maintainability. Differently from others, our solution allows to encapsulate environment components into modules as it remains independent from a particular BDI agent-oriented programming language.
Enhanced biomass and thermotolerance of Arabidopsis by SiERECTA isolated from Setaria italica L
Authors: Zheng Jiacheng , Huang Xiaoyi , Li Jieqin , He Qingyuan , Zhao Wan , Zeng Chaowu , Chen Haizhou , Zhan Qiuwen , Xu Zhaoshi
Published: December 2022

Foxtail millet is commonly used as a food and forage grass. ERECTA (ER) is a receptor-like kinase that can improve plant biomass and stress resistance. The sorghum SbER10_X1 gene was used as a probe to identify ER family genes on the Setaria italica genomes (SiERs), and determine the characteristics of the SiERs family. Herein, the structural features, expression patterns, and thermotolerance of SiERs function were identified by bioinformatics analysis, real-time PCR and transgenesis estimation. Results showed that SiERs had four members: two members were located on chromosome 1 with a total of six copies (SiER1_X1, SiER1_X2, SiER1_X3, SiER1_X4, SiER1_X5, and SiER1_X6), and two were on chromosome 4, namely, SiER4 (SiER4_X1 and SiER4_X2) and SiERL1. Among them, SiER1_X4 and SiER4_X1 were expressed highest in above-ground organs of foxtail millet, and actively responded to treatments with abscisic acid, brassinolide, gibberellin, and indole acetic acid. After overexpression of SiER1_X4 and SiER4_X1 in Arabidopsis, the plant height and biomass of the transgenic Arabidopsis significantly increased. Following high-temperature treatment, transgenic seedlings survived better compared to wild type. Transgenic lines showed higher SOD and POD activities, and expression level of AtHSF1 and AtBl1 genes significantly increased. These results indicated that SiER1_X4 and SiER4_X1 played important regulatory roles in plant growth and thermotolerance. The two genes provide potential targets for conventional breeding or biotechnological intervention to improve the biomass of forage grass and thermotolerance of field crops.
Comparative Efficacy between Streptokinase, Tenecteplase and Reteplase in ST Elevated Myocardial Infarction among Patients Attending Tertiary Care Hospital of Odisha
Authors: Sahu Lorika , Mohanty Nirmal Kumar , Goutam Siddhartha , Swain Trupti Rekha
Published: December 2022

Introduction: ST Elevation Myocardial Infarction (STEMI) is one of the most fatal emergencies contributing to significant morbidity and mortality due to coronary artery disease. Fibrinolytic agents are most effective agents used for the management of STEMI. However, there is a relative paucity of data comparing the effectiveness of thrombolytic agents that can provide insight for proper selection of this class of drugs. Aim: To compare the efficacy of streptokinase, tenecteplase, and reteplase in patients of STEMI in terms of post-thrombolytic resolution by observing reduction of ST-segment elevation at 90 minutes of thrombolytic and assessing for mortality within 30 days of therapy. Materials and Methods: This prospective, single-centre, observational, hospital-based study was conducted in the Department of Cardiology in collaboration with the Department of Pharmacology at Srirama Chandra Bhanja Medical College and Hospital, Odisha, India, from February 2020 to January 2022. The study involved 300 patients (100 patients in each group) being treated with streptokinase, or tenecteplase,or reteplase. A reduction of ≥50% of the initial ST elevation was considered as successful thrombolysis. The efficacy of the thrombolysis with these agents was assessed based on the extent of ST resolution in Electrocardiogram (ECG) at 90 minutes and observing 30 day mortality thereafter. Categorical data were evaluated using Chisquare test and the means were evaluated using Analysis of Variance (ANOVA). Results: There was no statistically significant difference between the three groups with respect to ST segment reduction. At 90 minutes of thrombolysis, 75%, 76%, 72% patients showed reduction in the ST segment in the Streptokinase, Tenecteplase and Reteplase group, respectively (p-value=0.79). A total of 9, 5 and 8 deaths were seen in the streptokinase, tenecteplase and reteplase group, respectively within a span 30 days (p-value=0.52). Conclusion: Streptokinase, tenecteplase and reteplase were equally efficacious for thrombolysis in terms of thrombus resolution and preventing mortality, when started early.
Association between Serum Sialic Acid Levels and Disease Severity in Psoriasis: A Case-control Study
Authors: Bhavyashree UG , Vedant Laddha , Vishal B , Pinto Malcolm , Shenoy Manjunath
Published: December 2022

