bluuebunny/crossref_metadata_2025 huggingface dataset:
International Consensus Definition of DNA Methylation Subgroups in Juvenile Myelomonocytic Leukemia
Authors: Schönung Maximilian , Meyer Julia , Nöllke Peter , Olshen Adam B. , Hartmann Mark , Murakami Norihiro , Wakamatsu Manabu , Okuno Yusuke , Plass Christoph , Loh Mignon L. , Niemeyer Charlotte M. , Muramatsu Hideki , Flotho Christian , Stieglitz Elliot , Lipka Daniel B.
Published: November 2020

Purpose:

Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML on the basis of DNA methylation patterns are lacking. We, therefore, sought to define an international consensus for DNA methylation subgroups in JMML and develop classification methods for clinical implementation.

Experimental Design:

Published DNA methylation data from 255 patients with JMML were used to develop and internally validate a classifier model. Accuracy across platforms (EPIC-arrays and MethylSeq) was tested using a technical validation cohort (32 patients). The suitability of both methods for single-patient classification was demonstrated using an independent cohort (47 patients).

Results:

Analysis of pooled, published data established three DNA methylation subgroups as a de facto standard. Unfavorable prognostic parameters (PTPN11 mutation, elevated fetal hemoglobin, and older age) were significantly enriched in the high methylation (HM) subgroup. A classifier was then developed that predicted subgroups with 98% accuracy across different technological platforms. Applying the classifier to an independent validation cohort confirmed an association of HM with secondary mutations, high relapse incidence, and inferior overall survival (OS), while the low methylation subgroup was associated with a favorable disease course. Multivariable analysis established DNA methylation subgroups as the only significant factor predicting OS.

Conclusions:

This study provides an international consensus definition for DNA methylation subgroups in JMML. We developed and validated methods which will facilitate the design of risk-stratified clinical trials in JMML.
The MEK/ERK Network as a Therapeutic Target in Human Cancer
Authors: Barbosa Renee , Acevedo Lucila A. , Marmorstein Ronen
Published: November 2020

The RAS–RAF–MEK–ERK pathway is the most well-studied of the MAPK cascades and is critical for cell proliferation, differentiation, and survival. Abnormalities in regulation resulting from mutations in components of this pathway, particularly in upstream proteins, RAS and RAF, are responsible for a significant fraction of human cancers and nearly all cutaneous melanomas. Activation of receptor tyrosine kinases by growth factors and various extracellular signals leads to the sequential activation of RAS, RAF, MEK, and finally ERK, which activates numerous transcription factors and facilitates oncogenesis in the case of aberrant pathway activation. While extensive studies have worked to elucidate the activation mechanisms and structural components of upstream MAPK components, comparatively less attention has been directed toward the kinases, MEK and ERK, due to the infrequency of oncogenic-activating mutations in these kinases. However, acquired drug resistance has become a major issue in the treatment of RAS- and RAF-mutated cancers. Targeting the terminal kinases in the MAPK cascade has shown promise for overcoming many of these resistance mechanisms and improving treatment options for patients with MAPK-aberrant cancers. Here, we will describe the role of MEK and ERK in MAPK signaling and summarize the current understanding of their interaction and activation mechanisms. We will also discuss existing approaches for targeting MEK and ERK, and the benefits of alternative strategies. Areas requiring further exploration will be highlighted to guide future research endeavors and aid in the development of alternative therapeutic strategies to combat surmounting drug resistance in treating MAPK-mediated cancers.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/19/3/361/F1.large.jpg.
Progesterone Receptor Is a Haploinsufficient Tumor-Suppressor Gene in Cervical Cancer
Authors: Park Yuri , Baik Seunghan , Ho Charles , Lin Chin-Yo , Chung Sang-Hyuk
Published: November 2020

Tumor-suppressor genes (TSG) are often deleted or transcriptionally suppressed in cancer. PGR codes for progesterone receptor (PR), a transcription factor whose function depends on its ligand. Although PR expression is often undetectable in cervical cancer, its relevance to the endocrine-related etiology of this prevalent gynecological disease remains unclear. In this study, we show that the deletion of one Pgr allele in cervical epithelium promoted spontaneous cervical cancer in human papilloma viral oncogene-expressing transgenic mice as efficiently as the ablation of both Pgr alleles. We also show that tumors arising in the transgenic mice with one or both Pgr alleles did not express PR or expressed at the reduced levels compared with the normal epithelium. PR status correlated with estrogen receptor α (ERα) status in the mouse model and the Cancer Genome Atlas (TCGA) dataset. TCGA data analyses revealed that PGR expression significantly decreased in cervical cancer and that the biallelic deletion of PGR was rare. Furthermore, low PGR expression was associated with poor prognosis in young patients with cervical cancer. These discoveries point to PGR as a haploinsufficient TSG in the uterine cervix. They also raise the possibility that the restoration of PGR expression may improve the survival rate.

