bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Graphitic Nitrogen and π‐Conjugated Functional Groups in Selective Oxidation of Alcohols: A DFT based Mechanistic Elucidation
Authors: Kumar Choutipalli Venkata Surya , Subramanian Venkatesan
Published: October 2019

Selective oxidation of alcohols to aldehydes is challenging reaction due to its accessibility to overoxidation. In this study, we have made an attempt to unravel the mechanistic aspects of selective oxidation of allyl alcohols that contain multiple functional groups catalyzed by N‐doped graphene. The role of graphitic nitrogen and the presence of π‐conjugated functional groups are demonstrated using the state‐of‐the‐art density functional theory calculations. The detailed reaction mechanism for aerobic oxidation of allyl alcohol (AA) and cinnamyl alcohol (CA) are investigated. The formation of activated oxygen species (AOS) over N‐doped graphene (NG) has been adopted from our previous report. The results revealed that ketonic AOS oxidizes allyl alcohols into aldehydes selectively with a relatively lower activation barrier of 20.1 kcal mol−1. The oxidation of alcohols with the AOS formed at the edge results in high activation barriers owing to its high thermodynamic stability. Similarly, AOS formed at the center leads to the formation of H2O2 along with high activation barriers. As a consequence, AOS formed at the center is less active when compared to ketonic AOS. The overoxidation of aldehyde is only possible due to the formation of H2O2. However, it is unlikely to happen due to unfavorable ambient conditions. The presence of multiple π‐conjugated functional groups is responsible for the significant reduction in the activation barriers of the second hydrogen transfer step due to the stabilization of intermediate by increasing the acidic nature of the intermediates. On the basis of the results, a generalized reaction mechanism has been proposed. These results would definitely shed light on the effective fabrication of catalysts for oxidation of alcohol and sustainable energy.
Adaptive backstepping tracking control of a car with n trailers based on RBF neural network
Authors: Jin Zengke , Liang Zhenying , Guo Pengfei , Zheng Mingwen
Published: October 2019

An adaptive control scheme based on a radial basis function neural network (RBFNN) is proposed for the kinematic model of a car with n trailers. Firstly, a chained system for a kinematic model of a car with n trailers is introduced, then the tracking error system is given. Secondly, a RBFNN controller is designed using the backstepping method and adaptive method, in which neural networks (NNs) are used to approximate the unknown functions in the error system. By using Lyapunov stability theory, the adaptive law of network weights is designed. This method ensures the stability of the error system. Simulation results are provided to verify the effectiveness of the approach.
Dynamic lag analysis reveals atypical brain information flow in autism spectrum disorder
Authors: Raatikainen Ville , Korhonen Vesa , Borchardt Viola , Huotari Niko , Helakari Heta , Kananen Janne , Raitamaa Lauri , Joskitt Leena , Loukusa Soile , Hurtig Tuula , Ebeling Hanna , Uddin Lucina Q. , Kiviniemi Vesa
Published: October 2019

This study investigated whole‐brain dynamic lag pattern variations between neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) by applying a novel technique called dynamic lag analysis (DLA). The use of 3D magnetic resonance encephalography data with repetition time = 100 msec enables highly accurate analysis of the spread of activity between brain networks. Sixteen resting‐state networks (RSNs) with the highest spatial correlation between NT individuals (n = 20) and individuals with ASD (n = 20) were analyzed. The dynamic lag pattern variation between each RSN pair was investigated using DLA, which measures time lag variation between each RSN pair combination and statistically defines how these lag patterns are altered between ASD and NT groups. DLA analyses indicated that 10.8% of the 120 RSN pairs had statistically significant (P‐value <0.003) dynamic lag pattern differences that survived correction with surrogate data thresholding. Alterations in lag patterns were concentrated in salience, executive, visual, and default‐mode networks, supporting earlier findings of impaired brain connectivity in these regions in ASD. 92.3% and 84.6% of the significant RSN pairs revealed shorter mean and median temporal lags in ASD versus NT, respectively. Taken together, these results suggest that altered lag patterns indicating atypical spread of activity between large‐scale functional brain networks may contribute to the ASD phenotype. Autism Res 2020, 13: 244–258. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.

Lay Summary

Autism spectrum disorder (ASD) is characterized by atypical neurodevelopment. Using an ultra‐fast neuroimaging procedure, we investigated communication across brain regions in adults with ASD compared with neurotypical (NT) individuals. We found that ASD individuals had altered information flow patterns across brain regions. Atypical patterns were concentrated in salience, executive, visual, and default‐mode network areas of the brain that have previously been implicated in the pathophysiology of the disorder.
A comparison of the ASD experience of low‐SES hispanic and non‐hispanic white parents
Authors: Ferguson Adriana , Vigil Debra C.
Published: October 2019

