bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of hydrogels with nanoparticles as surface-enhanced Raman scattered (SERS) substrates and their application in Raman imaging
Authors: Wu Chaochao , Li Fang , Lv Feng , Yao Pei , Bi Minghai , Xue Tao
Published: December 2020

A polyvinyl alcohol–silver nanoparticle (PVA–Ag NP) hydrogel was fabricated using a simple and facile method; it was used as a substrate for surface-enhanced Raman scattering (SERS). The Ag+ ions dispersed uniformly in the PVA network were reduced by NaBH4; this process was termed dipping method. Compared with conventional SERS substrates (e.g., colloidal suspensions), the prepared PVA–Ag NP hydrogel has prominent Raman enhancement effects for crystal violet (CV), and the detection limit was 10−12 M. It could also help detect rhodamine B, methylene blue, and 4-mercaptobenzoic acid. In addition to SERS, the reliable 3D porous structure was utilized in the Raman imaging of CV at 1621 cm−1 in a nude mouse.
Cavitation erosion behavior of nickel foam/polyurethane co-continuous composite
Authors: Wang J X , Jiang S L , Yang XG , Li S , Duan D L
Published: December 2020

The cavitation erosion behavior of Ni foam/polyurethane (PU) co-continuous composites under different experimental conditions was investigated using an ultrasonic vibration cavitation erosion device. Experimental results showed that the Ni foam metal skeleton structure had severe effects on the cavitation resistance of the composites. The composites with thick metal arris and large pore size exhibited good resistance to cavitation erosion. Stress waves had greater influence on the cavitation erosion behavior of composites than micro-jets. In a synergistic way of buffering stress wave in the resin phase and absorbing stress waves in the metal phase, the composites could exhibit better cavitation resistance than pure PU.
Aluminum and vanadium co-doping effects on the optical and electrical properties of oriented ZnO films
Authors: Okada Takeru , Tateyama Chisato , Kawashima Kotaro Hoshino Tomoyuki , Washio Katsuyoshi
Published: December 2020

The fabrication of bifunctional zinc-oxide thin films remains a challenge. Here, we investigate the effects of aluminum-vanadium co-doping on the electrical conductivity and the optical transparency of zinc oxide films. We find that by co-doping, aluminum enhances film transparency via zinc-vacancy-defect substitution, while vanadium enhances electrical conductivity. The roles of two dopants and defects are interesting information that is useful to applications of transparent conductive oxides.
Transient liquid phase bonding of silicon and direct bond copper via electroplating of tin-copper interlayers for power device applications
Authors: Kang Hyejun , Sharma Ashutosh , Lee Jung-Hyun , Jung Jae Pil
Published: December 2020

Joining technology of silicon semiconductors devices to direct bond copper (DBC) substrates in high-temperature power electronics packages is of utmost importance today. In this study, Sn–Cu solder was prepared by electroplating on a direct bonded copper (DBC) substrate. The electroplated DBC system thus prepared was TLP bonded with Si chip at 250 °C for 10 min under a vacuum atmosphere. The effect of electrical charge used for plating Sn–Cu solder, void fraction in the joint, Sn–Cu solder composition on the joining characteristics, and shear strength of the Si-DBC system were analyzed. The experimental results showed that the plating thickness increased almost linearly with plating time and electrical charge. A sound Sn–Cu solder plating thickness was obtained at 40 mA cm−2, 11 C cm−2, 20 min with 20 at% Cu in the deposit. Furthermore, the plated Sn–Cu solder layer transformed to Cu6Sn5 and Cu3Sn after joining at 250 °C for 10 min. The shear bonding strength of the Si/DBC joint increased with Cu content in the Sn–Cu solder until 20 at% in the Sn–Cu interlayer.
Toward efficient correction of multiqubit measurement errors: pair correlation method
Authors: Geller Michael R , Sun Mingyu
Published: December 2020

Measurement errors limit the performance of near-term quantum computers and their potential for practical application. However they are partly correctable after a calibration step that requires, for a complete implementation on a register of n qubits, 2
n
additional measurements. Here we introduce an approximate but efficient method for multiqubit measurement error characterization and mitigation requiring the classical processing of 2
n
× 2
n
matrices, but only O(4
k

n
2) measurements, where k = O(1) is the number of qubits in a correlation volume. We demonstrate and validate the method on an IBM Q processor with registers of 4 and 8 superconducting qubits.
Non-isothermal crystallization kinetics of an intermetallic CoSn phase
Authors: Khushaim Muna
Published: December 2020

Herein, the crystallization kinetics of the intermetallic CoSn phase, nucleated and grown in the microstructure of a binary CoSn alloy, have been reported. Differential scanning calorimetry traces under non-isothermal conditions were obtained and used to extract the activation energy (

E

α

) for the crystallization of the CoSn phase at various heating rates. The obtained values of

E

α

were validated by the application of several isoconversion methods. The minimum value of

E

α

was 1000 kJ mol−1, which occurred at 853 K. The observed behavior of

E

α

showed a strong temperature dependence, wherein it decreased with increasing temperature. This suggests that the rate constant for the crystallization of the CoSn phase is determined by the rates of two processes—nucleation and diffusion. The precise description of the crystallization process for the CoSn phase reveal that the reaction mechanism of this phase is following the first-order reaction.
Winter N2O accumulation and emission in sub-boreal grassland soil depend on clover proportion and soil pH
Authors: Byers Erin , Bleken Marina A , Dörsch Peter
Published: December 2020

