bluuebunny/crossref_metadata_2025 huggingface dataset:
American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients
Authors: Cuker Adam , Tseng Eric K. , Nieuwlaat Robby , Angchaisuksiri Pantep , Blair Clifton , Dane Kathryn , Davila Jennifer , DeSancho Maria T. , Diuguid David , Griffin Daniel O. , Kahn Susan R. , Klok Frederikus A. , Lee Alfred Ian , Neumann Ignacio , Pai Ashok , Righini Marc , Sanfilippo Kristen M. , Siegal Deborah , Skara Mike , Terrell Deirdra R. , Touri Kamshad , Akl Elie A. , Bou Akl Imad , Bognanni Antonio , Boulos Mary , Brignardello-Petersen Romina , Charide Rana , Chan Matthew , Dearness Karin , Darzi Andrea J. , Kolb Philipp , Colunga-Lozano Luis E. , Mansour Razan , Morgano Gian Paolo , Morsi Rami Z. , Muti-Schünemann Giovanna , Noori Atefeh , Philip Binu A. , Piggott Thomas , Qiu Yuan , Roldan Yetiani , Schünemann Finn , Stevens Adrienne , Solo Karla , Wiercioch Wojtek , Mustafa Reem A. , Schünemann Holger J.
Published: September 2021

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE).

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE.

Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021.

Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE.

Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.
The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection
Authors: Ward Daniel , Gørtz Sanne , Thomson Ernst Martin , Andersen Nynne Nyboe , Kjær Susanne K. , Hallas Jesper , Christensen Steffen , Fynbo Christiansen Christian , Bastrup Israelsen Simone , Benfield Thomas , Pottegård Anton , Jess Tine
Published: September 2021

Background

Immunosuppression may worsen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark.

Methods

We identified all SARS-CoV-2 test-positive patients from February 2020 to October 2020 and linked healthcare data from nationwide registers, including prescriptions for the exposure (immunosuppressant drugs). We estimated relative risks of hospital admission, intensive care unit (ICU) admission and death (each studied independently up to 30 days from testing) with a log-linear binomial regression adjusted for confounders using a propensity score-based matching weights model.

Results

A composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1.56 (95% CI 1.10–2.22)). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (adjusted relative risk 2.38 (95% CI 1.72–3.30)), which were also associated with an increased risk of hospital admission (adjusted relative risk 1.34 (95% CI 1.10–1.62)), but not of ICU admission (adjusted relative risk 1.76 (95% CI 0.93–3.35)); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors or interleukin inhibitors was not associated with an increased risk of hospitalisation, ICU admission or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine or chloroquine.

Conclusions

Exposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of coronavirus disease 2019 (COVID-19) in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.
Current status of premature mortality from four non-communicable diseases and progress towards the Sustainable Development Goal target 3.4: a population-based study in northeast China, 2004–2017
Authors: Liu Li , Li Yanxia , Song Junmin , Chen Qian , Li Shuang , Mu Huijuan , Na Jun , Zhang Rui , Yu Liya , Sun Wei , Pan Guowei
Published: September 2021

Background and aim

According to the United Nations’ Sustainable Development Goal (SDG) target 3.4, premature mortality from four non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes mellitus, collectively referred to as NCD4) should achieve a minimum decline of 33% in 2030 relative to 2015. This remains a challenge for China. This study aimed to evaluate the current status and progress towards this target in Liaoning Province, one of the three provinces in northeast China.

Methods

We calculated the premature mortality rates (PMRs) per year and average annual percentage changes (AAPCs) from NCD4 using mortality data between 2004 and 2017. The trend was analyzed in the whole population, as well as in subpopulations of gender (male/female) and inhabiting area (urban/rural). PMRs from NCD4 for 2030 were projected by fitting a linear regression based on the current trend, which was identified by a Joinpoint model.

Findings

In the whole population, only chronic respiratory diseases showed a significant decline (AAPC: − 6.5%, p < 0.05), while only cancer showed a significant increase (AAPC: + 1.3%, p < 0.05); taken together, NCD4 showed a significant increase (AAPC: + 0.6%, p < 0.05). In the subpopulations, while males showed a significant increase in NCD4 (AAPC: + 1.5%, p < 0.05), cardiovascular diseases (AAPC: + 1.7%, p < 0.05), cancer (AAPC: + 1.8%, p < 0.05), and diabetes mellitus (AAPC: + 4.2%, p < 0.05), females showed a significant decline in NCD4 (AAPC: − 1.2%, p < 0.05), cardiovascular diseases (AAPC: − 1.8%, p < 0.05), diabetes mellitus (AAPC: − 2.1%, p < 0.05), but showed a mild increase in cancer (AAPC: + 0.5%, p > 0.05). A comparative analysis of the projected PMRs for 2030 with the 2015 levels revealed that only chronic respiratory diseases are expected to achieve the SDG target 3.4, apart from in the urban male subpopulation.

