bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning algorithms can more efficiently predict biochemical recurrence after robot‐assisted radical prostatectomy
Authors: Ekşi Mithat , Evren İsmail , Akkaş Fatih , Arıkan Yusuf , Özdemir Osman , Özlü Deniz N. , Ayten Ali , Sahin Selcuk , Tuğcu Volkan , Taşçı Ali İ.
Published: July 2021

Objectives

To develop a model for predicting biochemical recurrence (BCR) in patients with long follow‐up periods using clinical parameters and the machine learning (ML) methods.

Materials Method

Patients who underwent robot‐assisted radical prostatectomy between January 2014 and December 2019 were retrospectively reviewed. Patients who did not have BCR were assigned to Group 1, while those diagnosed with BCR were assigned to Group 2. The patient's demographic data, preoperative and postoperative parameters were all recorded in the database. Three different ML algorithms were employed: random forest, K‐nearest neighbour, and logistic regression.

Results

Three hundred and sixty‐eight patients were included in this study. Among these patients, 295 (80.1%) did not have BCR (Group 1), while 73 (19.8%) had BCR (Group 2). The mean duration of follow‐up and duration until the diagnosis of BCR was calculated as 35.2 ± 16.7 and 11.5 ± 11.3 months, respectively. The multivariate analysis revealed that NLR, PSAd, risk classification, PIRADS score, T stage, presence or absence of positive surgical margin, and seminal vesicle invasion were predictive for BCR. Classic Cox regression analysis had an area under the curve (AUC) of 0.915 with a sensitivity and specificity of 90.6% and 79.8%. The AUCs for receiver‐operating characteristic curves for random forest, K nearest neighbour, and logistic regression were 0.95, 0.93, and 0.93, respectively. All ML models outperformed the conventional statistical regression model in the prediction of BCR after prostatectomy.

Conclusion

The construction of more reliable and potent models will provide the clinicians and patients with advantages such as more accurate risk classification, prognosis estimation, early intervention, avoidance of unnecessary treatments, relatively lower morbidity and mortality. The ML methods are cheap, and their powers increase with increasing data input; we believe that their clinical use will increase over time.
Evaluating aminophylline and progesterone combination treatment to modulate contractility and labor‐related proteins in pregnant human myometrial tissues
Authors: Lai Pei F. , Young Roger C. , Tribe Rachel M. , Johnson Mark R.
Published: July 2021

Progesterone (P4) and cyclic adenosine monophosphate (cAMP) are regarded as pro‐quiescent factors that suppress uterine contractions during pregnancy. We previously used human primary cells in vitro and mice in vivo to demonstrate that simultaneously enhancing myometrial P4 and cAMP levels may reduce inflammation‐associated preterm labor. Here, we assessed whether aminophylline (Ami; phosphodiesterase inhibitor) and P4 can reduce myometrial contractility and contraction‐associated proteins (CAPs) better together than individually; both agents are clinically used drugs. Myometrial tissues from pregnant non‐laboring women were treated ex vivo with Ami acutely (while spontaneous contracting) or throughout 24‐h tissue culture (±P4); isometric tension measurements, PKA assays, and Western blotting were used to assess tissue contractility, cAMP action, and inflammation. Acute (1 h) treatment with 250 and 750 μM Ami reduced contractions by 50% and 84%, respectively, which was not associated with a directly proportional increase in whole tissue PKA activity. Sustained myometrial relaxation was observed during 24‐h tissue culture with 750 μM Ami, which did not require P4 nor reduce CAPs. COX‐2 protein can be reduced by 300 nM P4 but this did not equate to myometrial relaxation. Ami (250 μM) and P4 (100 and 300 nM) co‐treatment did not prevent oxytocin‐augmented contractions nor reduce CAPs during interleukin‐1β stimulation. Overall, Ami and P4 co‐treatment did not suppress myometrial contractions more than either agent alone, which may be attributed to low specificity and efficacy of Ami; cAMP and P4 action at in utero neighboring reproductive tissues during pregnancy should also be considered.
Whole genome sequencing and bulked segregant analysis suggest a new mechanism of amitraz resistance in the citrus red mite, Panonychus citri (Acari: Tetranychidae)
Authors: Yu Shi‐Jiang , Cong Lin , Pan Qi , Ding Li‐Li , Lei Shuang , Cheng Lu‐Yan , Fang Yun‐Hong , Wei Zhi‐Tang , Liu Hao‐Qiang , Ran Chun
Published: July 2021

BACKGROUND

Amitraz is a broad‐spectrum insecticide/acaricide for the control of aphids, psyllids, ticks and mites. Current evidence suggests that ticks and phytophagous mites have developed strong resistance to amitraz. Previous studies have shown that multiple mechanisms are associated with amitraz resistance in ticks, but very few reports have involved Panonychus citri. We therefore used whole genome sequencing and bulked segregant analysis (BSA) to identify the mechanism underlying P. citri's resistance to amitraz.