Inclusion of legume species into grass leys reduces nitrogen (N) fertilizer need but increases the risk of freeze-thaw induced N2O emissions. We investigated how liming and presence of clover affect N2O accumulation under snowpack and its emission during freeze-thaw cycles in autumn and spring under sub-boreal conditions. A field experiment was performed in southern Norway in limed and control plots containing grasses only (fertilized with 270 kg N ha−1 yr−1), a grass-red clover mixture (fertilized with 140 kg N ha−1 yr−1) and unfertilized pure red clover. Soil air samples were collected at 8, 24, and 40 cm depths and analyzed for gas concentrations including N2O, and N2O fluxes measured by a fast-chamber robot. Red clover produced more N2O than the grass-only plots during freeze-thaw cycles in autumn and spring and accumulated more N2O under snow cover (emissions were not measured during this period). Contrary to expectations, limed red clover plots emitted more N2O than control plots during freeze-thaw cycles. Liming reduced subnivean N2O accumulation in grass-only but not in grass-clover or pure clover plots. After spring fertilization, grass-only plots had larger N2O emissions than red clover plots. Our data suggest that winter-sensitive, N-rich clover biomass fuels decomposition and nitrification, thereby increasing NO3
- and depleting O2, resulting in increased N2O emissions from denitrification. Although liming of pure clover leys exacerbated the risk of high N2O emissions during freeze-thaw, this effect was not observed in grass-clover mixtures. Interestingly, grass-clover mixtures also emitted less N2O than expected from their proportions and the emissions recorded in pure grass and clover stands. This warrants further studies into off-season functional diversity effects on N cycling and N2O loss in temperate and boreal forage production.
Data augmentation with Mobius transformations
Authors: Zhou Sharon , Zhang Jiequan , Jiang Hang , Lundh Torbjörn , Ng Andrew Y
Published: December 2020

Data augmentation has led to substantial improvements in the performance and generalization of deep models, and remains a highly adaptable method to evolving model architectures and varying amounts of data—in particular, extremely scarce amounts of available training data. In this paper, we present a novel method of applying Möbius transformations to augment input images during training. Möbius transformations are bijective conformal maps that generalize image translation to operate over complex inversion in pixel space. As a result, Möbius transformations can operate on the sample level and preserve data labels. We show that the inclusion of Möbius transformations during training enables improved generalization over prior sample-level data augmentation techniques such as cutout and standard crop-and-flip transformations, most notably in low data regimes.
CAFE: a software suite for analysis of paired-sample transposon insertion sequencing data
Authors: Abramova Anna , Osińska Adriana , Kunche Haveela , Burman Emil , Bengtsson-Palme Johan
Published: December 2020

Sequencing of transposon insertion libraries is used to determine the relative fitness of individual mutants at a large scale. However, there is a lack of tools for specifically analyzing data from such experiments with paired sample designs. Here, we introduce CAFE—Coefficient-based Analysis of Fitness by read Enrichment—a software package that can analyze data from paired transposon mutant sequencing experiments, generate fitness coefficients for each gene and condition and perform appropriate statistical testing on these fitness coefficients.

Availability and implementation

CAFE is implemented in Perl and R. The source code is freely available for download under the MIT License from https://github.com/bengtssonpalme/cafe and http://microbiology.se/software/cafe/

Supplementary information

Supplementary data are available at Bioinformatics online.
PC2P: parameter-free network-based prediction of protein complexes
Authors: Omranian Sara , Angeleska Angela , Nikoloski Zoran
Published: December 2020

Motivation

Prediction of protein complexes from protein–protein interaction (PPI) networks is an important problem in systems biology, as they control different cellular functions. The existing solutions employ algorithms for network community detection that identify dense subgraphs in PPI networks. However, gold standards in yeast and human indicate that protein complexes can also induce sparse subgraphs, introducing further challenges in protein complex prediction.

Results

To address this issue, we formalize protein complexes as biclique spanned subgraphs, which include both sparse and dense subgraphs. We then cast the problem of protein complex prediction as a network partitioning into biclique spanned subgraphs with removal of minimum number of edges, called coherent partition. Since finding a coherent partition is a computationally intractable problem, we devise a parameter-free greedy approximation algorithm, termed Protein Complexes from Coherent Partition (PC2P), based on key properties of biclique spanned subgraphs. Through comparison with nine contenders, we demonstrate that PC2P: (i) successfully identifies modular structure in networks, as a prerequisite for protein complex prediction, (ii) outperforms the existing solutions with respect to a composite score of five performance measures on 75% and 100% of the analyzed PPI networks and gold standards in yeast and human, respectively, and (iii,iv) does not compromise GO semantic similarity and enrichment score of the predicted protein complexes. Therefore, our study demonstrates that clustering of networks in terms of biclique spanned subgraphs is a promising framework for detection of complexes in PPI networks.

Availability and implementation

https://github.com/SaraOmranian/PC2P.