Implications:

The decreased expression of PR may increase the risk of cervical cancer in human papillomavirus–infected women.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/19/1/42/F1.large.jpg.
Hitting Gliomas When They Are Down: Exploiting IDH-Mutant Metabolic Vulnerabilities
Authors: Pirozzi Christopher J. , Yan Hai
Published: November 2020

Tumors mutated in IDH1 tend to have lower levels of the essential substrate NAD+. In this issue of Cancer Discovery, Nagashima and colleagues exploit this metabolic sensitivity by devising a combinatorial therapy that both further reduces the pools as well as sequesters the remaining substrate in PAR chains, sensitizing the cells to temozolomide and PARG inhibition.

See related article by Nagashima et al., p. 1672.
An Expanded Tool Kit for Modeling the Oncogenic Functions of KRAS
Authors: Kostyrko Kaja , Sweet-Cordero E. Alejandro
Published: November 2020

Zafra and colleagues developed new mouse models to study the role of specific KRAS mutations in pancreatic, lung, and colon cancer pathogenesis. Their studies clearly describe the distinct ability of these mutations to drive pathogenesis in a tissue-specific fashion.

See related article by Zafra et al., p. 1654.
Free Asparagine or Die: Cancer Cells Require Proteasomal Protein Breakdown to Survive Asparagine Depletion
Authors: Davidsen Kristian , Sullivan Lucas B.
Published: November 2020

The chemotherapeutic enzyme asparaginase depletes systemic asparagine to kill cancers; however, its efficacy thus far is limited to a subset of leukemias. Hinze and colleagues identify that inhibiting proteasomal release of asparagine can sensitize colorectal cancers to asparagine depletion, providing a potential avenue to repurpose asparaginase for treatment of solid tumors.

See related article by Hinze et al., p. 1690.
CD10-Positive Cutaneous PEComa: An Extremely Rare Skin Tumour
Authors: Ueberschaar Simon , Goebeler Matthias , Kneitz Hermann
Published: November 2020

We here present the case of a 67-year-old woman with a history of a slowly progressive, polypous nodule on her left wrist. The lesion was excised, and the histological analysis revealed a clear cell tumour that was relatively sharply demarked from the surrounding tissue extending into the subcutaneous tissue. The tumour showed a characteristic trabecular pattern in which the tumour cells were arranged around numerous vessels. The neoplastic cells had a predominantly epithelioid shape, granular eosinophilic to clear cytoplasm and prominent centrally located nucleoli. The histological differential diagnosis included a metastatic clear-cell renal cell carcinoma and a primary cutaneous perivascular epithelioid cell tumour (PEComa). Immunohistochemically, the tumour cells revealed homogenous expression of HMB-45, MiTF and CD10, whereas MART-1 and S100 were negative. Antibodies against actin marked the trabecularly arranged vessels, and the neoplastic cells yielded a patchy positivity against actin and desmin. Additional immunohistochemical stains against pan-cytokeratin, CAIX, PAX-8 and EMA were negative. Based on the morphologic and immunophenotypic findings, the histological diagnosis of a CD10-positive cutaneous PEComa was made.
Challenges Developing Deep Learning Algorithms in Cytology
Authors: McAlpine Ewen David , Pantanowitz Liron , Michelow Pamela M.
Published: November 2020

Background: The incorporation of digital pathology into routine pathology practice is becoming more widespread. Definite advantages exist with respect to the implementation of artificial intelligence (AI) and deep learning in pathology, including cytopathology. However, there are also unique challenges in this regard. Summary: This review discusses cytology-specific challenges, including the need to implement digital cytology prior to AI; the large file sizes and increased acquisition times for whole slide images in cytology; the routine use of multiple stains, such as Papanicolaou and Romanowsky stains; the lack of high-quality annotated datasets on which to train algorithms; and the considerable computer resources required, in terms of both computer infrastructure and skilled personnel, for computing and storage of data. Global concerns regarding AI that are certainly applicable to cytology include the need for model validation and continued quality assurance, ethical issues such as the use of patient data in developing algorithms, the need to develop regulatory frameworks regarding what type of data can be utilized and ensuring cybersecurity during data collection and storage, and algorithm development. Key Messages: While AI will likely play a role in cytology practice in the future, applying this technology to cytology poses a unique set of challenges. A broad understanding of digital pathology and algorithm development is desirable to guide the development of algorithms, as well as the need to be cognizant of potential pitfalls to avoid when incorporating the technology in practice.
Lässt sich anhand von klinischen Variablen der Binokularfunktion die langfristige Stabilität der postoperativen Augenstellung nach Korrektur einer intermittierenden Exotropie vorhersagen?
Authors: Wu Yidong , Xu Meiping , Zhang Junxiao , Zhou Jinjing , Wan Minghui , Dai Zhiyue , Peng Tingting , Min Seung Hyun , Hou Fang , Zhou Jiawei , Yu Xingpin
Published: November 2020

