bluuebunny/crossref_metadata_2025 huggingface dataset:
Propensity score methods for time‐dependent cluster confounding
Authors: Cafri Guy , Austin Peter C.
Published: May 2020

In observational studies, subjects are often nested within clusters. In medical studies, patients are often treated by doctors and therefore patients are regarded as nested or clustered within doctors. A concern that arises with clustered data is that cluster‐level characteristics (e.g., characteristics of the doctor) are associated with both treatment selection and patient outcomes, resulting in cluster‐level confounding. Measuring and modeling cluster attributes can be difficult and statistical methods exist to control for all unmeasured cluster characteristics. An assumption of these methods however is that characteristics of the cluster and the effects of those characteristics on the outcome (as well as probability of treatment assignment when using covariate balancing methods) are constant over time. In this paper, we consider methods that relax this assumption and allow for estimation of treatment effects in the presence of unmeasured time‐dependent cluster confounding. The methods are based on matching with the propensity score and incorporate unmeasured time‐specific cluster effects by performing matching within clusters or using fixed‐ or random‐cluster effects in the propensity score model. The methods are illustrated using data to compare the effectiveness of two total hip devices with respect to survival of the device and a simulation study is performed that compares the proposed methods. One method that was found to perform well is matching within surgeon clusters partitioned by time. Considerations in implementing the proposed methods are discussed.
Reconcile VAWA amendments, Title IX with tech tools that make compliance easier — and harder
Authors: McCarthy Claudine
Published: May 2020

When it comes to Title IX and the Violence Against Women Act amendments to the Clery Act, technology has made compliance more complicated, but certain technological tools can make compliance a bit easier. That's according to Joseph C. Storch, J.D., Associate Counsel in the Office of General Counsel at The State University of New York; and Gemma Rinefierd, Ed.D., Director of the Student Conduct Institute, also at SUNY; and Taylor Sinclair, J.D., System Director for Title IX at the Nebraska State College System. They spoke at Stetson University's Annual National Conference on Law and Higher Education about how to use technology to better meet or even exceed compliance requirements. They also provided insight about how technology can make the proper response to violence more complicated for higher ed officials, yet easier for students to commit certain violations, and how you can mitigate that.
Palbociclib‐letrozole as first‐line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study
Authors: Takahashi Masato , Masuda Norikazu , Nishimura Reiki , Inoue Kenichi , Ohno Shinji , Iwata Hiroji , Hashigaki Satoshi , Muramatsu Yasuaki , Umeyama Yoshiko , Toi Masakazu
Published: May 2020

Palbociclib is a highly selective, reversible, oral inhibitor of cyclin‐dependent kinases 4 and 6 that is approved to treat hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer. An open‐label, single‐arm, Japanese phase 2 study was conducted to investigate the efficacy and safety of palbociclib plus letrozole as first‐line treatment in 42 postmenopausal patients with estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer. The probability of progression‐free survival originally reported at 1 year was 75.0% (90% confidence interval, 61.3‐84.4), but median progression‐free survival was not attained at the primary analysis. In this report, updated efficacy and safety results with a longer follow‐up period are presented. The median duration of treatment in the updated analysis was 33.0 months (range, 1.8‐49.2). The probability of progression‐free survival at 1 year was 75.6% (90% confidence interval, 62.4‐84.7). Median progression‐free survival was 35.7 months (95% confidence interval, 21.7‐46.7). Objective response rate and disease control rate were 47.6% (95% confidence interval, 32.0‐63.6) and 85.7% (95% confidence interval, 71.5‐94.6), respectively. Common treatment‐related adverse events (all grades; grade 3/4) were neutropenia (100%; 93%), leukopenia (83%; 60%), and stomatitis (76%; 0%). Treatment‐related febrile neutropenia was reported in one patient. In general, no clinically meaningful deterioration in health‐related quality of life was observed. Palbociclib plus letrozole remained effective and tolerable in Japanese postmenopausal patients with estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer in this updated analysis.
Serine‐227 in the N‐terminal kinase domain of RSK2 is a potential therapeutic target for mantle cell lymphoma
Authors: Matsumura‐Kimoto Yayoi , Tsukamoto Taku , Shimura Yuji , Chinen Yoshiaki , Tanba Kazuna , Kuwahara‐Ota Saeko , Fujibayashi Yuto , Nishiyama Daichi , Isa Reiko , Yamaguchi Junko , Kawaji‐Kanayama Yuka , Kobayashi Tsutomu , Horiike Shigeo , Taniwaki Masafumi , Kuroda Junya
Published: May 2020

RSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL), an almost incurable disease subtype of non‐Hodgkin lymphoma. In this study, serine‐227 (RSK2Ser227) in the N‐terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL‐derived cell lines and in tumor tissues derived from five MCL patients. BI‐D1870, an inhibitor specific to RSK2‐NTKD, caused RSK2Ser227 dephosphorylation, and thereby, induced dose‐dependent growth inhibition via G2/M cell cycle blockade and apoptosis in four of the five cell lines, while one cell line showed only modest sensitivity. In addition, RSK2 gene knockdown caused growth inhibition in the four BI‐D1870‐sensitive cell lines. Comparative gene expression profiling of the MCL‐derived cell lines showed that inhibition of RSK2Ser227 by BI‐D1870 caused downregulation of oncogenes, such as c‐MYC and MYB; anti‐apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3, and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B, and BLNK. These findings show that targeting of RSK2Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis. In addition, we found favorable combinatory growth inhibitory effects of BI‐D1870 with inhibitors of BTK (ibrutinib), AKT (ipatasertib), and BCL2 (venetoclax) in cell characteristic‐dependent manners. These results provide a rationale for RSK2Ser227 in the NTKD as a potential therapeutic target in MCL and for future development of a novel bioavailable RSK2 NTKD‐specific inhibitor.
COVID‐19 will change our campuses forever
Authors: Zacarese Lawrence M.
Published: May 2020

Every three months when I sit down to write this column, I always try to choose a contemporary topic that, even though I am writing a few months ahead of publication, will still be relevant when readers see it. But as I pen this piece, I have never felt more confident that, when this column publishes, COVID‐19 will still be on everyone's mind.
Know what next steps to take after conducting campus threat assessments
Authors: McCarthy Claudine
Published: May 2020

ARLINGTON, Va. — Campus threat assessment teams often do a great job at assessing potential threats but struggle with knowing what next steps to take to successfully manage the situation. Beth Devonshire, J.D., Consultant; and Cathy Cocks, Associate, both with D. Stafford & Associates, explained how to develop logical next steps to follow after conducting threat assessments. During a presentation at the Association for Student Conduct Administration's annual conference, they offered guidance for applying investigative themes and questions and developing a mitigation plan.
Meet COVID‐19 challenges with enthusiasm, strong communication
Authors: Sutton Halley
Published: May 2020

James Gilman graduated from the University of New Haven in 1993. After he'd worked for the Connecticut State Police for 22 years, he returned to his alma mater, this time as the Chief of Police. “It was very exciting to get back to where I started,” Gilman said.
Adapt to the daily operations of campus security in the wake of COVID‐19
Authors: Rahn Josh
Published: May 2020

The COVID‐19 pandemic has upended the normal routines of colleges and universities across the nation. Campus security departments are no exception. With fewer people on campus, their responsibilities have changed but not lessened. Campus security leaders must also consider the health threats posed to their own staff as they make assignments and monitor the unfolding pandemic.
Americans increasingly view peers with mental illness as threats
Authors: Sutton Halley
Published: May 2020

Due to the prevalence of mass shootings, Americans increasingly view peers with mental illness as violent threats, despite scientific evidence that points to the contrary, according to a paper published in Health Affairs.
Closing up after TAVR
Authors: Turi Zoltan G.
Published: May 2020

Key Points

Techniques for vascular access and closure are highly heterogeneous and continue to evolve.

The combination of suture and collagen plug closure has theoretical benefits but also potential additive risk.

Because this is a small single site series, the claim for promising safety and efficacy should be made with caution.
Thoracic aortic disease: Can we safely cover the branches?
Authors: Shatila Wassim , Krajcer Zvonimir
Published: May 2020

Key Points

Thoracic aortic disease has usually been treated with surgery.

Thoracic endovascular aortic repair is challenging if supra‐aortic vessels are involved.

In situ fenestration of the main graft from a retrograde approach while using bare‐metal stents as bridge stents appears to be a safe and practical technique.
The Robin Hood effect!
Authors: Jolicoeur E. Marc , Henry Timothy D.
Published: May 2020

Key Points

Results from this analysis support the hypothesis that the reduction of the coronary sinus redistributes coronary flow in the myocardium.

The results from this analysis must be interpreted with caution; while being the first report of its kind, the small sample size and methodological flaws limit the generalizability of the findings.

Future studies should investigate the use of the coronary sinus reducer to improve myocardial function in patients with ischemic cardiomyopathy.
Mechanistic Study on the Selective Oxidation of Acrolein to Acrylic Acid concerning the Role of Water
Authors: Knoche Stefan , Heid Maurice , Gora Niklas , Ohlig Dominik , Drochner Alfons , Etzold Bastian , Vogel Herbert
Published: May 2020

The activity of Mo/V/W mixed oxide catalyst in the gas phase oxidation of acrolein to acrylic acid is tremendously influenced by addition of fed water. This effect of water is investigated and connected to the catalytic mechanism by several stationary kinetic measurements and transient response methods, such as temperature‐programmed reduction, oxidation and desorption experiments, special concentration‐programmed methods as well as H218O‐SSITKA and D2O‐SSITKA experiments. Furthermore, kinetic modeling, based on results of H218O‐SSITKA experiments in a wide temperature and feed water content range gives access to kinetic parameters of single reaction steps in the catalytic mechanism. The developed mechanism is not only able to describe conversion and selectivities, inclusively the effect of water, but also describes the 18O‐degree of labeling of all reaction components quantitatively.
Efficient H2O2 Production via H2O Oxidation on an Anode Modified with Sb‐Containing Mixed Metal Oxides
Authors: Miyase Yuta , Miseki Yugo , Gunji Takahiro , Sayama Kazuhiro
Published: May 2020

