bluuebunny/crossref_metadata_2025 huggingface dataset:
Crustal deformation across the western Altyn Tagh fault (86° E) from GPS and InSAR
Authors: Li Yanchuan , Nocquet Jean-Mathieu , Shan Xinjian
Published: September 2021

We combine Global Positioning System (GPS) velocity field with Interferometric Synthetic Aperture Radar (InSAR) results to study the interseismic deformation across the western Altyn Tagh fault (ATF) at longitude 86° E. GPS and InSAR data are consistent after correcting for the contribution from vertical deformation in the InSAR line-of-sight map. InSAR and GPS data identify an area of ∼2 mm a−1 sinistral shear and ∼6 mm a−1 of NS shortening located ∼150 km south of the ATF near the Manyi fault system. Excluding the data located in that area, Bayesian inversion of a 2-D profile across the ATF indicate a locking depth of 14.8 ± 3.5 km and a slip rate of 8.0 ± 0.4 mm a−1, lying at the lower range of previously published estimates. In addition, we find no significant offset between the fault at depth and the surface fault trace and no asymmetry of the interseismic profile that implicitly reveal lateral variations of the elastic strength across the ATF. Detailed analysis of InSAR profile across the fault show no distinguishable surface creep along the western ATF. Our study highlights how different data sets, data selection and model assumption might impact results on the ATF slip rate, locking depth and rheological contrast across the fault.
Co-producing an action-oriented framework for community-based Physical Activity Promotion in Germany
Authors: Kohler Simone , Helsper Natalie , Dippon Lea , Rütten Alfred , Abu-Omar Karim , Pfeifer Klaus , Semrau Jana
Published: September 2021

German National Recommendations for Physical Activity (PA) and PA Promotion recommend community-based approaches to promote PA at the local level with a focus on health equity. In addition, the German Federal Prevention Act addresses health equity and strengthens setting-based health promotion in communities. However, the implementation of both in the local context remains a challenge. This article describes Phase 1 of the KOMBINE project that aims to co-produce an action-oriented framework for community-based PA promotion focusing on structural change and health equity. (i) In a series of workshops, key stakeholders and researchers discussed facilitators, barriers and needs of community-based PA promotion focusing on health equity. (ii) The research team used an inductive approach to cluster all findings and to identify key components and then (iii) compared the key components with updated literature. (iv) Key components were discussed and incorporated into a gradually co-produced framework by the participants. The first result of the co-production process was a catalog of nine key components regarding PA-related health promotion in German communities. The comparison of key components with scientific evidence showed a high overlap. Finally, a six-phase action-oriented framework including key components for community-based PA promotion was co-produced. The six-phase action-oriented framework integrates practice-based and scientific evidence on PA-related health promotion and health equity. It represents a shared vision for the implementation of National Recommendations for PA and PA Promotion in Germany. The extent to which structural changes and health equity can be achieved is currently being investigated in pilot-studies.
Factors influencing the effectiveness of a Cooperative Planning approach in the school setting
Authors: Ptack Katharina , Strobl Helmut
Published: September 2021

The purpose of the Health.edu project was to develop, implement and evaluate effective and feasible measures addressing students' health-related knowledge and understanding (HKU) in physical education (PE) with a specific focus on a co-creation approach (Cooperative Planning). The general procedure was identical in the four intervention schools involved; however, effectiveness (i.e. an increase in HKU) differed. Therefore, the present study investigated how different contextual factors supported or hindered the Cooperative Planning approach (evaluation of program implementation). To consider different perspectives in the analysis, we used data triangulation. On the one hand, written protocols (N = 19) document relevant statements and decisions in each planning group meeting (scientific perspective). On the other hand, we captured the participating PE teachers’ (N = 8) individual attitudes after the Cooperative Planning process through semi-structured interviews (teachers’ perspective). Data were analysed via qualitative content analysis. We identified three relevant factors with influence on the Cooperative Planning approach. First, the Cooperative Planning intervention worked if teachers saw a benefit in providing evidence-based knowledge, reflected their teaching practices and made an effort to implement new teaching strategies. Second, it was beneficial to have students represented as partners in the decision-making process. Third, support from the principal appeared to be helpful but not mandatory for implementing progressive pedagogical concepts. Continuous monitoring and reflection on those factors by the leading project team might help facilitate subsequent interventions using Cooperative Planning.
Playing alone: can game design elements satisfy user needs in gamified mHealth services?
Authors: Mitchell Robert , Schuster Lisa , Jin Hyun Seung
Published: September 2021