Zielsetzung: Untersuchung, ob klinische Variablen der postoperativen Binokularfunktion die langfristige Stabilität der postoperativen Augenstellung nach Korrektur einer intermittierenden Exotropie bei Kindern vorhersagen können. Methode: Es erfolgte eine retrospektive Studie zu 39 Kindern (medianes Alter: 7 Jahre), die wegen einer intermittierenden Exotropie operativ behandelt worden waren und bei denen keine Überkorrektur erfolgt war (weniger als 10 Prismen-Dioptrien (PDPT) Exodeviation 1 Monat nach der Operation). Präoperativ sowie 1 Monat und 6 Monate nach der Operation und bei der letzten Nachuntersuchung (≥24 Monate) des Patienten wurden die Schielwinkel und Variablen der Binokularfunktion bestimmt. Wir untersuchten die Beziehung zwischen postoperativer Drift (Änderung der Augenstellung) und Variablen der Binokularfunktion (sensorische Funktion, konvergente Fusionsbreite und Stereosehschärfe). Ergebnisse: Die Erfolgsrate der Operation (Esophorie/-tropie ≤5 PDPT bis Exophorie/-tropie ≤10 PDPT) hatte 6 Monate nach der Operation auf 76,9% und zum Zeitpunkt der letzten Nachuntersuchungen der Patienten (im Mittel nach 37 Monaten) auf 53,8% abgenommen. Die mittlere Exodrift betrug zwischen 1 Monat nach der Operation und der letzten Nachuntersuchung bei Fernfixation 7,7 ± 9,2 PDPT (p < 0,001). Die Stereosehschärfe in der Ferne, die zentrale Fusion und die konvergente Fusionsbreite verbesserten sich nach der Operation signifikant (p < 0,05). Allerdings wurde keine signifikante Korrelation zwischen den Binokularfunktionen zu Beginn jeder Nachbeobachtungsphase und der postoperativen Drift beobachtet (alle p > 0,13). Schlussfolgerung: Unsere Beobachtungen weisen darauf hin, dass die klinischen Variablen sensorische Fusion, konvergente Fusionsbreite und Stereosehschärfe bei erfolgreich operierten Patienten, die 1 Monat nach der Operation keine Überkorrektur zeigen, nicht als robuste Prädiktoren für die langfristige Stabilität der postoperativen, korrigierten Augenstellung geeignet sind.
Therapy Algorithms for the Diagnosis and Treatment of Patients with Early and Advanced Breast Cancer
Authors: Schneeweiss Andreas , Bauerfeind Ingo , Fehm Tanja , Janni Wolfgang , Thomssen Christoph , Witzel Isabell , Wöckel Achim , Müller Volkmar ,   on behalf of the Commission Breast of the Working Group Gynecologic Oncology (AGO)
Published: November 2020

Background: In order to offer optimal treatment approaches based on available evidence, the Commission Breast of the Working Group Gynecologic Oncology (AGO) of the German Cancer Society developed therapy algorithms for eight complex treatment situations in primary and advanced breast cancer. Summary: Therapy algorithms for the following complex treatment situations are outlined in this paper: (neo)adjuvant therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer; axillary surgery and neoadjuvant chemotherapy; adjuvant endocrine therapy in premenopausal patients; adjuvant endocrine therapy in postmenopausal patients; hormone receptor (HR)-positive/HER2-negative metastatic breast cancer: strategies; HR-positive/HER2-negative metastatic breast cancer: endocrine-based first-line treatment; HER2-positive metastatic breast cancer: first to third-line; metastatic triple-negative breast cancer. Key Messages: The therapy options shown in these algorithms are based on the current AGO recommendations updated in January 2020 but cannot represent all evidence-based treatment options. Prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. Therefore, in individual cases, other evidence-based treatment options not listed here may also be appropriate and justified.
DISENGAGE Registry
Authors: Pellicano Mariano , Ciccarelli Giovanni , Xaplanteris Panagiotis , Di Gioia Giuseppe , Milkas Anastasios , Colaiori Iginio , Heyse Alex , Van Durme Frederik , Vanderheyden Marc , Bartunek Jozef , De Bruyne Bernard , Barbato Emanuele
Published: November 2020

Background:

During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making.

