bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal monitoring of cell metabolism in biopharmaceutical production using label‐free fluorescence lifetime imaging microscopy
Authors: Sternisha Shawn M. , Mukherjee Prabuddha , Alex Aneesh , Chaney Eric J. , Barkalifa Ronit , Wan Boyong , Lee Jang Hyuk , Rico‐Jimenez Jose , Žurauskas Mantas , Spillman Darold R. , Sripada Sobhana A. , Marjanovic Marina , Arp Zane , Galosy Sybille S. , Bhanushali Dharmesh S. , Hood Steve R. , Bose Sayantan , Boppart Stephen A.
Published: May 2021

Chinese hamster ovary (CHO) cells are routinely used in the biopharmaceutical industry for production of therapeutic monoclonal antibodies (mAbs). Although multiple offline and time‐consuming measurements of spent media composition and cell viability assays are used to monitor the status of culture in biopharmaceutical manufacturing, the day‐to‐day changes in the cellular microenvironment need further in‐depth characterization. In this study, two‐photon fluorescence lifetime imaging microscopy (2P‐FLIM) was used as a tool to directly probe into the health of CHO cells from a bioreactor, exploiting the autofluorescence of intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H), an enzymatic cofactor that determines the redox state of the cells. A custom‐built multimodal microscope with two‐photon FLIM capability was utilized to monitor changes in NAD(P)H fluorescence for longitudinal characterization of a changing environment during cell culture processes. Three different cell lines were cultured in 0.5 L shake flasks and 3 L bioreactors. The resulting FLIM data revealed differences in the fluorescence lifetime parameters, which were an indicator of alterations in metabolic activity. In addition, a simple principal component analysis (PCA) of these optical parameters was able to identify differences in metabolic progression of two cell lines cultured in bioreactors. Improved understanding of cell health during antibody production processes can result in better streamlining of process development, thereby improving product titer and verification of scale‐up. To our knowledge, this is the first study to use FLIM as a label‐free measure of cellular metabolism in a biopharmaceutically relevant and clinically important CHO cell line.
First Amendment knowledge and competence in United States residents
Authors: Bernstein Kimberly M. , Najdowski Cynthia J.
Published: May 2021

Lacking adequate knowledge about one's rights could inhibit the likelihood of exercising one's rights or lead one to unwittingly violate laws that place legitimate limits on these rights. Thus, the present research examines First Amendment knowledge as well as competence to apply this knowledge in relevant circumstances. Results revealed that one‐quarter of participants failed a test of objective knowledge on First Amendment rights. Furthermore, participants' belief in their ability varied depending on their level of knowledge, in line with the Dunning–Kruger effect. Participants also failed to transfer their limited objective knowledge to “real‐world” situations, exhibiting impaired First Amendment competence. These findings suggest that US residents' levels of knowledge and competence related to First Amendment rights and protections could be improved to promote a safe, knowledgeable, and democratic society.
Lost in transition: What refugee post‐migration experiences tell us about processes of social identity change
Authors: Ballentyne Susie , Drury John , Barrett Emma , Marsden Sarah
Published: May 2021

This paper presents findings based on over 40 hrs of rich, phenomenological narrative interview data in which five Syrian refugees describe their experiences of transitioning to a new life in Brazil. Using the Social Identity Model of Identity Change (SIMIC) as a framework for examining the relationship between a period of vulnerability, multiple social identities and wellbeing, interviews were combined with a “talking stones” technique. Key themes of identity “recovery” and “discovery” were consistent with the identity “gain” and “continuity” components of SIMIC. A theme of “adaptation” suggested that a process of continual identity construction and reconstruction is central to both outcomes. Further, themes relating to identity “constraint” suggests how some contexts can actively freeze identities, thus undermining agency and compromising wellbeing. The refugee stories analysed in this paper demonstrate how the SIMIC is a robust model for capturing many of the identity complexities within post‐migration life. Please refer to the supplementary material section to find this article's Community and Social Impact Statement.
A Potent, Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation
Authors: Wang Sijie , Alpsoy Aktan , Sood Surbhi , Ordonez‐Rubiano Sandra Carolina , Dhiman Alisha , Sun Yixing , Jiao Guanming , Krusemark Casey J. , Dykhuizen Emily C.
Published: May 2021

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N‐terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a Kd of 80 nM and displays 24‐1000‐fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.
Giant cerebriform melanocytic nevus of the scalp: A case report
Authors: Mohaghegh Fatemeh , Asilian Ali , Nabavinejad Samin , Rezaei Mina
Published: May 2021

Giant melanocytic nevus is a rare condition caused by benign proliferation of melanocytes. There is a slight risk of malignancy in these lesions which should be noticed especially when they become larger. GCMN can be removed by plastic surgery.
Fatal anaphylaxis to intravenous ondansetron: A case report
Authors: Sapkota Kalyan , Bhagat Roshan
Published: May 2021