Supplementary information

Supplementary data are available at Bioinformatics online.
A method for subtype analysis with somatic mutations
Authors: Liu Meiling , Liu Yang , Wu Michael C , Hsu Li , He Qianchuan
Published: December 2020

Motivation

Cancer is a highly heterogeneous disease, and virtually all types of cancer have subtypes. Understanding the association between cancer subtypes and genetic variations is fundamental to the development of targeted therapies for patients. Somatic mutation plays important roles in tumor development and has emerged as a new type of genetic variations for studying the association with cancer subtypes. However, the low prevalence of individual mutations poses a tremendous challenge to the related statistical analysis.

Results

In this article, we propose an approach, subtype analysis with somatic mutations (SASOM), for the association analysis of cancer subtypes with somatic mutations. Our approach tests the association between a set of somatic mutations (from a genetic pathway) and subtypes, while incorporating functional information of the mutations into the analysis. We further propose a robust p-value combination procedure, DAPC, to synthesize statistical significance from different sources. Simulation studies show that the proposed approach has correct type I error and tends to be more powerful than possible alternative methods. In a real data application, we examine the somatic mutations from a cutaneous melanoma dataset, and identify a genetic pathway that is associated with immune-related subtypes.

Availability and implementation

The SASOM R package is available at https://github.com/rksyouyou/SASOM-pkg. R scripts and data are available at https://github.com/rksyouyou/SASOM-analysis.

Supplementary information

Supplementary data are available at Bioinformatics online.
Neurofilament light predicts neurological outcome after subarachnoid haemorrhage
Authors: Garland Patrick , Morton Matt , Zolnourian Ardalan , Durnford Andrew , Gaastra Ben , Toombs Jamie , Heslegrave Amanda J , More John , Zetterberg Henrik , Bulters Diederik O , Galea Ian
Published: December 2020

To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1–3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L’s relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood–brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.
HGFDB: a collective database of helmeted guinea fowl genomics
Authors: Li Xuzhen , Li Zhi , Shen Quankuan , Pan Yunbin , Dong Xiao , Xu Zetan , Duan Shengchang , Li Yunfei , Du Yuan , Chen Shanshan , Ma Zhaocheng , Dong Yang
Published: December 2020

As a vigorous and hardy and an almost disease-free game bird, the domestic helmeted guinea fowl (Numida meleagris, hereafter HGF) has attracted considerable attention in a large number of genetic study projects. However, none of the current/recent avian databases are related to this agriculturally and commercially important poultry species. To address this data gap, we developed Helmeted Guinea Fowl Database (HGFDB), which manages and shares HGF genomic and genetic data. By processing the data of genome assembly, sequencing reads and genetic variations, we organized them into eight modules, which correspond to ‘Home’, ‘Genome’, ‘Re-sequence’, ‘Gene’, ‘Variation’, ‘Download’, ‘Tools’ and ‘Help’, HGFDB provides the most comprehensive view of the HGF genome to date and will be relevant for future studies on HGF structural and functional genomics and genetic improvement.

Database URL: http://hgfdb.ynau.edu.cn/
A case report of a transcarotid transcatheter aortic valve implantation with concomitant carotid endarterectomy
Authors: Sultan Sherif , Pate Gordon , Hynes Niamh , Mylotte Darren
Published: December 2020

Background

Transcarotid transcatheter aortic valve implantation (TAVI) is a worthwhile substitute in patients who might otherwise be inoperable; however, it is applied in <10% of TAVI cases. In patients with established carotid artery stenosis, the risk of complications is increased with the transcarotid access route.

Case summary

We report a case of concomitant transcarotid TAVI and carotid endarterectomy (CEA) in a patient with bovine aortic arch and previous complex infrarenal EndoVascular Aortic Repair (EVAR). The integrity and positioning of the previous EVAR endograft was risked by transfemoral access. The right subclavian artery was only 4.5 mm and the left subclavian was totally occluded so transcarotid access was chosen. The patient recovered well, with no neurological deficit and was discharged home after 72 h. He was last seen and was doing well 6 months post-procedure.

Discussion

In patients with severe aortoiliac disease, or previous aortic endografting, transfemoral access for TAVI can be challenging or even prohibitive. Alternative access sites such as transapical or transaortic are associated with added risk because they carry increased risk of major adverse cardiovascular events, longer intensive care unit and hospital stay, and increased cost. A transcaval approach for TAVI has also been reported but was not suitable for our patient due to prior EVAR. Concomitant TAVI via transcarotid access and CEA can be successful in experienced hands. This case highlights the importance of a team-based approach to complex TAVI cases in high-risk patients with complex vascular access.
Sporadic late-onset nemaline myopathy: a case report of a treatable cause of cardiac failure
Authors: Turnquist Casmir , Grogono Joanna C , Hofer Monika , Pitcher Alex
Published: December 2020

Background 

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired, adult-onset myopathy, characterized by proximal muscle weakness and the pathognomonic feature of nemaline rods in muscle fibres. Sporadic late-onset nemaline myopathy is associated with cardiac pathology in case reports and small case series, but the severity of cardiac disease is generally mild and rarely requires specific treatment. This case report describes severe heart failure as an early feature of SLONM, which responded to specific treatments, and highlights SLONM as a potentially reversible cause of heart failure.

