bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients
Authors: Vijenthira Abi , Gong Inna , Betschel Stephen D. , Cheung Matthew , Hicks Lisa K.
Published: June 2021

The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were searched up to 4 January 2021 to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease. The primary outcomes were seroprotection (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (<3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 [95% CI, 0.24-1.06] compared with healthy and of 0.44 [95% CI, 0.23-0.84] compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.
Factors associated with long-term care certification in older adults: a cross-sectional study based on a nationally representative survey in Japan
Authors: Momose Akira , Yamaguchi Satoko , Okada Akira , Ikeda-Kurakawa Kayo , Namiki Daisuke , Nannya Yasuhito , Kato Hideki , Yamauchi Toshimasa , Nangaku Masaomi , Kadowaki Takashi
Published: June 2021

Background

Long-term care (LTC) prevention is a pressing concern in ageing societies. To understand the risk factors of LTC, it is vital to consider psychological and social factors in addition to physical factors. Owing to a lack of relevant data, we aimed to investigate the social, physical and psychological factors associated with LTC using large-scale, nationally representative data to identify a high-risk population for LTC in terms of multidimensional frailty.

Methods

We performed a cross-sectional study using anonymised data from the 2013 Comprehensive Survey of Living Conditions conducted by the Ministry of Health, Labour and Welfare of Japan. Among the 23,730 eligible people aged 65 years or older and those who were not in hospitals or care facilities during the survey, 1718 stated that they had LTC certification. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with LTC certification.

Results

Factors positively associated with LTC certification in the multivariate analyses included older age, the interaction term between sex and age group at age 85–89 years, limb movement difficulties, swollen/heavy feet, incontinence, severe psychological distress (indicated by a Kessler Psychological Distress Scale [K6] score ≥ 13), regular hospital visits for dementia, stroke, Parkinson’s disease, chronic obstructive pulmonary disease, fracture, rheumatoid arthritis, kidney disease, diabetes and osteoporosis. Factors negatively associated with LTC certification included the presence of a spouse, regular hospital visits for hypertension and consulting with friends or acquaintances about worries and stress.

Conclusions

In summary, we identified the physical, psychological and social factors associated with LTC certification using nationally representative data. Our findings highlight the importance of the establishment of multidimensional approaches for LTC prevention in older adults.
Overcoming barriers to the adoption of locating technologies in dementia care: a multi-stakeholder focus group study
Authors: Freiesleben Silka Dawn , Megges Herlind , Herrmann Christina , Wessel Lauri , Peters Oliver
Published: June 2021

Background

Locating technologies are a subtype of assistive technology that aim to support persons with dementia by helping manage spatial orientation impairments and provide aid to care partners by intervening when necessary. Although a variety of locating devices are commercially available, their adoption has remained low in the past years. Several studies have explored barriers to the adoption of assistive technologies from the perspective of professional stakeholders, but in-depth explorations for locating technologies are sparse. Additionally, the inputs of business professionals are lacking. The aim of this study was to expand knowledge on barriers to the adoption of locating technologies from a multi-stakeholder professional perspective, and to explore strategies to optimize adoption.

Methods

In total, 22 professionals working in business (n = 7), healthcare (n = 6) and research (n = 9) fields related to gerontology and gerontechnology participated in our focus group study. Perceptions on the value of using locating technologies for dementia care, barriers to their adoption, as well as salient services and information dissemination strategies were explored. After verbatim transcription, transcripts were analysed following an inductive data-driven content analysis approach in MAXQDA.

Results

Six key adoption barriers centering on: (1) awareness-, (2) technological-, (3) product characteristic- and (4) capital investment-based limitations, (5) unclear benefits, as well as (6) ethical concerns emerged. The interplay between barriers was high. Five core themes on services and information dissemination strategies centering on: (1) digital autonomy support, (2) emergency support, (3) information dissemination actors, (4) product acquisition, and (5) product advertising were extracted.

Conclusions

Our study with interdisciplinary stakeholders expands knowledge on barriers to the adoption of locating technologies for dementia care, and reinforces recommendations that an interdisciplinary strategy is needed to optimize adoption. Also, our findings show that focusing on services to increase digital autonomy and on information dissemination strategies has been largely overlooked and may be particularly effective.
Genomic epidemiology of methicillin-resistant and -susceptible Staphylococcus aureus from bloodstream infections
Authors: Smith Joshua T. , Eckhardt Elissa M. , Hansel Nicole B. , Eliato Tahmineh Rahmani , Martin Isabella W. , Andam Cheryl P.
Published: June 2021

Background

Bloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.

Methods

We generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010–2018.

