bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic Performance Evaluation of RC Frame Designed Using Ethiopian and Chinese Seismic Codes
Authors: Getachew Kabtamu , Chen Deng-Hong , Peng Gang
Published: March 2020

This study presents the seismic performance evaluation of the reinforced concrete (RC) frame designed as per Ethiopian (based on EN1998‐1) and Chinese seismic codes to realize best practices within them. In the study, three‐model RC frames with 4‐, 8‐, and 12‐story are designed with the respective codes. Then, their seismic performances are evaluated using the nonlinear static (pushover) procedures of FEMA 356 and ATC 40 provisions. To validate the analysis result, dynamic nonlinear time history analysis is also made. The comparison parameters include elastic stiffness, peak strength, target displacement, and plastic hinge formation patterns in the structures. The results display many similarities in the global and local performances of the structures. Despite these, some noteworthy discrepancies are also noted. Besides, the performance point analysis revealed a significant difference in target displacement that reflects the two codes’ demand spectrum essential disagreements, particularly for the period of vibration greater than 2.0’s. In conclusion, the study highlighted the beneficial aspects of both codes, which will be useful for the future studies.
Identification of Fungal Pathogens of Mango and Soursop Fruits Using Morphological and Molecular Tools and Their Control Using Papaya and Soursop Leaf and Seed Extracts
Authors: Hernández-Guerrero Sara Elena , Balois-Morales Rosendo , Bautista-Rosales Pedro Ulises , López-Guzmán Graciela Guadalupe , Berumen-Varela Guillermo , Palomino-Hermosillo Yolotzin Apatzingan , Jimenez-Zurita José Orlando , Bello-Lara Juan Esteban , León-Fernandez Andrés Eloy
Published: March 2020

Fruit and vegetable products are susceptible to the attack of fungi during postharvest handling. Chemical fungicides are the most commonly used technique to control fungal diseases. However, an alternative product is the use of plant extracts, which have been reported inin vitroandin vivoconditions. The objective of this investigation was to identify one of the main pathogens of mango and soursop fruits using morphological and molecular tools as well as to evaluate thein vitroinhibitory effect of papaya and soursop leaf and seed extracts. Two pathogens were isolated and identified by their morphological and molecular characteristics from mango and soursop fruits. We obtained extracts from leaves and seeds of soursop and papaya using five solvents of increasing polarity (hexane, acetone, ethanol, methanol, and water) through the ultrasound-assisted extraction technique at a frequency of 35 kHz and 160 W for 14 min.In vitroevaluations of the extracts were performed using the Kirby–Bauer technique. The extracts with the highest percentage of inhibition were analyzed qualitatively and quantitatively using standardized techniques of colorimetry and spectrophotometry. Furthermore, we determined the content of total phenols, flavonoids, alkaloids, terpenoids, anthraquinones, coumarins, and saponins. As a result, we identified the pathogens asColletotrichum fructicolaandNectria haematococca. Aqueous extracts (water as a solvent) showed a higher percentage of inhibition of both pathogens compared with the other extracts. Furthermore, the aqueous extract of papaya leaf was the most effective among all extracts. The aqueous papaya leaf extract exhibited a percentage of inhibition of 49.86% forC. fructicolaand 47.89% forN. haematococca. The aqueous extracts of papaya leaf and seed (AqEPL and AqEPS) presented the greatest amount of metabolites (except anthraquinones and coumarins). The aqueous soursop leaf extract (AqESL) presented the greatest amount of phenols, tannins, and flavonoids (219.14 ± 8.52 mg GAE/L, 159.84 ± 10 mg GAE/g dm and 0.13 ± 1.12 × 10−4, respectively). The aqueous soursop seed extract (AqESS) had the highest saponin content with 1.2 ± 0.1 mg QSES/g dm and the papaya leaf accusative extract (AqEPL) had the highest alkaloid content (6.413 ± 1 × 10−3 mg AE/g dm) compared with the other extracts. The AqESS had a lower content of secondary metabolites (sterols, alkaloids, and saponins), while AqESL showed no presence of alkaloids and coumarins.
Primary Cutaneous CD30+ Anaplastic Large T Cell Lymphoma in a Patient Treated with Cyclosporine for Actinic Reticuloid
Authors: Gambichler T. , Patsinakidis N. , Susok L. , Segert M. H. , Doerler M.
Published: March 2020

Actinic reticuloid (AR)—a subtype of chronic actinic dermatitis—clinically and histopathologically shows lymphoma-like features. We report a male patient initially diagnosed with erythrodermic cutaneous T cell lymphoma (CTCL) who developed severe broadband photosensitivity. Clinical evaluation, histopathology, and phototesting were consistent with AR. The patient was treated with cyclosporine 150–300 mg/d. Under this therapy, he developed several times primary cutaneous anaplastic large cell lymphomas (C-ALCL) which in part tended to regress spontaneously under cyclosporine reduction. The association between cyclosporine treatment and development of C-ALCL and other CD30+ lymphoproliferative disorders has previously been reported in patients with atopic dermatitis, psoriasis, and transplant patients. In conclusion, the present case highlights the difficulties arising in the distinction between AR and CTCL and shows that long-term cyclosporine treatment may cause C-ALCL development in AR as well.
Association of Serum PSP/REG Iαwith Renal Function in Type 2 Diabetes Mellitus
Authors: Zhu Huimin , Zhu Xiangyun , Lin Hao , Liu Dechen , Dai Yu , Su Xianghui , Li Ling
Published: March 2020

