bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a (More) Critical FPA
Authors: Brummer Klaus
Published: October 2021

Contrary to other subfields of international relations, foreign policy analysis (FPA) has not experienced a “critical turn” yet. This research note suggests that this may be in part because FPA scholarship does already contain certain “critical” features, such as holding decision-makers to account and the incorporation of various “subordinated” actors in its analyses. Having said that, FPA scholarship tends to fall short on other dimensions of critical scholarship. That is, despite its relatively broad analytical net, it nonetheless silences certain actors, places little attention to the effects of foreign policy decisions, and shows a somewhat limited ethical-political engagement. While an outright critical turn is unlikely to be forthcoming not least for epistemological reasons, FPA would still benefit from a further infusion of critical insights.
A distinct inner nuclear membrane proteome inSaccharomyces cerevisiaegametes
Authors: Shelton Shary N , Smith Sarah E , Unruh Jay R , Jaspersen Sue L
Published: October 2021

The inner nuclear membrane (INM) proteome regulates gene expression, chromatin organization, and nuclear transport; however, it is poorly understood how changes in INM protein composition contribute to developmentally regulated processes, such as gametogenesis. We conducted a screen to determine how the INM proteome differs between mitotic cells and gametes. In addition, we used a strategy that allowed us to determine if spores synthesize their INM proteins de novo, rather than inheriting their INM proteins from the parental cell. This screen used a split-GFP complementation system, where we were able to compare the distribution of all C-terminally tagged transmembrane proteins in Saccharomyces cerevisiae in gametes to that of mitotic cells. Gametes contain a distinct INM proteome needed to complete gamete formation, including expression of genes linked to cell wall biosynthesis, lipid biosynthetic and metabolic pathways, protein degradation, and unknown functions. Based on the inheritance pattern, INM components are made de novo in the gametes. Whereas mitotic cells show a strong preference for proteins with small extraluminal domains, gametes do not exhibit this size preference likely due to the changes in the nuclear permeability barrier during gametogenesis. Taken together, our data provide evidence for INM changes during gametogenesis and shed light on mechanisms used to shape the INM proteome of spores.
Genomics analysis of hexanoic acid exposure inDrosophilaspecies
Authors: Drum Zachary A , Lanno Stephen M , Gregory Sara M , Shimshak Serena J , Ahamed Mukshud , Barr Will , Bekele Bethlehem , Biester Alison , Castro Colleen , Connolly Lauren , DelGaudio Nicole , Humphrey William , Karimi Helen , Karolczak Sophie , Lawrence Tay-Shaun , McCracken Andrew , Miller-Medzon Noah , Murphy Leah , Park Cameron , Park Sojeong , Qiu Chloe , Serra Kevin , Snyder Gigi , Strauss Alexa , Tang Spencer , Vyzas Christina , Coolon Joseph D
Published: October 2021

Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid volatiles that deter and are toxic to generalist insects. Drosophila sechellia has evolved resistance to these volatiles allowing it to feed almost exclusively on this host plant. The genetic basis of octanoic acid resistance has been the focus of multiple recent studies, but the mechanisms that govern hexanoic acid resistance in D. sechellia remain unknown. To understand how D. sechellia has evolved to specialize on M. citrifolia fruit and avoid the toxic effects of hexanoic acid, we exposed adult D. sechellia, D. melanogaster and D. simulans to hexanoic acid and performed RNA sequencing comparing their transcriptional responses to identify D. sechellia specific responses. Our analysis identified many more genes responding transcriptionally to hexanoic acid in the susceptible generalist species than in the specialist D. sechellia. Interrogation of the sets of differentially expressed genes showed that generalists regulated the expression of many genes involved in metabolism and detoxification whereas the specialist primarily downregulated genes involved in the innate immunity. Using these data, we have identified interesting candidate genes that may be critically important in aspects of adaptation to their food source that contains high concentrations of HA. Understanding how gene expression evolves during dietary specialization is crucial for our understanding of how ecological communities are built and how evolution shapes trophic interactions.
Population modeling with machine learning can enhance measures of mental health
Authors: Dadi Kamalaker , Varoquaux Gaël , Houenou Josselin , Bzdok Danilo , Thirion Bertrand , Engemann Denis
Published: October 2021

Background

Biological aging is revealed by physical measures, e.g., DNA probes or brain scans. In contrast, individual differences in mental function are explained by psychological constructs, e.g., intelligence or neuroticism. These constructs are typically assessed by tailored neuropsychological tests that build on expert judgement and require careful interpretation. Could machine learning on large samples from the general population be used to build proxy measures of these constructs that do not require human intervention?

Results

Here, we built proxy measures by applying machine learning on multimodal MR images and rich sociodemographic information from the largest biomedical cohort to date: the UK Biobank. Objective model comparisons revealed that all proxies captured the target constructs and were as useful, and sometimes more useful, than the original measures for characterizing real-world health behavior (sleep, exercise, tobacco, alcohol consumption). We observed this complementarity of proxy measures and original measures at capturing multiple health-related constructs when modeling from, both, brain signals and sociodemographic data.