Conclusion

Except for chronic respiratory diseases, NCD4 cannot be expected to achieve the SDG target 3.4 in the whole population of Liaoning Province. Under these circumstances, special attention should be paid to reducing the risks of cancer and providing preventative interventions for men.
Risk factors for depression during the COVID-19 pandemic: a longitudinal study in middle-aged and older adults
Authors: Rutland-Lawes Jamie , Wallinheimo Anna-Stiina , Evans Simon L.
Published: September 2021

Background

The COVID-19 pandemic and resultant social restrictions have had widespread psychological ramifications, including a rise in depression prevalence. However, longitudinal studies on sociodemographic risk factors are lacking.

Aims

To quantify longitudinal changes in depression symptoms during the pandemic compared with a pre-pandemic baseline, in middle-aged and older adults, and identify the risk factors contributing to this.

Method

A total of 5331 participants aged ≥50 years were drawn from the English Longitudinal Study of Ageing. Self-reported depression symptoms in June/July 2020 were compared with baseline data from 2–3 years prior. Regression models investigated sociodemographic and lifestyle variables that could explain variance in change in depression.

Results

Within-participant depression scores increased significantly from pre-pandemic levels: 14% met the criteria for clinical depression at baseline, compared with 26% during the pandemic. Younger age, female gender, higher depression scores at baseline, living alone and having a long-standing illness were significant risk factors. Gender-stratified regression models indicated that older age was protective for women only, whereas urban living increased risk among women only. Being an alcohol consumer was a protective factor among men only.

Conclusions

Depression in UK adults aged ≥50 years increased significantly during the pandemic. Being female, living alone and having a long-standing illness were prominent risk factors. Younger women living in urban areas were at particularly high risk, suggesting such individuals should be prioritised for support. Findings are also informative for future risk stratification and intervention strategies, particularly if social restrictions are reimposed as the COVID-19 crisis continues to unfold.
Recent Advances in the Management of Metastatic Prostate Cancer
Authors: Sayegh Nicolas , Swami Umang , Agarwal Neeraj
Published: September 2021

Management of metastatic prostate cancer has undergone a revolution over the past decade with the introduction of several novel agents and repurposing of others. Several clinical trials reported improved outcomes with the intensification of androgen deprivation therapy by the addition of docetaxel chemotherapy or novel hormonal agents (abiraterone, enzalutamide, or apalutamide) in the metastatic castration-sensitive state. Relugolix has been recently approved as the first oral gonadotropin-releasing hormone receptor antagonist agent with a superior cardiovascular side-effect profile, and serum testosterone suppression compared with a gonadotropin-releasing hormone agonist, leuprolide. Poly-ADP ribose polymerase inhibitors (olaparib and rucaparib) have demonstrated significant clinical benefit for patients harboring deleterious mutations in genes belonging to the homologous recombination repair pathway and have received Food and Drug Administration approval. Recently, lutetium-177-prostate-specific membrane antigen-617 with standard of care treatment has shown to improve overall survival in men with advanced-stage prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer. These recent approvals, successes, and the ongoing investigation of multiple novel agents are expected to continue to dramatically improve survival outcomes of men with metastatic prostate cancer in the coming years.
Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response
Authors: Foulkes Andrea S , Selvaggi Caitlin , Shinnick Daniel , Lumish Heidi , Kim Eunyoung , Cao Tingyi , Thaweethai Tanayott , Qian Jing , Lu Frances , Yan Joyce , Cheng David , He Wei , Clerkin Kevin J , Madhavan Mahesh V , Meigs James B , Triant Virginia A , Lubitz Steven A , Gupta Aakriti , Bassett Ingrid V , Reilly Muredach P
Published: September 2021

Background

Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.

Objective

To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes.

Methods

This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care.

Results

In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626).

Conclusion

Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
“Printed follyes”: Mountebanks and the Performance of Ambivalence within the Archive
Authors: Mayo Sarah
Published: September 2021

This article analyzes the ability of archival resources to make the especially transient and unstable performances of early modern mountebanks accessible and meaningful for performance studies research. Because mountebanks were itinerant performers and medical practitioners whose multiple roles challenged regulatory authorities and generated few lasting records, this article argues that mountebank performances may be best recovered and accessed by approaching the available archival materials not as records of fact, but of function. Documents like handbills associated with mountebanks were, after all, functional, inviting their readers to witness performances and test medical services. Self-authored documents like bills as well as representational and fictional texts replicate and reenact performative strategies attributed to mountebanks, namely, the cultivation of ambivalent rhetoric and compulsion to independent judgment of truth.
May Philosophy Flourish: Pantheisticon, Freemasonry, and Eighteenth-Century Ritual Philosophy
Authors: Camp Pannill
Published: September 2021

