bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthovoltage X-Rays Exhibit Increased Efficacy Compared with γ-Rays in Preclinical Irradiation
Authors: Bell Brett I. , Vercellino Justin , Brodin N. Patrik , Velten Christian , Nanduri Lalitha S.Y. , Nagesh Prashanth K.B. , Tanaka Kathryn E. , Fang Yanan , Wang Yanhua , Macedo Rodney , English Jeb , Schumacher Michelle M. , Duddempudi Phaneendra K. , Asp Patrik , Koba Wade , Shajahan Shahin , Liu Laibin , Tomé Wolfgang A. , Yang Weng-Lang , Kolesnick Richard , Guha Chandan
Published: August 2022

Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects. We therefore sought to compare the effects of orthovoltage X-rays with 1-mm Cu or Thoraeus filtration and 137Cs γ-rays using mouse models of acute radiation syndrome. Following whole-body irradiation, 30-day overall survival was assessed, and the lethal dose to provoke 50% mortality within 30-days (LD50) was calculated by logistic regression. LD50 doses were 6.7 Gy, 7.4 Gy, and 8.1 Gy with 1-mm Cu-filtered X-rays, Thoraeus-filtered X-rays, and 137Cs γ-rays, respectively. Comparison of bone marrow, spleen, and intestinal tissue from mice irradiated with equivalent doses indicated that injury was most severe with 1-mm Cu-filtered X-rays, which resulted in the greatest reduction in bone marrow cellularity, hematopoietic stem and progenitor populations, intestinal crypts, and OLFM4+ intestinal stem cells. Thoraeus-filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. This study reveals a dichotomy between physical dose and biological effect as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose reduction to achieve comparable biological effects.

Significance:

Understanding the significance of physical dose delivered using energetically different methods of radiation treatment will aid the transition from radionuclide γ-irradiators to orthovoltage X-irradiators.
Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance
Authors: Serra Violeta , Wang Anderson T. , Castroviejo-Bermejo Marta , Polanska Urszula M. , Palafox Marta , Herencia-Ropero Andrea , Jones Gemma N. , Lai Zhongwu , Armenia Joshua , Michopoulos Filippos , Llop-Guevara Alba , Brough Rachel , Gulati Aditi , Pettitt Stephen J. , Bulusu Krishna C. , Nikkilä Jenni , Wilson Zena , Hughes Adina , Wijnhoven Paul W.G. , Ahmed Ambar , Bruna Alejandra , Gris-Oliver Albert , Guzman Marta , Rodríguez Olga , Grueso Judit , Arribas Joaquin , Cortés Javier , Saura Cristina , Lau Alan , Critchlow Susan , Dougherty Brian , Caldas Carlos , Mills Gordon B. , Barrett J. Carl , Forment Josep V. , Cadogan Elaine , Lord Christopher J. , Cruz Cristina , Balmaña Judith , O'Connor Mark J.
Published: August 2022

Purpose:

PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance mechanisms exist, most resulting in restoration of HRR and protection of stalled replication forks. ATR inhibition was highlighted as a unique approach to reverse both aspects of resistance. Recently, however, a PARPi/WEE1 inhibitor (WEE1i) combination demonstrated enhanced antitumor activity associated with the induction of replication stress, suggesting another approach to tackling PARPi resistance.

Experimental Design:

We analyzed breast and ovarian patient-derived xenoimplant models resistant to PARPi to quantify WEE1i and ATR inhibitor (ATRi) responses as single agents and in combination with PARPi. Biomarker analysis was conducted at the genetic and protein level. Metabolite analysis by mass spectrometry and nucleoside rescue experiments ex vivo were also conducted in patient-derived models.

Results:

Although WEE1i response was linked to markers of replication stress, including STK11/RB1 and phospho-RPA, ATRi response associated with ATM mutation. When combined with olaparib, WEE1i could be differentiated from the ATRi/olaparib combination, providing distinct therapeutic strategies to overcome PARPi resistance by targeting the replication stress response. Mechanistically, WEE1i sensitivity was associated with shortage of the dNTP pool and a concomitant increase in replication stress.

Conclusions:

Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance including tumors without an underlying HRR deficiency. These preclinical insights are now being tested in several clinical trials where the PARPi is administered with either the WEE1i or the ATRi.
LncRNA A2M-AS1 Promotes Ferroptosis in Pancreatic Cancer via Interacting With PCBP3
Authors: Qiu Xin , Shi Qiuyue , Zhang Xianglian , Shi Xiaoyan , Jiang Haixing , Qin Shanyu
Published: August 2022

Ferroptosis is a newly-discovered cell death mechanism involved in the progression of various tumors, the role of noncoding RNAs (ncRNAs) in it was relatively less explored. This study identified the low levels of a recently studied long noncoding RNA (lncRNA), A2M-AS1, in pancreatic cancer and suggested its positive correlation with the overall survival time of patients with pancreatic cancer. A2M-AS1 was mainly localized in the cytoplasm, inhibiting the cellular proliferation, migration, and invasion as well as the tumor growth of the pancreatic cancer cells. Moreover, the Erastin-induced ferroptosis increased the expression levels of A2M-AS1. The overexpression of A2M-AS1 promoted ferroptosis in the pancreatic cancer, which was inhibited by the silencing of A2M-AS1. Mechanically, A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. In addition, the A2M-AS1/PCBP3 axis could facilitate the p38 activation and inhibit the phosphorylation of the AKT–mTOR signaling pathway; all these participate in regulating ferroptosis. In conclusion, the regulation of ferroptosis by targeting the A2M-AS1/PCBP3 axis might provide a novel target for the treatment of pancreatic cancer in the future.