The effect of the surface modification of a fluorine‐doped tin oxide (FTO) electrode with an Sb‐containing mixed metal oxide on the oxidative production of H2O2 from H2O was investigated. The initial faradaic efficiency for H2O2 production (FE(H2O2)) reached 98 % when CuSb2Ox/FTO was used as the anode, as a consequence of the suppression of O2 generation via four‐electron oxidation of H2O. InSbOx modification of FTO resulted in a suppression of the oxidative decomposition of H2O2 to O2. The double‐layer composite electrode InSbOx/CuSb2Ox/FTO indicated the advantageous traits of both Sb‐containing mixed metal oxides, and this composite electrode showed superior FE(H2O2), current‐potential dependence, and stability to other electrodes such as CuSb2Ox/FTO, InSbOx/FTO, and Al2O3/BiVO4/FTO.
When disaster strikes: The role of disaster planning and management in cancer care delivery
Authors: Sahar Liora , Nogueira Leticia M. , Ashkenazi Isaac , Jemal Ahmedin , Yabroff K. Robin , Lichtenfeld J. Leonard
Published: May 2020

The impact of disasters on the delivery of health services suggests that patients with cancer should be identified as a vulnerable population that requires additional attention and assistance during a disaster. Incorporating the special case of these patients into an event management framework can elevate resilience, decrease suffering, and save lives.
A hybrid echocardiography‐CFD framework for ventricular flow simulations
Authors: Hedayat Mohammadali , Patel Tatsat R. , Kim Taeouk , Belohlavek Marek , Hoffmann Kenneth R. , Borazjani Iman
Published: May 2020

Image‐based CFD is a powerful tool to study cardiovascular flows while 2D echocardiography (echo) is the most widely used noninvasive imaging modality for the diagnosis of heart disease. Here, echo is combined with CFD, that is, an echo‐CFD framework, to study ventricular flows. To achieve this, the previous 3D reconstruction from multiple 2D echo at standard cross sections is extended by: (a) reconstructing aortic and mitral valves from 2D echo and closing the left‐ventricle (LV) geometry by approximating a superior wall; (b) incorporating the physiological assumption of the fixed apex as a reference (fixed) point in the 3D reconstruction; and (c) incorporating several smoothing algorithms to remove the nonphysical oscillations (ringing) near the basal section. The method is applied to echo from a baseline LV and one after inducing acute myocardial ischemia (AMI). The 3D reconstruction is validated by comparing it against a reference reconstruction from many echo sections while flow simulations are validated against the Doppler ultrasound velocity measurements. The sensitivity study shows that the choice of the smoothing algorithm does not change the flow pattern inside the LV. However, the presence of the mitral valve can significantly change the flow pattern during the diastole phase. In addition, the abnormal shape of a LV with AMI can drastically change the flow during diastole. Furthermore, the hemodynamic energy loss, as an indicator of the LV pumping performance, for different test cases is calculated, which shows a larger energy loss for a LV with AMI compared to the baseline one.
Gromov‐Hausdorff Limits of Kähler Manifolds with Ricci Curvature Bounded Below II
Authors: Liu Gang , Szekelyhidi Gábor
Published: May 2020

We study noncollapsed Gromov‐Hausdorff limits of Kähler manifolds with Ricci curvature bounded below. Our main result is that each tangent cone is homeomorphic to a normal affine variety. This extends a result of Donaldson‐Sun, who considered noncollapsed limits of polarized Kähler manifolds with two‐sided Ricci curvature bounds. © 2019 Wiley Periodicals LLC
Optimal Error Estimates for Analytic Continuation in the Upper Half‐Plane
Authors: Grabovsky Yury , Hovsepyan Narek
Published: May 2020

Analytic functions in the Hardy class H2 over the upper half‐plane ℍ+ are uniquely determined by their values on any curve Γ lying in the interior or on the boundary of ℍ+. The goal of this paper is to provide a sharp quantitative version of this statement. We answer the following question: Given f of a unit H2‐norm that is small on Γ (say, its L2‐norm is of order ϵ), how large can f be at a point z away from the curve? When Γ ⊂ ∂ℍ+, we give a sharp upper bound on ∣f(z)∣ of the form ϵγ, with an explicit exponent γ = γ(z) ∈ (0, 1) and explicit maximizer function attaining the upper bound. When Γ ⊂ ℍ+ we give an implicit sharp upper bound in terms of a solution of an integral equation on Γ. We conjecture and give evidence that this bound also behaves like ϵγ for some γ = γ(z) ∈ (0, 1). These results can also be transplanted to other domains conformally equivalent to the upper half‐plane. © 2020 Wiley Periodicals, Inc.
Construction of an intelligent cellular automata model for historic landscape islands in Shanghai and fusion simulation
Authors: Wei Zhen , Zhang Wei
Published: May 2020

Historic landscape islands are a unique landscape phenomenon in the urbanization and modernization process in Shanghai. Shanghai has been fragmented and isolated at the landscape space level because of islanding, and its historic and cultural values have been broken and weakened. Therefore, it is urgent to implement fusion protection planning. Considering the islanding of urban historic landscape, cellular automata (CA) and neural network intelligent method were used to establish the intelligent CA model of Shanghai historic landscape islands and carry out computer simulation, expecting to provide a basis for studying urban historic landscapes in China via the intelligent evaluation of urban historic landscape islands and the establishment of an intelligent planning model. A technical path to alleviate landscape fragmentation and cultural value fracture of isolated islands was explored, so as to provide the latest theoretical basis for decision makers to manage historic landscape islands in Shanghai and offer reference for more scientific, intelligent, and efficient decision‐making.
Confidentiality of substance use disorder treatment records: Update
Authors: Knopf Alison
Published: May 2020