The safety and efficacy of ondansetron has led to its wider clinical use and this could increase unusual serious adverse events. Therefore, we emphasize the need for cautious use of ondansetron and beware and prepare for unusual adverse events.
Surgical management of a giant atrial septal aneurysm
Authors: Kumagai Motoyuki , Nishizawa Junichiro , Takehara Makoto , Shinoda Eiji , Minatoya Kenji
Published: May 2021

We experienced a very rare case of surgical management of a giant atrial septal aneurysm. It is an interesting case and is supported by preoperative, intraoperative, and pathology images.
A characteristic rash caused by Shiitake mushrooms – An emerging concern?
Authors: Maruthappu Thiviyani , Hader Zahra
Published: May 2021

Shiitake mushroom dermatitis is a striking rash that can present as an emergency. Despite the dramatic appearance, the rash is an idiosyncratic reaction which resolves spontaneously and does not progress to anaphylaxis.
A Showcase of Green Chemistry: Sustainable Synthetic Approach of Zirconium‐Based MOF Materials
Authors: Fu Jiarui , Wu Yi‐nan
Published: May 2021

Zirconium‐based metal‐organic framework materials (Zr−MOFs) have more practical usage over most conventional benchmark porous materials and even many other MOFs due to the excellent structural stability, rich coordination forms, and various active sites. However, their mass‐production and application are restricted by the high‐cost raw materials, complex synthesis procedures, harsh reaction conditions, and unexpected environmental impact. Based on the principles of “Green Chemistry”, considerable efforts have been done for breaking through the limitations, and significant progress has been made in the sustainable synthesis of Zr−MOFs over the past decade. In this review, the advancements of green raw materials and green synthesis methods in the synthesis of Zr−MOFs are reviewed, along with the corresponding drawbacks. The challenges and prospects are discussed and outlooked, expecting to provide guidance for the acceleration of the industrialization and commercialization of Zr−MOFs.
Artificial Supramolecular Pumps Powered by Light
Authors: Corra Stefano , Casimiro Lorenzo , Baroncini Massimo , Groppi Jessica , La Rosa Marcello , Tranfić Bakić Marina , Silvi Serena , Credi Alberto
Published: May 2021

The development of artificial nanoscale motors that can use energy from a source to perform tasks requires systems capable of performing directionally controlled molecular movements and operating away from chemical equilibrium. Here, the design, synthesis and properties of pseudorotaxanes are described, in which a photon input triggers the unidirectional motion of a macrocyclic ring with respect to a non‐symmetric molecular axle. The photoinduced energy ratcheting at the basis of the pumping mechanism is validated by measuring the relevant thermodynamic and kinetic parameters. Owing to the photochemical behavior of the azobenzene moiety embedded in the axle, the pump can repeat its operation cycle autonomously under continuous illumination. NMR spectroscopy was used to observe the dissipative non‐equilibrium state generated in situ by light irradiation. We also show that fine changes in the axle structure lead to an improvement in the performance of the motor. Such results highlight the modularity and versatility of this minimalist pump design, which provides facile access to dynamic systems that operate under photoinduced non‐equilibrium regimes.
Polythiolactone‐Decorated Silica Particles: A Versatile Approach for Surface Functionalization, Catalysis and Encapsulation
Authors: Kurka Dustin Werner , Niehues Maximilian , Kudruk Sergej , Gerke Volker , Ravoo Bart Jan
Published: May 2021

Invited for the cover of this issue is the group of Bart Jan Ravoo at Westfälische Wilhelms‐Universität Münster. The image depicts the “universal” post‐modification of silica particles coated with a polythiolactone polymer shell. Read the full text of the article at 10.1002/chem.202100547.
High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
Authors: Ollila Hely , Paajanen Juuso , Wolff Henrik , Ilonen Ilkka , Sutinen Eva , Välimäki Katja , Östman Arne , Anttila Sisko , Kettunen Eeva , Räsänen Jari , Kallioniemi Olli , Myllärniemi Marjukka , Mäyränpää Mikko I , Pellinen Teijo
Published: May 2021

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location‐specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all‐cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet‐derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00–1.03 and HR = 1.05, 95% CI = 1.00–1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence‐based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.
Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects
Authors: Shimizu Hidetoshi , Nishimura Yukiko , Shiide Youichi , Yoshida Kaori , Hirai Manabu , Matsuda Munetomo , Nakamaru Yoshinobu , Kato Yuichiro , Kondo Kazuoki
Published: May 2021