RESULTS

High‐quality assembly of the whole P. citri genome was completed, resulting in a genome of approximately 83.97 Mb and a contig N50 of approximately 1.81 Mb. Gene structure predictions revealed 11 577 genes, of which 10 940 genes were annotated. Trait‐associated regions in the genome were mapped with bulked segregant analysis and 38 candidate SNPs were obtained, of which T752C had the strongest correlation with the resistant trait, located at the 5′ untranslated region (UTR) of the β‐2R adrenergic‐like octopamine receptor gene. The mutation resulted in the formation of a short hairpin loop structure in mRNA and gene expression was down‐regulated by more than 50% in the amitraz‐resistant strain. Validation of the T752C mutation in field populations of P. citri found that the correlation between the resistance ratio and the base mutation was 94.40%.

CONCLUSION

Our results suggest that this 5′ UTR mutation of the β‐2R octopamine receptor gene, confers amitraz resistance in P. citri. This discovery provides a new explanation for the mechanism of pest resistance: base mutations in the 5′ untranslated region of target gene may regulate the susceptibility of pests to pesticides.
Anomalous Thermoelectric Transport Properties of Fe‐Rich Magnetic FeTe
Authors: Polash Md Mobarak Hossain , Vashaee Daryoosh
Published: July 2021

The interplay between magnetism and quantum effects has motivated several thermoelectric studies on iron‐telluride yet with little insight on the anomalous features in transport properties near magnetostructural transition temperature (≈70 K). A detailed investigation is carried out on Fe1.1Te by characterizing magnetic, heat capacity, galvanomagnetic, and thermoelectric transport properties to understand the electronic, magnetic, and structural origin of those anomalies. The magnetic susceptibility indicates a bicollinear stripe and short‐range ordering in the antiferromagnetic and paramagnetic domains, respectively. Hall conductivity and transverse magnetoresistance reveal a multicarrier transport impacted by spin fluctuations and magnons. Contributions from phonon‐drag and magnon‐drag are evaluated to understand the origin of the broad peak in antiferromagnetic thermopower. The peak at ≈50 K and the insignificant entropy contribution from the magnonic heat capacity support the phonon‐drag as the origin. The field‐dependent enhancement of thermal conductivity must be associated with field‐dependent spin‐phonon coupling modification. The field‐induced thermopower reduction can be attributed to the suppression of magnons or paramagnons, as evidenced by the magnetic susceptibility data. Above 70 K, the thermal conductivity drops sharply due to the structural change modifying phonon modes. Understanding these properties originated from the spin, and quantum effects are instrumental for designing high‐performance spin‐driven thermoelectrics.
Ontogenetic dependence of Nile crocodile (Crocodylus niloticus) isotope diet‐to‐tissue discrimination factors
Authors: Woodborne Stephan , Botha Hannes , Huchzermeyer David , Myburgh Jan , Hall Grant , Myburgh Albert
Published: July 2021

Rationale

The diet of wild Nile crocodiles (Crocodylus niloticus) is difficult to assess because they are cryptic and nocturnal predators that are extremely sensitive to disturbance by observers, and stomach content analysis is challenging, especially in large specimens. Stable light isotope analysis provides a means of assessing their diet, but diet‐to‐tissue discrimination factors have yet to be established for the species.

Methods

Isotope ratio (15N/14N and 13C/12C expressed as δ15N and δ13C) analyses of scutes, claws, and blood of farmed crocodiles of different sizes were compared with the isotope values of their lifelong diet, which comprises chickens from a single supplier.

Results

Systematic size dependence in the diet‐to‐tissue discrimination factors for scute collagen, scute keratin, and claw keratin is described in regression relationships against the snout to vent length. Fixed values are presented for erythrocytes and blood plasma because blood was not sampled from juveniles.

Conclusions

The diet‐to‐tissue discrimination factors help assess the diet of wild crocodiles. The diet of crocodiles from Lake Flag Boshielo shows a clear ontogenic shift, as has been seen in other studies, and the results strongly indicate a dependence on the terrestrial food web rather than a fish diet. That this population may exploit a terrestrial diet highlights potential conflicts for conserving Nile crocodiles outside protected areas.
Distributed consensus for multi‐agent systems via adaptive sliding mode control
Authors: Yu Zhiyong , Yu Shuzhen , Jiang Haijun , Hu Cheng
Published: July 2021