Introduction: Psoriasis is a chronic inflammatory disease distributed worldwide with varying prevalence among different geographical areas and ethnic groups. It has been recently found that oxidative stress is one of the important factors in the pathogenesis of psoriasis. The varied effects of oxidative stress include changes in cellular uptake, altered enzymatic activity of proteins, increased predisposition to aggregation and proteolysis, which subsequently alter their immunogenicity. Sialic Acid (SA) is an acetylated derivative of neuramic acid. It is a marker for acute phase inflammatory response, with increased levels observed in inflammatory diseases. Aim: To estimate the levels of SA in psoriasis patients and to correlate with the severity of the disease. Materials and Methods: This case-control study was conducted among 50 patients, diagnosed with psoriasis, and 50 age and sex-matched subjects without psoriasis. General, systemic and dermatological examination was carried out. The severity of psoriasis was assessed according to Psoriasis Area Severity Index (PASI). The serum was treated with ethanol and centrifugation to precipitate proteins. The SA of both the precipitate and supernatant was estimated based on the reaction of SA with the ninhydrin reagent. Calculation of sialic acid was done by the formula: OD of test/ OD of standard x Concentration of the standard. To establish a correlation student’s t-test was used. Results: There were 39 males and 11 females in each case and control group. The mean±SD age of cases and controls was 44.04±10.9 years and 44.10±9.996, respectively. The mean PASI value was 23.1666 ± 18.47. Mean SA in cases and controls were 35.792±2.124 and 28.556±3.854 (p-values <0.001). A positive correlation was observed between the free SA and psoriasis severity (p-value <0.001, r = 0.460). Conclusion: Higher levels of free serum SA were significantly associated with more severe forms of psoriasis.
Diffusion MRI of the Brain and Susceptibility Weighted Imaging (SWI) in Evaluation of Patients with Acute Stroke
Authors: Rahma Mahmoud Nabil Mohamed , Abokhadra Rania Sobhi Mohamed , El-Safa Ashraf Ali Abo , El-Ahwal Hanan Mohamed Saleh
Published: December 2022

Background: Magnetic resonance imaging (MRI) is useful not only in identifying ischemic lesions. Susceptibility-weighted imaging (SWI) is a new magnetic resonance procedure that utilizes the magnetic susceptibility variances of various tissues, such as iron, blood and calcification. The aim of this work was to highlight the role of addition of susceptibility weighted MR images to diffusion weighted images of the brain in diagnosis of cases with acute stroke.  

Methods: This prospective study included 30 subjects with clinical manifestations of acute stroke. All the subjects underwent history taking, routine laboratory tests, cardiologic assessment by echocardiogram and imaging modalities including non-contrast CT study and MRI of the brain.

Results: PVS on SWI was found in 23 (76.7%) cases, 6 (20%) cases had macro-hemorrhage (low signals) on SWI, and 1 (3.3%) patient had no SWI findings. DWI showed a sensitivity of (100%) and SWI showed a sensitivity of (96.7%) for detection of infarct All of the 30 (100 %) cases showed hyperintense signals on T2WIs, FLAIR sequences and on DWI and hypointense signals on ADC map.

Conclusions: SWI is a potential adjunct in those patients for detecting an asymmetric prominent hypointense vessels, positive DWI-SWI mismatch is considered as a marker of infarct expansion and an indicator of the ischemic penumbra.
Application of the Trapez-Method to the Calculation of Coupling Matrices between Uniaxial Guide Modes
Authors: Moukengue Charmolavy G. L. Nkouka , Kiminou B. Mafouna , Nguembo Odilon
Published: December 2022

In this paper, we determine the different possible couplings at the discontinuities of the two circular and rectangular waveguides using the trapez-method. The development of the normal modes of the fields allows us to obtain the amplitude of the fields of the transverse electric (TE) and magnetic (TM) modes. The calculation of the coupling integrals allows us to obtain the coupling matrices and to verify if the coupling is possible or not between the modes of these two waveguides.
NATIONAL EDUCATION POLICY 2020: REAFFIRMATION FOR EQUITABLE AND INCLUSIVE EDUCATION
Authors: Francis Jinu , Mathew Jasmine
Published: December 2022