The Coronavirus Aid, Relief, and Economic Security (CARES) Act signed into law March 27 eliminated the federal rules protecting the confidentiality of substance use disorder (SUD) treatment records. Those rules, codified under 42 CFR Part 2 of the federal regulations, are going to be changed. In an overview of the CARES Act amendments regarding confidentiality released by the Legal Action Center (LAC) in April, the law firm pointed out that the amendments don't take effect until March 27, 2021. Between now and then, the new regulations will be crafted. And that overview also includes recommendations for how the language of the new rule could mitigate against the damages expected when patients learn that their treatment may not be confidential.
Prescribing buprenorphine for adolescents via telephone
Authors: Knopf Alison
Published: May 2020

As this issue went to press, America was grappling with two epidemics — opioid overdoses and COVID‐19. We have already written about the growth of telepsychiatry, including for youth (see CPU, May 2020). Requiring in‐person visits is contraindicated by social distancing recommendations. And expanding treatment for opioid use disorder (OUD) as much as possible is viewed as one of the most important ways to cut back on overdose deaths. Authorities are trying to get out of the way of treating both epidemics.
Screening for primary immunodeficiency diseases by next‐generation sequencing in early life
Authors: Sun Jinqiao , Yang Lin , Lu Yulan , Wang Huijun , Peng Xiaomin , Dong Xinran , Cheng Guoqiang , Cao Yun , Wu Bingbing , Wang Xiaochuan , Zhou Wenhao
Published: May 2020

Objective

We aimed to use next‐generation sequencing (NGS) for the early diagnosis of primary immunodeficiency diseases (PIDs) and define its effects on medical management for an infant cohort in early life.

Methods

A single‐centre study was conducted from November 2015 to April 2018. Infants less than 3 months old with infections or abnormal white blood cell counts were enrolled in the study. Gene variants were analysed by NGS, and once a mutation was found in a PID‐associated gene, the immune functions associated with this mutation were detected. The diagnosis rate of PIDs in the cohort was the main outcome. The patients received corresponding management and follow‐up treatments.

Results

Among 2392 patients who were genetically tested with NGS, 51 infants were diagnosed with PIDs. Seven types of PIDs were detected, and the most common (25/51, 49%) were combined immunodeficiencies with associated or syndromic features. Thirty‐five patients (68.6%) were cured or had improved outcomes after being diagnosed with PID. The NGS cost was US$280 per case.

Conclusions

This study not only highlighted the potential of NGS to rapidly deliver molecular diagnoses of PIDs but also indicated that the prevalence of PIDs is underestimated. With broader use, this approach has the potential to alter clinical strategies.
Repurposing current therapeutics for treating COVID‐19: A vital role of prescription records data mining
Authors: Gurwitz David
Published: May 2020

Since its outbreak in late 2019, the SARS‐Cov‐2 pandemic already infected over 3.7 million people and claimed more than 250,000 lives globally. At least 1 year may take for an approved vaccine to be in place, and meanwhile millions more could be infected, some with fatal outcome. Over thousand clinical trials with COVID‐19 patients are already listed in ClinicalTrials.com, some of them for assessing the utility of therapeutics approved for other conditions. However, clinical trials take many months, and are typically done with small cohorts. A much faster and by far more efficient method for rapidly identifying approved therapeutics that can be repurposed for treating COVID‐19 patients is data mining their past and current electronic health and prescription records for identifying drugs that may protect infected individuals from severe COVID‐19 symptoms. Examples are discussed for applying health and prescription records for assessing the potential repurposing (repositioning) of angiotensin receptor blockers, estradiol, or antiandrogens for reducing COVID‐19 morbidity and fatalities. Data mining of prescription records of COVID‐19 patients will not cancel the need for conducting controlled clinical trials, but could substantially assist in trial design, drug choice, inclusion and exclusion criteria, and prioritization. This approach requires a strong commitment of health provides for open collaboration with the biomedical research community, as health provides are typically the sole owners of retrospective drug prescription records.
Deletion of c16orf45 in zebrafish results in a low fertilization rate and increased thigmotaxis
Authors: Li Tingting , Li Fei , Lin Jia , Zhang Yinglan , Zhang Qi , Sun Yanhe , Chen Xudong , Xu Mingqing , Wang Xu , Li Qiang
Published: May 2020

c16orf45 is located at 16p13.11, an important locus related to neurodevelopmental diseases. Clinical studies have demonstrated that c16orf45 is associated with various neurodevelopmental diseases. To further elucidate the effect of c16orf45 on neural development, we constructed a zebrafish model with a stably inherited c16orf45 deletion via CRISPR/Cas9 technology. We found that deletion of c16orf45 significantly reduced the zebrafish fertilization rate, and both females and males showed reduced fertility. Meanwhile, the homozygous c16orf45 knockout zebrafish showed a developmental delay at 24 hr postfertilization (hpf). However, morphological changes were not apparent after 2 days postfertilization (dpf). Notably, the results of behavioral experiments revealed increased thigmotaxis in c16orf45−/− zebrafish at 2 months. In conclusion, these findings demonstrate that c16orf45 plays an important role in nervous system and reproductive system.
IRB Policies for Obtaining Informed Consent from Non‐English‐Speaking People
Authors: McMillan Gianna
Published: May 2020

