bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia
Authors: Lai Lu‐Lu , Chen Yi‐Jun , Li Yun‐Lu , Lin Xiao‐Hong , Wang Meng‐Wen , Dong En‐Lin , Wang Ning , Chen Wan‐Jin , Lin Xiang
Published: August 2020

Objective

Recessive mutations in the CAPN1 gene have recently been identified in spastic paraplegia 76 (SPG76), a complex hereditary spastic paraplegia (HSP) that is combined with cerebellar ataxia, resulting in an ataxia‐spasticity disease spectrum. This study aims to assess the influence of CAPN1 variants on the occurrence of SPG76 and identify factors potentially contributing to phenotypic heterogeneity.

Methods

We screened a cohort of 240 unrelated HSP families for variants in CAPN1 using high‐throughput sequencing analysis. We described in detail the clinical and genetic features of the SPG76 patients in our cohort and summarized all reported cases.

Results

Six unreported CAPN1‐associated families containing eight patients with or without cerebellar ataxia were found in our cohort of HSP cases. These patients carried three previously reported homozygous truncating mutations (p.V64Gfs*103, c.759+1G>A, and p.R285*), and three additional novel compound heterozygous missense mutations (p.R481Q, p.P498L, and p.R618W). Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. In total, 33 pathogenic mutations were distributed along the three reported functional domains of calpain‐1 protein, encoded by CAPN1, with no hotspot region. A comparison of gender distribution between the two groups indicated that female SPG76 patients were significantly more likely to present with complicated HSP than male patients (P = 0.015).

Interpretation

Our study supports the clinically heterogeneous inter‐ and intra‐family variability of SPG76 patients, and demonstrates that gender and calpain‐1 linker structure may contribute to clinical heterogeneity in SPG76 cases.
Centromedian thalamic responsive neurostimulation for Lennox‐Gastaut epilepsy and autism
Authors: Kwon Churl‐Su , Schupper Alexander J. , Fields Madeline C. , Marcuse Lara V. , La Vega‐Talbott Maite , Panov Fedor , Ghatan Saadi
Published: August 2020

The RNS System is not approved in patients under 18, although a critical need for novel treatment modalities in this vulnerable population persist. We present two pediatric patients with drug‐resistant epilepsy secondary to Lennox‐Gastaut Syndrome (LGS) and autism spectrum disorder (ASD) treated with the RNS System. Both patients have experienced 75–99% clinical seizure reductions in >1 year of follow‐up. We illustrate that children with diffuse onset, multifocal epilepsy, including frontal and thalamic circuits thought to exist in the generation of LGS seizures, can be treated with responsive neurostimulation safely and effectively, targeting thalamic networks, and avoiding palliative disconnections and resections.
Guidance for Implementing Best Practice Therapeutic Exercise for Patients With Knee and Hip Osteoarthritis: What Does the Current Evidence Base Tell Us?
Authors: Holden Melanie A. , Button Kate , Collins Natalie J. , Henrotin Yves , Hinman Rana S. , Larsen Jesper B. , Metcalf Ben , Master Hiral , Skou Søren T. , Thoma Louise M. , Wellsandt Elizabeth , White Daniel K. , Bennell Kim
Published: August 2020

Therapeutic exercise is a recommended first‐line treatment for patients with knee and hip osteoarthritis (OA); however, there is little specific advice or practical resources to guide clinicians in its implementation. As the first in a series of projects by the Osteoarthritis Research Society International Rehabilitation Discussion Group to address this gap, we aim in this narrative review to synthesize current literature informing the implementation of therapeutic exercise for patients with knee and hip OA, focusing on evidence from systematic reviews and randomized controlled trials. Therapeutic exercise is safe for patients with knee and hip OA. Numerous types of therapeutic exercise (including aerobic, strengthening, neuromuscular, mind‐body exercise) may be utilized at varying doses and in different settings to improve pain and function. Benefits from therapeutic exercise appear greater when dosage recommendations from general exercise guidelines for healthy adults are met. However, interim therapeutic exercise goals may also be useful, given that many barriers to achieving these dosages exist among this patient group. Theoretically‐informed strategies to improve adherence to therapeutic exercise, such as patient education, goal‐setting, monitoring, and feedback, may help maintain participation and optimize clinical benefits over the longer term. Sedentary behavior is also a risk factor for disability and lower quality of life in patients with knee and hip OA, although limited evidence exists regarding how best to reduce this behavior. Current evidence can be used to inform how to implement best practice therapeutic exercise at a sufficient and appropriate dose for patients with knee and hip OA.
PDMPs grapple with new confidentiality rules for methadone patients
Authors: Knopf Alison
Published: August 2020

Methadone patients are facing the real possibility that, for the first time, their information will go into the state's prescription drug monitoring program (PDMP), but PDMPs themselves are confused about exactly how to go about making sure patients consent to the release of the information, ADAW has learned. Under the final rule, which took effect Aug. 14, amending 42 CFR Part 2, opioid treatment programs (OTPs) are now allowed to send patient information to the PDMP, but the final rule and the law still hold that patients must consent to the release of this information first.
Letter to the Editor
Authors: Knopf Alison
Published: August 2020