This study compared the experiences of Hispanic families, who were primarily of Mexican heritage, and non‐Hispanic White families from the United States both from low socioeconomic status (SES) backgrounds having a child with a diagnosis of Autism Spectrum Disorder (ASD). The Centers for Disease Control and Prevention (CDC) reports that Hispanic children are diagnosed with ASD 2 years later than non‐Hispanic White children [Baio et al., MMWR Surveillance Summaries 2018:67(SS‐6): 1–23]. However, there has been limited investigation in exploring how SES might impact both diagnosis and experience. A survey of basic demographic information and a qualitative survey were used for this study. Basic demographic information obtained included SES, parent educational level, age of diagnosis of the children, religious affiliation, and marital status. Hour‐long interviews were conducted to gather information about the personal experiences of these families relating to diagnoses and treatment. Comparative results of basic demographic information showed no difference in age of diagnosis between the two groups when SES was controlled. Although SES was controlled, the non‐Hispanic White families had a higher education level and were slightly wealthier. Qualitatively, similarities included family support, doctor response to parent concerns, and acceptance of diagnosis by family members and friends. Differences included religious views, acceptance of diagnosis, knowledge of developmental milestones, and finding resources. Most significantly, the findings indicate no difference in the age of diagnosis of ASD between the Hispanic and non‐Hispanic White children, which could be attributed to increased awareness and having access to a proactive parent organization. Autism Res 2019, 12: 1880–1890. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

This study showed that Hispanic and Non‐Hispanic White children from poor backgrounds got a diagnosis of Autism Spectrum Disorder (ASD) at the same age. Results show differences in religious views, acceptance of diagnosis, knowledge of milestones, and finding resources. This might be because people are more aware of ASD today and Hispanic families were involved with an active parent organization.
Population-based study of the prevalence and management of self-reported high pain scores in patients with non-resected pancreatic adenocarcinoma
Authors: Tung S , Coburn N G , Davis L E , Mahar A L , Myrehaug S , Zhao H , Earle C C , Nathens A , Hallet J
Published: October 2019

Background

Pain is a common debilitating symptom in pancreatic adenocarcinoma. This cohort study examined the use of, and factors associated with, pain-directed interventions for a high pain score in patients with non-curable pancreatic adenocarcinoma.

Methods

Administrative databases were linked and patients with non-resected pancreatic adenocarcinoma diagnosed between 2010 and 2016, who reported one or more Edmonton Symptom Assessment System (ESAS) score, were identified. A high pain score was defined as an ESAS score of at least 4. Outcomes were pain-directed interventions: opiates (in patients aged 65 years or more with universal drug coverage), nerve block and radiation therapy for a high pain score. Reduction in pain score of at least 1 point after pain-directed intervention was also evaluated. Modified Poisson regression was used to examine factors associated with pain-directed intervention.

Results

Among 2623 patients with a median age of 67 years, 1223 (46·6 per cent) were women, and 1621 (61·8 per cent) reported a high pain score at a median of 38 days after diagnosis. Of those with a high pain score, 75·6 per cent (688 of 910) received opiates, 13·5 per cent (219 of 1621) radiation and 1·2 per cent (19 of 1621) nerve block. The pain score decreased in 62·1 per cent of patients after administration of opiates, 73·4 per cent after radiation and all patients after nerve block. In multivariable analysis, no patient factor (age, sex, co-morbidity burden, rurality, income quintile) was associated with receipt of non-opiate pain-directed intervention for a high pain score. In patients aged at least 65 years, advanced age was associated with lower odds of opiate use.

Conclusion

Opiates are the most common pain-directed intervention for non-curable pancreatic adenocarcinoma, whereas radiation therapy and nerve blocks are seldom used. The lack of association between pain-directed interventions and patient factors points toward practice-driven patterns.
Management of the axilla after neoadjuvant chemotherapy for breast cancer
Authors: Vrancken Peeters M T F D
Published: October 2019

Minor international differences
Interactive three‐dimensional teaching models of the female and male pelvic floor
Authors: Wu Yi , Hikspoors Jill P.J.M. , Mommen Greet , Dabhoiwala Noshir F. , Hu Xin , Tan Li‐Wen , Zhang Shao‐Xiang , Lamers Wouter H.
Published: October 2019

Controversies regarding structure and function of the pelvic floor persist because of its poor accessibility and complex anatomical architecture. Most data are based on dissection. This “surgical” approach requires profound prior knowledge, because applying the scalpel precludes a “second look.” The “sectional” approach does not entail these limitations, but requires segmentation of structures and three‐dimensional reconstruction. This approach has produced several “Visible Human Projects.” We dealt with limited spatial resolution and difficult‐to‐segment structures by proceeding from clear‐cut to more fuzzy boundaries and comparing segmentation between investigators. We observed that the bicipital levator ani muscle consisted of pubovisceral and puborectal portions; that the pubovisceral muscle formed, together with rectococcygeal and rectoperineal muscles, a rectal diaphragm; that the external anal sphincter consisted of its subcutaneous portion and the puborectal muscle only; that the striated urethral sphincter had three parts, of which the middle (urethral compressor) was best developed in females and the circular lower (“membranous”) best in males; that the rectourethral muscle, an anterior extension of the rectal longitudinal smooth muscle, developed a fibrous node in its center (perineal body); that the perineal body was much better developed in females than males, so that the rectourethral subdivision into posterior rectoperineal and anterior deep perineal muscles was more obvious in females; that the superficial transverse perineal muscle attached to the fibrous septa of the ischioanal fat; and that the uterosacral ligaments and mesorectal fascia colocalized. To facilitate comprehension of the modified topography we provide interactive 3D‐PDFs that are freely available for teaching purposes. Clin. Anat. 33:275–285, 2020. © 2019 Wiley Periodicals, Inc.
Published Human Cadaveric Measurements Are Strongly Biased Toward the Elderly Population
Authors: Yammine Kaissar
Published: October 2019