Results

In silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966–1979) and 1946 for CC8 (95% HPD intervals: 1924–1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.

Conclusions

We conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.
Improving the quality of nursing documentation at a residential care home: a clinical audit
Authors: Moldskred Preben Søvik , Snibsøer Anne Kristin , Espehaug Birgitte
Published: June 2021

Background

Quality in nursing documentation holds promise to increase patient safety and quality of care. While high-quality nursing documentation implies a comprehensive documentation of the nursing process, nursing records do not always adhere to these documentation criteria. The aim of this quality improvement project was to assess the quality of electronic nursing records in a residential care home using a standardized audit tool and, if necessary, implement a tailored strategy to improve documentation practice.

Methods

A criteria-based clinical audit was performed in a residential care home in Norway. Quantitative criteria in the N-Catch II audit instrument was used to give an assessment of electronic nursing records on the following: nursing assessment on admission, nursing diagnoses, aims for nursing care, nursing interventions, and evaluation/progress reports. Each criterium was scored on a 0–3 point scale, with standard (complete documentation) coinciding with the highest score. A retrospective audit was conducted on 38 patient records from January to March 2018, followed by the development and execution of an implementation strategy tailored to local barriers. A re-audit was performed on 38 patient records from March to June 2019.

Results

None of the investigated patient records at audit fulfilled standards for recommended nursing documentation practice. Mean scores at audit varied from 0.4 (95 % confidence interval 0.3–0.6) for “aims for nursing care” to 1.1 (0.9–1.3) for “nursing diagnoses”. After implementation of a tailored multifaceted intervention strategy, an improvement (p < 0.001) was noted for all criteria except for “evaluation/progress reports” (p = 0.6). The improvement did not lead to standards being met at re-audit, where mean scores varied from 0.9 (0.8–1.1) for “evaluation/progress reports” to 1.9 (1.5–2.2) for “nursing assessment on admission”.

Conclusions

A criteria-based clinical audit with multifaceted tailored interventions that addresses determinants of practice may improve the quality of nursing documentation, but further cycles of the clinical audit process are needed before standards are met and focus can be shifted to sustainment of knowledge use.
An MR-based radiomics model for differentiation between hepatocellular carcinoma and focal nodular hyperplasia in non-cirrhotic liver
Authors: Ding Zongren , Lin Kongying , Fu Jun , Huang Qizhen , Fang Guoxu , Tang Yanyan , You Wuyi , Lin Zhaowang , Lin Zhan , Pan Xingxi , Zeng Yongyi
Published: June 2021

Purpose

We aimed to develop and validate a radiomics model for differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH) in non-cirrhotic livers using Gd-DTPA contrast-enhanced magnetic resonance imaging (MRI).

Methods

We retrospectively enrolled 149 HCC and 75 FNH patients treated between May 2015 and May 2019 at our center. Patients were randomly allocated to a training (n=156) and validation set (n=68). In total, 2260 radiomics features were extracted from the arterial phase and portal venous phase of Gd-DTPA contrast-enhanced MRI. Using Max-Relevance and Min-Redundancy, random forest, least absolute shrinkage, and selection operator algorithm for dimensionality reduction, multivariable logistic regression was used to build the radiomics model. A clinical model and combined model were also established. The diagnostic performance of the models was compared.

Results

Eight radiomics features were chosen for the radiomics model, and four clinical factors (age, sex, HbsAg, and enhancement pattern) were chosen for the clinical model. A combined model was built using the factors from the previous models. The classification accuracy of the combined model differentiated HCC from FNH in both the training and validation sets (0.956 and 0.941, respectively). The area under the receiver operating characteristic curve of the combined model was significantly better than that of the clinical model for both the training (0.984 vs. 0.937, p=0.002) and validation (0.972 vs. 0.903, p=0.032) sets.

Conclusions

The combined model provided a non-invasive quantitative method for differentiating HCC from FNH in non-cirrhotic liver with high accuracy. Our model may assist clinicians in the clinical decision-making process.
Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer
Authors: Zhang Jingtong , Zhou Qianghua , Xie Keji , Cheng Liang , Peng Shengmeng , Xie Ruihui , Liu Lixuan , Zhang Yangjie , Dong Wen , Han Jinli , Huang Ming , Chen Yuelong , Lin Tianxin , Huang Jian , Chen Xu
Published: June 2021

Background

Chemotherapy and/or immunotherapy are first-line treatments for advanced muscle-invasive bladder cancer (BCa), but the unsatisfactory objective response rate to these treatments yields poor 5-year patient survival. Discovery of therapeutic targets essential for BCa maintenance is critical to improve therapy response in clinic. This study evaluated the role of targeting WD repeat domain 5 (WDR5) with the small molecule compound OICR-9429 and whether it could be used to treat bladder cancer.

