bluuebunny/crossref_metadata_2025 huggingface dataset:
Game theory‐based metaheuristics for structural design optimization
Authors: Mahjoubi Soroush , Bao Yi
Published: May 2021

This paper presents game theory‐based strategies incorporated with metaheuristics to improve the computation efficiency and effectiveness in design optimization of civil engineering structures. The idea is that a structural optimization problem can be treated as a multiplayer game with optimization algorithms as the players. This study presents an innovative mixed game strategy and provides insights into domain decomposition schemes. Based on game theory strategies, six modified metaheuristic algorithms are proposed and demonstrated through a case study of a 30‐story mega‐braced frame‐core building with a complex configuration. Jaya algorithm is selected as the control to evaluate the proposed methods. The results show that the mixed game strategy helps reduce the computation cost by about 50%, while reducing the weights of the building by 4%, compared with the Jaya algorithm.
Personnel governance of corporatized public services: Effects of executive resources and corporation forms on turnover
Authors: Papenfuß Ulf , Schmidt Christian A.
Published: May 2021

Corporatization has potentials for public service provision but also induces far‐reaching governance challenges. Appointing executives for public corporations is a powerful personnel governance mechanism for public authorities to manage public service provision and resource dependencies. However, the theoretical understanding of executive turnover is limited. Drawing on resource dependence theory and embedding publicness fit perspectives, Cox regressions for 491 executives of 275 German municipal corporations between 2006 and 2016 show that politicized executives, executives with higher pay, and internally hired executives have a longer tenure and a lower turnover likelihood. Furthermore, the findings reveal different governance rationalities between different corporation forms by showing a higher likelihood of executive turnover in not profit‐making corporations than in profit‐making corporations. This highlights the theoretical needs and potentials to conceptually differentiate between these two corporation forms in future research. Overall, this study enhances the theoretical understanding of executive turnover and provides important research perspectives.

Die politischen Entscheidungen zur Auslagerung öffentlicher Aufgaben auf öffentliche Unternehmen haben hohe Potenziale für eine effektive und effiziente öffentliche Aufgabenerfüllung, führen aber zugleich zu weitreichenden Governance‐Herausforderungen. Die Besetzung von Mitgliedern des Top‐Managementorgans öffentlicher Unternehmen ist ein besonders relevanter personeller Governance‐Mechanismus für öffentliche Anteilseignern zur Steuerung der öffentlicher Aufgabenerfüllung und Ressourcenabhängigkeiten. Basierend auf der Theorie der Ressourcenabhängigkeiten und Publicness‐Fit‐Perspektiven zeigt eine Cox‐Analyse von 491 Top‐Managementmitgliedern aus 275 deutschen kommunalen Unternehmen zwischen 2006 und 2016, dass politisierte, intern‐nachbesetzte und Top‐Managementmitglieder mit höherem Vergütungsniveau eine längere Amtszeit und eine geringere Wechsel‐/Turnoverwahrscheinlichkeit aufweisen. Darüber hinaus zeigen die Ergebnisse unterschiedliche Governance‐Rationalitäten zwischen verschiedenen Unternehmensformen. Demnach ist die Turnoverwahrscheinlichkeit von Top‐Managementmitgliedern in nicht gewinnbringenden öffentlichen Unternehmen signifikant höher als in gewinnbringenden Unternehmen. Dies verdeutlicht den theoretischen Bedarf, diese beiden Unternehmensformen in der zukünftigen Forschung konzeptionell zu differenzieren. Insgesamt erweitert diese Studie das theoretische Verständnis zum Turnover von Top‐Managementmitgliedern und liefert wichtige Forschungsperspektiven.
Neonatal suppurative parotitis: Case reports and literature review
Authors: Mori Toshihiko , Shimomura Ryotaro , Ito Takuro , Iizuka Hironori , Hoshino Emiko , Hirakawa Satoshi , Sakurai Nodoka , Fuse Shigeto
Published: May 2021

Background

Neonatal suppurative parotitis is a rare disease, characterized mainly by unilateral parotid swelling with erythema and tenderness, and often purulent discharge from the Stensen’s duct into the oral cavity. Only 44 cases were reported in the English literature between 1970 and 2013.

Methods

A MEDLINE search was conducted using the terms acute, neonatal, newborn, suppurative, bacterial, purulent, parotitis, parotid swelling, and parotid abscess, limited to the English‐language literature starting from 2011. We reviewed all reported cases, together with two more managed cases in our hospital. We also describe the magnetic resonance imaging findings of the early stage of this disease.

Results

We identified 26 new cases since 2011. The total number of patients reviewed was 72, including our patients. The infection was unilateral in 83% of patients, and 67% of the affected patients were males. The serum amylase levels were generally not elevated despite marked parotid swelling. Of the causative agents of this disease, 65% were Staphylococcus aureus, of which 19% were methicillin‐resistant S. aureus. As the rate of cesarean section was high in patients with this disease, it was considered a risk factor. The diffusion‐weighted magnetic resonance images showed multiple punctate hyperintensity regions with reduced apparent diffusion coefficient, suggesting microabscess formation in the affected gland.