Understanding of anatomy is based on the study of anatomical variations. Morphometric variations can have important implications in surgical practice. The sizes of some anatomical structures are affected by age; however, cadavers used in anatomical research are usually of advanced age. The main aim of this study is to quantify the mean age of samples in cadaveric studies reporting morphometric values. PubMed was searched for the last 3 years to locate cadaveric studies reporting size values, excluding histological, forensic, and osteological collections. Out of the 390 potentially relevant papers, 109 (28%) studies did not report the ages of their samples. In total, 177 studies were included for analysis comprising 4,807 subjects. The most studied structures were those of the musculoskeletal system. The mean age of the pooled sample was 71.1 ± 11.0 years. The lowest reported age was 16 while the highest was 104 years. Univariate and multivariate analyses showed no correlation with any of the following variables: country of study, anatomical region, anatomical structure, or journal type. The mean age of cadavers used to measure the sizes of human anatomical structures falls largely within the senior age category. The reported values in an aging population will not necessarily mirror other populations such as the pediatric. The outcomes of surgeries that depend to some extent on tight morphometric values such as flap surgeries, microsurgery, tendon transfer, or mini‐invasive procedures could differ when they are performed on other age categories. More anatomical research is needed for better reporting of age‐related morphometric changes. Clin. Anat., 33:804–808, 2020. © 2019 Wiley Periodicals, Inc.
MiR‐26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/β‐catenin signaling
Authors: Hu Xiaobo , Wang Ruifang , Ren Zhigang , Liu Xiaorui , Gu Junsheng , Cui Guangying , Li Qinggang
Published: October 2019

Previous studies have indicated that Zinc ribbon domain‐containing 1 (ZNRD1) is attributed to the carcinogenesis of human tumors. However, the role of ZNRD1 and its regulation in hepatocellular carcinoma (HCC) are still largely unclear. In this study, we examined the expression profiles of ZNRD1 in HCC tissues by immunohistochemistry (IHC) and publicly datasets analysis. In vitro and in vivo experiments were conducted to identify the function of ZNRD1 in HCC. In addition, miRNA potentially targeting ZNRD1 was predicted by bioinformatics analysis and further verified via in vitro experiments. Our results revealed that ZNRD1 was frequently upregulated in HCC tissues compared with that in nontumor tissues. High ZNRD1 expression in HCC tissues was positively associated with advanced tumor stage and poor prognosis. Function experiments showed that knockdown of ZNRD1 inhibited cell growth and invasion in vitro, and suppressed tumor development in vivo. Moreover, ZNRD1 promoted the activation of Wnt/β‐catenin signaling pathway in HCC. Importantly, miR‐26b directly inhibited the transcription activity of ZNRD1. Overexpression of ZNRD1 dramatically abolished the inhibitory effects of miR‐26b on HCC cells. Taken together, our results uncover a novel mechanistic role for miR‐26b/ZNRD1 axis in HCC, proposing ZNRD1 inhibition as a potent therapeutic strategy for hepatocellular carcinoma.
Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion
Authors: Chaki Sankar P. , Barhoumi Rola , Rivera Gonzalo M.
Published: October 2019

Background

Podosomes are membrane‐bound adhesive structures formed by actin remodeling. They are capable of extracellular matrix (ECM) degradation, which is a prerequisite for cancer cell invasion and metastasis. The signaling mechanism of podosome formation is still unknown in cancer. We previously reported that Nck adaptors regulate directional cell migration and endothelial lumen formation by actin remodeling, while deficiency of Nck reduces cancer metastasis. This study evaluated the role of Nck adaptors in podosome biogenesis and cancer invasion.

Methods

This study was conducted in vitro using both healthy cells (Human Umbilical Vein Endothelial Cell, 3T3 fibroblasts) and cancer cells (prostate cancer cell line; PC3, breast cancer cell line; MDA‐MB‐231). Confocal and TIRF imaging of cells expressing Green Fluorescence Protein (GFP)  mutant under altered levels of Nck or downstream of kinase 1 (Dok1) was used to evaluate the podosome formation and fluorescent gelatin matrix degradation. Levels of Nck in human breast carcinoma tissue sections were detected by immune histochemistry using Nck polyclonal antibody. Biochemical interaction of Nck/Dok1 was detected in podosome forming cells using immune precipitation and far‐western blotting.

