bluuebunny/crossref_metadata_2025 huggingface dataset:
Scope of Outcomes in Trials and Observational Studies of Interventions Targeting Medication Adherence in Rheumatic Conditions: A Systematic Review
Authors: Kelly Ayano , Crimston-Smith Luke , Tong Allison , Bartlett Susan J. , Bekker Charlotte L. , Christensen Robin , De Vera Mary A. , de Wit Maarten , Evans Vicki , Gill Michael , March Lyn , Manera Karine , Nieuwlaat Robby , Salmasi Shahrzad , Scholte-Voshaar Marieke , Singh Jasvinder A. , Sumpton Daniel , Toupin-April Karine , Tugwell Peter , van den Bemt Bart , Verstappen Suzanne , Tymms Kathleen
Published: December 2019

Objective.

Nonadherence to medications is common in rheumatic conditions and associated with increased morbidity. Heterogeneous outcome reporting by researchers compromises the synthesis of evidence of interventions targeting adherence. We aimed to assess the scope of outcomes in interventional studies of medication adherence.

Methods.

We searched electronic databases to February 2019 for published randomized controlled trials and observational studies of interventions with the primary outcome of medication adherence including adults with any rheumatic condition, written in English. We extracted and analyzed all outcome domains and adherence measures with prespecified extraction and analysis protocols.

Results.

Overall, 53 studies reported 71 outcome domains classified into adherence (1 domain), health outcomes (38 domains), and adherence-related factors (e.g., medication knowledge; 32 domains). We subdivided adherence into 3 phases: initiation (n = 13 studies, 25%), implementation (n = 32, 60%), persistence (n = 27, 51%), and phase unclear (n = 20, 38%). Thirty-seven different instruments reported adherence in 115 unique ways (this includes different adherence definitions and calculations, metric, and method of aggregation). Forty-one studies (77%) reported health outcomes. The most frequently reported were medication adverse events (n = 24, 45%), disease activity (n = 11, 21%), bone turnover markers/physical function/quality of life (each n = 10, 19%). Thirty-three studies (62%) reported adherence-related factors. The most frequently reported were medication beliefs (n = 8, 15%), illness perception/medication satisfaction/satisfaction with medication information (each n = 5, 9%), condition knowledge/medication knowledge/trust in doctor (each n = 3, 6%).

Conclusion.

The outcome domains and adherence measures in interventional studies targeting adherence are heterogeneous. Consensus on relevant outcomes will improve the comparison of different strategies to support medication adherence in rheumatology.
Association Between Vitamin D Deficiency and Disease Activity, Disability, and Radiographic Progression in Early Rheumatoid Arthritis: The ESPOIR Cohort
Authors: Mouterde Gaël , Gamon Etienne , Rincheval Nathalie , Lukas Cédric , Seror Raphaele , Berenbaum Francis , Dupuy Anne-Marie , Daien Claire , Daurès Jean-Pierre , Combe Bernard
Published: December 2019

Objective.

To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA).

Methods.

Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire–Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes.

Results.

Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10–29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined (P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76).

Conclusion.

Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091]
Large-vessel Vasculitis Affecting the Aorta and its Branches in Relapsing Polychondritis: Case Series and Systematic Review of the Literature
Authors: Tomelleri Alessandro , Campochiaro Corrado , Sartorelli Silvia , Papa Maurizio , De Luca Giacomo , Cavalli Giulio , Baldissera Elena , Dagna Lorenzo
Published: December 2019

Objective

To describe the features of large-vessel vasculitis (LVV) as it affects the aorta and its branches in patients with relapsing polychondritis (RP).

Methods

Retrospective data and systematic literature review.

Results

Twenty-one patients were identified. LVV diagnosis was subsequent to RP and associated with extrachondral involvement in the majority of patients. Supraaortic vessels were more frequently involved (82%). Fourteen patients (67%) were treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and 7 (33%) with a biological DMARD (bDMARD). Vascular interventional procedures were performed in 10 patients (48%). Premature death due to cardiovascular complications was reported in 3 cases (14%).

Conclusion

Extraaortic LVV is a serious and overlooked RP manifestation. All patients with RP should be investigated for LVV.
Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus
Authors: Moore Stanley , Juo Hsin-Hsuan , Nielsen Christoffer T. , Tyden Helena , Bengtsson Anders A. , Lood Christian
Published: December 2019

Objective

Neutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity.

Methods

Levels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44–142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system.

Results

Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001).