Chronic health conditions have necessitated the need for behavioral interventions (such as exercise programs) outside of clinical contexts, increasingly managed through technology such as mobile health (mHealth) services. Gamification has emerged as a promising tool to facilitate greater engagement in these services; however, no studies investigate the links between specific game design elements (GDEs) and psychological or behavioral outcomes within a health context. This domain is motivationally complex and has shown resistance to the satisfaction of social (relatedness) needs, presenting a challenge to the design of gamification products for health promotion. Drawing on self-determination theory, this research demonstrates the strengths of a taxonomy based upon structural features of GDEs (such as social, narrative or reward elements) rather than the design intent definitions of these elements used in previous studies. This taxonomy is then used to assess the relationship between GDEs and psychological needs satisfaction in a survey (N = 236) of gamified exercise/fitness application users. Further qualitative interviews (N = 20) were conducted to clarify survey findings. This research demonstrates the positive association between control and presentation elements and autonomy satisfaction, and control and reward elements and competency satisfaction. However, it also suggests that player type and context may limit the ability for GDEs alone to support relatedness satisfaction in mHealth services. Implications for managers and researchers are discussed, particularly the strengths and weaknesses of using structural taxonomies in gamification assessment.
Parish councils, political inclusion, Liberal politics and the question of class: the 1894 elections as a forgotten phase in British democratization
Authors: Moore James
Published: September 2021

The creation of parish councils in 1894 has been somewhat neglected by historians of democratization and social class. This article explores how questions of political inclusion and class became important features of the first parish council elections. The National Liberal Federation and allied pressure groups encouraged electors to see the elections as a battle between working people and the privileged orders. Contrary to what is sometimes suggested, this demonstrates that ‘class politics’ was sometimes an important part of Liberal electoral strategy. Ultimately, the councils brought important changes to local political life, with working men elected to parishes in significant numbers.
Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues
Authors: Castaneda Andy B , Petty Lauren E , Scholz Markus , Jansen Rick , Weiss Stefan , Zhang Xiaoling , Schramm Katharina , Beutner Frank , Kirsten Holger , Schminke Ulf , Hwang Shih-Jen , Marzi Carola , Dhana Klodian , Seldenrijk Adrie , Krohn Knut , Homuth Georg , Wolf Petra , Peters Marjolein J , Dörr Marcus , Peters Annette , van Meurs Joyce B J , Uitterlinden André G , Kavousi Maryam , Levy Daniel , Herder Christian , van Grootheest Gerard , Waldenberger Melanie , Meisinger Christa , Rathmann Wolfgang , Thiery Joachim , Polak Joseph , Koenig Wolfgang , Seissler Jochen , Bis Joshua C , Franceshini Nora , Giambartolomei Claudia ,   Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Subclinical Working Group, Hofman Albert , Franco Oscar H , Penninx Brenda W J H , Prokisch Holger , Völzke Henry , Loeffler Markus , O'Donnell Christopher J , Below Jennifer E , Dehghan Abbas , de Vries Paul S
Published: September 2021

Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.
Sensitive quantification of m.3243A>G mutational proportion in non-retinal tissues and its relationship with visual symptoms
Authors: Mullin Nathaniel K , Anfinson Kristin R , Riker Megan J , Wieland Kelsey L , Tatro Nicole J , Scheetz Todd E , Mullins Robert F , Stone Edwin M , Tucker Budd A
Published: September 2021

The m.3243A>G mutation in the mitochondrial genome commonly causes retinal degeneration in patients with maternally inherited diabetes and deafness and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Like other mitochondrial mutations, m.3243A>G is inherited from the mother with a variable proportion of wild type and mutant mitochondrial genomes in different cells. The mechanism by which the m.3243A>G variant in each tissue relates to the manifestation of disease phenotype is not fully understood. Using a digital PCR assay, we found that the % m.3243G in skin derived dermal fibroblasts was positively correlated with that of blood from the same individual. The % m.3243G detected in fibroblast cultures remained constant over multiple passages and was negatively correlated with mtDNA copy number. Although the % m.3243G present in blood was not correlated with severity of vision loss, as quantified by Goldmann visual field, a significant negative correlation between % m.3243G and the age of onset of visual symptoms was detected. Altogether, these results indicate that precise measurement of % m.3243G in clinically accessible tissues such as skin and blood may yield information relevant to the management of retinal m.3243A>G-associated disease.
Interpreting the Right to Interpretation under Article 6(3)(e) ECHR: A Cautious Evolution in the Jurisprudence of the European Court of Human Rights?
Authors: Vogiatzis Nikos
Published: September 2021

This article explores how the European Court of Human Rights has interpreted the right to interpretation under Article 6(3)(e) ECHR—a topic which, despite its significance for the rule of law and access to justice, has received, to date, very limited scholarly attention. The key finding is that we are witnessing a ‘cautious evolution’: the Court has progressively—yet simultaneously cautiously—developed the standards and guarantees of this right, which is one of the rights of defence under Article 6(3) ECHR and a requirement of the fair trial. The analysis focuses, in particular, on (i) how general interpretative techniques that have been developed by the Strasbourg Court were applied by the Court in its jurisprudence concerning the said provision; (ii) on the interplay between the overall fairness of the trial and Article 6(3)(e) ECHR; and (iii) on Article 6(3)(e) ECHR and the relationship between legal assistance/legal aid and the right to interpretation. In addition, the article identifies possible areas of further development of this right.
Nutritional status determines apparent assimilative capacity and functional response of marine predatory fish
Authors: Andersen Niels Gerner , Neuenfeldt Stefan , Bogstad Bjarte , Andersen Ken Haste , Beyer Jan Erik
Published: September 2021