United States regulations for the protection of human research subjects prescribe parameters for documentation of valid informed consent, which include the stipulation that the process be in a “language understandable to the subject.” While significant energy has been devoted to improving the readability of consent documents, supplemental educational tools, and nuanced measurements of individual decisional capacity, there is little guidance about how to best meet the informational needs of adults with decisional capacity who do not speak English. This article reviews the institutional review board policies from the twenty‐one research centers that received the most funding from the National Institutes of Health in 2018 and compares their guidelines for obtaining informed consent from non‐English speakers. Inconsistent practices suggest the need for more assertive federal direction on what parameters constitute valid consent for this population. These practices also indicate a reluctance to directly engage the ethical underpinnings of consent policies for non‐English speakers.
A hidden mesencephalic variant of central pain
Authors: Convers Philippe , Creac’h Christelle , Beschet Albert , Laurent Bernard , Garcia‐Larrea Luis , Peyron Roland
Published: May 2020

Background

Central post‐stroke pain (CPSP) can arise after lesions anywhere in the central somatosensory pathways, essentially within the spinothalamic system (STS). Although the STS can be selectively injured in the mesencephalon, CPSP has not been described in pure midbrain infarcts.

Methods

Of more than 300 CPSP consecutive cases, we describe five patients who developed definite neuropathic pain following lesions circumscribed to the postero‐lateral mesencephalon.

Results

The mesencephalic lesion responsible for pain was always haemorrhagic and always involved the spinothalamic tract (STT), as demonstrated by suppressed laser‐evoked potentials in every case, with or without preserved lemniscal function. In three cases the midbrain injury could be ascribed to trauma, presumably from the cerebellar tentorium. As a result of the paucity of sensory symptoms, the pain was considered as ‘psychogenic’ in two of the patients until electrophysiological testing confirmed STT involvement.

Conclusion

Postero‐lateral midbrain lesions should be added to potential causes of CPSP. Because pain and spinothalamic deficits may be the only clinical sign, and because small lateral midbrain lesions may be difficult to trail with MRI, mesencephalic CPSP can be misdiagnosed as malingering or psychogenic pain for years.

Significance

Selective spinothalamic injury caused by small lateral midbrain lesions is a very rare cause of central post‐stroke pain that can remain undiagnosed for years. It appears to obey to haemorrhagic, sometimes post‐traumatic lesions. Sudden development of contralateral burning pain with isolated spinothalamic deficits may be the only localizing sign, which can be easily objectively detected with electrophysiological testing.
A Self‐contained Two‐electrode Nanosensor for Electrochemical Analysis in Aqueous Microenvironments
Authors: Scheibel Olivia V. , Schrlau Michael G.
Published: May 2020

We describe the development, fabrication, and characterization of a novel two‐electrode nanosensor contained within the tip of a needle‐like probe. This sensor consists of two, vertically aligned, carbon structures which function as individual electrodes. One of the carbon structures was modified by silver electrodeposition and chlorination to enable it to function as a pseudo‐reference electrode. Performance of this pseudo‐reference electrode was found to be comparable to that of commercially available Ag/AgCl reference electrodes. The unmodified carbon structure was employed as a working electrode versus the silver‐plated carbon structure to form a two‐electrode sensor capable of characterizing redox‐active analytes. The nanosensor was demonstrated to be capable of electrochemically characterizing the redox behavior of para‐aminophenol (PAP) in both bulk solutions and microenvironments. PAP was also measured in cell lysate to show that the nanosensor can detect small concentrations of analyte in heterogenous environments. As the working and reference electrodes are contained within a single nanoprobe, there was no requirement to position external electrodes within the electrochemical cell enabling analysis within very small domains. Due to the low‐cost manufacturing process, this nanoprobe has the potential to become a unique and widely accessible tool for the electrochemical characterization of microenvironments.
An Impedimetric Aptasensor Based on a Novel Line‐Pad‐Line Electrode for the Determination of VEGF165
Authors: Feng Ying , Xiao Shan , Xiong Xingliang , Wang Honglei , Kong Fankai , Li Yang , Zhang Yan , Chen Longcong
Published: May 2020

In this work, a novel, simple and label‐free line‐pad‐line electrode (LPLE) biosensor was developed for detection of vascular endothelial growth factor (VEGF165). DNA aptamer was used as a recognition element for high specificity to VEGF165, and original LPLE as the substrate electrode for high sensitivity of the biosensor. This sensor was prepared by immobilizing anti‐VEGF165 aptamers on the LPLE surface through gold‐sulfur (Au−S) bonding. Upon the addition of VEGF165, a large target‐induced conformational change in the surface‐immobilized aptamer was generated and caused variations in the interfacial properties,which led to a corresponding increase in the impedance magnitude of the LPLE. Finally, our results demonstrate that the calibration curve for VEGF165determination was linear over the range of 0.026‐31.4 fM with a detection limit as low as 0.017 fM.Additionally, our sensor was fabricated on printed circuit board (PCB) with a new electrode construction, and can potentially be implemented with the advantages of simplicity, low‐cost and easy mass production. Besides, considering its desirable sensitivity and specificity, the proposed use of LPLE provided a promising strategy for a wide variety of sensing applications.
COVID‐19: The residuals
Authors: Dennis Marguerite J.
Published: May 2020