In eighteenth-century Europe, ritual performance behavior was consciously used for philosophical purposes. The richest documented instances of this involved Freemasonry, a voluntary fraternal order that drew tens of thousands of men, across Europe and beyond, into a secretive ritual practice. Masons understood ritual, the core of Masonic “craft,” as a philosophical activity in itself. Supporting this claim requires a critique of the prevalent view that Freemasonry was uniquely compatible with specific Enlightenment philosophical constructs—constitutional monarchism in political thought and deistic Newtonianism in natural philosophy. Rather than expressing these specific philosophical views, Masonic ritual effectuated philosophical reflection apart from the outside world. John Toland's proto-Masonic ritual document Pantheisticon shows how early modern rituals fostered thinking in lodge settings and distinguished between Masonic and “profane” entities. On this basis it can be argued that performance in this era and beyond should be understood as the generative containment of knowledge.
The 3′UTR of the Drosophila CPEB translation factor gene orb2 plays a crucial role in spermatogenesis
Authors: Gilmutdinov Rudolf , Kozlov Eugene N. , Yakovlev Konstantin V. , Olenina Ludmila V. , Kotov Alexei A. , Barr Justinn , Zhukova Mariya , Schedl Paul , Shidlovskii Yulii V.
Published: September 2021

CPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process, orb2 mRNA and protein are localized within the developing spermatid. To evaluate the role of the orb2 mRNA 3′UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3′UTR, orb2R. This deletion disrupts the process of spermatid differentiation but has no apparent effect on meiosis. Differentiation abnormalities include defects in the initial polarization of the 64-cell spermatid cysts, mislocalization of mRNAs and proteins in the elongating spermatid tails, altered morphology of the elongating spermatid tails, and defects in the assembly of the individualization complex. These disruptions in differentiation appear to arise because orb2 mRNA and protein are not properly localized within the 64-cell spermatid cyst.
Flow cytometry allows rapid detection of protein aggregates in cellular and zebrafish models of spinocerebellar ataxia 3
Authors: Robinson Katherine J. , Tym Madelaine C. , Hogan Alison , Watchon Maxinne , Yuan Kristy C. , Plenderleith Stuart K. , Don Emily K. , Laird Angela S.
Published: September 2021

Spinocerebellar ataxia 3 (SCA3, also known as Machado–Joseph disease) is a neurodegenerative disease caused by inheritance of a CAG repeat expansion within the ATXN3 gene, resulting in polyglutamine (polyQ) repeat expansion within the ataxin-3 protein. In this study, we have identified protein aggregates in both neuronal-like (SHSY5Y) cells and transgenic zebrafish expressing human ataxin-3 with expanded polyQ. We have adapted a previously reported flow cytometry methodology named flow cytometric analysis of inclusions and trafficking, allowing rapid quantification of detergent insoluble forms of ataxin-3 fused to a GFP in SHSY5Y cells and cells dissociated from the zebrafish larvae. Flow cytometric analysis revealed an increased number of detergent-insoluble ataxin-3 particles per nuclei in cells and in zebrafish expressing polyQ-expanded ataxin-3 compared to those expressing wild-type human ataxin-3. Treatment with compounds known to modulate autophagic activity altered the number of detergent-insoluble ataxin-3 particles in cells and zebrafish expressing mutant human ataxin-3. We conclude that flow cytometry can be harnessed to rapidly count ataxin-3 aggregates, both in vitro and in vivo, and can be used to compare potential therapies targeting protein aggregates.

This article has an associated First Person interview with the first author of the paper.
Prion protein and prion disease at a glance
Authors: Zhu Caihong , Aguzzi Adriano
Published: September 2021

Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.
Interplay between myofibers and pro-inflammatory macrophages controls muscle damage in mdx mice
Authors: Saclier Marielle , Ben Larbi Sabrina , My Ly Ha , Moulin Eugénie , Mounier Rémi , Chazaud Bénédicte , Juban Gaëtan
Published: September 2021

Duchenne muscular dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. Our aim was to characterize cellular events leading to the alteration of macrophage properties and to modulate macrophage inflammatory status using the gaseous mediator hydrogen sulfide (H2S). Using co-culture experiments, we first showed that myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decreased number of nuclei per fiber, as well as reduced myofiber branching and fibrosis. Finally, we established the metabolic sensor AMP-activated protein kinase (AMPK) as a critical NaHS target in muscle macrophages. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment sustaining a pro-inflammatory macrophage status, which in turn favors myofiber damage, myofiber branching and establishment of fibrosis. Our results also highlight the use of H2S donors as a potential therapeutic strategy to improve the dystrophic muscle phenotype by dampening chronic inflammation.