Methods:

In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFR
eng
] and disengaged [FFR
dis
]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFR
eng
–FFR
dis
was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFR
eng
–FFR
dis
could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFR
eng
–FFR
dis
related to the stenosis location, that is, proximal and middle versus distal coronary segments.

Results:

Overall, FFR significantly changed after GC disengagement: FFR
eng
0.84±0.08 versus FFR
dis
0.80±0.09,
P
<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFR
eng
–FFR
dis
, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03;
P
=0.042).

Conclusions:

GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.
Feasibility of Transcatheter Aortic Valve Replacement in Prior Aortic Root Surgery
Authors: Brener Michael I. , Yamabe Tsuyoshi , Leb Jay , Khalique Omar K. , Takayama Hiroo , George Isaac
Published: November 2020

Background:

Aortic root replacement (ARR) introduces several anatomic complexities relevant to valve-in-valve (VIV)–transcatheter aortic valve replacement (TAVR) that may (1) increase the risk of coronary obstruction, (2) necessitate transcatheter valve overexpansion to accommodate large annuli, and (3) require alternative vascular access to navigate aortic kinking. Therefore, we aimed to quantify the feasibility of VIV-TAVR in patients who underwent aortic root surgery.

Methods:

Postoperative computed tomography scans were reviewed for consecutive patients who underwent ARR between 2005 and 2019 to obtain measurements relevant for VIV-TAVR planning. Virtual transcatheter valve to coronary ostia distance was measured to assess the risk of coronary obstruction. Root morphologies were classified into 1 of 4 groups based on aortic graft type, aortic diameter at the sinotubular junction, sinus height, estimated transcatheter heart valve height, and diameter. VIV-TAVR was projected to be complex in patients with an aortic kink, extremely large annulus, or heightened risk of coronary obstruction.

Results:

Among 848 patients who underwent ARR during the 15-year study period, qualifying contrast-enhanced scans post-ARR were performed in 81 patients. Complex VIV-TAVR was anticipated in 50.6% of subjects. Patients with abnormal root anatomy experienced increased odds of complex VIV-TAVR relative to patients with normal root physiology (ie, sinotubular junction diameter>transcatheter heart valve diameter, sinus height>transcatheter heart valve height) or those who received straight tube grafts (odds ratio, 4.53 [95% CI, 1.02–20.1],
P
=0.046). The odds of complex VIV-TAVR were also higher among patients who underwent aortic valve replacement–ARR with a stentless bioprosthesis (stentless versus stented, odds ratio, 4.63 [95% CI, 1.40–15.3],
P
=0.012; stentless versus valve-sparing ARR, odds ratio, 3.78 [95% CI, 1.14–12.5],
P
=0.029).

Conclusions:

ARR patients with atypical root morphologies or those who underwent valve replacement with stentless bioprostheses may be at high risk for complex VIV-TAVR. Prospective evaluation is required to assess the impact of these conclusions on procedural feasibility.
Live Imaging of Intracranial Lymphatics in the Zebrafish
Authors: Castranova Daniel , Samasa Bakary , Venero Galanternik Marina , Jung Hyun Min , Pham Van N. , Weinstein Brant M.
Published: November 2020

Rationale:

The recent discovery of meningeal lymphatics in mammals is reshaping our understanding of fluid homeostasis and cellular waste management in the brain, but visualization and experimental analysis of these vessels is challenging in mammals. Although the optical clarity and experimental advantages of zebrafish have made this an essential model organism for studying lymphatic development, the existence of meningeal lymphatics has not yet been reported in this species.

Objective:

Examine the intracranial space of larval, juvenile, and adult zebrafish to determine whether and where intracranial lymphatic vessels are present.

Methods and Results:

Using high-resolution optical imaging of the meninges in living animals, we show that zebrafish possess a meningeal lymphatic network comparable to that found in mammals. We confirm that this network is separate from the blood vascular network and that it drains interstitial fluid from the brain. We document the developmental origins and growth of these vessels into a distinct network separated from the external lymphatics. Finally, we show that these vessels contain immune cells and perform live imaging of immune cell trafficking and transmigration in meningeal lymphatics.