Implications:

A2M-AS1 might be a potential novel therapeutic target for patients with pancreatic cancer in the future.
Viral Clearance with Neutrophil Recovery in a Patient with Active COVID-19 Infection and Refractory Acute Myeloid Leukemia Who Underwent Successful Reinduction with Cytarabine/Idarubicin
Authors: Dean Erin A. , Brown Randy A. , Kaur Pavneet , Casaus Danielle V.
Published: August 2022

Administering myelosuppressive chemotherapy to patients with aggressive malignant hematologic disorders typically poses serious infectious complications, which can be exacerbated by the presence of active COVID-19 infection. We report on a case of a successfully treated fit elderly woman with refractory acute myeloid leukemia (AML) who also had mild COVID-19 infection and detectable viral load at the time she was found to have recurrent disease. Prior to initiation of reinduction treatment with cytarabine/idarubicin, this 2-dose COVID-19-vaccinated patient received antiviral therapy with remdesivir with resolution of upper respiratory symptoms. This was followed by sotrovimab on the third day of chemotherapy. Throughout her hospital course, she remained hemodynamically stable with one episode of neutropenic fever without other identified infections. Symptomatic reactivation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 was not observed. After achieving biopsy-confirmed morphologic remission of AML and with neutrophil recovery, the patient gradually cleared the virus, eventually testing negative on polymerase chain reaction test of the nasopharynx. This case underlines the importance of considering initiation of timely chemotherapy, although myelosuppressive, in appropriate patients with aggressive hematologic malignancies and concomitant SARS-CoV-2. It demonstrates management of active COVID-19 infection in this group of patients and the dynamics of SARS-CoV-2 viral load during leukemia treatment.
Bilateral Panuveitis and Exudative Retinal Detachments Associated with Alpelisib
Authors: Chong Yu Jeat , Azzopardi Matthew , Tallouzi Mohammad Omar , Spooner David , Masood Imran , Ghosh Yajati , Sreekantam Sreekanth
Published: August 2022

We report a case of alpelisib-induced uveitis. A 68-year-old female who had recently been given alpelisib for metastatic breast cancer presented with a 2-week history of bilateral worsening vision with a corresponding acute hypermetropic shift. Her unaided visual acuity was 6/60 in both eyes, with bilateral anterior uveitis, non-granulomatous keratic precipitates, posterior synechiae, and limited fundal view. There was also a mild iris bombe configuration, although the intraocular pressures were normal. Ocular ultrasound revealed bilateral uveal effusion, ciliary body congestion, dense vitreous cells, and exudative retinal detachments. These findings were also confirmed on multimodal imaging with widefield fundus photography (Optos) and optical coherence tomography. Based on the clinical features above, a diagnosis of alpelisib-induced panuveitis was diagnosed. She was then admitted and treated with a 3-day course of intravenous methylprednisolone and intensive topical steroids. Her clinical signs and symptoms started to improve, and she was discharged 4 days later. At 1 week of follow-up, her best-corrected visual acuity was 6/12 in both eyes, with broken posterior synechiae and resolution of exudative retinal detachments. This case highlights the importance of early ophthalmology involvement by the oncology team as oncology therapy can have potential unexpected ocular manifestations.
O papel da fase de planejamento na sustentabilidade econômica e social dos serviços de saneamento básico
Authors: Zaccariotto Caio Augusto Santos
Published: August 2022

O presente artigo tem por objetivo aferir a relevância da fase de planejamento nos serviços de saneamento básico, no sentido de se garantir a manutenção da modicidade tarifária e da sustentabilidade econômico-financeira dos contratos, bem como buscará descrever algumas das dificuldades enfrentadas neste processo e as potenciais soluções constantes de seu arcabouço normativo. O método utilizado foi qualitativo e descritivo, com a análise da legislação em vigor, dos planos municipais de saneamento básico de três capitais de estados brasileiros (São Paulo, Belo Horizonte e Goiânia) e da bibliografia sobre o tema do estudo. Ao final, o artigo pretende demonstrar que apenas pela prévia investigação empírica realizada pelos titulares, expressa em plano, poder-se-á adequadamente orientar a regulação e assim ministrar corretamente os mecanismos de intervenção tarifária (subsídios, subvenções e até mesmo isenções), não se permitindo tanto o abandono dos mais necessitados, quanto o enriquecimento sem causa de particulares, e mais importante, garantindo-se caminho mais seguro à consecução dos resultados almejados pelas diretrizes nacionais ao saneamento básico.
Os impactos dos serviços “over the top” no regime de serviço público sob a ótica da colisão entre direitos fundamentais positivados na Constituição da República Federativa do Brasil de 1988
Authors: Woltmann Angelita , Finger Otávio Martins
Published: August 2022