Conclusion

Population modeling with machine learning can derive measures of mental health from heterogeneous inputs including brain signals and questionnaire data. This may complement or even substitute for psychometric assessments in clinical populations.
1. An Introduction to Intellectual Property
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter examines the philosophical and justificatory context in which intellectual property rights (IPRs) have developed, and the international and regional frameworks that have emerged for their protection. It also considers some of the important contemporary debates surrounding IPRs, such as the interface with human rights and the notion of the public domain, and discusses how IP law might develop in the UK following its exit from the EU. There is a brief introduction on how to enforce IPRs.
3. Copyright II: Authorship, Ownership, Exploitation, Term, Moral Rights, and Economic Rights
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter discusses principles relating to the authorship and ownership of copyright, and the significance of this designation. It examines how owners of copyright can exploit their works by either assignment or licence and the circumstances in which courts can imply terms in the absence of parties having agreed as to how a copyright work can be exploited. The chapter discusses the term of copyright protection and also examines exclusive rights, both moral and economic in nature, that authors and owners respectively have in their copyright works.
4. Copyright III:Infringement, Exceptions, and Database Right
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter discusses the circumstances in which an owner’s economic rights may be infringed and the exceptions and limitations to copyright infringement, including fair dealing for research and private study, reporting current events, criticism or review, and quotation. The chapter explores recent cases relevant to these exceptions and how the UK’s departure from the EU may affect judicial interpretation and how technological protection measures interrelate with copyright exceptions. It also examines the sui generis database right.
8. Trade Marks III:Defences, the Loss of a Trade Mark, and Exhaustion of Rights
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter considers the limitations of the protection afforded by trade mark registration. It discusses the defences to infringement set out in Article 6 of the Trade Marks Directive and section 11 of the Trade Marks Act 1994; trade marks and comparative advertising; the ways in which it is possible to lose registered trade mark protection (through revocation and a finding of invalidity); and how trade mark rights might be exhausted.
12. Patents II: Novelty, Inventive Step, Sufficiency, and Support
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter discusses the requirements of patentability: novelty, inventive step, and sufficiency and support. Novelty means that the invention is new, i.e. is not anticipated. Under section 3 of the Patents Act 1977, an invention involves an inventive step ‘if it is not obvious to a person skilled in the art, having regard to any matter which forms part of the state of the art’. Patent applicants must also satisfy disclosure requirements. Section 14(3) provides that the specification of an application must disclose the invention in a manner clear and complete enough to be performed by the person skilled in the art (sufficiency of disclosure). Section 14(5)(c) provides that claims must be clear, concise, and supported by the description, a requirement (supported by the description).
6. Parliament: Scrutiny of Government
Authors: Thompson Brian , Gordon Michael , Tucker Adam
Published: October 2021

This chapter examines the operation of the UK’s parliamentary style of government, focusing on the role of Parliament in scrutinising the government. The chapter explains the crucial constitutional convention of ministerial responsibility to Parliament, using examples to demonstrate how it operates in practice. Having set out the principles, the chapter explores the practice of parliamentary scrutiny of government, including the role of select committees, debates and questions on the floor of the Commons, and the role of correspondence between MPs, their constituents, and the government. The chapter concludes by reviewing some reforms intended to re-balance power within Parliament, by strengthening the role of backbench MPs, creating a public petitions system to select topics for debate, and extending parliamentary oversight over public appointments.
11. The Availability of Judicial Review
Authors: Thompson Brian , Gordon Michael , Tucker Adam
Published: October 2021

This chapter deals with the availability of judicial review and its significance in the constitution. First, it considers the claim for judicial review and the exclusivity principle. It determines who can apply for judicial review and against whom and in respect of what activities judicial review may be sought. Next, it examines the discretionary nature of the remedies available in judicial review proceedings, including how the courts exercise this discretion. The chapter concludes with an examination of the courts’ response to legislative attempts to exclude or oust judicial review.
Coping with El Niño: phenotypic flexibility of reproductive traits in red squat lobster determines recruitment success
Authors: Flores Andrés , Wiff Rodrigo , Ahumada Mauricio , Queirolo Dante , Apablaza Pedro
Published: October 2021

Many organisms display changes in behaviour and life-history traits when facing variabilities in environmental conditions. A subset of these changes comprises reversible within-individual variations, known as phenotypic flexibility. Using red squat lobster (Pleuroncodes monodon) individuals harvested at the Humboldt Current Ecosystem (HCE), we evaluated how changes in habitat temperatures associated with warm El Niño (EN) conditions and cold La Niña conditions induce phenotypic flexibility in reproductive traits and how this flexibility affects recruitment success. The biological data were obtained from swept area surveys conducted between 2015 and 2020. Remotely sensed sea surface temperature (SST) data were used to compute anomalies (SSTA). Our results showed that females facing warmer environmental conditions carried more eggs with smaller sizes, and under cold conditions, females carried fewer eggs with larger sizes. The recruitments lagged by 1 year correlated positively with the egg density and negatively with the egg size. Our evidence shows that for phenotypic flexibility to be expressed in recruitment success, the warm conditions experienced by females should match good food availability for the planktonic stages. We discussed how climate change predictions for HCE will amplify responses of the reproductive traits of red squat lobster with strong impacts on recruitment likely.
Validation of the 3M™ Petrifilm™ Coliform Count Plate for Enumeration of Coliforms in Bottled Water: AOAC Performance Tested MethodSM 082101
Authors: Schumacher April J , Lingle Cari K , Silbernagel Karen M , Thompson-Strehlow Leslie
Published: October 2021

Background

The 3M™ Petrifilm™ Coliform Count (CC) Plate is a sample-ready-culture medium system which contains modified Violet Red Bile nutrients, a cold-water-soluble gelling agent, and a tetrazolium indicator that facilitates colony enumeration.

