bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Progress on the Development of Magnetically‐Responsive Micropillars: Actuation, Fabrication, and Applications
Authors: Ni Ke , Wang Zhengzhi
Published: January 2023

Stimuli‐responsive micro‐pillared structures can perform complex and precise tasks at the microscale through dynamic and reversible deformation of the pillars in response to external triggers. Magnetic field is one of the most common actuation strategies due to its incomparable advantages such as instantaneous response, remote and nondestructive control, and superior biocompatibility. Over the past decade, many researches are attempted to design and optimize magnetically‐responsive micropillars for a wide range of applications and great progresses are accomplished. In this review, the most important aspects of recent progress of magnetically‐responsive micropillars are covered to give a comprehensive and systematical introduction to this new field, from the actuation mechanisms, fabrication methods, and deformation patterns to the practical applications. The increasingly maturing fabrication techniques can provide low‐cost and large‐scale magnetic micropillars with homogeneous responses. Some advanced techniques are developed to fabricate micropillars with programmable and reprogrammable responses for site‐specific and reconfigurable actuations. On the other hand, practical applications for particle/droplet/light manipulation, flow generation, miniature swimming/climbing/carrying microrobots, tunable adhesion, cellular probe, fog collector, and anti‐ice surfaces are also summarized. Finally, current challenges that limit the industrial implementation are discussed and the authors’ perspectives on the future directions of magnetically‐responsive micropillars are stated.
Cell‐Sized Lipid Vesicles as Artificial Antigen‐Presenting Cells for Antigen‐Specific T Cell Activation
Authors: Chen Jui‐Yi , Agrawal Sudhanshu , Yi Hsiu‐Ping , Vallejo Derek , Agrawal Anshu , Lee Abraham P.
Published: January 2023

In this study, efficient T cell activation is demonstrated using cell‐sized artificial antigen‐presenting cells (aAPCs) with protein‐conjugated bilayer lipid membranes that mimic biological cell membranes. The highly uniform aAPCs are generated by a facile method based on standard droplet microfluidic devices. These aAPCs are able to activate the T cells in peripheral blood mononuclear cells, showing a 28‐fold increase in interferon gamma (IFNγ) secretion, a 233‐fold increase in antigen‐specific CD8 T cells expansion, and a 16‐fold increase of CD4 T cell expansion. The aAPCs do not require repetitive boosting or additional stimulants and can function at a relatively low aAPC‐to‐T cell ratio (1:17). The research presents strong evidence that the surface fluidity and size of the aAPCs are critical to the effective formation of immune synapses essential for T cell activation. The findings demonstrate that the microfluidic‐generated aAPCs can be instrumental in investigating the physiological conditions and mechanisms for T cell activation. Finally, this method demonstrates the feasibility of customizable aAPCs for a cost‐effective off‐the‐shelf approach to immunotherapy.
Nuclear Fructose‐1,6‐Bisphosphate Inhibits Tumor Growth and Sensitizes Chemotherapy by Targeting HMGB1
Authors: Li Yeyi , Fu Yuan , Zhang Yan , Duan Bilian , Zhao Yanli , Shang Man , Cheng Ying , Zhang Kai , Yu Qiujing , Wang Ting
Published: January 2023

Metabolites are important for cell fate determination. Fructose‐1,6‐bisphosphate (F1,6P) is the rate‐limiting product in glycolysis and the rate‐limiting substrate in gluconeogenesis. Here, it is discovered that the nuclear‐accumulated F1,6P impairs cancer cell viability by directly binding to high mobility group box 1 (HMGB1), the most abundant non‐histone chromosome structural protein with paradoxical roles in tumor development. F1,6P disrupts the association between the HMGB1 A‐box and C‐tail by targeting K43/K44 residues, inhibits HMGB1 oligomerization, and stabilizes P53 protein by increasing P53–HMGB1 interaction. Moreover, F1,6P lowers the affinity of HMGB1 for DNA and DNA adducts, which sensitizes cancer cells to chemotherapeutic drug(s)‐induced DNA replication stress and DNA damage. Concordantly, F1,6P resensitizes cancer cells with chemotherapy resistance, impairs tumor growth and enhances chemosensitivity in mice, and impedes the growth of human tumor organoids. These findings reveal a novel role for nuclear‐accumulated F1,6P and underscore the potential utility of F1,6P as a drug for cancer therapy.
Wormlike Perovskite Oxide Coupled with Phase‐Change Material for All‐Weather Solar Evaporation and Thermal Storage Applications
Authors: Irshad Muhammad Sultan , Arshad Naila , Zhang Jian , Song Changyuan , Mushtaq Naveed , Alomar Muneerah , Shamim Tariq , Dao Van-Duong , Wang Hao , Wang Xianbao , Zhang Han
Published: January 2023