Case summary 

A 65-year-old woman presented with progressive muscle weakness and a dramatic loss of muscle bulk in her thighs, followed by progressive effort breathlessness over an 18-month period. She required a wheelchair to ambulate. A diagnosis of SLONM was made on histopathological assessment of a muscle biopsy along with electron microscopy. An echocardiogram showed a severely dilated and impaired left ventricle. She was treated with standard heart failure medications and autologous stem cell transplantation, which resulted in improvement of both her cardiac and muscle function, and allowed her to walk again and resume near-normal functional performance status.

Discussion 

Cardiomyopathy can be a relatively early and life-threatening feature of SLONM and even in severe cases can be effectively treated with standard heart failure medications and autologous stem cell transplantation.
Atrial fibrillation in low- and middle-income countries: a narrative review
Authors: Santos Itamar S , Goulart Alessandra C , Olmos Rodrigo D , Thomas G Neil , Lip Gregory Y H , Lotufo Paulo A , Benseñor Isabela M ,   the NIHR Global Health Group on Atrial Fibrillation Management, Arasalingam Ajini , Benseñor Isabela , Brocklehurst Peter , Cheng Kar Keung , Feng Mei , Goulart Alessandra C , Greenfield Sheila , Guo Yutao , Guruparan Mahesan , Gusso Gustavo , Hao Wang , Humphreys Lindsey , Kumarendran Balachandran , Jolly Kate , Jowett Sue , Lancashire Emma , Lane Deirdre A , Li Xuewen , Li Yanguang , Lip Gregory Y H , Lobban Trudie , Lotufo Paulo , Manseki-Holland Semira , Moore David , Nirantharakumar Krishnarajah , Olmos Rodrigo , Santos Itamar S , Shantsila Alena , Szmigin Isabelle , Subaschandren Kumaran , Surenthirakumaran Rajendra , Neil Thomas G , Wang Jingya
Published: December 2020

Preventing premature non-communicable disease mortality necessitates a thorough review of one of the most important risk factors for stroke, which is atrial fibrillation (AF). The latter and AF-related stroke are still considered to be problems of high-income countries and are frequently overlooked in low- and middle-income countries (LMICs). In this narrative review, we provide an overview of studies that evaluated at least one of the following determinants of AF burden in LMICs: current epidemiology and trends, stroke prevention, health outcomes, and economic burden. Studies focusing on samples close to the general population (including community- and primary care-based samples) indicate sex-specific prevalence rates up to 7.4% in LMICs. Although AF prevalence is still higher in high-income countries than LMICs, the gap in AF burden between these two groups has been reducing in the past three decades. Oral anticoagulant (OAC) therapy for stroke prevention is underused in LMICs, and there are little data on OAC therapy in relation to stroke risk scores, such as CHA2DS2-VASc. Available data also points to higher morbidity and mortality for patient with AF in LMICs than their counterparts in high-income countries. Data on the consequent economic burden in LMICs is scarce, but it is reasonable to consider it will follow the same trend as that observed for health outcomes. Raising the visibility of AF as a public health problem in LMICs is necessary as a first step to providing adequate care for patients with this condition.
The Impact of the COVID-19 Epidemic on Older Adults in Rural and Urban Areas in Mexico
Authors: Rivera-Hernandez Maricruz , Ferdows Nasim B , Kumar Amit
Published: December 2020

Objectives

Mexico is among the countries in Latin America hit hardest by coronavirus disease 2019 (COVID-19). A large proportion of older adults in Mexico have high prevalence of multimorbidity and live in poverty with limited access to health care services. These statistics are even higher among adults living in rural areas, which suggest that older adults in rural communities may be more susceptible to COVID-19. The objectives of the article were to compare clinical and demographic characteristics for people diagnosed with COVID-19 by age group, and to describe cases and mortality in rural and urban communities.

Method

We linked publicly available data from the Mexican Ministry of Health and the Census. Municipalities were classified based on population as rural (<2,500), semirural (≥2,500 and <15,000), semiurban (≥15,000 and <100,000), and urban (≥100,000). Zero-inflated negative binomial models were performed to calculate the total number of COVID-19 cases, and deaths per 1,000,000 persons using the population of each municipality as a denominator.

Results

Older adults were more likely to be hospitalized and reported severe cases, with higher mortality rates. In addition, rural municipalities reported a higher number of COVID-19 cases and mortality related to COVID-19 per million than urban municipalities. The adjusted absolute difference in COVID-19 cases was 912.7 per million (95% confidence interval [CI]: 79.0–1746.4) and mortality related to COVID-19 was 390.6 per million (95% CI: 204.5–576.7).

Discussion

Urgent policy efforts are needed to mandate the use of face masks, encourage handwashing, and improve specialty care for Mexicans in rural areas.
Developing a New Behavioral Framework for Dementia Care Partner Resilience: A Mixed Research Synthesis
Authors: Zhou Yuanjin , O’Hara Avery , Ishado Emily , Borson Soo , Sadak Tatiana
Published: December 2020

Background and Objectives

Caring for a person living with dementia requires resilience, the capacity to recover and grow from challenging situations. Despite the increasing interest in assessing and promoting resilience for dementia care partners, behaviors that indicate this attribute are not well known. The aim of this study was to synthesize the literature to identify resilience-related behaviors and develop a new framework for future validation and intervention research.

