bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional expression of mitochondrial KCa3.1 channels in non-small cell lung cancer cells
Authors: Bulk Etmar , Todesca Luca Matteo , Bachmann Magdalena , Szabo Ildiko , Rieke Marius , Schwab Albrecht
Published: September 2022

Lung cancer is one of the leading causes of cancer-related deaths worldwide. The Ca2+-activated K+ channel KCa3.1 contributes to the progression of non-small cell lung cancer (NSCLC). Recently, KCa3.1 channels were found in the inner membrane of mitochondria in different cancer cells. Mitochondria are the main sources for the generation of reactive oxygen species (ROS) that affect the progression of cancer cells. Here, we combined Western blotting, immunofluorescence, and fluorescent live-cell imaging to investigate the expression and function of KCa3.1 channels in the mitochondria of NSCLC cells. Western blotting revealed KCa3.1 expression in mitochondrial lysates from different NSCLC cells. Using immunofluorescence, we demonstrate a co-localization of KCa3.1 channels with mitochondria of NSCLC cells. Measurements of the mitochondrial membrane potential with TMRM reveal a hyperpolarization following the inhibition of KCa3.1 channels with the cell-permeable blocker senicapoc. This is not the case when cells are treated with the cell-impermeable peptidic toxin maurotoxin. The hyperpolarization of the mitochondrial membrane potential is accompanied by an increased generation of ROS in NSCLC cells. Collectively, our results provide firm evidence for the functional expression of KCa3.1 channels in the inner membrane of mitochondria of NSCLC cells.
Succinct Permutation Graphs
Authors: Tsakalidis Konstantinos , Wild Sebastian , Zamaraev Viktor
Published: September 2022

We present a succinct data structure for permutation graphs, and their superclass of circular permutation graphs, i.e., data structures using optimal space up to lower order terms. Unlike concurrent work on circle graphs (Acan et al. in Theor Comput Sci, https://doi.org/10.1016/j.tcs.2022.06.022, 2022), our data structure also supports distance and shortest-path queries, as well as adjacency and neighborhood queries, all in optimal time. We present in particular the first succinct exact distance oracle for (circular) permutation graphs. A second succinct data structure also supports degree queries in time independent of the neighborhood’s size at the expense of an $$O(\log n/\log \log n)$$

O
(
log
n
/
log
log
n
)

-factor overhead in all running times. Furthermore, we develop a succinct data structure for the class of bipartite permutation graphs. We demonstrate how to run algorithms directly over our succinct representations for several problems on permutation graphs: Clique, Coloring, Independent Set, Hamiltonian Cycle, All-Pair Shortest Paths, and others. Finally, we initiate the study of semi-distributed graph representations; a concept that smoothly interpolates between distributed (labeling schemes) and centralized (standard data structures). We show how to turn some of our data structures into semi-distributed representations by storing only $$O(n)$$

O
(
n
)

bits of additional global information, circumventing the lower bound on distance labeling schemes for permutation graphs.
“Cognition in marine mammals: the strength of flexibility in adapting to marine life”
Authors: Hanke Frederike D. , Biolsi Kristy L. , Harley Heidi E.
Published: September 2022

In this theme issue, our multidisciplinary contributors highlight the cognitive adaptations of marine mammals. The cognitive processes of this group are highly informative regarding how animals cope with specifics of and changes in the environment, because, not only did modern marine mammals evolve from numerous, non-related terrestrial animals to adapt to an aquatic lifestyle, but some of these species regularly move between two worlds, land and sea. Here, we bring together scientists from different fields and take the reader on a journey that begins with the ways in which modern marine mammals (whales, dolphins, seals, sea lions and manatees) utilize their perceptual systems, next moves into studies of the constraints and power of individuals’ cognitive flexibility, and finally showcases how those systems are deployed in social and communicative contexts. Considering the cognitive processes of the different marine mammals in one issue from varying perspectives will help us understand the strength of cognitive flexibility in changing environments—in marine mammals and beyond.
Multiple internal resonances of rotating composite cylindrical shells under varying temperature fields
Authors: Liu Yunfei , Wang Jun , Hu Jiaxin , Qin Zhaoye , Chu Fulei
Published: September 2022

Composite cylindrical shells, as key components, are widely employed in large rotating machines. However, due to the frequency bifurcations and dense frequency spectra caused by rotation, the nonlinear vibration usually has the behavior of complex multiple internal resonances. In addition, the varying temperature fields make the responses of the system further difficult to obtain. Therefore, the multiple internal resonances of composite cylindrical shells with porosities induced by rotation with varying temperature fields are studied in this paper. Three different types of the temperature fields, the Coriolis forces, and the centrifugal force are considered here. The Hamilton principle and the modified Donnell nonlinear shell theory are used to obtain the equilibrium equations of the system, which are transformed into the ordinary differential equations (ODEs) by the multi-mode Galerkin technique. Thereafter, the pseudo-arclength continuation method, which can identify the regions of instability, is introduced to obtain the numerical results. The detailed parametric analysis of the rotating composite shells is performed. Multiple internal resonances caused by the interaction between backward and forward wave modes and the energy transfer phenomenon are detected. Besides, the nonlinear amplitude-frequency response curves are different under different temperature fields.
Hydrodynamic forces on emergent cylinders in non-uniform flow
Authors: Uchida Tatsuhiko , Ato Toshiki , Kobayashi Daisuke , Maghrebi Mahmoud F. , Kawahara Yoshihisa
Published: September 2022

