bluuebunny/crossref_metadata_2025 huggingface dataset:
The citizen as mere human: Litigating denationalization in post-9/11 UK
Authors: Hong Caylee
Published: July 2020

Since the publication of The Origins of Totalitarianism in 1951, Hannah Arendt’s phrase the ‘right to have rights’ and her claim that having rights depends on belonging to and being recognized by ‘some kind of organized community’ have become key provocations on citizenship, statelessness and human rights. Arendt, however, has been criticized as perpetuating a state-centric framework that scholars and activists alike have sought to reimagine. In particular, the French political theorist Jacques Rancière argues that Arendt’s ‘right to have rights’ formula is based on an artificial distinction between the social and the political, which creates an overly narrow definition of the political subject. This article contends that in the post-9/11 era, the distinction, often attributed to Arendt, between ‘Man’ and ‘Citizen’ is increasingly blurred; yet it suggests that this blurring does not necessarily offer any emancipatory potential. It argues that while national citizenship is still meaningful, being a citizen may not be so different from being a mere human in certain contexts. The article examines three sets of cases shaping the United Kingdom’s ‘regime of nationality deprivation’ in which people are stripped of their UK citizenship for terrorism-related offences: Al-Jedda (2013), Pham (2015, 2018) and K2 (2015). First, it explores the tensions in the regime’s attempt to reconcile a fundamental inconsistency between the recognition of the human right to nationality and the sovereignty of the state to define the citizen; and second, it considers the regime’s spatial control of the denationalization process whereby denationalization orders are commonly issued and thus also contested when the targeted citizen is outside the UK’s jurisdiction.
High atherogenic index of plasma and cardiovascular risk factors among Ghanaian breast cancer patients
Authors: Tagoe Emmanuel A , Dwamena-Akoto Eric , Nsaful Josephine , Aikins Anastasia R , Clegg-Lamptey Joe-Nat , Quaye Osbourne
Published: July 2020

Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated ( P < 0.05) in the breast cancer patients compared to the controls, but the reverse was observed for high-density lipoprotein cholesterol (HDL-c) ( P < 0.01). Obesity (odds ratio [OR] = 2.51, P = 0.015), hypertension (OR = 4.04, P < 0.001), AIP (OR = 10.44, P < 0.001), and dyslipidemia ( P < 0.01) were significantly associated with breast cancer. AIP correlated positively with age (r = 0.244, P < 0.05), body mass index (r = 0.225, P < 0.05), blood pressure ( P < 0.01), T. chol (r =0.418, P< 0.01), and TG (r = 0.880, P < 0.01), but inversely correlated with HDL-c (r = −0.460, P < 0.01). A greater proportion (88%) of the patients presented with advanced breast cancer. AIP and cardiovascular risk factors were high in the breast cancer patients. Considering that AIP and cardiovascular disease risk factors are of interest in breast cancer patients, further studies are needed to understand the effect of AIP and cardiovascular risk factors on breast cancer outcomes.
The Influence of Aortic Wall Elasticity on the False Lumen in Aortic Dissection: An In Vitro Study
Authors: Veger Hugo T. C. , Pasveer Erik H. , Westenberg Jos J. M. , Wever Jan J. , van Eps Randolph G. Statius
Published: July 2020

Background:

Hemodynamics, dissection morphology, and aortic wall elasticity have a major influence on the pressure in the false lumen. In contrast to aortic wall elasticity, the influence of hemodynamics and dissection morphology have been investigated often in multiple in vitro and ex vivo studies. The purpose of this study was to evaluate the influence of aortic wall elasticity on the diameter and pressure of the false lumen in aortic dissection.

Methods:

An artificial dissection was created in 3 ex vivo porcine aortas. The aorta models were consecutively positioned in a validated in vitro circulatory system with physiological pulsatile flow. Each model was imaged with ultrasound on 4 positions along the aorta and the dissection. At these 4 locations, pressure measurement was also performed in the true and false lumen with an arterial catheter. After baseline experiments, the aortic wall elasticity was adjusted with silicon and the experiments were repeated.

Results:

The aortic wall elasticity was decreased in all 3 models after siliconizing. In all 3 siliconized models, the diameters of the true and false lumen increased at proximal, mid, and distal location, while the mean arterial pressure did not significantly change.