Research Design and Methods

We searched English-language peer-reviewed articles (January 1991–June 2019) reporting qualitative or quantitative descriptions of resilience-related behaviors among dementia care partners. Thematic analysis was used to categorize behaviors into domains, identify the relationships among them, and generate a thematic map.

Results

Sixteen articles were identified according to predefined inclusion criteria. Four domains emerged: (a) problem–response behaviors (problem-solving, problem-distancing); (b) self-growth behaviors (self-care activities, spiritual-related activities, and developing and maintaining meaningful social relationships); (c) help-related behaviors (help-seeking and help-receiving); and (d) learning-related behaviors (learning from others and reflection). Definitions of each domain, identification of corresponding behaviors, and formulation of Care Partner Resilience (CP-R) behavioral framework were informed by mixed research synthesis results and other relevant literature.

Discussion and Implications

The CP-R framework emerged as a result of a new focus on identifying and cultivating strengths instead of evaluating strain and burden. It serves as a useful foundation for understanding the impact of specific behaviors on dementia care partner resilience. Once validated, this framework will inform the development of future measures, research, interventions, and policies for dementia care partners.
Findings of Sequential Pilot Trials of Aliviado Dementia Care to Inform an Embedded Pragmatic Clinical Trial
Authors: Lin Shih-Yin , Schneider Catherine E , Bristol Alycia A , Clancy Maureen , Sprague Sara A , Aldridge Melissa , Cortes Tara , Goldfeld Keith S , Kutner Jean S , Mitchell Susan L , Shega Joseph W , Wu Bei , Zhu Carolyn W , Brody Abraham A
Published: December 2020

Background and Objectives

Many investigators of Alzheimer’s disease and related dementias (AD/ADRD) are unfamiliar with the embedded pragmatic clinical trials (ePCTs) and the indispensable pilot phase preceding ePCTs. This paper provides a much-needed example for such a pilot phase and discusses implementation barriers and additional infrastructure and implementation strategies developed in preparation for a nationwide AD/ADRD ePCT.

Research Design and Methods

Two pilot trials were conducted in 2 hospices sequentially to refine and test Aliviado Dementia Care—Hospice Edition, a complex quality improvement intervention for advanced dementia symptom management. Readiness for the subsequent full-scale ePCT was assessed by three milestones: ≥80% training completion rate (“feasibility”), ≥80% posttraining survey respondents indicating intention for practice changes (“applicability”), and at least 1 Aliviado care plan/assessment instrument administered in ≥75% of dementia patients admitted to home hospice within 1-month posttraining (“fidelity”).

Results

Participants included 72 interdisciplinary team members and 11 patients with AD/ADRD across the pilots. Feasibility, applicability, and fidelity outcomes (92%, 93%, and 100%, respectively) all surpassed the preestablished milestones (80%, 80%, and 75%). Main implementation challenges were related to hospice staff turnover, integration of the Aliviado toolbox materials within the electronic health records, and hospices’ limited research experience and infrastructure.

Discussion and Implications

This pilot phase demonstrated feasibility, applicability, and fidelity required to proceed to the full-scale ePCT. Our study findings and discussions of additional infrastructure and implementation strategies developed following the pilot phase can inform researchers and clinicians interested in conducting AD/ADRD-related pilot studies for ePTCs or quality improvement initiatives.

Clinical Trials Registration Number

NCT03681119
Highly biocompatible super-resolution fluorescence imaging using the fast photoswitching fluorescent protein Kohinoor and SPoD-ExPAN with L
p-regularized image reconstruction
Authors: Wazawa Tetsuichi , Arai Yoshiyuki , Kawahara Yoshinobu , Takauchi Hiroki , Washio Takashi , Nagai Takeharu
Published: December 2020

Far-field super-resolution fluorescence microscopy has enabled us to visualize live cells in great detail and with an unprecedented resolution. However, the techniques developed thus far have required high-power illumination (102–106 W/cm2), which leads to considerable phototoxicity to live cells and hampers time-lapse observation of the cells. In this study we show a highly biocompatible super-resolution microscopy technique that requires a very low-power illumination. The present technique combines a fast photoswitchable fluorescent protein, Kohinoor, with SPoD-ExPAN (super-resolution by polarization demodulation/excitation polarization angle narrowing). With this technique, we successfully observed Kohinoor-fusion proteins involving vimentin, paxillin, histone and clathrin expressed in HeLa cells at a spatial resolution of 70–80 nm with illumination power densities as low as ~1 W/cm2 for both excitation and photoswitching. Furthermore, although the previous SPoD-ExPAN technique used L1-regularized maximum-likelihood calculations to reconstruct super-resolved images, we devised an extension to the Lp-regularization to obtain super-resolved images that more accurately describe objects at the specimen plane. Thus, the present technique would significantly extend the applicability of super-resolution fluorescence microscopy for live-cell imaging.
Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma
Authors: Balasubramanian Adithya , Gunjur Ashray , Hafeez Umbreen , Menon Siddharth , Cher Lawrence M , Parakh Sagun , Gan Hui Kong
Published: December 2020

Background

Improving outcomes of patients with glioblastoma (GBM) represents a significant challenge in neuro-oncology. We undertook a systematic review of key parameters of phase II and III trials in GBM to identify and quantify the impact of trial design on this phenomenon.