The main objective of conducting numerical simulations of flows in rivers with vegetation is to investigate the complex flow dynamics involved in non-equilibrium conditions. In such cases, it is inappropriate to apply the drag coefficient CD, which is typically derived based on uniform flows involving groups of infinitely long cylinders. This paper presents a method for evaluating the drag forces acting on emergent obstacles for non-uniform open-channel flows. This method is devised based on two sets of experiments: on flows with small-diameter cylinders, focusing on the water surface profiles through the group; and on flows with large-diameter cylinders, focusing on the local pressure distribution and local water surface profile around a target cylinder. In addition to the conventional drag force expression that includes CD, two new terms are proposed to account for the effects of water surface variation and pressure gradient in non-uniform open-channel flow on the drag. The first of these terms, which introduces the use of the Froude number to account for the effect of water surface variation, is derived theoretically and evaluated against past and present experimental results under uniform-flow conditions. On the other hand, the second of these terms, which includes the representative length of the separation zone to evaluate the effect of pressure gradient, is confirmed to be a necessity through numerical calculation of the longitudinal water surface profile in emergent cylinders. The incorporation of these two terms using a simple unified expression can help improve the accuracy of numerical simulations for practical problems of flows with emergent obstacles.
The methodologies to assess the effectiveness of non-pharmaceutical interventions during COVID-19: a systematic review
Authors: Banholzer Nicolas , Lison Adrian , Özcelik Dennis , Stadler Tanja , Feuerriegel Stefan , Vach Werner
Published: September 2022

Non-pharmaceutical interventions, such as school closures and stay-at-home orders, have been implemented around the world to control the spread of SARS-CoV-2. Their effectiveness in improving health-related outcomes has been the subject of numerous empirical studies. However, these studies show fairly large variation among methodologies in use, reflecting the absence of an established methodological framework. On the one hand, variation in methodologies may be desirable to assess the robustness of results; on the other hand, a lack of common standards can impede comparability among studies. To establish a comprehensive overview over the methodologies in use, we conducted a systematic review of studies assessing the effectiveness of non-pharmaceutical interventions between January 1, 2020 and January 12, 2021 (n = 248). We identified substantial variation in methodologies with respect to study setting, outcome, intervention, methodological approach, and effectiveness assessment. On this basis, we point to shortcomings of existing studies and make recommendations for the design of future studies.
Comparing reference point based interactive multiobjective optimization methods without a human decision maker
Authors: Chen Lu , Miettinen Kaisa , Xin Bin , Ojalehto Vesa
Published: September 2022

Interactive multiobjective optimization methods have proven promising in solving optimization problems with conflicting objectives since they iteratively incorporate preference information of a decision maker in the search for the most preferred solution. To find the appropriate interactive method for various needs involves analysis of the strengths and weaknesses. However, extensive analysis with human decision makers may be too costly and for that reason, we propose an artificial decision maker to compare a class of popular interactive multiobjective optimization methods, i.e., reference point based methods. Without involving any human decision makers, the artificial decision maker works automatically to interact with different methods to be compared and evaluate the final results. It makes a difference between a learning phase and a decision phase, that is, learns about the problem based on information acquired to identify a region of interest and refines solutions in that region to find a final solution, respectively. We adopt different types of utility functions to evaluation solutions, present corresponding performance indicators and propose two examples of artificial decision makers. A series of experiments on benchmark test problems and a water resources planning problem is conducted to demonstrate how the proposed artificial decision makers can be used to compare reference point based methods.
Cluster Expansions: Necessary and Sufficient Convergence Conditions
Authors: Jansen Sabine , Kolesnikov Leonid
Published: September 2022

We prove a new convergence condition for the activity expansion of correlation functions in equilibrium statistical mechanics with possibly negative pair potentials. For non-negative pair potentials, the criterion is an if and only if condition. The condition is formulated with a sign-flipped Kirkwood–Salsburg operator and known conditions such as Kotecký–Preiss and Fernández–Procacci are easily recovered. In addition, we deduce new sufficient convergence conditions for hard-core systems in $$\mathbb {R}^d$$

R

d

and $$\mathbb {Z}^d$$

Z

d

as well as for abstract polymer systems. The latter improves on the Fernández–Procacci criterion.
Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors
Authors: Mohammed Hamada H. H. , Ali Doaa Mohamed Elroby , Badr Mohamed , Habib Ahmed G. K. , Mahmoud Abobakr Mohamed , Farhan Sarah M. , Gany Shimaa Salah Hassan Abd El , Mohamad Soad A. , Hayallah Alaa M. , Abbas Samar H. , Abuo-Rahma Gamal El-Din A.
Published: September 2022

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06–42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15–3.25 µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06–1.53 µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03–3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01–7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.