Conclusions:

In this in vitro study, we showed that aortic wall elasticity is an important parameter altering the false lumen. An aortic wall with reduced elasticity results in an increased false lumen diameter in the mid and distal part of the false lumen. These results can only be transferred to corresponding clinical situations to a limited extent.
Infectious Flexor Tenosynovitis Following Trigger Finger Release: Incidence and Risk Factors
Authors: Stewart Christopher N. , Ward Christina M.
Published: July 2020

Background: Trigger finger release (TFR) is one of the most commonly performed hand procedures and typically results in restoration of normal finger function. However, uncommon postoperative complications such as deep infection can have devastating consequences. The goal of this study was to evaluate the incidence, risk factors, and characteristics of infectious flexor tenosynovitis occurring after TFR. Methods: We searched billing records for the Current Procedural Terminology code for TFR to identify all adult patients who underwent TFR at our institution over a 10-year period. We defined infectious tenosynovitis as any case where the patient underwent tendon sheath drainage or postoperative wound debridement within 6 months of the index TFR procedure. Medical records were reviewed to obtain patient demographic information, body mass index (BMI), tobacco use, history of diabetes mellitus, surgical setting (clinic vs outpatient surgery center), and surgical digit for all patients. In those patients treated for infection, we recorded hospital length of stay, number of operative procedures, and any culture results. Results: We identified a total of 18 infections out of 2307 procedures (1827 patients), for an incidence of 0.99%. Current smokers had a significantly higher incidence of infection than nonsmokers (1.77% vs 0.29%). On univariate analysis, smoking was closely associated with infection ( P ≤ .05). All infections occurred in overweight or obese patients by BMI criteria, but there was no difference in average BMI between patients with and without infection. History of diabetes, in-office surgery, patient age, and patient sex were not associated with a higher incidence of infection. Patients with infections spent an average of 4.1 days in the hospital, and 40% required multiple surgical procedures. The most common infectious organism cultured was Staphylococcus aureus, which was present in 67% of infections. Patients with isolated methicillin-sensitive S aureus on culture showed signs of infection within 3 weeks of the index procedure, whereas polymicrobial, coagulase-negative staphylococci or beta hemolytic streptococci were identified in patients presenting with infectious symptoms later. Conclusion: Infections after TFR are uncommon but are more likely to occur in patients who are current smokers and overweight or obese by BMI criteria. Methicillin-sensitive S aureus is the most likely causative organism, especially in patients presenting during the early postoperative course.
Relationship Between Morphological Change of Median Nerve and Clinical Outcome Before and After Open Carpal Tunnel Release: Ultrasonographic 1-Year Follow-up After Operation
Authors: Tajika Tsuyoshi , Kuboi Takuro , Endo Fumitaka , Chikuda Hirotaka
Published: July 2020

Background: The aims of this study were 2-fold: (1) to assess the morphological change of the median nerve in patients with carpal tunnel syndrome (CTS) preoperatively and at 6 and 12 months postoperatively; and (2) to analyze correlation between the changes in ultrasonographic findings and the changes in clinical findings after surgical decompression. Methods: Of the 28 patients with CTS, 34 wrists were treated with open carpal tunnel release. We evaluated them using the Boston questionnaire, Japanese Society for Surgery of the Hand Version of the Quick Disability of the Arm, Shoulder, and Hand questionnaire, nerve conduction study (NCS), and ultrasound preoperatively and at 6 and 12 months postoperatively. We measured the cross-sectional area (CSA) of the median nerve at the level of the proximal inlet of the carpal tunnel (CSAc) and more proximally at the level of the distal radioulnar joint (CSAd). Paired t tests and repeated measures analysis of variance of ranks were used to identify changes over time. The Spearman correlation coefficient by rank test was used for the analysis of the relation between the amount of change of CSA and the patient-rated questionnaire score and NCS findings. Results: Findings for CSAc, CSAd, and NCS and patient-rated outcomes at 6 and 12 months postoperatively were significantly lower than their preoperative values. However, no significant correlation was found between the postoperative changes in CSAc, CSAd, and clinical variables obtained preoperatively and postoperatively. Conclusions: Evaluation of sonographic imaging might not be helpful for assessing clinical conditions in patients with CTS after surgical decompression.
Protective Effect of Metformin on Sepsis Myocarditis in Zebrafish
Authors: Zhang Mingming , Sun Wei , Du Jianan , Gou Yawei , Liu Lingling , Wang Ruonan , Xu Xuesong
Published: July 2020

Purpose:

We found in previous study that metformin could treat sepsis myocarditis in a mouse model. We employed the zebrafish model organism to investigate the effect of metformin on sepsis myocarditis.