Methods

Studies between 2005 and 2019 inclusive were identified though MEDLINE search and manual bibliography searches. Phase II studies (P2T) were restricted to those referenced by the corresponding phase III trials (P3T). Clinical and statistical characteristics were extracted. For each P3T, corresponding P2T data was “optimally matched,” where same drug was used in similar schedule and similar population; “suboptimally matched” if dis-similar schedule and/or treatment setting; or “lacking.” Phase II/III transition data were compared by Pearson Correlation, Fisher’s exact or chi-square testing.

Results

Of 20 P3Ts identified, 6 (30%) lacked phase II data. Of the remaining 14 P3T, 9 had 1 prior P2T, 4 had 2 P2T, and 1 had 3 P2T, for a total of 20 P3T-P2T pairs (called dyads). The 13 “optimally matched” dyads showed strong concordance for mPFS (r2 = 0.95, P < .01) and mOS (r2 = 0.84, P < .01), while 7 “suboptimally matched” dyads did not (P > .05). Overall, 7 P3Ts underwent an ideal transition from P2T to P3T. “Newly diagnosed” P2Ts with mPFS < 14 months and/or mOS< 22 months had subsequent negative P3Ts. “Recurrent” P2Ts with mPFS < 6 months and mOS< 12 months also had negative P3Ts.

Conclusion

Our findings highlight the critical role of optimally designed phase II trials in informing drug development for GBM.
The Effect of Insurance on Appropriate Hospital Discharge Antibiotics for Patients With Staphylococcus aureus Bacteremia
Authors: McHale Thomas , Medder Jim , Geske Jenenne , Rupp Mark E , Van Schooneveld Trevor C
Published: December 2020

Background

Inappropriate antimicrobial therapy of Staphylococcus aureus bacteremia (SAB) is associated with worsened outcomes. The impact of insurance coverage on appropriate selection of antibiotics at discharge is poorly understood.

Methods

We used a retrospective cohort design to evaluate whether patients with SAB at a large academic medical center over 2 years were more likely to receive inappropriate discharge antibiotics, depending on their category of insurance. Insurance was classified as Medicare, Medicaid, commercial, and none. Logistic regression was used to determine the odds of being prescribed inappropriate discharge therapy.

Results

A total of 273 SAB patients met inclusion criteria, with 14.3% receiving inappropriate discharge therapy. In the unadjusted model, there was 2-fold increased odds of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively (odds ratio [OR], 2.08; 95% CI, 1.39–3.13). After controlling for discharge with nursing assistance and infectious diseases (ID) consult, there were 1.6-fold increased odds (OR, 1.57; 95% CI, 0.998–2.53; P = .064) of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively. We found that being discharged home without nursing assistance resulted in 4-fold increased odds of being prescribed inappropriate therapy (OR, 4.16; 95% CI, 1.77–9.77; P < .01), and failing to consult an ID team resulted in 59-fold increased odds of being prescribed inappropriate therapy (OR, 59.2; 95% CI, 11.4–306.9; P < .001).

Conclusions

We found strong evidence that noncommercial insurance, discharging without nursing assistance, and failure to consult ID are risk factors for being prescribed inappropriate antimicrobial therapy for SAB upon hospital discharge.
Rickettsia honei Infection in a Traveler Returning From India
Authors: Denison Amy M , Leitgeb Brooke , Obadiah Joseph M , Schwindt Anne , Ladd-Wilson Stephen G , Paddock Christopher D , Matkovic Eduard
Published: December 2020

We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses.
Effectiveness of Pain Neurophysiology Education on Musculoskeletal Pain: A Systematic Review and Meta-Analysis
Authors: Bülow Kasper , Lindberg Kasper , Vaegter Henrik Bjarke , Juhl Carsten Bogh
Published: December 2020

Objectives

To estimate the effectiveness and safety of Pain Neurophysiology Education (PNE) on pain, disability, and psychological distress at post-intervention and long-term (closest to twelve months after initiating the intervention) in musculoskeletal pain (MSKP).

Methods

Randomized Controlled Trials (RCT) were identified in six engines, reference lists, ClinicalTrials.gov, and by contacting key researches. Risk of bias was assessed using Cochrane Collaboration Risk of Bias Tool 2.0. Meta-analyses, using Restricted Maximum Likelihood Method, were conducted to estimate standardized mean differences (SMD) and overall quality of evidence was evaluated according to GRADE.

Results

In total, 18 RCTs (n = 1,585) were included. There was small to moderate effects of PNE on pain at post-intervention and long-term: SMD = -0.32 (95% confidence interval [CI]: −.58; −.05) and SMD = −0.40 (95% CI: −.78; −.03), respectively. On disability, PNE had a small effect at post-intervention: SMD = -0.17 (95% CI: −.34; −.01) but was insignificant at long-term: SMD = −0.27 (95% CI: −.59; .06). Likewise, there was a small to moderate effect on psychological distress at post-intervention: SMD = −0.36 (95% CI: −.67; −.06) but was insignificant at long-term: SMD = −0.37 (95% CI: −.75; .01). Quality of evidence was low across all outcomes. Additional analyses showed significant effects of PNE, corresponding to moderate effects, on pain and psychological distress at both time points in chronic MSKP.