O presente estudo objetiva averiguar os efeitos que os serviços denominados “over the top” podem incitar no regime de serviço público brasileiro, este de titularidade estatal, conforme rege a Constituição Federal de 1988. Com vistas a analisar tais impactos, a pesquisa faz um apanhado histórico da relação entre livre iniciativa e serviço público, bem como se atém à conceituação de serviço “over the top”. Igualmente, analisam-se os atributos do regime de serviço público brasileiro, apurando-se as formas de sua execução, que ocorre diretamente pelo Estado ou por intermédio de empresas delegatárias. Ao final, verifica-se a possibilidade de conciliar os serviços “over the top” com certos serviços públicos, de modo a viabilizar a prestação eficaz das atividades econômicas e beneficiar o consumidor. O método utilizado na pesquisa é o dedutivo, uma vez que, a partir de parâmetros fáticos, legais, doutrinários e jurisprudenciais, conclui-se acerca dos impactos que os serviços inovadores de tecnologia provocam nas atividades tradicionais prestadas em regime de serviço público.
Poder de polícia administrativa e livre exercício de trabalho, profissão e atividades econômicas no cenário pandêmico: reflexões sob a ótica dos princípios da proporcionalidade e motivação
Authors: Finger Otávio Martins
Published: August 2022

Com o advento da pandemia de coronavírus, o poder de polícia estatal foi utilizado de diversas formas pelas administrações públicas, sendo a principal medida adotada a restrição ao funcionamento do comércio, tendo em vista a necessidade de se conter a disseminação do vírus e o contágio das pessoas. Nesse sentido, o presente estudo busca examinar a origem e a extensão do direito fundamental ao livre exercício de trabalho, profissão e atividades econômicas em geral, restringido, no contexto pandêmico, pela imprescindibilidade de proteção de outros direitos de jaez constitucional, como a vida e a saúde coletiva. Ainda, pretende-se analisar a natureza e os limites do poder de polícia do Estado, que, com a ascensão do neoconstitucionalismo e a constitucionalização do direito administrativo, transmuta-se em instrumento de realização de direitos fundamentais, sendo, ao mesmo tempo, moderado por estes direitos. Assim, tendo em vista a necessidade de compatibilizar o uso do poder de polícia administrativa com o direito à liberdade profissional e de exercício de atividades econômicas, bem como com o direito à vida e à saúde, toma-se como parâmetro a ser observado pela Administração Pública os princípios da proporcionalidade e motivação
Modulating Lysine Crotonylation in Cardiomyocytes Improves Myocardial Outcomes
Authors: Cai Wenqian , Xu Dacai , Zeng Chui , Liao Fan , Li Ruiqi , Lin Yingjiong , Zhao Yue , Dong Wenyan , Wang Qingwen , Yang Haili , Wen Daqiang , Gu Jianbiao , Shentu Weihui , Yu Hongkui , Zhang Xiaochun , Wei Jianrui , Duan Jinzhu
Published: August 2022

Background:

Ischemic heart disease is a major global public health challenge, and its functional outcomes remain poor. Lysine crotonylation (Kcr) was recently identified as a post-translational histone modification that robustly indicates active promoters. However, the role of Kcr in myocardial injury is unknown. In this study, we aimed to clarify the pathophysiological significance of Kcr in cardiac injury and explore the underlying mechanism.

Methods:

We investigated the dynamic change of both the Kcr sites and protein level in left ventricular tissues at 2 time points following sham or cardiac ischemia-reperfusion injury, followed by liquid chromatography-coupled tandem mass tag mass spectrometry. After validation of the enriched protein Kcr by immunoprecipitation and Western blot, the function and mechanism of specific Kcr sites were further investigated in vitro and in vivo by gain- or loss-of-function mutations targeting Kcr sites of selected proteins.

Results:

We found that cardiac ischemia-reperfusion injury triggers preferential Kcr of proteins required for cardiomyocyte contractility, including mitochondrial and cytoskeleton proteins, which occurs largely independently of protein-level changes in the same proteins. Those exhibiting Kcr changes were associated not only with disruption of cardiomyocyte mitochondrial, sarcomere architecture, and gap junction but also with cardiomyocyte autophagy and apoptosis. Modulating site-specific Kcr of selected mitochondrial protein IDH3a (isocitrate dehydrogenase 3 [NAD+] alpha) at K199 and cytoskeletal protein TPM1 (tropomyosin alpha-1 chain) at K28/29 or enhancing general Kcr via sodium crotonate provision not only protects cardiomyocyte from apoptosis by inhibiting BNIP3 (Bcl-2 adenovirus E18 19-kDa–interacting protein 3)-mediated mitophagy or cytoskeleton structure rearrangement but also preserves postinjury myocardial function by inhibiting fibrosis and apoptosis.

