bluuebunny/crossref_metadata_2025 huggingface dataset:
Race does not predict skeletal‐related events and all‐cause mortality in men with castration‐resistant prostate cancer
Authors: Patel Devin N. , Howard Lauren E. , De Hoedt Amanda M. , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Klaassen Zachary W. , Terris Martha K. , Freedland Stephen J.
Published: May 2020

Background

The impact of race on prostate cancer skeletal‐related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration‐resistant prostate cancer (mCRPC).

Methods

The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan‐Meier method. Cox models tested the association between race and SREs and overall mortality.

Results

Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate‐specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59‐1.07) or overall mortality (HR, 0.87; 95% CI, 0.73‐1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes.

Conclusions

No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early‐stage disease.
Posttraumatic stress disorder and breast cancer: Risk factors and the role of inflammation and endocrine function
Authors: Brown Lauren C. , Murphy Amy R. , Lalonde Chloe S. , Subhedar Preeti D. , Miller Andrew H. , Stevens Jennifer S.
Published: May 2020

A breast cancer diagnosis can be a life‐changing and stressful experience that can lead to chronic mental health conditions such as posttraumatic stress disorder (PTSD). Greater than one‐third of patients initially diagnosed with PTSD after a diagnosis of breast cancer continue to have persistent or worsening PTSD symptoms after 4 years. An emerging body of literature has indicated several key environmental and biological risk factors for PTSD among survivors of breast cancer. Well‐recognized risk factors include having a history of childhood trauma, being nonwhite, obesity, younger age at the time of diagnosis, diagnosis with a higher stage of breast cancer, and short time since treatment. Of the emerging risk factors related to fear circuitry in the brain, 2 pathways of particular importance are the stress‐driven activation of inflammatory pathways and the long‐term effect of antiendocrine therapies. These central and peripheral responses during and after stress exposure are important because increased fear and anxiety can lead to the maintenance of PTSD and worse patient outcomes. Given the poor outcomes associated with PTSD and the high prevalence of breast cancer in women, more research to identify those women at heightened risk of PTSD after breast cancer is warranted to reduce the number of diagnoses and lessen the negative impact of this chronic mental health condition.
New mammography screening performance metrics based on the entire screening episode
Authors: Sprague Brian L. , Miglioretti Diana L. , Lee Christoph I. , Perry Hannah , Tosteson Anna A. N. , Kerlikowske Karla
Published: May 2020

Background

Established mammography screening performance metrics use the initial screening mammography assessment because they were developed for radiologist performance auditing, yet these metrics are frequently used to inform health policy and screening decision making. The authors have developed new performance metrics based on the final assessment that consider the entire screening episode, including diagnostic workup.

Methods

The authors used data from 2,512,577 screening episodes during 2005‐2017 at 146 facilities in the United States participating in the Breast Cancer Surveillance Consortium. Screening performance metrics based on the final assessment of the screening episode were compared with conventional metrics defined with the initial assessment. Results were also stratified by breast density and breast cancer risk.

Results

The cancer detection rates were similar for the final assessment (4.1 per 1000; 95% confidence interval [CI], 3.8‐4.3 per 1000) and the initial assessment (4.1 per 1000; 95% CI, 3.9‐4.3 per 1000). The interval cancer rate was 12% higher when it was based on the final assessment (0.77 per 1000; 95% CI, 0.71‐0.83 per 1000) versus the initial assessment (0.69 per 1000; 95% CI, 0.64‐0.74 per 1000), and this resulted in a modest difference in sensitivity (84.1% [95% CI, 83.0%‐85.1%] vs 85.7% [95% CI, 84.8%‐86.6%], respectively). Absolute differences in the interval cancer rate between final and initial assessments increased with breast density and breast cancer risk (eg, a difference of 0.29 per 1000 for women with extremely dense breasts and a 5‐year risk >2.49%).

Conclusions

Established screening performance metrics underestimate the interval cancer rate of a mammography screening episode, particularly for women with dense breasts or an elevated breast cancer risk. Women, clinicians, policymakers, and researchers should use final‐assessment performance metrics to support informed screening decisions.
Fluctuations of consciousness, mood, and science: The interhemispheric switch and sticky switch models two decades on
Authors: Miller Steven M.
Published: May 2020