This article considers the consensus of multi‐agent systems (MASs) with external disturbances by using sliding mode control. First, by establishing a novel sliding mode surface and designing a sliding mode control protocol with constant gains, the consensus of MASs with unknown bounded disturbances is studied. Second, based on the barrier function, a new type of adaptive sliding mode switching protocol is proposed, in which the control gains can be chosen randomly and the upper bound of the disturbance does not need to be known in a prior. By using this protocol, the consensus error can converge to any given region of zero in finite time. Moreover, the leaderless consensus and leader‐following tracking problem of MASs with general dynamics and external disturbances are also investigated via extending the proposed adaptive sliding mode protocol. Finally, some examples are presented to illustrate the effectiveness of the control strategies.
Animal‐human two‐shot images: Their out‐of‐context interpretation and the implications for zoo and conservation settings
Authors: Spooner Sarah Louise , Stride Jessica Rachael
Published: July 2021

Images containing both animals and humans (two‐shot images) are popular across social media and zoo advertising. However, these images, even when taken in ethical and conservation settings, have the potential for misinterpretation and may inadvertently promote the illegal wildlife trade, exotic pet trade or photo‐prop industries. We examined whether zoo visitors' (n = 531) attitudes and stated Willingness to Donate (WTD) altered depending on whether they viewed a two‐shot image set in a photo‐prop setting (typically associated with negative welfare) or in a zoo or wild setting. All images, including photo‐prop, were generally viewed positively regardless of context. Zoo‐based images received a greater number of comments relating to concern for the animal's environment or welfare compared to other images, although numbers were still relatively low. This indicates a lack of awareness about the photo‐prop industry and misconceptions about modern welfare practices in zoos, thus reflecting a need for improved education in these areas. Two‐shot images in zoo settings elicited significantly higher stated WTD than images in wild or photo‐prop settings or when an animal was pictured alone. Suggesting zoo‐based images may be more effective for conservation campaigns than traditional images of an animal in its environment. Furthermore, images featuring a uniformed keeper plus an animal do not appear to increasing desire for pet ownership, indicating that they can be used in zoo advertising with minimal negative consequences.
Explorable Uncertainty in Scheduling with Non-uniform Testing Times
Authors: Albers Susanne , Eckl Alexander
Published: July 2021

The problem of scheduling with testing in the framework of explorable uncertainty models environments where some preliminary action can influence the duration of a task. In the model, each job has an unknown processing time that can be revealed by running a test. Alternatively, jobs may be run untested for the duration of a given upper limit. Recently, Dürr et al. [4] have studied the setting where all testing times are of unit size and have given lower and upper bounds for the objectives of minimizing the sum of completion times and the makespan on a single machine. In this paper, we extend the problem to non-uniform testing times and present the first competitive algorithms. The general setting is motivated for example by online user surveys for market prediction or querying centralized databases in distributed computing. Introducing general testing times gives the problem a new flavor and requires updated methods with new techniques in the analysis. We present constant competitive ratios for the objective of minimizing the sum of completion times in the deterministic case, both in the non-preemptive and preemptive setting. For the preemptive setting, we additionally give a first lower bound. We also present a randomized algorithm with improved competitive ratio. Furthermore, we give tight competitive ratios for the objective of minimizing the makespan, both in the deterministic and the randomized setting.
On analytic bootstrap for interface and boundary CFT
Authors: Dey Parijat , Söderberg Alexander
Published: July 2021

Abstract

We use analytic bootstrap techniques for a CFT with an interface or a boundary. Exploiting the analytic structure of the bulk and boundary conformal blocks we extract the CFT data. We further constrain the CFT data by applying the equation of motion to the boundary operator expansion. The method presented in this paper is general, and it is illustrated in the context of perturbative Wilson-Fisher theories. In particular, we find constraints on the OPE coefficients for the interface CFT in 4 − ϵ dimensions (upto order $$ \mathcal{O} $$
O
(ϵ2)) with ϕ4-interactions in the bulk. We also compute the corresponding coefficients for the non-unitary ϕ3-theory in 6 − ϵ dimensions in the presence of a conformal boundary equipped with either Dirichlet or Neumann boundary conditions upto order $$ \mathcal{O} $$
O
(ϵ), or an interface upto order $$ \mathcal{O}\left(\sqrt{\epsilon}\right) $$
O

ϵ

.
Krylov improvements of the Uzawa method for Stokes type operator matrices
Authors: Axelsson Owe , Karátson János
Published: July 2021

The paper is devoted to Krylov type modifications of the Uzawa method on the operator level for the Stokes problem in order to accelerate convergence. First block preconditioners and their effect on convergence are studied. Then it is shown that a Krylov–Uzawa iteration produces superlinear convergence on smooth domains, and estimation is given on its speed.
A three-dimensional numerical analysis of moisture flow in wood and of the wood’s hygro-mechanical and visco-elastic behaviour
Authors: Florisson Sara , Vessby Johan , Ormarsson Sigurdur
Published: July 2021