Conclusions:

Our results indicate that Kcr modulation is a key response of cardiomyocytes to ischemia-reperfusion injury and may represent a novel therapeutic target in the context of ischemic heart disease.
Towards the Perfect Jung
Authors: Karimi Zanjani Asl Mohammad , Durand-Guédy David
Published: August 2022

This article presents a set of four multitext manuscripts made in Tabriz during the reign of the Safavid Shāh Sulaymān (r. 1666–1694). The texts are organized around one core abstruse text (lughuz) penned by the patron of the work, the vizier of Azarbayjan and mustawfī al-mamālik, Ẓahīr al-Dīn Ibrāhīm (d. 1102/1690). Analysis of these manuscripts, copied successively over a period of 12 years by the same hand, reveals the endeavours of the patron and the copyist to produce an artefact that was increasingly refined in terms of layout. The Sackler manuscript is the most recent and also the most accomplished. The amount of time and money put into this project is unusual for a non-royal patron. This editorial project might be linked to Ẓahīr al-Dīn’s political ambitions to find a position or to restore his reputation at the royal court at Isfahan.
Językowo-kulturowy obraz przestrzeni miejskiej Moskwy na przełomie XIX i XX wieku (na bazie słownika W. Jelistratowa)
Authors: Juszczak Bartosz
Published: August 2022

The Linguistic and Cultural Image of the Urban Space of Moscow in the Late Nineteenth and Early Twentieth Centuries (on the Basis of V. Elistratov’s Dictionary) The aim of this article is to reconstruct the linguistic and cultural image of Moscowat the turn of the twentieth century using the paradigm of cultural linguistics. This paradigm was selected as the theoretical framework of the study considering that it practically has not been applied in Russian linguistics. The article shows that the intricate image of the urban space is created by means of cultural elements (the coat of arms, the flag, the bugle call, architecture) and, most of all, linguistic elements whose major exponent is a given urban dialect. It is a wide-ranging construct whose lexis, apart from native elements, also includes a large number of foreign components and proprial (official and unofficial) vocabulary. The conglomerate of these elements can be regarded as a specific language of the urban space. Językowo-kulturowy obraz przestrzeni miejskiej Moskwy na przełomie XIX i XX wieku (na bazie słownika W. Jelistratowa) Artykuł podejmuje się rekonstrukcji językowo-kulturowych elementów przestrzeni miejskiej Moskwy w aspekcie diachronicznym (przełom XIX i XX wieku) przy użyciu metod lingwistyki kulturowej. Zasadność wyboru tego paradygmatu wynika z faktu, iż na gruncie językoznawstwa rosyjskiego nie jest on uprawiany. Artykuł pokazuje, że na skomplikowany obraz przestrzeni miejskiej składają się aspekty kulturowe (architektura, herb, hejnał, flaga), a przede wszystkim językowe (dialekt miejski, zapożyczenia obce, nieoficjalna urbanonimia). Wszystkie te elementy tworzą uniwersalny język przestrzeni, który może być zestawiany z innymi miastami Słowiańszczyzny.
Hurricane Ida (2021): Rapid Intensification Followed by Slow Inland Decay
Authors: Zhu Yi-Jie , Collins Jennifer M. , Klotzbach Philip J. , Schreck Carl J.
Published: August 2022

Hurricane Ida recently became one of the strongest hurricanes to hit Louisiana on record, with an estimated landfalling maximum sustained wind of 130 kt (1 kt ≈ 0.51 m s−1). Although Hurricane Ida made landfall at a similar time of year and landfall location as Hurricane Katrina (2005), Ida’s postlandfall decay rate was much weaker than Hurricane Katrina. This manuscript includes a comparative analysis of pre- and postlandfall synoptic conditions for Hurricane Ida and other historical major landfalling hurricanes (category 3+ on the Saffir–Simpson hurricane wind scale) along the Gulf Coast since 1983, with a particular focus on Hurricane Katrina. Abundant precipitation in southeastern Louisiana prior to Ida’s landfall increased soil moisture. This increased soil moisture along with extremely weak overland steering flow likely slowed the storm’s weakening rate postlandfall. Offshore environmental factors also played an important role, particularly anomalously high nearshore sea surface temperatures and weak vertical wind shear that fueled the rapid intensification of Ida just before landfall. Strong nearshore vertical wind shear weakened Hurricane Katrina before landfall, and moderate northward steering flow caused Katrina to move inland relatively quickly, aiding in its relatively fast weakening rate following landfall. The results of this study improve our understanding of critical factors influencing the evolution of the nearshore intensity of major landfalling hurricanes in the Gulf of Mexico. This study can help facilitate forecasting and preparation for inland hazards resulting from landfalling hurricanes with nearshore intensification and weak postlandfall decay.
Indispensable for dispensation: The agency and experience of Buddhist nuns in the early history of the bhikkhunī saṅgha
Authors: Chaturvedi Neekee
Published: August 2022

The entry of women into Buddhist monasticism was permitted with great reluctance and a special set of rules. Within the disciplinary framework of institutional subordination, Buddhist nuns created spaces that provided women with spiritual opportunities away from social and domestic ties. Although monks dominated both the Buddhist saṅgha and religious texts, the earliest nuns worked assiduously and creatively to strengthen their practice. This article explores early Buddhist texts to unravel gendered monastic experiences. The nuns could not have registered a vital presence in the history of Buddhism if they had remained passive members. Social relations before they joined the order, as well as the newly forged bonds within, played a significant role in their progress in comprehending and observing spiritual practices. When seen on their own terms, the position and contribution of nuns appear stronger and more agentive than has been usually assumed.
Examining Interactive Effects of PTSD and Deviant Peer Association for Predicting Violent Offending Risk
Authors: Wojciechowski Thomas
Published: August 2022