In “COMBINE follow‐up: Some heavy use of alcohol compatible with recovery” (see ADAW, Aug. 17, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32806), we wrote about a study by Katie Witkiewitz, Ph.D., published in Alcoholism: Clinical and Experimental Research, showing that some people can be in recovery but still drink heavily. We received the following commentary from Annie Peters, Ph.D., director of research and education at the National Association of Addiction Treatment Providers (NAATP).
Abrasion Indicators for Smart Surfaces Based on a Luminescence Turn‐On Effect in Supraparticles
Authors: Wenderoth Sarah , Granath Tim , Prieschl Johannes , Wintzheimer Susanne , Mandel Karl
Published: August 2020

Slight mechanical damage on surfaces or coatings caused, for example, by shear stress, is hardly detectable by simple means. Therefore, shear stress indicator particles for the creation of “interactive and communicating” coatings are presented. These are core‐shell supraparticles obtained by a two‐step spray‐drying assembly process from nanoparticle dispersions. Three different types of nanoparticles are used to create the supraparticles: dye‐doped silica nanoparticles responsible for the fluorescence signal, iron oxide nanoparticles acting as a fluorescence absorber, and pure silica nanoparticles regulating the indicator sensitivity. The creation of two different types of indicator systems is feasible by changing the nanoparticle arrangements within the supraparticle: A turn‐off and a turn‐on system, which indicate—after incorporation into a coating—shear stress by the decrease or the increase in the fluorescence intensity, respectively. Herein, two different mechanisms compete with each other: on the one hand, the change in the fluorescence signal due to physical light‐absorbing effects, and on the other hand, the abrasion of luminescent material. The clear superiority of the turn‐on system to achieve a reliable signal is demonstrated in this work. With the particle systems, interactive and communicating surface coatings are established.
Synthesis of Pyridothiazepines via a 1,5‐Dipolar Cycloaddition Reaction between Pyridinium 1,4‐Zwitterionic Thiolates and Activated Allenes
Authors: Cheng Bin , Zhang Xinping , Li Hui , He Yixuan , Li Yun , Sun Haiyan , Wang Taimin , Zhai Hongbin
Published: August 2020

The synthesis of pyridothiazepines has been achieved via a 1,5‐dipolar cycloaddition reaction between pyridinium 1,4‐zwitterionic thiolates and activated allenes conducted under thermal conditions. Meanwhile, a ring‐contraction reaction of the resulting pyridothiazepine derivatives via the extrusion of 3‐thioxoacrylates has also been described.

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Radical‐Mediated Non‐Dearomative Strategies in Construction of Spiro Compounds
Authors: Pawlowski R. , Skorka P. , Stodulski M.
Published: August 2020

In recent years, spirocyclic compounds have attracted a significant interest in medicinal chemistry due to their considerable biological activities. The general and widely used concept for spirocyclic compound synthesis is related with dearomatization of starting material. However, most of the libraries prepared using this concept comprise structure similarity. Therefore, preparation of structurally distinct libraries comprising varied functionality requires different approaches and that includes non‐dearomative pathways. In given review recent advance in the synthesis of structurally varied spirocycles via radical‐mediated non‐dearomative strategies is discussed. In this context, application of radical initiators or photoredox catalysis is described. The variety of the presented examples indicates the high potential of the visible‐light‐induced methodologies in spirocyclic compound synthesis, which can act as a very efficient green alternative to known procedures, offering mild reaction conditions and high functional group tolerance.

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COVID‐19 Policy Modeling in Sub‐Saharan Africa
Authors: Mueller Valerie , Sheriff Glenn , Keeler Corinna , Jehn Megan
Published: August 2020

After an initial delay, Sub‐Saharan Africa (SSA) is being hit by the pandemic. Demand for exports is falling and caseloads are rising. Governments have approached this crisis with a range of policy options. Optimal policy balances reduced infection rates with lost economic output. This paper discusses how an economic‐epidemiological model used to analyze policy in high‐income countries could be adapted to a context where poverty considerations are paramount. Differences in country characteristics across the continent affect benefits and costs of alternative policy designs. We conclude by highlighting data needs and model calibration challenges for COVID‐19 policy research in SSA.
Beef Cattle Markets and COVID‐19
Authors: Martinez Charles C. , Maples Joshua G. , Benavidez Justin
Published: August 2020

Cattle producers and markets faced massive disruptions due to COVID‐19 in both supply and demand for cattle and beef. Restaurant and food service shutdowns affected beef demand. Closures and slowdowns of beef processors caused a logjam of live cattle in the supply chain. The resulting effects on cattle producers at all levels were lower prices and abnormal cattle flows, but the magnitudes of those effects were not homogenous across size and type of cattle. In this article, we detail how the COVID‐19 pandemic has affected cattle markets and cattle producers across the different sectors. We also discuss policy responses and considerations.
Effects of row spacing, nitrogen, and mepiquat chloride application on yield and spatio‐temporal patterns of cotton bolls in the yellow river valley of China
Authors: Yan Wei , Li Fangjun , Xu Dongyong , Eneji A. Egrinya , Du Mingwei , Tian Xiaoli , Li Zhaohu
Published: August 2020