Conclusions

Acute suppurative parotitis should be considered in cases of swelling and tenderness in the parotid gland during the neonatal period. Multiple punctate hyperintensities in the parotid gland on the diffusion‐weighted images may indicate a retrograde bacterial infection from the Stensen’s duct.
Mental action
Authors: Peacocke Antonia
Published: May 2021

This paper summarizes the historical and contemporary importance of mental action in philosophy. Not every piece of mental activity is a mental action. A mental action is something you do mentally, and something for which you as a whole person are responsible. It can be something you do as a means to doing something else, in the case of complex (i.e. non‐basic) mental actions. The fact that you can perform complex mental actions implies that some thoughts have several contents under the several descriptions under which they are intentional. The nature of mental action helps to explain how you have special self‐knowledge of your own mental states. It also helps to explain how certain kinds of norms, including epistemic norms, gain application to thought.
Hardening foreign corporate accountability through mandatory due diligence in the European Union? New trends and persisting challenges
Authors: Schilling‐Vacaflor Almut , Lenschow Andrea
Published: May 2021

The negative externalities of global commodity chains and existing governance gaps have received wide scholarly attention. Indeed, many sectors including forest‐risk commodities (FRCs) like soy and beef from Brazil remain largely unregulated. This article analyzes ongoing policy‐making processes at European Union level to adopt new regulations for reducing accountability gaps: one regulation of FRCs and one general, cross‐sectoral directive on human rights and environmental due diligence. This article draws on and aims to contribute to previous research into foreign corporate accountability, therein analytically distinguishing between input, output, and surrogate accountability. This study shows that new policies will likely be more comprehensive than previous supply chain regulations, while their specific institutional design and stringency are highly contested. More in general, we argue that for hardening corporate accountability, due diligence politics will need to confront important governance challenges that have limited the potential of previous regulations, such as a lack of consequentiality of reporting obligations, weak state monitoring, limited stakeholder involvement, and difficulties to establish legal liability.
CRRT in developing world
Authors: Srisawat Nattachai , Chakravarthi Rajasekara
Published: May 2021

Continuous renal replacement therapy (CRRT) has become a mainstay therapy in the intensive care unit (ICU) and its utilization continues to increase in developed countries. The wide variations of CRRT practice, however, are evident in developing countries while clinicians in these resource‐limited countries encounter various barriers such as a limited number of nephrologists and trained staff, a gap of knowledge, machine unavailability, cultural and socioeconomic aspects, high‐cost therapy without reimbursement, and administrative as well as governmental barriers. In this article, we demonstrate the situation of CRRT and discuss the barriers of CRRT in a resource‐limited setting. We also discuss the strategies to improve CRRT practice. These recommendations can serve as a fundamental guideline for clinicians to implement CRRT in low‐resource settings.
Alternative = transformative? Investigating drivers of transformation in alternative food networks in Germany
Authors: Zoll Felix , Specht Kathrin , Siebert Rosemarie
Published: May 2021

In the hope for more sustainable agriculture and a stronger connection to their food, an increasing number of consumers participate in alternative food networks (AFNs) characterised by short food supply chains. However, it cannot be assumed that AFNs inherently transform the prevailing system and its respective practices around food. Thus, we apply a social innovation perspective to enable a comprehensive analysis of changed values, social practices and relations in AFNs. This article presents whether drivers of transformation occur in three different AFN models (Community Supported Agriculture (CSA), food co‐operatives (food co‐ops) and self‐harvest gardens) and how participants describe and perceive them in each model. Therefore, we conducted interviews with AFN producers and consumers, before applying qualitative content analysis. Interviewees describe a broad variety of transformed values, practices and relations: Especially CSA and food co‐ops bear transformative potential as their members report a strong reconnection of producers and consumers expressed through social interaction and community‐building. Self‐harvest gardeners predominantly seek individual capacity building and to have access to their own garden. We conclude that AFN participation fosters incremental transformation towards more sustainable practices around food and a respective value system, which can be a part of a bigger movement aimed at food system transformation.
Revealing temporal stay patterns in human mobility using large‐scale mobile phone location data
Authors: Yang Xiping , Fang Zhixiang , Xu Yang , Yin Ling , Li Junyi , Zhao Zhiyuan
Published: May 2021