Post-traumatic stress disorder and deviant peer association have been identified as robust risk factors predicting violent offending. However, there is a dearth of research which has examined interactive effects of these constructs for predicting violence perpetration. The present study utilized data from the Pathways to Desistance study to test for effects. Logistic regression was utilized to examine relationships. Results indicated that there was a significant and positive interaction between post-traumatic stress disorder and deviant peer association for predicting violent offending. Further examination of this relationship indicated that the disorder was a “for better or worse” condition, with low violent offending risk at low levels of deviant peer association and high risk at high levels of deviant peer association.
Customer Orientation and Financial Performance: Women in Top Management Teams Matter!
Authors: Srivastava Chandra , Kashmiri Saim , Mahajan Vijay
Published: August 2022

Using a longitudinal analysis of publicly traded Fortune 500 firms, the authors find support for their hypotheses that a relative increase in female influence in the top management team (FITMT) is positively associated with (1) customer orientation of the firm and (2) long-term financial performance (i.e., Tobin's q). They demonstrate that customer orientation partially mediates the relationship between FITMT and long-term financial performance. The authors also explore environmental and corporate governance factors that moderate the link between FITMT and customer orientation. They find that this link is attenuated for firms that operate under high environmental dynamism and low environmental discretion, and for firms with high family ownership. Having high female representation among board members and more marketing-experienced board members strengthens the link between FITMT and customer orientation. These findings have important implications for scholars, boards, chief executive officers, and investors interested in identifying environmental and corporate governance factors that facilitate a greater focus on customers at the highest levels of the firm.
Theorizing Māori-Philippine solidarities through agential realism and punk rock pedagogy
Authors: Romero Noah , Estellés Marta , Grant Wairehu
Published: August 2022

This article utilizes looks to punk rock pedagogy or the ways in which countercultural and decolonial ontologies are developed in punk subculture, to theorize Māori-Philippine relations in Aotearoa New Zealand. It uses an agential realist methodology to engage with the creative works of TOOMS, James Roque, and Marianne Infante (three New Zealand performing artists of Philippine ancestry). These works read through historiographic accounts of the Philippine diaspora to theorize how contemporary independent artists are reviving the ancestral bonds that once linked the Philippines and the Pacific. Theorizing Māori-Philippine relations through punk rock shows what Indigenous and immigrant peoples stand to gain when they decenter the colonizer and prioritize communing with one another.
Youth Perspectives on Barriers and Opportunities for the Development of a Peer Support Model to Promote Mental Health and Prevent Suicide
Authors: Libon Jackie , Alganion Jarlo , Hilario Carla
Published: August 2022

Suicide prevention is a public health priority. The purpose of this study was to elicit and document the perspectives of youth (ages 15–24) on the development of a peer support model for mental health promotion and suicide prevention for youth in small communities in western Canada. A qualitative descriptive approach informed by a socioecological framework was used to conduct the study. Eleven youth participated in a series of three co-design workshops. Data collection was conducted remotely using Zoom. Data were analyzed using thematic analysis. The following three themes are identified: (a) contextual factors for youth; (b) community spaces and social media; and (c) apps and integrated care. These themes elucidated challenges faced by the youth, strategies for reducing barriers for youth who need support, and opportunities for enhancing youth mental health through responsive community-identified services. Overall, youth were supportive of the potential use of peer support to augment services in their communities.
How Much Does Migration Affect Labor Supply in Europe? Methodological Insights and Contemporary Evidence from the European Union and Selected European Countries
Authors: Bagavos Christos
Published: August 2022

In Europe, the slowdown in working-age population growth and population aging pose challenges, particularly vis-à-vis the current and future volume of labor supply. Throughout the 2010s, these demographic transformations took place against a backdrop of increasing migration flows and stocks. This IMR Research Note aims to enrich the discussion of the aforementioned issues and to provide methodological and empirical evidence on the role of migration stocks in shaping changes over time in two main aspects of the European labor supply: the size of the labor force and aggregate labor force participation rates from 2006 to 2018. Based on annual LFS data, we use a mixed standardization and decomposition method to determine to what extent trends in the European labor supply are driven over time by changes in population or in labor force participation rates within specific groups selected on the basis of age, gender, birth country (native- versus foreign-born), and origin country (European Union versus non-European Union). Our Research Note points out that, despite the upward trend in the labor force participation rates of native-born women and of native-born persons aged 55 years and over, the increase in labor supply in the European Union and in the 10 European countries under study in this article between 2006 and 2018 was driven by foreign-born persons. These developments suggest that, in a context of political desire for less migration, international migration has become a structural feature of European labor markets.
Fringe nobles and boundary maintenance: An exploration
Authors: Winzler Tim
Published: August 2022

This article explores a sub-group of elites at the border to non-elites that I shall call fringe nobles. It develops the theoretical interest in this group, understood as a structural ideal-type. It then fleshes out the characteristics of it with the help of historical examples of relational studies of fringe nobles before complementing this with a case-study on study motivation of German fringe noble economics students. The habitus of this group is characterized by a taste for purification and field-specific extreme positions – in the field of contemporary economics, this seems expressed by the likely uptake of an ultraliberal position. The article then goes on to explore the links of this position-taking with a specific feeling of threat before turning to the position-taking of fringe noble economists in the field of politics. The article concludes with a plea for a sociology of fringe nobles by formulating further empirical and theoretical questions.
Losing Sight of Piecemeal Progress: People Lump and Dismiss Improvement Efforts That Fall Short of Categorical Change—Despite Improving
Authors: O’Brien Ed
Published: August 2022