Objective

To validate the 3M Petrifilm CC Plate method for bottled water through the AOAC®  Performance Tested Method(s)SM program.

Methods

The performance of the 3M Petrifilm CC Plate was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual Chapter 4, Section III.D for the enumeration of coliforms in bottled water. Matrix data were normalized by log10 transformation and performance indicators included repeatability and difference of means with 90 and 95% confidence intervals. Inclusivity, exclusivity, robustness, and product consistency and stability were evaluated.

Results

This study demonstrated that the 3M Petrifilm CC Plate method detects and enumerates coliforms from bottled water. The average log10 counts of the 3M Petrifilm CC Plate method were equivalent to or better than the average log10 counts of the reference method. Results from inclusivity and exclusivity studies demonstrated that the 3M Petrifilm CC Plate method differentiated coliforms from non-coliform strains. In product consistency, stability, and robustness testing, different lots of 3M Petrifilm CC Plates and small deviations in incubation time and temperature did not affect test results.

Conclusion

The 3M Petrifilm CC Plate method is an accurate and robust method for the enumeration of coliforms in bottled water.

Highlights

The 3M Petrifilm CC Plate allows for detection of confirmed coliforms within 24 h. Up to 20 sample-ready plates can be stacked during incubation, providing flexibility and saving space.
Integrating diverse data sources to predict disease risk in dairy cattle—a machine learning approach
Authors: Lasser Jana , Matzhold Caspar , Egger-Danner Christa , Fuerst-Waltl Birgit , Steininger Franz , Wittek Thomas , Klimek Peter
Published: October 2021

Livestock farming is currently undergoing a digital revolution and becoming increasingly data-driven. Yet, such data often reside in disconnected silos making them impossible to leverage their full potential to improve animal well-being. Here, we introduce a precision livestock farming approach, bringing together information streams from a variety of life domains of dairy cattle to study whether including more and diverse data sources improves the quality of predictions for eight diseases and whether using more complex prediction algorithms can, to some extent, compensate for less diverse data. Using three machine learning approaches of varying complexity (from logistic regression to gradient boosted trees) trained on data from 5,828 animals in 165 herds in Austria, we show that the prediction of lameness, acute and chronic mastitis, anestrus, ovarian cysts, metritis, ketosis (hyperketonemia), and periparturient hypocalcemia (milk fever) from routinely available data gives encouraging results. For example, we can predict lameness with high sensitivity and specificity (F1 = 0.74). An analysis of the importance of individual variables to prediction performance shows that disease in dairy cattle is a product of the complex interplay between a multitude of life domains, such as housing, nutrition, or climate, that including more and diverse data sources increases prediction performance, and that the reuse of existing data can create actionable information for preventive interventions. Our findings pave the way toward data-driven point-of-care interventions and demonstrate the added value of integrating all available data in the dairy industry to improve animal well-being and reduce disease risk.
Bisdemethoxycurcumin attenuates lipopolysaccharide-induced intestinal damage through improving barrier integrity, suppressing inflammation, and modulating gut microbiota in broilers
Authors: Zhang Jingfei , Yang Yuxiang , Han Hongli , Zhang Lili , Wang Tian
Published: October 2021

Bisdemethoxycurcumin has good antioxidant and anti-inflammatory effects and has been widely used as food and feed supplements in the form of curcuminoids. However, the beneficial effect of individual bisdemethoxycurcumin on preventing lipopolysaccharide (LPS)-induced inflamed intestinal damage is unclear. The present study aimed to investigate whether dietary bisdemethoxycurcumin supplementation could attenuate LPS-induced intestinal damage and alteration of cecal microbiota in broiler chickens. In total, 320 one-day-old male Arbor Acres broiler chickens with a similar weight were randomly divided into four treatments. The treatments were designed as a 2 × 2 factorial arrangement: basal diet (CON); 150 mg/kg bisdemethoxycurcumin diet (BUR); LPS challenge + basal diet (LPS); LPS challenge + 150 mg/kg bisdemethoxycurcumin diet (L-BUR). Results showed that dietary bisdemethoxycurcumin supplementation attenuated the LPS-induced decrease of average daily feed intake. LPS challenge compromised the intestinal morphology and disrupted the intestinal tight junction barrier. Dietary bisdemethoxycurcumin supplementation significantly increased villus length:crypt depth ratio and upregulated the mRNA expression of intestinal tight junction proteins. Moreover, a remarkably reduced mRNA expression of inflammatory mediators was observed following bisdemethoxycurcumin supplementation. The cecal microbiota analysis showed that bisdemethoxycurcumin supplementation increased the relative abundance of the genus Faecalibacterium while decreased the relative abundance of the genera Bacteroides and Subdoligranulum. In conclusion, dietary bisdemethoxycurcumin supplementation could counteract LPS-induced inflamed intestinal damage in broiler chickens by improving intestinal morphology, maintaining intestinal tight junction, downregulating pro-inflammatory mediators, and restoring cecal microbiota.
Racial and Ethnic Disparities in Breast Cancer: A Collaboration Between the American College of Radiology Commissions on Women and Diversity and Breast Imaging
Authors: Smetherman Dana , Biggs Kelly , Fayanju Oluwadamilola M , Grosskreutz Scott , Khan Zahra , Malak Sharp , Moseley Tanya , Smith-Graziani Demetria , Valero Vicente , Lightfoote Johnson
Published: October 2021