The neuroprotective agent edaravone is an intravenous treatment for amyotrophic lateral sclerosis. As intravenous administration burdens patients, orally administered treatments are needed. This phase 1, open‐label, single‐dose crossover study in 42 healthy adults evaluated bioequivalence of a 105‐mg edaravone oral suspension and intravenous edaravone (60 mg/60 min). The evaluation was whether the 90% confidence intervals (CIs) for the ratio of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity of unchanged edaravone were between the bioequivalence limit of 0.80 and 1.25. Metabolic profiles and elimination pathways were also compared between the 2 routes. Geometric mean ratios and 90%CIs of area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity for unchanged edaravone satisfied bioequivalence limits. The geometric mean ratio and its lower limit of 90%CI of Cmaxof the 105‐mg oral suspension compared with 60‐mg intravenous formulations for unchanged edaravone fell within bioequivalence limits. Both formulations showed triphasic plasma concentration–time profiles of unchanged edaravone after reaching Cmax. Plasma concentrations of edaravone inactive metabolites after oral administration were higher than with intravenous administration. Edaravone in both routes underwent urinary excretion, mainly as the glucuronide conjugate and, to a lesser extent, as the sulfate conjugate. Urinary excretion of unchanged edaravone was low, and urinary relative composition ratios of unchanged edaravone and metabolites were similar for both formulations. These findings showed equivalent exposure of the 105‐mg oral suspension of edaravone to the 60‐mg intravenous formulation, supporting further investigation of the oral suspension for treating amyotrophic lateral sclerosis.
Performance analysis of lattice reduction‐assisted precoder for multi‐user millimeter wave MIMO system
Authors: Kandar Debdatta , Sur Samarendra Nath , Singh Arun Kumar , Nandi Sukumar
Published: May 2021

Millimeter wave communication and massive MIMO technology are important ingredients for the future generation communication system. In this context, hybrid precoding (HP) is one of the most promising solutions, and it becomes utterly important in the case of the multi‐user scenario. In this paper, authors have analyzed the performance of the lattice reduction aided fully connected structured precoder for millimeter wave massive MIMO under multi‐user scenario. This paper deals with Korkine–Zolotareff (KZ) and Lenstra–Lenstra–Lovász (LLL) algorithms for the lattice reduction (LR). And the presented results show the performance comparison between zero forcing (ZF), minimum mean squared error (MMSE)‐based linear precoder with LLL algorithm‐based reduction‐based ZF (LLR‐ZF), LLR‐MMSE, KZ‐ZF, KZ‐MMSE, and Kalman filter‐based precoder. Here, the performance of the precoders has been evaluated based on spectral efficiency, energy efficiency diversity order, and bit error rate. This work conveys some important findings: (i) effectiveness of the lattice reduction aided precoder in multi‐user scenario; (ii) numerical results pointed out that at low SNR condition, KZ‐aided MMSE hybrid precoder provides 4‐dB performance than a Kalman filter‐based precoder; (iii) KZ‐MMSE hybrid precoder outperforms the other precoder.
Hybrid spectrum access in a cognitive radio‐enabled cooperative device‐to‐device network
Authors: Kumar Pradeep , Bhowmick Abhijit
Published: May 2021

In this paper, the performance of a co‐operative device‐to‐device (D2D) network is investigated. All the D2D users sense the cellular user (CU) spectrum and use it in hybrid mode: underlay and overlay. The expressions of throughput and outage are developed under the considered network scenario. An algorithm is proposed to optimize the sensing time to minimize the outage. The performance is investigated in terms of throughput and outage for several network parameters such as a number of D2D users, sensing time, signal‐to‐noise ratio (SNR), allowable interference threshold, and CU transmit power. Sensing time is optimized to minimize the outage. The interference threshold and target rate have a significant impact on network performance. The network has to suffer outage for lower values of allowable interference threshold and higher values of the target rate. The impact of channel fading on the network performance is also studied. A simulation model is developed in MATLAB on the basis of the analytical development of the considered network model.
Do all roads lead to resistance? State road density is the main impediment to gene flow in a flagship species inhabiting a severely fragmented anthropogenic landscape
Authors: Westekemper Katharina , Tiesmeyer Annika , Steyer Katharina , Nowak Carsten , Signer Johannes , Balkenhol Niko
Published: May 2021

Aim

Connectivity conservation is ideally based on empirical information on how landscape heterogeneity influences species‐specific movement and gene flow. Here, we present the first large‐scale evaluation of landscape impacts on genetic connectivity in the European wildcat (Felis silvestris), a flagship and umbrella species for connectivity conservation across Europe.

Location

The study was carried out in the core area of the distributional range of wildcats in Germany, covering about 186,000 km2of a densely populated and highly fragmented landscape.