Purpose. Pancreatic stone protein/regenerating protein I (PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iαlevels may reflect renal dysfunction. The purpose of this study was to detect the relationship between PSP/REG Iαand renal function in subjects with and without type 2 diabetes mellitus (T2DM).Methods. This cross-sectional study was conducted at Zhongda Hospital, affiliated with Southeast University in China. Serum PSP/REG Iαlevels were measured using a method of enzyme-linked immunosorbent assay. Baseline characteristics and biochemical parameters, such as blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA), were collected. The estimated glomerular filtration rate (eGFR) of each individual was calculated using the diagnostic criteria for renal function. Correlations between PSP/REG Iαand renal function parameters were analyzed by Spearman’s rank correlation coefficient using SPSS 20.0 software.Results. Serum PSP/REG Iαlevels were significantly higher in T2DM patients than those without T2DM (P<0.05). The level of PSP/REG Iαwas positively correlated with age, SCr, and BUN and negatively correlated with eGFR. The ordinal multiple logistic regression analysis further illustrated that PSP/REG Iαlevels were negatively related with eGFR in both groups after adjusting for other parameters.Conclusions. Serum PSP/REG Iαlevel is significantly upregulated in T2DM patients and reflects renal function in both T2DM and nondiabetic control groups. The relationship between PSP/REG Iαand eGFR suggested that PSP/REG Iαmight be a potential indicator of renal dysfunction.
RNF168-Mediated Ubiquitin Signaling Inhibits the Viability of BRCA1-Null Cancers
Authors: Krais John J. , Wang Yifan , Bernhardy Andrea J. , Clausen Emma , Miller Jessica A. , Cai Kathy Q. , Scott Clare L. , Johnson Neil
Published: March 2020

BRCA1 gene mutations impair homologous recombination (HR) DNA repair, resulting in cellular senescence and embryonic lethality in mice. Therefore, BRCA1-deficient cancers require adaptations that prevent excessive genomic alterations from triggering cell death. RNF168-mediated ubiquitination of γH2AX at K13/15 (ub-H2AX) serves as a recruitment module for the localization of 53BP1 to DNA break sites. Here, we found multiple BRCA1-mutant cancer cell lines and primary tumors with low levels of RNF168 protein expression. Overexpression of ectopic RNF168 or a ub-H2AX fusion protein induced cell death and delayed BRCA1-mutant tumor formation. Cell death resulted from the recruitment of 53BP1 to DNA break sites and inhibition of DNA end resection. Strikingly, reintroduction of BRCA1 or 53BP1 depletion restored HR and rescued the ability of cells to maintain RNF168 and ub-H2AX overexpression. Thus, downregulation of RNF168 protein expression is a mechanism for providing BRCA1-null cancer cell lines with a residual level of HR that is essential for viability. Overall, our work identifies loss of RNF168 ubiquitin signaling as a proteomic alteration that supports BRCA1-mutant carcinogenesis. We propose that restoring RNF168-ub-H2AX signaling, potentially through inhibition of deubiquitinases, could represent a new therapeutic approach.

Significance:

This study explores the concept that homologous recombination DNA repair is not an all-or-nothing concept, but a spectrum, and that where a tumor stands on this spectrum may have therapeutic relevance.

See related commentary by Wang and Wulf, p. 2720
HER2-Mediated Internalization of Cytotoxic Agents inERBB2Amplified or Mutant Lung Cancers
Authors: Li Bob T. , Michelini Flavia , Misale Sandra , Cocco Emiliano , Baldino Laura , Cai Yanyan , Shifman Sophie , Tu Hai-Yan , Myers Mackenzie L. , Xu Chongrui , Mattar Marissa , Khodos Inna , Little Megan , Qeriqi Besnik , Weitsman Gregory , Wilhem Clare J. , Lalani Alshad S. , Diala Irmina , Freedman Rachel A. , Lin Nancy U. , Solit David B. , Berger Michael F. , Barber Paul R. , Ng Tony , Offin Michael , Isbell James M. , Jones David R. , Yu Helena A. , Thyparambil Sheeno , Liao Wei-Li , Bhalkikar Anuja , Cecchi Fabiola , Hyman David M. , Lewis Jason S. , Buonocore Darren J. , Ho Alan L. , Makker Vicky , Reis-Filho Jorge S. , Razavi Pedram , Arcila Maria E. , Kris Mark G. , Poirier John T. , Shen Ronglai , Tsurutani Junji , Ulaner Gary A. , de Stanchina Elisa , Rosen Neal , Rudin Charles M. , Scaltriti Maurizio
Published: March 2020

Amplification of and oncogenic mutations in ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2-amplified or -mutant lung cancers. We show that cotreatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy.

Significance:

T-DM1 is clinically effective in lung cancers with amplification of or mutations in ERBB2. This activity is enhanced by cotreatment with irreversible pan-HER inhibitors, or ADC switching to T-DXd. These results may help address unmet needs of patients with HER2-activated tumors and no approved targeted therapy.