Since the 1980s, the mortality rate from breast cancer in the United States has dropped almost 40%. The quality of life and survival gains from early detection and improved treatment have not been shared equally by all ethnic groups, however. Many factors, including social determinants of health, unequal access to screening and oncologic care, and differences in incidence, tumor biology, and risk factors, have contributed to these unequal breast cancer outcomes. As breast radiologists approach their own patients, they must be aware that minority women are disproportionately affected by breast cancer at earlier ages and that non-Hispanic Black and Hispanic women are impacted by greater severity of disease than non-Hispanic White women. Guidelines that do not include women younger than 50 and/or have longer intervals between examinations could have a disproportionately negative impact on minority women. In addition, the COVID-19 pandemic could worsen existing disparities in breast cancer mortality. Increased awareness and targeted efforts to identify and mitigate all of the underlying causes of breast cancer disparities will be necessary to realize the maximum benefit of screening, diagnosis, and treatment and to optimize quality of life and mortality gains for all women. Breast radiologists, as leaders in breast cancer care, have the opportunity to address and reduce some of these disparities for their patients and communities.
Honey Bees and Industrial Agriculture: What Researchers are Missing, and Why it’s a Problem
Authors: Shanahan Maggie
Published: October 2021

Industrial agriculture is the root cause of many health problems that honey bees (Apis mellifera Linneaus, 1758) face, but honey bee researchers seldom call attention to this fact. We often discuss the stressors that contribute to colony loss (e.g., pathogens, pesticides, poor nutrition), but we rarely talk about where those stressors come from. This is a problem because we cannot resolve honey bee health issues unless we confront the systems that cause them harm. In this forum article, I unpack the relationship between honey bee health and industrial agriculture. I propose steps we can take to reframe our research to account for the impacts of this destructive system, and I discuss the uncomfortable questions that surface when we engage in this process. The goal of this article is to encourage conversation within the honey bee research community around the impacts of industrial agriculture, so that we can fully engage in the transformative change needed to support honey bee health.
Tenderness of the knee is associated with thinning of the articular cartilage evaluated with ultrasonography in a community-based cohort: The Nagahama study
Authors: Saito Motoo , Nishitani Kohei , Ito Hiromu , Ikezoe Tome , Furu Moritoshi , Okahata Akinori , Nigoro Kazuya , Kawata Tomotoshi , Nakamura Shinichiro , Kuriyama Shinichi , Tabara Yasuharu , Ichihashi Noriaki , Tsuboyama Tadao , Matsuda Fumihiko , Matsuda Shuichi
Published: October 2021

Objectives

This study aimed to elucidate the association between joint line tenderness (JLT) of the knee and knee joint structural changes evaluated with ultrasonography (US) for the early diagnosis of knee osteoarthritis (KOA).

Methods

This cross-sectional study included 121 participants (age 71.7 ± 5.8 years, 75 women) from a community-based population. Bilateral structural changes in the knee joint were evaluated with US, and the presence or absence of JLT was evaluated using a pressure algometer. Logistic regression analysis was performed to evaluate the odds ratios (ORs) of US findings for the presence of JLT. Moreover, when the analysis was limited to knees with pre-/early radiographic KOA, the ORs were also calculated using logistic regression analysis.

Results

Among the 242 knees, 38 had medial JLT, which was significantly associated with female sex (OR 11.87) and loss of cartilage thickness of the distal medial femoral condyle (CTh-MFC) (OR 0.12). Among 96 knees with Kellgren–Lawrence grade ≤ 2, 18 knees had medial JLT, which was also significantly associated with loss of CTh-MFC (OR 0.07) and medial osteophytes (OR 2.01).

Conclusions

JLT is significantly associated with thinning of the femoral cartilage and larger osteophytes in elderly patients, even in those with pre-/early radiographic KOA.
Left ventricle diastolic dysfunction in idiopathic inflammatory myopathies: A meta-analysis and systematic review
Authors: Zhang Yiwen , Yang Xiaoqian , Qin Li , Luo Qiang , Wang Han
Published: October 2021

Objectives

Recent studies have confirmed that heart failure is one of the most important causes of death in patients with idiopathic inflammatory myopathy (IIM). Left ventricle diastolic dysfunction (LVDD) is closely associated with heart failure. Our aim is to determine if the prevalence of LVDD is increased in IIM patients.