The emergence of large‐scale human spatiotemporal tracing data inspired researchers to investigate human mobility patterns from different perspectives with potential implications for urban planning, traffic management, and emergency response. Previous studies investigated the mechanism of human mobility by constructing spatial mobility motifs based on mobile phone datasets, but ignored their temporal characteristics. To compensate for this, this study extracted temporal stay patterns based on spatial mobility motifs. Using mobile phone location data from Shenzhen, China, we identified stop location sequences for users and constructed home‐based mobility motifs according to predefined rules, and observed that approximately 97% of users can be characterized by the 10 identified home‐based mobility motifs. We designed a method to quantify the similarity of temporal stay characteristics, and the primary temporal stay patterns were extracted by classifying users with similar stay rhythms. Our results enrich the knowledge of human travel behavior from both spatial and temporal perspectives.
Detection and inhibition of IgE antibodies reactive with cross‐reactive carbohydrate determinants in an ELISA for allergen‐specific IgE in horses
Authors: Enck Kevin M. , Lee Kenneth W. , McKinney Brennan H. , Blankenship Karen D. , Montesano Cathe
Published: May 2021

Background

It has been demonstrated that immunoglobulin (Ig)E specific for cross‐reactive carbohydrate determinants (CCD) is present in the serum of sensitized humans, dogs and cats, and that these CCD‐specific antibodies might confound serological testing.

Hypothesis/Objective

The objective was to determine whether or not CCD‐reactive antibodies occur in horses and to investigate the prevalence of CCD‐reactive IgE antibodies in equine sera using a monoclonal cocktail‐based enzyme‐linked immunosorbent assay designed to detect allergen‐specific IgE in horses, and to evaluate a means for successful inhibition of these CCD.

Methods and materials

Sera from 28 horses suspected of clinical allergy were evaluated, with and without a proprietary inhibitor which contains carbohydrates derived from bromelain (BROM‐CCD), using a panel of 72 allergens that include 15 grasses, 17 trees, nine weeds, five mites, 12 fungi, 12 insects and two environmental allergens.

Results

Twenty‐five samples were shown to be reactive to at least one of the allergens, and 15 were reactive to 10 allergens or more. BROM‐CCD had minimal effect on the mite reactivity in any of the positive samples; however, substantial inhibition for pollen allergens (trees, grasses and weeds) was demonstrable. Reduction in signal to pollens ranged from 20% to 100% for samples that were inhibited by CCD‐BROM.

Conclusions and Clinical Importance

These results demonstrate that CCD‐reactive IgE antibodies are evident in horses and that BROM‐CCD can be effective in reducing reactions with these irrelevant carbohydrates and will likely yield a more accurate in vitro allergen reactivity profile for selection of allergens included in an immunotherapeutic regime.
Short‐term outcomes of 59 dogs treated for ilial body fractures with locking or non‐locking plates
Authors: Petrovsky Brian , Knuth Taylor , Aponte‐Colón Cristina , Hoefle William , Kraus Karl , Naiman Jaron , Yuan Lingnan , Mochel Jonathan P. , Zellner Eric
Published: May 2021

Objective

To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures.

Design

Retrospective study.

Animals

Fifty‐nine dogs (63 hemipelves).

Methods

Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non‐locking plate system (NLS). Perioperative, long‐term complications, and follow‐up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories.

Results

LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow‐up time was 8 weeks (3–624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures.

Conclusion

The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS.

Clinical Relevance

Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short‐term implant failure.
Attitudes to English in contemporary Malaysia
Authors: Ng Jia Chi , Diskin‐Holdaway Chloé
Published: May 2021

This article examines the attitudes that Malaysians of different backgrounds hold towards the English language in Malaysia, as well as how they perceive ‘Standard Malaysian English’ and ‘Colloquial Malaysian English’, in terms of status and solidarity. The study administered an online questionnaire, which included an embedded matched‐guise experiment, to 77 Malaysian respondents in Malaysia and Australia. Findings indicated a range of divergent and at times contradictory views of Malaysian English, illuminating how Malaysians are in different stages of acceptance of Malaysian English as a legitimate variety of English. Through an examination of individual participant responses, the study also shows that Malaysians are attuned to and hold certain stereotypes towards ‘ethnic’ varieties or ‘ethnolects’ of Malaysian English, providing insight into how issues of race and ethnicity, embedded within the broader socio‐political context and language ecology of the nation, have influenced contemporary language attitudes.
Influence of Chronotype on Motor Behavior in Healthy Individuals: Analyses of Manual Dexterity in Different Times of the Day
Authors: Nogueira Nathálya Gardênia de Holanda Marinh , Ferreira Bárbara de Paula , Narciso Fernanda Veruska , Parma Juliana Otoni , Leão Sara Edith Souza de Assis , Lage Guilherme Menezes , Fernandes Lidiane Aparecida
Published: May 2021

