bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic STAMP2 alleviates polychlorinated biphenyl‐induced steatosis and hepatic iron overload in NAFLD models
Authors: Kim Hye Young , Park Chul Hee , Park Joon Beom , Ko Kangeun , Lee Mi Hwa , Chung Jin , Yoo Young Hyun
Published: May 2022

Polychlorinated biphenyls (PCBs) have been associated with neurotoxicity, hepatoxicity, oncogenicity, and endocrine‐disrupting effects. Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL/6 mice. Male C57Bl/6 mice were fed a standard diet or a 60% high‐fat diet and exposed to Aroclor 1260 (10 mg/kg or 20 mg/kg) or PCB 126 (1 mg/kg or 5 mg/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5 weeks) for 6 weeks. In mice, both Aroclor 1260 and PCB 126‐induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure‐induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB‐induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB‐induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB‐induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure‐induced NAFLD.
Material and food exploration by zoo‐housed animals can inform cognition and enrichment apparatus design
Authors: Clark Fay E. , Chivers Lucy , Pearson Olivia
Published: May 2022

To robustly study zoo animal cognition and provide effective enrichment, we must provide animals with carefully designed apparatus made from appropriate (safe, attractive, practical) materials. However, all too often, this design phase is overlooked or omitted from the literature. We evaluated how a troop of 12 ring‐tailed lemurs (Lemur catta) explored a range of novel materials and whole foods during outdoor social testing. These items were not intended to test cognition or be enriching; rather we viewed them as the potential “building blocks” from which to build our future apparatus. Lemurs preferred to explore wooden surfaces, but had no preference for manipulanda made from different materials. Large amounts of metal and untreated wood should be avoided in the future; metal produced too much heat and glare, and wood was damaged by biting/chewing. Lemurs used one or two hands to explore manipulanda, and simple touching was more common than twisting or pulling. However, lemurs were most likely to explore by smell than touch or by mouth. Social testing preserved “normal” conditions for the lemurs, including natural food stealing and scrounging in high‐ and low‐ranking individuals, respectively. Our findings culminated in the development of a static, low‐level cognitive task apparatus, constructed from modular plastic units. We encourage other researchers to report how they develop cognitive and enrichment apparatuses and consider a similar preference‐testing approach.
In Vivo Tracking of Bacterial Colonization in Different Murine Models Using Bioluminescence: The Example of Salmonella
Authors: Koczerka Michaël , Lantier Isabelle , Pinard Anne , Morillon Marie , Deperne Justine , Gal-Mor Ohad , Grépinet Olivier , Virlogeux-Payant Isabelle
Published: May 2022

Applications of bioluminescence for the in vivo study of pathogenic microorganisms are numerous, ranging from the quantification of virulence gene expression to measuring the effect of antimicrobial molecules on the colonization of tissues and organs by the pathogen. Most studies are performed in mice, but recent works demonstrate that this technique is applicable to larger animals like fish, guinea pigs, ferrets, and chickens. Here, we describe the construction and the utilization of a constitutively luminescent strain of Salmonella Typhimurium to monitor in vivo and ex vivo the colonization of mice in the gastroenteritis, typhoid fever, and asymptomatic carriage models of Salmonella infection.
Plant-Based Cell-Free Transcription and Translation of Recombinant Proteins
Authors: Buntru Matthias , Vogel Simon , Finnern Ricarda , Schillberg Stefan
Published: May 2022

Plant cell-free lysates contain all the cellular components of the protein biosynthesis machinery, providing an alternative to intact plant cells, tissues, and whole plants for the production of recombinant proteins. Cell-free lysates achieve rapid protein production (within hours or days) and allow the synthesis of proteins that are cytotoxic or unstable in living cells. The open nature of cell-free lysates and their homogeneous and reproducible performance is ideal for protein production, especially for screening applications, allowing the direct addition of nucleic acid templates encoding proteins of interest, as well as other components such as enzyme substrates, chaperones, artificial amino acids, or labeling molecules. Here we describe procedures for the production of recombinant proteins in the ALiCE (Almost Living Cell-free Expression) system, a lysate derived from tobacco cell suspension cultures that can be used to manufacture protein products for molecular and biochemical analysis as well as applications in the pharmaceutical industry.
Decay of the charged Higgs boson and the top quark in two-Higgs-doublet model at NNLO in QCD
Authors: Shen Xiao-Min , Hu YaLu , Sun ChuanLe , Gao Jun
Published: May 2022