The Random House Dictionary of the English Language defines residual as “that which remains.”
Lead your team through crisis
Authors: House Vicki
Published: May 2020

There are numerous traits and skills needed to lead a team. However, when we lead through a crisis that could ultimately shift how we do business, inherent traits woven through a leader keep us moving forward through rapid change and nurture our team in the process. Whether we like it or not, life is wrapped in change, and it is here to stay. Learning new ways of doing things draws us out of our comfort zones. But when change is thrust upon us, pushing us out of our comfort zone, our response is our choice. As leaders dare to step out of their comfort zones and teach their team the advantages of making bold but responsible decisions, lasting excellence can be secured for our institutions.
Gain perspective, expand your network by presenting internationally
Authors: Pavlik Amelia
Published: May 2020

Being part of something. This is the concept that's at the heart of why Joshua LaFave opted to start presenting at international conferences.
Heterogeneity in the dynamic change of cognitive function among older Chinese people: A growth mixture model
Authors: Qiu Peiyuan , Zeng Miao , Kuang Weihong , Meng Steven Siyao , Cai Yan , Wang Huali , Wan Yang
Published: May 2020

Objectives

Our aim is to distinguish different trajectories of cognitive change in Chinese geriatric population and identify risk factors for cognitive decline in each subpopulation.

Methods

We obtained data from five waves (2002, 2005, 2008, 2011, 2014) of the Chinese Longitudinal Health Longevity Survey, using the Chinese Mini‐Mental State Examination (C‐MMSE) as a proxy for cognitive function. We applied growth mixture modeling (GMM) to identify heterogeneous subpopulations and potential risk factors.

Results

Our sample included 3859 older adults, 1387 (48.7%) male and 1974 (51.2%) female with age range of 62 to 108 (average of 74.5) at initial survey. Using GMM and best fit statistics, we identified two distinct subgroups in respect to their longitudinal cognitive function: (a) cognitively stable (87.8%) group with 0.49 C‐MMSE points decline per 3 years, and (b) cognitively declining (12.2%) group with 6.03 C‐MMSE points decline per 3 years. Of note, cognitive activities were protective, and hearing and visual impairments were risk factors in both groups. Diabetes, hypertension, stroke and cardiovascular disease were associated with cognitive decline in the cognitively declining group. Physical activities, and intake of fresh vegetables, fruits, and fish products were protective in the cognitively stable group.

Conclusions

Using GMM, we identified heterogeneity in trajectories of cognitive change in older Chinese people. Moreover, we found risk factors specific to each subgroup, which should be considered in future studies.
Does cognitive function in older bipolar patients depend on recurrent or current mood symptoms?
Authors: Schouws Sigfried N. T. M. , Korten Nicole , Beekman Aartjan T. F. , Stek Max L. , Dols Annemieke
Published: May 2020

Background

Cognitive impairment in patients with bipolar disorder (BD) is viewed as an integral part of the disorder that seems to be rather stable and even present in euthymic state. Current mood symptoms influence cognition negatively and multiple mood episodes could lead to more severe psychopathology and cognitive impairment, resulting in a hypothesized neuroprogressive course of BD. The influence of current mood symptoms and recurrent mood episodes on cognitive functioning warrants further exploration.

Methods

Cohort 1 included 20 hypomanic and 21 depressed older adults with bipolar disorder (OABD) of which 20 were reassessed in the euthymic state and 50 healthy subjects. Cohort 2 included 27 OABD who had no recurrent mood episodes during 5 years and 29 who had recurrent mood episodes during 5 years. Neuropsychological examination including tests for memory, executive function, attention and verbal fluency was performed repeatedly in all subjects.

Results

In cohort 1 cross‐sectional analyses showed that hypomanic, depressed and euthymic patients groups did not differ from each other with respect to their cognitive functioning, except for attention, which was poorer only in depressed patients. Regardless of mood state patients experienced significantly worse cognitive functioning compared to the healthy subjects. Within subject comparisons revealed that performance on memory tasks was worse in patients with current mood symptoms; depressed patients were more impaired in the learning condition and hypomanic patients were more impaired in delayed recall. In cohort 2 cognitive functioning was not different in patients with or without recurrence in 5 year follow‐up.