See related commentary by Rolfo and Russo, p. 643.

This article is highlighted in the In This Issue feature, p. 627
Histone Deacetylase Inhibitors and IL21 Cooperate to Reprogram Human Effector CD8+ T Cells to Memory T Cells
Authors: Wang Junmei , Hasan Farah , Frey Amanda C. , Li Haiyan S. , Park Jungsun , Pan Ke , Haymaker Cara , Bernatchez Chantale , Lee Dean A. , Watowich Stephanie S. , Yee Cassian
Published: March 2020

Clinical response rates after adoptive cell therapy (ACT) are highly correlated with in vivo persistence of the infused T cells. However, antigen-specific T cells found in tumor sites are often well-differentiated effector cells with limited persistence. Central memory CD8+ T cells, capable of self-renewal, represent desirable ACT products. We report here that exposure to a histone deacetylase inhibitor (HDACi) and IL21 could reprogram differentiated human CD8+ T cells into central memory–like T cells. Dedifferentiation of CD8+ T cells was initiated by increased H3 acetylation and chromatin accessibility at the CD28 promoter region. This led to IL21-mediated pSTAT3 binding to the CD28 region, and subsequent upregulation of surface CD28 and CD62L (markers of central memory T cells). The reprogrammed cells exhibited enhanced proliferation in response to both IL2 and IL15, and a stable memory-associated transcriptional signature (increased Lef1 and Tcf7). Our findings support the application of IL21 and HDACi for the in vitro generation of highly persistent T-cell populations that can augment the efficacy of adoptively transferred T cells.
Excessive Costimulation Leads to Dysfunction of Adoptively Transferred T Cells
Authors: Wijewarnasuriya Dinali , Bebernitz Christina , Lopez Andrea V. , Rafiq Sarwish , Brentjens Renier J.
Published: March 2020

Although clinical responses with CD19-targeting chimeric antigen receptor (CAR) T-cell treatment have been observed in patients with certain hematologic malignancies, high rates of disease relapse highlight the necessity to understand and improve mechanisms of CAR T-cell failure. Because T-cell dysfunction is thought to contribute to CAR T-cell treatment failure, understanding what mechanisms drive T cells into this dysfunctional state may aid optimal design of efficacious CAR T cells. Dysfunctional CAR T cells have been characterized as having upregulated inhibitory receptors and decreased cytolytic capabilities. Previous studies have identified a role for sustained CAR CD3ζ signaling in CAR T-cell dysfunction. Here, we demonstrate a mechanism that drives dysfunction in CAR T cells through excessive costimulation. Fully activated CD19-targeted CAR T cells were rendered dysfunctional upon stimulation with both endogenous CD28 stimulation and CAR-mediated CD28 costimulation. Costimulation-driven dysfunction of CAR T cells was demonstrated in a syngeneic immunocompetent mouse model, in which CAR T cells were activated with signals 1 (CD3ζ), 2 (CD28), and 3 (IL12). Thus, we show that CAR T-cell dysfunction can be driven through excessive CD28 and 4-1BB costimulation.

See related article by Drakes et al., p. 743
Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review
Authors: Sheehan Michael , Tanimu Sabo , Tanimu Yusuf , Engel Jessica , Onitilo Adedayo
Published: March 2020

Hypercalcemia is an ominous development in the course of malignancy associated with a mean survival of only several months. A majority of cases of hypercalcemia are related to humoral hypercalcemia of malignancy (HHM), where hypercalcemia is caused by increased levels of circulating parathyroid hormone-related protein (PTHrP). Mainstay treatments in the management of HHM are intravenous fluids, intravenous bisphosphonates, and subcutaneous denosumab, although hypercalcemia oftentimes recurs despite these efforts. We present a case of advanced non-small cell lung cancer with PTHrP-mediated hypercalcemia that proved resistant to standard therapy. A trial of oral cinacalcet was initiated and improved calcium levels for 2 months despite a progressive rise in PTHrP and prior to subsequent disease progression. Based on the current body of literature, we propose that this calcium-lowering effect of cinacalcet occurs due to a potential effect on renal calcium excretion.
Effect of 12-Week Interventions Involving Nordic Walking Exercise and a Modified Diet on the Anthropometric Parameters and Blood Lipid Profiles in Overweight and Obese Ex-Coal Miners
Authors: Sadowska-Krępa Ewa , Gdańska Agnieszka , Rozpara Michał , Pilch Wanda , Přidalová Miroslava , Bańkowski Sebastian
Published: March 2020