Marine predatory fish face unpredictable prey environments, ranging from abundance to scarcity of food. Dimensioning their assimilative system to accommodate gorging and fasting is therefore a central life history choice. Assimilative capacity experiments typically operate with sustained feeding to satiation, and therefore ignore the fluctuations in natural feeding opportunities. A more relevant description of the adaptive response is the episodic capacity associated with binge feeding (hyperphagia). We develop the theoretical foundation to define episodic and sustained capacity and its allometry. Extensive empirical evidence on marine piscivorous fish at higher latitudes confirms that the episodic capacity scales almost linearly with predator body mass (exponent approximately 0.95), producing an increasing factorial hyperphagic scope (exponent approximately 0.20). Our synthesis overturns the reigning steady state perspective on assimilative capacity. The fish can utilize an episodic capacity, typically twice the size of the sustained capacity, resulting in local dynamics of functional responses with profound implications for scaling-up to ecosystem level.
Attribution of Conduct to a State
Authors: de Stefano Carlo
Published: September 2021

This article examines the application of ARSIWA’s provisions on attribution of conduct to a State in international investment law and arbitration. In particular, it critically analyses the rules of attribution of conduct codified in ARSIWA Articles 4 (conduct of organs of a State), 5 (conduct of persons or entities exercising elements of governmental authority), 7 (excess of authority or contravention of instructions) and 8 (conduct directed or controlled by a State). A central message of the present contribution pertains to the methodological demand for an inclusive perspective by adjudicators as to the public international law dimension of investor-State dispute settlement and the direct applicability therein of ARSIWA’s customary rules on attribution.
Modified Nuss procedure with a novel steel bar in patients with pectus excavatum post-congenital heart surgery
Authors: Liu Siming , Wang Lei , Zhang Hongkun , Zeng Wenhui , Hu Fengqing , Xiao Haibo , Li Guoqing , Mei Ju , Zhu Jiaquan
Published: September 2021

OBJECTIVES

Pectus excavatum (PE) can be secondary in patients who underwent sternotomy for cardiac surgery. Retrosternal adhesions increase the complexity and risk of traditional Nuss repair. Thus, we summarized the outcomes of our modified Nuss procedure using a newly designed bar.

METHODS

A retrospective analysis was performed on 35 patients who underwent modified PE repair after open heart surgery from January 2011 to July 2019. The surgery was performed using a novel bar with no need for intraoperative reshaping and rotation, assisted by thoracoscopy and subxiphoid incision when necessary.

RESULTS

There were 19 males and 16 females with a median age of 5.3 years (interquartile range, 4.1–10.9) at PE repair. All patients underwent the modified procedure uneventfully with no death. The median operating time was 70 min. Twenty-nine (82.9%) patients required subxiphoid incision assistance. There was 1 case (2.8%) with unexpected sternotomy due to intraoperative bleeding. The median length of postoperative hospital stay was 4 days. During the median 3.5 years of follow-up, no bar dislocation was found and 30 (85.7%) patients had their bars removed with no recurrence recorded. After PE repair, the Haller index improved significantly (2.6 ± 0.4 vs 4.9 ± 1.3, P < 0.05) and further decreased till the time of bar removal (2.5 ± 0.4 vs 2.6 ± 0.4, P < 0.05). All patients were satisfied with the cosmetic outcome.

CONCLUSIONS

The novel bar can be placed and removed easily with a low rate of adverse events. This modified Nuss procedure seems to be a safe, effective and convenient approach for the management of PE after cardiac surgery.
Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan
Authors: Inoue-Choi Maki , Freedman Neal D , Saito Eiko , Tanaka Shiori , Hirabayashi Mayo , Sawada Norie , Tsugane Shoichiro , Usui Yoshiaki , Ito Hidemi , Wang Chaochen , Tamakoshi Akiko , Takeuchi Taro , Kitamura Yuri , Utada Mai , Ozasa Kotaro , Sugawara Yumi , Tsuji Ichiro , Wada Keiko , Nagata Chisato , Shimazu Taichi , Mizoue Tetsuya , Matsuo Keitaro , Naito Mariko , Tanaka Keitaro , Katanoda Kota , Inoue Manami ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: September 2021

Background

Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.

Methods

We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983–1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.

Results

The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1–10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose–response manner. HRs (95% CIs) were 1.27 (0.97–1.66), 1.45 (1.33–1.59) and 1.49 (1.38–1.62) for 1–2, 3–5 and 6–10 CPD, respectively, in men; 1.28 (1.01–1.62), 1.49 (1.34–1.66) and 1.68 (1.55–1.81) for 1–2, 3–5 and 6–10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.