Fourteen experiments ( N = 10,556 adult participants, including more than 20,000 observed choices across 25 issues) documented how people perceive and respond to relative progress out in the world, revealing a robust “negative-lumping” effect. As problematic entities worked to better their ways, participants shifted to dismiss them if they fell short of categorical reform—despite distinctions in improvement. This increased dismissal of relative gains as “all the same” was driven by the belief that falling short signals an eschewal of doing the bare minimum and lacking serious intent to change, making these gains seem less deserving of recognition. Critically, participants then “checked out”: They underrewarded and underinvested in efforts toward “merely” incremental improvement. Finally, in all experiments, participants lumped together absolute failures but not absolute successes, highlighting a unique blindness to gradations of badness. When attempts to eradicate a problem fail, people might dismiss smaller but critical steps that were and can still be made.
Utilizing blood filter paper and ear punch samples for the detection of rabbit hemorrhagic disease virus 2 by RT-rtPCR
Authors: Jennings-Gaines Jessica E. , Luukkonen Katie L. , Robbins Kara M. , Edwards William H. , Vogt Nadine A. , Vogt Adam A. , Allen Samantha E.
Published: August 2022

Rabbit hemorrhagic disease virus 2 (RHDV2), a virulent and contagious viral pathogen that affects wild and domestic lagomorph populations, was identified in Wyoming, USA in December 2020. A surveillance program was developed involving full-carcass submission and liver analysis, although carcass quality as a result of predation and decomposition impeded analysis. To increase the number of submissions and provide flexibility to field staff, we evaluated 2 sample types: 77 dried blood on filter paper samples, 66 ear punch samples. At initial sampling, test specificity and sensitivity of the RT-rtPCR utilizing dried blood on filter paper and ear punch samples were both 100% compared to liver. Filter paper results were consistent over time; sensitivity stayed >96% through weeks 2, 4, and 6, with a maximum mean difference of 6.0 Ct from baseline liver Ct values (95% CI: 5.0–7.3) at 6 wk. Test sensitivity of the ear punch sample at 1, 3, 5, and 7 wk post-sampling remained at 100%, with a maximum mean difference of 5.6 Ct from baseline liver Ct values (95% CI: 4.3–6.9) at 5 wk. Filter paper and ear punch samples were suitable alternatives to liver for RHDV2 surveillance in wild lagomorph populations. Alternative sampling options provide more flexibility to surveillance programs, increase testable submissions, and decrease exposure of field personnel to zoonotic disease agents.
Anatomical Study of Domain Rescue of Palatal Length in Patients With a Wide Cleft Palate: Buccal Flap Reconstruction in Primary Palatoplasty
Authors: Morrison Kerry A. , Park Jenn , Rochlin Danielle , Lico Margaret , Flores Roberto L.
Published: August 2022

Background

This study characterizes the potential loss of velar length in patients with a wide cleft and rescue of this loss of domain by local flap reconstruction, providing anatomic evidence in support of primary lengthening of the soft palate during palatoplasty.

Methods

A retrospective review was conducted of all patients with a cleft palate at least 10mm in width, who underwent primary palatoplasty with a buccal flap prior to 18 months of age over a 2-year period. All patients underwent primary palatoplasty with horizontal transection of the nasal mucosa, which was performed after nasal mucosa repair, but prior to muscular reconstruction. The resulting palatal lengthening was measured and the mucosal defect was reconstructed with a buccal flap.

Results

Of the 22 patients included, 3 (13.6%) had a history of Pierre Robin sequence, and 5 (22.7%) had an associated syndrome. No patients had a Veau I cleft, 7 (31.8%) had a Veau II, 12 (54.5%) had a Veau III, and 3 had (13.6%) a Veau IV cleft. All patients had a right buccal flap during primary palatoplasty. The mean cleft width at the posterior nasal spine was 10.6  ±  2.82mm, and mean lengthening of the velum after horizontal transection of the nasal mucosa closure was 10.5  ±  2.23mm. There were 2 (9.1%) fistulas, 1 (4.5%) wound dehiscence, 1 (4.5%) 30-day readmission, and no bleeding complications.

Conclusions

Patients with a wide cleft palate have a potential loss of 1cm velar length. The buccal flap can rescue the loss of domain in palatal length, and potentially improve palatal excursion.
Upadacitinib for the Treatment of Rheumatoid Arthritis: An Extensive Review
Authors: Boyce Eric G. , Rogan Edward L. , C. Lui May
Published: August 2022

Objectives:

To review the characteristics, efficacy, safety, pharmacoeconomics, and place in therapy of upadacitinib, a Janus kinase (JAK) inhibitor, in the treatment of rheumatoid arthritis (RA).

Data Sources:

PubMed (January 2003-May 2022) was searched using upadacitinib and ABT-494.

Study Selection and Data Extraction:

Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety data.