Methods

We analysed the expression and clinical prognosis of WDR5 in a TCGA cohort. The pharmacological role of OICR-9429 was further investigated in vitro and in vivo. RNA sequencing, western blot, and chromatin immunoprecipitation (ChIP) were utilized to explored the mechanism underlying OICR-9429-induced WDR5 inhibition.

Results

First, we found that WDR5 expression was upregulated in BCa and was associated with histologic grade, metastasis status, histologic subtype, and molecular subtype. High WDR5 expression level was also correlated with shorter overall survival (OS) in BCa. The WDR5 inhibitor OICR-9429 reduced cell viability by decreasing H3K4me3 levels but not WDR5 levels in T24, UM-UC-3, and TCCSUP BCa cells. OICR-9429 suppressed the proliferation of BCa cells by blocking the G1/S phase transition. Next, OICR-9429 enhanced apoptosis and chemosensitivity to cisplatin in BCa cells. In addition, OICR-9429 independently inhibited the motility and metastatic behaviour of BCa cells. In vivo experiments further revealed that OICR-9429 suppressed tumour growth, enhanced chemosensitivity, and reduced the toxicity of cisplatin in BCa. Notably, WDR5 was positively correlated with programmed death-ligand 1 (PD-L1) expression, and OICR-9429 suppressed immune evasion by blocking PD-L1 induced by IFN-γ. Mechanistically, some cell cycle-, antiapoptosis-, DNA repair-, metastasis-, and immune evasion-related genes, including BIRC5, XRCC2, CCNB1, CCNE2, PLK1, AURKA, FOXM1, and PD-L1 were identified to be directly regulated by OICR-9429 in a H3K4me3-dependent manner.

Conclusions

Our novel finding is that the WDR5 inhibitor, OICR-9429, suppressed proliferation, metastasis and PD-L1-based immune evasion while enhancing apoptosis and chemosensitivity to cisplatin in BCa by blocking the WDR5-MLL complex mediating H3K4me3 in target genes. Hence, our findings offer insight into a multipotential anticancer compound, OICR-9429, which enhances the antitumour effect of cisplatin or immunotherapy in BCa.
RNA-binding protein IMP3 is a novel regulator of MEK1/ERK signaling pathway in the progression of colorectal Cancer through the stabilization of MEKK1 mRNA
Authors: Zhang Meng , Zhao Senlin , Tan Cong , Gu Yanzi , He Xuefeng , Du Xiang , Li Dawei , Wei Ping
Published: June 2021

Background

MEK1/ERK signaling pathway plays an important role in most tumor progression, including colorectal cancer (CRC), however, MEK1-targeting therapy has little effective in treating CRC patients, indicating there may be a complex mechanism to activate MEK1/ERK signaling pathway except RAS activated mechanism.

Methods

To investigate the clinical significance of IMP3, we analyzed its expression levels in publicly available dataset and samples from Fudan University Shanghai Cancer Center. The effects of IMP3 on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. To investigate the role of IMP3 in colon carcinogenesis, conditional IMP3 knockout C57BL/6 mice was generated. The IMP3/MEKK1/MEK/ERK signaling axis in CRC was screened and validated by RNA-sequencing, RNA immunoprecipitation, luciferase reporter and western blot assays.

Results

We find RNA binding protein IMP3 directly bind to MEKK1 mRNA 3′-UTR, which regulates its stability, promote MEKK1 expression and sequentially activates MEK1/ERK signaling. Functionally, IMP3 promote the malignant biological process of CRC cells via MEKK1/MEK1/ERK signaling pathway both in vitro and in vivo, Moreover, IMP3−/− mice show decreased the expression of MEKK1 as well as colorectal tumors compared with wild-type mice after treatment with azoxymethane/dextran sodium sulfate. Clinically, the expression of IMP3 and MEKK1 are positive correlated, and concomitant IMP3 and MEKK1 protein levels negatively correlate with metastasis in CRC patients. In addition, MEK1 inhibitor in combination with shRNA-IMP3 have a synergistic effect both in vitro and in vivo.