Science and medicine aim to identify verifiable and replicable truths. However, the paths to such truths are frequently characterized by swinging pendulums of opposing perspectives. This is especially so in human neuroscience and the brain‐based clinical sciences, where the target of investigation is the most complex of all biological systems. This article overviews a set of interrelated neuroscientific and clinical hypotheses, models, experiments, and predictions with which I have been involved for the last two decades. Traversing visual neuroscience, consciousness science, genetics, chronobiology, and biological and clinical psychiatry, the work illustrates how developments in science and medicine can occur through a combination of synthesis, serendipity, and experimentation. The article also reflects on doing science with the inimitable John “Jack” Pettigrew, and outlines how Pettigrew and I conceived, proposed, tested, and developed two new scientific models—one on neural mechanisms of binocular rivalry, the other on the pathophysiology of bipolar disorder. I also provide an update on various aspects of our models and data, and describe lessons learned from Pettigrew on how perspectives in science exhibit their own fluctuations, ironically like the very phenomena on which we worked.
Lighting source classification applied in color images to contrast enhancement
Authors: Dehesa‐González Mario , Rosales‐Silva Alberto J. , Gallegos‐Funes Francisco J. , Kinani Jean M. V. , Ramos‐Díaz Eduardo
Published: May 2020

A novel methodology is proposed to identify the distribution of the intensity of the illuminant across a real‐world image; with this information, the image can be classified as a homogeneous or nonhomogeneous lighting source. A criterion is proposed for deciding whether the illumination in the tested image is homogeneous or nonhomogeneous. This criterion is based on well‐established methods that are dedicated to improving color characteristics and are commonly used to determine the color of the lighting source during a captured scene. The classification of homogeneous or nonhomogeneous illumination in real‐world images is implemented in the BSD500 database, and the results are compared with a manual classification of images—proposed under subjective criteria—by the authors; in this way, one can analyze how the lighting source affects the image. This procedure provides a classification methodology for real‐world image databases found in the scientific literature.
High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer
Authors: Wang Minyu , Huang Yu‐Kuan , Kong Joseph CH , Sun Yu , Tantalo Daniela G , Yeang Han Xian Aw , Ying Le , Yan Feng , Xu Dakang , Halse Heloise , Di Costanzo Natasha , Gordon Ian R , Mitchell Catherine , Mackay Laura K , Busuttil Rita A , Neeson Paul J , Boussioutas Alex
Published: May 2020

Objectives

To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed.

Methods

The association of GC patients’ outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts.

Results

Increased CD4+FOXP3+ T‐cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4+FOXP3+ T cells had a close interaction with CD8+ T cells rather than tumor cells. High densities of CD4+FOXP3+ T cells and CD8+ T cells (High‐High) independently predicted prolonged patient survival. Furthermore, the interferon‐gamma (IFN‐γ) gene signature and PDL1 expression were up‐regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High‐High group also had excellent survival. The High‐High GS/CIN tumors were coupled with increased frequencies of Tbet+CD4+ T cells and central memory CD4+ T cells in the peripheral blood.

Conclusion

These novel findings identify the combination of CD8+ T cells and FOXP3+CD4+ T cells as a significant prognostic marker for GC patients, which also could potentially be targeted and applied in the combination therapy with immune checkpoint blockades in precision medicine.
Comparison of two human organoid models of lung and intestinal inflammation reveals Toll‐like receptor signalling activation and monocyte recruitment
Authors: Jose Shyam Sushama , De Zuani Marco , Tidu Federico , Hortová Kohoutková Marcela , Pazzagli Lucia , Forte Giancarlo , Spaccapelo Roberta , Zelante Teresa , Frič Jan
Published: May 2020

Objectives

The activation of immune responses in mucosal tissues is a key factor for the development and sustainment of several pathologies including infectious diseases and autoimmune diseases. However, translational research and personalised medicine struggle to advance because of the lack of suitable preclinical models that successfully mimic the complexity of human tissues without relying on in vivo mouse models. Here, we propose two in vitro human 3D tissue models, deprived of any resident leucocytes, to model mucosal tissue inflammatory processes.

Methods

We developed human 3D lung and intestinal organoids differentiated from induced pluripotent stem cells to model mucosal tissues. We then compared their response to a panel of microbial ligands and investigated their ability to attract and host human primary monocytes.

Results

Mature lung and intestinal organoids comprised epithelial (EpCAM+) and mesenchymal (CD73+) cells which responded to Toll‐like receptor stimulation by releasing pro‐inflammatory cytokines and expressing tissue inflammatory markers including MMP9, COX2 and CRP. When added to the organoid culture, primary human monocytes migrated towards the organoids and began to differentiate to an ‘intermediate‐like’ phenotype characterised by increased levels of CD14 and CD16.