Conclusions

Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD.
Genotyping Cyclospora cayetanensis From Multiple Outbreak Clusters With An Emphasis on a Cluster Linked to Bagged Salad Mix—United States, 2020
Authors: Barratt Joel , Ahart Lauren , Rice Marion , Houghton Katelyn , Richins Travis , Cama Vitaliano , Arrowood Michael , Qvarnstrom Yvonne , Straily Anne
Published: September 2021

Cyclosporiasis is a diarrheal illness caused by the foodborne parasite Cyclospora cayetanensis. Annually reported cases have been increasing in the United States prompting development of genotyping tools to aid cluster detection. A recently developed Cyclospora genotyping system based on 8 genetic markers was applied to clinical samples collected during the cyclosporiasis peak period of 2020, facilitating assessment of its epidemiologic utility. While the system performed well and helped inform epidemiologic investigations, inclusion of additional markers to improve cluster detection was supported. Consequently, investigations have commenced to identify additional markers to enhance performance.
Immune discrimination of the environmental spectrum through C-type lectin receptors
Authors: Torigoe Shota , Schutt Charles R , Yamasaki Sho
Published: September 2021

Our bodies are continuously assaulted by infection and tissue damage; most of these injurious insults are primarily sensed by immune receptors to maintain tissue homeostasis. Although immune recognition of proteins or nucleic acids has been well characterized, the molecular mechanisms by which immune receptors discriminate lipids to elicit suitable immune responses remain elusive. Recent studies have demonstrated that the C-type lectin receptor family functions as immune sensors for adjuvant lipids derived from pathogens and damaged tissues, thereby promoting innate/acquired immunity. In this review, we will discuss how these receptors recognize lipid components to initiate appropriate, but sometimes deleterious, immune responses against environmental stimuli. We will also discuss an aspect of inhibitory C-type lectin receptors; their ligands might reflect normal self which silences the immune response regarded as “silence”-associated molecular patterns or may be associated with escape strategies of pathogens as “evasion”-associated molecular patterns.
The interaction between the immune system and the peripheral sensory nerves in pruritus
Authors: Irie Hiroyuki , Kabashima Kenji
Published: September 2021

Pruritus is a skin-specific sensation that is observed in various skin diseases, especially in inflammatory skin diseases such as atopic dermatitis, and is deeply involved in their pathogenesis. Pruritus also adversely affects patients’ sleep and mental health, placing a heavy burden on daily life. As such, pruritus control is important to the maintenance of health. The mechanism of pruritus has recently been clarified and the discovery of various pruritus mediators, the identification of specific nerves that transmit pruritus and the accumulation of knowledge on pruritus perception have led to a better understanding of all aspects of pruritus generation, transmission and recognition. In the case of pruritus caused by dermatitis, immune cells infiltrating the skin secrete inflammatory cytokines, which also act on peripheral nerves as pruritus mediators and induce an inflammatory response. Interestingly, there has been accumulating evidence that peripheral nerves are also involved in the inflammation via neuropeptides. In this article, we summarize the findings on pruritus mediators secreted by immune cells and the roles of peripheral nerves in pruritus in terms of their interactions with immunity.
Current and future options for treating complicated skin and soft tissue infections: focus on fluoroquinolones and long-acting lipoglycopeptide antibiotics
Authors: Eckmann Christian , Tulkens Paul M
Published: September 2021

Bacterial skin and soft tissue infections are among the most common bacterial infections and constitute a major burden for patients and healthcare systems. Care is complicated by the variety of potential pathogens, some with resistance to previously effective antimicrobial agents, the wide spectrum of clinical presentations and the risk of progression to life-threatening forms. More-efficient care pathways are needed that can reduce hospital admissions and length of stay, while maintaining a high quality of care and adhering to antimicrobial stewardship principles. Several agents approved recently for treating acute bacterial skin and skin structure infections have characteristics that meet these requirements. We address the clinical and pharmacological characteristics of the fourth-generation fluoroquinolone delafloxacin, and the long-acting lipoglycopeptide agents dalbavancin and oritavancin.
Re-engineering a mobile-CRISPR/Cas9 system for antimicrobial resistance gene curing and immunization inEscherichia coli
Authors: He Yu-Zhang , Kuang Xu , Long Teng-Fei , Li Gong , Ren Hao , He Bing , Yan Jin-Ru , Liao Xiao-Ping , Liu Ya-Hong , Chen Liang , Sun Jian
Published: September 2021

Objectives

In this study, we developed an IS26-based CRISPR/Cas9 system as a proof-of-concept study to explore the potential of a re-engineered bacterial translocatable unit (TU) for curing and immunizing against the replication genes and antimicrobial resistance genes.

Methods

A series of pIS26-CRISPR/Cas9 suicide plasmids were constructed, and specific guide RNAs were designed to target the replication gene of IncX4, IncI2 and IncHI2 plasmids, and the antibiotic resistance genes mcr-1, blaKPC-2 and blaNDM-5. Through conjugation and induction, the transposition efficiency and plasmid-curing efficiency in each recipient were tested. In addition, we examined the efficiency of the IS26-CRISPR/Cas9 system of cell immunity against the acquisition of the exogenous resistant plasmids by introducing this system into antimicrobial-susceptible hosts.