Conclusion

Our study demonstrates that IMP3 regulates MEKK1 in CRC, thus activating the MEK1/ERK signaling in the progression of colorectal cancer, Furthermore, these results provide new insights into potential applications for combining MEK1 inhibitors with other target therapy such as IMP3 in preclinical trials for CRC patients.
Interfering with Tumor Hypoxia for Radiotherapy Optimization
Authors: Telarovic Irma , Wenger Roland H. , Pruschy Martin
Published: June 2021

Hypoxia in solid tumors is an important predictor of treatment resistance and poor clinical outcome. The significance of hypoxia in the development of resistance to radiotherapy has been recognized for decades and the search for hypoxia-targeting, radiosensitizing agents continues. This review summarizes the main hypoxia-related processes relevant for radiotherapy on the subcellular, cellular and tissue level and discusses the significance of hypoxia in radiation oncology, especially with regard to the current shift towards hypofractionated treatment regimens. Furthermore, we discuss the strategies to interfere with hypoxia for radiotherapy optimization, and we highlight novel insights into the molecular pathways involved in hypoxia that might be utilized to increase the efficacy of radiotherapy.
Spontaneous fetal reduction in triplets and prolongation of twin pregnancy for 111 days as an outpatient: a case report
Authors: Rubagumya Davis , Kaguta Munawar , Mdachi Ernie , Abeid Muzdalfat , Kidanto Hussein
Published: June 2021

Background

Multiple gestation has been on the rise because of advancement in assisted reproductive technology. Triplet pregnancy is associated with fetal loss and preterm birth as its major complications. Spontaneous triplet pregnancy is rare. In the case of fetal loss, delayed interval delivery has been used to achieve delivery of the retained fetuses. There is no common approach to delayed interval delivery.

Case

A 31-year-old East African lady with spontaneous triplet pregnancy presented to our institution at gestation age of 19 weeks with features of threatened miscarriage. One fetus was miscarried, and delayed interval delivery was done as an outpatient. At gestation age of 35 weeks, she delivered healthy twins by cesarean section.

Conclusion

Delayed interval delivery improves neonatal outcomes of high-order pregnancy after fetal loss even in a resource-limited setting.
RIG-I, a novel DAMPs sensor for myoglobin, activates NF-κB/caspase-3 signaling in CS-AKI model
Authors: Wang Peng-Tao , Li Ning , Wang Xin-Yue , Chen Jia-Le , Geng Chen-Hao , Liu Zi-Quan , Fan Hao-Jun , Lv Qi , Hou Shi-Ke , Gong Yan-Hua
Published: June 2021

Background

Acute kidney injury (AKI) is the main life-threatening complication of crush syndrome (CS), and myoglobin is accepted as the main pathogenic factor. The pattern recognition receptor retinoicacid-inducible gene I (RIG-I) has been reported to exert anti-viral effects function in the innate immune response. However, it is not clear whether RIG-I plays a role in CS-AKI. The present research was carried out to explore the role of RIG-I in CS-AKI.

Methods

Sprague-Dawley rats were randomly divided into two groups: the sham and CS groups (n = 12). After administration of anesthesia, the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions. The rats in both groups were denied access to food and water. Rats were sacrificed at 12 h or 36 h after pressure was relieved. The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination. In addition, RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI. Furthermore, NRK-52E cells were treated with 200 μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level. The cells and cell supernatant samples were collected at 6 h or 24 h. Small interfering RNAs (siRNA) was used to knock down RIG-I expression. The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative Real-time PCR (qPCR), Western blotting analysis, and immunohistochemistry (IHC) staining. Tumor necrosis factor-α (TNF-α) was detected by ELISA. Co-Immunoprecipitation (Co-IP) assays were used to detect the interaction between RIG-I and myoglobin.

Results

RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway. qPCR, Western blotting, and IHC assays showed that RIG-I, nuclear factor kappa-B (NF-κB) P65, p-P65, and the apoptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group (P < 0.05). However, the levels of interferon regulatory factor 3 (IRF3), p-IRF3 and the antiviral factor interferon-beta (IFN-β) showed no significant changes between the sham and CS groups. Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group. Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.

Conclusion

RIG-I is a novel damage-associated molecular patterns (DAMPs) sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI. In the development of CS-AKI, specific intervention in the RIG-I pathway might be a potential therapeutic strategy for CS-AKI.
Memorie letterarie nel Convivio di Dante
Authors: Arduini Beatrice
Published: June 2021

Focusing on book 4 of Dante’s Convivio (The Banquet), this article analyzes the complexity of the unfinished poetic and philosophical treatise that the poet wrote at the beginning of his exile. The relevance of the Convivio within Dante’s overall production can be attributed to the presence of numerous themes dear to the poet, which sometimes emerge only in nuce and sometimes already in a mature form in the treatise. Nonetheless, Dante took many of these subjects and linguistic experimentations and elaborated on them in his later works. In particular, book 4 functions as a precedent for some of the choices, themes, and styles subsequently developed in the Commedia. However, when the inspiration for the Convivio as a vehicle for both poetic and prose production is supplanted by the larger and even more ambitious project of his Commedia, Dante abandoned the treatise and left its linguistic mission unfinished.
Movement in Repose
Authors: Eldridge Aaron Frederick
Published: June 2021