A three-dimensional numerical model was employed in simulating nonlinear transient moisture flow in wood and the wood’s hygro-mechanical and visco-elastic behaviour under such conditions. The model was developed using the finite element software Abaqus FEA®, while taking account of the fibre orientation of the wood. The purpose of the study was to assess the ability of the model to simulate the response of wood beams to bending and to the climate of northern Europe. Four-point bending tests of small and clear wood specimens exposed to a constant temperature and to systematic changes in relative humidity were conducted to calibrate the numerical model. A validation of the model was then performed on the basis of a four-point bending test of solid timber beams subjected to natural climatic conditions but sheltered from the direct effects of rain, wind and sunlight. The three-dimensional character of the model enabled a full analysis of the effects of changes in moisture content and in fibre orientation on stress developments in the wood. The results obtained showed a clear distinction between the effects of moisture on the stress developments caused by mechanical loads and the stress developments caused solely by changes in climate. The changes in moisture that occurred were found to have the strongest effect on the stress state that developed in areas in which the tangential direction of the material was aligned with the exchange surface of the beams. Such areas were found to be exposed to high-tension stress during drying and to stress reversal brought about by the uneven drying and shrinkage differences that developed between the outer surface and the inner sections of the beams.
Effects of moisture and cellulose fibril angle on the tensile properties of native single Norway spruce wood fibres
Authors: Horbelt Nils , Dunlop John W. C. , Bertinetti Luca , Fratzl Peter , Eder Michaela
Published: July 2021

Isolated single wood fibres with cellulose fibril angles from 10 to 43° were tested in microtensile tests under controlled temperature and relative humidity of 5, 50, 75, 90% and in the wet state. This systematic study provides experimental stiffness and strength data, calculated on cell wall cross sections. It has been shown that stiffness reduction with increasing moisture content is more pronounced in fibres with large cellulose fibril angles. Interestingly, stiffness reduction in fibres with low cellulose fibril angles has been observed for the fully hydrated state only. The experimental dataset was fed into a model to determine moisture dependent stiffness of the hemicellulose-lignin-matrix and the stresses acting on the fibrils and the matrix.
Correction to: Gadoxetic acid‑enhanced MRI in primary sclerosing cholangitis: added value in assessing liver function and monitoring disease progression
Authors: Elkilany Aboelyazid , Geisel Dominik , Müller Tobias , Fischer Andreas , Denecke Timm
Published: July 2021

A correction to this paper has been published: https://doi.org/10.1007/s00261-021-03155-z
Quantitative CT perfusion imaging in patients with pancreatic cancer: a systematic review
Authors: Perik T. H. , van Genugten E. A. J. , Aarntzen E. H. J. G. , Smit E. J. , Huisman H. J. , Hermans J. J.
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can provide additional diagnostic information compared to the limited accuracy of the current standard, contrast-enhanced CT (CECT). This systematic review evaluates CTP for diagnosis, grading, and treatment assessment of PDAC. The secondary goal is to provide an overview of scan protocols and perfusion models used for CTP in PDAC. The search strategy combined synonyms for ‘CTP’ and ‘PDAC.’ Pubmed, Embase, and Web of Science were systematically searched from January 2000 to December 2020 for studies using CTP to evaluate PDAC. The risk of bias was assessed using QUADAS-2. 607 abstracts were screened, of which 29 were selected for full-text eligibility. 21 studies were included in the final analysis with a total of 760 patients. All studies comparing PDAC with non-tumorous parenchyma found significant CTP-based differences in blood flow (BF) and blood volume (BV). Two studies found significant differences between pathological grades. Two other studies showed that BF could predict neoadjuvant treatment response. A wide variety in kinetic models and acquisition protocol was found among included studies. Quantitative CTP shows a potential benefit in PDAC diagnosis and can serve as a tool for pathological grading and treatment assessment; however, clinical evidence is still limited. To improve clinical use, standardized acquisition and reconstruction parameters are necessary for interchangeability of the perfusion parameters.

Graphic abstract
Aerofoil self-noise radiations subjected to serration flap angles
Authors: Woodhead P. C. , Chong T. P. , Joseph P. F. , Vathylakis A.
Published: July 2021

Besides the investigation of the aeroacoustics responses of an asymmetric aerofoil subjected to serrated trailing edge flap angles from negative (flap-down) to positive (flap-up), this paper also provides a new perspective on the physical mechanisms of broadband noise reduction by a serrated trailing edge. The blade-loading effect, which is a function of the length and flap angle for a straight/non-serrated trailing edge flat plate, plays a considerable role in the self-noise radiation that is hitherto less recognised. When the same trailing edge flat plate is cut into a sawtooth serration shape, the self-noise reduction will be underpinned simultaneously by both the serration effect (dominant) and the blade-loading effect. The results demonstrate that the far-field radiation of a serrated aerofoil can be manipulated significantly depending on the direction of the flap angle. In the flap-down configuration, the blade-loading will become a negative factor that causes a deterioration of the noise reduction performance across the entire frequency range. In the flap-up configuration, three spectral frequencies zones can be defined. At the low-frequency zone, the diminished cross-flow at the sawtooth gaps will impede the noise reduction capability. At the central-frequency zone, the re-distribution of the turbulence sources and reduction in the turbulence spanwise length scales will enhance the noise reduction performance. Improvement in the noise performance can also be achieved at the high-frequency zone owing to the lack of interaction between the cross-flow and sawtooth structure. A new concept is positively demonstrated by varying the serration flap angle as a periodic function across the spanwise direction (spanwise wavy serration). When compared to a non-flap serrated trailing edge, the spanwise wavy serration is found to further increase the noise reduction level between the central and high-frequency regions.