Methods and Results:

Wild-type zebrafish was used to establish a sepsis myocarditis model and combined with image software analysis and cytokine detection, the protective dose of metformin was determined. The results showed that immersion with Escherichia coli could cause 75% mortality in zebrafish and make larvae appear as characteristics of severe sepsis myocarditis. Pretreatment with 10 mM metformin for 3 hours could effectively reduce heart congestion and swelling in zebrafish with sepsis myocarditis and increased the heart rate. It could reduce the mortality and prolong the survival time of zebrafish with sepsis myocarditis; Tg(mpx: EGFP) transgenic zebrafish were adopted to explore the number of neutrophils in zebrafish heart before and after metformin protection, and metformin could maintain the number of neutrophils in zebrafish heart; quantitative real-time reverse transcription–polymerase chain reaction showed that metformin could reduce the expression of pro-inflammatory factors, tumor necrosis factor-α and interleukin (IL)-6, and could promote the anti-inflammatory factor, transforming growth factor-β and IL-10 expression.

Conclusion:

We established a zebrafish sepsis myocarditis model and applied metformin in advance to provide a protective effect on the zebrafish heart.
Effect of roller bearing elasticity on spiral bevel gear dynamics
Authors: Hua Xia , Chen Zaigang
Published: July 2020

The dynamics of spiral bevel gears have gained increasing importance due to concerns relating to noise and durability. This is because the mesh force acting on the gear teeth is amplified under dynamic conditions, potentially reducing the fatigue life of the gears. Furthermore, a sizable dynamic force can be transmitted to the housing, inducing structure-born gear whine. The elasticity of the bearings can influence the dynamics of spiral bevel gears. In this article, the finite element formulation of a spiral bevel geared rotor dynamic system is applied to investigate the influence of bearing elasticity on the dynamics of spiral bevel gears. The designs and configurations of rear axles are modeled and analyzed for real-world applications, to gain an enhanced practical understanding of the effect of bearing stiffness on spiral bevel gear dynamics.
Positive youth development related athlete experiences and coach behaviors following a targeted coach education course
Authors: MacDonald Dany J , Camiré Martin , Erickson Karl , Santos Fernando
Published: July 2020

The purpose of this study was to examine if a positive youth development (PYD) coach education course would (i) result in more positive developmental experiences perceived by athletes of participant coaches and (ii) increase the frequency of PYD-oriented behaviors exhibited by participant coaches. A total of 14 coaches and 270 athletes participated in the study. Eight coaches ( Mage = 38.0 years) overseeing 154 athletes ( Mage = 13.8 years) were in the control group, while six coaches ( Mage = 36.7 years) overseeing 116 athletes ( Mage = 13.9 years) were in the experimental group. The 10-week intervention combined a group-based PYD coach education course with individualized coach meetings. Seven practices per coach were observed and recorded at baseline ( n = 2), intervention ( n = 3), and follow-up ( n = 2). Athletes completed measures of coach-athlete relationships and sport experiences at the three time points. Results of the 2 × 3 (group × time) mixed ANOVAs demonstrated that coaches in the intervention group increased the frequency of their PYD-oriented behaviors during the intervention but returned to levels slightly above baseline at follow-up. Coaches in the control group did not change their behaviors over the same period. Athlete reports of their developmental experiences were high at all time points and did not change over time. Findings suggest PYD coach education has the potential to influence coach behavior, but further research is required to determine how to create sustained changes for coaches and increases in athletes’ perceived positive developmental experiences.
Effects of a Matrine- and Sophoridine-Containing Herbal Compound Medicine (AH-05) on Liver Cancer
Authors: Li Yanchu , Chen Lu , Pu Rong , Zhou Lu , Zhou Xufeng , Li Xianyong
Published: July 2020

Herbal medicine can present an alternative way of treating liver cancer. Here, we explored a matrine- and sophoridine-containing herbal compound medicine (AH-05) extracted from Adenophora capillaris, Sophora flavescens, Astragalus, and other plants. H22 and HepG2 cell models, as well as an H22 xenograft model, were established. Cell proliferation and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The activation of AKT/mTOR and nuclear factor-κB (NF-κB) pathways in tumor cells and the polarization of CD4/CD8 T cells in the spleen were tested. To assess safety, hematological toxicity and pathology of the liver, kidney, spleen, and intestine were evaluated. AH-05 inhibited cell viability in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the activation of NF-κB p50, NF-κB p65, AKT, p-AKT Ser473, and mTOR was suppressed. In addition, AH-05 promoted CD4+ T cell polarization in the spleen. With regard to safety, slight intestinal mucosa edema was observed, but no severe pathological or hematological toxicity was detected. AH-05 exhibited its therapeutic effects against liver cancer by regulating the AKT/mTOR and NF-κB signaling pathways, and the immune environment, by promoting CD4+ T cell polarization in the spleen. Thus, AH-05 represents a potential supplementary herbal compound medicine for liver cancer.
Response and closure to: A comment on “Constant deceleration approach for the penetration analysis of rigid projectiles into concrete targets: Revisited” by D.Z. Yankelevsky and V.R. Feldgun, Int. J. Prot. Struct., pp. 1–18 (2020)
Authors: Yankelevsky David Z , Feldgun Vladimir R
Published: July 2020