Results

This study aimed to eliminate the replication genes and antimicrobial resistance genes using pIS26-CRISPR/Cas9. Three plasmids with different replicon types, including IncX4, IncI2 and IncHI2 in three isolates, two pUC19-derived plasmids, pUC19-mcr-1 and pUC19-IS26mcr-1, in two lab strains, and two plasmids bearing blaKPC-2 and blaNDM-5 in two isolates were all successfully eliminated. Moreover, the IS26-based CRISPR/Cas9 system that remained in the plasmid-cured strains could efficiently serve as an immune system against the acquisition of the exogenous resistant plasmids.

Conclusions

The IS26-based CRISPR/Cas9 system can be used to efficiently sensitize clinical Escherichia coli isolates to antibiotics in vitro. The single-guide RNAs targeted resistance genes or replication genes of specific incompatible plasmids that harboured resistance genes, providing a novel means to naturally select bacteria that cannot uptake and disseminate such genes.
The impact of non-antimicrobial drug agents on the acquisition of ESBL-producing Enterobacterales in non-critical care wards in a German university hospital: an exploratory, matched case–control study
Authors: Klauke Paula , Schwab Frank , Gastmeier Petra , Maechler Friederike ,   the R-GNOSIS WP5 study group, Behnke M , Blok H , Bonten M J , Brun-Buisson C , Canton R , Cooper B S , Diaz-Agero C , Fankhauser C , Gastmeier P , Golembus J , Goossens H , Hansen S , Harbarth S , Huttner B D , Kloosterman F , Kola A , Kuperberg A , Lammens C , Leus F , Lopez N , Maechler F , Malhotra S , Ruiz-Garbajosa P , Schotsman J , Schwab F , Triay C
Published: September 2021

Objectives

To investigate therapeutical drugs other than antimicrobials as risk factors for the acquisition of ESBL-producing Enterobacterales (ESBL-E).

Methods

This matched case–control study is based on rectal surveillance screening data obtained during a larger trial between 2014 and 2016 upon patients’ admission and at least once before discharge in eight non-ICU wards. Patients with ward-acquired ESBL-E (cases) were matched 1:1 to non-ESBL-E carriers (controls) based on ward, number of screening samples, days at risk and Charlson comorbidity index (CCI). Daily medication data were documented according to the Anatomical Therapeutic Chemical classification system. Multivariable conditional logistic regression models were used to calculate risk factors for ESBL-E acquisition.

Results

Of the 232 cases and 232 controls analysed, baseline characteristics such as gender (male 56.9%), median age (65 years old, IQR 52–74), number of screening samples (N = 3, IQR 2–4), days to first sample (2, IQR 1–2), days at risk (8, IQR 6–11) and CCI (4, IQR 2–6) were similar. Multivariable analysis showed that glucocorticoids, opium alkaloids and selective β-2-adrenoreceptor agonists increased the chance to detect ESBL-E (OR 1.07, 95% CI 1.001–1.13, P = 0.047; OR 1.06, 95% CI 1.007–1.12, P = 0.027; and OR 1.31, 95% CI 1.105–1.55, P = 0.001, respectively), while antihistamines decreased it (OR 0.61, 95% CI 0.39–0.97, P = 0.034). In a sensitivity analysis, including drugs prescribed to at least 50 patients, proton pump inhibitors remained as risk factors (OR 1.049, 95% CI 1.001–1.100, P = 0.047).

Conclusions

In a non-ICU setting, drugs other than antimicrobials were determined as potential independent risk factors for ESBL-E acquisition.
Adverse clinical outcomes associated with carbapenem-resistantAcinetobacter(CRA) infections: a systematic review and meta-analysis
Authors: Ling Weiping , Furuya-Kanamori Luis , Ezure Yukiko , Harris Patrick N A , Paterson David L
Published: September 2021

Background

Carbapenem-resistant Acinetobacter (CRA) infections have been associated with increased morbidity and mortality in hospitalized patients. This systematic review and meta-analysis aimed to quantify the association between CRA infections and adverse clinical outcomes.

Methods

Three databases (i.e. PubMed, EMBASE and Scopus) were searched for epidemiological studies that compared mortality, severe sepsis or shock, or bacteraemia among adult inpatients with CRA infections and those with carbapenem-susceptible Acinetobacter (CSA) infections. The pooled ORs for the three outcomes were estimated using the inverse variance heterogeneity model.

Results

Thirty-four studies were included. Patients with CRA infections had higher odds of mortality (31 studies, OR = 2.10, 95% CI: 1.58–2.79, I2=60.6%) and severe sepsis or septic shock (7 studies, OR = 1.51, 95% CI: 1.09–2.09, I2=0%) compared with CSA-infected patients. There was no difference in the odds of bacteraemia (four studies, OR = 1.39, 95% CI: 0.79–2.46, I2=38.1%). CRA-infected patients presented with worse comorbidity at admission (e.g. APACHE score) (eight studies, standardized mean difference = 0.25, 95% CI: −0.01 to 0.52) and had lower frequency of appropriate antibiotic therapy. Results were consistent when pooling 16 study-adjusted risk estimates for mortality. There was no difference in risk of mortality from CRA infection when compared across geographical regions, country income, median year of enrolment and day of mortality from infection onset.