Conclusion

NET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.
Nostalgia, novelty, and the subversion of authority in "The Testaments of the Twelve Patriarchs"
Authors: De Bruin Tom
Published: December 2019

The Testaments of the Twelve Patriarchs, by negotiating the authorship and authority of its derivative readings, discusses the place of Israel vis-à-vis Christianity through almost fannish retellings of the lives of the patriarchs of Israel. The text thereby walks a line between nostalgic and novel readings of foundational narratives, in some places perpetuating canonical authority and in others subverting it. The outcome of this interplay is the displacement of the Israelite author and Christianization of Israelite history. Contemporary fan fiction studies discourse provides tools for analyzing this negotiation of textual authority.
The queen of Sheba as a transformative work protagonist
Authors: Oudová Holcátová Barbara
Published: December 2019

The story of the queen of Sheba has often puzzled commentators with its numerous late transformations, which are both colorful and sexual. The transformations of the queen of Sheba's story invoke many of the patterns familiar from fan fiction. Such transformations of ancient tales also provide preliminary explanations of why the themes in the various versions of her story appear again and again. This too shows parallels with fan fiction.
Gender, voice, and canon
Authors: Barenblat Rachel
Published: December 2019

The Jewish tradition of midrash (exegetical/interpretive fiction) parallels the fannish tradition of creating fan works in more ways than one. In the twentieth century, both contexts saw the rise of women's voices, shifting or commenting on androcentric canon—and in both contexts today, that gender binarism is giving way to a more complicated and multifaceted tapestry of priorities and voices.
Navigating Catholicism and queerness in "Daredevil" fan works
Authors: Griffin Alexandria
Published: December 2019

In Daredevil (2015–18) fan works, fans confront the character of Daredevil, who is portrayed in the Netflix TV series of the same name as explicitly religious, namely Catholic. This means that fan works seeking to explore sexuality, especially same-sex sexuality, must confront Catholicism's prohibition on extramarital sex, including same-sex sexual relations. I examine how fan works use Daredevil as a site from which to examine and debate Catholicism and queerness.
Queering the Anglo-Saxons through their psalms
Authors: Mussies Martine
Published: December 2019

For fan fiction based on the TV serial drama The Last Kingdom (2014–), some fan fiction authors use fragments of the translations of the Psalms by King Alfred of Wessex (849–899) to firmly ground their stories in the historical reimagination of the Anglo-Saxons. In the short story "Æthelflaed and Lagertha," fan fiction writer Bandi Crawford uses an Alfredian psalm to connect The Last Kingdom to another major TV series, Vikings (2013–). By developing bisexual and biromantic story lines along the lines of Alfredian psalms, the author constructs a twenty-first-century neomedieval-based culture in which the Alfredian psalms are reinterpreted or critically reexamined through a queer lens, thereby negotiating more diversity within a favorite show's story world.
Use of Pesticides in Agricultural Products and Its Impact on Human Health: A Review
Authors: Kaur Tejinder , Sinha A. K.
Published: December 2019

n the present review paper, reviews of recent research findings on health effects of pesticides on agricultural products has been highlighted. The review reveals that although the concentration of the health literature has been on individuals who are in direct contact with pesticides, e.g. farmers, and the literature on preference elicitation has focused on those with indirect exposure like the consumers. On reviewing it was found that majority of farmers used crop rotation and control by hand methods, also they were aware about the pesticide use. In contrast, a few of the farmers used cultural and biological methods. Although they are interested to use seeds which are pest resistance, they cannot use those because of non-availability of seeds. Few of the studies, reported excessive sweating (36.5%), burning/stinging/itching of eyes (35.7%), dry/sore throat (25.5%), and excessive salivation (14.1%), all were more prevalent among sprayers. Men experienced excessive sweating and eye and throat problems as associated with pesticide exposure. One of the study disclosed that increased risk was observed for some specific classes of pesticides. The study concludes that there are many inherent problems in conducting large-scale experiments to directly assess the causation of the human health problems associated with the use of pesticides.
Increasing the targeting scope and efficiency of base editing with Proxy‐BE strategy
Authors: Liu Yin , Li Guanglei , Yang Guang , Gu Huifeng , Huang Shisheng , Yu Wenxia , Qin Guizhen , Liu Xinyi , Zhou Fuling , Huang Xingxu , Wei Yongchang
Published: December 2019

Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy‐clustered regularly interspaced short palindromic repeats strategy, termed Proxy‐BE, to increase gene editing efficiency. Specifically, a nuclease‐dead Cas9 (dCas9) was bound to the sequence about 20–30 base pair away from the target site, potentially improving access to the DNA and, thus, providing a better editing microenvironment for base editors. Our findings confirm that nuclease‐dead Streptococcus pyogenes Cas9 can assist the base editors SaKKH‐BE3 and dCpf1‐BE to double their canonical base editing efficiency. This work provides a new approach to enhance base editing, extending its scope for biological research and gene therapy.
Radical‐Cation‐Induced Crossed [2+2] Cycloaddition of Electron‐Deficient Anetholes Initiated by Iron(III) Salt
Authors: Horibe Takahiro , Katagiri Kei , Ishihara Kazuaki
Published: December 2019

Radical cation‐induced crossed [2+2] cycloaddition of electron‐deficient anetholes was developed with the use of Fe(OTf)3 as an initiator. Various 1,2‐diarylcyclobutanes can be synthesized in high yields with high diastereoselectivity from electron‐deficient anetholes, which have been less explored using conventional methods. This practical reaction system can be used for a decagram‐scale reaction (12 gram), in which the resulting product can be transformed to 1,2‐dicarbonyl compounds.