The purpose of this discussion and closure is to address the comments presented by Rosenberg, Dekel, and Kositski on our paper (Yankelevsky and Feldgun). Our paper aimed at revisiting the constant deceleration approach for the penetration analysis of rigid projectiles into concrete. Their comments claim for inaccuracies and misleading statements that are responded in our present discussion. We clarify that the constant deceleration approach cannot represent the penetration in concrete. We discuss their comments and highlight their inaccuracies and incorrect statements and point out at the weaknesses and limitations of the constant deceleration approach. We hope that our clarifications and discussion will help to improve the suggested constant deceleration approach, enhance the awareness to its limitations, and direct to approaches that do consider the variable deceleration time history of the projectile motion in concrete.
Rare male cancers: Effect of social deprivation on a cohort of penile cancer patients
Authors: Rewhorn Matthew J , Shin Je Song , Hendry Jane , McKay Alastair , Vint Ross , Leung Hing Y , Meddings Robert N , Hendry David S , Fraser Michael
Published: July 2020

Background:

Penile cancer is a rare disease, with approximately 600 cases diagnosed every year in the UK. In this study, we assessed the impact of social deprivation on penile cancer, concentrating on incidence, disease factors, surgical treatment and mortality within our ‘Supranetwork’ population.

Methods:

All cases of penile cancer in the West of Scotland were identified from the uro-oncology multidisciplinary team meetings over a 10-year period covering January 2008 to December 2017. Patients underwent treatment within the remit of a centralised service, and social deprivation was determined using the Scottish Index of Multiple Deprivation (SIMD), which is the Scottish government’s official tool to identify areas of multiple deprivations.

Results:

A total of 278 patients were identified, with an age range of 27–97 years ( M=64 years). The incidence of penile cancer in SIMD category 1 (most deprived) is 7.2/100,000 population at risk compared to 2.8/100,000 population at risk in SIMD category 5 (least deprived). Histologically, a higher proportion of aggressive grade 3 cancers (45% vs. 16%, p=0.03) and more advanced N2/N3 nodal disease (63% vs. 33%, p=0.04) was found in SIMD category 1 compared to SIMD category 5, suggesting higher incidence of delayed presentation with more advanced and aggressive disease in the most deprived populations.

Conclusions:

The level of social deprivation shows a significant association with penile cancer incidence, tumour grade and stage at time of diagnosis, with a resulting disproportionate impact on morbidity and mortality in the most deprived cohort of patients. Public awareness and efforts to increase earlier diagnoses of penile cancer in these ‘hard to reach’ men should be an important step in improving overall outcomes from penile cancer.
New Trends in Formative-Summative Evaluations for Adult Education
Authors: Bin Mubayrik Haifa F.
Published: July 2020

The aim of this article was to review the different evaluation approaches for adult learners and the effect on promoting the quality of teaching and learning. This study aimed to identify new trends in adult education formative-summative evaluations. Data were collected from multiple peer-reviewed sources in a comprehensive literature review covering the period from January 2014 to March 2019. A total of 22 peer-reviewed studies were included in this study. Results were systematically analyzed to answer three questions as follows: what are the new trends in the summative and formative evaluations of adult learners? What are the new trends in the summative and formative evaluations of adult learners engaged in distance learning? And what are the outcomes/drawbacks in the summative and formative evaluations of adult learners? An analysis of the existing literature indicated that those who instruct adults must use a wide variety of pre- and post-assessment tools to match students’ differences with their needs. It also highlighted the importance of “assessment for learning” rather than “assessment of learning” and “learning-oriented assessment” (LOA) for lifelong learning, thus preparing adult learners for future responsibilities and decision making. It also indicated the importance of reflection and immediate feedback for the adult learner. Assessment of mental phenomena such as creativity should have defined terms. The findings of this article supported the argument for more attention to be paid to new trends in evaluations used in adult education. One important result of this kind of evaluation is its facilitation of self-confidence within the adult learning setting.
Anti-MDA-5 Dermatomyositis With Development of Drug-Mediated Necrolytic Skin Lesions
Authors: Case Robert A. , Patel Vishal , Mejia-Otero Carolina , Siroy Alan E. , Patel Divya C.
Published: July 2020