Conclusion

We show that human mucosal organoids exhibit proper immune functions and successfully mimic an immunocompetent tissue microenvironment able to host patient‐derived immune cells. Our experimental set‐up provides a novel tool to tackle the complexity of immune responses in mucosal tissues which can be tailored to different human pathologies.
Blastic plasmacytoid dendritic cell neoplasm with a history of cytopenia: A case report
Authors: Yan Miao , Wang Wensheng , Cen Xinan , Wang Lihong , Sun Yuhua , Wang Bingjie , Ou Jinping , Nong Lin , Ren Hanyun , Zhu Ping , Wang Mangju
Published: May 2020

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy arising from plasmacytoid dendritic cell precursors. The disease typically manifests in the skin, but it also evolves into a leukemic phase or can be complicated by other myeloid malignancies, especially myelomonocytic tumors. The association between these neoplasms is not fully elucidated. We report a case of BPDCN with a history of cytopenia that was supposed to be chronic myelomonocytic leukemia. The patient received intensive chemotherapy and achieved complete remission, but soon relapsed. The successive occurrence of myelomonocytic neoplasm and BPDCN is in accordance with the fact that they evolve from a common cell origin with a multilineage potential for myelomonocytic and plasmacytoid dendritic cell differentiation. This case may shed further light on the mystery of biology and the histogenesis of BPDCN.
Bringing up baby: Maternal responsiveness, secondary attachments, and the development of infant social competence in wild olive baboons (Papio anubis)
Authors: Most Corinna A. , Strum Shirley C.
Published: May 2020

Caregiver responsiveness and presence of secondary attachments play a crucial role in children's socio‐cognitive and emotional development, but little is known of their effect on the development of non‐human primates. Here we present the results of a 16‐month behavioral study conducted on 22 wild infant olive baboons (Papio anubis) at the Uaso Ngiro Baboon Project, Kenya. This is the first study to examine the effects of maternal responsiveness and secondary attachments on the development of infant social behavior in a wild primate species that does not breed cooperatively. The data track maternal responsiveness and the rates of two behavioral indicators of infant social competence—orienting toward interactions and social play—over the course of the first year of life. Maternal responsiveness decreased as infants grew older, while infant orientation toward interactions and play behavior increased. Infants with poorly responsive mothers were more likely to have secondary attachments, and infants with secondary attachments to siblings oriented more frequently to social interactions than those with secondary attachments to adult/subadult males or with no secondary attachments. These findings indicate that variation in maternal responsiveness and presence of secondary attachments can influence the development of social competence in olive baboon infants.
Evolution of defense and herbivory in introduced plants—Testing enemy release using a known source population, herbivore trials, and time since introduction
Authors: Brandenburger Claire R. , Kim Martin , Slavich Eve , Meredith Floret L. , Salminen Juha‐Pekka , Sherwin William B. , Moles Angela T.
Published: May 2020

The enemy release hypothesis is often cited as a potential explanation for the success of introduced plants; yet, empirical evidence for enemy release is mixed. We aimed to quantify changes in herbivory and defense in introduced plants while controlling for three factors that might have confounded past studies: using a wide native range for comparison with the introduced range, measuring defense traits without determining whether they affect herbivore preferences, and not considering the effect of time since introduction. The first hypothesis we tested was that introduced plants will have evolved lower levels of plant defense compared to their source population. We grew South African (source) and Australian (introduced) beach daisies (Arctotheca populifolia) in a common‐environment glasshouse experiment and measured seven defense traits. Introduced plants had more ash, alkaloids, and leaf hairs than source plants, but were also less tough, with a lower C:N ratio and less phenolics. Overall, we found no difference in defense between source and introduced plants. To determine whether the feeding habits of herbivores align with changes in defense traits, we conducted preference feeding trials using five different herbivore species. Herbivores showed no overall preference for leaves from either group. The second hypothesis we tested was that herbivory on introduced plant species will increase through time after introduction to a new range. We recorded leaf damage on herbarium specimens of seven species introduced to eastern Australia and three native control species. We found no change in the overall level of herbivory experienced by introduced plants since arriving in Australia.

Conclusion

In the field of invasion ecology, we need to rethink the paradigm that species introduced to a new range undergo simple decreases in defenses against herbivores. Instead, plants are likely to employ a range of defense traits that evolve in both coordinated and opposing ways in response to a plethora of different biotic and abiotic selective pressures.
A new variance ratio metric to detect the timescale of compensatory dynamics
Authors: Zhao Lei , Wang Shaopeng , Hallett Lauren M. , Rypel Andrew L. , Sheppard Lawrence W. , Castorani Max C. N. , Shoemaker Lauren G. , Cottingham Kathryn L. , Suding Katharine , Reuman Daniel C.
Published: May 2020