Graphical abstract
Social Capital and Its Returns as an Explanation for Early Labor Market Success of Majority and Minority Members in the Netherlands
Authors: Baalbergen Ids , Jaspers Eva
Published: September 2022

This paper tests whether social capital can explain differences in labor market success between ethnic majority and minority members. To overcome problems of reverse causality—labor market success is not only the result of social capital, but also leads to better networks—the focus is on adolescents who enter the labor market. Data from the ‘Children of Immigrants Longitudinal Survey’ are used (N = 2574) and matched to register data from Statistics Netherlands. Hypotheses are tested with structural equation models and a longitudinal approach. Two different mechanisms are tested: the capital deficit and the return deficit. Ethnic majority and minority members do not differ in social capital, thus refuting the capital deficit hypothesis. However, for majority members, the upper reachability of their social capital negatively affects chances of unemployment and positively affects chances of having a permanent contract. For minority members, no such effects were observed, indicating that the same level of social capital that benefits majorities, does not benefit minorities. More research into the return deficit minority members face is needed.
Identification and complete genome sequencing of a divergent olive virus T isolate and an olive leaf yellowing-associated virus isolate naturally infecting olive trees in Greece
Authors: Katsiani Asimina , Panailidou Polina , Mathioudakis Matthaios , Katis Nikolaos , Maliogka Varvara I.
Published: September 2022

Several new full genome sequences of olive viruses came to light recently via high-throughput sequencing (HTS) analysis. In this study, total RNA HTS analysis of two Greek olive trees revealed the presence of an olive virus T (OlVT) isolate and an olive leaf yellowing-associated virus (OLYaV) isolate. The full viral genome of OlVT isolate (50Ch) is composed of 6862 nucleotides encoding for three proteins (replicase, movement protein, and capsid protein) with typical betaflexiviruses’ genomic features. However, both sequence and phylogenetic data analysis exhibited high levels of variability between 50Ch and the previously characterized OlVT isolates. In addition, the almost full genome of the Greek OLYaV isolate (OL2) was obtained, which is composed of 16,693 nucleotides encoding for 11 open reading frames (ORFs) and shares common genomic features with the recently characterized OLYaV isolates from Spain and Brazil. Sequence and phylogenetic analysis revealed high similarity between these three isolates. Due to problems encountered with the detection of both viruses, new nested RT-PCR assays were developed and applied. In addition, recombination events were observed in OlVT isolates (50Ch GR-168), thus highlighting the potential role of this mechanism in the evolution of the virus. This study is adding further knowledge to the limited information available about these recently characterized olive infecting viral pathogens and highlights their widespread distribution in Greece, one of the most important olive producing countries of the world.
A probabilistic hazard and risk assessment of exposure to metals and organohalogens associated with a traditional diet in the Indigenous communities of Eeyou Istchee (northern Quebec, Canada)
Authors: Moriarity Robert J. , Tsuji Leonard J. S. , Liberda Eric N.
Published: September 2022

Hunting, trapping, and fishing are part of an Indigenous lifestyle in subarctic Canada. However, this lifestyle may be a route of exposure to contaminants and may pose a risk for the people who rely on a subsistence diet. Monte Carlo simulations for the chemical concentration of eight game species and one fish species were carried out by randomly sampling 10,000 samples from the contaminant measures for each species. We then calculated a probabilistic non-carcinogenic hazard quotient or carcinogenic risk values to estimate the human health risk of exposure to contaminants. Of the species examined, ducks were of concern for potential carcinogenic risk. There was a modeled probabilistic 95th-percentile risk associated with the consumption of ducks and polybrominated biphenyl (PBB) congener 153 in boys, women, and men (1.09 × 10−6, 1.57 × 10−6, and 2.17 × 10−6, respectively) and, to a lesser extent, with geese and polychlorinated biphenyl (PCB) congener 153 in men (1.19 × 10−6). Contaminant concentration in the intake rate (food consumption) for PBB congener 153 exposure risk was more important than that for PCB congener 153, where intake rate had greater relevance. The consumption of waterfowl may increase the exposure to organohalogens; however, there are health and wellness benefits associated with the harvesting and consumption of subsistence foods that must also be considered. We recommend follow-up species-specific studies focused on ducks to clarify and elucidate the results in the present study.
Differences in detoxification mechanism and gene expression changes of sulfur metabolism in coping with the air pollutant SO2 between the resistant and ordinary poplar variety
Authors: Feng Jinxia , Wang Luyi , Liu Wenxin , Wan Xianchong , Chen Zhicheng , Zhao Jiaping
Published: September 2022