A 59-year-old male presented with 1 month of progressive dyspnea, 30-lb weight loss, and skin changes on the digits of the hands. In the 4 weeks prior to admission, he was admitted and treated twice for pneumonia at another hospital and received intravenous (IV) vancomycin, ceftriaxone, and azithromycin for a total of 10 days. After admission, he underwent computed tomography imaging of chest, which revealed findings suggestive of interstitial lung disease but given the fact that infection was not ruled out, empiric antibiotics were initiated. The skin lesions on the fingers were felt to be consistent with Gottron’s papules, and his overall constellation of findings were felt to be consistent with dermatomyositis (DM). Over the following 3 days, he developed diffuse, violaceous skin lesions, elevation of liver transaminases, and severe thrombocytopenia. The skin lesions progressed to epidermal necrosis. He developed erosions of the oral mucosa and scrotum. Before skin biopsy results were finalized, IV immunoglobulin and IV dexamethasone were started empirically for suspected DM and immune-mediated thrombocytopenia. His laboratory abnormalities normalized within a week. Biopsy results of the skin were consistent with Stevens-Johnson syndrome (SJS). Autoantibody test for anti-MDA5 were positive, confirming a diagnosis of anti-MDA5 associated DM. Subsequent development of SJS was likely due to antibiotic exposure in the preceding month. Simultaneous development of anti-MDA5 DM and SJS raises the question of a link between the 2 conditions. To our knowledge, this is the first reported association of these 2 conditions reported in the literature.
The Case for Translanguaging in Black Immigrant Literacies
Authors: Smith Patriann
Published: July 2020

Black immigrant youth in the United States tend to be considered a new model minority because of the perception that they perform academically better than their African American peers. Yet, Black immigrant youth face challenges with literacy performance that often go unnoticed by teachers, which amplifies the invisibility of their literacies. I assert that nuances presented in the literacies of Black immigrant youth as they become Black, become immigrants, and become speakers of racialized Englishes, necessitate the use of a theoretical lens that allows researchers to foreground race and mediate the linguistic and cultural expectations of these youth. To demonstrate, I propose the lens of translanguaging premised on an integrated model of multilingualism. This perspective provides a basis for foregrounding racialized language to facilitate an ideological understanding surrounding how Black immigrant youth leverage Englishes in their individual linguistic repertoires (i.e., I-languages) to enact literacies. At the same time, it provides an opportunity to understand how these youth engage the often-imposed structural rules of shared grammars within and across these Englishes (i.e., E-languages) in ways that influence these literacies. By presenting Black Caribbean immigrant youth’s literacies as a unique example to foreground racialized language via translanguaging for examining the Englishes of bidialectal youth, I encourage researchers to empower youth to navigate theoretical tensions that remain central to translanguaging research. More broadly, I invite researchers to think beyond dichotomies while clarifying what it means for youth of color from varied backgrounds to leverage their literacies and thrive.
A Lifetime of Language, Literacy, Identity, and Solidarity
Authors: Nieto Sonia
Published: July 2020

In this personal reflection, Sonia Nieto recounts the lessons she learned about language and literacy from learning to speak Spanish and then English; to reading and writing; and the impact of these lessons on her identity, teaching, research, and life; and, more broadly, on the fields of education and literacy.
Methotrexate and rheumatoid arthritis associated interstitial lung disease
Authors: Juge Pierre-Antoine , Lee Joyce S. , Lau Jessica , Kawano-Dourado Leticia , Rojas Serrano Jorge , Sebastiani Marco , Koduri Gouri , Matteson Eric , Bonfiglioli Karina , Sawamura Marcio , Kairalla Ronaldo , Cavagna Lorenzo , Bozzalla Cassione Emanuele , Manfredi Andreina , Mejia Mayra , Rodríguez-Henriquez Pedro , González-Pérez Montserrat I. , Falfán-Valencia Ramcés , Buendia-Roldán Ivette , Pérez-Rubio Gloria , Ebstein Esther , Gazal Steven , Borie Raphaël , Ottaviani Sébastien , Kannengiesser Caroline , Wallaert Benoît , Uzunhan Yurdagul , Nunes Hilario , Valeyre Dominique , Saidenberg-Kermanac'h Nathalie , Boissier Marie-Christophe , Wemeau-Stervinou Lidwine , Flipo René-Marc , Marchand-Adam Sylvain , Richette Pascal , Allanore Yannick , Dromer Claire , Truchetet Marie-Elise , Richez Christophe , Schaeverbeke Thierry , Lioté Huguette , Thabut Gabriel , Deane Kevin D. , Solomon Joshua J. , Doyle Tracy , Ryu Jay H. , Rosas Ivan , Holers V. Michael , Boileau Catherine , Debray Marie-Pierre , Porcher Raphaël , Schwartz David A. , Vassallo Robert , Crestani Bruno , Dieudé Philippe
Published: July 2020

Question addressed by the study

Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.