How does tradition, a transmission of body and language, disclose a form of life? This article takes as its point of departure Talal Asad’s methodological pivot away from the modern concept of “belief” to Ludwig Wittgenstein’s concept of “form of life.” It elaborates the philosophical and anthropological implications of a rigorous notion of form of life through Asad’s concept of tradition and Martin Heidegger’s rereading of Aristotle’s physis. Interrupting this theoretical argument, a scene from the author’s ethnographic fieldwork with Orthodox Christian ascetics in Lebanon exemplifies the challenge (and insistence) of form of life. The article then turns to consider a powerful reading of form of life grounded in Baruch Spinoza’s theory of emanation and vitalist univocity. While echoing the concerns of this article, Spinoza’s philosophical ethic defers the central question posed by “form of life” by making the latter a world-producing apparatus. That approach to form of life foregrounds the possibility of being other than what one is, rather than the crucial question of “still experience” and its dynamic repose. The article concludes by reading this still experience alongside C. Nadia Seremetakis’s work in Greece, which details the work of stillness and memory, the deathly pain of history, as sites where the cultivation of noncontemporaneous forms of life are brought into relief.
An Immanence without the World
Authors: Dubilet Alex
Published: June 2021

This essay proposes to rethink the conceptual associations that bind immanence to the secular and oppose it to (divine) transcendence. It asks: What if immanence is divorced from the conceptual opposition between the world and its openings to (divine) other(s), between enclosure and the trace of a transcendent outside? What might arise if immanence is severed from its link with secularity, if it ceases to be merely another conceptual support in secularism’s metaphysical armature? To pursue these questions, the essay engages a variety of materials, including medieval mysticism, anthropological critiques of the secular, work in Black studies, critiques of the subject, and François Laruelle’s non-philosophical thought. The result links immanence more intimately with dispossession than with the subject’s self-possession—and entwines it with the undercommons, as the atopic lowest place, rather than with the nomos and topos imposed by the (modern) world and its regime of the proper. Immanence is thought of as anti- and antenomian force, a groundless ground coming underneath the conceptual logics of the world, its normative order of things, and life lived according to its distributions. As a result, rather than a weapon in modernity’s endless self-justifying polemics with religion, immanence opens forth trajectories for its destitution and delegitimation.
How to Make a Class
Authors: Pasquinelli Matteo
Published: June 2021

It was not a cybernetician but a neoliberal economist who provided the first systematic treatise on connectionism or, as it would later be known, the paradigm of artificial neural networks. In his 1952 book The Sensory Order, Friedrich Hayek advanced a connectionist theory of the mind already far more advanced than the theory of symbolic artificial intelligence, whose birth is redundantly celebrated in 1956 with the exalted Dartmouth workshop. In this text Hayek provided a synthesis of Gestalt principles and considerations of artificial neural networks, even speculating about the possibility of a machine fulfilling a similar function of “the nervous system as an instrument of classification,” auguring what we call today a “classifier algorithm.” This article shows how Hayek’s connectionist theory of the mind was used to shore up a specific and ideological view of the market and schematically reconstructs Hayek’s line of argumentation from his economic paradigm backward to his theory of cognition. Eventually, in Hayek’s interpretation, connectionism provides a relativist cognitive paradigm that justifies the “methodological individualism” of neoliberalism.
Homens de negócios no século XXI: três possibilidades em perspectiva
Authors: Motta Rodrigo Guimarães , Corá Maria Amélia Jundurian
Published: June 2021

Manoel, Leandro e Joverley são homens de negócios brasileiros que construíram suas carreiras ao longo das últimas décadas do século passado e as primeiras deste. Com trajetórias de vida muito distintas, os três tiveram pontos de partida, familiar e social, diferentes, assim como a formação acadêmica e profissional. Mesmo assim, cada um à sua maneira, obteve destaque nos negócios, seja como empresário ou como executivo. A partir dessas três histórias de vida, os alunos são convidados pelo professor responsável por ministrar o caso de ensino a refletir de forma crítica sobre as disposições herdadas e adquiridas de cada um desses homens de negócios, sob a óptica da sociologia disposicionalista e dos conceitos de Pierre Bourdieu. Além disso, é introduzido o conceito de tipo ideal, tal qual elaborado por Max Weber, e o tipo ideal de homem de negócio contemporâneo, segundo o livro de Sá, O homem de negócios contemporâneo (2011), no qual versa sobre a proximidade entre os variados perfis. Os alunos são também orientados a fazer uma reflexão individual sobre os contextos social, acadêmico e econômico em que estão eles próprios inseridos e, nesse momento precoce de sua trajetória, de qual tipo ideal se aproximam como indivíduos.
ORGANIZATION OF THE KAMCHATKA POLICE AND ITS ACTIVITIES IN THE 1920s
Authors: PASECHNIK ALEKSANDR
Published: June 2021