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An improved subgrid scale model for front‐tracking based simulations of mass transfer from bubbles
Authors: Claassen Claire M. Y. , Islam Shafiul , Peters E. A. J. F. (Frank) , Deen Niels G. , Kuipers J. A. M. (Hans) , Baltussen Maike W.
Published: December 2019

Gas–liquid bubble column reactors are often used in industry because of their favorable mass transfer characteristics. The bubble mass boundary layer in these systems is generally one order of magnitude thinner than the momentum boundary. To resolve it in simulations, a subgrid scale model will account for the sharp concentration variation in the vicinity of the interface. In this work, the subgrid scale model of Aboulhasanzadeh et al., Chem Eng Sci, 2012, 75:456–467 embedded in our in‐house front tracking framework, has been improved to prevent numerical mass transfer due to remeshing operations. Furthermore, two different approximations of the mass distribution in the boundary layer have been tested. The local and global predicted Sherwood number has been verified for mass transfer from bubbles in the creeping and potential flow regimes. In addition, the correct Sherwood number has been predicted for free rising bubbles at several Eötvös and Morton numbers with industrial relevant Schmidt numbers (103–105).
Hand morphometrics, electrodermal activity, and stone tools haptic perception
Authors: Fedato Annapaola , Silva‐Gago María , Terradillos‐Bernal Marcos , Alonso‐Alcalde Rodrigo , Martín‐Guerra Elena , Bruner Emiliano
Published: December 2019

Objectives

Tool use requires integration among sensorial, biomechanical, and cognitive factors. Taking into account the importance of tool use in human evolution, changes associated with the genus Homo are to be expected in all these three aspects. Haptics is based on both tactile and proprioceptive feedbacks, and it is associated with emotional reactions. Previous analyses have suggested a difference between males and females, and during haptic exploration of different typologies of stone tools. Here, we analyze the correlation between electrodermal reactions during stone tool handling and hand morphology to provide evidence of possible allometric factors shared by males and females.

Methods

Electrodermal analysis was used to investigate some specific parameters involved in these reactions, such as changes in the level of attention and arousal. We analyzed the responses of 46 right‐handed adults to 20 distinct stone tools while blindfolded.

Results

Females have smaller hands and a wider range of electrodermal reactions. Within males and females, hand diameters and general hand size do not correlate with the degree of electrodermal level and response.

Conclusions

Sex differences in electrodemal reaction during stone tool handling are apparently not due to the effect of hand size or proportions. Differences between males and females are better interpreted as real sex differences, either due to a biological or cultural influences. Hand size does not influence the degree of arousal or attention during tool exploration, suggesting that other factors trigger individual reactions. These results add to a general cognitive approach on hand‐tool evolution and tool sensing.
Low digit ratio (2D:4D) is associated with early natural menopause
Authors: Kirchengast Sylvia , Dottolo Elisabeth , Praxmarer Elisa , Huber Johannes
Published: December 2019

Objectives

Intrauterine environmental conditions may affect the number of primordial follicles and in this way the timing of menopause. The aim of the present study was to investigate association patterns between right hand digit ratio, that is, 2D:4D ‐ as an indicator of prenatal androgen and estrogen exposure, and age at menopause.

Methods

One hundred sixty‐nine women, who had experienced natural menopause, were enrolled in the study. Length of second and fourth finger were measured directly from the palmar side and digit ratios of both hands were calculated. For further analyses the digit ratio of the right hand was used only. Additionally, smoking habits, body weight and body height, body mass index and the number of children were determined. Multiple regression analyses were used to test association patterns between digit ratio and age at menopause, body height, BMI, nicotine consumption as well as number of births and age at menopause.

Results

Age at menopause correlated significantly positively with the digit ratio. A more feminine digit ratio is associated with a higher age at menopause, while a low digit ratio, interpreted as a hint of a higher androgen exposure during prenatal phase was associated with a lower age at menopause.