Background: Overweight and obesity after retirement are likely to be caused by unhealthy eating habits and the energy intake exceeding the energy expenditure. Objectives: This study was designed to assess the effects of two 12-week interventions involving, respectively, either regular physical activity or a modified lower-calorie diet on the anthropometric parameters and blood lipid profiles in overweight and obese retired miners with lipid disorders. Design: The study participants (n = 30, aged 58.7 ± 4.1 years, body height 174.8 ± 7.3 cm, body weight 96.6 ± 13.9 kg) were randomly assigned to 2 intervention groups: the Nordic walking group (NW), which exercised with intensity from 60 to 70% of participants’ maximal heart rates for 1 h 3 times a week, and the modified diet group (MD). Modification of the diet consisted of reducing the daily energy intake by 30%, increasing the dietary content of mono- and polyunsaturated fatty acids and dietary fiber, and reducing the proportion of saturated fatty acids. The variables assessed at baseline and after 6 and 12 weeks were: anthropometric parameters (body weight, fat mass content [FM], fat percentage [BF], BMI, waist circumference [WC], hip circumference [HC], and waist-to-hip ratio [WHR]) and blood lipid indicators (total cholesterol [TC], triglycerides [TG], low density lipoprotein cholesterol [LDL-C], and high density lip­oprotein cholesterol [HDL-C]). Results: The body weight of the participants in the NW was lower at week 12 by an average of 5 kg, BMI by 6%, FB by 19%, FM by 15%, WC by 8%, HC by 6%, and WHR by 3%. In the MD, the respective decreases were 8 kg and 8, 25, 20, 6, 2, and 7%. In the MD, the postintervention concentrations of TC and TG were within the reference range. Conclusion: Both 12-week interventions improved the anthropometric parameters and blood lipid profiles of retired heavy manual workers, with the improvements being more pronounced in the dieting group.
Current Standards in the Endoscopic Management of Bladder Cancer: A Survey Evaluation among Urologists in German-Speaking Countries
Authors: Suarez-Ibarrola Rodrigo , Hein Simon , Farin Erik , Waldbillig Frank , Kriegmair Maximilian C. , Ritter Manuel , Klingler Hans C. , Herrmann Thomas R.W. , Gratzke Christian , Miernik Arkadiusz
Published: March 2020

Introduction: To assess the current diagnostic, treatment, and documentation strategies for bladder cancer (BC) in German-speaking countries. Materials and Methods: A 14-item web-based survey was distributed among members of the German, Austrian, and Swiss Associations of Urology, addressing physicians who perform cystoscopies and transurethral resection of bladder tumors (TURB). Results: The survey was responded to by 308 of 5,564 urologists with a mean age of 49.5 years (response rate: 5.5%). The majority of participants (57.3%) practice in an outpatient setting. White light cystoscopy only is used by 60.2%, with additional photodynamic diagnosis and narrow band imaging by 36.8 and 12.5%, respectively. Endoscopic findings are documented in written form by 93.5%, followed by image capture (33.7%) and a central data archive (20.8%). Inpatient hospital urologists document cystoscopic findings by freehand drawing (21.4 vs. 11.4%, p = 0.017), and with a fixed bladder scheme (31.3 vs. 7.4%, <0.05) significantly more frequently. Cystoscopic findings are mainly conveyed to other health professionals in written form (77.4%), and significantly more often by inpatient urologists (p < 0.05). Conclusions: Significant differences exist in the approach to documenting and communicating cystoscopic BC findings. Accurate graphic documentation of lesions, visualization of the mucosa’s totality, and meticulous consultation of previous surgical reports require improvements to reduce recurrence and progression rates.
Cognitive Reserve Attenuates 6-Year Decline in Executive Functioning after Stroke
Authors: Ihle Andreas , Gouveia Élvio R. , Gouveia Bruna R. , Cheval Boris , Sieber Stefan , Cullati Stéphane , Kliegel Matthias
Published: March 2020

Aims: We investigated whether the longitudinal relationship between history of stroke and subsequent decline in executive functioning over 6 years differed by cognitive reserve. Methods: We analyzed longitudinal data from 897 older adults (mean age, 74.33 years) tested on the Trail Making Test (TMT) in two waves 6 years apart. Participants reported information on key frequently used proxies of lifelong cognitive reserve accumulation (i.e., education, occupation, and leisure activity engagement), and history of stroke. Results: There was a significant interaction of stroke with leisure activity engagement on latent change in executive functioning. Specifically, only for individuals with low (but not those with high) leisure activity engagement, history of stroke significantly predicted a steeper subsequent decline in executive functioning across 6 years (i.e., increases in TMT completion time). Conclusion: The detrimental aftereffects of stroke on subsequent decline in executive functioning may be attenuated in individuals who have accumulated greater cognitive reserve through leisure activity engagement across their life.
Aortic Aneurysms and Dissections Series: Part II
Authors: Shen Ying H. , LeMaire Scott A. , Webb Nancy R. , Cassis Lisa A. , Daugherty Alan , Lu Hong S.
Published: March 2020

Aortic structure and function are controlled by the coordinated actions of different aortic cells and the extracellular matrix. Several pathways have been identified that control the aortic wall in a cell-type–specific manner and play diverse roles in various phases of aortic injury, repair, and remodeling. This complexity of signaling in the aortic wall poses challenges to the development of therapeutic strategies for treating aortic aneurysms and dissections. Here, in part II of this Recent Highlights series on aortic aneurysms and dissections, we will summarize recent studies published in
Arteriosclerosis, Thrombosis, and Vascular Biology
that have contributed to our knowledge of the signaling pathway–related mechanisms of aortic aneurysms and dissections.
Renin-Angiotensin System Blockers and the COVID-19 Pandemic
Authors: Danser A.H. Jan , Epstein Murray , Batlle Daniel
Published: March 2020