Methods

We performed a time- and language-restricted literature search to identify studies conducted to compare the echocardiographic parameters in IIM patients and controls. Mean differences were used to calculate the effect sizes of the echocardiographic parameters.

Results

A total of 13 studies met the inclusion criteria and comprised a total of 227 juvenile dermatomyositis (JDM) patients, 391 adult IIM patients, and 550 controls. The adult IIM patients had lower mitral annular early diastolic velocity (eʹ) and peak of early diastolic flow velocity/peak of late diastolic flow velocity (E/A) ratio compared to controls. The mean left atrial dimension and E/eʹ ratio was higher in adult IIM patients as compared to controls. Similarly, in JDM patients, the decreased eʹ was also observed.

Conclusion

Patients with IIM were more likely to have echocardiographic parameters indicative of diastolic dysfunction. The early heart assessments should be performed in IIM patients.
Ultrasonography of IgG4-related dacryoadenitis and sialadenitis: Imaging features and clinical usefulness
Authors: Komori Takahiro , Inoue Dai , Izumozaki Akira , Sugiura Takumi , Terada Kanako , Yoneda Norihide , Toshima Fumihito , Yoshida Kotaro , Kitao Azusa , Kozaka Kazuto , Takahira Masayuki , Kawano Mitsuhiro , Kobayashi Satoshi , Gabata Toshifumi
Published: October 2021

Objectives

To clarify the ultrasonographic features of immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS) and their usefulness in clinical diagnostic sessions.

Methods

By re-evaluating 96 consecutive patients with IgG4-related disease, we identified 54 patients (male:female = 37:17; median age, 69.5 years) who underwent lacrimal or submandibular gland (LG or SG, respectively) ultrasonography and computed tomography (CT). Their clinical and ultrasonographic features were retrospectively analysed. Radio-pathological correlations were also examined in LG (23 cases) and SG lesions (20 cases). Additionally, the diagnostic accuracy of CT for LG/SG lesions was evaluated.

Results

Abnormal ultrasonographic findings were detected in 33 (LGs) and 38 (SGs) patients, and most of them were observed bilaterally. All lesions were well demarcated and demonstrated diffuse low-echoic areas (rocky pattern) or multiple low-echoic nodules surrounded by high-echoic linear shadows (cobblestone pattern) corresponding to intra-lobular inflammation and inter-lobular fibrosis. Moreover, 42% (LGs; 14/33) and 42% (SGs; 16/38) patients had glandular lesions without clinical symptoms associated with the affected glands. The diagnostic accuracy of CT was ∼80% for LG and 55% for SG.

Conclusions

Ultrasonographic findings in IgG4-DS included diffuse or nodular low-echoic areas with linear high-echoic structures corresponding to inflamed lobules and inter-lobular fibrosis. These findings can help detect IgG4-DS.
A pooled analysis of serious infections and herpes zoster-related disease in Asian patients with rheumatoid arthritis treated with peficitinib (ASP015K) over a median of 3 years
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Kato Daisuke , Kaneko Yuichiro , Fukuda Musashi , Izutsu Hiroyuki , Rokuda Mitsuhiro
Published: October 2021

Objective

To analyse serious infection (SI) and herpes zoster-related disease (HZD) during long-term treatment of rheumatoid arthritis with the oral Janus kinase inhibitor, peficitinib (ASP015K).

Methods

This was a post hoc analysis of pooled data from one Phase 2b study and two Phase 3 studies and final data from a long-term extension study of peficitinib in Asian rheumatoid arthritis patients. Two pooled datasets were analysed (Phase 3 studies and Phase 2/3 studies). Univariate and multivariate Cox regression analyses explored relationships between exposure-adjusted incidence rate of SI and HZD, peficitinib dose, and baseline factors.

Results

Total peficitinib exposure for 1052 patients receiving once-daily peficitinib in the pooled Phase 2/3 Asian studies was 2998.9 patient-years. Exposure-adjusted incidence rates (95% confidence interval) of SI and HZD were 2.7 (2.2, 3.4) and 6.9 (6.0, 8.0) per 100 patient-years, respectively, in pooled Phase 2/3 studies. Advanced age was prognostic for SI and HZD, while baseline prednisolone dose was prognostic for SI. There was no temporal relationship between either adverse event and prolonged peficitinib administration.

Conclusions

As expected in this peficitinib-treated population, older patients had increased risk of SI and HZD, and those receiving higher prednisolone doses had increased risk of SI.
Otitis media with ANCA-associated vasculitis: A retrospective study of 30 patients
Authors: Tabei Akifumi , Sakairi Toru , Ohishi Yuko , Watanabe Mitsuharu , Nakasatomi Masao , Hamatani Hiroko , Ikeuchi Hidekazu , Kaneko Yoriaki , Hiromura Keiju
Published: October 2021

Objectives

Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a new category of otitis media in which cases of otitis media due to ANCA-associated vasculitis (AAV) are classified, regardless of ANCA variant or ANCA serotype. We aimed to describe the clinical features and course of patients with OMAAV and identify factors associated with hearing outcomes.

Methods

We retrospectively analysed 30 patients with OMAAV, classified based on the criteria proposed by the Japan Otological Society in 2016.