В монографии рассмотрен процесс формирования органов милиции на территории Северо-Востока России в 1917-1922 гг. в условиях постоянно изменяющейся политической ситуации. На основании широкого круга источников исследованы правовые основы функционирования, организационная структура, в также кадровое и материальное обеспечение милиции Камчатской губернии (округа) в 1920-е годы. Особое внимание уделено специфике организации деятельности камчатской милиции и различным формам народного участия в охране общественного порядка в указанный хронологический промежуток. Издание адресовано преподавателям социально-гуманитарных дисциплин, студентам, работникам органов внутренних дел и других органов государственной власти, интересующимся историей милиции на региональном уровне. Монография рекомендована к изданию методическим советом ФГБОУ ВПО «Российская академия народного хозяйства и государственной службы при Президенте Российской Федерации, Петропавловск-Камчатский филиал.
Types of communication activities
Authors: Bashlueva Mariya
Published: June 2021

The article deals with the presence of a fairly large number of types of communication activities. The study tells about the two-way nature of language communication. determines the presence of different roles performed by the individuals participating in it. Each of these roles, which we will call types of communicative or linguistic activity, is a complex psychophysiological complex with a pronounced specificity. The same general property of communication implies the presence of two groups of types of communicative activity: productive types associated with the transmission or production of a message, and receptive types serving the receiving end of the communication line. The distinction between the productive and the receptive in language communication is, therefore, not a terminological excess, but a fact of primary importance, arising from the very nature of language information exchange. The second factor complicating the communicative activity of the members of the language team is the presence of two forms of language communication: sound (oral) and written. The coexistence and frequent alternation of two forms of language communication makes it necessary to "translate" written messages into sound and sound into written ones, which is associated with the presence of two specific types of communicative activity: reading aloud and writing speech. The third factor that contributes to the diversity of roles performed by individuals in language communication is the multiplicity of sound and written languages on our planet. To serve the exchange of information between multilingual teams, there are special types of communication activities associated with translation from one sound or written language to another. However, the article does not claim to cover all the necessary material.
Training technologies for employees of internal affairs bodies in the framework of moral and psychological training
Authors: Sumina Ekaterina , Kutyepova Marina
Published: June 2021

The article examines the moral and psychological training of the personnel of the internal affairs bodies of the Russian Federation as a type of educational work. Analyzed the regulatory legal framework for the organization and conduct of moral and psychological training of employees of internal affairs bodies. The moral and psychological training of the employees of the internal affairs bodies of the Russian Federation is aimed at the formation of the state and at the same time patriotic worldview among the employees of the internal affairs bodies, as well as the professional culture of an employee of the internal affairs bodies. One of the goals of moral and psychological training is the formation of employees of internal affairs bodies of moral and psychological readiness to perform official tasks in any conditions of the situation. In connection with the versatility of the moral and psychological training of personnel, attention is paid to the organizational aspects of conducting classes. The main features of the moral and psychological training of employees of the internal affairs bodies of the Russian Federation are highlighted. Emphasis is placed on the forms of conducting classes on moral and psychological training. The article discusses training technologies that are or can be used in organizing and conducting classes on the moral and psychological training of personnel of the internal affairs bodies of the Russian Federation. The article presents analytical data from a survey of employees of the territorial bodies of internal affairs of the Ministry of Internal Affairs of Russia.
In Silico Targeting DENV2's Prefusion Envelope Protein by Several Natural Products' Bioactive Compounds
Authors: Hidayatullah Arief , Putra Wira Eka , - Sustiprijatno , Permatasari Galuh Wening , Salma Wa Ode , Widiastuti Diana , Susanto Hendra , Muchtaromah Bayyinatul , Tirto Sari Dewi Ratih , Ningsih Febby Nurdiya , Heikal Muhammad Fikri , Yusuf Alyana Mahdavikia Rosyada , Arizona Aliyya Suci
Published: June 2021