Indias New Education Policy 2020 sets the stage for equitable and inclusive education envisioned by the United Nations Fourth Sustainable Development Goal. The policy proposes strategies to strengthen the education system so that all children in India can afford school. This paper details the policy recommendations for the equitable distribution of facilities there by the socio-economically disadvantaged groups to enjoy the benefits of education in schools and higher education institutions. Apart from enabling mechanisms, and an inclusive curriculum, the policy suggests training for teachers and recruitment of specialists such as special educators, counselors, and trained social workers.
ANALYSIS OF INCLUSIVE EDUCATION WITH AN ECOLOGICAL PERSPECTIVE
Authors: T.R Rajeemol , Joseph Dr. M.K.
Published: December 2022

Inclusive education is an emerging approach to integrating special education with general education to aim for an equitable and quality education system. Children with disabilities experience many problems when exposed to the general environment. Incorporating them into mainstream education calls for constructive collaboration among all stakeholders. This paper analyses the case of a child who has been attending regular school for 11 years from an ecological perspective and attempts to understand the influence of stakeholders at different levels of the ecosystem. The results of this analysis affirm the need for collaborative efforts of all stakeholders in integrating special education into general education.
CHILDREN OF COMMERCIAL SEX WORKERS AND INCLUSIVE EDUCATION
Authors: Sebastian Tiara , Mathew Lija Mary , I.P. Dr. Sr. Sunirose
Published: December 2022

The law stipulates that every child has essential fundamental rights such as the right to education, health, life, security, participation and protection from exploitation, yet these rights are frequently denied to children from marginalised groups due to some systemic biases. Children of Commercial sex workers (CSW), like their mothers, are victims of social ostracism, suffering from self-esteem issues, social isolation, and low quality of life. These children are often left behind and efforts make to bring them back to mainstream society by ensuring education and other fundamental needs are limited. This study explains the various laws, treaties and policies which promote the education of the marginalised population. The study also attempts to investigate the major psychosocial issues faced by these children in accessing education and the potential ways to promote the education of the children of Commercial Sex Workers.
Her Enduring Gift
Authors: Suneja Gita
Published: December 2022

In this essay, the author shares a story about the memories and importance that a gift from her mother has held throughout her life.
Association of Treatment Type and Loss to Follow-up With Tractional Retinal Detachment in Proliferative Diabetic Retinopathy
Authors: Tsui Jonathan C. , Yu Yinxi , VanderBeek Brian L.
Published: December 2022

Importance

The association of proliferative diabetic retinopathy (PDR) interventions of panretinal photocoagulation (PRP) and intravitreal injections (IVIs) with tractional retinal detachment (TRD) is unclear.

Objectives

To determine whether different treatment types or a 6-month or longer period of loss to follow-up (LTFU) is associated with TRD.

Design, Setting, and Participants

This nested case-control study included data from January 1, 2000, to June 30, 2021, of patients with PDR. Those who progressed to TRD were matched to non-TRD controls up to a 5:1 ratio. Exclusion criteria included 2 or fewer years in the plan, history of nondiabetic retinopathy, vitreous hemorrhage, previous RD, or any other surgically indicated diagnosis. Patient data were obtained from a deidentified commercial and Medicare Advantage medical claims database. Statistical analysis was performed from January to May 2022.

Exposures

Primary exposures of interest were prior treatment (PRP, IVI, both) and any period of 6 months or longer in which the patient received no eye care.

Main Outcomes and Measures

Odds ratios (ORs) of IVI only compared with PRP and 6-month or longer LTFU on development of TRD.

Results

After application of inclusion and exclusion criteria, a total of 214 patients (mean [SD] age, 55.6 [12.4] years; 115 female [53.7%]) with PDR and TRD were matched to 978 controls (mean [SD] age, 65.6 [11.3] years; 507 female [51.8%]) with only PDR. Among patients with TRD, 69 (32.2%) were treated with laser only, 17 (7.9%) were treated with injection only, 39 (18.2%) were treated with both, and 89 (41.6%) had no prior treatment. Among patients in the PDR-only group, 207 (21.2%) received laser only, 83 (8.5%) received injection only, 57 (5.8%) received both, and 631 (64.5%) received no treatment. After adjusted analysis, no difference in odds of TRD for patients who received injection only compared with patients who received laser only was found (adjusted OR [aOR], 0.56; 95% CI, 0.27-1.14). Patients who received both treatments had higher odds of TRD compared with those who received laser only (aOR, 2.33; 95% CI, 1.21-4.48), and patients who had no treatment had lower odds of TRD (aOR, 0.46; 95% CI, 0.29-0.71; P < .001 for treatment category). Similarly, no difference was seen in the odds of TRD between those with LTFU for 6 months or longer and those without LTFU (aOR, 0.72; 95% CI, 0.49-1.07; P = .11).