Results

This study demonstrates that ectopic expression of Nck1 and Nck2 can induce the endothelial podosome formation in vitro. Nck silencing by short‐hairpin RNA blocked podosome biogenesis and ECM degradation in cSrc‐Y530F transformed endothelial cells in this study. Immunohistochemical analysis revealed the Nck overexpression in human breast carcinoma tissue sections. Immunoprecipitation and far‐western blotting revealed the biochemical interaction of Nck/p62Dok in podosome forming cells.

Conclusions

Nck adaptors in interaction with Dok1 induce podosome biogenesis and ECM degradation facilitating cancer cell invasion, and therefore a bona fide target of cancer therapy.
HPLC‐DAD Analysis, Antioxidant and Protective Effects of Tunisian Rhanterium suaveolens against Acetamiprid Induced Oxidative Stress on Mice Erythrocytes
Authors: Chelly Sabrine , Chelly Meryam , Salah Hichem Ben , Athmouni Khaled , Bitto Alessandra , Sellami Hanen , Kallel Choumous , Bouaziz‐Ketata Hanen
Published: October 2019

The present study was performed to assess the HPLC‐DAD analysis as well as antioxidant and protective effects of Tunisian Rhanterium suaveolens (Rs) against acetamiprid (ACT) induced oxidative stress on mice erythrocytes. The in vitro assays showed that the methanolic extract of Rs has an impressive antioxidant effect proved by testing the total antioxidant and scavenging activities using BCB, DPPH and ABTS assays, respectively. Moreover, qualitative and quantitative analysis using HPLC‐DAD revealed the richness of Rs in polyphenols where p‐Coumaric, Apigenin‐7‐glucoside and Ferulic acid were detected as the most abundant polyphenols. In the in vivo experiment, ACT, used as a toxicity model, was given to mice at a dose of 20 mg/kg. The latter was the origin of hemolytic anemia characterized by a significant decrease in red blood cells, hemoglobin and hematocrit levels and an increase in bilirubin, LDH, osmotic fragility, reticulocytes and white blood cells number. Characteristic erythrocyte morphological alterations were also determined as spherocytosis, schistocytosis and dacryocystitis. The oxidative status of ACT‐treated mice was also altered manifested by a significant increase in MDA and GSH levels and a decrease in SOD, CAT and GPx activities. When receiving the Rs methanolic extract at a dose of 300 mg/kg, all the parameters cited above were restored in mice. These remarkable corrections could only confirm the important antioxidant effect and the noticeable protective properties that possess Rs owing to its broad range of secondary bioactive metabolites.
Identification of patients at higher risk for myocardial injury following elective coronary artery intervention
Authors: Abu Sharar Haitham , Helfert Stefanie , Vafaie Mehrshad , Pleger Sven T. , Chorianopoulos Emmanuel , Bekeredjian Raffi , Katus Hugo A. , Giannitsis Evangelos
Published: October 2019

Objectives

To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI).

Background

The substantially higher analytical power of high‐sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies.

Methods

Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition.

Results

The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively.

Conclusions

After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI‐related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.
Vascular complications associated with percutaneous left ventricular assist device placement: A 10‐year US perspective
Authors: Patel Nilay , Sharma Akshit , Dalia Tarun , Rali Aniket , Earnest Matthew , Tadros Peter , Wiley Mark , Hockstad Eric , Mehta Ashwani , Thors Axel , Hance Kirk , Gupta Kamal
Published: October 2019

Background

Over the last decade, there has been a significant increase in the use of percutaneous left ventricular assist devices(p‐LVADs). p‐LVADs are being increasingly used during complex coronary interventions and for acute cardiogenic shock. These large bore percutaneous devices have a higher risk of vascular complications. We examined the vascular complication rates from the use of p‐LVAD in a national database.

Methods

We conducted a secondary analysis of the National In‐patient Sample (NIS) dataset from 2005 till 2015. We used the ICD‐9‐CM procedure codes 37.68 and 37.62 for p‐LVAD placement regardless of indications. We investigated common vascular complications, defining them by the validated ICD 9 CM codes. χ2 test and t test were used for categorical and continuous variables, respectively for comparison.

Results

A total of 31,263 p‐LVAD placements were identified during the period studied. A majority of patients were male (72.68%) and 64.44% were white. The overall incidence of vascular complications was 13.53%, out of which 56% required surgical treatment. Acute limb thromboembolism and bleeding requiring transfusion accounted for 27.6% and 21.8% of all vascular complications. Occurrence of a vascular complication was associated with significantly higher in‐hospital mortality (37.77% vs. 29.95%, p < .001), length of stay (22.7 vs. 12.2 days, p < .001) and cost of hospitalization ($ 161,923 vs. $ 95,547, p < .001).