Interfacial solar‐driven water evaporation has shown promising prospects in desalination technology. However, the lower photothermal conversion efficiency caused by the intermittent nature of sunlight and salt accumulation remains a significant challenge for continuous desalination. Herein, the hierarchical design of interfacial solar evaporation is reported, which realizes enhanced photothermal conversion, waste heat storage/release, and effective thermal management for continuous desalination. The solar evaporator is composed of worm‐like SrCoO3 perovskite oxide anchored on super hydrophilic polyurethane (PU) foam succeeded by in situ polymerization of conducting polypyrrole (SrCoO3@PPy). The energy storage system is introduced within polyurethane matrix by a paraffin block followed by a tongue‐and‐groove structure for convective water transportation, and a heat recovery unit largely reduces heat losses. The solar evaporator possesses excellent evaporation rates (2.13 kg m−2 h−1) along with 93% solar‐to‐vapor conversion efficiency under 1 kw m−2 solar irradiation owing to its minimum equivalent evaporation enthalpy and (0.85 kg m−2 h−1) under intermittent solar irradiation as compared to conventional solar evaporators. More importantly, state‐of‐the‐art experimental investigations validate waste heat recovery/release and the salt‐resistant capability of solar evaporators optimized by computational fluid dynamic simulation. This study breaks conventional solar interfacial evaporation's limitations and demonstrates stable desalination under intermittent sunlight.
Changes in self‐ and study partner–perceived cognitive functioning in relation to amyloid status and future clinical progression: Findings from the SCIENCe project
Authors: Dubbelman Mark A. , Sikkes Sietske A. M. , Ebenau Jarith L. , van Leeuwenstijn Mardou S. S. A. , Kroeze Lior A. , Trieu Calvin , van Berckel Bart N. M. , Teunissen Charlotte E. , van Harten Argonde C. , van der Flier Wiesje M.
Published: January 2023

Introduction

We investigated changes in self‐ and study partner–reported self‐perceived cognitive decline in relation to amyloid pathology and clinical progression, in a sample of cognitively normal individuals.

Methods

A total of 404 participants (63 ± 9 years, 44% female) and their study partners completed the Cognitive Change Index (CCI) yearly (0.7–6.8 follow‐up years; n visits = 1436). Baseline and longitudinal associations between (change in) CCI scores, amyloid, and clinical progression were modeled in linear mixed models and Cox regressions.

Results

CCI–study partner scores of amyloid‐positive individuals increased over time (B = 1.79, 95% confidence interval [CI] = [0.51, 3.06]), while CCI–self scores remained stable (B = −0.45, 95% CI = [−1.77, 0.87]). Ten‐point higher baseline CCI–study partner (hazard ratio [HR] = 1.75, 95% CI = [1.30, 2.36]) and CCI–self scores (HR = 1.90, 95% CI = [1.40, 2.58]) were associated with an approximately 2‐fold increased risk of progression to mild cognitive impairment or dementia.

Discussion

Study partner–reported but not self‐perceived complaints increase over time in amyloid‐positive individuals, supporting the value of longitudinal study partner report, even in initially cognitively normal individuals.
Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART
Authors: Ehrenberg Alexander J. , Kelberman Michael A. , Liu Kathy Y. , Dahl Martin J. , Weinshenker David , Falgàs Neus , Dutt Shubir , Mather Mara , Ludwig Mareike , Betts Matthew J. , Winer Joseph R. , Teipel Stefan , Weigand Alexandra J. , Eschenko Oxana , Hämmerer Dorothea , Leiman Marina , Counts Scott E. , Shine James M. , Robertson Ian H. , Levey Allan I. , Lancini Elisa , Son Gowoon , Schneider Christoph , Egroo Maxime Van , Liguori Claudio , Wang Qin , Vazey Elena M. , Rodriguez‐Porcel Federico , Haag Lena , Bondi Mark W. , Vanneste Sven , Freeze Whitney M. , Yi Yeo‐Jin , Maldinov Mihovil , Gatchel Jennifer , Satpati Abhijit , Babiloni Claudio , Kremen William S. , Howard Robert , Jacobs Heidi I. L. , Grinberg Lea T.
Published: January 2023

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD‐associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention.

Highlights

Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages.

Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration.

Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia.

Biomarkers of neuromodulatory integrity would be value‐creating for dementia care.

Neuromodulatory nuclei present strategic prospects for disease‐modifying therapies.
An Exact and Practical Classical Strategy for 2D Graph State Sampling
Authors: Zhang Shihao , Bao Jiacheng , Sun Yifan , Li Lvzhou , Sun Houjun , Zhang Xiangdong
Published: January 2023

Constant‐depth quantum circuits that prepare and measure graph states on 2D grids are proved to possess a computational quantum advantage over their classical counterparts due to quantum nonlocality and are also well suited for demonstrations on current superconducting quantum processor architectures. To simulate the partial or full sampling of 2D graph states, a practical two‐stage classical strategy that can exactly generate any number of samples (bit strings) from such circuits is proposed. The strategy is inspired by exploiting specific properties of a hidden linear function problem solved by the target quantum circuit, which in particular combines traditional classical parallel algorithms and an explicit gate‐based constant‐depth classical circuit together. A theoretical analysis reveals that on average each sample can be obtained in nearly constant time for sampling specific circuit instances of large size. Moreover, the feasibility of the theoretical model is demonstrated by implementing typical instances up to 25 qubits on a moderate field programmable gate array platform. Therefore, the strategy can be used as a practical tool for verifying experimental results obtained from shallow quantum circuits of this type.
An automated pipeline for supervised classification of petal color from citizen science photographs
Authors: Perez‐Udell Rachel A. , Udell Andrew T. , Chang Shu‐Mei
Published: January 2023

Premise

Petal color is an ecologically important trait, and uncovering color variation over a geographic range, particularly in species with large distributions and/or short bloom times, requires extensive fieldwork. We have developed an alternative method that segments images from citizen science repositories using Python and k‐means clustering in the hue‐saturation‐value (HSV) color space.