Understanding the mechanisms governing ecological stability—why a property such as primary productivity is stable in some communities and variable in others—has long been a focus of ecology. Compensatory dynamics, in which anti‐synchronous fluctuations between populations buffer against fluctuations at the community level, are a key theoretical mechanism of stability. Classically, compensatory dynamics have been quantified using a variance ratio approach that compares the ratio between community variance and aggregate population variance, such that a lower ratio indicates compensation and a higher ratio indicates synchrony among species fluctuations. However, population dynamics may be influenced by different drivers that operate on different timescales, and evidence from aquatic systems indicates that communities can be compensatory on some timescales and synchronous on others. The variance ratio and related metrics cannot reflect this timescale specificity, yet have remained popular, especially in terrestrial systems. Here, we develop a timescale‐specific variance ratio approach that formally decomposes the classical variance ratio according to the timescales of distinct contributions. The approach is implemented in a new R package, called tsvr, that accompanies this paper. We apply our approach to a long‐term, multisite grassland community dataset. Our approach demonstrates that the degree of compensation vs. synchrony in community dynamics can vary by timescale. Across sites, population variability was typically greater over longer compared to shorter timescales. At some sites, minimal timescale specificity in compensatory dynamics translated this pattern of population variability into a similar pattern of greater community variability on longer compared to shorter timescales. But at other sites, differentially stronger compensatory dynamics at longer compared to shorter timescales produced lower‐than‐expected community variability on longer timescales. Within every site, there were plots that exhibited shifts in the strength of compensation between timescales. Our results highlight that compensatory vs. synchronous dynamics are intrinsically timescale‐dependent concepts, and our timescale‐specific variance ratio provides a metric to quantify timescale specificity and relate it back to the classic variance ratio.
Risk assessment in PAH using quantitative CMR tricuspid regurgitation: relation to heart catheterization
Authors: Hedström Erik , Bredfelt Anna , Rådegran Göran , Arheden Håkan , Ostenfeld Ellen
Published: May 2020

Aims

Improved risk stratification is of value for decision making in pulmonary arterial hypertension (PAH). Right heart catheterization combined with quantitative tricuspid regurgitation (TR) by cardiovascular magnetic resonance (CMR) may provide this. The aims were to study: (i) to what extent quantitative TR is associated with event‐free survival; (ii) how quantitative TR is related to known prognostic markers in PAH; and (iii) to what extent quantitative TR and right atrial pressure determine right atrial dilation.

Methods and results

Fifty patients (63 ± 17 years) with PAH referred for CMR were included. Volumes and pulmonary artery flow by CMR and pressure and vascular resistance by right heart catheterization were obtained. Composite outcome was lung transplantation or death. Four transplantations and 27 deaths occurred over a median of 2.7 years. A trend towards higher hazard ratio was shown for TR volume (TRV; 2.1, 95% CI 1.0–4.4) and TR fraction (TR%; 1.6, 95% CI 0.8–3.3) above median. TRV and TR% correlated with right ventricular (RV) end‐diastolic (TRV r = 0.50; TR% r = 0.39) and end‐systolic (TRV r = 0.35; TR% r = 0.30) volumes, pulmonary vascular resistance (TRV r = 0.28; TR% r = 0.43), N terminal pro brain natriuretic peptide (TRV r = 0.65; TR% r = 0.68), cardiac index (TRV r = −0.32; TR% r = −0.54), pulmonary artery stroke volume (TRV r = −0.32; TR% r = −0.58) and effective RV ejection fraction by pulmonary artery quantitative flow (TRV r = −0.56; TR% r = −0.69), but not RVEF. Both TR% and right atrial pressure determined right atrial volumes (r2 = 0.38; r2 = 0.48).

Conclusions

A clear trend towards worse outcome with larger TRV or TR% was shown; however, the number of events was insufficient for significant outcome differences. Prognostic value of quantitative TR should be investigated in a larger multicentre cohort. Effective RV ejection fraction may be considered an improved measure of RV function in PAH.
Cyclopentadienylnickel Chelates with Secondary or Tertiary Phosphane Tethers Bearing Imidazol‐2‐ylidene Ligands
Authors: Werner Irina , Kohser Stefanie , Butenschön Holger
Published: May 2020

Treatment of cyclopentadienylnickel chloro or bromo chelates bearing either a tertiary 2‐(di‐tert‐butyl)phosphanylethyl or a secondary 2‐(2,4,6‐trimethylphenyl)phosphanylethyl tether with imidazolylidene (Arduengo carbene) ligands results in cationic or electroneutral carbene complexes with either a decoordinated or a chelated tether. The outcome depends on the nature of the carbene, the counter anion, and the reactant stoichiometry. The results are the basis of ongoing investigations directed towards a deprotonation of the chelated cationic complexes with a secondary phosphorus atom.
EEG findings in acutely ill patients investigated for SARS‐CoV‐2/COVID‐19: A small case series preliminary report
Authors: Galanopoulou Aristea S. , Ferastraoaru Victor , Correa Daniel J. , Cherian Koshi , Duberstein Susan , Gursky Jonathan , Hanumanthu Rajani , Hung Christine , Molinero Isaac , Khodakivska Olga , Legatt Alan D. , Patel Puja , Rosengard Jillian , Rubens Elayna , Sugrue William , Yozawitz Elissa , Mehler Mark F. , Ballaban‐Gil Karen , Haut Sheryl R. , Moshé Solomon L. , Boro Alexis
Published: May 2020

Objective

Acute encephalopathy may occur in COVID‐19‐infected patients. We investigated whether medically indicated EEGs performed in acutely ill patients under investigation (PUIs) for COVID‐19 report epileptiform abnormalities and whether these are more prevalent in COVID‐19 positive than negative patients.