Results

Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, double-positive ANCA, and double-negative ANCA were identified in 47%, 33%, 7%, and 13% of the patients, respectively. All patients subjected to audiometry showed hearing impairments, and 85% were affected bilaterally. Mixed- and sensorineural-type hearing impairments were identified in 80% and 20% of impaired ears, respectively. Hypertrophic pachymeningitis (HPM) was identified in 37% of the patients. Immunosuppressive therapy was administered to 93% of patients, and the median air conduction hearing levels at pre- and post-treatment were 66.1 dB and 43.4 dB, respectively, indicating significant hearing improvements. HPM and a long interval between disease onset and treatment initiation were significantly correlated with poor hearing prognosis.

Conclusions

OMAAV develops under any type of ANCA-serology and typically causes mixed or sensorineural bilateral hearing loss. The early initiation of immunosuppressive therapy and the absence of HPM were associated with good hearing outcomes.
Epidemiology and clinical characteristics of systemic sclerosis overlap syndrome (SSc-OS), and the factors significantly associated with SSc-OS in Thai patients with systemic sclerosis
Authors: Jantarat Apichart , Muangchan Chayawee
Published: October 2021

Objective

To investigate the epidemiology and characteristics of systemic sclerosis (SSc) overlap syndrome (SSc-OS).

Methods

This study included patients enrolled in the Siriraj Systemic Sclerosis Cohort registry during November 2013 to September 2019. SSc-OS was defined as SSc patients who also met criteria for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), Sjogren, and/or antiphospholipid antibody syndrome. Baseline and 1-year characteristics were compared between SSc and SSc-OS.

Results

185 patients (age 50.3 ± 11.4 years, 85.4% female, disease duration 2.7 years, 75.1% diffuse cutaneous subset, 75.6% anti-Scl-70 positivity) were included. The incidence and prevalence rate of SSc-OS was 3.2/100 patient-years and 17.8%. Regarding SSc-OS, 12.4%, 2.2%, 1.1%, 1.6%, and 0.5% of patients were classified as SSc-RA, SSc-SLE, SSc-PM, SSc-RA-SLE, and SSc-SLE-PM. SSc-OS had a higher prevalence of limited cutaneous subset (lcSSc), usual interstitial pneumonia, finger contractures, ESR >20 mm/hr., globulin >3.5 g/dL, rheumatoid factor, anti-citrullinated peptide antibody, and antiphospholipid antibodies. LcSSc subset (OR: 11.3, 95%CI: 2.0-62.6) and globulin >3.5 g/dL (OR: 6.2, 95%CI: 1.6–23.6) were associated with SSc-OS.

Conclusion

SSc-OS is associated with the lcSSc subset. RA is the most common overlap syndrome. LcSSc patients with globulin >3.5 g/dL are associated with SSc-OS.
BrainApp: Using near-patient sensing through a mobile app and machine learning in brain tumour patients
Authors: Anwar Nur Aizaan , Williams Matthew
Published: October 2021

Aims

1. To assess the feasibility, acceptability, and performance of a mobile app, 'BRIAN', developed by The Brain Tumour Charity (BTC), in collecting data on quality of life (QOL), activity and sleep, for predicting disease progression in adult brain tumour patients.

2. To generate a prospectively collected dataset of patient measures obtained through mobile devices in brain tumour patients and healthy volunteers.

3. To assess compliance and performance of micro-challenges (hand coordination, visual memory, speech and facial features) in study participants using a mobile application.

4. To assess differences and systematic variation in micro-challenge performance between healthy volunteers and brain tumour patients.

5. To assess factors associated with micro-challenge performance in brain tumour patients, the relationship between micro-challenges and standard measures of QoL and disease progression.

6. To assess the diagnostic performance of different machine learning models in detecting brain tumour progression.

Method

This abstract describes the protocol for a multi-centre observational non-randomised phase II trial for adult brain tumour patients and healthy volunteers in the UK. Participants will use the BRIAN mobile app, developed by BTC to help individuals cope with a brain tumour, and share their journey with both researchers and clinicians. Participants will be required to enter information on their medical background, mood, and QOL; have the option to link fitness trackers to the app; as well as perform mini-games which assess speech, coordination, facial features and reaction time. Patients will have their brain imaging and histopathology report submitted to the sponsor. We will then investigate the correlation and temporal relation of these multimodal data with conventional measures of disease progression. We will use traditional statistical methods initially (i.e. descriptive statistics and multilevel modelling), which will then inform the development of a machine learning model in predicting brain tumour progression.

Results

The BRIAN app is currently being beta-tested by healthy volunteers from the Computational Oncology Lab, Imperial College London. We are in the process of obtaining ethical approval for the trial.

Conclusion

This study may enable the development of a tool that allows us to detect earlier signs of disease progression, and so offer earlier treatment and preservation of quality of life; and hence the best course of action. Such a tool would also be non-invasive, cheap, quick, and can be used by patients in the comfort of their own homes.
GlioCova: Treatment and hospital admissions for patients with GBM in England
Authors: Mauricaite Radvile , Calvez Kerlann Le , Williams Matthew
Published: October 2021

Aims

Data on the treatment and outcomes of patients with primary brain tumours in England is sparse. The GlioCova project uses linked national data from England to explore the incidence, treatment, outcomes, and treatment costs of all adult brain tumour patients in all 50,000 patients in England from 2013 – 2018. Here we present initial results from patients with glioblastoma (GBM).