Conclusions

Low digit ratio is associated with an earlier onset of natural menopause.
Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan
Authors: Lee Chung‐Lin , Tan Louis Tan Hock‐Cheong , Lin Hsiang‐Yu , Hwu Wuh‐Liang , Lee Ni‐Chung , Chien Yin‐Hsiu , Chuang Chih‐Kuang , Wu Mei‐Hwan , Wang Jou‐Kou , Chu Shao‐Yin , Lin Ju‐Li , Lo Fu‐Sung , Su Pen‐Hua , Hsu Chia‐Chi , Ko Yu‐Yuan , Chen Ming‐Ren , Chiu Hui‐Ching , Lin Shuan‐Pei
Published: December 2019

RASopathies are developmental diseases caused by mutations in rat sarcoma–mitogen‐activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS‐related disorders (NSRD), including cardio‐facio‐cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu‐Chi General Hospital, Chang‐Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross‐sectional and color Doppler echocardiography, electrocardiographic findings, and follow‐up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype–cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.
Gain‐of‐function pathogenic variants in SMAD4 are associated with neoplasia in Myhre syndrome
Authors: Lin Angela E. , Alali Abdulrazak , Starr Lois J. , Shah Nidhi , Beavis Anna , Pereira Elaine M. , Lindsay Mark E. , Klugman Susan
Published: December 2019

Myhre syndrome is an increasingly diagnosed rare syndrome that is caused by one of two specific heterozygous gain‐of‐function pathogenic variants in SMAD4. The phenotype includes short stature, characteristic facial appearance, hearing loss, laryngotracheal stenosis, arthritis, skeletal abnormalities, learning and social challenges, distinctive cardiovascular defects, and a striking fibroproliferative response in the ear canals, airways, and serosal cavities (peritoneum, pleura, pericardium). Confirmation of the clinical diagnosis is usually prompted by the characteristic appearance with developmental delay and autistic‐like behavior using targeted gene sequencing or by whole exome sequencing. We describe six patients (two not previously reported) with molecularly confirmed Myhre syndrome and neoplasia. Loss‐of‐function pathogenic variants in SMAD4 cause juvenile polyposis syndrome and we hypothesize that the gain‐of‐function pathogenic variants observed in Myhre syndrome may contribute to neoplasia in the patients reported herein. The frequency of neoplasia (9.8%, 6/61) in this series (two new, four reported patients) and endometrial cancer (8.8%, 3/34, mean age 40 years) in patients with Myhre syndrome, raises the possibility of cancer susceptibility in these patients. We alert clinicians to the possibility of detecting this syndrome when cancer screening panels are used. We propose that patients with Myhre syndrome are more susceptible to neoplasia, encourage increased awareness, and suggest enhanced clinical monitoring.
Three‐dimensional analysis of sexual dimorphism in the soft tissue morphology of the upper airways in a human population
Authors: Bastir Markus , Megía Irene , Torres‐Tamayo Nicole , García‐Martínez Daniel , Piqueras Francisco M. , Burgos Manuel
Published: December 2019

Objectives

Several studies have analyzed the sexual dimorphism of the skeletal cranial airways. This study aimed to quantify the three‐dimensional (3D) morphology of the soft tissues of the upper airways in a human population. We addressed hypotheses about morphological features related to respiratory and energetic aspects of nasal sexual dimorphism.

Methods

We reconstructed 3D models of 41 male and female soft tissue nasal airways from computed tomography data. We measured 280 landmarks and semilandmarks for 3D‐geometric morphometric analyses to test for differences in size and 3D morphology of different functional compartments of the soft tissue airways.

Results

We found statistical evidence for sexual dimorphism: Males were larger than females. 3D features indicated taller and wider inflow tracts, taller outflow tracts and slightly taller internal airways in males. These characteristics are compatible with greater airflow in males.

Discussion

The differences in 3D nasal airway morphology are compatible with the respiratory‐energetics hypothesis according to which males differ from females because of greater energetic demands. Accordingly, structures related to inflow and outflow of air show stronger signals than structures relevant for air‐conditioning.
At the world's edge: Reconstructing diet and geographic origins in medieval Iceland using isotope and trace element analyses
Authors: Walser Joe W. , Kristjánsdóttir Steinunn , Gröcke Darren R. , Gowland Rebecca L. , Jakob Tina , Nowell Geoff M. , Ottley Chris J. , Montgomery Janet
Published: December 2019

Objectives

A multi‐isotope study was conducted on individuals buried at Skriðuklaustur monastery (AD 1493–1554) to investigate their geographic origins and dietary composition. Comparative material from individuals excavated from Skeljastaðir, an inland farm site was also analyzed.