Conclusions

There is a high incidence of vascular complications with p‐LVAD placement including need for vascular surgery. These complications are associated with a higher in‐hospital, LOS and hospitalization costs. These findings should be factored into the decision‐making for p‐LVAD placement.
Severe myocarditis due to influenza A(H1N1)pdm09 viral infection in a young woman successfully treated with intravenous zanamivir: A case report
Authors: Mazzitelli Maria , Garofalo Eugenio , Bruni Andrea , Barreca Giorgio Settimo , Quirino Angela , Giancotti Aida , Serapide Francesca , Indolfi Ciro , Matera Giovanni , Navalesi Paolo , Trecarichi Enrico Maria , Torti Carlo , Longhini Federico ,   The IMAGES (Integrated MAnaGEment of Sepsis) Group
Published: October 2019

In patients with influenza‐related myocarditis, prompt diagnosis and treatment are important. Intravenous zanamivir can be an alternative to oral oseltamivir, especially in severe cases and when drug intestinal malabsorption is suspected or proven.
Crystal Engineering with Multipoint Halogen Bonding: Double Two‐Point Donors and Acceptors at Work
Authors: Bulfield David , Engelage Elric , Mancheski Lucas , Stoesser Julian , Huber Stefan M.
Published: October 2019

The combination of singly or doubly bidentate halogen‐bond donors with double bidentate acceptors was investigated as a supramolecular synthon in crystal engineering. The crystal topologies obtained feature novel halogen‐bonding motifs like double two‐point recognition and infinite chains or networks based on two‐point interactions. Induced conformational changes in the double bidentate halogen‐bond donors could be exploited to obtain different 1D and 2D networks. All solid‐state studies were accompanied by DFT calculations to predict and rationalize the outcome.
Side‐on‐End‐on Coordination of Dinitrogen on a Polynuclear Vanadium Nitride Cluster Anion [V5N5]−
Authors: Cheng Xin , Li Zi‐Yu , Mou Li‐Hui , Ren Yi , Liu Qing‐Yu , Ding Xun‐Lei , He Sheng‐Gui
Published: October 2019

The side‐on‐end‐on coordination of N2 can be very important to activate and functionalize this very stable molecule. However, such coordination has rarely been reported. This study reports a gas‐phase species (a polynuclear vanadium nitride cluster anion [V5N5]−) that can capture N2 efficiently (12 %), and the quantum chemistry modelling suggests an unusual side‐on‐end‐on coordination. The cluster anions were generated by laser ablation and the reaction with N2 has been characterized by mass spectrometry, photoelectron imaging spectroscopy, and density functional theory calculations. The back‐donation interactions between the localized d–d bonding orbitals on the low‐coordinated dual metal (V) sites and the antibonding π* orbitals of N2 are the driving forces to adsorb N2 with a high binding energy (about 2.0 eV).
Cyclotriphosphate: A Brief History, Recent Developments, and Perspectives in Synthesis
Authors: Bezold Dominik , Dürr Tobias , Singh Jyoti , Jessen Henning J.
Published: October 2019

There has been a recent upsurge in the study and application of approaches utilizing cyclotriphosphate 1 (cyclo‐TP, also known as trimetaphosphate, TMP) and/or proceeding through its analogues in synthetic chemistry to access modified oligo‐ and polyphosphates. This is especially useful in the area of chemical nucleotide synthesis, but by no means restricted to it. Enabled by new high yielding and easy‐to‐implement methodologies, these approaches promise to open up an area of research that has previously been underappreciated. Additionally, refinements of concepts of prebiotic phosphorylation chemistry have been disclosed that ultimately rely on cyclo‐TP 1 as a precursor, placing it as a potentially central compound in the emergence of life. Given the importance of such concepts for our understanding of prebiotic chemistry in combination with the need to readily access modified polyphosphates for structural and biological studies, this paper will discuss selected recent developments in the field of cyclo‐TP chemistry, briefly touch on ultraphosphate chemistry, and highlight areas in which further developments can be expected.
Quality‐of‐life assessment in French patients with metastatic melanoma in real life
Authors: Kandel Marguerite , Dalle Stéphane , Bardet Aurélie , Allayous Clara , Mortier Laurent , Dutriaux Caroline , Guillot Bernard , Leccia Marie‐Thérèse , Dalac Sophie , Legoupil Delphine , Saiag Philippe , Montaudie Henri , Arnault Jean‐Philippe , Brunet‐Possenti Florence , Grob Jean‐Jacques , DeQuatrebarbes Julie , Beylot‐Barry Marie , Lesimple Thierry , Aubin François , Maubec Eve , Granel‐Brocard Florence , Stoebner Pierre‐Emmanuel , Dupuy Alain , Dreno Brigitte , Michiels Stefan , Lebbe Céleste , Borget Isabelle
Published: October 2019

Background

Significant progress was recently observed in the treatment of metastatic melanoma (MM). With >50% of patients now reaching a second line of treatment and a significant improvement in the survival rate, an assessment of quality of life (QoL) during the whole course of the disease becomes necessary. The objective of this study was to describe the QoL of patients with MM in France, from their diagnosis of advanced disease to their death, in real life.

Methods

QoL data were collected through MelBase, a prospective, French, multicentric cohort dedicated to the follow‐up of adults with MM. QoL was assessed using the EuroQoL‐5D questionnaire and the Functional Assessment of Cancer Treatment (FACT)‐Melanoma questionnaire at the time of study inclusion, every 3 months, and at the time of each treatment change until death. To assess longitudinal changes from baseline to death, mixed‐effect models for repeated‐measures analyses were used to control for baseline covariates.