Methods

Our method uses k‐means clustering to aggregate like‐color pixels in sample images to generate the HSV color space encapsulating the color range of petals. Using the HSV values, our method isolates photographs containing clusters in that range and bins them into a classification scheme based on user‐defined categories.

Results

We demonstrate the application of this method using two species: one with a continuous range of variation of pink‐purple petals in Geranium maculatum, and one with a binary classification of white versus blue in Linanthus parryae. We demonstrate results that are repeatable and accurate.

Discussion

This method provides a flexible, robust, and easily adjustable approach for the classification of color images from citizen science repositories. By using color to classify images, this pipeline sidesteps many of the issues encountered using more traditional computer vision applications. This approach provides a tool for making use of large citizen scientist data sets.
Finite‐horizon Q‐learning for discrete‐time zero‐sum games with application to H∞$$ {H}_{\infty } $$ control
Authors: Liu Mingxiang , Cai Qianqian , Meng Wei , Li Dandan , Fu Minyue
Published: January 2023

In this paper, we investigate the optimal control strategies for model‐free zero‐sum games involving the control. The key contribution is the development of a Q‐learning algorithm for linear quadratic games without knowing the system dynamics. The finite‐horizon setting is more practical than the infinite‐horizon setting, but it is difficult to solve the time‐varying Riccati equation associated with the finite‐horizon setting directly. The proposed algorithm is shown to solve the time‐varying Riccati equation iteratively without the use of models, and numerical experiments on aircraft dynamics demonstrate the algorithm's efficiency.
Detoxification of furanic aldehydes of the hemicellulosic hydrothermal hydrolysate of brewers’ spent grains by continuous adsorption on a fixed‐bed column
Authors: Torres‐Mayanga Paulo C. , Castro Luiz E. N. , Azambuja Suellen P. H. , Lachos‐Perez Daniel , Brown Avery B. , Timko Michael T. , Goldbeck Rosana , Forster‐Carneiro Tânia , Rostagno Mauricio A.
Published: January 2023

During the process of subcritical water hydrolysis of lignocellulosic compounds, such as brewers' spent grains, some toxic compounds can be formed due to the breakdown of the cellulose structure. These compounds are known as furanic aldehydes, and they are inhibitors of microorganisms that are used in different processes, such as fermentation and anaerobic digestion, among others. The detoxification and conditioning of these hydrolysates are required before their use in other processes that require low concentrations of toxins. One of the mechanisms that can be used to diminish those compounds is the adsorption process. For this reason, this study evaluated at‐line and in‐line purification strategies using different adsorbents in fixed‐bed columns to remove furanic aldehydes from a model feed simulating hydrolysate from subcritical water hydrolysis. The model feed consisted of simple sugars and furanic aldehydes at appropriate concentrations. The selected adsorbents were silica‐C18, hydrocarbons, and activated carbon. The results indicate that, among the adsorbents that were studied, activated carbon was the most efficient for the removal of both 5‐hydroxymethylfurfural and furfural. The activated carbon removed >99% of furanic aldehydes in the experiments conducted in the at‐line system. Sequential subcritical water hydrolysis followed by either at‐line or in‐line purification is promising for integrated inexpensive and efficient hydrolysate purification.
The Bayesian simulation study (BASIS) framework for simulation studies in statistical and methodological research
Authors: Kelter Riko
Published: January 2023

Statistical simulation studies are becoming increasingly popular to demonstrate the performance or superiority of new computational procedures and algorithms. Despite this status quo, previous surveys of the literature have shown that the reporting of statistical simulation studies often lacks relevant information and structure. The latter applies in particular to Bayesian simulation studies, and in this paper the Bayesian simulation study framework (BASIS) is presented as a step towards improving the situation. The BASIS framework provides a structured skeleton for planning, coding, executing, analyzing, and reporting Bayesian simulation studies in biometrical research and computational statistics. It encompasses various features of previous proposals and recommendations in the methodological literature and aims to promote neutral comparison studies in statistical research. Computational aspects covered in the BASIS include algorithmic choices, Markov–chain‐Monte‐Carlo convergence diagnostics, sensitivity analyses, and Monte Carlo standard error calculations for Bayesian simulation studies. Although the BASIS framework focuses primarily on methodological research, it also provides useful guidance for researchers who rely on the results of Bayesian simulation studies or analyses, as current state‐of‐the‐art guidelines for Bayesian analyses are incorporated into the BASIS.
Relative likelihood ratios for neutral comparisons of statistical tests in simulation studies
Authors: Huang Qiuxi , Trinquart Ludovic
Published: January 2023