Materials and methods

Bone collagen was extracted from 50 humans (Skriðuklaustur and Skeljastaðir) and 25 animals (Skriðuklaustur) and analyzed for δ13C, δ15N, and δ34S. Dental enamel samples from 31 individuals (Skriðuklaustur) were also analyzed for 87Sr/86Sr, δ18O, δ13C, and trace elements (Pb, Sr, Zn, Ba).

Results

The mean value determined from individuals from Skriðuklaustur (n = 36) was δ13C = −18.7 ± 0.8‰, δ15N = 12.8 ± 1.1‰, and δ34S = 9.0 ± 1.6‰, whereas at Skeljastaðir (n = 14), it was δ13C = −20.5 ± 0.8‰, δ15N = 7.8 ± 0.9‰, and δ34S = 9.4 ± 1.6‰. At Skriðuklaustur, human dental enamel samples (n = 31) provided a 87Sr/86Sr range of 0.7060–0.7088, δ18Ophosphate from 13.9 to 16.1‰ and δ13Ccarbonate from −16.6 to −12.9‰. Inferred drinking water (δ18Odw) values range from −12.3 to −8.9‰. Sr concentrations range from 25.8 to 156.7 ppm, Ba from 0.11 to 0.81 ppm, Zn from 43.8 to 145.8 ppm, and Pb from 0.13 to 9.40 ppm.

Discussion

A combination of results indicates that the people from Skriðuklaustur were born in Iceland, but some lived inland during childhood while others lived closer to the coast. Since Skriðuklaustur was a hospital, these individuals may have sought medical treatment at the monastery. The δ13C and δ15N values determined from bone collagen indicate that the people residing at Skriðuklaustur consumed a diet high in marine protein, while those residing at Skeljastaðir exhibit values more consistent with terrestrial resources.
Persistent wheezing caused by carvedilol overdose in a non‐asthmatic man
Authors: Nakanishi Misuzu , Kuriyama Akira , Onodera Mutsuo
Published: December 2019

Background

Cardiovascular dysfunction is the main manifestation of β‐blocker intoxication; however, respiratory manifestations have rarely been reported.

Case Presentation

A 41‐year‐old man, who had ingested 300 mg carvedilol in a suicide attempt, was transferred to our emergency department. The patient had wheezing on arrival; however, he had no known history of bronchial asthma. In the absence of signs of heart failure, we gave the patient inhaled procaterol, a short‐acting β2 agonist. The wheezing disappeared approximately 60 h after carvedilol ingestion and did not recur thereafter.

Conclusion

We report a case of wheezing caused by carvedilol intoxication. Although rare, clinicians should recognize that wheezing or bronchospasm can develop following β‐blocker intoxication, for which a short‐acting β2 agonist could be indicated.
Recent Advances in Covalent Organic Frameworks for Catalysis
Authors: Liu Jianguo , Wang Nan , Ma Longlong
Published: December 2019

Covalent organic frameworks (COFs) as an emerging type of crystalline porous materials, have obtained considerable attention recently. They have exhibited diverse structure and attractive performance in various catalytic reactions. It is highly expected to have a systematic and comprehensive review summing up COFs‐derived catalysts in homogeneous and heterogeneous catalysis, which is favorable to the judicious design of an efficient catalyst for targeted reaction. Herein, we focus on summarizing recent and significant developments in COFs materials, with an emphasis on both the synthetic strategies and targeted functionalization, and categorize it in accordance with the different types of catalytic reactions. Their potential catalysis applications are reviewed thoroughly. Moreover, a personal view about the future development of COFs catalysts with respect to the large‐scale production is also discussed.
Systematic oversizing of service lines and water meters
Authors: Douglas Christopher , Buchberger Steven , Mayer Peter
Published: December 2019

Sizing service lines and water meters for buildings is a common exercise with important implications for utilities and consumers. Selecting the diameter of a service line requires designers to balance economics and performance. Small‐diameter pipes may minimize cost but impair service with high head loss; larger pipes may ensure adequate pressure but increase the cost of the premise plumbing system. The water meter must also be sized to perform reliably and accurately while measuring both high and low flows. In this investigation, flow data from 43 buildings fitted with water‐conserving fixtures were collected at 10‐s logging intervals for 2 weeks. It was found that 37 of the 43 sites would likely have benefited from a smaller water meter. Of the 37 sites, 29 could likely have also been fitted with a smaller service line and not violated a 10‐ft/s water‐velocity limit that some building codes impose.
Understanding the correlation between artificial insemination and offspring health outcomes
Authors: Navarro‐Rubio Sonsoles , Güell Francisco
Published: December 2019

Although numerous articles have shown intracytoplasmic sperm injection and in vitro fertilization to be correlated with increased risk of disease, a few works have been published on the risks associated with artificial insemination. Meanwhile, questions about the possible causes underlying these correlations have remained in the background. The main objective of this work is not to review the risks associated with artificial insemination, but rather to describe how developmental processes may be affected by these techniques. Thus, we offer a theoretical framework for understanding the possible causes that underlie the correlation between low‐complexity or milder techniques and offspring health outcomes.
Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation
Authors: Gomez‐Pinedo Ulises , Cuevas Jesús Adriel , Benito‐Martín María Soledad , Moreno‐Jiménez Lidia , Esteban‐Garcia Noelia , Torre‐Fuentes Laura , Matías‐Guiu Jordi A. , Pytel Vanesa , Montero Paloma , Matías‐Guiu Jorge
Published: December 2019

Introduction

Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination.