Conclusions

CRA-infected patients had worse clinical outcomes. This might be due to delay in appropriate antibiotic therapy, patients being sicker at admission and CRA strains potentially being more virulent than CSA strains. Improving appropriateness of antibiotic therapy in CRA-infected patients could reduce adverse clinical outcomes.
Clinical, Methodological, and Practical Considerations for Algorithmic Testing in Autoimmune Serology
Authors: Sepiashvili Lusia , Kenyon Stacy M
Published: September 2021

Background

Autoimmune serology tests are central to the classification, screening, diagnosis, and monitoring of a variety of autoimmune disorders. To improve the appropriateness of serologic evaluation and support laboratory resource utilization, reflex testing approaches have been proposed and implemented across clinical laboratories. Reflex testing involves a staged approach where an initial test result triggers subsequent tests based on prespecified rules.

Content

Various reflex testing approaches in the context of antinuclear antibody-associated rheumatic disease, antineutrophil cytoplasmic autoantibody-associated vasculitis, celiac disease, and myasthenia gravis are reviewed here. Clinical, analytical, and practical considerations of reflex testing implementation are addressed as well as associated limitations and challenges.

Serology reflex testing algorithms for the evaluation of autoimmune diseases can support clinical diagnosis and laboratory resource use but may be challenging to implement and are often applied variably across institutions. Assessments of evidence-driven guidelines, clinical impact, and impact on laboratory workflow are essential to this task.
A model for building a national, patient-driven database to track contraceptive use in women with rare diseases
Authors: Josephy Tatiana , Loeffler Deena R , Pam Molly , Godfrey Emily M
Published: September 2021

Data on the safety and effectiveness of contraception among women with rare diseases are critical and sorely lacking. To fill this gap, we propose a national, patient-driven database that tracks contraceptive safety and effectiveness among women with rare diseases. We built a pilot database focusing on women with cystic fibrosis in 3 phases: (1) database design input from patients and experts, (2) merging of contraceptive survey data with relevant clinical outcomes from the Cystic Fibrosis Foundation Patient Registry (CFFPR), and (3) forming a data guide to facilitate accessible output data. We successfully linked 62 contraceptive survey variables with 362 relevant clinical outcome variables for 150 patients. This pilot represents a breakthrough in linking contraceptive data to disease-specific outcomes and informs how to build a national, patient-driven contraceptive database for women with rare diseases.
Loved As-Is: How God Salience Lowers Interest in Self-Improvement Products
Authors: Grewal Lauren , Wu Eugenia C , Cutright Keisha M
Published: September 2021

Consumers often desire to become better versions of themselves. Reflecting this interest in self-improvement, the marketplace offers consumers a wide range of products and services that promise to improve or better the consumer in some way. But, in a world with unlimited opportunities to spend one’s time and money, what influences whether consumers will invest in products that enable self-improvement? We demonstrate that the degree to which God is salient has a negative effect on individuals’ preferences for consumption choices with self-improvement features compared to equally attractive options that do not include such features. We propose that this is because thoughts of God activate a greater sense of being loved for who you are (“loved ‘as-is’”), making self-improvement a lower priority. We demonstrate this basic effect across several experiments as well as archival data, provide process evidence through mediation and moderation, and address alternative explanations. We also identify important boundary conditions: God salience is less likely to decrease interest in self-improvement products when consumers do not believe in God, and when God is considered to be a punishing (vs. loving) entity.
Limits of buyer-driven governance for sustainability: inherent challenges of fragmented supplier networks
Authors: Alexander Rachel
Published: September 2021

This article questions retailers’ role as buyers driving production. Exploring a network involving Indian suppliers of UK retailers’ cotton garments, limitations preventing coercive buyer power from controlling production practices are identified. Overall, the dominant system of large-scale fragmented supplier networks connecting raw materials to final products accommodates commercially viable practices causing social or environmental challenges. While some pressures effectively span complex networks, buyers’ practice-related demands do not. Dissecting the ‘drivenness’ concept, this study shows multipolar governance within an industry often considered buyer-driven. Also, it furthers critiques of private governance’s effectiveness, indicating the need for alternative governance frameworks or network structures.
Surveillance of patients with stage I or II colorectal cancer in Japan: a JCOG study group questionnaire survey
Authors: Moritani Konosuke , Shida Dai , Kanemitsu Yukihide , Shunsuke Tsukamoto , Hamaguchi Tetsuya , Shimada Yasuhiro ,   Colorectal Cancer Study Group of the Japan Clinical Oncology Group (JCOG)
Published: September 2021