Method

We used a linked dataset from the national cancer registration system in England including all adult patients diagnosed with a malignant or benign brain tumour between 2013 and 2018 (51,775 patients in total).

Glioblastoma patients were selected based on ICD-10 codes (C70, C71, C72), morphology codes (9440, 9441, 9442), and grade (G4, G3, GX and NA) from the national cancer registry. We extracted data on treatment (radiotherapy, chemotherapy, brain surgery or biopsy) and measured how many patients who had adjuvant Temozolomide completed 6 cycles.

Results

We identified 15,294 glioblastoma patients. Most had glioblastoma morphology (14,924), followed by gliosarcoma (264) and giant cell glioblastoma (106). Almost all had a cranial tumour (C71) while 17 had a tumour originating in the spinal cord, cranial nerves or other part of central nervous system (C72). Median age was 66 (IQR=17) and 60% were male. 51.9% (7,935) underwent surgery; an additional 18.2% (2,784) had a biopsy; 3,701 (24.2%) out of 15,294 patients received radiotherapy (only) and 316 (2.1%) received chemotherapy (only). 5,520 (36.1%) received both radiotherapy and chemo. Out of 4,101 GBM patients receiving temozolomide after radiotherapy, only 1,535 (37.4%) completed 6 cycles. The 7,935 GBM patients who had surgery had a median length of stay in hospital of 5 days (IQR=6) while those that had a biopsy had a median of 3 days (IQR=6).

Conclusion

We have presented a description of treatment of all GBM patients in England over a five-year period. This is the first time we have been able to understand detailed treatment patterns at a national scale, and significantly extends previous analyses. Further work will look at patient safety indicators, variation across centres and costs of treatment.

Acknowledgements

We would like to thank the GlioCova Expert Advisory Group for their input and discussion.

This work uses data provided by patients and collected by the NHS as part of their care and support.
Efficacy and Safety of CyberKnife Stereotactic Radiosurgery in Acromegaly
Authors: Seguna Desiree , Akker Scott , Ahlquist James , Pal Aparna , Brooke Antonia , Lewis Rachel , Plowman P N , Evanson Jane , Panday Pratistha , Drake William Martyn
Published: October 2021

Aims

Objective: Active acromegaly is associated with increased mortality. While surgery is the mainstay of treatment, it is not always curative. In selected cases, CyberKnife stereotactic radiosurgery (CK SRS) can be used as adjuvant treatment in patients with persistent disease.

Method

Methodology: Biochemical response was measured using serum IGF-1 levels, calculated as a percentage of the upper limit of normal (% ULN). Levels were recorded prior to treatment, at 6-12 months post-treatment and at the most recent follow-up. Anterior pituitary hormone deficits were assessed before and after treatment. Tumour size was followed-up using MRI.

Results

10 patients (7 male, mean age 36 yrs [+/- 12.6, SD]) with acromegaly were treated with CK SRS. 9 were treated following failure to attain biochemical remission with TSS. 1 had primary CK SRS. 2 had previous conventional fractionated external beam radiotherapy.

Median tumour diameter was 6 mm (IQR 5.2-10.5 mm), with cavernous sinus invasion in 2 cases. The dose was 20-24Gy/1#. 4 patients were on dopamine agonist, 4 on somatostatin analogue and 2 on pegvisomant. Mean follow-up 31.6 months (+/- 13.5 months, SD).

Median IGF-1 % ULN was 146% pre-treatment (IQR 126.5-208.5), 109% at 6-12 months (IQR 76.5-131%) and 71% (IQR 59-91%) at last follow-up. Mean radiological follow-up 16.6 months (+/- 15.9 months, SD). No cases showed tumour enlargement.

One patient developed secondary hypothyroidism. Side-effects: headache (7 patients), blurred vision (1 patient), fatigue/nausea (1 patient). No new visual fields defects, cranial nerve palsies, cerebrovascular events or secondary tumours.

Conclusion

Conclusions: CK SRS appears safe and effective in selected patients with acromegaly, when there is failure to attain biochemical cure with surgery and in patients intolerant or resistant to medical treatment.
Cranial Meningiomas Requiring Cranioplasty
Authors: Norrington Max , Millward Christopher , Doherty John , Mustafa Mohammad , Humphries Thomas , Gillespie Conor , Richardson George , Islim Abdurrahman , Jenkinson Michael , Brodbelt Andrew
Published: October 2021

Aims

Bone infiltration in association with intracranial meningioma (4.5% of cases) and primary intraosseous meningioma (2%) are rare. Management can be challenging, as cranial vault reconstruction may be required. This study aimed to examine the surgical techniques used and outcomes in this patient population.

Method

A single-centre, retrospective cohort study was conducted between January 2010 and September 2020. All adult patients who required cranial reconstruction due to bone involvement of their meningioma were included. Patient demographics, tumour characteristics, operative details, complications, and outcomes were examined. Statistical analyses were performed using SPSS v24.0.