This study investigated the influence of chronotype on motor behavior in a manual dexterity task performed at different times of the day. Sixteen healthy adults of each chronotype (morning, evening, and neither), as measured by the Morningness–Eveningness Questionnaire, practiced both conditions of the Grooved Pegboard Test either in the morning or in the afternoon to early evening. The “neither” chronotype (65.12 ± 7.46) was outperformed (ps ≤ .03) by both the morning (56.09 ± 7.21) and evening (58.94 ± 7.53) chronotypes when the task had higher cognitive and motor demand but was not outperformed in the task with lower demand (morning = 18.46 ± 2.11; evening = 19.34 ± 2.79; neither = 21.47 ± 2.54; p > .05). No difference between the morning and evening chronotypes was found at the different times of the day (ps > .05), suggesting that a manual dexterity task is not sufficiently demanding to be influenced by chronotype.
Programmable Bloch polaritons in graphene
Authors: Xiong Lin , Li Yutao , Jung Minwoo , Forsythe Carlos , Zhang Shuai , McLeod Alexander S. , Dong Yinan , Liu Song , Ruta Frank L. , Li Casey , Watanabe Kenji , Taniguchi Takashi , Fogler Michael M. , Edgar James H. , Shvets Gennady , Dean Cory R. , Basov D. N.
Published: May 2021

When light-matter polaritons travel in periodic media, they acquire properties akin to Bloch quasi-particles in crystals.
Structural insights into integrin α5β1opening by fibronectin ligand
Authors: Schumacher Stephanie , Dedden Dirk , Nunez Roberto Vazquez , Matoba Kyoko , Takagi Junichi , Biertümpfel Christian , Mizuno Naoko
Published: May 2021

Integrin α5β1structures in resting and active states with ligand fibronectin reveal key interactions for integrin opening.
Realizing a 14% single-leg thermoelectric efficiency in GeTe alloys
Authors: Bu Zhonglin , Zhang Xinyue , Shan Bing , Tang Jing , Liu Hongxia , Chen Zhiwei , Lin Siqi , Li Wen , Pei Yanzhong
Published: May 2021

This work demonstrates GeTe alloys for efficient thermoelectric waste-heat recovery.
Application of a sub–0.1-mm
3
implantable mote for in vivo real-time wireless temperature sensing
Authors: Shi Chen , Andino-Pavlovsky Victoria , Lee Stephen A. , Costa Tiago , Elloian Jeffrey , Konofagou Elisa E. , Shepard Kenneth L.
Published: May 2021

This paper presents a sub–0.1-mm
3
, fully integrated, injectable ultrasonic wireless device for biomedical temperature sensing.
Nonlinear infrared polaritonic interaction between cavities mediated by molecular vibrations at ultrafast time scale
Authors: Xiang Bo , Wang Jiaxi , Yang Zimo , Xiong Wei
Published: May 2021

Strong coupling enables delocalized intercavity nonlinearity by combining the photon delocalization and molecular anharmonicity.
Structures of the human Mediator and Mediator-bound preinitiation complex
Authors: Chen Xizi , Yin Xiaotong , Li Jiabei , Wu Zihan , Qi Yilun , Wang Xinxin , Liu Weida , Xu Yanhui
Published: May 2021

A complete PIC-Mediator structure

As a critical transcription coactivator, the multisubunit Mediator complex binds RNA polymerase II (Pol II), facilitates preinitiation complex (PIC) assembly, and stimulates transcription and phosphorylation of the Pol II C-terminal domain (CTD). However, how these critical transcriptional events are coordinated by Mediator is not fully understood. Chen
et al.
determined the structures of human Mediator and Mediator-bound PIC in distinct conformational states, the latter of which represents a complete PIC-Mediator complex assembled on the 14-subunit transcription factor IID (TFIID). The structures show that Mediator undergoes reorganization during PIC-Mediator assembly, sandwiches and facilitates phosphorylation of Pol II CTD, and works with TFIID to organize TFIIH in PIC for transcription initiation.

Science
, abg0635, this issue p.
eabg0635
IL-1R1–dependent signaling coordinates epithelial regeneration in response to intestinal damage
Authors: Cox Christian B. , Storm Elaine E. , Kapoor Varun N. , Chavarria-Smith Joseph , Lin David L. , Wang Lifen , Li Yun , Kljavin Noelyn , Ota Naruhisa , Bainbridge Travis W. , Anderson Keith , Roose-Girma Merone , Warming Søren , Arron Joseph R. , Turley Shannon J. , de Sauvage Frederic J. , van Lookeren Campagne Menno
Published: May 2021

IL-1 acts on stromal and innate lymphoid cells to coordinate the repair response to distinct types of intestinal damage.
Effect of Melanin Biosynthesis Inhibition on the Antifungal Susceptibility of Chromoblastomycosis Agents
Authors: Heidrich Daiane , Pagani Danielle Machado , Koehler Alessandra , Alves Karine de Oliveira , Scroferneker Maria Lúcia
Published: May 2021

Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by genera of melanized fungi:
Fonsecaea
,
Cladophialophora
,
Phialophora
,
Exophiala
, and
Rhinocladiella
. Melanin is a virulence factor known to influence antifungal susceptibility. A specific inhibitor of melanin biosynthesis is tricyclazole.
Vaginal Isolates of Candida glabrata Are Uniquely Susceptible to Ionophoric Killer Toxins Produced by Saccharomyces cerevisiae
Authors: Fredericks Lance R. , Lee Mark D. , Eckert Hannah R. , Li Shunji , Shipley Mason A. , Roslund Cooper R. , Boikov Dina A. , Kizer Emily A. , Sobel Jack D. , Rowley Paul A.
Published: May 2021

Compared to other species of
Candida
yeasts, the growth of
Candida glabrata
was inhibited by many different strains of
Saccharomyces
killer yeasts. The ionophoric K1 and K2 killer toxins were broadly inhibitory to all clinical isolates of
C. glabrata
from patients with recurrent vulvovaginal candidiasis despite high levels of resistance to clinically relevant antifungal therapeutics.
Overcoming the Challenges of Pyrazinamide Susceptibility Testing in Clinical Mycobacterium tuberculosis Isolates
Authors: Mok Simone , Roycroft Emma , Flanagan Peter R. , Montgomery Lorraine , Borroni Emanuele , Rogers Thomas R. , Fitzgibbon Margaret M.
Published: May 2021

Pyrazinamide (PZA) is one of the first-line agents used for the treatment of tuberculosis. However, current phenotypic PZA susceptibility testing in the Bactec MGIT 960 system is unreliable, and false resistance is well documented.
Therapeutic Application of Lantibiotics and Other Lanthipeptides: Old and New Findings
Authors: van Staden Anton Du Preez , van Zyl Winschau F. , Trindade Marla , Dicks Leon M. T. , Smith Carine
Published: May 2021

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, with modifications that are incorporated during biosynthesis by dedicated enzymes. Various modifications of the peptides are possible, resulting in a highly diverse group of bioactive peptides that offer a potential reservoir for use in the fight against a plethora of diseases.
Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh
Authors: Brar Himmat Singh , Marathi Rachana
Published: May 2021

Drug-induced liver injury is an uncommon yet fatal cause of liver injury. Black cohosh is a herbal supplement that is derived fromActaea racemosa. It has been used for vasomotor symptoms in postmenopausal women, but it can cause liver injury. A 50-year-old Afro-American woman presented with a 2-month history of malaise, itching and severe jaundice. The labs showed elevation of bilirubin and alkaline phosphatase. The patient had a history of black cohosh use for postmenopausal symptoms before she developed her current symptoms. The extensive workup for infective and autoimmune pathology was negative. Black cohosh was discontinued. The patient improved clinically, and her liver enzymes normalised 6 months after the discontinuation of black cohosh. This report emphasises the need to recognise black cohosh as a potential hepatotoxic agent and to monitor the liver enzymes for a patient on black cohosh.
Mascara-induced nasolacrimal duct obstruction
Authors: Scollo Paolo , Davies Rhys , O'Donovan Dominic , Rene Cornelius
Published: May 2021

A 35-year-old woman underwent left external dacryocystorhinostomy (DCR) following a recent bout of left acute dacryocystitis. She had a right DCR 14 years earlier. Her relatively young age of presentation prompted suspicion of secondary nasolacrimal duct obstruction and, although the left lacrimal sac appeared macroscopically normal peroperatively, a lacrimal sac biopsy was taken. Histopathology revealed florid chronic inflammation, with abundant granular brown pigment and polarisable crystals suggestive of an exogenous material in the lacrimal sac mucosa compatible with mascara. After initial improvement, her epiphora has recurred 1-year postoperatively, but her ocular discharge has resolved. Mascara-induced conjunctival pigmentation is well established. However, there are very few published reports of nasolacrimal duct obstruction due to mascara. Since cosmetic application of mascara and kohl eyeliner is widespread, patients and practitioners should be aware of their potential to migrate into the lacrimal apparatus and cause chronic inflammation with secondary nasolacrimal duct obstruction.
Complications associated with intrathecal drug delivery in a paediatric patient with Niemann-Pick type C
Authors: Rodriguez Ciancio Jose Ignacio Rodriguez , Aquilina Kristian
Published: May 2021