Japanese Society for Cancer of the Colon and Rectum guidelines recommend regular, more intensive surveillance of patients who have undergone curative resection of pathological stages I–III colorectal cancer compared with guidelines in Western countries. We conducted a questionnaire survey to clarify the status of surveillance for patients with stage I or II colorectal cancer in high-volume centers in Japan on behalf of the Colorectal Cancer Study Group of the Japan Clinical Oncology Group. Questionnaires were distributed in September 2019. The response rate was 98.3% (59/60 institutions). The survey results indicated that about half of colorectal cancer specialists in Japan perform surveillance for stages I and II colorectal cancer according to the Japanese Society for Cancer of the Colon and Rectum guidelines. For stages I and II disease, 45% and 55% of surgeons, respectively, perform surveillance less intensively than recommended. Our findings suggest the possibility of less intensive surveillance for patients with stage I or II colorectal cancer in Japan.
α1A and α1C form microtubules to display distinct properties mainly mediated by their C-terminal tails
Authors: Diao Lei , Liu Ming-Yi , Song Yin-Long , Zhang Xu , Liang Xin , Bao Lan
Published: September 2021

Microtubules consisting of α/β-tubulin dimers play critical roles in cells. More than seven genes encode α-tubulin in vertebrates. However, the property of microtubules composed of different α-tubulin isotypes is largely unknown. Here, we purified recombinant tubulin heterodimers of mouse α-tubulin isotypes including α1A and α1C with β-tubulin isotype β2A. In vitro microtubule reconstitution assay detected that α1C/β2A microtubules grew faster and underwent catastrophe less frequently than α1A/β2A microtubules. Generation of chimeric tail-swapped and point-mutation tubulins revealed that the carboxyl-terminal (C-terminal) tails of α-tubulin isotypes largely accounted for the differences in polymerization dynamics of α1A/β2A and α1C/β2A microtubules. Kinetics analysis showed that in comparison to α1A/β2A microtubules, α1C/β2A microtubules displayed higher on-rate, lower off-rate, and similar GTP hydrolysis rate at the plus-end, suggesting a contribution of higher plus-end affinity to faster growth and less frequent catastrophe of α1C/β2A microtubules. Furthermore, EB1 had a higher binding ability to α1C/β2A microtubules than to α1A/β2A ones, which could also be attributed to the difference in the C-terminal tails of these two α-tubulin isotypes. Thus, α-tubulin isotypes diversify microtubule properties, which, to a great extent, could be accounted by their C-terminal tails.
Interactions of Age and Blood Immune Factors and Noninvasive Prediction of Glioma Survival
Authors: Molinaro Annette M , Wiencke John K , Warrier Gayathri , Koestler Devin C , Chunduru Pranathi , Lee Ji Yoon , Hansen Helen M , Lee Sean , Anguiano Joaquin , Rice Terri , Bracci Paige M , McCoy Lucie , Salas Lucas A , Christensen Brock C , Wrensch Margaret , Kelsey Karl T , Taylor Jennie W , Clarke Jennifer L
Published: September 2021

Background

Tumor-based classification of human glioma portends patient prognosis, but considerable unexplained survival variability remains. Host factors (eg, age) also strongly influence survival times, partly reflecting a compromised immune system. How blood epigenetic measures of immune characteristics and age augment molecular classifications in glioma survival has not been investigated. We assess the prognostic impact of immune cell fractions and epigenetic age in archived blood across glioma molecular subtypes for the first time.

Methods

We evaluated immune cell fractions and epigenetic age in archived blood from the University of California San Francisco Adult Glioma Study, which included a training set of 197 patients with IDH-wild type, 1p19q intact, TERT wild type (IDH/1p19q/TERT-WT) glioma, an evaluation set of 350 patients with other subtypes of glioma, and 454 patients without glioma.

Results

IDH/1p19q/TERT-WT patients had lower lymphocyte fractions (CD4+ T, CD8+ T, natural killer, and B cells) and higher neutrophil fractions than people without glioma. Recursive partitioning analysis delineated 4 statistically significantly different survival groups for patients with IDH/1p19q/TERT-WT based on an interaction between chronological age and 2 blood immune factors, CD4+ T cells, and neutrophils. Median overall survival ranged from 0.76 years (95% confidence interval = 0.55-0.99) for the worst survival group (n = 28) to 9.72 years (95% confidence interval = 6.18 to not available) for the best (n = 33). The recursive partitioning analysis also statistically significantly delineated 4 risk groups in patients with other glioma subtypes.

Conclusions

The delineation of different survival groups in the training and evaluation sets based on an interaction between chronological age and blood immune characteristics suggests that common host immune factors among different glioma types may affect survival. The ability of DNA methylation-based markers of immune status to capture diverse, clinically relevant information may facilitate noninvasive, personalized patient evaluation in the neuro-oncology clinic.
Real-World Use of Bone-Modifying Agents in Metastatic Castration-Sensitive Prostate Cancer
Authors: Mitchell Aaron P , Mishra Meza Akriti , Panageas Katherine S , Lipitz-Snyderman Allison , Bach Peter B , Morris Michael J
Published: September 2021

Background

Bone-modifying agent (BMA) therapy is recommended for metastatic castration-resistant prostate cancer but not metastatic castration-sensitive prostate cancer (mCSPC). BMA treatment in mCSPC may therefore constitute overuse.