In this study, two poplar varieties with different resistance to sulfur dioxide were selected for a comparative experiment. SO2 fumigation to the poplars was carried out under controlled conditions to determine the variation in the activity of enzymes, the content of metabolites and the expression of enzymes genes in pathways of sulfur metabolism in plants. The results showed that the activity of enzymes and the content of sulfur metabolites were closely related to the response of the poplars to SO2 stress. Populus × euramericana cv. 'Purui' had two ways of detoxification: oxidation detoxification, oxidizing sulfite (SO32−) to sulfate SO42− by sulfite oxidase; reductive detoxification, SO32− being reduced to S2− by sulfite reductase (SiR). Moreover, OASTL and SAT activity, and levels of cysteine (CYS) and glutathione (GSH) also increased in P. × euramericana cv. 'Purui' in response to SO2 fumigation, and the gene expression encoding Glutathione S-transferases (GST), and some enzymes in cysteine and methionine metabolism was up-regulated. For Populus × euramericana cv. '74/76' with weaker resistance to sulfur dioxide, it only detoxified by increasing the activity of SiR, and but down-regulated the expression of gene encoding 3'-phosphoadenosine 5'-phosphosulfate synthase (PAPSS), which could affect the consumption of sulfite in the exposure to SO2. Thus, the SO2-resistant difference of the two poplar varieties is mainly attributed to variation in activity of the enzymes and content of their metabolites in pathways of sulfur metabolism, and gene expression of some enzymes in cysteine and methionine metabolism also plays a role in the resistant difference.
In vivo immunomodulation of IL6 signaling in a murine multiple trauma model
Authors: Malysch Tom , Reinhold Jens Michael , Becker Christopher A. , Schmidt-Bleek Katharina , Kleber Christian
Published: September 2022

A significant number of trauma patients die during the ICU phase of care because of a severe immune response. Interleukin-6 (IL6) plays a central role within that immune response, signaling through a membrane-bound (IL6-R) and a soluble IL6 receptor (sIL6-R). IL6 and the sIL6-R can form an agonistic IL6/sIL6-R-complex, activating numerous cells that are usually not IL6 responsive, a process called trans-signaling. We attempted to demonstrate that modulation of the IL6 signaling (classic signaling and trans-signaling) can attenuate the devastating immune response after trauma in a murine multiple trauma model. Mice were allocated to three study arms: sham, fracture or polytrauma. Half of the animals had the application of an IL6-R antibody following an intervention. After a pre-set time, blood samples were analysed for IL6 and sIL6-R serum levels, organs were analysed for neutrophil infiltration and end organ damage was evaluated. IL6 and sIL6-R showed a rapid peak after fracture, and much more markedly after polytrauma. These parameters were reduced significantly by globally blocking IL6 signaling via IL6-R antibody (Mab) application. Shock organ analysis also illustrated significant neutrophil infiltration following polytrauma, which was also abated via IL6-R Mab application. Furthermore, end organ damage was reduced by IL6-R Mab application. The study results prove the regulatory role of IL6 signaling pathways in polytrauma, with haemorrhagic shock being a major trigger of inflammatory response. Modulation of IL6 signaling shows promise in the prevention of adverse events like organ failure following major trauma and might be a target for in vivo immunomodulation to reduce mortality in severely injured patients, but further evaluation regarding classic IL6 signaling and IL6 trans-signaling is needed.
Prosaposin Reduces α-Synuclein in Cells and Saposin C Dislodges it from Glucosylceramide-enriched Lipid Membranes
Authors: Kojima Rika , Zurbruegg Mark , Li Tianyi , Paslawski Wojciech , Zhang Xiaoqun , Svenningsson Per
Published: September 2022

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder affecting over 1% of the 65 + age population. Saposin C, a lysosomal protein required for the normal activity of glucocerebrosidase (GCase), may serve as a disease modifier in PD. Saposin C is cleaved from its precursor, Prosaposin (PSAP), which is secreted as an uncleaved protein and exerts neuroprotective effects. In this study, we aim to elucidate the neuroprotective roles of PSAP and saposin C in PD by evaluating their effects on α-synuclein accumulation in human neuroblastoma cells. Stable overexpression of PSAP reduced monomeric α-synuclein levels in SH-SY5Y cells, while PSAP knockdown by small interfering RNA led to the opposite effect, and those effects were independent of GCase activity. Autophagy flux was decreased by stable PSAP overexpression. Furthermore, a flow-through assay revealed that recombinant saposin C was able to detach α-synuclein from artificial glucosylceramide-enriched lipid membranes at the lysosomal pH. Taken together, our findings provide further evidence that PSAP and saposin C as key proteins involved in α-synuclein clearance by dislodging it from lipid membranes.
Internet voting: the role of personality traits and trust across three parliamentary elections in Estonia
Authors: Sindermann Cornelia , Rozgonjuk Dmitri , Solvak Mihkel , Realo Anu , Vassil Kristjan
Published: September 2022