When comparing the performance of two or more competing tests, simulation studies commonly focus on statistical power. However, if the size of the tests being compared are either different from one another or from the nominal size, comparing tests based on power alone may be misleading. By analogy with diagnostic accuracy studies, we introduce relative positive and negative likelihood ratios to factor in both power and size in the comparison of multiple tests. We derive sample size formulas for a comparative simulation study. As an example, we compared the performance of six statistical tests for small‐study effects in meta‐analyses of randomized controlled trials: Begg's rank correlation, Egger's regression, Schwarzer's method for sparse data, the trim‐and‐fill method, the arcsine‐Thompson test, and Lin and Chu's combined test. We illustrate that comparing power alone, or power adjusted or penalized for size, can be misleading, and how the proposed likelihood ratio approach enables accurate comparison of the trade‐off between power and size between competing tests.
A novel LC–MS/MS approach to [19F]‐alfatide and alfatide for application in preclinical pharmacokinetics
Authors: Ren Kaiyue , Yuan Yanjuan , Shao Qing , Qiao Hongqun
Published: January 2023

For the further study of [19F]‐alfatide, the development of highly sensitive analytical methods for its determination is an urgent issue. In this paper, a method for simultaneously determining [19F]‐alfatide and alfatide using liquid chromatography/tandem mass spectrometry was created and validated. The plasma samples were pretreated using the protein precipitation method. Poroshell 120 EC‐C18 (4.6 × 50 mm, 2.7 μm, Agilent) was used for the separation of the analytes to be measured. The mobile phase, consisting of acetonitrile and water (0.1% acetic acid, 50:50, v/v), was delivered at a flow rate of 0.60 ml/min for sample analysis. Positive electrospray ionization was performed using multiple‐reaction monitoring with transitions of m/z 715.2 → 636.6 for [19F]‐alfatide, the ion pairs 700.3 → 851.5 for alfatide and the ion pairs 237.1 → 194.2 for carbamazepine (internal standard). According to the results, the method had high specificity, precision and accuracy as well as an extended linear range. The matrix effect and extraction recovery were also acceptable. The method was successfully applied to the pharmacokinetic study of [19F]‐alfatide in rats.
Facilitators and obstacles to therapeutic alliance among patients with anorexia nervosa: A qualitative dyadic research
Authors: Lev Ari Hagar S. , Gur Eitan , Lotan‐Wohl Michal , Bernstein Zoe L. , Tuval‐Mashiach Rivka
Published: January 2023

Objective

Studies indicate a significant challenge for therapists in forming a therapeutic alliance (TA) with patients coping with anorexia nervosa (AN). While TA is a significant predictor of treatment outcomes, and AN treatment has low success rates, little is known about factors that affect the formation of an alliance and its quality in the treatment of AN. This study aimed at examining the factors associated with alliance formation, as perceived by patient–therapist dyads throughout AN therapy.

Methods

A total of 18 dyads of patients with AN and their therapists were recruited from an eating disorder unit. The semistructured interviews focussed on the TA between the therapist and patient and examined facilitators towards, and barriers to, TA formation. Data analysis followed a thematic approach.

Results

The data analysis revealed an overarching theme: the mutual wish of the patient and therapist to form a close relationship and related challenges. This theme was divided into subthemes: (1) the role of self‐disclosure of affection; (2) the meaning of the therapeutic setting; (3) coping with relationship ruptures; and (4) the importance of empathic acknowledgements.

Conclusion

A major barrier to TA formation between patients with AN and their therapists is patients' conflict between a need for meaningful relationships and fear of re‐experiencing disappointment and pain. Self‐disclosures of affection, flexible treatment setting, acknowledgement of therapists' empathic failures and ability to see things from patients' perspectives are perceived by therapists and patients to facilitate alliance formation. This study also presents practical implications derived from these themes.
Effects of temperature, reaction time, atmosphere, and catalyst on hydrothermal liquefaction of Chlorella
Authors: Haque Tarek Md. Anamul , Brdecka Michael , Salas Valeria Duran , Jang Ben
Published: January 2023

Hydrothermal liquefaction (HTL) is the direct conversion of wet biomass into bio‐oil at high temperature (200–400°C) and high pressure (10–25 MPa). In this work, we investigated HTL with 4.5 g of Chlorella and 45 ml of water/ethanol (1:1 vol. ratio) in a 100 ml reactor. Bio‐oils produced are characterized via elemental analysis, thermogravimetric analysis, and gas chromatography–mass spectrometry (GC–MS). HTL of Chlorella was investigated at 240 and 250°C for 0 and 15 min under an air or H2 atmosphere and with and without 5% zeolite Y. Temperature increased the bio‐oil yield from 38.75% at 240°C to 43.04% at 250°C for 15 min reaction time. Longer reaction time increased the bio‐oil yield at 250°C from 39.14% for 0 min to 43.04% for 15 min. The H2 atmosphere had a significant effect for HTL at 240°C. Zeolite Y increased the bio‐oil yield significantly from 32.03% to 43.06% at 250°C for 0 min. The carbon content of bio‐oil increased with the temperature while the oxygen content decreased. The boiling point distribution of bio‐oils in the range of 110–300°C varies with temperature, and atmosphere. At 240°C for 15 min, the 110–300°C range increased from 31.19% in air (240‐15‐air) to 39.25% in H2 (240‐15‐H2). The H2 atmosphere increased the content of hydrocarbons, alcohols, and esters from 69.61% in air (240‐0‐air) to 82.83% in H2 (240‐0‐H2). Overall, temperature, reaction time, atmosphere, and catalyst all significantly influenced the yield and/or quality of bio‐oils from HTL of Chlorella.
In Situ Synthesis of Branched Block Copolymer Assemblies via RAFT Dispersion Polymerization Using Branched Macro‐RAFT Agents†
Authors: Zhao Shanzhi , Zhang Li , Tan Jianbo
Published: January 2023

Comprehensive Summary

Here, we demonstrate the use of branched macromolecular reversible addition‐fragmentation chain transfer (macro‐RAFT) agents in RAFT dispersion polymerization, to access branched block copolymers as well as well‐defined branched block copolymer assemblies. Two types of branched macro‐RAFT agents were first synthesized by using either a monofunctional chain transfer monomer or a difunctional chain transfer monomer in RAFT polymerization, and subsequently utilized in RAFT dispersion polymerization. It was found that only branched macro‐RAFT agents synthesized from the difunctional chain transfer monomer could lead to colloidally stable assemblies with well‐defined morphologies. Reaction conditions including monomer concentration, degree of polymerization (DP) of the core‐forming block, and DP of the solvophilic segment on morphologies of branched block copolymer assemblies were investigated in detail. Size exclusion chromatography (SEC) analysis further confirmed the successful formation of branched block copolymers by using branched macro‐RAFT agents. This work on the synthesis of branched block copolymer assemblies by RAFT dispersion polymerization offers new opportunities for the rational design of polymer assemblies with well‐defined structures.
Phase 1 Clinical Results for NP10679, a pH‐sensitive GluN2B‐selective N‐methyl‐d‐aspartate Receptor Inhibitor
Authors: Zaczek Robert , Traynelis Stephen F. , Dingledine Ray , Koszalka George W. , Laskowitz Daniel T.
Published: January 2023

NP10679 is a context‐dependent and subunit‐selective negative allosteric modulator of N‐methyl‐d‐aspartate (NMDA) receptors. It is a more potent inhibitor of GluN2B‐containing NMDA receptors at the acidic levels of extracellular pH (eg, 6.9) found in the penumbral regions associated with cerebral ischemia than at physiological pH. This property allows NP10679 to act selectively in ischemic tissue while minimizing the nonselective blockade of NMDA receptors in healthy brain, thereby reducing on‐target adverse effects. We report the results of a first‐in‐human pharmacokinetic and safety phase 1 clinical trial in healthy volunteers receiving single or multiple doses of NP10679 (NCT04007263). We found that NP10679 was well‐tolerated and with a half‐life of 20 hours, which is amenable to once per day dosing. The only notable side effect in this clinical trial was modest somnolence at higher doses, atypical in that the subject could easily be aroused. The overall results suggest that NP10679 is a candidate for further development for use in acute brain injury, such as ischemic stroke or aneurysmal subarachnoid hemorrhage, as well as for use in neuropsychiatric indications.
Employee Accommodations
Authors: Lyerly Eric
Published: January 2023

An overview of the key topics faced by disability services providers with citations to noteworthy cases, statutes, regulations, and additional sources.
Prevalence, characteristics and outcomes of older patients with hereditary versus wild‐type transthyretin amyloid cardiomyopathy
Authors: Porcari Aldostefano , Razvi Yousuf , Masi Ambra , Patel Rishi , Ioannou Adam , Rauf Muhammad U. , Hutt David F. , Rowczenio Dorota , Gilbertson Janet , Martinez‐Naharro Ana , Venneri Lucia , Whelan Carol , Lachmann Helen , Wechalekar Ashutosh , Quarta Candida Cristina , Merlo Marco , Sinagra Gianfranco , Hawkins Philip N. , Fontana Marianna , Gillmore Julian D.
Published: January 2023

Aims

Transthyretin amyloid cardiomyopathy (ATTR‐CM) is often assumed to be associated with wild‐type TTR genotype (ATTRwt) in elderly patients (aged ≥70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of transthyretin (TTR) variants among elderly patients diagnosed with ATTR‐CM.

Methods and results

Data from consecutive patients over 70 years of age diagnosed with ATTR‐CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all‐cause mortality. The study population consisted of 2029 patients with ATTR‐CM (median age 79 years at diagnosis, 13.5% females, 80.4% Caucasian). Variant ATTR‐CM (ATTRv‐CM) was diagnosed in 20.7% (n = 421) of the study population of whom 327 (77.7%) carried V122I, 47 (11.2%) T60A, 16 (3.8%) V30M and 31 (7.3%) other pathogenic TTR variants. During a median (range) follow‐up of 29 (12–48) months, ATTRv‐CM was associated with increased all‐cause mortality compared to ATTRwt‐CM, with the poorest survival observed in V122I‐associated ATTRv‐CM (p < 0.001). Univariable and multivariable logistic regression analyses in those with ATTR‐CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p < 0.001), female sex (OR 2.73, p < 0.001), Afro‐Caribbean ethnicity (OR 65.5, p < 0.001), atrial fibrillation (OR 0.65, p = 0.015), ischaemic heart disease (OR 0.54, p = 0.007), peripheral polyneuropathy (OR 5.70, p < 0.001) and orthostatic hypotension (OR 6.29, p < 0.001) to be independently associated with ATTRv‐CM.

Conclusion

Up to 20.7% of elderly patients with ATTR‐CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR‐CM regardless of age.
Use of patient‐reported outcomes in heart failure: from clinical trials to routine practice
Authors: Savarese Gianluigi , Lindenfeld Joann , Stolfo Davide , Adams Kirkwood , Ahmad Tariq , Desai Nihar R. , Ammirati Enrico , Gottlieb Stephen S. , Psotka Mitchell A. , Rosano Giuseppe M.C. , Allen Larry A.
Published: January 2023

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient‐reported outcomes (PROs) aim to switch traditional care to a more patient‐centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care.
Emerging concepts in oligodendrocyte and myelin formation, inputs from the zebrafish model
Authors: Masson Mary‐Amélie , Nait‐Oumesmar Brahim
Published: January 2023

Oligodendrocytes (OLs) are the myelinating cells of the central nervous system (CNS), which are derived from OL precursor cells. Myelin insulates axons allowing the saltatory conduction of action potentials and also provides trophic and metabolic supports to axons. Interestingly, oligodendroglial cells have the capacity to sense neuronal activity, which regulates myelin sheath formation via the vesicular release of neurotransmitters. Neuronal activity‐dependent regulation of myelination is mediated by specialized interaction between axons and oligodendroglia, involving both synaptic and extra‐synaptic modes of communications. The zebrafish has provided key advantages for the study of the myelination process in the CNS. External development and transparent larval stages of this vertebrate specie combined with the existence of several transgenic reporter lines provided key advances in oligodendroglial cell biology, axo‐glial interactions and CNS myelination. In this publication, we reviewed and discussed the most recent knowledge on OL development and myelin formation, with a focus on mechanisms regulating these fundamental biological processes in the zebrafish. Especially, we highlighted the critical function of axons and oligodendroglia modes of communications and calcium signaling in myelin sheath formation and growth. Finally, we reviewed the relevance of these knowledge's in demyelinating diseases and drug discovery of pharmacological compounds favoring myelin regeneration.
Breast and cervical cancer screening rates in student‐run free clinics: A systematic review
Authors: Xiao Sophia Y. , Major Catherine Kendall , O'Connell Katie A. , Lee David , Lin Christine , Sarino Esther , Chen Kevin
Published: January 2023

Objective

To assess rates of breast and cervical cancer screening at student‐run free clinics to understand challenges and strategies for advancing quality and accessibility of women's health screening.

Methods

The authors performed a systematic search of publications in Ovid MEDLINE, PubMed, Web of Science, and Google Scholar databases from database inception to 2020. English‐language publications assessing rates of breast and cervical cancer screening in student‐run free clinics were included.

Structured data extraction was completed for each publication by two reviewers independently. Risk of bias was assessed using a modified Agency for Healthcare Research and Quality checklist. Results were synthesized qualitatively because of study heterogeneity.

Results

Of 3634 references identified, 12 references met study inclusion criteria. The proportion of patients up‐to‐date on breast cancer screening per guidelines ranged from 45% to 94%. The proportion of patients up‐to‐date on cervical cancer screening per guidelines ranged from 40% to 88%.

Conclusion

Student‐run free clinics can match breast and cervical cancer screening rates among uninsured populations nationally, although more work is required to bridge the gap in care that exists for the underinsured and uninsured.
Testing identifying assumptions in bivariate probit models
Authors: Acerenza Santiago , Bartalotti Otávio , Kédagni Désiré
Published: January 2023

This paper considers the bivariate probit model's identifying assumptions: linear index specification, joint normality of errors, instrument exogeneity, and relevance. First, we develop sharp testable equalities that detect all possible observable violations of the assumptions. Second, we propose an easy‐to‐implement testing procedure for the model's validity using existing inference methods for intersection bounds. The test achieves correct empirical size and performs well in detecting violations of the conditions in simulations. Finally, we provide a road map on what to do when the bivariate probit model is rejected, including novel bounds for the average treatment effect that relax the normality assumption.
A new graph parameter to measure linearity
Authors: Charbit Pierre , Habib Michel , Mouatadid Lalla , Naserasr Reza
Published: January 2023

Consider a sequence of Lexicographic Breadth‐First‐Search vertex orderings where each ordering is used to break ties for . Since the total number of vertex orderings of a finite graph is finite, this sequence must end in a cycle of vertex orderings. The possible length of this cycle is the main subject of this work. Intuitively, we prove for graphs with a known notion of linearity (e.g., interval graphs with their interval representation on the real line), this cycle cannot be too big, no matter which vertex ordering we start with. More precisely, it was conjectured by Dusart and Habib that for cocomparability graphs, the size of this cycle is always 2, independent of the starting order. Furthermore Stacho asked whether for arbitrary graphs, the size of such a cycle is always bounded by the asteroidal number of the graph. In this work, while we answer this latter question negatively, we provide support for the conjecture on cocomparability graphs by proving it for the subclass of domino‐free cocomparability graphs. This subclass contains cographs, proper interval, interval and cobipartite graphs. We also provide simpler independent proofs for each of these cases which lead to stronger results on this subclasses.
Preventive effect of tilapia skin collagen hydrolysates on ulcerative colitis mice based on metabonomic and16 S rRNAgene sequencing
Authors: Chen Zhaoni , Nong Yunyuan , Wang Qianyi , Feng Linlin , He Ying , Guo Bingjian , Qin Yuelian , Zhong Xinyu , Qin Jinghua , Wei Jinbin , Dong Min , Pan Shihan , Su Zhiheng
Published: January 2023

BACKGROUND

Tilapia skin collagen hydrolysates (TSCHs) are the product of enzymatic hydrolysis of collagen, which is mainly extracted from tilapia skin. The components of TSCHs have recently been reported to play a preventive role in dextran sulfate sodium (DSS)‐induced ulcerative colitis (UC). However, it has not been illustrated whether TSCHs can prevent against DSS‐induced UC via the gut microbiota and its derived metabolites.

RESULTS

TSCHs are mainly composed of amino acids, which have similar characteristics to collagen, with most having a molecular weight below 5 kDa. In a mouse model of UC, TSCHs had no toxic effect at a dose of 60 g kg−1and could reduce body weight changes, colon length, histopathological changes and score, and the level of the serum inflammatory cytokine interleukin (IL)‐6. Concurrently, 16 S rRNA sequencing showed that TSCHs significantly reduced the abundance of Bacteroidetes and Proteobacteria at the phylum level andnorank_f__MuribaculaceaeandEscherichia‐Shigellaat the genus level, while they increased the abundance of Firmicutes at the phylum level andLachnoclostridium,Allobaculum,Enterorhabdus, andunclassified__f__Ruminococcaceaeat the genus level. Target metabolomic analysis showed that TSCHs elevated the concentration of total acid, acetic acid, propanoic acid, and butanoic acid, but reduced isovaleric acid concentrations. Moreover, Pearson correlation analysis revealed thatAllobaculum,unclassified_Ruminococcaceae, andEnterorhabduswere positively correlated with acetic acid and butyric acid, but notEscherichia‐Shigella.

CONCLUSION

These findings suggest that TSCHs can prevent UC by modulating gut microbial and microbiota‐derived metabolites. © 2023 Society of Chemical Industry.
In vitro Nasodine Can be an Effective Antibiofilm Agent for Biofilms that May Cause CRS
Authors: Hale Samuel J M , Lux Christian A , Kim Raymond , Biswas Kristi , Tucker Simon , Friedland Peter , Mackenzie Brett Wagner , Douglas Richard G
Published: January 2023

Objectives

Bacterial biofilms on the sinonasal mucosa, especially biofilms of Staphylococcus aureus, are associated with greater severity and recalcitrance of chronic rhinosinusitis (CRS). There are few, if any, antibiofilm agents suitable for sinonasal application available for the management of this problem. Nasodine® Nasal Spray (Nasodine) is a 0.5% povidone‐iodine‐based formulation that has been developed for sinonasal application. We investigated the antibiofilm efficacy of Nasodine to determine whether it may be a candidate for the treatment of biofilm‐associated CRS.

Methods

Biofilms of S. aureus ATCC 6538 were grown in vitro using the Centers for Disease Control biofilm reactor. Intact biofilms were treated by immersion in 0.9% saline (control), half concentration Nasodine, or full concentration Nasodine for between 5 min and 6 h. Further biofilm cells were dispersed into suspension then treated for between 30 s and 5 min. Surviving bacteria were then enumerated by culture and counting colonies, and the log10 reduction in viable bacteria was compared with control.

Results

Nasodine demonstrated time and concentration‐dependent bacterial killing against intact biofilm. Statistically significant reductions in viable bacteria from intact biofilms were seen with exposures as brief as 5 min. Nasodine consistently eradicated dispersed biofilm within 1 min.

Conclusion

Nasodine is highly active against biofilms of S. aureus ATCC 6538 in vitro. Biofilm killing is impeded by the presence of the intact biofilm structure.

Lay summary:

In chronic rhinosinusitis (CRS), bacterial communities called biofilms are associated with more severe inflammation. An iodine‐based nasal spray called Nasodine almost completely eradicates bacterial biofilms after 6 h of exposure. Nasodine may be useful for treating CRS. Laryngoscope, 133:2490–2495, 2023
Functional and Symmetry Outcomes After Forehead Flap Reconstruction of Medial Peri‐Ocular Defects
Authors: Agarwal Aarti , Philips Ramez , Landers Kathryn , Savitch Samantha , Barbarite Eric , Krein Howard , Heffelfinger Ryan
Published: January 2023

Background

Orbital defects have a profound impact on orbital function and symmetry of the face and are difficult to reconstruct given the complexity of this area. The paramedian forehead flap (PMFF) has not been well studied in reconstruction of orbital defects.

Methods

Retrospective review of patients who underwent reconstruction of periorbital defects with PMFF between 2016 and 2021. Variables were ocular adnexal asymmetry, functional outcomes, and orbital complications.