Methods

Through a case–control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.

Results

Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24–0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19–0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26–0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001).

Answer to the question

Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.
The associations of interstitial lung abnormalities with cancer diagnoses and mortality
Authors: Axelsson Gisli T. , Putman Rachel K. , Aspelund Thor , Gudmundsson Elias F. , Hida Tomayuki , Araki Tetsuro , Nishino Mizuki , Hatabu Hiroto , Gudnason Vilmundur , Hunninghake Gary M. , Gudmundsson Gunnar
Published: July 2020

An increased incidence of lung cancer is well known among patients with idiopathic pulmonary fibrosis. It is not known whether interstitial lung abnormalities,i.e.early fibrotic changes of the lung, are a risk factor for lung cancer in the general population.

The study's objective was to assess whether interstitial lung abnormalities were associated with diagnoses of, and mortality from, lung cancer and other cancers. Data from the AGES-Reykjavik study, a cohort of 5764 older Icelandic adults, were used. Outcome data were ascertained from electronic medical records. Gray's tests, Cox proportional hazards models and proportional subdistribution hazards models were used to analyse associations of interstitial lung abnormalities with lung cancer diagnoses and lung cancer mortality as well as diagnoses and mortality from all cancers.

There was a greater cumulative incidence of lung cancer diagnoses (p<0.001) and lung cancer mortality (p<0.001) in participants with interstitial lung abnormalities than in others. Interstitial lung abnormalities were associated with an increased hazard of lung cancer diagnosis (hazard ratio 2.77) and lung cancer mortality (hazard ratio 2.89) in adjusted Cox models. Associations of interstitial lung abnormalities with all cancers were found in models including lung cancers but not in models excluding lung cancers.

People with interstitial lung abnormalities are at increased risk of lung cancer and lung cancer mortality, but not of other cancers. This implies that an association between fibrotic and neoplastic diseases of the lung exists from the early stages of lung fibrosis and suggests that interstitial lung abnormalities could be considered as a risk factor in lung cancer screening efforts.
Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism
Authors: Suzuki Yoshiro , Sawada Hirotake , Tokumasu Tomoko , Suzuki Shigeru , Ninomiya Shinsuke , Shirai Masaru , Mukai Tokuo , Saito Claire T. , Nishimura Gen , Tominaga Makoto
Published: July 2020

Maternal–fetal calcium (Ca2+) transport in the placenta plays a critical role in maintaining fetal bone mineralization. Mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been identified as causative mutations of transient neonatal hyperparathyroidism due to insufficient maternal–fetal Ca2+ transport in the placenta. In this study, we found two novel mutations in subjects that have transient neonatal hyperparathyroidism. TRPV6 carrying the mutation p.Arg390His that localizes to the outer edge of the first transmembrane domain (S1) showed impaired trafficking to the plasma membrane, whereas TRPV6 having the mutation p.Gly291Ser in the sixth ankyrin repeat (AR) domain had channel properties that were comparable those of WT channels, although the increases in steady-state intracellular Ca2+ concentration could have led to Ca2+ overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca2+ concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca2+-selective channels.
Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistant Staphylococcus aureus
Authors: Kifelew Legesse Garedew , Warner Morgyn S. , Morales Sandra , Vaughan Lewis , Woodman Richard , Fitridge Robert , Mitchell James G. , Speck Peter
Published: July 2020

Background

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistantStaphylococcus aureusis frequently isolated from DFU infections. Bacteriophages (phages) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of threeS. aureus Myoviridaephages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I clinical trials, in treatment of multidrug-resistant (MDR)S. aureusinfections.

Results

Wounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. At the end of the treatment period, there was a significant decrease (p < 0.001) in bacterial load and wound size in infected phage- and vancomycin-treated groups compared with infected saline-treated mice. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No mortality was recorded associated with infections, and post-mortem examinations did not show any evident pathological lesions other than the skin wounds. No adverse effects related to the application of phages were observed.