Conclusions:

This discovery establishes the zebrafish as a important new model for experimental analysis of meningeal lymphatic development and opens up new avenues for probing meningeal lymphatic function in health and disease.
Endothelial FGFR1 (Fibroblast Growth Factor Receptor 1) Deficiency Contributes Differential Fibrogenic Effects in Kidney and Heart of Diabetic Mice
Authors: Li Jinpeng , Liu Haijie , Srivastava Swayam Prakash , Hu Qiongying , Gao Rongfen , Li Shaolan , Kitada Munehiro , Wu Gaosong , Koya Daisuke , Kanasaki Keizo
Published: November 2020

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis. We have reported that N-acetyl-seryl-aspartyl- lysyl-proline (AcSDKP) restored levels of diabetes mellitus-suppressed FGFR1 (fibroblast growth factor receptor 1), the endothelial receptor essential for combating EndMT. However, the molecular regulation and biological/pathological significance of the AcSDKP-FGFR1 relationship has not been elucidated yet. Here, we demonstrated that endothelial FGFR1 deficiency led to AcSDKP-resistant EndMT and severe fibrosis associated with EndMT-stimulated fibrogenic programming in neighboring cells. Diabetes mellitus induced severe kidney fibrosis in endothelial FGFR1-deficient mice (
FGFR1

fl/fl

; VE-cadherin-Cre:
FGFR1
EKO
) but not in control mice (FGFR1
fl/fl
); AcSDKP completely or partially suppressed kidney fibrosis in control or FGFR1
EKO
mice. Severe fibrosis was also induced in hearts of diabetic FGFR1
EKO
mice; however, AcSDKP had no effect on heart fibrosis in FGFR1
EKO
mice. AcSDKP also had no effect on EndMT in either kidney or heart but partially suppressed epithelial-to-mesenchymal transition in kidneys of diabetic FGFR1
EKO
mice. The medium from FGFR1-deficient endothelial cells stimulated TGFβ (transforming growth factor β)/Smad-dependent epithelial-to-mesenchymal transition in cultured human proximal tubule epithelial cell line, AcSDKP inhibited such epithelial-to-mesenchymal transition. These data demonstrated that endothelial FGFR1 is essential as an antifibrotic core molecule as the target of AcSDKP.
Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Wang Katherine M. , Stedman Margaret R. , Chertow Glenn M. , Chang Tara I.
Published: November 2020

SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.
Long-Term Blood Pressure Variability and Risk of Cardiovascular Disease Events Among Community-Dwelling Elderly
Authors: Ernst Michael E. , Chowdhury Enayet K. , Beilin Lawrence J. , Margolis Karen L. , Nelson Mark R. , Wolfe Rory , Tonkin Andrew M. , Ryan Joanne , Woods Robyn L. , McNeil John J. , Reid Christopher M. ,   for the ASPREE Investigator Group
Published: November 2020

High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-individual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08–1.70];
P
=0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04–2.33];
P
=0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07–2.79];
P
=0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04–1.54];
P
=0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for individuals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously.

Registration—

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT01038583; URL:
https://www.isrctn.com
; Unique identifiers: ISRCTN83772183.
Evaluating Cognitive Relationships with Resting-State and Task-driven Blood Oxygen Level-Dependent Variability
Authors: Millar Peter R. , Ances Beau M. , Gordon Brian A. , Benzinger Tammie L. S. , Morris John C. , Balota David A.
Published: November 2020

Recent functional magnetic resonance imaging studies have reported that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is positively associated with task performance and, thus, may reflect a behaviorally sensitive signal. However, it is not clear whether estimates of resting-state and task-driven BOLD variability are differentially related to cognition, as they may be driven by distinct sources of variance in the BOLD signal. Moreover, other studies have suggested that age differences in resting-state BOLD variability may be particularly sensitive to individual differences in cardiovascular, rather than neural, factors. In this study, we tested relationships between measures of behavioral task performance and BOLD variability during both resting-state and task-driven runs of a Stroop and an animacy judgment task in a large, well-characterized sample of cognitively normal middle-aged to older adults. Resting-state BOLD variability was related to composite measures of global cognition and attentional control, but these relationships were eliminated after correction for age or cardiovascular estimates. In contrast, task-driven BOLD variability was related to attentional control measured both inside and outside the scanner, and importantly, these relationships persisted after correction for age and cardiovascular measures. Overall, these results suggest that BOLD variability is a behaviorally sensitive signal. However, resting-state and task-driven estimates of BOLD variability may differ in the degree to which they are sensitive to age-related, cardiovascular, and neural mechanisms.
Jaideep Mazumdar: a passionate, silent researcher who left treasures behind

Authors: BHATTACHARJEE AVISHEK , BANDYOPADHYAY SUBIR
Published: November 2020

Not applicable
Review of the genus Valdasus Stål, 1860 (Heteroptera, Miridae, Cylapinae), with descriptions of four new species from Brazil, Ecuador and French Guiana
Authors: WOLSKI ANDRZEJ , CHÉROT FRÉDÉRIC , CARPINTERO DIEGO LEONARDO
Published: November 2020