Methods

We used data of 975 wildcats genotyped at 14 microsatellites and an individual‐based landscape genetic framework to assess the importance of twelve landscape variables for explaining observed genetic connectivity. For this, we optimized landscape resistance surfaces for all variables and compared their relative impacts using multiple regression on distance matrices and commonality analysis.

Results

Genetic connectivity was best explained by a synergistic combination of six landscape variables and isolation by distance. Of these variables, road density had by far the strongest individual impact followed by synergistic effects of agricultural lands and settlements. Subsequent analyses involving different road types revealed that the strong effect of road density was largely due to state roads, while highways and federal roads had a much smaller, and county roads only a negligible impact.

Main conclusions

Our results highlight that landscape‐wide genetic connectivity in wildcats across Germany is strongly shaped by the density of roads and in particular state roads, with higher densities providing larger resistance to successful dispersal. These findings have important implications for conservation planning, as measures to mitigate fragmentation effects of roads (e.g., over‐ or underpasses) often focus on large, federally managed transportation infrastructures. While these major roads exert local barrier effects, other road types can be more influential on overall connectivity, as they are more abundant and more widespread across the landscape.
Environmental variation drives continental‐scale synchrony of European beech reproduction
Authors: Bogdziewicz Michał , Hacket‐Pain Andrew , Ascoli Davide , Szymkowiak Jakub
Published: May 2021

Spatial synchrony is the tendency of spatially separated populations to display similar temporal fluctuations. Synchrony affects regional ecosystem functioning, but it remains difficult to disentangle its underlying mechanisms. We leveraged regression on distance matrices and geography of synchrony to understand the processes driving synchrony of European beech masting over the European continent. Masting in beech shows distance‐decay, but significant synchrony is maintained at spatial scales of up to 1,500 km. The spatial synchrony of the weather cues that drive interannual variation in reproduction also explains the regional spatial synchrony of masting. Proximity played no apparent role in influencing beech masting synchrony after controlling for synchrony in environmental variation. Synchrony of beech reproduction shows a clear biogeographical pattern, decreasing from the northwest to southeast Europe. Synchrony networks for weather cues resemble networks for beech masting, indicating that the geographical structure of weather synchrony underlies the biogeography of masting synchrony. Our results support the hypothesis that environmental factors, the Moran effect, are key drivers of spatial synchrony in beech seed production at regional scales. The geographical patterns of regional synchronization of masting have implications for regional forest production, gene flow, carbon cycling, disease dynamics, biodiversity, and conservation.
Monitoring vertebrate biodiversity of a protected coastal wetland using eDNA metabarcoding
Authors: Saenz‐Agudelo Pablo , Delrieu‐Trottin Erwan , DiBattista Joseph D. , Martínez‐Rincon Diego , Morales‐González Sarai , Pontigo Felipe , Ramírez Paula , Silva Andrea , Soto Mauricio , Correa Cristian
Published: May 2021

Monitoring plans using environmental DNA have the potential to offer a standardized and cost‐efficient method to survey biodiversity in aquatic ecosystems. Among these ecosystems, coastal wetlands are key elements that serve as transition zones between marine and freshwater ecosystems and are today the target of many conservation and restoration efforts. In this sense, eDNA monitoring could provide a rapid and efficient tool for studying and generating baseline biodiversity information to guide coastal wetland management programs. Here, we test an eDNA metabarcoding assay as a tool to characterize vertebrate biodiversity in one of the largest coastal wetlands of Chile, the Rio Cruces Wetland, a Ramsar designated site since 1981. We sampled surface water from 49 sites along the entire wetland. Our eDNA approach detected 91genera of vertebrates including amphibians, fishes, mammals, and birds, as well as identified several cryptic, exotic, and endangered species. Our results also indicated that the spatial distribution of eDNA from different species is spatially structured despite the complex hydrodynamics inherent in this wetland due to the influence of daily tidal regimes. For amphibians and fishes, the number of taxa detected with eDNA was higher in the periphery of the wetland, and increased with proximity to the ocean, a pattern consistent with small‐scale spatial sensitivity for some species and eDNA accumulation downstream for others. Birds and mammals showed somewhat more idiosyncratic distributions. Taken together, our results add to the growing body of evidence showing eDNA can serve as a rapid cost‐effective tool to characterize vertebrate communities in protected coastal wetlands, where visual surveys are difficult and animal collections are often prohibited. The use of multiple primer sets is also recommended as it facilitates the detection of ephemeral terrestrial organisms and resident aquatic organisms that make use of these wetlands.
3D Carambola‐Like CuO/TiO2 Nanotube Heterostructures via Low‐Temperature Solution Process for Photocatalytic Activity
Authors: Ren Shuai , Zhang Jiejing , Lu Huiqing , Gao Shiyong , Li Lin , Rong Ping , Zhang Xiaolei , Liu Yi , Sang Dandan
Published: May 2021