Graphic abstract
Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement
Authors: Piazza Cesare , Paderno Alberto , Sjogren Elisabeth V. , Bradley Patrick J. , Eckel Hans E. , Mäkitie Antti , Matar Nayla , Paleri Vinidh , Peretti Giorgio , Puxeddu Roberto , Quer Miquel , Remacle Marc , Vander Poorten Vincent , Vilaseca Isabel , Simo Ricard
Published: July 2021

Purpose

To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT].

Methods

Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process.

Results

The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up.

Conclusion

Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented.
An unusual suicide by self-waterboarding: forensic pathological issues
Authors: Galante Nicola , Terzi Marco , Gentile Guendalina , Tambuzzi Stefano , Zoja Riccardo
Published: July 2021

The authors present the first case, to the best of our knowledge, of a preplanned suicide by self-waterboarding. Waterboarding (WB) is a military method of torture in which water is poured into the nostrils and the mouth of a victim, to evoke the sensation of asphyxiation by drowning. The victim was a 22-year-old male student, who was found dead and naked in the bathtub. His head was covered by a soaked canvas bag, and his hands were tied with two nylon ropes and a padlock. The water jet of the showerhead was specifically directed at the victim’s head, so that the canvas bag could be soaked with water. The cause of death was defined as the combination of asphyxiation by drowning with the direct suffocation provoked by the soaked canvas bag in the context of the waterboarding practice. Finally, the authors discuss the differential diagnosis regarding the modality (suicide versus homicide) through which this case of waterboarding was performed. The case is intended to be used as source data for similar forensic cases, where a multidisciplinary approach is advisable in such complex cases.
Cadaver surgical training in Japan: its past, present, and ideal future perspectives
Authors: Shichinohe Toshiaki , Kobayashi Eiji
Published: July 2021

The framework for cadaver surgical training (CST) in Japan was established in 2012, based on the “Guidelines for Cadaver Dissection in Education and Research of Clinical Medicine” of the Japan Surgical Society (JSS) and the Japanese Association of Anatomists. Subsequently, the Ministry of Health, Labor and Welfare allocated funding from its budget for CST. By 2019, CST was being practiced in 33 medical schools and universities. Currently, the CST Promotion Committee of the JSS reviews each CST report submitted by medical schools and universities and provides guidance based on professional autonomy. This paper outlines the history of CST in Japan and presents a plan for its future. To sustain and oversee CST implementation, an operating organization, funded by stakeholders, such as government agencies, academic societies, and private companies, is needed.
Milestones in genetics of cerebellar ataxias
Authors: Krygier Magdalena , Mazurkiewicz-Bełdzińska Maria
Published: July 2021

Cerebellar ataxias (CAs) comprise a group of rare, neurological disorders characterized by extensive phenotypic and genetic heterogeneity. The core clinical feature is the cerebellar syndrome, which is often accompanied by other neurological or non-neurological signs. In the last 30 years, our understanding of the CA etiology has increased significantly, and numerous ataxia-associated genes have been discovered. Conventional variants or tandem repeat expansions, localized in the coding or non-coding DNA sequences, lead to hereditary ataxia, which can display different patterns of inheritance. Advances in molecular techniques have enabled a rapid and cost-effective detection of causative variants in a significant number of CA patients. However, despite performing extensive investigations, a definite diagnosis is still unknown in the majority of affected individuals. In this review, we discuss the major advances in the genetics of CAs over the last 30 years, focusing on the impact of next-generation sequencing on the genetic landscape of childhood- and adult-onset CAs. Additionally, we outline possible directions for further genetic research in hereditary and sporadic CAs in the era of increasing application of whole-genome sequencing and genome-wide association studies in various neurological disorders.
Correction to: Neck cooling induces blood pressure increase and peripheral vasoconstriction in healthy persons
Authors: Koehn Julia , Wang Ruihao , de Rojas Leal Carmen , Kallmünzer Bernd , Winder Klemens , Köhrmann Martin , Kollmar Rainer , Schwab Stefan , Hilz Max J.
Published: July 2021

A Correction to this paper has been published: https://doi.org/10.1007/s10072-021-05355-3
Activation of AQP2 water channels by protein kinase A: therapeutic strategies for congenital nephrogenic diabetes insipidus
Authors: Ando Fumiaki
Published: July 2021