Dengue caused by the dengue virus (DENV) is a severe health problem in tropical regions such as Southeast Asia, especially Indonesia. Indonesian have used rhizome as traditional medicine for 1300 years. This study investigated the compounds from Kaempferia galanga, Curcuma longa, Zingiber officinale, Curcuma aeruginosa, Curcuma zanthorrhiza, Alpinia galanga, and Allium sativum as antivirals agents, explicitly targeting the DENV envelope protein to inhibit viral fusion. This study involved 121 bioactive compounds and DENV2's prefusion envelope protein. The virtual screening and molecular docking were done through occupied the Lipinski rule of five checker (http://www.scfbio-iitd.res.in/software/drugdesign/lipinski.jsp) and AutoDock Vina (https://pyrx.sourceforge.io/) respectively. The top nine compounds with the strongest binding affinity were galangin, kampferide, demetoxy curcumin, bisdemethoxycurcumin, β-selinene, 6-(hydroxymethyl)-1,4,4-trimethylbicyclo[3.1.0]hexan-2-ol, piperine, estra-1,3, 5(10)-trien-17β-ol, and curcumin. These compounds' affinity values were significantly lower, around 45-62%, than chloroquine. Most of them interact with the kl hairpin and hydrophobic pocket formed by residues Val130, Leu135, Phe193, Leu198, and Phe279of critical domains that can interfere with the conformational change and rearrangement of protein dimer in the post-fusion stage. This study suggested that the galangin, demethoxycurcumin, and bisdemethoxycurcumin are considered the most potential compounds to be developed as anti-prefusion E DENV2 low-affinity and intense interaction with those.

Keywords: DENV2, envelope protein, in silico, viral fusion, viral infection
Loss and Longevity: Rhetorics and Tactics of Early Modern Women's Writing
Authors: Coolahan Marie-Louise
Published: June 2021

Abstract: This article assesses the place of scholarship on early modern women's writing, interrogating the conditions for sustaining, as well as recovering, women writers. The paradigm of loss has been both enabling and limiting for research in this area, capturing the excitement of discovery and innovation but with rhetorical pitfalls that impact upon longevity in the literary canon. The article evaluates various strategies for dissemination of research, also advocating for a set of practices around public engagement beyond the academy. The situatedness and fluidity of the literary canon are considered in the context of women's writing but also debates around decolonizing the curriculum. Perspective, location, and time are determinants of literary and intellectual value. The discussion concludes by proposing an "action plan," a set of tactics available to those in the field that might support the longevity and sustained presence of early modern women in the canon of literature as well as the wider community.
Is There Room for Judith Shakespeare and Her Brother, Too?
Authors: McCarthy Erin A.
Published: June 2021

Abstract: This essay considers the future of scholarship on early modern women writers in light of structural issues in the twenty-first-century academy. By drawing upon a dataset comprising 21,053 scholarly works (books, book chapters, articles, doctoral dissertations, editions, and translations), it quantifies the relationship between scholarship on early modern women and the field at large. It pays particular attention to Shakespeare and his outsize influence. The essay advances two major claims: first, that even scholars without a particular interest in women or gender must become informed about women's diverse contributions to literate culture and, second, that early modernists must decide what we would like our contracting field to be and what values we will collectively embrace.
Variation isn’t that hard: Morphosyntactic choice does not predict production difficulty
Authors: Gardner Matt Hunt , Uffing Eva , Van Vaeck Nicholas , Szmrecsanyi Benedikt
Published: June 2021

The following paper explores the link between production difficulty and grammatical variability. Using a sub-sample of the Switchboard Corpus of American English (285 transcripts, 34 speakers), this paper shows that the presence of variable contexts does not positively correlate with two metrics of production difficulty, namely filled pauses (umanduh) and unfilled pauses (speech planning time). When 20 morphosyntactic variables are considered collectively (N=6,268), there is no positive effect. In other words, variable contexts do not correlate with measurable production difficulties. These results challenge the view that grammatical variability is somehow sub-optimal for speakers, with additional burdensome cognitive planning.
Deep learning for classification of pediatric chest radiographs by WHO’s standardized methodology
Authors: Chen Yiyun , Roberts Craig S. , Ou Wanmei , Petigara Tanaz , Goldmacher Gregory V. , Fancourt Nicholas , Knoll Maria Deloria
Published: June 2021

Background

The World Health Organization (WHO)-defined radiological pneumonia is a preferred endpoint in pneumococcal vaccine efficacy and effectiveness studies in children. Automating the WHO methodology may support more widespread application of this endpoint.

Methods

We trained a deep learning model to classify pneumonia CXRs in children using the World Health Organization (WHO)’s standardized methodology. The model was pretrained on CheXpert, a dataset containing 224,316 adult CXRs, and fine-tuned on PERCH, a pediatric dataset containing 4,172 CXRs. The model was then tested on two pediatric CXR datasets released by WHO. We also compared the model’s performance to that of radiologists and pediatricians.