Results

QoL was assessed in 1435 patients who were included in the study between 2013 and 2018. The median follow‐up was 9.4 months, and 47% of patients died during follow‐up. During first‐line treatment, the model‐based, mean utility score was 0.830 (95% CI, 0.818‐0.843), the mean FACT‐General score was 77.22 (95% CI, 76.23‐78.22), and the mean FACT‐Melanoma score was 129.46 (95% CI, 128.02‐130.90). At the time of a change in treatment line, there was a decrease of −0.027 (95% CI, −0.03, −0.02) in the utility score, −1.82 (95% CI, −1.88, −1.76) in the FACT‐General score, and −2.98 (95% CI, −3.05, −2.91) in the FACT‐Melanoma score compared with first‐line treatment.

Conclusions

In the MelBase cohort, the QoL among patients with MM seems to be fairly stable over the whole disease course, although a small but significant decrease at time therapy is changed is observed.
Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts
Authors: Lange Jane M. , Laviana Aaron A. , Penson David F. , Lin Daniel W. , Bill‐Axelson Anna , Carlsson Sigrid V. , Newcomb Lisa F. , Trock Bruce J. , Carter H. Ballentine , Carroll Peter R. , Cooperberg Mathew R. , Cowan Janet E. , Klotz Laurence H. , Etzioni Ruth B.
Published: October 2019

Background

Active surveillance (AS) is an accepted means of managing low‐risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts.

Methods

Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life‐years (LYs), and quality‐adjusted LYs.

Results

Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5‐year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5‐year biopsy schedules in terms of LYs (range of differences, 0.04‐0.16 LYs) and quality‐adjusted LYs (range of differences, −0.02 to 0.09 quality‐adjusted LYs).

Conclusions

Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.
One‐Step Synthesis of a Coral‐Like Cobalt Iron Oxyhydroxide Porous Nanoarray: An Efficient Catalyst for Oxygen Evolution Reactions
Authors: Li Yao , Zhang Wenqian , Song Zhicui , Zheng Qiaoji , Xie Fengyu , Long Enyan , Lin Dunmin
Published: October 2019

The design of high‐efficiency and cost‐effective electrocatalysts is one of the most crucial factors for facilitating the oxygen evolution reaction (OER). Therefore, we prepared CoxFe1‐xOOH with coral‐like nanonet arrays on carbon cloth (CC) as high‐performance OER catalysts by a facile hydrothermal method. The resulting CoxFe1‐xOOH was characterized by X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, and X‐ray photoelectron spectrometry. When serving as a catalyst electrode in the OER, Co0.875Fe0.125OOH/CC exhibits excellent catalytic activity. Co0.875Fe0.125OOH/CC has a low overpotential of 300 mV at a current density of 20 mA cm−2 (150 mV less than that of FeOOH/CC) and a small Tafel slope of 83 mV dec−1 in 1.0 M KOH in OER. Moreover, it also has a superior electrochemical durability for more than 50 h.
Acetaminophen‐Induced Liver Damage in Hepatic Steatosis
Authors: García‐Román Rebeca , Francés Rubén
Published: October 2019

One of the most used painkillers is acetaminophen (APAP), which is safe at the right dose. However, several studies have described populations susceptible to APAP‐induced liver damage, mainly in livers with steatosis. Thus, clinicians should consider the presence of obesity and other chronic liver diseases like nonalcoholic fatty liver disease (NAFLD) when indicating treatment with APAP. Liver damage from this drug is generated through its metabolite N‐acetyl‐p‐benzoquinone imine, which is detoxified with glutathione (GSH). Prior depletion of GSH in steatotic hepatocytes plays a key role in APAP‐induced hepatotoxicity in people with obesity and NAFLD. The knowledge about the damage to the liver or APAP in susceptible people like the obese and those with NAFLD is of great relevance for the sanitary sector because it would imply strategies of different therapeutic approach in such patients. This paper reviews the role of APAP in liver damage in the presence of obesity, NAFLD, and nonalcoholic steatohepatitis.
Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity
Authors: Nissen Michael D. , Kusakabe Manabu , Wang Xuehai , Simkin Guillermo , Gracias Deanne , Tyshchenko Kateryna , Hill Ainsleigh , Meskas Justin , Hung Stacy , Chavez Elizabeth A. , Ennishi Daisuke , Aoki Tomohiro , Sarkozy Clementine , Connors Joseph M. , Farinha Pedro , Slack Graham W. , Gascoyne Randy D. , Brinkman Ryan R. , Scott David W. , Steidl Christian , Weng Andrew P.
Published: October 2019