Some countries offer options to vote in elections remotely via the internet. However, not all voters take up this opportunity. This study investigates the role of the Five-Factor Model personality traits in the choice to use internet voting, and the potential mediating effects of trust in internet voting, controlling for sociodemographic variables. Survey data collected after national elections in Estonia in 2011 (N = 482), 2015 (N = 535), and 2019 (N = 546) were analyzed. Agreeableness was positively correlated with trust in internet voting in all samples. Additionally, Agreeableness was related to internet voting via trust, but not in all samples. Internet voting was predicted by higher trust in internet voting, better PC literacy, and speaking Estonian at home, across all samples. These results indicate that easy access to, and trust in, internet voting may play a bigger role in the decision to use internet voting than personality traits.
Age-Related Differences in the Perception of Robotic Referential Gaze in Human-Robot Interaction
Authors: Morillo-Mendez Lucas , Schrooten Martien G. S. , Loutfi Amy , Mozos Oscar Martinez
Published: September 2022

There is an increased interest in using social robots to assist older adults during their daily life activities. As social robots are designed to interact with older users, it becomes relevant to study these interactions under the lens of social cognition. Gaze following, the social ability to infer where other people are looking at, deteriorates with older age. Therefore, the referential gaze from robots might not be an effective social cue to indicate spatial locations to older users. In this study, we explored the performance of older adults, middle-aged adults, and younger controls in a task assisted by the referential gaze of a Pepper robot. We examined age-related differences in task performance, and in self-reported social perception of the robot. Our main findings show that referential gaze from a robot benefited task performance, although the magnitude of this facilitation was lower for older participants. Moreover, perceived anthropomorphism of the robot varied less as a result of its referential gaze in older adults. This research supports that social robots, even if limited in their gazing capabilities, can be effectively perceived as social entities. Additionally, this research suggests that robotic social cues, usually validated with young participants, might be less optimal signs for older adults.
Isotopic reconstruction of the subsistence strategy for a Central Italian Bronze Age community (Pastena cave, 2nd millennium BCE)
Authors: Cortese Francesca , De Angelis Flavio , Achino Katia Francesca , Bontempo Luana , di Cicco Maria Rosa , Gatta Maurizio , Lubritto Carmine , Salari Leonardo , Silvestri Letizia , Rickards Olga , Rolfo Mario Federico
Published: September 2022

The Pastena cave is located in central Italy, and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management, analysing the findings there discovered. Carbon and nitrogen stable isotope analysis was carried out on 40 charred seeds, six faunal remains, and four human individuals, investigating the whole bio-archaeological material available. To the best of our knowledge, this is one of the first papers presenting stable isotope analysis on carpological remains dated to the Italian Early-Middle Bronze Age. The obtained results are consistent with a diet based on terrestrial protein, mainly on plants, and secondly on animal products. The data suggest that plants, especially broad beans, were partially subjected to human management, while livestock was managed through different husbandry strategies. The cooperation between archaeological studies and molecular analysis allows us to contribute to clarifying the economic strategies for a Central Italian community in a scenario that is still poor in published data.
Exploration of biomarkers for the diagnosis, treatment and prognosis of cervical cancer: a review
Authors: Arip Masita , Tan Lee Fang , Jayaraj Rama , Abdullah Maha , Rajagopal Mogana , Selvaraja Malarvili
Published: September 2022

As the fourth most diagnosed cancer, cervical cancer (CC) is one of the major causes of cancer-related mortality affecting females globally, particularly when diagnosed at advanced stage. Discoveries of CC biomarkers pave the road to precision medicine for better patient outcomes. High throughput omics technologies, characterized by big data production further accelerate the process. To date, various CC biomarkers have been discovered through the advancement in technologies. Despite, very few have successfully translated into clinical practice due to the paucity of validation through large scale clinical studies. While vast amounts of data are generated by the omics technologies, challenges arise in identifying the clinically relevant data for translational research as analyses of single-level omics approaches rarely provide causal relations. Integrative multi-omics approaches across different levels of cellular function enable better comprehension of the fundamental biology of CC by highlighting the interrelationships of the involved biomolecules and their function, aiding in identification of novel integrated biomarker profile for precision medicine. Establishment of a worldwide Early Detection Research Network (EDRN) system helps accelerating the pace of biomarker translation. To fill the research gap, we review the recent research progress on CC biomarker development from the application of high throughput omics technologies with sections covering genomics, transcriptomics, proteomics, and metabolomics.
Distributional Validation of Precipitation Data Products with Spatially Varying Mixture Models
Authors: Warr Lynsie R. , Heaton Matthew J. , Christensen William F. , White Philip A. , Rupper Summer B.
Published: September 2022