Background

Congenital nephrogenic diabetes insipidus (NDI) is primarily caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R). Renal unresponsiveness to the antidiuretic hormone vasopressin impairs aquaporin-2 (AQP2) water channel activity and water reabsorption from urine, resulting in polyuria. Currently available symptomatic treatments inadequately reduce patients’ excessive amounts of urine excretion, threatening their quality of life. In the past 25 years, vasopressin/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) has been believed to be the most important signaling pathway for AQP2 activation. Although cAMP production without vasopressin is the reasonable therapeutic strategy for congenital NDI caused by V2R mutations, the efficacy of candidate drugs on AQP2 activation is far less than that of vasopressin.

Results

Intracellular distribution and activity of PKA are largely controlled by its scaffold proteins, A-kinase anchoring proteins (AKAPs). Dissociating the binding of AKAPs and PKA significantly increased PKA activity in the renal collecting ducts and activated AQP2 phosphorylation and trafficking. Remarkably, the AKAPs–PKA disruptor FMP-API-1 increased transcellular water permeability in isolated renal collecting ducts to the same extent as vasopressin. Moreover, derivatives of FMP-API-1 possessed much more high potency. FMP-API-1/27 is the first low-molecular-weight compound to be discovered that can phosphorylate AQP2 more effectively than preexisting drug candidates.

Conclusion

AKAP-PKA disruptors are a promising therapeutic target for congenital NDI. In this article, we shall discuss the pathophysiological roles of PKA and novel strategies to activate PKA in renal collecting ducts.
Strategy for fast manufacturing of 3D hydrodynamic focusing multilayer microfluidic chips and its application for flow-based synthesis of gold nanoparticles
Authors: Wang Yanwei , Seidel Michael
Published: July 2021

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.
Vagueness in Medicine: On Disciplinary Indistinctness, Fuzzy Phenomena, Vague Concepts, Uncertain Knowledge, and Fact-Value-Interaction
Authors: Hofmann Bjørn
Published: July 2021

This article investigates five kinds of vagueness in medicine: disciplinary, ontological, conceptual, epistemic, and vagueness with respect to descriptive-prescriptive connections. First, medicine is a discipline with unclear borders, as it builds on a wide range of other disciplines and subjects. Second, medicine deals with many indistinct phenomena resulting in borderline cases. Third, medicine uses a variety of vague concepts, making it unclear which situations, conditions, and processes that fall under them. Fourth, medicine is based on and produces uncertain knowledge and evidence. Fifth, vagueness emerges in medicine as a result of a wide range of fact-value-interactions. The various kinds of vagueness in medicine can explain many of the basic challenges of modern medicine, such as overdiagnosis, underdiagnosis, and medicalization. Even more, it illustrates how complex and challenging the field of medicine is, but also how important contributions from the philosophy can be for the practice of medicine. By clarifying and, where possible, reducing or limiting vagueness, philosophy can help improving care. Reducing the various types of vagueness can improve clinical decision-making, informing individuals, and health policy making.
Toward autonomous robotic prostate biopsy: a pilot study
Authors: Maris Bogdan , Tenga Chiara , Vicario Rudy , Palladino Luigi , Murr Noe , De Piccoli Michela , Calanca Andrea , Puliatti Stefano , Micali Salvatore , Tafuri Alessandro , Fiorini Paolo
Published: July 2021

Purpose

We present the validation of PROST, a robotic device for prostate biopsy. PROST is designed to minimize human error by introducing some autonomy in the execution of the key steps of the procedure, i.e., target selection, image fusion and needle positioning. The robot allows executing a targeted biopsy through ultrasound (US) guidance and fusion with magnetic resonance (MR) images, where the target was defined.

Methods

PROST is a parallel robot with 4 degrees of freedom (DOF) to orient the needle and 1 DOF to rotate the US probe. We reached a calibration error of less than 2 mm, computed as the difference between the needle positioning in robot coordinates and in the US image. The autonomy of the robot is given by the image analysis software, which employs deep learning techniques, the integrated image fusion algorithms and automatic computation of the needle trajectory. For safety reasons, the insertion of the needle is assigned to the doctor.

Results

System performance was evaluated in terms of positioning accuracy. Tests were performed on a 3D printed object with nine 2-mm spherical targets and on an anatomical commercial phantom that simulates human prostate with three lesions and the surrounding structures. The average accuracy reached in the laboratory experiments was $$ 1.30 \pm 0.44\, \text {mm}$$

1.30
±
0.44

mm

in the first test and $$ 1.54 \pm 0.34\, \text {mm}$$

1.54
±
0.34

mm

in the second test.