The genus Valdasus Stål, 1860 is reviewed. Four species are described as new: Valdasus favrei n. sp., V. ferrerai n. sp., V. flavinotum n. sp., and V. henryi n. sp. V. erebeus Distant, 1883 and V. stygius Distant, 1883 are transferred again to Valdasus (original combination reestablished) from Peltidocylapus Poppius and they are redescribed along with the type species V. schoenherri Stål, 1860. Presence of V. bolivianus in Argentina is challenged after new analysis of female specimen mentioned in literature.
Notes on the genus Astenus Dejean, 1833 in the Mediterranean and adjacent regions. A new species from Turkey, seven new synonyms, and additional records (Coleoptera: Staphylinidae: Paederinae)
Authors: ANLAŞ SİNAN
Published: November 2020

Based on the study of types and additional material, new taxonomic and faunistic data on some species of the genus Astenus from the Mediterranean and adjacent regions are presented. Astenus henrii sp. n. from Turkey is described, illustrated, and distinguished from related congeners. The following new synonyms are proposed: Astenus procerus (Gravenhorst, 1806) = A. rufopacus Reitter, 1909 syn. n. = A. circumflexus circumflexus Jarrige, 1952 syn. n. = A. circumflexus scutellaris Coiffait, 1970 syn. n. = A. obliquus Jarrige, 1952 syn. n. = A. baali Coiffait, 1960 syn. n.; A. melanurus (Küster, 1853) = A. adonis Coiffait, 1960 syn. n.; A. thoracicus (Baudi di Selve, 1857) =A. jordanicus Coiffait, 1981 syn. n.
The records of Pagurus trigonocheirus (Stimpson, 1858) (Crustacea: Decapoda: Paguridae) from the continental coasts of the Peter the Great Bay of the Sea of Japan with the list of hermit crab species from the area
Authors: MARIN IVAN
Published: November 2020

The sublittoral hermit crab Pagurus trigonocheirus (Stimpson, 1858) (Crustacea: Decapoda: Paguridae) is recorded from depths of 80–200 m along the continental coastline of the Peter the Great Bay, Sea of Japan. The exact sampling localities as well as photographs of live specimens are presented in the paper. Doubtful records of hermit crabs from the southern Russian coastline of the Sea of Japan are also discussed.
The millipede genus Sibiriulus Gulička, 1963 revisited, with the description of a new species from the Altais, southwestern Siberia, Russia (Diplopoda: Julida: Julidae)
Authors: NEFEDIEV PAVEL S. , NEFEDIEVA JULIA S. , KRUGOVA TATIANA M.
Published: November 2020

Sibiriulus mikhaljovae sp. nov. is described from the Altai Province, southwestern Siberia, Russia. This new species differs from its congeners mainly by the presence of a longitudinal crest inside the apical fovea of the gonopod mesomere. Brief descriptive remarks concerning several previously described Sibiriulus species allow for the definition of the genus to be supplemented and refined. All eight currently known species of Sibiriulus are keyed.
Observations of Stably Stratified Flow through a Microscale Gap
Authors: Vassallo Daniel , Krishnamurthy Raghavendra , Menke Robert , Fernando Harindra J. S.
Published: November 2020

This paper reports the findings of a comprehensive field investigation on flow through a mountain gap subject to a range of stably stratified environmental conditions. This study was embedded within the Perdigão field campaign, which was conducted in a region of parallel double-ridge topography with ridge-normal wind climatology. One of the ridges has a well-defined gap (col) at the top, and an array of in situ and remote sensors, including a novel triple Doppler lidar system, was deployed around it. The experimental design was mostly guided by previous numerical and theoretical studies conducted with an idealized configuration where a flow (with characteristic velocity U
0 and buoyancy frequency N) approaches normal to a mountain of height h with a gap at its crest, for which the governing parameters are the dimensionless mountain height G = Nh/U
0 and various gap aspect ratios. Modified forms of G were proposed to account for real-world atmospheric variability, and the results are discussed in terms of a gap-averaged value G

c
. The nature of gap flow was highly dependent on G

c
, wherein a nearly neutral flow regime (G

c
< 1), a transitional mountain wave regime [G

c
~ O(1)], and a gap-jetting regime [G

c
> O(1)] were identified. The measurements were in broad agreement with previous numerical and theoretical studies on a single ridge with a gap or double-ridge topography, although details vary. This is the first-ever detailed field study reported on microscale [O(100) m] gap flows, and it provides useful data and insights for future theoretical and numerical studies.
Statewide Seasonal Variations of Infections Within the Intensive Care Unit Among the Trauma Population
Authors: Clark Jason M. , Durrani Hamza , Hagan Josh D. , Watson Carrie , Richards Winston T. , Taylor Dana , Ang Darwin N.
Published: November 2020

Background

Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill.