Diffuse large B‐cell lymphoma (DLBCL) is the most common histologic subtype of non‐Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell‐of‐origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B‐cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B‐cells from each patient occupied unique regions in 37‐dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case, we were able to demonstrate direct correspondence between protein‐level phenotypic subsets and DNA mutation‐defined subclones. In summary, CyTOF analysis can resolve both intertumoral and intratumoral heterogeneity among primary samples and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones. © 2019 International Society for Advancement of Cytometry
Cervical cytology reproducibility and associated clinical and demographic factors
Authors: Hwang Hyunsoo , Follen Michele , Guillaud Martial , Scheurer Michael , MacAulay Calum , MacAulay Calum , Staerkel Gregg A. , van Niekerk Dirk , Yamal Jose‐Miguel
Published: October 2019

Background

Although the Pap test has been the standard screening method for cervical precancer/cancer detection, it has been criticized for having a relatively low sensitivity and a low reproducibility between pathologists. There is limited knowledge about inter‐rater agreement and what clinical and demographic factors are associated with disagreements between pathologists reading the same Pap smear.

Methods

This study aimed to assess inter‐ and intra‐ rater agreement of the Pap smear in 1619 cytologic slides with biopsy confirmation, using kappa statistics. Clinical and demographic factors associated with higher odds of inter‐rater agreement were also examined and stratified by histologic diagnosis grade.

Results

Using a five grade classification system, the overall kappa statistics for total, inter‐rater, and intra‐rater samples were 0.62, 0.57, and 0.88 (unweighted) and 0.83, 0.81, and 0.95 (weighted), respectively. In stratified analyses by histologic grade, total kappas ranged from 0.40 (atypia) to 0.64 (human papilloma virus/CIN 1). Factors such as referral for abnormal Pap test (diagnostic vs screening population), recruiting site, and parity were found to be associated with higher agreement between the two cytologic readings.

Conclusions

We observed relatively higher levels of agreement compared with other studies. However, variability was considerable and agreement was generally moderate, suggesting that cervical screening test accuracy and reproducibility needs to be improved.
Palaeoenvironments and elemental geochemistry across the marine Permo‐Triassic boundary section, Guryul Ravine (Kashmir, India) and a comparison with other North Indian passive margin sections
Authors: Brookfield Michael E. , Stebbins Alan G. , Williams Jeremy C. , Wolbach Wendy S. , Hannigan Robyn , Bhat Ghulam M.
Published: October 2019

The Guryul Permian–Triassic sediments were deposited on a passive margin in a partially enclosed basin, at a latitude of about 45°S along the southern margin of the Neotethys Ocean. The closest modern analogy is the Japan Sea rotated into a southern hemisphere orientation. Guryul element variations are subdued, mostly lithological, and take place across the change from the dominantly sandy shallow‐water Permian Zewan Formation into the dominantly shaly deeper‐water latest Permian–Triassic Khunamuh Formation, and not at the palaeontological Permian–Triassic boundary. The overall geochemistry of the Guryul sediments is very similar to that of the Ulleung Basin in the Japan Sea, where the sediments are 40%–60% eolian from loess and redeposited loess in the North China Basin. The overall Guryul geochemistry indicates that the sediments were derived from dominantly silica‐rich continental rather than silica‐poor sources although with some more silica‐poor inputs at times. Element ratios suggest increasing aridity and wind abrasion across the Permian–Triassic boundary. Various geochemical redox proxies suggest mainly oxic depositional conditions, with episodes of anoxia, but with little systematic variation across the extinction boundary. Productivity proxies suggest a slight decrease across the Permian–Triassic boundary, and at least one more decreased interval in the Early Triassic. The similar geochemistry of other localities indicate that the Guryul geochemical changes are regional in extent and representative of the North Indian Permian–Triassic passive margin. The lack of consistent element geochemical changes across the boundary accompanied by significant C, S, and other isotopic changes suggests that atmospheric and oceanic chemistry rather than physical changes, such as provenance, climate and sea‐level changes, drove the Permian–Triassic environmental changes and extinctions at least on the mid‐latitude Tethyan shelf of northern India.
Gene expression response to a nematode parasite in novel and native eel hosts
Authors: Bracamonte Seraina E. , Johnston Paul R. , Monaghan Michael T. , Knopf Klaus
Published: October 2019

Invasive parasites are involved in population declines of new host species worldwide. The high susceptibilities observed in many novel hosts have been attributed to the lack of protective immunity to the parasites which native hosts acquired during their shared evolution. We experimentally infected Japanese eels (Anguilla japonica) and European eels (Anguilla anguilla) with Anguillicola crassus, a nematode parasite that is native to the Japanese eel and invasive in the European eel. We inferred gene expression changes in head kidney tissue from both species, using RNA‐seq data to determine the responses at two time points during the early stages of infection (3 and 23 days postinfection). At both time points, the novel host modified the expression of a larger and functionally more diverse set of genes than the native host. Strikingly, the native host regulated immune gene expression only at the earlier time point and to a small extent while the novel host regulated these genes at both time points. A low number of differentially expressed immune genes, especially in the native host, suggest that a systemic immune response was of minor importance during the early stages of infection. Transcript abundance of genes involved in cell respiration was reduced in the novel host which may affect its ability to cope with harsh conditions and energetically demanding activities. The observed gene expression changes in response to a novel parasite that we observed in a fish follow a general pattern observed in amphibians and mammals, and suggest that the disruption of physiological processes, rather than the absence of an immediate immune response, is responsible for the higher susceptibility of the novel host.
What drives genetic and phenotypic divergence in the Red‐crowned Ant tanager (Habia rubica, Aves: Cardinalidae), a polytypic species?
Authors: Ramírez‐Barrera Sandra M. , Velasco Julián A. , Orozco‐Téllez Tania M. , Vázquez‐López Alma M. , Hernández‐Baños Blanca E.
Published: October 2019