During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.
PCSK9 Protein and rs562556 Polymorphism Are Associated With Arterial Plaques in Healthy Middle‐Aged Population: The STANISLAS Cohort
Authors: Ferreira João Pedro , Xhaard Constance , Lamiral Zohra , Borges‐Canha Marta , Neves João Sérgio , Dandine‐Roulland Claire , LeFloch Edith , Deleuze Jean‐François , Bacq‐Daian Delphine , Bozec Erwan , Girerd Nicolas , Boivin Jean‐Marc , Zannad Faiez , Rossignol Patrick
Published: March 2020

Background

PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds low‐density lipoprotein receptor, preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis. The PCSK9‐rs562556 variant has been reported as a gain‐of‐function mutation. The aim of this study was to determine whether the PCSK9–low‐density lipoprotein receptor–rs562556 axis is associated with carotid artery plaques between 2 visits separated by almost 20 years in a longitudinal population cohort.

Methods and Results

The STANISLAS (Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux) cohort is a longitudinal familial cohort from the Lorraine region of France. Participants attending 2 visits (visit 1 and visit 4) separated by 18.5 years (mean) were included (n=997). Carotid artery plaques were determined with standardized vascular echography. The mean age of the adult population at visit 1 was 42±5 years. At visit 4, 203 (20.4%) participants had arterial plaques. Participants who developed arterial plaques were older (42.7±5.4 versus 41.7±4.7 years), more often male (60% versus 49%), smokers (29% versus 18%), with diabetes mellitus (6% versus 3%), and higher cholesterol levels (low‐density lipoprotein cholesterol, 1.6±0.4 versus 1.5±0.3 g/L) (all
P
<0.05). The independent factors associated with arterial plaques were age, smoking, and low‐density lipoprotein cholesterol. Higher PCSK9 levels were associated with arterial plaques on top of the clinical model (odds ratio, 2.14; 95% CI,= 1.28–3.58); the missense mutation coding the single‐nucleotide polymorphism rs562556 was associated with both higher PCSK9 concentration and incident carotid arterial plaques.

Conclusions

Higher PCSK9 concentration was associated with the development of arterial plaques almost 20 years in advance in a healthy middle‐aged population. Mutations of the single‐nucleotide polymorphism rs562556 associated with both PCSK9 levels and arterial plaques reinforce the potential causality of our findings. PCSK9 inhibitors could be useful for primary cardiovascular prevention.
Coronary Angiography and Intervention in Women Resuscitated From Sudden Cardiac Death
Authors: May Teresa , Skinner Kristina , Unger Barbara , Mooney Michael , Patel Nainesh , Dupont Allison , McPherson John , McMullan Paul , Nielsen Niklas , Seder David B. , Kern Karl B.
Published: March 2020

Background

Coronary artery disease is the primary etiology for sudden cardiac arrest in adults, but potential differences in the incidence and utility of invasive coronary testing between resuscitated men and women have not been extensively evaluated. Our aim was to characterize angiographic similarities and differences between men and women after cardiac arrest.

Methods and Results

Data from the International Cardiac Arrest Registry–Cardiology database included patients resuscitated from out‐of‐hospital cardiac arrest of presumed cardiac origin, admitted to 7 academic cardiology/resuscitation centers during 2006 to 2017. Demographics, clinical factors, and angiographic findings of subjects were evaluated in relationship to sex and multivariable logistic regression models created to predict both angiography and outcome. Among 966 subjects, including 277 (29%) women and 689 (71%) men, fewer women had prior coronary artery disease and more had prior congestive heart failure (
P
=0.05). Women were less likely to have ST‐segment–elevation myocardial infarction (32% versus 39%,
P
=0.04). Among those with ST‐segment–elevation myocardial infarctions, identification and distribution of culprit arteries was similar between women and men, and there were no differences in treatment or outcome. In patients without
ST
‐segment elevation post‐arrest, women were overall less likely to undergo coronary angiography (51% versus 61%,
P
<0.02), have a culprit vessel identified (29% versus 45%,
P
=0.03), and had fewer culprits acutely occluded (17% versus 28%,
P
=0.03). Women were also less often re‐vascularized (44% versus 52%,
P
<0.03).

Conclusions

Among cardiac arrest survivors, women are less likely to undergo angiography or percutaneous coronary intervention than men. Sex disparities for invasive therapies in post‐cardiac arrest care need continued attention.
Stroke Prognostic Scores and Data-Driven Prediction of Clinical Outcomes After Acute Ischemic Stroke
Authors: Matsumoto Koutarou , Nohara Yasunobu , Soejima Hidehisa , Yonehara Toshiro , Nakashima Naoki , Kamouchi Masahiro
Published: March 2020

Background and Purpose—

Several stroke prognostic scores have been developed to predict clinical outcomes after stroke. This study aimed to develop and validate novel data-driven predictive models for clinical outcomes by referring to previous prognostic scores in patients with acute ischemic stroke in a real-world setting.