We report on a male subject with a diagnosis of Niemann-Pick type C (NPC). He received an experimental medicinal product intrathecally initially via lumbar puncture (LP) and eventually via intrathecal drug delivery device. Shortly after implantation, the device catheter migrated outside of the intrathecal space and coiled subcutaneously. The treatment continued via LP after removal of the device. A subdural haematoma developed after repeated LPs. It was surgically evacuated and the patient recovered with sequelae. Surgically implanted drug delivery devices are designed to bypass the blood–brain barrier and deliver a medicinal product directly into the cerebrospinal fluid circulation. Their use has extended into the field of neurodegenerative disorders. Significant adverse events can occur at any given time after implantation including neurological injury, dislodgement or displacement of any of its components, infection and drug-related complications; all can significantly affect the quality of life of patients. Repeated LPs also carry significant risk.
Immunoglobulin A–specific deficiency induces spontaneous inflammation specifically in the ileum
Authors: Nagaishi Takashi , Watabe Taro , Kotake Kunihiko , Kumazawa Toshihiko , Aida Tomomi , Tanaka Kohichi , Ono Ryuichi , Ishino Fumitoshi , Usami Takako , Miura Takamasa , Hirakata Satomi , Kawasaki Hiroko , Tsugawa Naoya , Yamada Daiki , Hirayama Kazuhiro , Yoshikawa Soichiro , Karasuyama Hajime , Okamoto Ryuichi , Watanabe Mamoru , Blumberg Richard S , Adachi Takahiro
Published: May 2021

Objective

Although immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism.

Design

We generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging.

Results

We obtained two lines, with one that contained a <50 base pair deletion in the cytoplasmic region of the IgA allele (IgA tail-mutant; IgAtm/tm) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA−/−). IgA−/−exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4+T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca2+biosensor showed that IgA−/−had elevated Ca2+signalling in Peyer’s patch B cells. On the other hand, IgAtm/tmseemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder.

Conclusion

IgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum.
Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women
Authors: Hur Jinhee , Otegbeye Ebunoluwa , Joh Hee-Kyung , Nimptsch Katharina , Ng Kimmie , Ogino Shuji , Meyerhardt Jeffrey A , Chan Andrew T , Willett Walter C , Wu Kana , Giovannucci Edward , Cao Yin
Published: May 2021

Objective

Sugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined.

Design

In the Nurses’ Health Study II (1991–2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13–18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs.

Results

We documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; ptrend=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13–18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%–36% lower risk of EO-CRC.

Conclusion

Higher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.
COVID-19, lockdowns and motor vehicle collisions: empirical evidence from Greece
Authors: Vandoros Sotiris
Published: May 2021

Reduced mobility during COVID-19 lockdowns means not only fewer vehicles at risk of collision, but also an opportunity to speed on empty streets. The objective of this paper is to examine the impact of the first wave of the pandemic and the first lockdown on motor vehicle collisions (MVCs) and associated injuries and deaths in Greece. Using monthly data at the regional unit level, I provide descriptive evidence and subsequently follow a difference-in-differences econometric approach, comparing trends in 2020 with those of the previous 5 years while controlling for unemployment and petrol prices. I found a steep decline in collisions, injuries and deaths compared with what would have been otherwise expected. In March and April 2020, there were about 1226 fewer collisions, 72 fewer deaths, 40 fewer serious injuries and 1426 fewer minor injuries compared with what would have been expected in the absence of the pandemic.
Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas
Authors: Arnone Claudia Manuela , Polito Vinicia Assunta , Mastronuzzi Angela , Carai Andrea , Diomedi Francesca Camassei , Antonucci Laura , Petrilli Lucia Lisa , Vinci Maria , Ferrari Francesco , Salviato Elisa , Scarsella Marco , De Stefanis Cristiano , Weber Gerrit , Quintarelli Concetta , De Angelis Biagio , Brenner Malcolm K , Gottschalk Stephen , Hoyos Valentina , Locatelli Franco , Caruana Ignazio , Del Bufalo Francesca
Published: May 2021

Background

Pediatric high-grade gliomas (pHGGs) are among the most common and incurable malignant neoplasms of childhood. Despite aggressive, multimodal treatment, the outcome of children with high-grade gliomas has not significantly improved over the past decades, prompting the development of innovative approaches.

Methods

To develop an effective treatment, we aimed at improving the suboptimal antitumor efficacy of oncolytic adenoviruses (OAs) by testing the combination with a gene-therapy approach using a bispecific T-cell engager (BiTE) directed towards the erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2), conveyed by a replication-incompetent adenoviral vector (EphA2 adenovirus (EAd)). The combinatorial approach was tested in vitro, in vivo and thoroughly characterized at a molecular level.

Results

After confirming the relevance of EphA2 as target in pHGGs, documenting a significant correlation with worse clinical outcome of the patients, we showed that the proposed strategy provides significant EphA2-BiTE amplification and enhanced tumor cell apoptosis, on coculture with T cells. Moreover, T-cell activation through an agonistic anti-CD28 antibody further increased the activation/proliferation profiles and functional response against infected tumor cells, inducing eradication of highly resistant, primary pHGG cells. The gene-expression analysis of tumor cells and T cells, after coculture, revealed the importance of both EphA2-BiTE and costimulation in the proposed system. These in vitro observations translated into significant tumor control in vivo, in both subcutaneous and a more challenging orthotopic model.