Conclusion

Topical application of phage cocktail AB-SA01 is effective, as shown by bacterial load reduction and wound closure, in the treatment of diabetic wound infections caused by MDRS. aureus. Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistantS. aureusDFU infections.
Participants who were difficult to recruit at baseline are less likely to complete a follow-up questionnaire – results from the German National Cohort
Authors: Rach Stefan , Günther Kathrin , Hadeler Birte
Published: July 2020

Background

With declining response proportions in population-based research the importance of evaluating the effectiveness of measures aimed at improving response increases. We investigated whether an additional flyer with information about the study influences participation in a follow-up questionnaire and the time participants take to send back filled questionnaire.

Methods

In a trial embedded within the German National Cohort we compared responses to invitations for a follow-up questionnaire either including a flyer with information about the cohort study or not including it. Outcomes of interest were participation in the follow-up (yes vs. no) and time to response (in days). We analyzed paradata from baseline recruitment to account for differences in recruitment history between participants.

Results

Adding a flyer to invitations did neither influence the likelihood of participation in the follow-up (OR 0.94, 95% CI: 0.80, 1.11), nor the time it took participants to return completed questionnaires (β̂ = 1.71, 95% CI: − 1.01, 4.44). Subjects who, at baseline, needed to be reminded before eventually participating in examinations and subjects who scheduled three or more appointments until eventually completing baseline examinations were less likely to complete the follow-up questionnaire and, if they did, took more time to complete questionnaires.

Conclusions

Evaluating the effectiveness of measures aimed at increasing response can help to improve the allocation of usually limited resources. Characteristics of baseline recruitment can influence response to follow-up studies and therefore information about recruitment history (i.e., paradata) might prove useful to tailor follow-up recruitments to those who were difficult to recruit during baseline. To this end, however, it is necessary to routinely and meticulously collect paradata during recruitment.
APOE – a genetic marker of comorbidity in subjects with morbid obesity
Authors: Farup Per G. , Rootwelt Helge , Hestad Knut
Published: July 2020

Background

In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity.

Methods

The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Check-list 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles.

Results

One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity.

Conclusions

The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.
Study protocol for an open-label, single-arm, phase Ib/II study of combination of toripalimab, nab-paclitaxel, and gemcitabine as the first-line treatment for patients with unresectable pancreatic ductal adenocarcinoma
Authors: Shui Lin , Cheng Ke , Li Xiaofen , Shui Pixian , Zhou Xiaohan , Li Jian , Yi Cheng , Cao Dan
Published: July 2020

Background

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a dismal response to single-use of immune checkpoint inhibitors (ICIs). ICIs combined with systemic therapy has shown efficacy and safety in various solid tumors. Nab-paclitaxel and gemcitabine (AG), as the standard first-line treatment for advanced PDAC, has been widely used in recent years. The combination of ICIs and AG chemotherapy appears to be a promising option in the treatment of PDAC.

Methods

This is an open-label, single-arm, and single-center phase Ib/II trial. The enrolled subjects are the unresectable (locally advanced or metastatic) PDAC patients without previous systemic treatments. All subjects receive an intravenous injection of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on day 1 and day 8, along with toripalimab 240 mg at day 1 every 3 weeks. The subjects may discontinue the treatment because of progression disease (PD), intolerable toxicities, requirements of patients or researchers. For local advanced patients who are evaluated as partial response (PR), surgeons need to assess the surgical possibility. The primary objective of this trial is to evaluate the safety and overall survival (OS) of this combination therapy; and the secondary objective is related to the assessment of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and the rate of resection or R0 resection after receiving toripalimab plus AG treatment. Besides, we expect to identify the predictive biomarkers (such as MMR protein and PD-L1 expression, the number of TILs, the small RNA of EBV and so on) and explore the correlation between these biomarkers and tumor response to this combined regimen.

Discussion

This trial is the first attempt to evaluate the efficacy and safety of the combination of toripalimab plus AG chemotherapy as a first-line treatment for unresectable PDAC patients. The results of this phase Ib/II study will provide preliminary evidence for further assessment of this combined therapeutic regimen for unresectable PDAC patients.

Trial registration

Trial registration: ChiCTR (ChiCTR2000032293). Registered 25 April 2020 - Retrospectively registered.
Unilateral multifocal choroiditis following EBV-positive mononucleosis responsive to immunosuppression: a case report
Authors: Borkar P. P. , Grassi M. A.
Published: July 2020

Background

Multifocal choroiditis (MFC) is a relatively uncommon bilateral inflammatory chorioretinopathy affecting Caucasian young women with myopia. We present images from a case of completely unilateral multifocal choroiditis following EBV-positive mononucleosis that demonstrated a dramatic clinical response to immunosuppression.