Conclusions

We introduced a first prototype of a prostate biopsy robot that has the potential to increase the detection of clinically significant prostate cancer and, by including some level of autonomy, to simplify the procedure, to reduce human errors and shorten training time. The use of a robot for the biopsy of the prostate will create the possibility to include also a treatment, such as focal ablation, to be delivered through the same system.
A systematic review on AI/ML approaches against COVID-19 outbreak
Authors: Dogan Onur , Tiwari Sanju , Jabbar M. A. , Guggari Shankru
Published: July 2021

A pandemic disease, COVID-19, has caused trouble worldwide by infecting millions of people. The studies that apply artificial intelligence (AI) and machine learning (ML) methods for various purposes against the COVID-19 outbreak have increased because of their significant advantages. Although AI/ML applications provide satisfactory solutions to COVID-19 disease, these solutions can have a wide diversity. This increase in the number of AI/ML studies and diversity in solutions can confuse deciding which AI/ML technique is suitable for which COVID-19 purposes. Because there is no comprehensive review study, this study systematically analyzes and summarizes related studies. A research methodology has been proposed to conduct the systematic literature review for framing the research questions, searching criteria and relevant data extraction. Finally, 264 studies were taken into account after following inclusion and exclusion criteria. This research can be regarded as a key element for epidemic and transmission prediction, diagnosis and detection, and drug/vaccine development. Six research questions are explored with 50 AI/ML approaches in COVID-19, 8 AI/ML methods for patient outcome prediction, 14 AI/ML techniques in disease predictions, along with five AI/ML methods for risk assessment of COVID-19. It also covers AI/ML method in drug development, vaccines for COVID-19, models in COVID-19, datasets and their usage and dataset applications with AI/ML.
DRAC: a delta recurrent neural network-based arithmetic coding algorithm for edge computing
Authors: Shan Bowei , Fang Yong
Published: July 2021

This paper develops an arithmetic coding algorithm based on delta recurrent neural network for edge computing devices called DRAC. Our algorithm is implemented on a Xilinx Zynq 7000 Soc board. We evaluate DRAC with four datasets and compare it with the state-of-the-art compressor DeepZip. The experimental results show that DRAC outperforms DeepZip and achieves 5X speedup ratio and 20X power consumption saving.
Can Person-Centred, Strength Based Programmes Impact on Parents’ Engagement in Education?
Authors: Wilson Suzanne
Published: July 2021

Parental responsibility is often the focus of research and policy surrounding closing the attainment gap between low-income students and their wealthier peers. This article describes a pilot intervention programme which aimed to enable better parental support of their children with their schoolwork and educational engagement. Through interviews with the parents and facilitators involved with the pilot, this article provides an example of how strength-based interventions can promote parental engagement in education in marginalised groups, such as families considered disadvantaged. The programme consisted of six one-to-one sessions with 25 parents. Semi-structured interviews with five parents and four facilitators revealed that parents reported increased self-efficacy and confidence in supporting their children’s education. Key features of the programme contributing to sustainable changes were the programmes person-centred approach and the use of strength-based strategies. The qualitative analysis provides only short-term accounts of behavioral change, but despite these shortcomings the results provide tentative evidence for the efficacy of a brief solution focused programme in supporting low-income parents’ engagement. More research is needed using larger sample sizes with longer data collection periods.
Mild cognitive impairment: when nutrition helps brain energy rescue—a report from the EuGMS 2020 Congress
Authors: Cunnane Stephen C. , Sieber Cornel C. , Swerdlow Russell H. , Cruz-Jentoft Alfonso J.
Published: July 2021

Background

Mild cognitive impairment (MCI) is characterized by a decline in cognition and mainly affects older individuals above the age of 60. The global incidence of MCI varies, but it is often underdiagnosed and untreated. There is a distinct lack of approved pharmacologic options to treat MCI. There is, however, evidence to support the efficacy of nutritional interventions, such as ketogenic supplements/diets, which offer ketones as an alternative energy source to brain cells. This article explores the effect of ketones on metabolic activity in the brain and the mechanisms by which ketogenic medium-chain triglycerides (kMCTs) induce ketosis in patients with MCI.

Key takeaways

This article reviews the effect of ketogenic supplements/diets on brain metabolism, including evidence supporting the efficacy of ketones as an efficient fuel for the brain. It discusses the use of oral nutritional ketogenic supplements, with particular reference to the 6-month randomized controlled BENEFIC trial, which showed that consumption of a kMCT drink, BrainXpert Energy Complex, improved cognitive performance in individuals with MCI compared with placebo.