Materials and Methods

A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed.

Results

A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09).

Discussion

Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.
Are Nomograms Useful in Predicting Upstage From Ductal Carcinoma In Situ to Invasive Carcinoma Requiring Sentinel Lymph Node Biopsy?
Authors: Kapadia Sonam , Lee Albert , Kaji Amy H. , Ozao-Choy Junko , Dauphine Christine
Published: November 2020

The upstage rate from ductal carcinoma in situ (DCIS) on core biopsy to invasive carcinoma at definitive excision ranges from 20 to 30%. Nomograms have been developed to aid in the prediction of upstaging so as to guide surgical planning with respect to performance of sentinel lymph node biopsy (SLNB). The aim of this study was to evaluate the ability of these nomograms to predict upstaging within our public hospital population. A retrospective review of patients with DCIS from 2013 to 2018 at a single institution was performed. Individualized probability of upstage was calculated using the Samsung Medical Center (SMC) and Annals of Surgical Oncology (ASO) nomograms. Areas under the receiver operating characteristic curves were calculated to assess the discriminative power of each. Of 105 patients with DCIS, 31 (29.5%) were upstaged to invasive disease. The SMC and ASO nomograms demonstrated area under the curves (AUCs) of .65 (OR = 1.023, 95% CI 1.004-1.042, P = .02) and .60 (OR = 1.035, 95% CI 1.003-1.068, P = .03), respectively. While SMC provided greater discrimination in our cohort, the performance of these nomograms as reliable clinical adjuncts to guide SLNB decision-making in this cohort was less than optimal and thus should not be the sole factor in determining individual upstage risk.
Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature
Authors: Feng Austin Y. , Jin Michael C. , Wong Sandy , Pepper Jon-Paul , Jackler Robert , Vaisbuch Yona
Published: November 2020

Objective:

We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature.

Patient:

61 F with right facial palsy.

Intervention:

Following a single intravenous dexamethasone injection with oral steroids over 2 months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation.

Outcome and Results:

The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8 months, facial function has improved substantially (HB 2/6).

Conclusion:

Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3 months.
Using Structural Equations to Test a Multi-Theoretical Framework with Data on Cyberstalking Victimization in Iran: Self-Control, Control Deficit, Peers’ Online Deviant Behaviors, and Online Deviant Lifestyles
Authors: Kabiri Saeed , Choi Jaeyong , Shadmanfaat Seyyedeh Masoomeh (Shamila) , Lee Julak
Published: November 2020

Although there exists a growing amount of empirical literature documenting the correlates of cyberstalking victimization, research has yet to elaborate on the potential mechanisms that can explain the risk for cyberstalking victimization. We proposed an integrated theory, which combined low self-control, control deficit, peers’ online deviant behavior, and online deviant lifestyles based on previous research. We tested this integrated theory specifically for cyberstalking victimization using original data from a sample of 408 Iranian college women. Relying on structural equation modeling, we found that low self-control and peers’ online deviant behaviors were significantly associated with cyberstalking victimization not only directly but also indirectly via online deviant lifestyles. Overall, our findings yielded strong support for the integrated model to explain cyberstalking victimization.
Impact of Exchange Rate Changes on the Trade Balance of India: An Asymmetric Nonlinear Cointegration Approach
Authors: Bhat Sajad Ahmad , Bhat Javed Ahmad
Published: November 2020

Applying an asymmetric model, the study reported no evidence of J-curve phenomenon in case of India. In the short-run currency appreciation deteriorates the trade balance and currency depreciation improves it. In the long-run, again the similar response is observed, however, only the impact of currency depreciation is statistically significant. Increase in domestic demand deteriorates the trade balance by a greater magnitude than improvement is observed due to the decline in domestic demand conditions. Finally, foreign demand hike improves the trade balance relatively by a higher magnitude; however, the impact of a foreign demand decline is statistically insignificant.

JEL Codes: F4, F41, F42
Local public innovation: an analysis of its perceived impacts on public performance
Authors: Queyroi Yoann , Carassus David , Maurel Christophe , Favoreu Christophe , Marin Pierre
Published: November 2020

This article explores public innovations implemented by local authorities, which consider them as a key means of improving their performance in response to a restrictive context. The authors thus propose to grasp the impacts of these innovations in terms of perceived performance from a global and multidimensional point of view. Based on a quantitative study conducted among French local authorities, this research first presents the results obtained from a theoretical point of view, providing insight into the multiple impacts of implementing innovations within the public sector. Then, at the managerial level, the study identifies specific impacts for each type of public innovation, the aim being to structure the innovation portfolio of public organisations.