Methods

In this retrospective case series, adult COVID‐19 inpatient PUIs underwent EEGs for acute encephalopathy and/or seizure‐like events. PUIs had 8‐channel headband EEGs (Ceribell; 20 COVID‐19 positive, 6 COVID‐19 negative); 2 more COVID‐19 patients had routine EEGs. Overall, 26 Ceribell EEGs, 4 routine and 7 continuous EEG studies were reviewed. EEGs were interpreted by board‐certified clinical neurophysiologists (n = 16). EEG findings were correlated with demographic data, clinical presentation and history, and medication usage. Fisher's exact test was used.

Results

We included 28 COVID‐19 PUIs (30‐83 years old), of whom 22 tested positive (63.6% males) and 6 tested negative (33.3% male). The most common indications for EEG, among COVID‐19‐positive vs COVID‐19‐negative patients, respectively, were new onset encephalopathy (68.2% vs 33.3%) and seizure‐like events (14/22, 63.6%; 2/6, 33.3%), even among patients without prior history of seizures (11/17, 64.7%; 2/6, 33.3%). Sporadic epileptiform discharges (EDs) were present in 40.9% of COVID‐19‐positive and 16.7% of COVID‐19‐negative patients; frontal sharp waves were reported in 8/9 (88.9%) of COVID‐19‐positive patients with EDs and in 1/1 of COVID‐19‐negative patient with EDs. No electrographic seizures were captured, but 19/22 COVID‐19‐positive and 6/6 COVID‐19‐negative patients were given antiseizure medications and/or sedatives before the EEG.

Significance

This is the first preliminary report of EDs in the EEG of acutely ill COVID‐19‐positive patients with encephalopathy or suspected clinical seizures. EDs are relatively common in this cohort and typically appear as frontal sharp waves. Further studies are needed to confirm these findings and evaluate the potential direct or indirect effects of COVID‐19 on activating epileptic activity.
Relation between vitamin D and impulse behaviours in patients with eating disorder: a pilot observational study
Authors: Todisco Patrizia , Meneguzzo Paolo , Vogazianos Paris , Garolla Alice , Antoniades Athos , Tozzi Federica
Published: May 2020

Objective

There is growing evidence that vitamin D levels have a role not only in bone health and energy metabolism, but also for supporting nervous system and brain functions, including impulsivity. Impulsive behaviours are considered characteristics of great relevance in patients with Eating Disorders (ED) both for the course of the illness and for the treatment. The aim of this study is to examine the relationship between impulsive behaviours and vitamin D in patients with ED.

Method

236 patients with a diagnosis of ED, consecutively recruited at an ED ward between 2014 and 2018, were enrolled. Patients were classified as impulsive or non‐impulsive based on the presence of clinically relevant impulsive behaviours.

Results

Impulsive patients were found to have statistically significant lower levels of vitamin D than non‐impulsive (p = .007). A threshold value of 20.4 ng/ml for discriminating impulsive from non‐impulsive patients was found.

Discussion

This hypothesis generating study partially confirmed a relationship between vitamin D deficiency and impulsive behaviours in ED spectrum mediated by body weight, even if results were not confirmed after corrected by obesity. No definitive conclusion may be taken on whether the effect is reduced due to the loss of power. Future directions are discussed.
Estimating the timescale of fluvial response to anthropogenic disturbance using two generations of dams on the South River, Massachusetts, USA
Authors: Dow Samantha , Snyder Noah P. , Ouimet William B. , Martini Anna M. , Yellen Brian , Woodruff Jonathan D. , Newton Robert M. , Merritts Dorothy J. , Walter Robert C.
Published: May 2020