Data Synthesis:

In randomized, double-blind, controlled clinical studies, upadacitinib demonstrated statistically significant improvement in RA symptoms as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) when compared with csDMARD monotherapy or to adalimumab or abatacept in combination with csDMARD therapy in patients with RA. American College of Rheumatology 20% response rates were 68% to 79% for upadacitinib monotherapy and 64% to 84% for upadacitinib plus csDMARD therapy, compared with 28% to 59% for csDMARD-only therapy and 63% to 74% for biologic DMARD (bDMARD) plus csDMARD therapy. Long-term extension studies demonstrated similar findings. Upadacitinib had similar rates of serious infections, herpes zoster, major cardiovascular events, and venous thromboembolic events as other JAK inhibitors. Upadacitinib was similar in cost to tofacitinib and twice as high as baricitinib based on current estimated costs to patients, but actual costs may vary.

Relevance to Patient Care and Clinical Practice:

Upadacitinib is an alternative therapy to other JAK inhibitors and bDMARDs in patients with moderate to severe RA who have had an inadequate response to a tumor necrosis factor inhibitor alone or in combination with a csDMARD.

Conclusions:

Upadacitinib is an effective JAK inhibitor for use in RA.
Intravenous route for folate supplementation in a patient with celiac disease treated by pemetrexed-based chemotherapy for non-small-cell lung cancer
Authors: Beaurain Marie , Rioufol Catherine , Vantard Nicolas , Teixeira Alexandre , Baudouin Amandine , Herledan Chloe , Souquet Pierre-Jean , Couraud Sebastien , Ranchon Florence
Published: August 2022

Introduction

Oral folic acid supplementation is essential for patients treated with pemetrexed, to prevent the risk of severe hematologic toxicity. In case of intestinal absorption disorder, no recommendations exist for intravenous folic acid supplementation.

Case report

We describe a 74-year-old patient with multimetastatic non-small-cell lung adenocarcinoma, receiving first-line chemotherapy with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg intravenously every 3 weeks. The patient presented neglected celiac disease, resulting in malabsorption syndrome with iron and folic acid deficiency. The question was how to administer folic acid supplementation during the pemetrexed-based chemotherapy.

Management and outcomes

Intravenous injection of 200 mg levoleucovorin on day 1 of cycle 1 of pemetrexed-based chemotherapy was administered and well tolerated. During the second cycle, the levoleucovorin perfusion was not renewed by omission. The patient was hospitalized for 7 days because of febrile aplasia. Piperacillin–tazobactam was started, and then switched to amoxicillin–clavulanate plus ciprofloxacin. After this episode of post-chemotherapy febrile aplasia, it was decided to systematically supplement the patient with intravenous levoleucovorin, with blood folate concentration monitoring at each cycle. At 16 months after start of treatment, the patient was in complete remission, indicating that the immune-chemotherapy was effective, with no further febrile neutropenia.

Discussion/conclusion

This case report highlights intravenous levoleucovorin supplementation as an alternative to oral folic acid if needed during pemetrexed–antifolate-based chemotherapy.
Lethality of Police Shootings and Proximity to Trauma Centers
Authors: Hanink Peter A. , Renner Matthew , Bates Christopher J.
Published: August 2022

Studies of police shootings have typically focused upon demographic characteristics, police departmental characteristics, or more traditionally criminological characteristics such as crime rate. We use police shooting incidents to examine what role a less examined factor—proximity to a trauma center—has on whether the injured civilian dies or survives. We improve on previous work by estimating both distances and drive times along road networks. Findings from this study underscore the importance of prevention of police shootings, compared to after the fact responses, for reducing the numbers of homicides by police.
An engineering drag losses model for rolling bearings
Authors: Morales-Espejel G. E. , Wemekamp A. W.
Published: August 2022

Rolling bearing friction is an important measure of bearing performance. With increasing industrial trends of energy savings and CO2 footprint reduction, rolling bearing friction has become a very important parameter in the machinery design and selection process. Particular importance have high-speed applications like spindles or electrical vehicle traction drives and gearboxes. Since handling thermal effects has become an important problem to solve in these applications, oil lubrication is gaining interest due to its cooling capacity. Bearing friction is made of rolling, sliding and drag losses components in oil lubricated bearings. In this paper the emphasis is given to the drag losses component, which becomes the most critical in oil bath in medium and high-speed applications. An engineering model is derived for the calculation of this component for medium and potentially high speeds. The results are compared with experimental measurements (in-house and literature). In general, good agreement is found between the engineering model and the experimental results.
Re-thinking brand extension theory: Parents, siblings and off-spring or landlords and tenants?
Authors: Hede Anne-Marie , Kerrigan Finola , Thyne Maree
Published: August 2022

Brand extensions strategies are aimed at extracting further value from an existing brand. The brand family metaphor, which has resonated with marketing scholars and practitioners for decades, has promulgated the use of analogies such as parents, siblings and off-spring to describe resulting brand-to-brand relationships. In this paper however, we question whether this metaphor and its analogical mappings, still hold relevance given we are in an ‘era of liquid modernity’ (Bauman, 2000) where notions of family may be less prescriptive. Through our analysis of interview data with practitioners who work on literary film adaptations, we found that the relationships among original and extended brands may be better conceptualised using an alternative metaphor: ‘brand for rent’. Our analysis revealed that in many contemporary brand-to-brand relationships, the relationship between the two brands is not solid, but rather fluid with a ‘distance’ between them; and the relationship contractual rather than familial. Our findings indicate that this alternative metaphor may have particular merit as marketplaces adapt to increasingly fluid contexts, where novel brand extension strategies and brand-to-brand relationships are emerging. We suggest further exploration of the metaphor and consideration of others, to further assist to theorise the diversity in contemporary brand extension practice.
Emplacing category dynamics: Houselessness and the emergence of transitional micro-housing villages
Authors: Awad Mohamed Hassan
Published: August 2022