Mechanical harvesting of cotton is an inevitable trend in China due to the current shortage of farm labor. Row spacings of spindle‐type pickers are adjustable between 76 and 102 cm. However, it is not clear which is better for cotton production in the Yellow River Valley. This field study was conducted under stalk incorporation during 2016–2018, and consisted of experiments of row spacing × nitrogen (N) and row spacing × mepiquat chloride (MC). A split‐plot with four replications was used; row spacings (76, 92 and 102 cm) were assigned as main plots at equal population of 90 000 plants ha−1, and N (0, 105, 210 kg ha−1) or MC rates (0, 140, 281 and 394 g ha−1) as subplots. The wider row spacings (92 and 102 cm) yielded as much as the narrower spacing (76 cm) in 2016 and 2018, but out‐yielded the latter in the wet year (2017) due to the greater number of bolls. Nitrogen application had marginal effects on cotton yield. Mepiquat chloride application increased lint yield by increasing boll weight in 2016–2017, but decreased yield by reducing boll number at the highest rate (394 g ha−1) in the dry year of 2018. Considering plants spaced 92 cm more resistant to lodging than those spaced 102 cm, we suggest the 92 cm spacing may be selected. In addition, the 105–210 kg N ha−1and the 140–281 g MC ha−1 were recommended to balance N removal in seed cotton and get higher or stable yield, respectively.
Early detection of black Sigatoka in banana leaves using hyperspectral images
Authors: Ugarte Fajardo Jorge , Bayona Andrade Oswaldo , Criollo Bonilla Ronald , Cevallos‐Cevallos Juan , Mariduena‐Zavala María , Ochoa Donoso Daniel , Vicente Villardón José Luis
Published: August 2020

Premise

Black Sigatoka is one of the most severe banana (Musa spp.) diseases worldwide, but no methods for the rapid early detection of this disease have been reported. This paper assesses the use of hyperspectral images for the development of a partial‐least‐squares penalized‐logistic‐regression (PLS–PLR) model and a hyperspectral biplot (HS biplot) as a visual tool for detecting the early stages of black Sigatoka disease.

Methods

Young (three‐month‐old) banana plants were inoculated with a conidia suspension of the black Sigatoka fungus (Pseudocercospora fijiensis). Selected infected and control plants were evaluated using a hyperspectral imaging system at wavelengths in the range of 386–1019 nm. PLS–PLR models were run on the hyperspectral data set. The prediction power was assessed using leave‐one‐out cross‐validation as well as external validation.

Results

The PLS–PLR model was able to predict the presence of the disease with a 98% accuracy. The wavelengths with the highest contribution to the classification ranged from 577 to 651 nm and from 700 to 1019 nm.

Discussion

PLS–PLR and HS biplot effectively estimated the presence of black Sigatoka disease at the early stages and can be used to graphically represent the relationship between groups of leaves and both visible and near‐infrared wavelengths.
Trial‐to‐Trial Variability in Electrodermal Activity to Odor in Autism
Authors: Haigh Sarah M. , Endevelt‐Shapira Yaara , Behrmann Marlene
Published: August 2020

Abnormal trial‐to‐trial variability (TTV) has been identified as a key feature of neural processing that is related to increased symptom severity in autism. The majority of studies evaluating TTV have focused on cortical processing. However, identifying whether similar atypicalities are evident in the peripheral nervous system will help isolate perturbed mechanisms in autism. The current study focuses on TTV in responses from the peripheral nervous system, specifically from electrodermal activity (EDA). We analyzed previously collected EDA data from 17 adults with autism and 19 neurotypical controls who viewed faces while being simultaneously exposed to fear (fear‐induced sweat) and neutral odors. Average EDA peaks were significantly smaller and TTV was reduced in the autism group compared to controls, particularly during the fear odor condition. Amplitude and TTV were positively correlated in both groups, but the relationship was stronger in the control group. In addition, TTV was reduced in those with higher Autism Quotient scores but only for the individuals with autism. These findings confirm the existing results that atypical TTV is a key feature of autism and that it reflects symptom severity, although the smaller TTV in EDA contrasts with the previous findings of greater TTV in cortical responses. Identifying the relationship between cortical and peripheral TTV in autism is key for furthering our understanding of autism physiology.

Lay Summary

We compared the changes in electrodermal activity (EDA) to emotional faces over the course of repeated faces in adults with autism and their matched controls. The faces were accompanied by smelling fear‐inducing odors. We found smaller and less variable responses to the faces in autism when smelling fear odors, suggesting that the peripheral nervous system may be more rigid. These findings were exaggerated in those who had more severe autism‐related symptoms.
Phlorotannins as HIV Vpu inhibitors, an in silico virtual screening study of marine natural products
Authors: Langarizadeh Mohammad Amin , Abiri Ardavan , Ghasemshirazi Saeid , Foroutan Nazanin , Khodadadi Arash , Faghih‐Mirzaei Ehsan
Published: August 2020

The importance of new effective treatment methodologies for human immunodeficiency virus (HIV) is undeniable for the medical society. Viral protein U (Vpu), one of the disparaged accessory proteins of HIV, is responsible for the dissemination of viral particles, and HIV mutants lacking Vpu protein have remarkably reduced pathogenicity. Here, we explored the marine natural products to find the leading structures which can potentially inhibit the activity of Vpu in silico. To fulfill this goal, we set up a virtual screening based on molecular docking to evaluate the binding capacity of different marine products to Vpu. For validation, we used molecular dynamics simulation and monitored the root mean square deviation value and binding interactions. The results were intriguing when we realized that the hit compounds (phlorotannins) had previously been identified as reverse transcriptase and HIV protease inhibitors. This research inaugurates a new road to combat HIV by multifaceted mode of action of these marine natural products without putting the normal cells in jeopardy (with their safe toxicological profile).
Understanding adult education in community contexts: A critical realist perspective
Authors: Jones Katy
Published: August 2020