Methods

In this retrospective cohort study using linked Surveillance, Epidemiology, and End Results–Medicare data, we included patients diagnosed with stage IV prostate adenocarcinoma from 2007 to 2015 who were 66 years of age or older at diagnosis and had received androgen-deprivation or antiandrogen therapy. We excluded patients who had previously received BMAs or had existing osteoporosis, osteopenia, hypercalcemia, or prior bone fracture. The primary outcome was receipt of BMA (zoledronic acid or denosumab) within 180 days of diagnosis (emergence of CRPC within this time frame is unlikely). The secondary outcome was receipt of a BMA within 90 days. Exposures of interest included practice location (physician office vs hospital outpatient) and the specialty (medical oncologist vs urologist) of the treating physician.

Results

Our sample included 2627 patients, of whom 52.9% were treated by medical oncologists and 47.1% by urologists; 77.7% and 22.3% received care in physician office and hospital outpatient locations, respectively. Overall, 23.6% received a BMA within 180 days; 18.4% did within 90 days. BMA therapy was more common among patients treated by oncologists (odds ratio = 8.23, 95% confidence interval = 6.41 to 10.57) and in physician office locations (odds ratio = 1.33, 95% confidence interval = 1.06 to 1.69). Utilization has increased: 17.3% of patients received BMAs from 2007 to 2009 (17.3% zoledronic acid, 0% denosumab) and 28.1% from 2012 to 2015 (8.4% zoledronic acid, 20.3% denosumab).

Conclusions

Among patients with mCSPC who had no evidence of high osteoporotic fracture risk, more than one-quarter have received BMAs in recent years. This overuse may lead to excess costs and toxicity.
Prospective Cohort Study of Pre- and Postdiagnosis Obesity and Endometrial Cancer Survival
Authors: Kokts-Porietis Renée L , McNeil Jessica , Morielli Andria R , Cook Linda S , Courneya Kerry S , Friedenreich Christine M
Published: September 2021

Background

Disease-free survival (DFS) and overall survival (OS) associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer survivors.

Methods

Endometrial cancer survivors diagnosed between 2002 and 2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peridiagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed-up until death or March 20, 2019. Cox proportional regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with DFS and OS. Statistical tests were 2-sided.

Results

A total of 540 and 425 cancer survivors were assessed peridiagnosis and follow-up, respectively. During the median 14.2 years of follow-up (range = 0.3-16.5 years), 132 participants had a recurrence and/or died (DFS), with 111 deaths overall (OS). Reduced DFS was noted with greater recalled weight 1 year before diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI 1 year before diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peridiagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peridiagnosis waist circumference of at least 88 cm was associated with decreased DFS (HR = 1.94, 95% CI = 1.24 to 3.03) and OS (HR = 1.90, 95% CI = 1.16 to 3.13). A twofold decrease in DFS and OS was associated with a BMI of at least 5% or weight change from 1 year before diagnosis to peridiagnosis. No associations were observed for the assessment during follow-up.

Conclusions

One-year before- and peridiagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from 1 year before to peridiagnosis may provide an important indication of future survival in this population.
Children’s Interpretation of Sentences Containing Multiple Scalar Terms
Authors: Bill Cory , Pagliarini Elena , Romoli Jacopo , Tieu Lyn , Crain Stephen
Published: September 2021

Sentences containing the scalar term “some”, such as “The pig carried some of his rocks”, are usually interpreted as conveying the scalar inference that the pig did not carry all of his rocks. Previous research has reported that when interpreting such sentences, children tend to derive fewer of these scalar inferences than adults ( Noveck (2001); Papafragou & Musolino (2003); Guasti et al. (2005), among others). One approach to explaining these results contends that children have difficulties accessing the alternative sentences involved in the derivation of such scalar inferences. This ‘Alternatives-based’ approach raises the possibility that children’s performance may improve if certain scalar terms are presented together in the same sentence, for example, if a sentence contains both an existential quantifier and a universal quantifier, as in “Every pig carried some of his rocks”. Such ‘EverySome’ sentences have been associated with the inference that not every pig carried all of his rocks, as well as the stronger inference that none of the pigs carried all of his rocks (see Chemla & Spector (2011), among others). We present two experiments that explore the possibility that children might more readily derive scalar inferences from sentences containing such a combination of scalar terms. Experiment 1 investigates children’s interpretation of sentences containing only the quantifier some and replicates the previously established finding of fewer inference-based interpretations by children compared to adults. Experiment 2 explores children’s interpretation of sentences in which “some” is embedded under “every”, and reveals that adults and children access inference-based interpretations of such sentences at similar rates. Moreover, adults and children appear to differ with regards to which of the two possible inferences their interpretations are based on. We discuss the implications of the experimental results for our understanding of children’s acquisition of scalar inferences and for proposals that attempt to capture differences between adults’ and children’s interpretive preferences.