Recent studies suggest a critical yet unexplored role for local places such as cities and communities in category research. In this study, I investigate how places, as the nexus of cultural, political, and material influences, can shape category dynamics, especially in the early phases of category emergence. I synthesize insights from category work with recent conceptualizations of places as geographically bounded spaces, imbued with meanings and material forms. I conducted an in-depth qualitative field study of the emergence and expansion of a new category, transitional micro-housing villages, also known as Tiny Home Villages, in Eugene, a mid-size city in the United States in 2011–2019. The study unpacks the role of nested places in triggering, enabling, and constraining actors and their work to create, legitimate, and expand a category. Specifically, I highlight the role of local material forms and how actors can mobilize local spaces, technologies, and practices to advance their goals in contested category dynamics.
Effectiveness of treatment for 31 patients with seropositive autoimmune autonomic ganglionopathy in Japan
Authors: Hayashi Toshiyuki , Nakane Shunya , Mukaino Akihiro , Higuchi Osamu , Yamakawa Makoto , Matsuo Hidenori , Kimura Kazumi
Published: August 2022

Background:

Autoimmune autonomic ganglionopathy (AAG) is characterized by serum autoantibodies against the ganglionic acetylcholine receptor (gAChR). Immunomodulatory treatments may alleviate AAG symptoms, but the most appropriate treatment strategy is unclear.

Objective:

This study aimed to confirm the effectiveness of treatments, particularly immunotherapy, in patients with seropositive AAG in Japan, as well as to determine the most effective treatment and the best assessment method for clinical response to treatment.

Methods:

We collected data from a previous cohort study of patients with seropositive AAG. The clinical autonomic and extra-autonomic symptoms were objectively counted and subjectively assessed using the modified Composite Autonomic Symptom Score. Post-treatment changes in the gAChR antibody level were evaluated.

Results:

Thirty-one patients received immunotherapy. Among them, 19 patients received intravenous methylprednisolone; 27, intravenous immunoglobulin; 3, plasma exchange; 18, oral steroids; 2, tacrolimus; 1, cyclosporine; and 1, mycophenolate mofetil. Patients who received immunotherapy showed improvements in the total number of symptoms (from 6.2 ± 2.0 to 5.1 ± 2.0) and modified Composite Autonomic Symptom Score (from 37.4 ± 15.3 to 26.6 ± 12.8). Orthostatic intolerance, sicca, and gastrointestinal symptoms were ameliorated by immunotherapy. Immunotherapy decreased the antibody levels (gAChRα3 antibodies, from 2.2 ± 0.4 to 1.9 ± 0.4, p = 0.08; gAChRβ4 antibodies, from 1.6 ± 0.1 to 1.0 ± 0.2, p = 0.002), but antibody levels increased in 10 patients despite immunotherapy. The rate of improvement in the total number of symptoms was higher in patients with combined therapy than in patients with non-combined therapy (70.7% vs 28.6%).

Conclusions:

The scores in many items on the rating scale decreased after immunotherapy in patients with seropositive AAG, particularly in the combined immunotherapy group. However, more accurate assessment scales for clinical symptoms and multicenter randomized, placebo-controlled prospective studies are warranted to establish future treatment strategies.
Cost-effectiveness analysis of nivolumab plus ipilimumab versus chemotherapy as the first-line treatment for unresectable malignant pleural mesothelioma
Authors: Yang Liu , Cao Xueqiong , Li Na , Zheng Bin , Liu Maobai , Cai Hongfu
Published: August 2022

Introduction:

This study evaluated the cost-effectiveness of nivolumab plus ipilimumab (NI) versus pemetrexed plus cisplatin/carboplatin (C) as the first-line treatment for unresectable malignant pleural mesothelioma (MPM) from the perspective of US payers.

Methods:

A 10-year partitioned survival model was constructed using survival and safety data from the CheckMate 743 clinical trial. The output metrics of the model included the patient’s lifetime quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results.

Results:

Among all randomized patients, group NI had an ICER of $475,677/QALY relative to group C. Among patients with epithelioid histology, group NI had an ICER of $760,955/QALY. Among patients with non-epithelioid histology, group NI had an ICER of $418,348/QALY. The ICERs of all three populations exceeded the willingness-to-pay threshold ($150,000). The results of one-way sensitivity analysis revealed that the cost of nivolumab had a great influence on the results. The results of probabilistic sensitivity analysis demonstrated that the possibility of NI being more economical in all randomized patients and in patients with non-epidemiology histology was 0. In patients with epithelioid histology, the probability that NI had an economic advantage was 0.6%.

Conclusions:

From the perspective of US payers, in patients with unresectable MPM, NI has no economic advantage over C.