Third‐sector community organisations are important sites for learning, especially for the most excluded groups in society. However, scant attention has been paid to the various factors shaping educational provision in community contexts, and how these interact to shape the provision available to marginalised populations. This article presents new evidence addressing this gap, through drawing on interview data from practitioners working in the UK homelessness sector. It identifies a range of factors shaping educational provision in these community contexts. These are: service user need and demand; staff roles and capacity; organisational purpose and structures; national policies; support from other adult education providers; non‐governmental finance; and volunteers. With some modification, and placed within an overarching critical realist framework, it is argued that these findings are consistent with Boeren’s comprehensive lifelong learning participation model. The article concludes that so long as government policy and related funding continues to ignore and fails to support educational provision in these settings, it will remain piecemeal and highly contingent on the contribution of volunteers and short‐term funding.
Investigating the change in the photophysical properties of a trio of tetraphenylcyclopentadienone derivatives with varied groups on the aromatic rings in the 3‐ and 4‐positions
Authors: Orozco Arnoldo J. , Joachim Kole , Ruiz Henry D. , Fronczek Frank R. , Isovitsch Ralph
Published: August 2020

Organic compounds with electronic properties, such as a small band gap, are useful in areas ranging from organic field effect transistors to solar cells. Such organic compounds can possess conjugation and/or aromatic systems, with one example being tetraphenylcyclopentadienone and its derivatives. A trio of dramatically coloured tetraphenylcyclopentadienone derivatives with varied substituents on the aromatic rings in the 3‐ and 4‐positions were prepared. Their identities were confirmed using the usual methods, for example 1H nuclear magnetic resonance (NMR) spectroscopy, and their purity quantified using elemental analysis. The X‐ray crystal structure of compound 2 was determined. Its notable structural features involved the cyclopentadienone core with its distinct C−C and C=C bond lengths and its overall nonplanarity, both of which served to mitigate its antiaromatic nature. Chloroform solutions of compounds 2–4 exhibited absorption spectra with three absorption bands at approximately 250, 350, and 500 nm that were assigned to (π)→(π*) transitions. Computational chemistry methods assisted in assigning the observed transitions to a specific molecular orbital combination in the structures of 2–4. Emission in the red end of the visible spectrum (550–625 nm) was observed from chloroform solutions of all three of the prepared compounds.
Microscopic insight to specificity of metal ion cofactor in DNA cleavage by restriction endonuclease EcoRV
Authors: Mandal Sasthi Charan , Maganti Lakshmi , Mondal Manas , Chakrabarti Jaydeb
Published: August 2020

Restriction endonucleases protect bacterial cells against bacteriophage infection by cleaving the incoming foreign DNA into fragments. In presence of Mg2+ ions, EcoRV is able to cleave the DNA but not in presence of Ca2+, although the protein binds to DNA in presence of both metal ions. We make an attempt to understand this difference using conformational thermodynamics. We calculate the changes in conformational free energy and entropy of conformational degrees of freedom, like DNA base pair steps and dihedral angles of protein residues in Mg2+(A)‐EcoRV‐DNA complex compared to Ca2+(S)‐EcoRV‐DNA complex using all‐atom molecular dynamics (MD) trajectories of the complexes. We find that despite conformational stability and order in both complexes, the individual degrees of freedom behave differently in the presence of two different metal ions. The base pairs in cleavage region are highly disordered in Ca2+(S)‐EcoRV‐DNA compared to Mg2+(A)‐EcoRV‐DNA. One of the acidic residues ASP90, coordinating to the metal ion in the vicinity of the cleavage site, is conformationally destabilized and disordered, while basic residue LYS92 gets conformational stability and order in Ca2+(S) bound complex than in Mg2+(A) bound complex. The enhanced fluctuations hinder placement of the metal ion in the vicinity of the scissile phosphate of DNA. Similar loss of conformational stability and order in the cleavage region is observed by the replacement of the metal ion. Considering the placement of the metal ion near scissile phosphate as requirement for cleavage action, our results suggest that the changes in conformational stability and order of the base pair steps and the protein residues lead to cofactor sensitivity of the enzyme. Our method based on fluctuations of microscopic conformational variables can be applied to understand enzyme activities in other protein‐DNA systems.
Strain engineering for high‐level 5‐aminolevulinic acid production in Escherichia coli
Authors: Miscevic Dragan , Mao Ju‐Yi , Kefale Teshager , Abedi Daryoush , Moo‐Young Murray , Perry Chou C.
Published: August 2020