The high mountain regions of Asia contain more glacial ice than anywhere on the planet outside of the polar regions. Because of the large population living in the Indus watershed region who are reliant on melt from these glaciers for fresh water, understanding the factors that affect glacial melt along with the impacts of climate change on the region is important for managing these natural resources. While there are multiple climate data products (e.g., reanalysis and global climate models) available to study the impact of climate change on this region, each product will have a different amount of skill in projecting a given climate variable, such as precipitation. In this research, we develop a spatially varying mixture model to compare the distribution of precipitation in the High Mountain Asia region as produced by climate models with the corresponding distribution from in situ observations from the Asian Precipitation—Highly Resolved Observational Data Integration Towards Evaluation (APHRODITE) data product. Parameter estimation is carried out via a computationally efficient Markov chain Monte Carlo algorithm. Each of the estimated climate distributions from each climate data product is then validated against APHRODITE using a spatially varying Kullback–Leibler divergence measure. Supplementary materials accompanying this paper appear online.
Myxolipoma of hand in a child: case report of a rare tumor
Authors: Deka Jeena Bordoloi , Shah Mohit Veer Kumar , Shah Ritu , Bhatnagar Nidhi , Bortolotto Chandra , Jiménez Fernando
Published: September 2022

Lipomatous tumors account for less than 10% of tumors in the pediatric population. Myxolipomas (a subset of lipoma characterised by mature adipose tissue and abundant mucoid substance) are found to be even rarer. There are a few case reports in different body parts like heart, kidney, oral cavity, epiglottis, cervical and mediastinal regions. However, there are no case reports on the involvement of the hands in any age group. High resolution ultrasound is the imaging modality of choice for the initial evaluation of superficial soft tissue tumors, their site, nature and extent. In conjunction with clinical findings and age of presentation, it helps in narrowing down the differential diagnosis and planning the management. Hyperechoic fatty tumors in the pediatric hand are mostly benign and includes lipomas, lipoblastomas and fibrous hamartomas of infancy as the main differentials. A definitive diagnosis is based on a histo-pathological and molecular cytogenetic examination. This article presents a never before reported case of a rare, large, myxolipoma of the hand in a 22-month-old boy.
Clinical characteristics and outcomes of a patient population with atypical hemolytic uremic syndrome and malignant hypertension: analysis from the Global aHUS registry
Authors: Halimi Jean-Michel , Al-Dakkak Imad , Anokhina Katerina , Ardissino Gianluigi , Licht Christoph , Lim Wai H. , Massart Annick , Schaefer Franz , Walle Johan Vande , Rondeau Eric
Published: September 2022

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA.

Methods

This analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (n = 71) and without (n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension.

Results

While demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01–0.87],P = 0.036).

Conclusions

These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA.

Trial registration details

Atypical Hemolytic-Uremic Syndrome (aHUS) Registry.

Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).

Graphical abstract
Asymptotics for the twisted eta-product and applications to sign changes in partitions
Authors: Bridges Walter , Franke Johann , Garnowski Taylor
Published: September 2022

We prove asymptotic formulas for the complex coefficients of $$(\zeta q;q)_\infty ^{-1}$$

(
ζ
q
;
q
)

∞

-
1

, where $$\zeta $$
ζ
is a root of unity, and apply our results to determine secondary terms in the asymptotics for p(a, b, n), the number of integer partitions of n with number of parts congruent a modulo b. Our results imply that, as $$n \rightarrow \infty $$

n
→
∞

, the difference $$p(a_1,b,n)-p(a_2,b,n)$$

p

(

a
1

,
b
,
n
)

-
p

(

a
2

,
b
,
n
)

for $$a_1 \ne a_2$$

a
1

≠

a
2

oscillates like a cosine when renormalized by elementary functions. Moreover, we give asymptotic formulas for arbitrary linear combinations of $$\{p(a,b,n)\}_{1 \le a \le b}.$$

{
p

(
a
,
b
,
n
)

}

1
≤
a
≤
b

.
Occupational risk assessment based on employees’ knowledge and awareness of hazards in mining
Authors: Patyk Michał , Nowak-Senderowska Dagmara
Published: September 2022