Aim

The effects of geographic and environmental variables on patterns of genetic and phenotypic differentiation have been thoroughly studied. Ecological speciation involves reproductive isolation due to divergent natural selection that can result in a positive correlation between genetic divergence and adaptive phenotypic divergence (isolation by adaptation, IBA). If the phenotypic target of selection is unknown or not easily measured, environmental variation can be used as a proxy, expecting positive correlation between genetic and environmental distances, independent of geographic distances (isolation by environment, IBE). The null model is that the amount of gene flow between populations decreases as the geographic distance between them increases, and genetic divergence is due simply to the neutral effects of genetic drift (isolation by distance, IBD). However, since phenotypic differentiation in natural populations may be autocorrelated with geographic distance, it is often difficult to distinguish IBA from the neutral expectation of IBD. In this work, we test hypotheses of IBA, IBE, and IBD in the Red‐crowned Ant tanager (Habia rubica).

Location

Mesoamerica (Mexico—Central America) and South America.

Taxon

Habia rubica (Aves: Cardinalidae).

Methods

We compiled genetic data, coloration, and morphometric data from specimens from collections in Mexico and the United States. We used the Multiple Matrix Regression with Randomization (MMRR) approach to evaluate the influence of geographic and environmental distances on genetic and phenotypic differentiation of H. rubica at both phylogroup and population levels.

Results

Our results provide strong evidence that geographic distance is the main driver of genetic variation in H. rubica. We did not find evidence that climate variation is driving population differentiation in this species across a widespread geographic region.

Main conclusions

Our data point to geographic isolation as the main factor structuring genetic variation within populations of H. rubica and suggest that climate is not playing a major role in genetic differentiation within this species.
Slowing down wolves to protect boreal caribou populations: a spatial simulation model of linear feature restoration
Authors: Spangenberg Matthias C. , Serrouya Robert , Dickie Melanie , DeMars Craig A. , Michelot Théo , Boutin Stan , Wittmann Meike J.
Published: October 2019

In Canada, boreal caribou (Rangifer tarandus caribou) are declining in numbers, in part due to increased predation by wolves (Canis lupus). One management option to reduce wolf–caribou interactions and thus protect caribou is to remove man‐made linear features (LFs), structures such as roads, trails, and cut lines, which are used by wolves as traveling paths. Linear features increase wolf traveling speed and could additionally facilitate wolf entry into caribou habitat. Our goal was to quantify the expected effect of LF removal on caribou mortality and investigate whether this LF restoration could be a sufficient measure to stop caribou declines. We simulated the effects of LF restoration on caribou adult and calf survival in spatially explicit wolf–caribou encounter models. The models were parameterized using Global Positioning System (GPS) data, hidden Markov models (HMMs), and information from the published literature. Complete LF restoration decreased wolf traveling speed and thus reduced caribou mortality. The proportional reduction in adult caribou mortality ranged from 10 to 25% of its original value, and the proportional reduction in calf mortality ranged from 8 to 23%, depending on caribou density, number of wolf packs, kill probability given an encounter, and detection distance of wolves for caribou. Building on the model output, we used empirical caribou data to calculate the effects of reduced mortalities on the finite rate of annual population change, . Assuming that 25% or less of calf mortality was wolf‐related, stayed below one, that is, populations kept declining, even with complete LF restoration. With 50% of calf mortality due to wolves, caribou populations stopped declining () if adult and calf mortality were reduced by at least 19 to 24%. However, these values were not achieved in a majority of the parameter combinations in our study, not even with complete LF restoration. Given that LF restoration as a single measure is unlikely to stop boreal caribou populations from declining, we used a case example to illustrate how LF restoration could make a small contribution in a portfolio of short‐term and long‐term management options to reduce wolf predation on caribou.
Reactivity of Woollins' Reagent toward 2‐En‐1‐imines (Schiff Bases): A Facile Approach to Synthesize New Selenium‐Phosphorus‐Nitrogen Heterocycles
Authors: Hua Guoxiong , Cordes David B. , Slawin Alexandra M. Z. , Woollins J. Derek
Published: October 2019

Woollins' Reagent serves as a reductive cycloaddition reagent, reacting with 2‐en‐1‐imines containing a conjugated C=C bond group (Schiff bases) leading to a series of four‐, five‐, six‐membered 1,2‐azaphospholidines incorporating one or two N–P=Se linkages. Ten single‐crystal X‐ray structures confirming the formation of these small N–P–Se heterocycles are reported.