This article has an associated First Person interview with the first author of the paper.
Conceptualizing an inquiry-based lingua-cultural learning through telecollaborative exchanges
Authors: Ismailov Murod
Published: September 2021

In recent years, telecollaboration has been gaining popularity among scholars, teachers, and students engaged in foreign language education because it facilitates the use of Internet-mediated communication tools to connect language and culture learners in geographically distant locations. Telecollaboration, as currently viewed in academic and classroom settings, places greater emphasis on the development of learners’ intercultural communicative competence. The problem with this approach is that this process may not consider the possibility that learners engaged in online intercultural exchanges could have limited or no knowledge about certain aspects of their own lingua-culture. We argue that, for learners to effectively share lingua-cultural knowledge with their online peers abroad, there must be a framework that supports the construction of learners’ own intra-cultural knowledge to provide a solid foundation for intercultural learning and communication. In this paper, we develop an inquiry-based model of telecollaboration incorporating both inquiry and online exchange based on the inquiry cycle, which includes engagement, exploration, explanation, elaboration, and evaluation. This paper builds a case for the application of inquiry-based telecollaboration in a real classroom environment, which could not only help learners obtain and eventually share more authentic, deeper knowledge about their lingua-culture, but also promote informed intercultural exchange.
Design of financial incentive interventions to improve lifestyle behaviors and health outcomes: A systematic review
Authors: Miranda J. Jaime , Pesantes M. Amalia , Lazo-Porras María , Portocarrero Jill , Diez-Canseco Francisco , Carrillo-Larco Rodrigo M. , Bernabe-Ortiz Antonio , Trujillo Antonio J. , Aldridge Robert W.
Published: September 2021

Background: Financial incentives may improve the initiation and engagement of behaviour change that reduce the negative outcomes associated with non-communicable diseases. There is still a paucity in guidelines or recommendations that help define key aspects of incentive-oriented interventions, including the type of incentive (e.g. cash rewards, vouchers), the frequency and magnitude of the incentive, and its mode of delivery.  We aimed to systematically review the literature on financial incentives that promote healthy lifestyle behaviours or improve health profiles, and focused on the methodological approach to define the incentive intervention and its delivery. The protocol was registered at PROSPERO on 26 July 2018 (CRD42018102556).

Methods: We sought studies in which a financial incentive was delivered to improve a health-related lifestyle behaviour (e.g., physical activity) or a health profile (e.g., HbA1c in people with diabetes). The search (which took place on March 3rd 2018) was conducted using OVID (MEDLINE and Embase), CINAHL and Scopus.

Results: The search yielded 7,575 results and 37 were included for synthesis. Of the total, 83.8% (31/37) of the studies were conducted in the US, and 40.5% (15/37) were randomised controlled trials. Only one study reported the background and rationale followed to develop the incentive and conducted a focus group to understand what sort of incentives would be acceptable for their study population. There was a degree of consistency across the studies in terms of the direction, form, certainty, and recipient of the financial incentives used, but the magnitude and immediacy of the incentives were heterogeneous.

Conclusions: The available literature on financial incentives to improve health-related lifestyles rarely reports on the rationale or background that defines the incentive approach, the magnitude of the incentive and other relevant details of the intervention, and the reporting of this information is essential to foster its use as potential effective interventions.
Quantification of fetal organ sparing in maternal low-protein dietary models
Authors: Serpente Patricia , Zhang Ying , Islimye Eva , Hart-Johnson Sarah , Gould Alex P.
Published: September 2021

Background: Maternal malnutrition can lead to fetal growth restriction. This is often associated with organ sparing and long-lasting physiological dysfunctions during adulthood, although the underlying mechanisms are not yet well understood.

Methods: Low protein (LP) dietary models in C57BL/6J mice were used to investigate the proximal effects of maternal malnutrition on fetal organ weights and organ sparing at embryonic day 18.5 (E18.5).

Results:  Maternal 8% LP diet induced strikingly different degrees of fetal growth restriction in different animal facilities, but adjustment of dietary protein content allowed similar fetal body masses to be obtained. A maternal LP diet that restricted fetal body mass by 40% did not decrease fetal brain mass to the same extent, reflecting positive growth sparing of this organ. Under these conditions, fetal pancreas and liver mass decreased by 60-70%, indicative of negative organ sparing. A series of dietary swaps between LP and standard diets showed that the liver is capable of efficient catch-up growth from as late as E14.5 whereas, after E10.5, the pancreas is not.