Methods—

We used retrospective data of 4237 patients with acute ischemic stroke who were hospitalized in a single stroke center in Japan between January 2012 and August 2017. We first validated point-based stroke prognostic scores (preadmission comorbidities, level of consciousness, age, and neurological deficit [PLAN] score, ischemic stroke predictive risk score [IScore], and acute stroke registry and analysis of Lausanne [ASTRAL] score in all patients; Houston intraarterial recanalization therapy [HIAT] score, totaled health risks in vascular events [THRIVE] score, and stroke prognostication using age and National Institutes of Health Stroke Scale-100 [SPAN-100] in patients who received reperfusion therapy) in our cohort. We then developed predictive models using all available data by linear regression or decision tree ensembles (random forest and gradient boosting decision tree) and evaluated their area under the receiver operating characteristic curve for clinical outcomes after repeated random splits.

Results—

The mean (SD) age of the patients was 74.7 (12.9) years and 58.3% were men. Area under the receiver operating characteristic curves (95% CIs) of prognostic scores in our cohort were 0.92 PLAN score (0.90–0.93), 0.86 for IScore (0.85–0.87), 0.85 for ASTRAL score (0.83–0.86), 0.69 for HIAT score (0.62–0.75), 0.70 for THRIVE score (0.64–0.76), and 0.70 for SPAN-100 (0.63–0.76) for poor functional outcomes, and 0.87 for PLAN score (0.85–0.90), 0.88 for IScore (0.86–0.91), and 0.88 ASTRAL score (0.85–0.91) for in-hospital mortality. Internal validation of data-driven prediction models showed that their area under the receiver operating characteristic curves ranged between 0.88 and 0.94 for poor functional outcomes and between 0.84 and 0.88 for in-hospital mortality. Ensemble models of a decision tree tended to outperform linear regression models in predicting poor functional outcomes but not in predicting in-hospital mortality.

Conclusions—

Stroke prognostic scores perform well in predicting clinical outcomes after stroke. Data-driven models may be an alternative tool for predicting poststroke clinical outcomes in a real-world setting.
Trends in Stroke Incidence in High-Income Countries in the 21st Century
Authors: Li Linxin , Scott Catherine A. , Rothwell Peter M. ,   on behalf of the Oxford Vascular Study
Published: March 2020

Background and Purpose—

Population-based studies provide the most reliable data on stroke incidence. A previous systematic review of population-based studies suggested that stroke incidence in high-income countries decreased by 42% between the 1970s and early 2000s. However, it is uncertain whether this trend of steady decline has been maintained in more recent periods.

Methods—

Data from OCSP (Oxfordshire Community Stroke Project; 1981–1986) and OXVASC (Oxford Vascular Study; 2002–2017) along with other published population-based stroke incidence studies that reported temporal trends of stroke incidence since 1990 in high-income countries were included. Age-standardized relative incidence rate ratios were calculated for each study and then pooled with inverse-variance weighted random-effects meta-analysis. Projection estimates were calculated for the number of incident stroke patients in the United Kingdom from year 2015 to 2045.

Results—

In Oxfordshire, stroke incidence fell by 32% from OCSP to OXVASC, with a similar trend before or after year 2000. With the projected aging population, if the age-specific stroke incidence continued to decrease at its current rate (6% every 5 years), there would still be a 13% increase of the number of first-ever strokes in the United Kingdom up to year 2045. Incorporating the Oxfordshire data with other 12 population-based studies, stroke incidence declined steadily between the 1990s and 2010s within each study, resulting in a 28% decline over an average period of 16.5 years (pooled incidence rate ratio, 0.72 [95% CI, 0.66–0.79];
P
<0.0001). The trend was the same for men (0.69 [95% CI, 0.61–0.77];
P
<0.0001) and women (0.66 [95% CI, 0.59–0.74];
P
<0.0001) and remained consistent after year 2010 in OXVASC. Proportion of disabling or fatal stroke also decreased over time (early versus later period, 53.6% versus 46.1%;
P
=0.02).

Conclusions—

Stroke incidence is continuing to decline with steady rate in Oxfordshire and in other high-income settings. However, the absolute number of strokes occurring is not falling.
Forging a Public Sphere: José Leonilson in the Folha de São Paulo
Authors: Morgan Nicholas C.
Published: March 2020

Between 1991 and 1993, the artist José Leonilson contributed a weekly illustration to Folha de São Paulo, Brazil’s highest circulation daily newspaper. This article argues that these drawings inserted a minoritarian voice into the public sphere in a way that contested its normative operations by emphasizing the micropolitical and the intimate, often through allegory. Some of the illustrations address AIDS, to which Leonilson succumbed two weeks after the last was published, and this article situates his work in relation to the intertwining discourses around sexuality, public health and media in Brazil at the time. What emerges is a conception of mass media and of publicness as a space of fiction that could, paradoxically, be instrumentalized in the face of the increasing standardization of previously deviant and unclassified sexualities.
Comparison of bibliographic data sources: Implications for the robustness of university rankings
Authors: Huang Chun-Kai (Karl) , Neylon Cameron , Brookes-Kenworthy Chloe , Hosking Richard , Montgomery Lucy , Wilson Katie , Ozaygen Alkim
Published: March 2020