CuO/TiO2 heterostructures have been synthesized via a facile low‐temperature solution method. The resultant heterostructures present a three‐dimensional hierarchical morphology of carambola‐like CuO integrated with TiO2 nanotubes (NTs), confirmed by means of SEM, TEM, EDS, XRD and XPS. And time‐dependent evolutions of morphology show that the CuO grow from the initial leaf‐shaped nanosheets and eventually form carambola‐like structures. The UV/Vis absorption spectrum indicates that the carambola‐like CuO/TiO2 NTs have strong absorption in the UV light region as well as in the visible light region. The study on evaluating photocatalytic activity indicates that the carambola‐like CuO/TiO2 NTs can degrade 40 % of Rhodamine B, exhibiting enhanced photocatalytic activity compared with TiO2 NTs. Moreover, the photocatalytic mechanism of the carambola‐like CuO/TiO2 NT heterostructures is expounded.
Design of NiFe‐based nanostructures for efficient oxygen evolution electrocatalysis
Authors: Shi Yue , Zhang Dan , Miao Hongfu , Zhan Tianrong , Lai Jianping
Published: May 2021

The excessive using of fossil energy has caused serious environmental pollution, and the development and utilization of new energy sources have been a continuing research direction of concern. The synergistic effect of Ni and Fe is beneficial to reduce the reaction energy barrier of oxygen evolution reaction (OER), therefore NiFe based catalyst represents a very promising non‐precious metal OER catalyst. This minireview focuses on the optimization strategies for NiFe based catalysts, summarizes the research progress made in recent years, and discusses the mechanisms involved in these strategies. After composition and structure optimization, the catalytic activity and stability of NiFe based catalysts have been improved, which is beneficial to OER. Finally, the development direction and research prospect of NiFe based catalysts are provided with a reasonable outlook.
Validation of semi‐automated anatomically labeled SEEG contacts in a brain atlas for mapping connectivity in focal epilepsy
Authors: Taylor Kenneth N. , Joshi Anand A. , Hirfanoglu Tugba , Grinenko Olesya , Liu Ping , Wang Xiaofeng , Gonzalez‐Martinez Jorge A. , Leahy Richard M. , Mosher John C. , Nair Dileep R.
Published: May 2021

Objective

Stereotactic electroencephalography (SEEG) has been widely used to explore the epileptic network and localize the epileptic zone in patients with medically intractable epilepsy. Accurate anatomical labeling of SEEG electrode contacts is critically important for correctly interpreting epileptic activity. We present a method for automatically assigning anatomical labels to SEEG electrode contacts using a 3D‐segmented cortex and coregistered postoperative CT images.

Method

Stereotactic electroencephalography electrode contacts were spatially localized relative to the brain volume using a standard clinical procedure. Each contact was then assigned an anatomical label by clinical epilepsy fellows. Separately, each contact was automatically labeled by coregistering the subject's MRI to the USCBrain atlas using the BrainSuite software and assigning labels from the atlas based on contact locations. The results of both labeling methods were then compared, and a subsequent vetting of the anatomical labels was performed by expert review.

Results

Anatomical labeling agreement between the two methods for over 17 000 SEEG contacts was 82%. This agreement was consistent in patients with and without previous surgery (P = .852). Expert review of contacts in disagreement between the two methods resulted in agreement with the atlas based over manual labels in 48% of cases, agreement with manual over atlas‐based labels in 36% of cases, and disagreement with both methods in 16% of cases. Labels deemed incorrect by the expert review were then categorized as either in a region directly adjacent to the correct label or as a gross error, revealing a lower likelihood of gross error from the automated method.

Significance

The method for semi‐automated atlas‐based anatomical labeling we describe here demonstrates potential to assist clinical workflow by reducing both analysis time and the likelihood of gross anatomical error. Additionally, it provides a convenient means of intersubject analysis by standardizing the anatomical labels applied to SEEG contact locations across subjects.
Power‐domain non‐orthogonal multiple access based full‐duplex one‐way wireless relaying network
Authors: Ozduran Volkan , Huda Mahmood Nurul , Chergui Hatim
Published: May 2021

This study investigates power‐domain non‐orthogonal multiple access based wireless information exchange process. The investigation considers a dual‐hop non‐regenerative full‐duplex wireless one‐way relaying networks in the system model, where the source terminal transmits two different types of information and subtracts the interference signal at the destination by using successive interference cancellation technique. The outage probability, error probability, achievable rate, and ergodic rate of the considered system is analytically derived. In addition, optimum power allocation coefficients and relay terminal position are determined using the optimization techniques. Monte‐Carlo simulation results validate the analytical and asymptotic derivations. The derived analytical expressions are found closely in agreement with the system level numerical results.
Dynamics of photosynthetic induction and relaxation within the canopy of rice and two wild relatives
Authors: Acevedo‐Siaca Liana G. , Dionora Jacqueline , Laza Rebecca , Paul Quick William , Long Stephen P.
Published: May 2021