Conclusions: This study highlights that the reproducibility of LP fetal growth restriction studies between laboratories can be improved by careful calibration of maternal dietary protein content. LP diets that induce 30-40% restriction of prenatal growth provide a good model for fetal organ sparing. For the liver, recovery of growth following protein restriction is efficient throughout fetal development but, for the pancreas, transient LP exposures spanning the progenitor expansion phase lead to an irreversible fetal growth deficit.
Coding, robotics and socio-emotional learning: developing a palette of virtues
Authors: Umaschi Bers Marina
Published: September 2021

This paper describes a pedagogical approach, Coding as Another language (CAL) to teach programming and computational thinking in early childhood. The CAL curriculum connects powerful ideas from the discipline of computer science with ideas from literacy in a way that is developmentally appropriate for children 4-8 years of age. CAL is free and can be used with two widely available programming environments for young children: the free on-screen ScratchJr app and the KIBO robotics kit that doesnt require keyboards or screens. Through 24 lessons centered on books, CAL emphasizes creative play and self-expression by positioning the learning of programming as the mastering of a new symbolic language. In addition, CAL provides opportunities for socio-emotional development in the context of a collaborative play-based learning environment, a coding playground, in which there is purposeful exploration of ethical and moral values and intentional promotion of positive behaviors and chrachter strenghs.
Fulminant Haemolysis Following Endoscopic Retrograde Cholangiopancreatography
Authors: Bibi Mário , Viana Susana , Leitão Cátia , Moço Rui , Eremina Yuliana O.
Published: September 2021

We report the case of a 77-year-old-man with a history of type 2 diabetes mellitus who underwent endoscopic retrograde cholangiopancreatography (ERCP) because of a gallstone in the common bile duct. Thirty-six hours after the procedure, the patient developed persistent fever and epigastric pain associated with de novo jaundice. Massive haemolysis (with exuberant spherocytosis) occurred and patient died in 3 hours. Clostridium perfringens was isolated in the blood cultures. Massive haemolysis associated with C. perfringens has a high mortality rate. Management involves a high index of suspicion after gastrointestinal procedures like ERCP, surgical consultation, antibiotic therapy, transfusion of red cell concentrates and, potentially, hyperbaric oxygen therapy.
Long COVID and breathlessness: an overview
Authors: Robinson Patricia
Published: September 2021

This article offers a review of what is known so far about post-acute covid-19 and the underlying pathophysiology related to this condition. The main focus will be on the respiratory symptoms. It will then explore how community nurses can monitor and support patients with symptoms of breathlessness with a supporting discussion of the current recommendations for the management and treatment of patients presenting with symptoms of breathlessness. Palliation of symptoms will be highlighted but managing the supportive care needs for patients affected by COVID-19 and nearing the end of life is outside the scope of this article.
Initiating compression therapy for those living with heart failure
Authors: Saucedo Dumitriu , Evans Nicholas , Lim Chung Sim
Published: September 2021

Compression therapy is used to treat leg symptoms arising from chronic venous disease and lymphoedema. Heart failure, which is traditionally regarded as a contraindication for compression therapy, is prevalent among patients with such leg symptoms. This article aims to assess the evidence on the safety and effectiveness of compression therapy, as well as recommending the assessment and measures required when initiating compression therapy in patients with heart failure. Recent evidence suggests that initiating compression therapy in patients with stable and compensated heart failure is safe if appropriate precautionary measures are undertaken. However, there is still insufficient evidence to support the safety of compression therapy in patients with severe and decompensated heart failure. A standardised, evidence-based guideline on compression therapy in patients with heart failure will help medical and nursing professionals and improve informed consent for the patients.
High Photocatalytic Performance of Modified Bismuth Oxychloride Semiconductor under Sunlight
Authors: Thattil Preeja. P. , Rose A. Leema
Published: September 2021

In recent years, the bismuth compounds have gained much interest due to their potential applications in the field of Photocatalysis. In our present work, Bismuth oxychloride Photocatalyst and Aluminium fluoride doped Bismuth oxychloride photocatalyst were synthesized by simple chemical methods using Bismuth nitrate pentahydrate as the precursor. The synthesized photocatalysts were characterized by different analytical techniques such as X-ray diffraction analyses, Ultra Violet –Diffuse reflectance spectrum, Field Emission – Scanning Electron Microscopy, Energy dispersive X-ray analyses,Fourier transform infrared spectroscopy studies and BET surface area analysis. The photocatalytic performances of the as-synthesized doped and undoped Bismuth oxychloride photocatalyst were tested towards the degradation of Acid green 1 dye. The parameters such as the effect of pH, catalyst concentration and initial dye concentration are optimized, and the kinetic studies are carried out for the photocatalytic dye degradation process. The experimental results showed that about 80% of the Acid green 1 dye got decolourized within 90 minutes by effective air purging under natural sunlight radiation in the presence of the AlF-BiOCl photocatalyst under optimized conditions.
Study of the Stability and Chemical Reactivity of a Series of Tetrazole Pyrimidine Hybrids by the Density Functional Theory Method (DFT)
Authors: Ehouman Ahissandonatien , Kouakou Adjoumanirodrigue , Diarrassouba Fatogoma , Ouattara Hakim Abdel Aziz , Niamien Paulin Marius
Published: September 2021