Conclusions

Overall quality of evidence was low, supporting PNE being safe and having small to moderate effects on pain at both time points, and on disability as well as psychological distress at post-intervention.
Effects of calcium–magnesium carbonate and calcium–magnesium hydroxide as supplemental sources of magnesium on microbial fermentation in a dual-flow continuous culture
Authors: Arce-Cordero J A , Monteiro H F , Brandao V L N , Dai X , Bennett S L , Faciola A P
Published: December 2020

Supplemental sources of Mg can also aid in ruminal pH regulation due to their alkaline properties. Magnesium oxide (MgO) is the most common source of Mg for ruminants and can help controlling ruminal pH; however, the alkaline potential of other sources of Mg has not been evaluated. We aimed to evaluate the inclusion of calcium–magnesium carbonate (CaMg(CO3)2) and calcium–magnesium hydroxide (CaMg(OH)4) alone or in combination as supplemental sources of Mg in corn silage-based diets and its impact on ruminal microbial fermentation. We hypothesized that inclusion of CaMg(OH)4 would allow for ruminal fermentation conditions resulting in a greater pH compared to the inclusion of CaMg(CO3)2. Four treatments were defined by the supplemental source of Mg in the diet: 1) Control (100% MgO, plus sodium sesquicarbonate as a buffer); 2) CO3 [100% CaMg(CO3)2]; 3) OH [100% CaMg(OH)4]; and 4) CO3/OH [50% Mg from CaMg(CO3)2, 50% Mg from CaMg(OH)4]. Nutrient concentration was held constant across treatments (16% CP, 30% NDF, 1.66 Mcal NEl/kg, 0.67% Ca, and 0.21% Mg). Four fermenters were used in a 4 × 4 Latin square design with four periods of 10 d each. Samples were collected for analyses of nutrient digestibility, soluble Mg, VFA, and NH3, while pH was measured at 0, 1, 2, 4, 6, 8, and 10 h post morning feeding to estimate % time when pH was below 6 (pH-B6) and area under the pH curve for pH below 6.0 (pH-AUC). Bacteria pellets were harvested for 15N analysis and estimates of N metabolism. Treatment effects were analyzed with the mixed procedure of SAS, while effects of using either CaMg(CO3)2 or CaMg(OH)4 as Mg source in comparison to Control treatment were evaluated by orthogonal contrasts. Similar pH-related variables were observed for Control, OH, and CO3/OH treatments, which had smaller pH-AUC and pH-B6 than CO3 (P ≤ 0.01). Butyrate molar proportion was greater in Control and CO3/OH than in CO3 and OH (P = 0.04). Orthogonal contrasts showed lower flow of bacterial N (P = 0.04), lower butyrate molar proportion (P = 0.08) and greater pH-AUC (P = 0.05) for diets with CaMg(CO3)2 in comparison with the Control. Concentration of soluble Mg in ruminal fluid (P = 0.73) and nutrient digestibility (P ≥ 0.52) were similar across treatments. Under the conditions of this experiment, using CaMg(OH)4 alone or combined with CaMg(CO3)2 allowed for a less acidic ruminal fermentation pattern than a diet with only CaMg(CO3)2.
Soybean molasses to replace corn for feedlot lambs on growth performance, carcass characteristics, and meat quality
Authors: Arruda Maria Carolina G , Almeida Marco Tulio C , Bertoco João Pedro A , Pereira-Junior Sérgio A G , Castro-Filho Edivilson S , Feliciano Andresa L , Rodrigues Julia L , Torres Rodrigo N S , Costa Rayanne V , Grilo Lívia M S F S S , Ezequiel Jane M B
Published: December 2020