Material and methods

We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site.

Results

Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms.

Conclusion

Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.
Daniel Smith Lamb (1843–1929): A window into the early histories of the Army Medical Museum and Howard University Medical School
Authors: Wright James R. , Spatola Brian
Published: December 2019

U.S. Army doctor Daniel Smith Lamb was a significant figure in the history of American pathology during its formative years. For 55 years (1865–1920), Lamb performed hundreds of autopsies in and around Washington, D.C. and personally collected over 1,500 gross pathology specimens for the Army Medical Museum. His work began at the close of the Civil War and continued on through World War I, contributing substantially to gross pathological and histological studies that documented wartime pathology, thus further contributing to the training of Army doctors. Specimens he collected also include material from autopsies he conducted on President James Garfield, his assassin Charles Guiteau, and other historical figures. Under the auspices of the Army Medical Museum, he conducted autopsies across the city of Washington for the museum's collection, many of which survive to this day at the National Museum of Health and Medicine. He served under 12 U.S. Army Surgeons General and 11 Museum Curators and was noted to be a steadying influence during a time of constant leadership changes at that institution. Lamb was known throughout Washington, D.C. as an advocate of medical education for African‐Americans and women. While working at the Museum, he simultaneously served for 46 years as professor of anatomy at Howard University (1877–1923). He wrote seminal histories of the institutions with which he was associated and in so doing also contributed significantly to the study of the history of medicine.
Mapping the genicular arteries to provide a caution zone during knee surgery
Authors: Barner Kyle L. , Mayer Catherine M. , Orth Charles , Tran Quoc V. , Olinger Anthony B. , Wright Barth W.
Published: December 2019

Introduction

Reports from the current literature show a lack of detail with depictions of the genicular arteries (GA). The intricate anatomy and infrequency of operating in the posterior knee may lead to surgeons being unfamiliar with the anatomy. The goal of this cadaveric study was to quantitatively map the arteries and create a caution zone that can be utilized when preparing and performing surgical procedures involving the knee.

Materials and methods

The left knees of 46 cadavers were used. The distance of the GAs were from the joint line (JL) (+, superior to JL; −, inferior to JL) was measured in two locations: popliteal artery (PA) branch point and medial/lateral knee. The angle the artery traveled between these two points in the posterior knee was measured. A caution map was created.

Results

The superolateral GA branched from PA at +47.3 mm and traveled superiorly at 57.7° to +52.2 mm at the lateral knee. The superomedial GA branched from PA at +55.2 mm and traveled superiorly at 66.8° to +57.3 mm at the medial knee. The inferolateral GA branched from PA at −0.6 mm. It traveled superiorly at 74.1° or inferiorly at 62.1° to −1.0 mm at the lateral knee. The inferomedial GA branched from the PA at +9.9 mm. It traveled inferiorly at 21.2° to −33 mm at the medial knee.

Conclusion

The GAs have a predictable pattern of location in the knee. There is a mismatch between medical textbooks and reality regarding arterial depictions. Knowledge regarding where the arteries are located may help reduce vascular complications in patients in the future.
Clinical implications of nervus intermedius variants in patients with geniculate neuralgia: Let anatomy be the guide
Authors: Clifton William E. , Grewal Sanjeet , Lundy Larry , Cheshire William P. , Tubbs R. Shane , Wharen Robert E.
Published: December 2019

Geniculate neuralgia (GN) is an uncommon, but severe, condition that is characterized by excruciating paroxysmal pain in the seventh cranial nerve's cutaneous distribution of general somatic afferent fibers carried through the nervus intermedius (NI). GN becomes a surgical disease in refractory cases of pain after exhaustive medical management. Surgical intervention in the form of microvascular decompression and nerve sectioning has been investigated with good patient outcomes. Despite this, there are limited guidelines on either technique's appropriateness in specific operative scenarios. In our 30‐year experience in GNs surgical management, we have found that a detailed knowledge of the NIs anatomy, variants, and intraoperative surgical anatomic findings are the key to choosing the most appropriate intervention, and may provide the answer to why some patients fail to experience pain relief after surgery. These anatomic variants also may explain why many patients commonly do not experience side effects related to the visceral efferent and special afferent fibers after nerve sectioning.
A risk prediction model for heart failure hospitalization in type 2 diabetes mellitus
Authors: Williams Brent A. , Geba Daniela , Cordova Jeanine M. , Shetty Sharash S.
Published: December 2019

Background

Antidiabetic therapies have shown disparate effects on hospitalization for heart failure (HHF) in clinical trials. This study developed a prediction model for HHF in type 2 diabetes mellitus (T2DM) using real world data to identify patients at high risk for HHF.