Wild rice species are a source of genetic material for improving cultivated rice (Oryza sativa) and a means to understand its evolutionary history. Renewed interest in non‐steady‐state photosynthesis in crops has taken place due its potential in improving sustainable productivity. Variation was characterized for photosynthetic induction and relaxation at two leaf canopy levels in three rice species. The wild rice accessions had 16%–40% higher rates of leaf CO2 uptake (A) during photosynthetic induction relative to the O. sativa accession. However, O. sativa had an overall higher photosynthetic capacity when compared to accessions of its wild progenitors. Additionally, O. sativa had a faster stomatal closing response, resulting in higher intrinsic water‐use efficiency during high‐to‐low light transitions. Leaf position in the canopy had a significant effect on non‐steady‐state photosynthesis, but not steady‐state photosynthesis. The results show potential to utilize wild material to refine plant models and improve non‐steady‐state photosynthesis in cultivated rice for increased productivity.
Retrospective confidence judgments: Meta‐analysis of functional magnetic resonance imaging studies
Authors: Martín‐Luengo Beatriz , Zinchenko Oksana , Dolgoarshinnaia Aleksandra , Leminen Alina
Published: May 2021

Confidence in our retrieved memories, that is, retrospective confidence, is a metamemory process we perform daily. There is an abundance of applied research focusing on the metamemory judgments and very diverse studies including a wide range of clinical populations. However, the neural correlates that support its functioning are not well defined impeding the implementation of noninvasive neuromodulatory clinical interventions. To address the neural basis of metamemory judgments, we ran a meta‐analysis, where we used the activation likelihood estimation method on the 19 eligible functional magnetic resonance imaging studies. The main analysis of retrospective confidence revealed concordant bilateral activation in the parahippocampal gyrus, left middle frontal gyrus, and right amygdala. We also run an analysis between the two extreme levels of confidence, namely, high and low. This additional analysis was exploratory, since the minimum amount of articles reporting these two levels was not reached. Activations for the exploratory high > low confidence subtraction analysis were the same as observed in the main analysis on retrospective confidence, whereas the exploratory low > high subtraction showed distinctive activations of the right precuneus. The involvement of the right precuneus emphasizes its role in the evaluation of low confidence memories, as suggested by previous studies. Overall, our study contributes to a better understanding of the specific brain structures involved in confidence evaluations. Better understanding of the neural basis of metamemory might eventually lead to designing more precise neuromodulatory interventions, significantly improving treatment of patients suffering from metamemory problems.
The effects of audits and fines on upcoding in neonatology
Authors: Groß Mona , Jürges Hendrik , Wiesen Daniel
Published: May 2021

Upcoding is a common type of fraud in healthcare. However, how audit policies need to be designed to cope with upcoding is not well understood. We provide causal evidence on the effect of random audits with different probabilities and financial consequences. Using a controlled laboratory experiment, we mimic the decision situation of obstetrics staff members to report birth weights of neonatal infants. Subjects' payments in the experiment depend on their reported birth weights and follow the German non‐linear diagnosis‐related group remuneration for neonatal care. Our results show that audits with low detection probabilities only reduce fraudulent birth‐weight reporting, when they are coupled with fines for fraudulent reporting. For audit policies with fines, increasing the probability of an audit only effectively enhances honest reporting, when switching from detectable to less gainful undetectable upcoding is not feasible. Implications for audit policies are discussed.
The value of health—Empirical issues when estimating the monetary value of a quality‐adjusted life year based on well‐being data
Authors: Himmler Sebastian , Stöckel Jannis , van Exel Job , Brouwer Werner B. F.
Published: May 2021

Decisions on interventions or policy alternatives affecting health can be informed by economic evaluations, like cost‐benefit or cost‐utility analyses. In this context, there is a need for valid estimates of the monetary equivalent value of health (gains), which are often expressed in € per quality‐adjusted life years (QALYs). Obtaining such estimates remains methodologically challenging, with a recent addition to the health economists' toolbox, which is based on well‐being data: The well‐being valuation approach. Using general population panel data from Germany, we put this approach to the test by investigating several empirical and conceptual challenges, such as the appropriate functional specification of income utility, the choice of health utility tariffs, or the health state dependence of consumption utility. Depending on specification, the bulk of estimated € per QALY values ranged from €20,000–60,000, with certain specifications leading to more considerable deviations, underlining persistent practical challenges when applying the well‐being valuation methodology to health and QALYs. Based on our findings, we formulate recommendations for future research and applications.
Intravesical injection of onabotulinumtoxinA in neurogenic overactive bladder patients with human T‐cell leukemia virus type 1‐associated myelopathy: A single‐institution case series
Authors: Matsuo Tomohiro , Nakamura Tatsufumi , Sato Katsuya , Miyata Yasuyoshi , Sakai Hideki
Published: May 2021

Introduction

Neurogenic overactive bladder is a main feature of human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis. We successfully performed intravesical onabotulinumtoxinA therapy for refractory neurogenic overactive bladder due to human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis.