Herein, we report the development of a microbial bioprocess for high‐level production of 5‐aminolevulinic acid (5‐ALA), a valuable non‐proteinogenic amino acid with multiple applications in medical, agricultural, and food industries, using Escherichia coli as a cell factory. We first implemented the Shemin (i.e., C4) pathway for heterologous 5‐ALA biosynthesis in E. coli. To reduce, but not to abolish, the carbon flux toward essential tetrapyrrole/porphyrin biosynthesis, we applied clustered regularly interspersed short palindromic repeats interference (CRISPRi) to repress hemB expression, leading to extracellular 5‐ALA accumulation. We then applied metabolic engineering strategies to direct more dissimilated carbon flux toward the key precursor of succinyl‐CoA for enhanced 5‐ALA biosynthesis. Using these engineered E. coli strains for bioreactor cultivation, we successfully demonstrated high‐level 5‐ALA biosynthesis from glycerol (~30 g L−1) under both microaerobic and aerobic conditions, achieving up to 5.95 g L−1 (36.9% of the theoretical maximum yield) and 6.93 g L−1 (50.9% of the theoretical maximum yield) 5‐ALA, respectively. This study represents one of the most effective bio‐based production of 5‐ALA from a structurally unrelated carbon to date, highlighting the importance of integrated strain engineering and bioprocessing strategies to enhance bio‐based production.
Associations between apparent diffusion coefficient values and histopathological tissue alterations in myopathies
Authors: Meyer Hans‐Jonas , Schneider Ilka , Emmer Alexander , Kornhuber Malte , Surov Alexey
Published: August 2020

Objectives

Diffusion‐weighted imaging (DWI) can reflect histopathologic changes in muscle disorders. The present study sought to elucidate possible associations between histopathology derived from muscle biopsies and DWI in myositis and other myopathies.

Methods

Nineteen patients (10 women, 52.6%) with a mean age 51.43 ± 19 years were included in this retrospective study. Apparent diffusion coefficients (ADC) were evaluated with a histogram approach of the biopsied muscle. The histopathology analysis included the scoring systems proposed by Tateyama et al., Fanin et al., Allenbach et al. and immunhistochemical stainings for MHC, CD68, CD8, and CD4.

Results

There was a tendency that skewness was lowered with increasing Tateyama score, but it did not reach statistical significance (p = .14). No statistical differences for the other scores were identified. There was a tendency that kurtosis was higher in MHC negative stained patient compared to positive patients, but statistically significance was not reached (p = .07). ADC histogram parameters did not correlate with CD68 and CD8 positive stained cells. There was a trend for skewness to correlate with the amount of CD4‐positive cells (r = .57, p = .07).

Conclusion

The present study could not identify statistical significant associations between DWI and histopathology in muscle diseases based upon a small patient sample. Presumably, the investigated histopathology scores are more specific for certain disease aspects, whereas ADC values reflect the whole cellularity of the investigated muscle, which might cause the negative results.
Identification of a novel prognostic DNA methylation signature for lung adenocarcinoma based on consensus clustering method
Authors: Cai Qidong , He Boxue , Xie Hui , Zhang Pengfei , Peng Xiong , Zhang Yuqian , Zhao Zhenyu , Wang Xiang
Published: August 2020

Abnormal DNA methylation persists throughout carcinogenesis and cancer development. Hence, gene promoter methylation may act as a prognostic tool and provide new potential therapeutic targets for patients with lung adenocarcinoma (LUAD). In this study, to explore prognostic methylation signature, data regarding DNA methylation and RNA‐seq, and clinical data of patients with LUAD from the Cancer Genome Atlas database (TCGA) were downloaded. After data preprocessing, the methylation data were divided into training (N = 405) and test sets (N = 62). Then, patients in the training set were assigned to five subgroups based on their different methylation levels using the consensus clustering method. We comprehensively analyzed the survival information, methylation levels, and clinical variables, including American Joint Committee on Cancer (AJCC) stage, tumor‐node‐metastasis (TNM) staging, age, smoking history, and gender of these five groups. Subsequently, we identified a 16‐CpG prognostic signature and constructed a prognostic model, which was verified in the test set. Further analyses showed stable prognostic performance in the stratified cohorts. In conclusion, the new predictive DNA methylation signature proposed in this study may be used as an independent biomarker to assess the overall survival of LUAD patients and provide bioinformatics information for development of targeted therapy.
Maintenance rituximab in Veterans with follicular lymphoma
Authors: Halwani Ahmad S. , Rasmussen Kelli M. , Patil Vikas , Morreall Deborah , Li Catherine , Yong Christina , Burningham Zachary , Dawson Keith , Masaquel Anthony , Henderson Kevin , DeLong‐Sieg Elisha , Sauer Brian C.
Published: August 2020

Real‐world practice patterns and clinical outcomes in patients with follicular lymphoma (FL), including the adoption of maintenance rituximab (MR) therapy in the United States (US), have been reported in few studies since the release of the National LymphoCare Study almost a decade ago. We analyzed data from the largest integrated healthcare system in the United States, the Veterans Health Administration (VHA), to identify rates of adoption and effectiveness of MR in FL patients after first‐line (1L) treatment. We identified previously untreated patients with FL in the VHA between 2006 and 2014 who achieved at least stable disease after chemoimmunotherapy or immunotherapy. Among these patients, those who initiated MR within 238 days of 1L composed the MR group, whereas those who did not were classified as the non‐MR group. We examined the effect of MR on progression‐free survival (PFS) and overall survival (OS). A total of 676 patients met our inclusion criteria, of whom 300 received MR. MR was associated with significant PFS (hazard ratio [HR]=0.55, P < .001) and OS (HR = 0.53, P = .005) compared to the non‐MR group, after adjusting by age, sex, ethnicity, geographic region, diagnosis period, stage, grade at diagnosis, hemoglobin, lactate dehydrogenase (LDH), Charlson comorbidity index (CCI), 1L treatment regimen, and response to 1L treatment. These results suggest that in FL patients who do not experience disease progression after 1L treatment in real‐world settings, MR is associated with a significant improvement in both PFS and OS. Maintenance therapy should be considered in FL patients who successfully complete and respond to 1L therapy.
Management and outcomes of coronary artery perforations treated with the block and deliver technique
Authors: Sanz Sanchez Jorge , Garbo Roberto , Gagnor Andrea , Oreglia Jacopo , Mazzarotto Pietro , Maurina Matteo , Regazzoli Damiano , Gasparini Gabriele L.
Published: August 2020

Abstract

Objectives and Background

Coronary artery perforation (CAP) is a potentially life‐threatening complication during percutaneous coronary interventions (PCI) and the best strategy for its management is yet to be proved. We aimed to analyze the safety, efficacy, and long‐term clinical outcomes of the block and deliver (BAD) technique, as only anecdotal cases are reported in literature.