Conclusions and Relevance

Results of this case-control analysis suggest that there is no increased risk of TRD associated with IVI-only treatment or with 6-month or longer periods of LTFU, which supports the findings of other investigations. Nonetheless, LTFU rates continue to remain high in patients with PDR, which can contribute to substantial vision loss regardless of treatment regimen.
Intraoperative Use of Wide-Field Optical Coherence Tomography to Evaluate Tissue Microstructure in the Oral Cavity and Oropharynx
Authors: Badhey Arvind K. , Schwarz Julia S. , Laitman Benjamin M. , Veremis Brandon M. , Westra William H. , Yao Mike , Teng Marita S. , Genden Eric M. , Miles Brett A.
Published: December 2022

Importance

Involvement of deep margins represents a significant challenge in the treatment of oropharyngeal cancer, and given practical limitations of frozen-section analysis, a need exists for real-time, nondestructive intraoperative margin analysis. Wide-field optical coherence tomography (WF-OCT) has been evaluated as a tool for high-resolution adjunct specimen imaging in breast surgery, but its clinical application in head and neck surgery has not been explored.

Objective

To evaluate the utility of WF-OCT for visualizing microstructures at margins of excised oral and oropharyngeal tissue.

Design, Setting, and Participants

This nonrandomized, investigator-initiated qualitative study evaluated the feasibility of the Perimeter Medical Imaging AI Otis WF-OCT device at a single academic center. Included participants were adults undergoing primary ablative surgery of the oral cavity or oropharynx for squamous cell carcinoma in 2018 and 2019. Data were analyzed in October 2019.

Exposures

Patients were treated according to standard surgical care. Freshly resected specimens were imaged with high-resolution WF-OCT prior to routine pathology. Interdisciplinary interpretation was performed to interpret WF-OCT images and compare them with corresponding digitized pathology slides. No clinical decisions were made based on WF-OCT image data.

Main Outcomes and Measures

Visual comparisons were performed between WF-OCT images and hematoxylin and eosin slides.

Results

A total of 69 specimens were collected and scanned from 53 patients (mean [SD] age, 59.4 [15.2] years; 35 [72.9%] men among 48 patients with demographic data) undergoing oral cavity or oropharynx surgery for squamous cell carcinoma, including 42 tonsillar tissue, 17 base of the tongue, 4 buccal tissue, 3 mandibular, and 3 other specimens. There were 41 malignant specimens (59.4%) and 28 benign specimens (40.6%). In visual comparisons of WF-OCT images and hematoxylin and eosin slides, visual differentiation among mucosa, submucosa, muscle, dysplastic, and benign tissue was possible in real time using WF-OCT images. Microarchitectural features observed in WF-OCT images could be matched with corresponding features within the permanent histology with fidelity.

Conclusions and Relevance

This qualitative study found that WF-OCT imaging was feasible for visualizing tissue microarchitecture at the surface of resected tissues and was not associated with changes in specimen integrity or surgical and pathology workflow. These findings suggest that formal clinical studies investigating use of WF-OCT for intraoperative analysis of deep margins in head and neck surgery may be warranted.
Ryanodine receptor 2 promotes colorectal cancer metastasis by the ROS/BACH1 axis
Authors: Chen Tianwei , Zhang Xilin , Ding Xufen , Feng Jing , Zhang Xueli , Xie Dong , Wang Xiang
Published: December 2022