Case presentation

We retrospectively reviewed four neurogenic overactive bladder patients with human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis who underwent bladder wall injections of onabotulinumtoxinA from April to October 2020. All patients were female. Their median age was 66 (range, 63–71) years. They were previously treated with β3‐adrenergic receptor agonists or anticholinergic drugs alone or in combination for ≥12 weeks. However, insufficient results were obtained. After 4 weeks of intravesical onabotulinumtoxinA therapy, overactive bladder symptoms improved and maximum cystometric capacity increased in all cases.

Conclusion

Intravesical onabotulinumtoxinA therapy may be useful for treating refractory overactive bladder due to human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis.
Refracture and mortality following hospitalization for severe osteoporotic fractures: The Fractos Study
Authors: Roux Christian , Thomas Thierry , Paccou Julien , Bizouard Geoffray , Crochard Anne , Toth Emese , Lemaitre Magali , Maurel Frédérique , Perrin Laure , Tubach Florence
Published: May 2021

Severe osteoporotic fractures (hip, proximal humerus, pelvic, vertebral and multiple rib fractures) carry an increased risk of mortality. This retrospective cohort study in the French national healthcare database aimed to estimate refracture and mortality rates after severe osteoporotic fractures at different sites, and to identify mortality‐related variables. A total of 356,895 patients hospitalized for severe osteoporotic fracture between 2009 and 2014 inclusive were analyzed. The cohort was followed for 2 to 8 years up to the study end or until the patient died. Data were extracted on subsequent hospitalizations, refracture events, treatments, comorbidities of interest and survival. Time to refracture and survival were described using Kaplan‐Meier analysis by site of fracture and overall. Mortality risk factors were identified using a Cox model. Hip fractures accounted for 60.4% of the sample (N = 215,672). In the 12 months following fracture, 58,220 patients (16.7%) received a specific osteoporosis treatment, of whom 21,228 were previously treatment‐naïve. The 12‐month refracture rate was 6.3% (95% confidence interval [CI], 6.2%–6.3%), ranging from 4.0% (95% CI, 3.7%–4.3%) for multiple rib fractures to 7.8% (95% CI, 7.5%–8.1%) for pelvic fractures. Twelve‐month all‐cause mortality was 12.8% (95% CI, 12.7%–12.9%), ranging from 5.0% (95% CI, 4.7%–5.2%) for vertebral fractures to 16.6% (95% CI, 16.4%–16.7%) for hip fractures. Osteoporosis‐related mortality risk factors included fracture site, previous osteoporotic fracture (hazard ratio 1.21; 95% CI, 1.18–1.23), hip refracture (1.74; 95% CI, 1.71–1.77), and no prior osteoporosis treatment (1.24; 95% CI, 1.22–1.26). Comorbid cancer (3.15; 95% CI, 3.09–3.21) and liver disease (2.54; 95% CI, 2.40–2.68) were also strongly associated with mortality. In conclusion, severe osteoporotic fractures, including certain non‐hip nonvertebral fractures, carry a high burden in terms of mortality and refracture risk. However, most patients received no anti‐osteoporotic treatment. The findings emphasize the importance of better management of patients with severe fractures, and of developing effective strategies to reduce fracture risk in patients with osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Short‐Term Increased Physical Activity During Early Life Affects High‐Fat Diet–Induced Bone Loss in Young Adult Mice
Authors: Chen Jin‐Ran , Lazarenko Oxana P , Carvalho Eugenia , Blackburn Michael L , Shankar Kartik , Wankhade Umesh D , Børsheim Elisabet
Published: May 2021