Our theoretical study of stability and reactivity was carried out on six (06) molecules of a series of pyrimidine tetrazole hybrids (PTH) substituted with H, F, Cl, Br, OCH3 and CH3 atoms and groups of atoms using the density function theory (DFT). Analysis of the thermodynamic formation quantities confirmed the formation and existence of the series of molecules studied. Quantum chemical calculations at the B3LYP / 6-311G (d, p) level of theory determined molecular descriptors. Global reactivity descriptors were also determined and analyzed. Thus, the results showed that the compound PTH_1 is the most stable, and PTH_5 is the most reactive and nucleophilic. Similarly, the compound PTH_4 is the most electrophilic. The analysis of the local descriptors and the boundary molecular orbitals allowed us to identify the preferred atoms for electrophilic and nucleophilic attacks.
Synthesis and Antimicrobial Study of Thiophene Clubbed Thiazolyl Carbohydrazides
Authors: Mhaske Sadhana Dhondibhau
Published: September 2021

Thiophene containing thiazolyl carbohydrazide on reaction with various aryl isothiocynates yields thiosemicarbazides which were transformed into 1,2,4- substituted thiazoles by Hantzsch synthesis and characterized by spectral methods. Most of the synthesized new thiosemicarbazides are found to be promisingly effective against tested bacterial strains and exhibited moderate activitytested fungal strains. Most of the 1, 2,4- substituted thiazoles are weakly active against test organisms.
Bioactivity Study of Thiophene and Pyrazole Containing Heterocycles
Authors: Kale Nitin V , Salve Supriya P. , Karale Bhausaheb K. , Mhaske Sadhana D. , Dare Sushama B.
Published: September 2021

Chalcones3a-fwere prepared by reacting thiophene containing pyrazolyl aldehyde (2) with different 2-hydroxy acetophenones 1a-f. The compounds3a-f were transformed into different Pyrazolines 4a-f. The formation of chromene derivatives 5a-f occurred from the cyclization of 3a-f, which were then transformed into pyrazole derivatives 6a-f. Newly synthesized compounds have promising antibacterial activity against S.typhii and S.aureus, while weak activity against B.subtilis and E.coli. Compounds 5d and 6d had significant antifungal action towardsA. niger, while most of the compounds were moderately active towards T.viride. Some of the synthesized compounds showed promising α-amylase inhibitory activity at 1 mg/mL concentration.
Bio Synthesis of Beta Vulgaris Mediated ZnO Nanoparticles and Their Anti-Bacterial, Anti-Fungal, Anti-Diabetic and Anti-Cancer Activities
Authors: F Femina. , Thabassoom H. Asia , Ruby S. Auxilia , Florence J. Felicita
Published: September 2021

Plant extract mediated metal or metal oxide nanoparticles is a promising alternate to the chemical and physical methods. Application of nanoparticles in various fields get increased widely due to their properties. Current study involves the eco-friendly method of synthesis and pharmacological applications of zinc oxide nanoparticles (ZnO-NPs) using the aqueous beetroot (Beta vulgaris) extract. Aqueous Beta vulgaris extract has multiple bio-active phytochemicals especially antioxidants like anthocyanins and betacyanins, also reported a rich source of minerals. Synthesized ZnONPs were characterized with the aid of UV-Vis spectroscopy, FTIR, SEM, XRDand EDX. Antibacterial results suggests that, Beta vulgaris mediated ZnONPspossessthe maximum zone of inhibition against Escherichia coli then Staphylococcus aureus. On anti-fungal activity synthesized ZnONPS revealed greater inhibitory effect against Candida albicans fungi than the Aspergillusflavus. Synthesized ZnONPs exhibits the noticeable pharmacological activities against the anti-diabetic and anti-cancer activities (MCF-7 cell line, IC50=35.4µg/ml). This study has suggested an effective replacement for the hazardous chemical methods and lead to a cost-effective, environmentally -friendly method which can also be used as an antimicrobial, anti-diabetic and anti-cancer agents.
Microwave-irradiated synthesis and Biological applications of Transition metal (II) complexes of Unsymmetrical Quadridentate (ON NO donor) Schiff base ligand
Authors: Srivastava K P , Yadav U S , Singh Pragya
Published: September 2021