Analyses and assessments of hazards occurring in work processes are carried out by teams, in which there is usually one representative of the personnel, as the embodiment of the active participation of employees in the assessment of occupational risks. This is why the article presents research on all employees’ knowledge and awareness about risks in their work environment. The research was carried out in the form of an employee survey in one of the open-pit mines, at workstations dealing with the loading and transporting of excavated material. The survey included a list of 40 hazards divided into four groups: (1) hazards related to machines and equipment used, (2) hazards related to exposure, (3) hazards with an impact extending beyond the workstation and (4) hazards of an ergonomic nuisance nature, where employees were required to indicate which hazards apply to their workplaces and determine their level of significance, probability of occurrence and the scale of possible effects. In this way, a hierarchical identification of threats occurring at the analyzed workplaces was made, and the obtained results were used to determine the amount of occupational risk both for specific workstations and for the whole technological process. The measures of the magnitude of occupational risk obtained using the proposed method have showed that, according to the respondents, greatest risks at the workstation are associated with moving machines and vehicles and with mobile equipment. Equally important risks, which were often mentioned by employees, were those directly related to their health, i.e., related to ergonomic nuisance and exposure. Threats resulting from geological and mining conditions, considered typical for mining, were important for the surveyed miners but they were not the most important owing to proper prevention, good organization of work and high safety culture The active involvement of the crew in the process of assessing occupational hazards allowed to identify the significance of each hazard, in the opinion of the personnel working at various places and to use this ranking for determining occupational risk levels in the mining company concerned. The research has also outlined another goal to be achieved: a comparison of the relative significance of hazards identified by the employees and of the hazards listed in occupational risk assessment matrices used by mines.
Loss of disability-adjusted life years due to heat-related sleep disturbance in the Japanese
Authors: Ihara Tomohiko , Narumi Daisuke , Fukuda Sanae , Kondo Hiroaki , Genchi Yutaka
Published: September 2022

The purpose of this study was to quantify the sleep disturbances caused by climate change using disability-adjusted life years (DALY). The revised sleep quality index for daily sleep (SQIDS2), a self-administered questionnaire for daily sleep quality, was developed to assess daily sleep disturbances. This questionnaire referenced and simplified the Pittsburgh Sleep Quality Index (PSQI). This study was conducted in Nagoya City in August 2011 and 2012. Sleep quality was measured using SQIDS2 and PSQI. A total of 574 participants in 2011 and 710 in 2012 responded to the survey. The sleep disturbance prevalence calculated from the SQIDS2 score was correlated with the daily minimum temperature (p = 0.0067). This score increased when the daily minimum temperature was above 24.8 °C. When correcting for the PSQI score, DALY loss due to heat-related sleep disturbances in Nagoya City (population: 2,266,851) was estimated to be 81.8 years in 2012. This value was comparable to the DALY loss due to heatstroke. Sleep disturbance due to climate change was quantified using the DALY based on the PSQI. Legislators must recognize the critical impact of the damage caused by sleep disturbances due to high temperatures at night. Additionally, a daily minimum temperature of 25 °C should be the starting point when establishing a goal or guideline for nighttime temperature.
Laser Soldering and Welding for Ossicular Reconstruction: An in Vitro Test
Authors: Park Moon Suh , Min Hun Ki
Published: September 2022

To evaluate the possibility of laser application in ossicular reconstruction, soldering and welding of bony tissue with proteineous materials was performed by using a Co2 laser, and the bonding strength of these materials was measured with a gradual weighing system. The soldered and welded surface of bone was observed with a scanning electron microscope. Additionally, welding of human ossicles and synthetic materials was experimentally tried with lasers, and morphologic changes were observed and recorded. A scanning electron microscopic examination was also done. A 40% albumin solution and commercial fibrin glue showed the best bonding strength. Bridging of denatured protein solder may be a mechanism of bonding. Polycel was melted by using a laser beam, and melted Polycel covered the surface of the ossicle. However, the bonding strength was not enough to use, and exact measurement of bonding strength was not possible. These results suggested the possibility of laser soldering and welding in ossicular reconstruction, especially with ossicle or cortical bone.
Extended High‐Frequency Ototoxicity Induced by the First Administration of Cisplatin
Authors: Sakamoto Masayuki , Kaga Kimitaka , Kamio Tomokazu
Published: September 2022

The ototoxicity induced by cisplatin results in high‐frequency hearing loss. The sound‐pressure thresholds at extended high frequencies of 8 to 20 kHz were measured in 12 patients with head and neck cancer before and after the first administration of cisplatin. Ototoxicity was defined statistically by the newly introduced regression‐line analysis. This analysis revealed that the threshold of 1 of the 12 patients increased evenly from 8 to 10 kHz, and the damage to the hearing system of this patient was permanent. The reasons for such a low rate of ototoxicity might be the long‐term administration of low doses of cisplatin and the addition of fosfomycin.
Oxygenation of Advanced Head and Neck Cancer: Prognostic Marker for the Response to Primary Radiochemotherapy
Authors: Vanselow Bernhard , Eble Michael J. , Rudat Volker , Wollensack Petra , Conradt Christian , Dietz Andreas
Published: September 2022