Hypothesis

Type 2 diabetics at high risk for HHF can be identified using information generated during usual clinical care.

Methods

This electronic medical record‐ (EMR‐) based retrospective cohort study included patients with T2DM free of HF receiving healthcare through a single, large integrated healthcare system. The primary endpoint was HHF, defined as a hospital admission with HF as the primary diagnosis. Cox regression identified the strongest predictors of HHF from 80 candidate predictors derived from EMRs. High risk patients were defined according to the 90th percentile of estimated risk.

Results

Among 54,452 T2DM patients followed on average 6.6 years, estimated HHF rates at 1, 3, and 5 years were 0.3%, 1.1%, and 2.0%. The final 9‐variable model included: age, coronary artery disease, blood urea nitrogen, atrial fibrillation, hemoglobin A1c, blood albumin, systolic blood pressure, chronic kidney disease, and smoking history (c = 0.782). High risk patients identified by the model had a >5% probability of HHF within 5 years.

Conclusions

The proposed model for HHF among T2DM demonstrated strong predictive capacity and may help guide therapeutic decisions.
Dual targeting of cholinesterase and amyloid beta with pyridinium/isoquinolium derivatives
Authors: Chakravarty Harapriya , Ju Yaojun , Chen Wen‐Hua , Tam Kin Y.
Published: December 2019

With the surge in the cases of Alzheimer's disease (AD) over the years, several targets have been explored to curb the disease. Cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), remain to be the available targets that are amendable to currently approved treatments. In this study, a series of novel compounds based on tramiprosate, a highly specific amyloid beta (Aβ) inhibitor, was designed to inhibit AChE, BuChE, and Aβ aggregation. In particular, the addition of a pyridinium/isoquinolinium ring to the tramiprosate moiety (to give compounds 3a–j) led to an increase in the binding affinity for the catalytic active site of cholinesterase, which was hampered by the presence of sulfonic acid. Exclusion of the sulfonic acid moiety led to a novel but effective class of cholinesterase inhibitors (9a–w). in vitro Aβ aggregation inhibition assay indicated that compounds 3a–j, 9e–f, 9i–l, 9q, 9r, 9u–w, and 12 could inhibit over 10% Aβ aggregation at 1 mM concentration. Cholinesterase inhibition assay suggested that compounds 9g, 9h, 9o, and 9q–t exhibit over 70% inhibition on both AChE and BuChE at a concentration of 100 μM. Amongst the designed molecules, compound 9r (ca 18% at 1 mM) showed comparable inhibitory effect on the inhibition of Aβ aggregation with tramiprosate (ca 20% at 1 mM), along with impressive cholinesterase inhibitory potential (AChE IC50 = 13 μM and BuChE IC50 = 12 μM), acceptable toxicity and ability to pass through blood brain barrier, which could be used to ameliorate the phenotypes of AD in preclinical models.
Loading protocols for experimental seismic qualification of members in conventional and emerging steel frames
Authors: Fang Cheng , Ping Yiwei , Chen Yiyi
Published: December 2019

Quasi‐static testing is one of the most commonly used experimental methods for examining the seismic performance of structural members. However, consistent loading protocols for experimental seismic qualification of members in emerging steel frames such as self‐centering braced frames (SCBFs) as well as in some conventional ones including buckling‐restrained braced frames (BRBFs) are still lacking. This paper aims to propose standardized loading protocols based on time‐history dynamic analysis on a series of prototype building frames, including steel SCBFs, BRBFs, and moment‐resisting frames (MRFs), where both far‐field and near‐fault earthquakes are considered. The methodology for the development of the loading protocols involves ground motion selection and scaling, design and analysis of prototype buildings, analysis results processing, and rainflow cycle counting, together with extra justification steps. The proposed loading protocols are consistently derived based on the MCE‐level seismic hazard and 84th percentile values of key seismic demand parameters. These parameters are number of damaging cycles Nt, maximum inter‐story drift θmax, inter‐story drift range Δθi, sum of inter‐story drift range ΣΔθi, and residual inter‐story drift θr. The analysis confirms the variations in these seismic demands imposed on the different structural systems under different types of ground motions, highlighting the necessity of developing separate loading protocols for the different cases. The assumptions, decisions, and judgments made during the development of the loading protocols are elaborated, and the conditions and restrictions are outlined. The rationality of the proposed loading protocols is further justified through demonstrating the cumulative distribution function and energy dissipation demand of the systems.
Shape‐preserving finite elements in cylindrical and spherical geometries: The double Jacobian approach
Authors: Morgan Jason P. , Taramón Jorge M. , Hasenclever Jörg
Published: December 2019