There is no targeted therapy for KRAS proto‐oncogene, GTPase (KRAS)‐mutant metastatic colorectal cancer (mCRC) because the underlying mechanism remains obscure. Based on bioinformatic analysis, this study aims to elucidate a potential gene target for which an approved drug is available, and to reveal the function as well as the underlying mechanism of the candidate gene. Here, we identified that ryanodine receptor 2 (RyR2) expression was upregulated in KRAS‐mutant mCRC, and that this promoted cancer cell metastasis. S107, an approved drug to inhibit calcium release from RyR2 in the clinic, inhibited cancer cell metastasis both in vitro and in vivo. High expression of RyR2 predicts poor survival in our patient cohort. CRC patients with serosa invasion and vascular tumor thrombus are characterized by high RyR2 expression. Analysis of expression profiles upon RyR2 knockdown and inhibition, revealed a set of metastasis‐related molecules, and identified BTB domain and CNC homolog 1 (BACH1) as the main transcription factor regulated by RyR2. RyR2 regulates cellular reactive oxygen species (ROS) levels, which activates nuclear factor erythroid 2‐related factor 2 (Nrf2; also known as NFE2L2) and HMOX1 expression, and thus BACH1 accumulation. Collectively, this study provides evidence that the RyR2/ROS/BACH1 axis may be a potential intervention target for CRC metastasis.
One‐Step Preparation of an Injectable Hydrogel Scaffold System Capable of Sequential Dual‐Growth Factor Release to Maximize Bone Regeneration
Authors: Kim Jun , Kim Young‐Min , Song Soo‐Chang
Published: December 2022

Numerous growth factors are involved in the natural bone healing process, which is precisely controlled in a time‐ and concentration‐dependent manner. Mimicking the secretion pattern of growth factors could be an effective means to maximize the bone regeneration effect. However, achieving the sequential delivery of various growth factors without the use of multiple materials or complex scaffold designs is challenging. Herein, an injectable poly(organophosphazene) hydrogel scaffold (IPS) encapsulating bone morphogenetic protein (BMP)‐2 and TGFβ‐1 (IPS_BT) is studied to mimic the sequential secretion of growth factors involved in natural bone healing. The IPS_BT system is designed to release TGFβ‐1 slowly while retaining BMP‐2 for a longer period of time. When IPS_BT is injected in vivo, the hydrogel is replaced by bone tissue. In addition, angiogenic (CD31 and alpha‐smooth muscle actin (α‐SMA)) and stemness (Nanog and SOX2) markers are highly upregulated in the early stages of bone regeneration. The IPS system developed here has promising applications in tissue engineering because 1) various amounts of the growth factors can be loaded in one step, 2) the release pattern of each growth factor can be controlled via differences in their molecular interactions, and 3) the injected IPS can be degraded and replaced with regenerated bone tissue.
Achieving Efficient Solution‐Processed Blue Narrowband Emitting OLEDs with Small Efficiency Roll‐Off by Using a Bulky TADF Sensitizer with High Reverse Intersystem Crossing Rate
Authors: Chen Liang , Chang Yufei , Shu Haiyang , Li Qiang , Shi Song , Wang Shumeng , Wang Lixiang
Published: December 2022

Solution‐processed organic light‐emitting diodes (OLEDs) based on multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters exhibit high color purity for next‐generation ultrahigh‐definition display. However, they suffer from low efficiency and large efficiency roll‐off due to slow triplet exciton upconversion of MR‐TADF emitters, resulting in serious triplet exciton quenching. Here, efficient solution‐processed blue MR‐TADF OLEDs featured with small efficiency roll‐off are developed by using a new bulky TADF sensitizer consisting of five di‐tert‐butylcarbazoles and one triazine with high reverse intersystem crossing rate of 2.0 × 107 s−1, which can rapidly convert triplet excitons to singlet ones to avoid exciton quenching. The Dexter energy transfer from the sensitizer to the MR‐TADF emitter is blocked by using tertiary butyl groups as the bulky unit in the sensitizer to increase the intermolecular distance for ensuring fast upconversion of triplet excitons on the sensitizer. And then the singlet excitons on sensitizer transfer to the emitter through long‐range Förster resonance energy transfer for narrowband emission. As a result, a maximum external quantum efficiency of 23.9% is achieved for the sensitized devices, slightly declining to 21.5% at a practical luminance of 1000 cd m−2. To the best of the authors’ knowledge, this is the best result for solution‐processed blue MR‐TADF OLEDs.
Organic Acid to Nitrile: A Chemoenzymatic Three‐Step Route
Authors: Winkler Margit , Horvat Melissa , Schiefer Astrid , Weilch Victoria , Rudroff Florian , Pátek Miroslav , Martínková Ludmila
Published: December 2022

Various widely applied compounds contain cyano‐groups, and this functional group serves as a chemical handle for a whole range of different reactions. We report a cyanide free chemoenzymatic cascade for nitrile synthesis. The reaction pathway starts with a reduction of carboxylic acid to aldehyde by carboxylate reductase enzymes (CARs) applied as living cell biocatalysts. The second – chemical – step includes in situ oxime formation with hydroxylamine. The final direct step from oxime to nitrile is catalyzed by aldoxime dehydratases (Oxds). With compatible combinations of a CAR and an Oxd, applied in one‐pot two‐step reactions, several aliphatic and aryl‐aliphatic target nitriles were obtained in more than 80% conversion. Phenylacetonitrile, for example, was prepared in 78% isolated yield. This chemoenzymatic route does not require cyanide salts, toxic metals, or undesired oxidants in contrast to entirely chemical procedures.