Methods

From January 2016 to January 2020, all consecutive patients treated with the BAD technique at five high‐volume centers in Italy were retrospectively identified.

Results

25 CAPs treated with the BAD technique were included. The most frequently perforated artery was the left anterior descending artery (32%) and spring‐coil wires with a hydrophilic coating were the most common culprit wires (68%). Mean sealing time was 46.9 ± 60.1 min, with no significant differences between CTO‐PCIs and non‐CTO PCIs (p = .921). Acute successful sealing of the CAP was achieved in 96% of the cases. Immediate cardiac tamponade occurred in 28% of patients, four during CTO PCI and three during non‐CTO PCI (p = .55). Two patients required pericardiocentesis during hospitalization, one patient developed acute kidney injury, and one patient underwent cardiac surgery due to severe mitral regurgitation. At 1‐year follow‐up no significant differences were observed between groups in terms of POCE (25 vs 25%, p = .628) and its individual components.

Conclusion

The BAD technique proved to be effective for the management of CAP, showing high successful sealing rates. Rates of in‐hospital events and at 1‐year follow‐up did not significantly differ between patients suffering CAP during CTO revascularization or during non‐CTO PCI.
Size‐Dependent and Self‐Catalytic Gold@Prussian Blue Nanoparticles for the Electrochemical Detection of Hydrogen Peroxide
Authors: Zhang Minwei , Zhang Wenrui , Engelbrekt Christian , Hou Chengyi , Zhu Nan , Chi Qijin
Published: August 2020

ABSTRACT: Prussian blue (PB) nanoparticle (NP)‐based nanomaterials have become a subject of intense interest, because of their intriguing physical and chemical properties that differ from their bulk counterparts, leading to novel applications in electrocatalysis. However, the size effect of PB NPs on the electrocatalytic performance is still ambiguous and hinders further applications for the study of biomimetic sensors. In this work, a new approach to synthesize core‐shell Au@PB NPs is presented, using gold nanoparticles as catalysts for the fabrication of size‐controllable, highly stable, water‐soluble, biologically compatible and highly electrochemically active PB NPs. As a result, all sizes of Au@PB NPs display high electrochemical activity towards peroxidase biomimicry. Furthermore, the size effect of PB‐based electrocatalysis has been investigated, showing the best performance for 18 nm Au@PB NPs. This insight could be used for the design and application of PB‐based nanomaterials in biosensors.
Effect of salinity on the germination of wheat and barley in South Africa
Authors: Bagwasi Gaesejwe , Agenbag Gert A. , Swanepoel Pieter A.
Published: August 2020

Field crops are most susceptible to salt stress in the early stages of growth. There is a general belief that barley (Hordeum vulgare L.) is more salt‐tolerant than wheat (Triticum aestivum L.), yet little is known regarding the response of different South African wheat and barley cultivars to saline conditions. An experiment was conducted to study the effects of salinity on seed germination in three South African spring wheat cultivars (SST 027, SST 056, and SST 087) and three spring barley cultivars (Nemesia, Erica, and Hessekwa). The experiment was conducted in petri dishes in a growth incubator at a constant temperature of 20 °C for 7 d. Seeds were exposed to five NaCl solutions with electrical conductivity (EC) levels of 4, 8, 12, 16, and 20 dS m−1 and were compared with those exposed to a solution with an EC of 0 dS m−1 (distilled water), which served as a control. The experiment design was a completely randomized design. The study showed that salinity influenced seed germination in all wheat and barley cultivars. Although all cultivars showed a reduction in total germination percentage with increasing salinity from EC levels of 0 to 20 dS m−1, the differences were only significant (P < .05) at high EC levels (16–20 dS m−1). Wheat cultivars outperformed barley cultivars at EC levels of 0, 4, 8, 12, and 16 dS m−1. The study showed that salinity influenced seed germination in both wheat and barley, but barley was less salt‐tolerant during germination than wheat.
Monodentate AIEgen Anchored on Metal‐Organic Framework for Fast Fluorescence Sensing of Phosphate
Authors: Gao Xinli , Pei Lei , Xue Wenjuan , Huang Hongliang , Gao Zhuqing , Zhao Xudong
Published: August 2020