Recent clinical studies suggest that the degree of tumor oxygenation may be predictive of the response of radiation therapy for cancer. In an exploratory investigation of cervical lymph node metastases in 27 patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx, this relationship was investigated by means of oxygen measurements with an Eppendorf Po2 histograph. The measurements were made before the start of radiation therapy and after the first week of therapy. Clinical response was evaluated 6 weeks after the completion of therapy. Before therapy, marked hypoxia was observed in the lymph node metastases, with a mean Po2 value of 16.1 ± 8.2 mm Hg and a hypoxic fraction (Po2 < 10 mm Hg) of 56.4% ± 20.0%. After the first week of radiation (9 Gy) there was a general reoxygenation (ΔPo2 = 5.0 ± 10.1 mm Hg, P < 0.05; Δhypoxic fraction = −11.3% ± 31.3%, P = 0.11). A relationship between the degree of reoxygenation and tumor response was not observed. Patients without at least partial lymph node response (n = 8) showed poorer pretherapeutic oxygenation (Po2 mean = 11.1 ± 2.9 mm Hg) than those who responded to the therapy (n = 19, PO2 mean = 18.2 ± 8.8 mm Hg). In this investigation of a defined set of patients with advanced carcinoma of the oropharynx and hypopharynx, we found that pretherapeutic oxygenation data are predictive for the therapeutic response to radiation therapy or radiochemotherapy.
Epithelial Differentiation in Developing Murine Eustachian Tube and Middle Ear
Authors: Park Keehyun , Lee Young Don , Park Hong‐Joon , Chun Young‐Myoung
Published: September 2022

Detailed information on how an epithelial differentiation occurred in the developing eustachian tube and middle ear would be helpful in understanding both normal physiology and pathology of the tubotympanum. This study was undertaken to establish patterns of laminin and E‐cadherin in the embryonic mouse eustachian tube and middle ear by use of immunohistochemistry at a stage when epithelial differentiation is taking place. This study was also designed to clarify the role of the middle ear mesenchyme. During the development of the eustachian tube, relatively high immunoreactivity to laminin was observed in the epithelium at gestational days 16 and 17, when the developments of ciliated and secretory cells were first observed. At the time of birth, in contrast to epithelium of the eustachian tube, epithelium of the middle ear cavity showed predominant expression of laminin and E‐cadherin. These findings suggest that the expressions of laminin and E‐cadherin may be correlated with maturation of the epithelium in the eustachian tube and middle ear and that the epithelial differentiation of the developing murine eustachian tube and middle ear may be controlled by epithelial‐mesenchymal interaction and cell‐to‐cell interaction.
Facial Nerve Stimulation and Postparotidectomy Facial Paresis
Authors: Reilly Jacquelyn , Myssiorek David
Published: September 2022

OBJECTIVE

We sought to evaluate the association of intraoperative facial nerve stimulation and postoperative facial nerve paresis/paralysis.

STUDY DESIGN AND SETTING

Eighty‐nine consecutive patients who underwent parotidectomy by a single surgeon were retrospectively analyzed for age, gender, size of tumor, tumor histology, and intraoperative use of a facial nerve stimulator.

RESULTS

Facial paresis developed in 22% (10 of 46) of the patients who were stimulated and 22% (5 of 23) of the nonstimulated patients. These results were not statistically significant (P = 1.0000). There was no permanent paralysis in either group. The tumor type and size and gender and age of the patient did not affect the outcome.

CONCLUSION

There was no difference in the incidence of postoperative facial nerve paresis or paralysis between the stimulated and nonstimulated patients. Routine use of a stimulator is not necessary during parotid surgery because its use does not prevent or promote facial nerve injury.
Follow‐up of 366 Ears after Tympanostomy Tube Insertion: Why is it Draining?
Authors: Kalcioglu M. Tayyar , Cokkeser Yasar , Kizilay Ahmet , Ozturan Orhan
Published: September 2022

OBJECTIVE

Tympanostomy tube insertion is one of the most frequently performed procedures in otolaryngology. Complications, such as otorrhea, tympanosclerosis, and cholesteatoma, have been reported in the literature after its application.

STUDY DESIGN

This study reports the complications encountered with 239 children (439 ears) with a follow‐up of 7 to 73 months (median, 29 months) after tympanostomy tube insertion. Hearing results and middle ear pressures were compared and complications were noted in 366 ears that were available for the study.

RESULTS

Otorrhea developed in 3 (0.8%) cases. Tympanosclerosis was seen in 74 (20.2%) cases. Tympanic membrane perforation, retraction pocket, granulation tissue, and atelectasis were seen in 4.6%, 5.2%, 1.1%, and 6%, respectively. No patients developed cholesteatoma after tube insertion. Hearing results were improved postoperatively in 93.4% of patients (median, 14.2 dB) and worse in 6.6% of patients (median, 8.3 dB). The average extrusion time was 7.3 months for grommet and 16.3 months for T‐tubes.

CONCLUSION

Multifactor etiologies show some unsolved or misunderstood underlying pathology, or unmentioned environmental factor such as atopy due to rich flora and humidity might exist to consider in the pathophysiology of the otorrhea.