Conclusions

The combination of OA and EphA2-BiTE gene therapy strongly enhances the antitumor activity of OA, inducing the eradication of highly resistant tumor cells, thus supporting the clinical translation of the approach.
Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma
Authors: Leidner Rom , Crittenden Marka , Young Kristina , Xiao Hong , Wu Yaping , Couey Marcus A , Patel Ashish A , Cheng Allen C , Watters Amber L , Bifulco Carlo , Morris George , Rushforth Lessli , Nemeth Shorin , Urba Walter J , Gough Michael , Bell R Bryan
Published: May 2021

Background

Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone.

Methods

The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment.

Results

Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated.

Conclusion

These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer.

Trial registration number

This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.
Determinants of LV dP/dtmaxand QRS duration with different fusion strategies in cardiac resynchronisation therapy
Authors: Odland Hans Henrik , Holm Torbjørn , Gammelsrud Lars Ove , Cornelussen Richard , Kongsgaard Erik
Published: May 2021

Background

We designed this study to assess the acute effects of different fusion strategies and left ventricular (LV) pre-excitation/post-excitation on LV dP/dtmaxand QRS duration (QRSd).

Methods

We measured LV dP/dtmaxand QRSd in 19 patients having cardiac resynchronisation therapy (CRT). Two groups of biventricular pacing were compared: pacing the left ventricle (LV) with FUSION with intrinsic right ventricle (RV) activation (FUSION), and pacing the LV and RV with NO FUSION with intrinsic RV activation. In the NO FUSION group, the RV was paced before the expected QRS onset. A quadripolar LV lead enabled distal, proximal and multipoint pacing (MPP). The LV was stimulated relative in time to either RV pace or QRS-onset in four pre-excitation/post-excitation classes (PCs). We analysed the interactions of two groups (FUSION/NO FUSION) with three different electrode configurations, each paced with four different degrees of LV pre-excitation (PC1–4) in a statistical model.

Results

LV dP/dtmaxwas higher with NO FUSION than with FUSION (769±46 mm Hg/s vs 746±46 mm Hg/s, p<0.01), while there was no difference in QRSd (NO FUSION 156±2 ms and FUSION 155±2 ms). LV dP/dtmaxand QRSd increased with LV pre-excitation compared with pacing timed to QRS/RV pace-onset regardless of electrode configuration. Overall, pacing LV close to QRS-onset (FUSION) with MPP shortened QRSd the most, while LV dP/dtmaxincreased the most with LV pre-excitation.

Conclusion

We show how a beneficial change in QRSd dissociates from the haemodynamic change in LV dP/dtmaxwith different biventricular pacing strategies. In this study, LV pre-excitation was the main determinant of LV dP/dtmax, while QRSd shortens with optimal resynchronisation.
Impact of emergency medical service delays on time to reperfusion and mortality in STEMI
Authors: Alrawashdeh Ahmad , Nehme Ziad , Williams Brett , Smith Karen , Brennan Angela , Dinh Diem T , Liew Danny , Lefkovits Jeffrey , Stub Dion
Published: May 2021

Objectives

To explore the relationship between emergency medical service (EMS) delay time, overall time to reperfusion and clinical outcome in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

Methods

This was a retrospective observational study of 2976 patients with STEMI who presented to EMS and underwent PPCI between January 2014 and December 2017. We performed multivariable logistic models to assess the relationship between EMS delay time and 30-day mortality and to identify factors associated with system delay time.

Results

EMS delay time accounted for the first half of total system delay (median=59 min (IQR=48–77)). Compared with those who survived, those who died had longer median EMS delay times (59 (IQR=11–74) vs 74 (IQR=57–98), p<0.001). EMS delay time was independently associated with a higher risk of mortality (adjusted OR 1.20; 95% CI 1.02 to 1.40, for every 30 min increase), largely driven by complicated patients with cardiogenic shock or cardiac arrest. Independent predictors of longer EMS delay times were older age, women, cardiogenic shock, cardiac arrest, prehospital notification and intensive care management. Although longer EMS delay times were associated with shorter door-to-balloon times, total system delay times increased with increasing EMS delay times.