Soybean molasses (SBM) is a byproduct of the manufacture of soy protein concentrate and has high energy value. This byproduct has a high potential for use in the nutrition of ruminant animals, mainly in the replacement of other energy feeds such as corn grain. The objective of this study was to evaluate the inclusion of SBM to replace corn grain up to 30% dry matter (DM) in the total diet on growth performance, feeding behavior, carcass characteristics, and meat quality of feedlot lambs (½ Santa Inês × ½ Dorper). Forty intact male lambs with an initial average body weight of 20.6 ± 2.5 kg and approximate age of 120 d were used. The animals were distributed in four treatments (0%, 10%, 20%, and 30% SBM), divided into five randomized blocks according to the initial weight and adapted for 16 d, with diets containing increasing concentrations of concentrate and SBM. Feeding behavior was analyzed at the beginning, middle, and final of the finishing period, and when animals reached 42 d on the finishing diet they were slaughtered. Data were evaluated using SAS software (version 9.4), by polynomial orthogonal contrasts, where the growth performance, carcass characteristics, and meat quality values were analyzed as randomized blocks, and the feeding behavior data as randomized blocks with a repeated measure over time. Significant differences were detected for the contrast 0 vs. SBM treatments, which the inclusion of SBM caused an increase (P ≤ 0.05) in ash intake but decreased the ether extract intake. The intake of DM in % body weight was higher for SBM treatments than 0% treatment (P ≤ 0.05). Feeding behavior, ruminating while lying down and drinking water presented a decreasing linear effect (P ≤ 0.05), and for feeding, efficiency increased with the addition of SBM (P ≤ 0.05). Fatty acids C14:0, C17:0, C17:1, C18:2n6c, C20:2, and C20:3n6 showed lower values ​​with the inclusion of SBM (P ≤ 0.05), while fatty acids C22:0 and C22:6n3 increased. The values ​​of n6 polyunsaturated fatty acids and n-6/n-3 ratio were lower (P ≤ 0.05) for SBM treatments. The values ​​of total polyunsaturated fatty acids showed a decreasing linear effect (P ≤ 0.05) with the inclusion of SBM. The use of up to 30% SBM in DM did not impair animal growth performance and feeding behavior did not cause damages to carcass parameters and still made the meat healthier, improving the n-6/n-3 ratio, therefore can be used to feed finishing lambs.
Shexiang Baoxin Pill Attenuates Ischemic Injury by Promoting Angiogenesis by Activation of Aldehyde Dehydrogenase 2
Authors: Hu Jingjing , Zhao Yongchao , Wu Yonghui , Yang Kun , Hu Kai , Sun Aijun , Ge Junbo
Published: December 2020

Promoting angiogenesis is a critical treatment strategy for ischemic cardiovascular diseases. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine, has been reported to be capable of relieving angina and improve heart function by promoting angiogenesis. The aim of this study was to determine the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in SBP-induced angiogenesis. Left femoral artery ligation was performed in wild-type mice (WT) and ALDH2 knockout mice, which were administrated with SBP (20 mg/kg/d) or equal volume saline per day by gastric gavage for 2 weeks. Perfusion recovery, angiogenesis in chronic hind limb ischemia, was significantly improved in the WT + SBP group than in the WT group. However, these beneficial effects were absent in ALDH2 knockout mice. In vitro, hypoxia impaired the ability of proliferation, migration and tube formation, sprouting angiogenesis, and promoted apoptosis in cardiovascular microvascular endothelial cells, whereas the hypoxia damage was restored by SBP. The protective effect of SBP was remarkably weakened by ALDH2 knockdown. Furthermore, SBP suppressed hypoxia-induced ALDH2/protein kinase B (AKT)/mammalian target of rapamycin pathways. In conclusion, this study demonstrated that SBP protected lower limb from ischemia injury through the ALDH2-dependent pathway. The protective mechanism of SBP in cardiovascular microvascular endothelial cells was partly mediated through ALDH2/AKT/mammalian target of rapamycin pathways.
Weight loss outcomes in premenopausal versus postmenopausal women during behavioral weight loss interventions: a systematic review and meta-analysis
Authors: Thomson Zoe O. , Kelly Jaimon T. , Sainsbury Amanda , Reeves Marina M.
Published: December 2020

Importance:

Weight loss may be difficult for young women with obesity to achieve due to competing priorities (caring for children and/or full-time work), limiting their ability to engage in weight loss interventions. Older or postmenopausal women may also face challenges to weight loss such as caring responsibilities and menopause. Menopausal status may reflect differences in weight loss.

Objective:

This study compared changes in weight, fat mass, and lean mass in premenopausal versus postmenopausal women in dietary weight loss trials.

Evidence review:

We reviewed publications from January 2000 to June 2020 evaluating a weight loss intervention with a dietary component, with or without exercise, and reporting weight loss of premenopausal and postmenopausal women. Where available, data on mean change from baseline for weight, fat mass, and lean mass of premenopausal and postmenopausal groups were entered into Review Manger for meta-analyses. Differences between menopausal groups were compared in subgroups of studies for intervention characteristics (diet-only vs diet and exercise; dietary modification vs meal replacement; < 24 wks vs ≥24 wks duration).

Findings:

Seven publications (10 interventions, n = 791) were included; three single-arm trials, two randomized controlled trials, and two comparative effectiveness trials. In meta-analyses, there were no statistically significant differences between premenopausal and postmenopausal women (shown as premenopausal minus postmenopausal) for change in weight (0.58 [95% confidence interval −0.12 to 1.28] kg, n = 7 interventions), fat mass (0.73 [−0.25 to 1.70] kg, n = 6 interventions), or lean mass (−0.5 6[−1.48 to 0.36] kg, n = 4 interventions). However, a statistically significant subgroup difference was observed for fat mass change between menopausal groups (premenopausal minus postmenopausal) when comparing diet-only (1.28 [0.23 to 2.33] kg, n = 4 interventions) versus diet and exercise interventions (−0.09 [−0.51 to 0.32]kg, n = 2 interventions). No differences were shown in any other subgroups.

Conclusions and relevance:

This review provides some evidence to suggest weight loss interventions may not need to be tailored to women's menopausal status. However, given the small number of studies, short intervention duration in most publications (≤ 6 mo) and unclear retention rates in premenopausal versus postmenopausal groups of some publications, menopausal group differences should be examined in existing and future trials where the appropriate data have been collected.