Universities are increasingly evaluated on the basis of their outputs. These are often converted to simple and contested rankings with substantial implications for recruitment, income, and perceived prestige. Such evaluation usually relies on a single data source to define the set of outputs for a university. However, few studies have explored differences across data sources and their implications for metrics and rankings at the institutional scale. We address this gap by performing detailed bibliographic comparisons between Web of Science (WoS), Scopus, and Microsoft Academic (MSA) at the institutional level and supplement this with a manual analysis of 15 universities. We further construct two simple rankings based on citation count and open access status. Our results show that there are significant differences across databases. These differences contribute to drastic changes in rank positions of universities, which are most prevalent for non-English-speaking universities and those outside the top positions in international university rankings. Overall, MSA has greater coverage than Scopus and WoS, but with less complete affiliation metadata. We suggest that robust evaluation measures need to consider the effect of choice of data sources and recommend an approach where data from multiple sources is integrated to provide a more robust data set.
A principled methodology for comparing relatedness measures for clustering publications
Authors: Waltman Ludo , Boyack Kevin W. , Colavizza Giovanni , van Eck Nees Jan
Published: March 2020

There are many different relatedness measures, based for instance on citation relations or textual similarity, that can be used to cluster scientific publications. We propose a principled methodology for evaluating the accuracy of clustering solutions obtained using these relatedness measures. We formally show that the proposed methodology has an important consistency property. The empirical analyses that we present are based on publications in the fields of cell biology, condensed matter physics, and economics. Using the BM25 text-based relatedness measure as the evaluation criterion, we find that bibliographic coupling relations yield more accurate clustering solutions than direct citation relations and cocitation relations. The so-called extended direct citation approach performs similarly to or slightly better than bibliographic coupling in terms of the accuracy of the resulting clustering solutions. The other way around, using a citation-based relatedness measure as evaluation criterion, BM25 turns out to yield more accurate clustering solutions than other text-based relatedness measures.
Injury patterns in elderly cyclists and motorcyclists presenting to a tertiary trauma centre in Singapore
Authors: Cheong HS , Tham KY , Chiu LQ
Published: March 2020

INTRODUCTION With Singapore’s ageing population, there are increasing numbers of elderly cyclists and motorcyclists. Compared to younger riders, this cohort sustains more injuries and has poorer outcomes. This study aimed to describe and compare patient demographics, injury patterns and outcomes among elderly cyclists and motorcyclists at a Level 1 trauma centre. METHODS Data of all cyclists, motorcyclists and pillion riders aged 65 years and above who presented to the emergency department after accidents from 1 January 2013 to 31 December 2017 was extracted from the hospital’s trauma registry and reviewed. RESULTS Cyclists and motorcyclists formed 42.0% and 58.0%, respectively, of 157 recruited patients. At the time of the accident, 40.8% of the patients were employed. The mean age of the patients was 71.6 ± 5.8 years. Extremities and pelvic girdle injuries (61.1%) were the most frequent, followed by chest injuries (48.4%), and head and neck injuries (40.1%). Among severe injuries (defined as Abbreviated Injury Scale score ≥ 3), chest injuries (39.5%) were the most common, followed by head and neck injuries (36.3%). The overall mortality rate was 9.6%, with cyclists at nearly three times the risk compared to motorcyclists. More cyclists than motorcyclists (18.2% vs. 11.0%) required intensive care. There were no significant differences in the length of hospital stay between cyclists and motorcyclists. CONCLUSION Elderly riders have unique injury patterns and consume significant healthcare resources. Trauma systems need to acknowledge this changing injury epidemiology and equip trauma centres with the necessary resources targeted at elderly patients. Future work should focus on strategies to minimise extremity and chest injuries.
On Anatomical Enumeration and Difference in Early Sanskrit Medical Literature
Authors: Selby Martha Ann
Published: March 2020

What does it mean to inventory all the components of the human body, and what do those inventories tell us about medical ideas and practice? I compare the lists of body parts in the śārīra-sthānas (sections relating to the body) of the Caraka-saṃhitā (ca. first century CE) and the Suśruta-saṃhitā (ca. second century CE). Rather than provide a detailed list of differences, I contemplate what these differences “mean” in terms of counting as a practice and of how we might think about these two texts as articulations of the concerns of the “theorist-physicians” of the Caraka-saṃhitā and the “anatomist-surgeons” of the Suśruta-saṃhitā. How might a close comparative reading of these passages—an “emic” reading, if you will—shed light on medical practice in early India and its relationship with metaphysical concerns, issues of selfhood, sexual “difference,” and the problem of understanding what cannot be seen with the naked eye?
The Gendered Networking of Diplomats
Authors: Niklasson Birgitta
Published: March 2020

The aim of this study is to contribute to a deeper understanding of the gendered condi- tions under which diplomats network. We still have limited knowledge of how female diplomats network when serving abroad in strongly male-dominated contexts. To what extent do they experience token tendencies (visibility, assimilation and contrast) and how are these tendencies perceived to affect their access to important contacts? Based on 28 interviews with diplomats and civil servants from the Swedish Ministry for Foreign Affairs (MFA), this study compares how female and male diplomats are expected and perceived to network. The results indicate that the greater visibility of female diplomats makes them assimilate to a stereotypical gender role that closely resembles that of diplomatic wives. Women thus legitimise their presence in the MFA and make it less intrusive. Still, they experience contrast in silent resistance and con- stant reminders of their presence in a gender-inappropriate profession.
Hobbes on Sexual Morality
Authors: Sreedhar Susanne
Published: March 2020