Herein, a novel sensor (TPE‐UiO‐66) was designed via anchoring monodentate tetraphenylethylene (TPE) onto UiO‐66 framework. The combination of the distinct aggregation‐induced emission (AIE) of TPE and the easy replacement of monodentate linker by guest phosphate, makes TPE‐UiO‐66 an ideal platform for sensing HPO42–. Experimental results indicate that TPE‐UiO‐66 can selectively sense HPO42– from other common anions. The limit of detection (LOD) can reach to 5.56 μmol·L–1 and more importantly, TPE‐UiO‐66 also exhibits an ultra‐fast equilibrium response of 2 min, far faster than those of other sensors especially for UiO‐66‐NH2. The combination of experimental analysis and density functional theory (DFT) calculations demonstrates that the high selectivity, high sensitivity and fast response of HPO42– detection by TPE‐UiO‐66 can be attributed to the stronger coordination interactions of HPO42– with Zr‐O cluster of UiO‐66 than that of TPE molecule. This study not only provides a potential probe for phosphate, but also represents a novel strategy to design stimuli‐responsive fluorescent MOF‐based sensors via using monodentate AIEgens.
A Gaussian alternative to using improper confidence intervals
Authors: Plante André
Published: August 2020

The problem posed by exact confidence intervals (CIs) which can be either all‐inclusive or empty for a nonnegligible set of sample points is known to have no solution within CI theory. Confidence belts causing improper CIs can be modified by using margins of error from the renewed theory of errors initiated by J. W. Tukey—briefly described in the article—for which an extended Fraser's frequency interpretation is given. This approach is consistent with Kolmogorov's axiomatization of probability, in which a probability and an error measure obey the same axioms, although the connotation of the two words is different. An algorithm capable of producing a margin of error for any parameter derived from the five parameters of the bivariate normal distribution is provided. Margins of error correcting Fieller's CIs for a ratio of means are obtained, as are margins of error replacing Jolicoeur's CIs for the slope of the major axis. Margins of error using Dempster's conditioning that can correct optimal, but improper, CIs for the noncentrality parameter of a noncentral chi‐square distribution are also given.
Influence of chromatic and lighting on the visual environment of the elderly: A critical literature review
Authors: Guerry Estelle , Caumon Céline , Bécheras Elodie , Zissis Georges
Published: August 2020

The use of color and lighting as factors for adapting the housing of the elderly is tending to develop, in response to demographic data on the aging of the population and its impact on lifestyles. Adapting the environment for those over 60 years has become a national issue for public policy. So this article takes stock of the studies carried out on this issue. We have to review all the literature devoted to this subject, focusing on research products dealing with the color and light interaction in the indoor environment of seniors.
Model‐Based Meta‐Analysis Compares DAS28 Rheumatoid Arthritis Treatment Effects and Suggests an Expedited Trial Design for Early Clinical Development
Authors: Leil Tarek A. , Lu Yasong , Bouillon‐Pichault Marion , Wong Robert , Nowak Miroslawa
Published: August 2020

A nonlinear mixed effects modeling approach was used to conduct a model‐based meta‐analysis (MBMA) of longitudinal, summary‐level, baseline‐corrected 28‐joint Disease Activity Score (ΔDAS28) clinical trial data from seven approved rheumatoid arthritis (RA) drugs (abatacept, adalimumab, certolizumab, etanercept, rituximab, tocilizumab, and tofacitinib), representing 130 randomized clinical trials in 27,355 patients. All of the drugs except tocilizumab were found to have relatively similar ΔDAS28 time courses and efficacy (baseline‐corrected and placebo‐corrected) at 24 weeks and beyond of approximately 0.87–1.3 units in the typical RA patient population. Tocilizumab was estimated to have a differentially greater response of 1.99 at 24 weeks, likely due to its disproportionate effect on the acute‐phase cytokine interleukin‐6. Baseline DAS28, disease duration, percentage of male participants, and the year of conduct of the trial were found to have statistically significant effects on the timing and/or magnitude of ΔDAS28 in the control arms. Clinical trial simulations using the present MBMA indicated that abatacept, certolizumab, etanercept, tocilizumab, and tofacitinib would be expected to have a greater than 70% probability of showing a statistically significant difference vs. control at Week 6 with a sample size of ~ 30 patients per arm. In future RA clinical trials, an interim analysis conducted as early as 6 weeks after treatment initiation, with relatively small sample sizes, should be sufficient to detect the ΔDAS28 treatment effect vs. placebo.
Benefit–Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment‐Resistant Depression
Authors: Katz Eva G. , Hough David , Doherty Teodora , Lane Rosanne , Singh Jaskaran , Levitan Bennett
Published: August 2020

This post hoc analysis assessed the benefit–risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment‐resistant depression (TRD). The Benefit–Risk Action Team framework was utilized to assess the benefit–risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or responders in induction studies and proportion of stable remitters or stable responders who remained relapse‐free in the maintenance study. Risks were death, suicidal ideation, most common adverse events (AEs), and potential long‐term risks. Per 100 patients on esketamine + AD vs. AD + placebo in induction therapy, 5–21 additional patients would remit and 14–17 additional patients would respond. In maintenance therapy, 19–32 fewer relapses would occur with esketamine. In both cases, there was little difference in serious or severe common AEs (primarily dissociation, vertigo, and dizziness). These findings support a positive benefit–risk balance for esketamine + AD as induction and maintenance treatment in patients with TRD.
Examining Environmental Sustainability Metrics—Nitrogen Balance
Authors: Flis Sally , Jones John
Published: August 2020

As companies and farmers seek to show progress towards sustainability goals, they need metrics to assess and document progression. Nitrogen balance—or N‐balance—is one frequently used metric to assess the sustainability of nitrogen management. Earn 0.5 CEUs in Nutrient Management by reading this article and taking the quiz at www.certifiedcropadviser.org/education/classroom/classes/854.
Soybean Cyst Nematode Management in the Western Corn Belt
Authors: Winsor Susan
Published: August 2020