Conclusions

Although OABD had worse cognitive functioning than healthy subjects, there was a quite stable pattern of cognitive impairment, regardless of current or recurrent mood episodes. These results do not provide consistent support for the hypothesis of neuroprogression in BD.
Prevision of multidisciplinary head and neck cancer survivorship care during the 2019 novel coronavirus pandemic
Authors: Nilsen Marci Lee , Clump David A. , Kubik Mark , Losego Karen , Mrozek Alyssa , Pawlowicz Elizabeth , Pickford Debra , Sridharan Shaum , Traylor Katie , Wasserman‐Wincko Tamara , Young Kelly , Zandberg Dan , Johnson Jonas T.
Published: May 2020

The 2019 Coronavirus Pandemic challenges the delivery of care for patients with head and neck cancer. An important aspect of this care has been the evolution of enhanced survivorship services, which include surveillance for recurring cancer and prevention of second primaries. The application of evidence‐based approaches to the identification and management of treatment and tumor‐related toxicities has embraced the use of validated patient‐reported outcomes instruments, health promotion, and care coordination. In this manuscript, we describe how our multidisciplinary team of survivorship providers has accommodated to the need to provide patients with social distancing while acknowledging the importance of continued care during treatment and through the spectrum of survivorship.
Acute high‐dose titanium dioxide nanoparticle exposure alters gastrointestinal homeostasis in mice
Authors: Kurtz Courtney C. , Mitchell Samantha , Nielsen Kaitlyn , Crawford Kevin D. , Mueller‐Spitz Sabrina R.
Published: May 2020

Human exposure to a wide variety of engineered nanoparticles (NPs) is on the rise and use in common food additives increases gastrointestinal (GI) exposure. Host health is intricately linked to the GI microbiome and immune response. Perturbations in the microbiota can affect energy harvest, trigger inflammation and alter the mucosal barrier leading to various disease states such as obesity and inflammatory bowel diseases. We hypothesized that single high‐dose titanium dioxide (TiO2) NP exposure in mice would lead to dysbiosis and stimulate mucus production and local immune populations. Juvenile mice (9‐10 weeks) were gavaged with 1 g/kg TiO2 NPs and examined for changes in mucosa‐associated bacteria abundance, inflammatory cytokines, mucin expression and body mass. Our data provide support that TiO2 NP ingestion alters the GI microbiota and host defenses promoting metabolic disruption and subsequently weight gain in mice.
Pseudo‐real‐time retinal layer segmentation for high‐resolution adaptive optics optical coherence tomography
Authors: Janpongsri Worawee , Huang Joey , Ng Ringo , Wahl Daniel J. , Sarunic Marinko V. , Jian Yifan
Published: May 2020

We present a pseudo‐real‐time retinal layer segmentation for high‐resolution Sensorless Adaptive Optics‐Optical Coherence Tomography (SAO‐OCT). Our pseudo‐real‐time segmentation method is based on Dijkstra's algorithm that uses the intensity of pixels and the vertical gradient of the image to find the minimum cost in a geometric graph formulation within a limited search region. It segments six retinal layer boundaries in an iterative process according to their order of prominence. The segmentation time is strongly correlated to the number of retinal layers to be segmented. Our program permits en face images to be extracted during data acquisition to guide the depth specific focus control and depth dependent aberration correction for high‐resolution SAO‐OCT systems. The average processing times for our entire pipeline for segmenting six layers in a retinal B‐scan of 496 × 400 and 240 × 400 pixels are around 25.60 and 13.76 ms, respectively. When reducing the number of layers segmented to only two layers, the time required for a 240 × 400 pixel image is 8.26 ms.
Bioglass‐based scaffolds coated with silver nanoparticles: Synthesis, processing and antimicrobial activity
Authors: Oliveira Rodrigo L. M. S. , Barbosa Lucas , Hurtado Carolina R. , Ramos Lucas de P. , Montanheiro Thaís L. A. , Oliveira Luciane D. , Tada Dayane B. , Trichês Eliandra de Sousa
Published: May 2020

Over the past few years, several tridimensional synthetic bone grafts, known as scaffolds, are being developed to overcome the autologous grafts limitations. Among the materials used on the production of scaffolds, the 45S5 bioglass stands out due to its capacity of bonding to hard and soft tissues. Silver nanoparticles are well‐known for their antimicrobial properties and their incorporation on the scaffold may promote its antimicrobial response, avoiding microorganism proliferation on the materials surface. This study proposes a simple way to coat 45S5 bioglass‐based scaffolds with silver nanoparticles. The scaffolds were obtained by the sponge replication technique and the silver nanoparticles were incorporated by soaking under ultrasonic stirring. The antimicrobial activity of the scaffolds was analyzed against three different microbial strains: S. aureus, P. aeruginosa, and C. albicans. Due to the heat treatment during the scaffold production, the bioglass crystalized mainly in a sodium calcium silicate phase, forming a glass–ceramic scaffold. The silver nanoparticles were coated in a well‐distributed manner throughout the scaffold, while avoiding their aggregation. The coated scaffold inhibited the growth of all the analyzed microorganism. Therefore, the use of ultrasonic stirring to coat the bioglass scaffold with silver nanoparticles showed to be an efficient way to promote its antimicrobial response.
Microtopographical patterns promote different responses in fibroblasts and Schwann cells: A possible feature for neural implants
Authors: Mobini Sahba , Kuliasha Cary A. , Siders Zachary A. , Bohmann Nicole A. , Jamal Syed‐Mustafa , Judy Jack W. , Schmidt Christine E. , Brennan Anthony B.
Published: May 2020