Points for practitioners

An increasing number of innovations are being introduced in the public sector. However, the impact of these innovations on public performance is often not assessed. That is why by focusing our research on French local authorities, we guide managers both in analysing this influence by distinguishing several types of innovation and performance, and in building a portfolio of innovations in line with the internal resources of their local authority, as well as the public service provided in response to the needs of the territory.
Emulsion electrospun polylactic acid/Apocynum venetum nanocellulose nanofiber membranes with controlled sea buckthorn extract release as a drug delivery system
Authors: Wang Lu , Wang Chenmeizi , Wang Ling , Zhang Qingle , Wang Ying , Xia Xin
Published: November 2020

Prolonging the duration of drug action and reducing toxicity play a vital role in wound administration as they reduce the chance of infection and decrease complications and cost. This study reports the natural antioxidant procyanidins extracted from sea buckthorn (SBT) and laboratory-manufactured Apocynum venetum cellulose nanofiber as core drugs. The sustained-release nanofiber membrane was prepared by electrospinning on polylactic acid/polyvinyl pyrrolidone nanofibers. High-performance liquid chromatography-mass spectrometry was used to identify the phenolic compounds in SBT extracts and confirmed the presence of procyanidins with a content of 0.0345 mg/g. The nanofiber membrane was characterized through transmission electron microscopy, encapsulation efficiency, in vitro drug-release study and antioxidant assay. The results indicated that the extracted procyanidins were successfully encapsulated in the core–sheath structure nanofibers, and the encapsulation efficiency of nanofiber membranes reached 83.84%. In vitro measurements of the delivery showed this core–sheath structure could significantly alleviate the drug burst release, which is followed by a linear and smooth release within 30 hours. Further tests showed that the removal efficiency of 2,2-diphenyl-1-picrylhydrazyl reached 88.62%, indicating that the membranes had high antioxidant activity. This work implies that the combination of Apocynum venetum nanocellulose and emulsion electrospun fibers has promising potential applications in tissue engineering or drug delivery.
The acquisition of causatives in Q’anjob’al Maya
Authors: Mateo Pedro Pedro
Published: November 2020

Causatives have received considerable attention in first language acquisition. Of Mayan languages, acquisition of the causative has only been investigated for K’iche’ and Tzotzil, based on longitudinal and spontaneous data. K’iche’-speaking children do not acquire morphological causatives until the age of 3 years, while children acquiring Tzotzil start producing morphological causatives around the age of 2 years. The marked difference in the age of acquisition of causatives in K’iche’ and in Tzotzil has been explained through a morphological difference between causatives in the two languages. This paper, based on longitudinal and spontaneous data, examines acquisition of the causative in Q’anjob’al, a third Mayan language. The question is whether the findings in K’iche’ and Tzotzil are reproduced, or whether the acquisition of Q’anjob’al causatives follows a third, yet-unattested, trajectory.

The results show that three Q’anjob’al children, of the age range 1;9-3;0, 2;3-4;0, and 2;7-3;6, acquire the morphological and periphrastic causatives during the third year of life, although these children produce more periphrastic causatives than morphological causatives. Longitudinal and spontaneous studies in K’iche’ and Tzotzil have reported the acquisition of the morphological causative, but not the acquisition of periphrastic causatives. The Q’anjob’al children’s production of more periphrastic causatives might be due to their exposure to a special V1V2 construction, which is a general feature of Q’anjob’al. The Q’anjob’al child data show that even related languages in which causatives are expressed through similar morphemes can show strikingly different acquisition trajectories.
Link prediction in supernetwork: Risk perception of emergencies
Authors: Ma Ning , Liu Yijun , Li Liangliang
Published: November 2020

After an emergency incident occurs, how to identify risks, predict trends and scientifically cope before the crisis erupts is the basic starting point of this study. In this study, a supernetwork model of the risk perception in emergencies is innovatively constructed from the perspective of the governance of risks. This supernetwork model includes three subnetworks: the similar relationship subnetwork that is composed of newly occurring emergencies, the chain relationship subnetwork that is composed of historical emergencies and the co-occurrence relationship subnetwork that is composed of the risk elements for emergencies. Afterwards, the feature similarity algorithm is applied to quantify the relations between newly occurring emergencies and historical emergencies, and then, the link prediction algorithm is applied to predict the risk elements that may be derived from the newly occurring emergencies. This will be beneficial to enhancing the scientific accuracy of decision-making by managers when coping with emergencies risks.