An efficient and environmentally benign method using microwave irradiation (MWI) have been applied for the synthesis of mononuclear square planar transition metal (II) [e.g. Co2+, Ni2+ and Cu2+] complexes with an unsymmetrical tetradentate bi-anionic Schiff base ligand. All the eco-friendly synthesized transition metal complexes were characterised by elemental analysis, conductivity & magnetic moment measurements and common spectroscopic methods (vis. IR, UV-Visible and 1H NMR spectroscopy respectively). The biological evaluation as anti-bacterial and human pathogenic anti-fungal activities of the investigating compounds show that the investigated complexes were found to be far active than the ligand towards tested microbes under the identical experimental conditions and the antimicrobial activity trend follows the order: Cu-complex > Co-complex > Ni-complex > Ligand
Potential Use of Copper Oxide Nanoparticles from Solanum Trilobatum Against Pathogenic Bacteria
Authors: Bharathy M. Stella , Jeyaleela G. Dayana , Vimala J. Rosaline , Agila A. , Hemadevi M.
Published: September 2021

Recently, the biosynthesis of metal oxide nanoparticles using plant extract gained great attention compared to other methods. In this work, CuO nanomaterial was synthesized by using the leaf extract of Solanum trilobatum. Synthesized copper oxide nanoparticles were characterized by UV, FT-IR, XRD, SEM, and EDX to determine the functional group, crystalline size, shape, and elemental composition of the synthesized nanoparticles. The X-ray diffraction and SEM results confirmed that the synthesized CuO NPs were crystalline in nature and the average size was found to be 38.34 nm. The spherical shape of CuO NPs was reported in the green approach, but first-time pentagons, cubes, and elongated forms of CuO NPs are found in this work. The EDX studies showed that the Solanum trilobatum mediated CuO NPs contain 53.57 % of copper and 46.43% of oxygen. Synthesized CuO NPs were tested against the five pathogenic bacteria and they showed a very good zone of inhibition compared with copper sulfate and plant extract. Especially against Escherichia Coli, Solanum trilobatum mediated CuO NPs performed well inhibitory effect.
Statistical Analysis of Outpatients Trends at Korean Medicine Hospitals of Daejeon University by Region before and after COVID-19
Authors: Cha Hyun Ji , Kim Beom Seok , Sung Ki Jung , Lee Young Rok , Choi Hyeon Kyu , Kim Min Ju , Lee Ye Ji , Jeon Ju Hyun , Kim Young Il
Published: September 2021

Objectives: This study is designed to statistically analyze data of outpatients visiting for recent 3 years. The purpose is to identify tendencies of patients who visit the hospitals before and after COVID-19. Methods: This study retrospectively analyzed the medical records of 452,487 patients who visited to the Daejeon·Cheonan·Cheongju Korean Medicine Hospital of Daejeon University from January 1, 2018 to August 31, 2020. The data is classified according to year, month, gender, age, and visit type. The statistical analysis was performed using IBM SPSS 25.0. Results: The total number of patients decreased in 2020 compared to before 2020, and the number of patients in each hospital also decreased from the previous year. According to the year of each hospital, the difference by year was not statistically significant at Daejeon Hospital, but Cheonan and Cheongju Hospital showed statistical difference. The change in monthly according to the year by hospital has continued to decrease from January to March in 2020, unlike the previous year, which recovered from a decline in March. In the analysis of patients by age, there was no statistically significant difference in the number of patients in the above 60s according to the year, while those under 60s have a tendency to significantly decrease.. Conclusion: We expect that the results of this study will be used as reference materials in analyzing effects of COVID-19 at health care utilization.
Inhibitory Effects of GGX on Lung Injury of Chronic Obstructive Lung Disease (COPD) Mice Model
Authors: Kim Tae Hyeon , Yang Won Kyung , Lee Su Won , Kim Seung Hyung , Lyu Yee Ran , Park Yang Chun
Published: September 2021

Objectives: This study is aimed to evaluate the protective effects of GGX on lung injury of Chronic Obstructive Lung Disease (COPD) mice model. Materials and Methods: C57BL/6 mice were challenged with lipopolysaccharide (LPS) and cigarette smoke extract (CSE) and then treated with vehicle only (Control group), dexamethasone 3 ㎎/㎏ (Dexa group), gam-gil-tang 200 ㎎/㎏ (GGT group), GGX 100, 200, and 400 ㎎/㎏ (GGX group). After sacrifice, its bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed with cytospin, Enzyme-Linked Immunosorbent Assay (ELISA), real-time polymerase chain reaction (PCR) and hematoxylin & eosin (H&E), and Masson’s trichrome staining. Results: In the COPD model, GGX significantly inhibited the increase of neutrophils, TNF-α, IL-17A, CXCL-1, MIP2 in BALF and TNF-α, IL-1β, IL-10 mRNA expression in lung tissue. It also decreased the severity of histological lung injury. Conclusion: This study suggests the usability of GGX for COPD patients by controlling lung tissue injury.
Kerr-nonlinearity-assisted NIR nonreciprocal absorption in a VO2-based core–shell composite integrated with 1D nonlinear multilayers
Authors: Rashidi Shiva , Entezar Samad Roshan , Rashidi Arezou
Published: September 2021

We theoretically investigate the nonreciprocal optical response of a one-dimensional multilayer possessing nonlinear (NL) Kerr dielectrics hybridized with a

V
O

2

-based core–shell structure. As a consequence of parameter optimization, it is found that semiconductor-to-metallic reconfiguring of relatively thin

V
O

2

nanoinclusions with a core–shell radius ratio of 0.95 is accompanied by enhanced multispectral near-infrared absorption of the system for both forward and backward incidences of light. However, increasing intensity of the incident wave bends the resonant wavelengths due to the NL response of Kerr dielectrics. When the incident light is well set up for an appropriate non-resonant wavelength, the absorption contrast between two directions of incidence enhances in some ranges of intensities due to the NL Kerr effect. There is also the possibility of reaching S-shaped bistable absorption. These features make the modeled system suitable for designing near-infrared absorptive diodes or isolators.
Label-free automated neutropenia detection and grading using deep-ultraviolet microscopy
Authors: Ojaghi Ashkan , Casteleiro Costa Paloma , Caruso Christina , Lam Wilbur A. , Robles Francisco E.
Published: September 2021

Neutropenia is a condition identified by an abnormally low number of neutrophils in the bloodstream and signifies an increased risk of severe infection. Cancer patients are particularly susceptible to this condition, which can be disruptive to their treatment and even life-threatening in severe cases. Thus, it is critical to routinely monitor neutrophil counts in cancer patients. However, the standard of care to assess neutropenia, the complete blood count (CBC), requires expensive and complex equipment, as well as cumbersome procedures, which precludes easy or timely access to critical hematological information, namely neutrophil counts. Here we present a simple, low-cost, fast, and robust technique to detect and grade neutropenia based on label-free multi-spectral deep-UV microscopy. Results show that the developed framework for automated segmentation and classification of live, unstained blood cells in a smear accurately differentiates patients with moderate and severe neutropenia from healthy samples in minutes. This work has significant implications towards the development of a low-cost and easy-to-use point-of-care device for tracking neutrophil counts, which can not only improve the quality of life and treatment-outcomes of many patients but can also be lifesaving.
In vivo harmonic generation microscopy for monitoring the height of basal keratinocytes in solar lentigines after laser depigmentation treatment
Authors: Wu Pei-Jhe , Chen Sheng-Tse , Liao Yi-Hua , Sun Chi-Kuang
Published: September 2021

The development of solar lentigines (SLs) is related to chronic ultraviolet exposure-induced cell senescence. We have previously demonstrated that basal keratinocyte enlargement is a morphological hallmark of skin senescence correlated to the process of skin aging, while clinical studies on the long-term monitoring of the cellular morphological changes in SLs after laser treatment are lacking. In this study, we have developed the harmonic generation microscopy (HGM) for in vivo monitoring the height of basal keratinocytes (HBK) and had administered Q-switched ruby laser or picosecond 532-nm Nd:YAG laser treatment on each side of the face of 25 Asian patients with facial SLs, respectively. In vivo HGM imaging was conducted to longitudinally analyze HBK and the horizontal cell size (HCS). Before treatment, the HBK was significantly higher in the SLs lesional area than that in the adjacent normal region, whereas there was no significant difference in the HCS. After treatment, the lesional HBK remained significantly higher than normal skin regardless of the laser treatment used. Our study indicates that the basal keratinocytes remain abnormal after laser treatment and demonstrates the capability of in vivo HGM for longitudinal, quantitative monitoring of cell senescence and therapeutic effect in SLs.
Gain in time-dependent media—a new mechanism
Authors: Pendry J. B. , Galiffi E. , Huidobro P. A.
Published: September 2021

Time-dependent systems do not in general conserve energy, invalidating
much of the theory developed for static systems and turning our
intuition on its head. This is particularly acute in luminal space-time crystals, where the structure
moves at or close to the velocity of light. Conventional Bloch wave
theory no longer applies, energy grows exponentially with time, and a
new perspective is required to understand the phenomenology. In this
paper, we identify a new mechanism for amplification: the compression
of lines of force that are nevertheless conserved in number.