Centuries‐long intensive land‐use change in the north‐eastern United States provides the opportunity to study the timescale of geomorphic response to anthropogenic disturbances. In this region, forest‐clearing and agricultural practices following EuroAmerican settlement led to deposition of legacy sediment along valley bottoms, including behind mill dams. The South River in western Massachusetts experienced two generations of damming, beginning with mill dams up to 6‐m high in the eighteenth–nineteenth century, and followed by construction of the Conway Electric Dam (CED), a 17‐m‐tall hydroelectric dam near the watershed outlet in 1906. We use the mercury (Hg) concentration in upstream deposits along the South River to constrain the magnitude, source, and timing of inputs to the CED impoundment. Based on cesium‐137 (137Cs) chronology and results from a sediment mixing model, remobilized legacy sediment comprised% of the sediment load in the South River prior to 1954; thereafter, from 1954 to 1980s, erosion from glacial deposits likely dominated (63 ± 14%), but with legacy sediments still a substantial source (37 ± 14%). We also use the CED reservoir deposits to estimate sediment yield through time, and find it decreased after 1952. These results are consistent with high rates of mobilization of legacy sediment as historic dams breached in the early twentieth century, and suggest rapid initial response to channel incision, followed by a long decay in the second half of the century, that is likely dependent on large flood events to access legacy sediment stored in banks. Identifying sources of sediment in a watershed and quantifying erosion rates can help to guide river restoration practices. Our findings suggest a short fluvial recovery time from the eighteenth–nineteenth century to perturbation during the first half of the twentieth century, with subsequent return to a dominant long‐term signal from erosion of glacial deposits, with anthropogenic sediment persisting as a secondary source. © 2020 John Wiley & Sons, Ltd.
Investigation of new products and reaction kinetics for myricetin in DMEM via an in situ UPLC–MS–MS analysis
Authors: Cao Hui , Yi Lunzhao , Zhong Jiayi , Högger Petra , Wang Mingfu , Prieto Miguel‐Angel , Simal‐Gandara Jesus , Xiao Jianbo
Published: May 2020

Myricetin, with its pyrogallol B‐ring, is evidently instable in DMEM (Dulbecco's modified Eagle's) medium at 37°C. However, the underlying mechanism of this instability is not clear yet. Herein, the reaction products of myricetin in DMEM were investigated via an in situ UPLC–MS–MS analysis. Myricetin was mixed with prewarmed DMEM in an autosampler screw top vial for UPLC. Immediately, a 50‐µl sample was automatically injected every 50 min. Myricetin was highly stable in dimethyl sulfoxide (DMSO) when kept at 37°C for 2 weeks. Myricetin was very unstable in DMEM at 37°C and largely converted to new products A (m/z = 635.07) and B (m/z = 633.05) within 1 min. Another new product, C (m/z = 469.04), was detected after the fourth injection (150 min). Myricetin was much more stable in DMEM at 4°C as compared to 37°C. There was a minor conversion of myricetin to the new product A (m/z = 635.07) within 1.0 min, but it subsequently increased until the sixth injection (250 min), and disappeared after the fifteenth injection (700 min). In summary, myricetin first formed a dimer A (m/z = 635.07) and then was oxidized to B (m/z = 633.05), which was finally degraded to C (m/z = 469.04) in DMEM. This process was significantly affected by the temperature, and low temperature is helpful to detect the unstable products.
On the economics and the future prospects of battery electric vehicles
Authors: Ajanovic Amela , Haas Reinhard
Published: May 2020

Currently, the electrification of passenger cars is seen as one of the key strategies for heading toward a sustainable transport system. Of special interest are battery electric vehicles (BEVs), which can enable significant emission reductions if electricity used is produced from renewable energy sources. However, mainly due to their high investment costs (retail purchase price) of BEVs, they are currently not economically competitive with conventional fossil‐fueled vehicles without different supporting policy measures. This paper analyzes current costs and future prospects for BEVs compared to conventional petrol cars looking at the total costs of ownership. Furthermore, the future prospects are investigated considering technological learning for BEVs, CO2 taxes for fuels, and various other policy framework conditions such as rebates for the purchase of the BEVs. The major conclusions are as follows: (i) to improve the economics of BEVs, a very important aspect is the introduction of CO2‐based fuel taxes; (ii) regarding economics, the second important aspect is the reduction of the investment costs of the BEVs due to technological learning, especially of the battery; (iii) in addition, the introduction of CO2‐based registration taxes for the purchase of passenger cars makes sense; (iv) subsidies or rebates for the purchase of a BEV maybe a measure successful in the short term and helpful to stimulate technological learning; (v) by far, the highest uncertainty regarding the future prospects of BEVs is how fast technological learning will take place, especially for the battery, and how the future development of batteries will be. © 2020 The Authors. Greenhouse Gases: Science and Technology published by Society of Chemical Industry and John Wiley & Sons, Ltd.
In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester
Authors: Jaimes Camilo , Machado‐Rivas Fedel , Afacan Onur , Khan Shadab , Marami Bahram , Ortinau Cynthia M. , Rollins Caitlin K. , Velasco‐Annis Clemente , Warfield Simon K. , Gholipour Ali
Published: May 2020