Conclusion

Increasing EMS delay times, particularly those result from haemodynamic complications, increase total time to reperfusion and are associated with 30-day mortality after STEMI. All efforts should be made to monitor and reduce EMS delay times for timely reperfusion and better outcome.
Gravitational waves in neutrino plasma and NANOGrav signal
Authors: Pandey Arun Kumar
Published: May 2021

The recent finding of the gravitational wave (GW) signal by the NANOGrav collaboration in the nHZ frequency range has opened up the door for the existence of stochastic GWs. In the present work, we have argued that in a hot dense neutrino asymmetric plasma, GWs could be generated due to the instability caused by the finite difference in the number densities of the different species of the neutrinos. The generated GWs have amplitude and frequency in the sensitivity range of the NANOGrav observation. We have shown that the GWs generated by this mechanism could be one of the possible explanations for the observed NANOGrav signal. We have also discussed generation of GWs in an inhomogeneous cosmological neutrino plasma, where GWs are generated when neutrinos enter a free streaming regime. We show that the generated GWs in an inhomogeneous neutrino plasma cannot explain the observed NANOGrav signal. We have also calculated the lower bound on magnetic fields’ strength using the NANOGrav signal and found that to explain the signal, the magnetic fields’ strength should have at least value $$\sim 10^{-12}$$

∼

10

-
12

G at an Mpc length scale.
Influence of relative humidity and air temperature on the stopping position of the automatic tool changer in a CNC machine when using a pneumatic cylinder
Authors: Van Hung Pham , Thuy Duong Nguyen
Published: May 2021

The automatic tool changer (ATC) in computerized numerical control (CNC) milling machine often uses pneumatic dynamic sources. Friction in the pneumatic cylinder affects the ATC’s stopping position; this friction depends on many factors, including the air environment’s relative humidity and temperature. This paper presents the results of research on the effects of relative humidity (RH) and air temperature (T) on the stopping position of an ATC using a pneumatic cylinder. Studies were conducted at temperatures of [Formula: see text]C, [Formula: see text]C and [Formula: see text]C and relative humidity values of 51%, 75% and 99% for different speeds of the pneumatic cylinder (30, 50 and 100 mm/s). The results show that when the humidity increases from 51% to 99% and the temperature increases from [Formula: see text]C to [Formula: see text]C, the friction force decreases. The friction force is related to the relative humidity and temperature of the air. Thus, the deviation of the ATC’s stopping position depends on the relative humidity and temperature of the area under investigation.
Corrosion mechanism and degradation behavior of basalt fiber-reinforced composites in sulfuric acid solution
Authors: Ha Jin-Cheol , Park Soo-Jeong , Kim Yun-Hae
Published: May 2021

Epoxy resins reinforced by basalt fibers were treated with a sulfuric acid solution for different periods and concentrations. The tensile strength of the composites was examined after the treatment. The fracture surfaces were characterized using scanning electron microscopy and energy-dispersive X-ray spectroscopy. The tensile strengths of the sulfuric acid solution-treated samples showed a decreasing trend with treating times and concentrations. However, after 250–500 h of treatment time, the tensile strengths showed an increasing trend. Based on the experimental results, the possible corrosion mechanisms were explored. Sulfuric acid leads to insoluble sulfur oxide formation with high C, Ca and Fe element contents on the fiber surface. With the continuation of sulfuric acid reaction, a thin corrosion shell covers the whole fiber surface. The thickest corrosion shell caused a significant increase in the tensile strength at the breaking of basalt fibers.
The braid group and its presentation
Authors: Wajnryb Bronislaw
Published: May 2021

In this paper, we recall the geometric definition of the braid group by Emil Artin and we give a complete, elementary geometric/topological proof of the standard presentation of the braid group on [Formula: see text] strings.
A Modified Extensor Carpi Ulnaris Tenodesis with the Sauvé-Kapandji Procedure
Authors: Kim Jongmin , Van Royen Kjell , Tsai Tsu-Min
Published: May 2021

Background: Since the Sauvé-Kapandji procedure was introduced in 1936, many modifications were created using dynamic stabilizer, such as the ECU (extensor carpi ulnaris), the FCU (flexor carpi ulnaris), pronator teres to solve proximal ulnar stump pain. We believe that this modification is also another option for distal ulnar stump instability.

Methods: From January 1998 to February 2017, there were 13 patients received the Sauvé-Kapandji (S-K) procedure with tenodesis of the ECU to the carpus and interosseous membrane. The average age at operation was 52 years (range, 28 to 63 years). Four had traumatic arthritis (two from distal radial fracture malunion, two had instability of distal radioulnar joint from Essex-Lopresti injury), four had primary osteoarthritis of the distal radio-ulnar joint, two had rheumatoid arthritis, one had gouty arthritis, two had madelung deformity. The average follow-up was 30 months (range, 15 to 72 months).

Results: Postoperative pronation/supination of the forearm had significantly improved with the exception of the wrist flexion/extension. After surgery, the mean radioulnar distance was narrowed from 11 mm to 9 mm, but no significant difference in 12 patients. All patients had improved in wrist pain, 10 patients had no pain and 3 patients with mild pain over the distal ulnar stump. The mean grip strength had significantly improved from 51% of the contralateral side to 75%. The lateral and stress X-ray films showed no instability of the distal ulnar stump after surgery.

Conclusions: In conclusion, the modified S-K procedure using the tenodesis of ECU provides a multi-directional stability and is a reliable surgical procedure for distal radioulnar disorders.