Results

The average area under the receiver operating characteristic curve (AUC) for primary endpoint pneumonia (PEP) across 10-fold validation of PERCH images was 0.928; average AUC after testing on WHO images was 0.977. The model’s classification performance was better on test images with high inter-observer agreement; however, the model still outperformed human assessments in AUC and precision-recall spaces on low agreement images.

Conclusion

A deep learning model can classify pneumonia CXR images in children at a performance comparable to human readers. Our method lays a strong foundation for the potential inclusion of computer-aided readings of pediatric CXRs in vaccine trials and epidemiology studies.
The leucine-NH4+ uptake regulator Any1 limits growth as part of a general amino acid control response to loss of La protein by fission yeast
Authors: Cherkasova Vera , Iben James R. , Pridham Kevin J. , Kessler Alan C. , Maraia Richard J.
Published: June 2021

Thesla1+gene ofSchizosachharoymces pombeencodes La protein which promotes proper processing of precursor-tRNAs. Deletion ofsla1(sla1Δ) leads to disrupted tRNA processing and sensitivity to target of rapamycin (TOR) inhibition. Consistent with this, media containing NH4+inhibits leucine uptake and growth ofsla1Δ cells. Here, transcriptome analysis reveals that genes upregulated insla1Δ cells exhibit highly significant overalp with general amino acid control (GAAC) genes in relevant transcriptomes from other studies. Growth in NH4+media leads to additional induced genes that are part of a core environmental stress response (CESR). Thesla1Δ GAAC response adds to evidence linking tRNA homeostasis and broad signaling inS.pombe. We provide evidence that deletion of the Rrp6 subunit of the nuclear exosome selectively dampens a subset of GAAC genes insla1Δ cells suggesting that nuclear surveillance-mediated signaling occurs inS.pombe. To study the NH4+-effects, we isolatedsla1Δ spontaneous revertants (SSR) of the slow growth phenotype and found that GAAC gene expression and rapamycin hypersensitivity were also reversed. Genome sequencing identified a F32V substitution in Any1, a known negative regulator of NH4+-sensitive leucine uptake linked to TOR. We show that3H-leucine uptake by SSR-any1-F32Vcells in NH4+-media is more robust than bysla1Δ cells. Moreover, F32V may alterany1+function insla1Δ vs.sla1+cells in a distinctive way. Thus deletion of La, a tRNA processing factor leads to a GAAC response involving reprogramming of amino acid metabolism, and isolation of theany1-F32Vrescuing mutant provides an additional specific link.
Genomic locus proteomic screening identifies the NF-κB signaling pathway components NFκB1 and IKBKG as transcriptional regulators of Ripk3 in endothelial cells
Authors: Gao Siqi , Menendez Matthew , Kurylowicz Katarzyna , Griffin Courtney T.
Published: June 2021

The receptor-interacting protein kinase 3 (RIPK3) is a multi-functional protein best known for facilitating cellular necroptosis and inflammation. Recent evidence from our lab indicates that RIPK3 expression must be tightly regulated in endothelial cells to promote angiogenesis, to maintain vascular integrity during embryogenesis, and to provide protection from postnatal atherosclerosis. RIPK3 activity and stability are regulated by post-translational modifications and caspase-dependent cleavage. However, less is known about the transcriptional regulation ofRipk3. Here we utilized an unbiased CRISPR-based technology called genomic locus proteomics (GLoPro) to screen transcription factors and coregulatory proteins associated with theRipk3locus in a murine endothelial cell line. We found that 41 nuclear proteins are specifically enriched at theRipk3locus, including the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway components NFκB1 and IKBKG. We further verified that NFκB1 and IKBKG directly bind theRipk3promoter and prevent TNFα-inducedRipk3transcription in cultured human primary endothelial cells. Moreover, NFκB1 prevents RIPK3-mediated death of primary endothelial cells. These data provide new insights into NF-κB signaling andRipk3transcriptional regulation in endothelial cells.
Multisystem inflammatory syndrome (MIS-C) in Pakistani children: A description of the phenotypes and comparison with historical cohorts of children with Kawasaki disease and myocarditis
Authors: Mohsin Shazia S. , Abbas Qalab , Chowdhary Devyani , Khalid Farah , Sheikh Abdul Sattar , Ali Khan Zuviya Ghazala , Aslam Nadeem , Bhatti Omaima Anis , Inam Maha , Saleem Ali Faisal , Bhutta Adnan T.
Published: June 2021

Objectives

To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts.

Methods

All children (1 month– 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C.

Results

Thirty children with median age of 24 (interquartile range (IQR)1–192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis.

Conclusions

Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes.