bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractConstant‐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

AbstractPremisePetal 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.MethodsOur 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.ResultsWe 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.DiscussionThis 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

AbstractIn 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

AbstractDuring 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

AbstractStatistical 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

AbstractWhen 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

AbstractFor 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

AbstractObjectiveStudies 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.MethodsA 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.ResultsThe 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.ConclusionA 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

AbstractHydrothermal 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 SummaryHere, 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

AbstractNP10679 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.
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

AimsTransthyretin 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 resultsData 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.ConclusionUp 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

AbstractHeart 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.