The chronic reliability of bioelectronic neural interfaces has been challenged by foreign body reactions (FBRs) resulting in fibrotic encapsulation and poor integration with neural tissue. Engineered microtopographies could alleviate these challenges by manipulating cellular responses to the implanted device. Parallel microchannels have been shown to modulate neuronal cell alignment and axonal growth, and Sharklet™ microtopographies of targeted feature sizes can modulate bio‐adhesion of an array of bacteria, marine organisms, and epithelial cells due to their unique geometry. We hypothesized that a Sharklet™ micropattern could be identified that inhibited fibroblasts partially responsible for FBR while promoting Schwann cell proliferation and alignment. in vitro cell assays were used to screen the effect of Sharklet™ and channel micropatterns of varying dimensions from 2 to 20 μm on fibroblast and Schwann cell metrics (e.g., morphology/alignment, nuclei count, metabolic activity), and a hierarchical analysis of variance was used to compare treatments. In general, Schwann cells were found to be more metabolically active and aligned than fibroblasts when compared between the same pattern. 20 μm wide channels spaced 2 μm apart were found to promote Schwann cell attachment and alignment while simultaneously inhibiting fibroblasts and warrant further in vivo study on neural interface devices. No statistically significant trends between cellular responses and geometrical parameters were identified because mammalian cells can change their morphology dependent on their environment in a manner dissimilar to bacteria. Our results showed although surface patterning is a strong physical tool for modulating cell behavior, responses to micropatterns are highly dependent on the cell type.
Increased CCL24 and CXCL7 levels in the cerebrospinal fluid of patients with neurosyphilis
Authors: Li Xin‐Xin , Zhang Jing , Wang Zhao‐Yuan , Chen Si‐Qi , Zhou Wei‐Fang , Wang Ting‐Ting , Man Xiao‐Yong , Zheng Min
Published: May 2020

Background

Monocytes are recruited into the cerebrospinal fluid (CSF) of patients with neurosyphilis, suggesting abnormal chemokine expression. We aimed to investigate the aberrant expression of chemokines in the CSF of these patients.

Methods

CSF and serum samples were collected from patients with neurosyphilis between July 2017 and June 2019 in the Dermatology Department, Second Affiliated Hospital of Zhejiang University. Differences in the expression of 38 chemokines between patients with and without neurosyphilis were detected using RayBio® Human Chemokine Antibody Array C1. CCL24 and CXCL7 levels in the patients’ CSF and serum were further measured using RayBio® CCL24 and CXCL7 ELISA kits.

Results

Ninety‐three CSF and serum samples of patients with syphilis were collected. Antibody array analysis showed that the CSF levels of CCL24 (P = .0185), CXCL7 (P < .0001), CXCL13 (P < .0001), CXCL10 (P < .0001), and CXCL8 (P < .0001) were significantly higher in patients with than without neurosyphilis. ELISA confirmed significantly higher CCL24 and CXCL7 levels in the CSF of patients with than without neurosyphilis (CCL24: 6.082 ± 1.137 pg/mL vs 1.773 ± 0.4565 pg/mL, P = .0037; CXCL7: 664.3 ± 73.19 pg/mL vs 431.1 ± 90.54 pg/mL, P = .0118). Increased CCL24 and CXCL7 expression was seen throughout all neurosyphilis stages, had moderate diagnostic efficiency for neurosyphilis, and correlated poorly with CSF cell count and Venereal Disease Research Laboratory titer. CSF CCL24 levels also correlated poorly with CSF protein concentration.

Conclusion

Abnormally high CSF chemokines levels may play a role in the pathogenesis of neurosyphilis.
Optimal pH set point for simultaneous production and pertraction of n‐caproic acid: an experimental and simulation study
Authors: A Gehring Tito , A Cavalcante Willame , S Colares Aldo , Angenent Largus T , T Santaella Sandra , Lübken Manfred , C Leitão Renato
Published: May 2020

BACKGROUND

The high rate production of n‐caproic acid (C6) through chain elongation can be achieved with the use of pertraction systems for the continuous and selective extraction of C6. However, although the biological conversion processes are enhanced at a neutral pH, high extraction efficiency depends on acidic conditions. Understanding of these divergent pH effects is fundamental for a reliable operation and scale‐up of these C6‐producing systems.

RESULTS

A bench‐scale anaerobic filter (12.8 L) fed with fermented sugarcane at organic loading rates of ≈7.2 g of chemical oxygen demand (COD) L−1 day−1 achieved C6 production rates of 2.1 and 3.8 gCOD L−1 day−1, without and with in‐line extraction, respectively. Compared to previous studies, a high average extraction rate of 24.7 gCOD m−2 day−1 was observed due to a high reactor volume‐to‐membrane‐area ratio. The novel model described here with biological and pertraction processes for continuously operated systems indicates that an optimal operative pH can simultaneously maximize C6 production and extraction. The hydraulic retention time was another key parameter for balancing inhibition by undissociated C6 and losses due to nonextracted C6.

CONCLUSIONS

Sugarcane biorefineries can produce C6, which has a market value that is >10‐fold higher than ethanol. Simulations of chain elongation processes require the implementation of hydrogenotrophic methanogens to allow for a comprehensive description of ethanol consumption together with the C6 formation, in‐line C6 extraction processes, and formation of gaseous by‐products. Although these simulations were possible using parameter sets from the literature, further studies are needed for parameter identification, especially under inhibition at low pH. © 2020 Society of Chemical Industry