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Mn‐Mediated Radical Cascade Cyclization of 1,6‐Enynes with Arylboronic Acids to Access Dihydrobenzo[b]fluorenones
Authors: Raji Reddy Chada , Chandrakant Kajare Roshan , Punna Nagender
Published: December 2022

Herein, we report the synthesis of functionalized dihydro‐benzo[b]fluorenones through a manganese‐mediated cascade radical cyclization ofβ‐alkynyl propenones [1,6‐enynes] with arylboronic acids. In the present strategy, the in‐situ generated aryl radical undergoes chemo‐selective addition followed by 5‐exo‐trigcyclization. The reaction is emphasized by high atom‐ and step‐economy with the construction of three new C−C bonds to access the dihydrobenzo[b]fluorenones in 68–81% yield under mild reaction conditions. The synthetic efficacy of the developed method is evidenced by the construction of new C−C and C−N bonds.

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Recent Advance in Transition Metal‐Catalyzed Carboxylic Acid Guided B−H Functionalization of Carboranes
Authors: Wang Qian , Liu Bifu , Feng Kejun , Hashmi A. Stephen K.
Published: December 2022

Carboranes, a three‐dimensional class of carbon‐boron molecular clusters with remarkable electronic, physical, chemical characteristics, have proved as useful building blocks in boron neutron capture therapy agents, supramolecular design, optoelectronics, nanomaterials and organometallic/coordination chemistry. Thus, various organic modifications of the B−H and C−H functionalities in carboranes have been developed. These methods with great success utilize directing groups, such as carboxylic acids, to achieve a selective B−H functionalization of carboranes. The carboxyl group can be easily introduced to carboranes and then be removed after reactions. On the other hand, assisted by the carboxyl group a highly regioselective electrophilic attack at the electron‐rich positions B(4) and B(5) of the cage generates five‐membered metallacyclic intermediates, which then undergo further transformation. In this review, we show that transition metal‐catalyzed decarboxylation cross coupling reactions offer an opportunity for the selective and direct B−H activation of carboranes.

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PPDPF Promotes the Development of Mutant KRAS‐Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1
Authors: Ni Qian‐Zhi , Zhu Bing , Ji Yan , Zheng Qian‐Wen , Liang Xin , Ma Ning , Jiang Hao , Zhang Feng‐Kun , Shang Yu‐Rong , Wang Yi‐Kang , Xu Sheng , Zhang Er‐Bin , Yuan Yan‐Mei , Chen Tian‐Wei , Yin Fen‐Fen , Cao Hui‐Jun , Huang Jing‐Yi , Xia Ji , Ding Xu‐Fen , Qiu Xiao‐Song , Ding Kai , Song Chao , Zhou Wen‐Tao , Wu Meng , Wang Kang , Lui Rui , Lin Qiu , Chen Wei , Li Zhi‐Gang , Cheng Shu‐Qun , Wang Xiao‐Fan , Xie Dong , Li Jing‐Jing
Published: December 2022

The guanine nucleotide exchange factor (GEF)
SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic‐specific deletion of PPDPF profoundly inhibits tumor development in KRASG12D‐driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP‐binding sites severely impair the tumor‐promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1–PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF‐SOS1 axis, and provides a promising therapeutic target for PDAC.
Lipid‐Peptide‐mRNA Nanoparticles Augment Radioiodine Uptake in Anaplastic Thyroid Cancer
Authors: Li Qinglin , Zhang Lizhuo , Lang Jiayan , Tan Zhuo , Feng Qingqing , Zhu Fei , Liu Guangna , Ying Zhangguo , Yu Xuefei , Feng He , Yi Heqing , Wen Qingliang , Jin Tiefeng , Cheng Keman , Zhao Xiao , Ge Minghua
Published: December 2022

Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.
Anion‐Dependent Polarization and Piezoelectric Power Generation in Hybrid Halide MAPbX3 (X = I, Br, and Cl) Thin Films with Out‐of‐Plane Structural Adjustments
Authors: Kim Da Bin , Jo Kyeong Su , Park Kwan Sik , Cho Yong Soo
Published: December 2022

Anion‐dependent differences in the electromechanical energy harvesting capability of perovskite halides have not been experimentally demonstrated thus far. Herein, anion‐dependent piezoelectricity and bending‐driven power generation in high‐quality methylammonium lead halide MAPbX3 (X = I, Br, and Cl) thin films are explored; additionally, anisotropic in situ strain is imposed to improve energy harvesting under tensile bending. After applying the maximum in situ strain of −0.73% for all the halide thin films, the MAPbI3 thin‐film harvester exhibited a peak voltage/current of ≈23.1 V/≈1703 nA as the best values, whereas MAPbBr3 and MAPbCl3 demonstrated ≈5.6 V/≈176 nA and ≈3.3 V/≈141 nA, respectively, under identical bending conditions. Apart from apparent ferroelectricity of tetragonal MAPbI3, origin of the piezoelectricity in both cubic MAPbBr3 and MAPbCl3 is explored as being related to organic–inorganic hydrogen bonding, lattice distortion, and ionic migration, with experimental supports of effective piezoelectric coefficient and grain boundary potential. Conclusively, piezoelectricity of the cubic halides is assumed to be due to their soft polarity modes and relatively low elastic modulus with vacancies contributing to space‐charge polarization. In the case of ferroelectric MAPbI3, the distortion of PbI6 octahedra and atomic displacement within each octahedron are quantitatively estimated.
Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions
Authors: Heng Boon Chin , Bai Yunyang , Li Xiaochan , Lim Lee Wei , Li Wang , Ge Zigang , Zhang Xuehui , Deng Xuliang
Published: December 2022

Bone degeneration associated with various diseases is increasing due to rapid aging, sedentary lifestyles, and unhealthy diets. Living bone tissue has bioelectric properties critical to bone remodeling, and bone degeneration under various pathological conditions results in significant changes to these bioelectric properties. There is growing interest in utilizing biomimetic electroactive biomaterials that recapitulate the natural electrophysiological microenvironment of healthy bone tissue to promote bone repair. This review first summarizes the etiology of degenerative bone conditions associated with various diseases such as type II diabetes, osteoporosis, periodontitis, osteoarthritis, rheumatoid arthritis, osteomyelitis, and metastatic osteolysis. Next, the diverse array of natural and synthetic electroactive biomaterials with therapeutic potential are discussed. Putative mechanistic pathways by which electroactive biomaterials can mitigate bone degeneration are critically examined, including the enhancement of osteogenesis and angiogenesis, suppression of inflammation and osteoclastogenesis, as well as their anti‐bacterial effects. Finally, the limited research on utilization of electroactive biomaterials in the treatment of bone degeneration associated with the aforementioned diseases are examined. Previous studies have mostly focused on using electroactive biomaterials to treat bone traumatic injuries. It is hoped that this review will encourage more research efforts on the use of electroactive biomaterials for treating degenerative bone conditions.
Faradic Side Reactions at Novel Carbon Flow‐Through Electrodes for Desalination Studied in a Static Supercapacitor Architecture
Authors: Molaei Arman , Crispin Xavier
Published: December 2022

Desalination by capacitive deionization (CDI) is a promising technique to combine desalination and energy storage. The efficiency of charge storage process, which is equivalent to the desalination process, depends strongly on the presence of Faradic side reactions on the electrode. Herein, the performance of a new low‐cost designed flow‐through electrode with porous carbon nanoparticles (CP) coating on carbon‐fiber paper (CFP) is evaluated. The CP layer enables high capacitance while the CFP core makes fluid dynamics along and across the electrode. The electrodes are evaluated by studying the effective operational CDI parameters, such as operational voltage, degassing of electrolyte, and salt concentration. The Faradic side reaction and its effect on charge efficiency (CE) are evaluated which are estimated to decrease to 46% by liquid flow bringing dissolved oxygen from the air‐electrolyte interface to the electrode. The CE enhances to 59% with a salt concentration of 1 m. By purging N2 gas, CE is much higher (>85%) with a maximum efficiency of 97% at 0.6 V. Three regimes of the complex kinetic of side reactions are found involving various species such as O2, H2O2, H2, and carbon oxidation and the implication of those regimes for real applications are discussed.
Development of a quantitative semi‐mechanistic model of Alzheimer's disease based on the amyloid/tau/neurodegeneration framework (the Q‐ATN model)
Authors: Mazer Norman A. , Hofmann Carsten , Lott Dominik , Gieschke Ronald , Klein Gregory , Boess Frank , Grimm Hans Peter , Kerchner Geoffrey A. , Baudler‐Klein Monika , Smith Janice , Doody Rachelle S. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: December 2022