Results

Eighteen patients met inclusion criteria. Mean defect size was 11.1 ± 7.5 cm. The most common subsite involved was medial canthus in 88.9% of patients. There was no statistically significant difference between mean medial canthus to midline ratio and mean medial brow to midline ratio when compared to the assumed normal of 1. The medial canthus to pupil ratio and medial canthus to lateral canthus ratio had a statistically significant mean difference from 1.0 (p = 0.003 for both). In 22.2% of patients, the orbit was functional with impairment; the remaining had no impairment. Surgical sequelae occurred in 12/18 (66.7%) of patients, most commonly epiphora in 9/18 (50%) of patients, and ectropion in 5/18 (27.7%).

Conclusion

The PMFF is feasible for medial periorbital reconstruction with acceptable functional and symmetrical outcomes and low morbidity.

Level of Evidence

4 Laryngoscope, 133:2584–2589, 2023
Featured Front Cover
Authors: Pricope Narcisa G. , Daldegan Gabriel A. , Zvoleff Alex , Mwenda Kevin M. , Noon Monica , Lopez‐Carr David
Published: January 2023

The cover image is based on the Research Article Operationalizing an integrative socio‐ecological framework in support of global monitoring of land degradation by Narcisa G. Pricope et al., https://doi.org/10.1002/ldr.4447.

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What Is Hemidystonia?
Authors: Vizcarra Joaquin A. , Jinnah Hyder A.
Published: January 2023

Background

Hemidystonia is defined as dystonia restricted to one side of the body. It is traditionally believed to result from a lesion in the contralateral hemisphere.

Objectives

To describe a series of hemidystonia patients without lesions on brain imaging.

Methods

We searched for individuals with potential hemidystonia who were included in the Dystonia Coalition or Movement Disorder Society Genetic mutation database (MDSgene), and conducted a systematic review.

Results

We found 10 individuals classified as hemidystonia or with homolateral limb dystonia among 3696 cases enrolled by the Dystonia Coalition, 9 cases in MDSgene, and one idiopathic case in the literature. None had evidence of a brain lesion. Body distributions used to define hemidystonia varied considerably and were not always restricted to one side of the body.

Conclusions

Hemidystonia may be idiopathic or genetic, without any obvious brain lesion. The varied use of the term suggests the need for more specific clinical criteria to define “half the body.”
A high‐gain quasi‐Yagi antenna using nested metaresonator structures
Authors: Turan Goksel , Odabasi Hayrettin
Published: January 2023

This article proposes a high‐gain quasi‐Yagi antenna using nested metaresonator structures with a systematic design approach. The nested metaresonators are used as a director element instead of conventional strip directors. The gain enhancement of the proposed antenna is based on strong electromagnetic coupling between the driver and metaresonator director elements. The proposed antenna has a gain of 7.6–9 dBi with a bandwidth of 8.6% between 2.43 and 2.65 GHz ( dB). It achieves a maximum gain increase of 4 dBi compared to the conventional quasi‐Yagi antenna and 2 dBi compared to the four‐director quasi‐Yagi antenna. The proposed antenna can be used for wireless communication applications that require high gain.
Extracellular vesicles: Focus on peri‐implantation period of pregnancy in pigs
Authors: Guzewska Maria M. , Szuszkiewicz Joanna , Kaczmarek Monika M.
Published: January 2023

The establishment of cell‐to‐cell communication between the endometrium and the developing embryo is the most important step in successful mammalian pregnancy. Close interaction between the uterine luminal epithelium and trophoblast cells requires triggering timely molecular dialog for successful maternal recognition of pregnancy, embryo implantation, and placenta development. Quite recently, extracellular vesicles (EVs) carrying unique molecular cargo emerged as evolutionarily conserved mediators of cell‐to‐cell communication during early pregnancy. To date, the presence of EVs at the embryo–maternal interface has been demonstrated in numerous mammals, including domestic livestock, such as pigs. However, few studies have focused on revealing the mechanism of EV‐mediated crosstalk between developing early embryos and receptive endometrium. Over the past years, it has appeared that understanding the role of EVs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes current knowledge of EVs, specifically in relation to the peri‐implantation period in pigs, characterized by common features of embryo implantation and high embryonic mortality in mammals.
Nonconvex optimization for third‐order tensor completion under wavelet transform
Authors: Yu Quan , Bai Minru
Published: January 2023

The main aim of this paper is to develop a nonconvex optimization model for third‐order tensor completion under wavelet transform. On the one hand, through wavelet transform of frontal slices, we divide a large tensor data into a main part tensor and three detail part tensors, and the elements of these four tensors are about a quarter of the original tensors. Solving these four small tensors can not only improve the operation efficiency, but also better restore the original tensor data. On the other hand, by using concave correction term, we are able to correct for low rank of tubal nuclear norm (TNN) data fidelity term and sparsity of ‐norm data fidelity term. We prove that the proposed algorithm can converge to some critical point. Experimental results on image, magnetic resonance imaging and video inpainting tasks clearly demonstrate the superior performance and efficiency of our developed method over state‐of‐the‐arts including the TNN and other methods.