Conclusion

While there is a need for more long-term studies, results from the BENEFIC trial revealed the benefits of a brain-specific ketogenic supplement, as a nutritional intervention, on cognitive performance in individuals with MCI.
Life satisfaction and sustainability: a policy framework
Authors: Barrington-Leigh Christopher P.
Published: July 2021

The growing maturity of the “science of happiness” raises the prospect of enabling government policy to be more accountable to the measurable subjective experience of the population. In its ideal form, the application of this science promises to inform decision makers about the likely distribution of life satisfaction resulting from any prospective policy, allowing for the selection of more optimal policy. Such “budgeting for wellbeing” invites three natural objections, beyond normative quibbles with the subjective objective: (1) non-incremental changes are unlikely in large bureaucracies, so a new accounting system for devising and costing government policies and budgets is too radical, (2) governments do not have an authoritative set of credible cost/benefit coefficients to use in analysis, and (3) long-run objectives, risks, and environmental considerations cannot be feasibly captured in quantitative projections of human subjective wellbeing. Three institutions are needed to address these challenges. I describe (a) an evolving collection of largely objective indicators for monitoring progress, with life satisfaction providing quantitative structure and overarching visibility to the system, (b) a publicly curated, evidence-based Database of Happiness Coefficients, and (c) independent public agencies that decide on a growing list of material constraints on the economy. Rather than overwhelmingly novel, these features have antecedents and analogues. Moreover, most civil service decision-making and projection-making apparatuses need not change. Also, there will be no less room nor less need for political debate and platforms. While shifting society to human-centred measures of progress may be radically transformative in the long run, it can be initiated smoothly and non-disruptively.
Applying the Proportionality Principle to COVID-19 Certificates
Authors: PARIS Evelyn
Published: July 2021

With the SARS-CoV-2 pandemic entering its second year, public and private actors alike grow eager to achieve some semblance of normality. In this context, the idea of “vaccination passports” or “immunity certificates” as a means of resuming social and economic activity has been gaining momentum all around the world. This article aims to provide a legal analysis of this initiative through the lens of the proportionality principle. A proportionality test is conducted in order to determine whether the degree of infringement of the human rights implicated is balanced by the potential of a certification system to mitigate the risks of the virus. The results from this analysis show that the targeted aims can be achieved through already existing measures with a lesser impact on civil and fundamental human rights. Moreover, in a context of uncertainty around the immunopathology of COVID-19, the introduction of these certificates presents ethical and scientific challenges, which lead us to believe that this measure is unlikely to play a central role in stopping the spread of the disease, and it could set the pace for a dangerous precedent, allowing for extensive discrimination and exacerbating already existing inequalities and disparities.
Implementing presidential particularism: bureaucracy and the distribution of federal grants
Authors: Napolio Nicholas G.
Published: July 2021

Do agencies implement the president's particularistic goals uniformly? This paper clarifies the presidential particularism literature by explicitly considering the mechanism through which the president pursues their policy goals: executive agencies. The constellation of bureaucratic agencies responsible for allocating grants plays a key role in facilitating or frustrating presidential policy priorities. Using a dataset of 21 agencies over 14 years, I find that only agencies ideologically proximate to the president engage in particularism benefiting the president. I find no evidence that politicization influences agency implementation of particularism. Critically, the moderating effect of the bureaucracy on particularism only occurs for distributive programs over which agencies have discretion. When disbursing formula grants written by Congress but administered by the bureaucracy with little or no discretion, ideological distance between agencies and presidents has no effect on particularism.
Foreign Aid and Soft Power: Great Power Competition in Africa in the Early Twenty-first Century
Authors: Blair Robert A. , Marty Robert , Roessler Philip
Published: July 2021

Is foreign aid an effective instrument of soft power? Does it generate affinity for donor countries and the values they espouse? This article answers these questions in the context of Chinese aid to Africa and the competing aid regime of the United States. The study combines data on thirty-eight African countries from Afrobarometer, AidData, and the Aid Information Management Systems of African finance and planning ministries. The authors use spatial difference-in-differences to isolate the causal effects of Chinese and US aid. The study finds that Chinese aid to Africa does not increase (and may in fact reduce) beneficiaries’ support for China. By contrast, US aid appears to increase support for the United States and to strengthen recipients’ commitment to liberal democratic values, such as the belief in the importance of elections. Chinese aid does not appear to weaken this commitment, and may strengthen it. The study also finds that Chinese aid increases support for the UK, France and other former colonial powers. These findings advance our understanding of the conditions under which competing aid regimes generate soft power and facilitate the transmission of political principles and ideals.
Flattening the Illiquidity Curve: Retail Trading During the COVID-19 Lockdown
Authors: Ozik Gideon , Sadka Ronnie , Shen Siyi
Published: July 2021

This article studies the impact of retail investors on stock liquidity during the COVID-19 pandemic lockdown in spring 2020. Retail trading exhibits a sharp increase, especially among stocks with high COVID-19–related media coverage. Retail trading attenuated the rise in illiquidity by roughly 40% but less so for high-media-attention stocks. Causality is addressed using the staggered implementation of the stay-at-home advisory across U.S. states. The results highlight that ample free time and access to financial markets facilitated by fintech innovations to trading platforms are significant determinants of retail-investor stock market participation.