Despite the vast amount of scholarship on Hobbes’s philosophy, his writings on sexuality have gone largely unexplored. This paper offers an interpretation of Hobbes’s writing on that topic. I argue that if we pay attention to his remarks on sexuality, we can retrieve a coherent account of sexual morality, one that takes a strong stance against doctrines of natural sexual morality, replacing them with a commitment to positivism about sexual norms. With this reconstruction of the Hobbesian view of sexual morality in hand, I conclude by exploring some of its implications from a contemporary feminist perspective.
Heteroradulum yunnanensis sp. nov. (Auriculariales, Basidiomycota) evidenced by morphological characters and phylogenetic analyses in China

Authors: GUAN QIAN-XIN , LIU CHAO-MAO , ZHAO TANG-JIE , ZHAO CHANG-LIN
Published: March 2020

A new wood-inhabiting fungal species, Heteroradulum yunnanensis, is proposed based on a combination of morphological features and molecular evidence. The species is characterized by an annual growth habit, resupinate basidiomata with odontoid hymenial surface (50–100 µm long), more or less pronounced yellow stains in older basidiomata, a monomitic hyphal system with thin-walled, clamped generative hyphae and two to three-celled basidia and cylindrical, hyaline, thin-walled, smooth, IKI–, CB– basidiospores measuring as 17–24 ×5–8 µm. Sequences of ITS and LSU nrRNA gene regions of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and bayesian inference methods. The phylogenetic analyses based on molecular data of ITS+nLSU sequences showed that Heteroradulum yunnanensis formed a monophyletic lineage with a strong support (100% BS, 100% BP, 1.00 BPP) and then grouped with H. adnatum.
Hydrocotyle simulans (Araliaceae), a new perennial species from south-eastern Australia

Authors: PERKINS ANDREW J.
Published: March 2020

Hydrocotyle simulans, a new perennial species from south-eastern Australia, is here described with associated illustration, photographic images and distribution map. The new species is restricted mostly to freshwater swamps in coastal areas of south-eastern South Australia, southern Victoria and to the Furneaux Group of islands, off the north-eastern coast of Tasmania. Hydrocotyle simulans resembles both H. plebeya and H. pterocarpa, in having orbicular-cordate to reniform leaves, hydathodes along leaf lamina margins and broadly ovate to orbicular stipules with entire margins. It differs from these taxa by a combination of characters, such as reflexed white trichomes congregated at the petiole apices, ovate floral bracts with basal lobes, subsessile flowers with pale to dark crimson petals and lenticular mericarps with minutely rugulose surfaces when mature.
Note on Strobilanthes sanjappae (Acanthaceae)

Authors: SANTHOSH KUMAR ETTICKAL SUKUMARAN , RAJVIKRAMAN RAMACHANDRAKURUP , PRAKASHKUMAR RAVEENDRAN PILLAI
Published: March 2020

The plieteial genus Strobilanthes Blume (1826: 781) is the second largest genus in the family Acanthaceae. It consists of about 465 species widely distributed in tropical and subtropical regions of South and South East Asia (Mabberley 2017; Jomy 2018). About 150 species have been reported from India, of these 62 are reported from South India (Carine & Scotland 2002, Venu 2006).
Dendrochirotida (Echinodermata: Holothuroidea) from the northeastern coast of Brazil
Authors: PRATA JÉSSICA , DE CASTRO MANSO CYNTHIA LARA , CHRISTOFFERSEN MARTIN LINDSEY
Published: March 2020

The study presents a review of the Dendrochirotida species from shallow waters of the northeastern coast of Brazil. A total of 1,268 specimens were analyzed and 24 species were recorded, which were classified into 16 genera of Cucumariidae, Psolidae, Phyllophoridae, and Sclerodactylidae. Detailed descriptions and figures of the taxonomic characters are provided to facilitate species identification. Notes on morphological variation, geographic distribution, and habitat are also provided. We suggest two new species for science, Thyone brasiliana sp. nov. and Havelockia nietae sp. nov., the new combination Parathyone braziliensis (Verrill, 1868) and the first record of Euthyonidiella trita (Sluiter, 1910) for the Brazilian coast. The bathymetric ranges are expanded for Coronatum baiensis, Euthyonidiella trita, Stolus cognatus, and Thyonidium seguroensis.
Taxonomic confusion among gall-thrips and host-plants, with three new
combinations from the genus Austrothrips (Thysanoptera, Phlaeothripidae)
Authors: MOUND LAURENCE
Published: March 2020

The genus Austrothrips is considered a nomen dubium because the types are lost and the type species description is uninformative. Austrothrips flavitibia Moulton is transferred to the genus Teuchothrips and Austrothrips vanuaensis Moulton is transferred to the genus Solomonthrips. The gall-inducing Austrothrips cochinchinensis Karny is transferred to Ocnothrips as a senior synonym of the type species, O. indicus. The host of cochinchinensis is recognised as a vine-like shrub, Getonia floribunda, that is widespread between western India and southeast China.