We present a new technique, the “double Jacobian,” to solve problems in cylindrical or spherical geometries, for example, the Stokes flow problem for convection in Earth's mantle. Our approach combines the advantages of working simultaneously in Cartesian and polar or spherical coordinates. The governing matrix equations are kept in Cartesian coordinates, thereby preserving their Cartesian symmetry. However, the element geometry is described as a linear simplex in polar or spherical coordinates, thereby preserving appropriate cylindrical or spherical surfaces and internal interfaces. Isoparametric representations can still be used to define complex surface shapes. Using linear polar or spherical elements allows search routines for triangular or tetrahedral simplexes to rapidly find arbitrary points in terms of their polar or spherical coordinates. The double Jacobian approach becomes especially powerful when element sizes vary strongly within the mesh, while the exact cylindrical or spherical surfaces or internal interfaces have to be preserved, as happens in several geophysical applications.
Real time prediction of irregular periodic time series data
Authors: Zhang Kaimeng , Ng Chi Tim , Na Myung Hwan
Published: December 2019

By means of a novel time‐dependent cumulated variation penalty function, a new class of real‐time prediction methods is developed to improve the prediction accuracy of time series exhibiting irregular periodic patterns: in particular, the breathing motion data of the patients during robotic radiation therapy. It is illustrated that for both simulated and empirical data involving changes in mean, trend, and amplitude, the proposed methods outperform existing forecasting methods based on support vector machines and artificial neural network in terms of prediction accuracy. Moreover, the proposed methods are designed so that real‐time updates can be done efficiently with O(1) computational complexity upon the arrival of a new signal without scanning the old data repeatedly.
The role of chromatin remodeling complexes in Schwann cell development
Authors: Fröb Franziska , Wegner Michael
Published: December 2019

Schwann cells develop from neural crest cells in an ordered series of events and give rise to myelinating and nonmyelinating subtypes. In their mature state, myelinating Schwann cells produce myelin sheaths that provide trophic support to axons and allow saltatory conduction in the vertebrate peripheral nervous system. Each step of Schwann cell development requires defined changes in chromatin structure that are catalyzed by chromatin remodeling complexes. Over the last years, all major types of chromatin remodeling complexes have been detected in Schwann cells and several have been functionally analyzed. SWI/SNF‐type, CHD‐type, and INO80/SWR‐type chromatin remodelers in particular have been shown to interact with multiple cell‐type specific transcription factors and histone modifiers and to be important regulators of Schwann cell development. As a result of different recruitment strategies, each chromatin remodeler targets defined genomic areas and impacts unique mechanisms at specific stages of Schwann cell development. Chromatin remodeling complexes undoubtedly constitute essential components of the Schwann cell regulatory network.
Achieving financial risk protection through a national Social Health Insurance Programme in Nigeria: Perspectives of enrollees and healthcare providers
Authors: Ebunoha Gladys N. , Ughasoro Maduka D. , Nwakoby Ifeoma C. , Onwujekwe Obinna E.
Published: December 2019

Introduction

Out‐of‐pocket (OOP) payment adversely affects universal financial risk protection (UFRP) and the achievement of Universal Health Coverage (UHC). Since the introduction of a Formal Sector Social Health Insurance Programme (FSSHIP) in Nigeria, the extent to which it has provided UFRP is still largely unknown. This study therefore assessed this from the perspectives of both enrollees and healthcare providers.

Methods

The study was undertaken in Enugu state, Nigeria. The subjects were randomly selected primary enrollees and health care providers. An interviewer‐administered questionnaire was used for data collection on service utilization under the FSSHIP, as well as out‐of‐pocket payment of healthcare expenditure.

Results

Out of 333 formal sector workers interviewed, 283 (85%) were registered in the FSSHIP and 61.1% of them utilized FSSHIP. Among these, 89.8% of them used OOP to pay for about 95.2% of the healthcare expenditure. From the perspectives of the providers, 97.6%, patients still paid using OOP.

Conclusion

The FSSHIP is not providing UFRP as expected. This weakens the effectiveness of the FSSHIP to ensure UFRP and ultimately UHC. The NHIS should modify the FSSHIP to provide UFRP and eliminate both the high level of OOP and the proportion of expenditure it covers.