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm2 images and 12 diffusion‐sensitized images at b = 500 s/mm2). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.
UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt/β‐catenin signaling
Authors: Li Liang , Duan Qiuhui , Zeng Zhiyang , Zhao Jindong , Lu Jiawei , Sun Jialiang , Zhang Jiqin , Siwko Stefan , Wong Jiemin , Shi Tieliu , Zhang Xueli , Liu Mingyao , Chen Jinlian , Li Dali
Published: May 2020

Intestinal tumors mainly originate from transformed crypt stem cells supported by Wnt signaling, which functions through downstream critical factors enriched in the intestinal stem/progenitor compartment. Here, we show Uhrf2 is predominantly expressed in intestinal crypts and adenomas in mice and is transcriptionally regulated by Wnt signaling. Upregulated UHRF2 correlates with poor prognosis in colorectal cancer patients. Although loss of Uhrf2 did not affect intestinal homeostasis and regeneration, tumor initiation and progression were inhibited, leading to a markedly prolonged life span in Uhrf2 null mice on an ApcMin background. Uhrf2 deficiency also strongly reduced primary tumor organoid formation suggesting impairment of tumor stem cells. Moreover, ablation of Uhrf2 suppressed tumor cell proliferation through downregulation of the Wnt/β‐catenin pathway. Mechanistically, Uhrf2 directly interacts with and sumoylates Tcf4, a critical intranuclear effector of the Wnt pathway. Uhrf2 mediated SUMOylation stabilized Tcf4 and further sustained hyperactive Wnt signaling. Together, we demonstrate that Wnt‐induced Uhrf2 expression promotes tumorigenesis through modulation of the stability of Tcf4 for maintaining oncogenic Wnt/β‐catenin signaling. This is a new reciprocal feedforward regulation between Uhrf2 and Wnt signaling in tumor initiation and progression.
Improving pharmaceutical care education in Uganda through sustainable experiential programs and research
Authors: Bohan KarenBeth H. , Flores Emily K. , Rajab Kalidi , Nambatya Winnie , Nicol Melanie R. , Crowe Susie J. , Manning Dana H. , Eneh Prosperity , Adome Richard Odoi
Published: May 2020

This paper details collaboration in elective global health Advanced Pharmacy Practice Experiences (APPEs) between six schools of pharmacy, four in the United States (U.S.) and two in Uganda. This collaboration was initiated to build capacity within Uganda to advance pharmacy practice by strengthening pharmaceutical care education and research, and to provide benefits in the global and public health education and research for U.S. students and each partner University. Makerere University and Mbarara University of Science and Technology in Uganda sought out collaborations to improve pharmacy education in Uganda and alleviate shortages in faculty they have experienced in expanding pharmacy training. In response to this need, Wilkes University, Binghamton University, the University of Minnesota, and East Tennessee State University developed faculty‐led APPEs to help model and teach the principles of clinical pharmaceutical care. These faculty‐led APPEs occur in various Ugandan locations throughout the year and incorporate Ugandan and U.S. students as co‐learners. Ugandan and U.S. faculty act as co‐facilitators of didactic, experiential, and research learning experiences. APPE activities include modeling the provision of pharmaceutical care, interprofessional patient care on inpatient wards, joint didactic lectures and case presentations, skills laboratory sessions, and research components. Developed to serve the needs of both the U.S. and Ugandan partners, the elective global health APPEs to Uganda have grown to be sustainable, mutually beneficial collaborations between the six schools of pharmacy and the Ugandan partners. Formal and informal communications between all of the entities involved have helped support continuity of these programs. We recommend such initiatives to other countries and institutions desiring to improve training for pharmaceutical care to advance pharmacy practice.
Automated synthesis of 68Ga/177Lu‐PSMA on the Trasis miniAllinOne
Authors: Sørensen Mikkel A. , Andersen Valdemar L. , Hendel Helle Westergren , Vriamont Charles , Warnier Corentin , Masset Julien , Huynh Tri Hien Viet
Published: May 2020

Prostate‐specific membrane antigen (PSMA)‐based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [68Ga]PSMA‐HBED‐CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP‐compliant production of [68Ga]PSMA‐HBED‐CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP‐compliant production of the radiotherapeutic [177Lu]PSMA‐I&T using the same synthesis module. PSMA‐based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration‐resistant PCa, and GMP‐compliant routine production methods are therefore called for. This report highlights how PSMA‐based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.
The anti‐HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV‐2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID‐19 infections
Authors: Musarrat Farhana , Chouljenko Vladimir , Dahal Achyut , Nabi Rafiq , Chouljenko Tamara , Jois Seetharama D. , Kousoulas Konstantin G.
Published: May 2020