Introduction

A quantitative model of Alzheimer's disease (AD) based on the amyloid/tau/neurodegeneration biomarker framework (Q‐ATN model) was developed to sequentially link amyloid positron emission tomography (PET), tau PET, medial temporal cortical thickness, and clinical outcome (Clinical Dementia Rating – Sum of Boxes; CDR‐SB).

Methods

Published data and biologically plausible mechanisms were used to construct, calibrate, and validate the model. Clinical trial simulations were performed for different anti‐amyloid antibodies, including a 5‐year simulation of subcutaneous gantenerumab treatment.

Results

The simulated time‐course of biomarkers and CDR‐SB was consistent with natural history studies and described the effects of several anti‐amyloid antibodies observed in trials with positive and negative (or non‐significant) outcomes. The 5‐year simulation predicts that the beneficial effects of continued anti‐amyloid treatment should increase markedly over time.

Discussion

The Q‐ATN model offers a novel approach for linking amyloid PET to CDR‐SB, and provides theoretical support for the potential clinical benefit of anti‐amyloid therapy.

Highlights

A semi‐mechanistic model was developed to link amyloid/tau/neurodegeneration biomarkers to clinical outcome (Q‐ATN model).

The Q‐ATN model describes the disease progression seen in natural history studies.

Model simulations agree well with mean data from the aducanumab EMERGE study.

A 5‐year simulation of gantenerumab predicts greater benefit with longer treatment.
Volume atrophy in medial temporal cortex and verbal memory scores in American Indians: Data from the Strong Heart Study
Authors: Suchy‐Dicey Astrid , Su Yi , Buchwald Dedra S , Manson Spero M. , Reiman Eric M
Published: December 2022

Introduction

Distinguishing Alzheimer's disease (AD) patient subgroups may optimize positive clinical outcomes. Cortical atrophy is correlated with memory deficits, but these associations are understudied in American Indians.

Methods

We collected imaging and cognition data in the Strong Heart Study (SHS), a cohort of 11 tribes across three regions. We processed 1.5T MRI using FreeSurfer and iterative principal component analysis. Linear mixed models estimated volumetric associations with diabetes.

Results

Over mean 7 years follow‐up (N = 818 age 65–89 years), overall volume loss was 0.5% per year. Significant losses associated with diabetes were especially strong in the right hemisphere. Annualized hippocampal, parahippocampal, entorhinal atrophy were worse for men, older age, diabetes, hypertension, stroke; and associated with both encoding and retrieval memory losses.

Discussion

Our findings suggest that diabetes is an important risk factor in American Indians for cortical atrophy and memory loss. Future research should examine opportunities for primary prevention in this underserved population.
Light‐Fueled Transformations of a Dynamic Cage‐Based Molecular System
Authors: Ovalle Marco , Kathan Michael , Toyoda Ryojun , Stindt Charlotte N. , Crespi Stefano , Feringa Ben L.
Published: December 2022

In a chemical equilibrium, the formation of high‐energy species—in a closed system—is inefficient due to microscopic reversibility. Here, we demonstrate how this restriction can be circumvented by coupling a dynamic equilibrium to a light‐induced E/Z isomerization of an azobenzene imine cage. The stable E‐cage resists intermolecular imine exchange reactions that would “open” it. Upon switching, the strained Z‐cage isomers undergo imine exchange spontaneously, thus opening the cage. Subsequent isomerization of the Z‐open compounds yields a high‐energy, kinetically trapped E‐open species, which cannot be efficiently obtained from the initial E‐cage, thus shifting an imine equilibrium energetically uphill in a closed system. Upon heating, the nucleophile is displaced back into solution and an opening/closing cycle is completed by regenerating the stable all‐E‐cage. Using this principle, a light‐induced cage‐to‐cage transformation is performed by the addition of a ditopic aldehyde.