Mechanical stresses associated with physical activity (PA) have beneficial effects on increasing BMD and improving bone quality. However, a high‐fat diet (HFD) and obesity tend to have negative effects on bone, by increasing bone marrow adiposity leading to increased excretion of proinflammatory cytokines, which activate RANKL‐induced bone resorption. In the current study, whether short‐term increased PA via access to voluntary wheel running during early life has persistent and protective effects on HFD‐induced bone resorption was investigated. Sixty 4‐week‐old male C57BL6/J mice were divided into two groups postweaning: without or with PA (access to voluntary running wheel 7–8 km/day) for 4 weeks. After 4 weeks with or without PA, mice were further subdivided into control diet or HFD groups for 8 weeks, and then all animals were switched back to control diet for an additional 4 weeks. Mice from the HFD groups were significantly heavier and obese; however, after 4 weeks of additional control diet their body weights returned to levels of mice on continuous control diet. Using μ‐CT and confirmed by pQCT of tibias and spines ex vivo, it was determined that bone volume and trabecular BMD were significantly increased with PA in control diet animals compared with sedentary animals without access to wheels, and such anabolic effects of PA on bone were sustained after ceasing PA in adult mice. Eight weeks of a HFD deteriorated bone development in mice. Unexpectedly, early‐life PA did not prevent persistent effects of HFD on deteriorating bone quality; in fact, it exacerbated a HFD‐induced inflammation, osteoclastogenesis, and trabecular bone loss in adult mice. In accordance with these data, signal transduction studies revealed that a HFD‐induced Ezh2, DNA methyltransferase 3a, and nuclear factor of activated T‐cells 1 expression were amplified in nonadherent hematopoietic cells. In conclusion, short‐term increased PA in early life is capable of increasing bone mass; however, it alters the HFD‐induced bone marrow hematopoietic cell‐differentiation program to exacerbate increased bone resorption if PA is halted. © 2021 Arkansas Children's Nutrition Center. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Impaired bone microarchitecture and strength in patients with tumor-induced osteomalacia
Authors: Zanchetta María Belén , Jerkovich Fernando , Nuñez Selva , Mocarbel Yamile , Pignatta Analía , Elías Natalia , Díaz Adriana Graciela , Roganovich Juan Manuel , Vigovich Carlos , Balonga María Celeste , Cohen Ana Carolina , Mumbach Giselle , Gonzalez Sofía , Plantalech Luisa , Fradinger Erich , Zanchetta José Rubén
Published: May 2021

Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).
Development and validation of prognostic model to predict mortality among cirrhotic patients with acute variceal bleeding: A retrospective study
Authors: Chirapongsathorn Sakkarin , Akkarachinores Kuntapon , Chaiprasert Amnart
Published: May 2021

Background and Aim

Acute variceal bleeding (AVB) is a serious complication associated with high mortality. The aim of our study was to investigate mortality predictors and to develop a new simplified prognostic model among cirrhotic patients with AVB.

Methods

A simplified prognostic model was developed using multiple logistic regression after identifying significant predictors of 6‐week mortality.

Results

A total of 713 consecutive patients with AVB were enrolled. The 6‐week overall mortality rate was 18%. Multivariate analysis showed that shock, model for end‐stage liver disease (MELD) score, high‐risk stigmata of esophageal varices on endoscopic finding, and Glasgow Blatchford score were independent predictors of mortality. A new logistic model using these variables was developed. This model (cutoff value ≥ 4) area under the receiver operating characteristics (AUROC) was 0.93 and significantly higher than that of MELD score alone (0.74). Two validation analyses showed that the AUROC of our model was consistently high. The 6‐week rebleeding rate was 25.3%. Multivariate analysis showed that MELD score, Glasgow Blatchford score, history of upper GI bleeding, shock, and alcohol use were independent predictors of rebleeding.

Conclusion

Our new simplified model accurately and consistently predicted 6‐week mortality among patients with AVB using objective variables measured at admission. Patients with higher MELD scores should be closely monitored due to the higher probability of 6‐week rebleeding.
Occurrence of hepatitis in an elderly woman during the treatment of pembrolizumab for right advanced renal pelvis, ureteral cancer, and bladder cancer
Authors: Asatani Shinya , Kanda Tatsuo , Honda Masayuki , Ishii Tomotaka , Yamana Yoichiro , Kaneko Tomohiro , Mizutani Taku , Takahashi Hiroshi , Kumagawa Mariko , Sasaki Reina , Masuzaki Ryota , Kanezawa Shini , Matsumoto Naoki , Nirei Kazushige , Yamagami Hiroaki , Moriyama Mitsuhiko
Published: May 2021

Recently, the use of immune checkpoint inhibitors (ICIs) with or without chemotherapeutic agents has been increasing in the treatment for advanced cancer. Here, we report the occurrence of liver failure after the use of pembrolizumab in an 82‐year‐old woman with metastatic liver disease derived from right advanced renal pelvis, ureteral cancer, and bladder cancer. She was successfully treated with 0.6 mg/kg daily prednisolone. In patients treated with ICIs, ICI‐induced hepatitis is occasionally observed. Even if patients are older, it appears important to diagnose and treat ICI‐induced hepatitis earlier by multidisciplinary therapies including steroid treatment. This is a first report of pembrolizumab‐induced liver failure in elder patient with age over 80 years. Even if patients are older, it appears important to diagnose and treat ICI‐induced hepatitis earlier by multidisciplinary therapies including steroid treatment.