Results

There were 30 patients (17 female; 56.7%), median age 54 yrs (range 28-86 yrs), of whom 25 (83.3%) had bone infiltration, and 5 (16.7%) had primary intraosseous meningioma. Only 10 patients had a Simpson I or II resection. Twenty-eight had 'on-table' primary cranioplasties. Materials used were titanium (n=13; 43.3%), acrylic (n=10; 33.3%), PMMA (n=5; 16.7%), and hydroxyapatite (n=2; 6.7%). There were 9 (mostly minor) surgical complications and only one wound infection. Twelve patients had WHO grade II tumours, and 14 required radiotherapy. Ten patients (33.3%) had re-operation for recurrent tumour, with a median time to progression of 41 months. At 6 months, 24 patients had a performance score less than 2.

Conclusion

On-table cranioplasty provides a lower risk surgical option for patients with high risk meningiomas.
An audit on the diagnosis of primary CNS lymphoma
Authors: Joe Dorothy , Yin Lucia , Kassam Shireen , Cikurel Katia , Lavrador Jose-Pedro , Vergani Francesco , Gullan Richard , Bhangoo Ranjeev , Ashkan Keyoumars , Finnerty Gerald
Published: October 2021

Aims

Primary central nervous system lymphoma (PCNSL) is a rare form of non–Hodgkin lymphoma with exclusive manifestations in the central nervous system, leptomeninges and eyes. It forms around 5% of all primary brain tumours. It is an aggressive tumour which has a poor prognosis if left untreated. It is imperative that diagnosis is made timely so treatment can be started promptly. Therefore, we performed an audit looking into the speed of diagnostic process of PCNSL in our tertiary Neuro–oncology Unit.

Method

Single-centre retrospective review of PCNSL cases referred to a tertiary Neuro–Oncology Unit over a six month period from June to November 2020.

Results

A total of 1309 cases were discussed in the Neuro–oncology MDT meeting over the study period. Fourteen cases (6 male, 8 female; median age [range] 66 [59–83] years) were identified as highly likely PCNSL. Neuroimaging suggested PCNSL as the likely diagnosis in twelve patients. Twelve patients were started on steroids after CT or MRI brain scans. Nine patients had a surgical target and proceeded to have diagnostic brain biopsy. Two patients had different working diagnoses and three patients were deemed unsuitable for brain surgery. One patient required repeat brain biopsy. A tissue diagnosis was made in twelve patients. One patient deteriorated rapidly and one patient had a brain lesion that was deemed too high risk for surgery. The median time between neuroimaging and biopsy was 25 days. The median time taken from first investigation to the pathological confirmation of PCNSL was 36 days (range 6–86 days).

Conclusion

The chief reason for delay in diagnosis of PCNSL was that patients were started on steroids before diagnostic investigations were completed. Steroids caused the brain lesions to become smaller or disappear. Accordingly, time was needed to allow withdrawal of steroids before diagnostic investigations could be repeated. Diagnostic delays may have been exacerbated by logistical issues associated with COVID–19. We propose that there needs to be greater awareness of how early introduction of steroids can markedly delay the diagnosis of PCNSL.
US-Focused Conceptual Health Care Decision-Analytic Models Examining the Value of Pivmecillinam Relative to Current Standard-of-Care Agents Among Adult Patients With Uncomplicated Urinary Tract Infections due to Enterobacterales
Authors: Lodise Thomas P , Henriksen Anne Santerre , Hadley Thomas , Patel Nimish
Published: October 2021

Background

Pivmecillinam is approved for the treatment of adults with uncomplicated urinary tract infection (uUTI) in Canada and Europe and is pending United States (US) Food and Drug Administration submission for consideration for approval. US-focused health care decision-analytics were developed to define the value of an agent like pivmecillinam relative to current standard-of-care (SOC) agents among adult patients with Enterobacterales uUTIs based on its improved microbiologic activity against common Enterobacterales.

Methods

The model population was 100 theoretical adult outpatients with Enterobacterales uUTIs under 4 different uUTI first-line empiric treatment scenarios (ie, pivmecillinam, nitrofurantoin, trimethoprim-sulfamethoxazole [SXT], or fluoroquinolones). The total mean uUTI-related 30-day costs, including inappropriate treatment costs, were calculated for each regimen. The range of pivmecillinam regimen costs that conferred cost savings relative to the current SOC agents based on its potentially improved microbiologic activity against common Enterobacterales was determined.

Results

The 30-day uUTI-related costs associated with nitrofurantoin, SXT, and fluoroquinolones were $655.61, $687.57, and $659.69, respectively. The pivmecillinam neutral regimen cost thresholds that resulted in the same uUTI-related 30-day per-patient costs for nitrofurantoin, SXT, and fluoroquinolones were $83.50, $115.45, and $87.58, respectively. The overall antimicrobial susceptibility improvement required with pivmecillinam fixed at $200/regimen, for it to be cost savings relative to SOC agents, was 28%.

Conclusions

The analyses suggests that an agent like pivmecillinam, if approved in the US, has the potential to reduce the economic burden associated with inappropriate treatment of adult outpatients with uUTIs, especially in patients at high risk for an Enterobacterales uUTI that is resistant to SOC agents.