Case presentation

A 20-year-old woman with bilateral high myopia (−6D) and a documented normal prior retinal examination presented with visual loss in the right eye 2 months following confirmed Epstein-Barr virus (EBV) positive mononucleosis. Ophthalmoscopic examination showed completely unilateral placoid lesions of variable age. The left eye was unaffected. Fluorescein angiography revealed active leakage, especially in the parafovea. Spectral domain optical coherence tomography (SD-OCT) demonstrated sub-retinal pigment epithelial nodular deposits, some of which were confluent with overlying intra-retinal fluid and indistinct margins. Upon treatment with the immunosuppressant azathioprine there was significant resolution of the lesions in her right eye along with improvement in vision.

Conclusion

This is a rare case of completely unilateral MFC following an episode of EBV positive mononucleosis that showed a dramatic response to immunosuppression.
Impact of substandard and falsified antimalarials in Zambia: application of the SAFARI model
Authors: Jackson Kathryn D. , Higgins Colleen R. , Laing Sarah K. , Mwila Chiluba , Kobayashi Tamaki , Ippolito Matthew M. , Sylvia Sean , Ozawa Sachiko
Published: July 2020

Background

Many countries are striving to become malaria-free, but global reduction in case estimates has stagnated in recent years. Substandard and falsified medicines may contribute to this lack of progress. Zambia aims to eliminate their annual burden of 1.2 million pediatric malaria cases and 2500 child deaths due to malaria. We examined the health and economic impact of poor-quality antimalarials in Zambia.

Methods

An agent-based model, Substandard and Falsified Antimalarial Research Impact (SAFARI), was modified and applied to Zambia. The model was developed to simulate population characteristics, malaria incidence, patient care-seeking, disease progression, treatment outcomes, and associated costs of malaria for children under age five. Zambia-specific demographic, epidemiological, and cost inputs were extracted from the literature. Simulations were run to estimate the health and economic impact of poor-quality antimalarials, the effect of potential artemisinin resistance, and six additional malaria focused policy interventions.

Results

We simulated annual malaria cases among Zambian children under five. At baseline, we found 2610 deaths resulting in $141.5 million in annual economic burden of malaria. We estimated that elimination of substandard and falsified antimalarials would result in an 8.1% (n = 213) reduction in under-five deaths, prevent 937 hospitalizations, and realize $8.5 million in economic savings, annually. Potential artemisinin resistance could further increase deaths by 6.3% (n = 166) and cost an additional $9.7 million every year.

Conclusions

Eliminating substandard and falsified antimalarials is an important step towards a malaria-free Zambia. Beyond the dissemination of insecticide-treated bed nets, indoor residual spraying, and other malaria control measures, attention must also be paid to assure the quality of antimalarial treatments.
Acceptability of a hypothetical preventative HIV vaccine among people who use drugs in Vancouver, Canada
Authors: Fleming Taylor , Valleriani Jenna , Ng Cara , Maher Lisa , Small Will , McNeil Ryan
Published: July 2020

Background

As research on HIV vaccines continues to advance, studies exploring the feasibility of this intervention are necessary to inform uptake and dissemination strategies with key populations, including people who use drugs (PWUD).

Methods

We conducted 25 in-depth qualitative interviews examining HIV vaccine acceptability among PWUD in Vancouver, Canada. Participants were recruited from an ongoing prospective cohort of HIV-negative PWUD. Data were coded using NVivo, and analyzed thematically.

Results

Acceptability was framed by practical considerations such as cost and side effects, and was influenced by broader trust of government bodies and health care professionals. While an HIV vaccine was perceived as an important prevention tool, willingness to be vaccinated was low. Results suggest that future vaccine implementation must consider how to minimize the burden an HIV vaccine may place on PWUD. Centering the role of health care providers in information dissemination and delivery may assist with uptake.

Conclusions

Our findings suggest improvements in care and improved patient-provider relationships would increase the acceptability of a potential HIV vaccine among this population.
Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats
Authors: Li Ying , Jiang Jiliang , Tong Liangcheng , Gao Tingting , Bai Lei , Xue Qing , Xing Jianxin , Wang Qin , Lyu Haoran , Cai Min , Sun Zhongyang
Published: July 2020

Background

Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury.

Methods

The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-κB pathway members.

Results

Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-κB pathways.

Conclusions

Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.