This is the second article of a four‐part series on soybean cyst nematode management. This article focuses on the western Corn Belt (specifically Nebraska and Kansas). Last issue, we discussed the Corn Belt in general; this issue, we’ll talk about some of the challenges unique to Nebraska and Kansas. Subsequent articles will address the South and the Mid‐Atlantic states. Earn 1 CEU in Integrated Pest Management by reading this article and taking the quiz at www.certifiedcropadviser.org/education/classroom/classes/858.
Sowing date, genotype choice, and water environment control soybean yields in central Argentina
Authors: Vitantonio‐Mazzini Lucas N. , Gómez Damián , Gambin Brenda L. , Di Mauro Guido , Iglesias Rodrigo , Costanzi Jerónimo , Jobbágy Esteban G. , Borrás Lucas
Published: August 2020

Soybean [Glycine max (L.) Merr.] is one of the most important crops worldwide, and Argentina is the third largest global grain producer and the worlds´ largest meal exporter. Under the continuous challenge of increasing crop yields, especially in the central temperate region of the country, there is a growing need to optimize management in relation to the environment that each specific farm and paddock presents. Understanding the impact of available technologies and management options can help optimize crop design. Here, we identify and quantify the effect of the most relevant variables affecting soybean yield by analyzing a database that includes 53 field trials with four common commercial genotypes, reporting 50 management and environmental variables. Linear mixed‐effect models revealed that two management decisions (genotype and sowing date selection) and three environmental variables (rainfall during the reproductive crop period from R1 to R7, soil type [Hapludoll vs. Argiudoll], and water table presence above or below 2 m of depth from the surface) helped explain ∼40% of total yield variability, which ranged from 1,675 to 7,226 kg ha−1 and averaged 5,133 kg ha−1. Water table presence generated higher and more stable yields particularly in coarse‐textured Hapludolls and under low‐rainfall conditions. Results highlight specific management and environmental conditions that affect soybean crop yields in the region, pointing to effective pathways toward yield gap reductions.
To meet grand challenges, agricultural scientists must engage in the politics of constructive collective action
Authors: Jordan N. , Gutknecht J. , Bybee‐Finley K. A. , Hunter M. , Krupnik T. J. , Pittelkow C. M. , Prasad P. V. V. , Snapp S.
Published: August 2020

Agriculture now faces grand challenges, with crucial implications for the global future. These include the need to increase production of nutrient‐dense food, to improve agriculture's effects on soil, water, wildlife, and climate, and to enhance equity and justice in food and agricultural systems. We argue that certain politics of constructive collective action—and integral involvement of agricultural scientists in these politics—are essential for meeting grand challenges and other complex problems facing agriculture in the 21st century. To spur reflection and deliberation about the role of politics in the work of agricultural scientists, we outline these politics of constructive collective action. These serve to organize forceful responses to grand challenges through coordinated and cooperative action taken by multiple sectors of society. In essence, these politics entail (1) building bonds of affinity within a heterogenous network, (2) developing a shared roadmap for collective action, and (3) taking sustained action together. These emerging politics differ markedly from more commonly discussed forms of political activity by scientists, e.g., policy advisory, policy advocacy, and protest. We present key premises for our thesis, and then describe and discuss a politics of constructive collective action, the necessary roles of agricultural scientists, and an agenda for exploring and expanding their engagement in these politics.
Filling the gaps in gene banks: Collecting, characterizing, and phenotyping wild banana relatives of Papua New Guinea
Authors: Eyland David , Breton Catherine , Sardos Julie , Kallow Simon , Panis Bart , Swennen Rony , Paofa Janet , Tardieu François , Welcker Claude , Janssens Steven B. , Carpentier Sebastien C.
Published: August 2020

Since natural habitats are disappearing fast, there is an urgent need to collect, characterize, and phenotype banana (Musa spp.) crop wild relatives to identify unique genotypes with specific traits that fill the gaps in our gene banks. We report on a collection mission in Papua New Guinea carried out in 2019. Seed containing bunches were collected from Musa peekelii ssp. angustigemma (N.W.Simmonds) Argent (3), M. schizocarpa N. W. Simmonds (4), M. balbisiana Colla (3), M. acuminata ssp. banksii (F. Muell.) Simmonds (14), M. boman Argent (3), M. ingens Simmonds (2), M. maclayi ssp. maclayi F.Muell. ex Mikl.‐Maclay (1), and M. lolodensis Cheesman (1). This material, together with the seeds collected during a previous mission in 2017, form the basis for the development of a wild banana seed bank. For characterization and phenotyping, we focused on the most ubiquitous indigenous species of Papua New Guinea: M. acuminata ssp. banksii, the ancestor of most edible bananas. We calculated that the median genomic dissimilarity of the M. acuminata ssp. banksii accessions was 4% and that they differed at least 5% from accessions present in the International Transit Centre, the world's largest banana gene bank. High‐throughput phenotyping revealed drought avoidance strategies with significant differences in root/shoot ratio, soil water content sensitivity, and response towards vapor pressure deficit (VPD). We deliver a proof of principle that the wild diversity is not yet fully covered in the gene banks and that wild M. acuminata ssp. banksii populations contain individuals with unique traits, useful for drought tolerance breeding programs.