Severe acute respiratory syndrome coronavirus‐2 (SARS CoV‐2) is the causative agent of the coronavirus disease‐2019 (COVID‐19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV‐2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID‐19. These results suggest that SARS CoV‐2 is able to spread from cell‐to‐cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA‐approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S‐n‐ and S‐o‐mediated cell fusion with complete inhibition at a 10‐μM concentration. In‐silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S‐n‐ and S‐o‐mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV‐2 symptoms appear.
Protective effect of ginsenoside Rk1, a major rare saponin from black ginseng, on cisplatin‐induced nephrotoxicity in HEK‐293 cells
Authors: Hu Jun‐Nan , Xu Xing‐Yue , Jiang Shuang , Liu Ying , Liu Zhi , Wang Ying‐Ping , Gong Xiao‐Jie , Li Ke‐Ke , Ren Shen , Li Wei
Published: May 2020

Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin‐induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin‐induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK‐293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin‐induced elevated protein levels of Bax, cleaved caspase‐3, cleaved caspase‐9, and decreased protein level of Bcl‐2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti‐oxidation and anti‐apoptosis effects.
Infection control measures of a Taiwanese hospital to confront the COVID‐19 pandemic
Authors: Chang Ya‐Ting , Lin Chun‐Yu , Tsai Ming‐Ju , Hung Ching‐Tzu , Hsu Chia‐Wen , Lu Po‐Liang , Hou Ming‐Feng
Published: May 2020

The World Health Organization announced the coronavirus disease 2019 (COVID‐19) outbreak a pandemic on 12 March 2020. Although being in proximity to China, the original epicenter of the COVID‐19 outbreak, Taiwan has maintained a low number of COVID‐19 cases despite its close social ties and heavy traffic between Taiwan and China. Containment strategies executed by the Taiwanese government have attracted global attention. Similarly, in‐hospital settings, high alertness and swift responses to the changing outbreak situation are necessary to ensure hospital staff members' safety so they can continue to save patients' lives. Herein, we present infection control measures that can be adopted in hospital settings that were executed in a Taiwanese hospital to confront the COVID‐19 pandemic, including emergency preparedness and responses from the hospital administration, education, surveillance, patient flow arrangement, the partition of hospital zones, and the prevention of a systemic shutdown by using the “divided cabin, divided flow” strategy. The measures implemented by a Taiwan hospital during the COVID‐19 pandemic may not be universally applicable in every hospital. Nonetheless, the presented infection control methods have been practically executed and can be referenced or modified to fit each hospital's unique condition.
Bioinspired All‐Polyester Diblock Copolymers Made from Poly(pentadecalactone) and Poly(3‐hydroxycinnamate): Synthesis and Polymer Film Properties
Authors: Saar Julia S. , Shi Yue , Lienkamp Karen
Published: May 2020

A bioinspired diblock copolymer is synthesized from pentadecalactone and 3‐hydroxy cinnamic acid. Poly(pentadecalactone) (PPDL) with a molar mass of up to 43 000 g mol−1 is obtained by ring‐opening polymerization initiated by propargyl alcohol. Poly(3‐hydroxycinnamate) (P3HCA) is obtained by polycondensation and end‐functionalized with 3‐azido propanol. The two functionalized homopolymers are connected via 1,3‐dipolar Huisgen addition to yield the block copolymer PPDL‐triazole‐P3HCA. The structure of the block copolymer is confirmed by proton NMR, FTIR spectroscopy and GPC. By analyzing the morphology of polymer films made from the homopolymers, from a 1:1 homopolymer blend, and from the PPDL‐triazole‐P3HCA block copolymer, clearly distinct micro‐ and nanostructures are revealed. Quantitative nanomechanical measurements reveal that the block copolymer PPDL‐triazole‐P3HCA has a DMT modulus of 22.3 ± 2.7 MPa, which is lower than that of the PPDL homopolymer (801 ± 42 MPa), yet significantly higher than that of the P3HCA homopolymer (1.77 ± 0.63 MPa). Thermal analytics show that the melting point of PPDL‐triazole‐P3HCA is similar to PPDL (89–90 °C), while it has a glass transition temperature similar to P3HCA (123–124 °C). Thus, the semicrystalline, potentially degradable all‐polyester block copolymer PPDL‐triazole‐P3HCA combines the thermal properties of either homopolymer, and has an intermediate elastic modulus.
Sharp multi‐weighted bounds for multilinear fractional rough operators and Cohen–Gosselin type commutators
Authors: Tao Xiangxing , Yu Xiao
Published: May 2020

In the article, we consider the multilinear fraction maximal operators and the multilinear fraction integrals with rough kernels, we introduce a new class for ‐weights tuple , and prove the optimal constant estimates of the sharp multi‐weighted bounds for both operators. We also show the sharp multi‐weighted bounds for the Cohen–Gosselin type multi‐commutator of the both operators.