Abstract

We present numerical calculations of the partial width of the charged Higgs boson decay into a top quark, H− → $$ \overline{t} $$

t
¯

+ b + X, and the partial width of the top quark decay into a light charged Higgs boson t → H+ + b + X at next-to-next-to-leading order (NNLO) in QCD, based on a factorization formula of the jet mass. The NNLO corrections significantly reduce the renormalization scale dependence of the partial decay width in both cases. We show relative size of the NNLO corrections for different charged Higgs boson masses and for different renormalization scales. The NNLO corrections are about 16% (1%) of the leading order widths for the charged Higgs boson mass of 200 GeV (2000 GeV), while it is quite small for the top quark decay. Our analyses are independent of the detailed structure of the Yukawa couplings, and can be applied to various new physics models, as demonstrated by the decay branching ratio in different types of the two-Higgs-doublet models.
Instanton expansions and phase transitions
Authors: Stout John
Published: May 2022

Abstract

A central object in any axionic theory is its periodic potential, which is typically generated by instantons. The goal of this paper is to understand what physically happens to the theory when we lose control of the potential’s instanton expansion. We argue, using the Yang-Lee theory of phase transitions, that the theory breaks down in the classic sense: states become light. However, these states are not necessarily light for all values of the axion and there can be large regions where the effective description remains valid. We find alternative expressions for the effective potential in terms of the properties of these light states, which remain useful even when the instanton expansion breaks down, and thus initiate a push beyond the lamppost of large instanton actions. Most of these questions are motivated by the axionic Weak Gravity Conjecture, which we reformulate without reference to instanton actions. We also comment on its ability to constrain large-field axion inflation.
Krylov complexity in saddle-dominated scrambling
Authors: Bhattacharjee Budhaditya , Cao Xiangyu , Nandy Pratik , Pathak Tanay
Published: May 2022

Abstract

In semi-classical systems, the exponential growth of the out-of-time-order correlator (OTOC) is believed to be the hallmark of quantum chaos. However, on several occasions, it has been argued that, even in integrable systems, OTOC can grow exponentially due to the presence of unstable saddle points in the phase space. In this work, we probe such an integrable system exhibiting saddle-dominated scrambling through Krylov complexity and the associated Lanczos coefficients. In the realm of the universal operator growth hypothesis, we demonstrate that the Lanczos coefficients follow the linear growth, which ensures the exponential behavior of Krylov complexity at early times. The linear growth arises entirely due to the saddle, which dominates other phase-space points even away from itself. Our results reveal that the exponential growth of Krylov complexity can be observed in integrable systems with saddle-dominated scrambling and thus need not be associated with the presence of chaos.
Genomic prediction of zinc-biofortification potential in rice gene bank accessions
Authors: Rakotondramanana Mbolatantely , Tanaka Ryokei , Pariasca-Tanaka Juan , Stangoulis James , Grenier Cécile , Wissuwa Matthias
Published: May 2022

Key message

A genomic prediction model successfully predicted grain Zn concentrations in 3000 gene bank accessions and this was verified experimentally with selected potential donors having high on-farm grain-Zn in Madagascar.

Increasing zinc (Zn) concentrations in edible parts of food crops, an approach termed Zn-biofortification, is a global breeding objective to alleviate micro-nutrient malnutrition. In particular, infants in countries like Madagascar are at risk of Zn deficiency because their dominant food source, rice, contains insufficient Zn. Biofortified rice varieties with increased grain Zn concentrations would offer a solution and our objective is to explore the genotypic variation present among rice gene bank accessions and to possibly identify underlying genetic factors through genomic prediction and genome-wide association studies (GWAS). A training set of 253 rice accessions was grown at two field sites in Madagascar to determine grain Zn concentrations and grain yield. A multi-locus GWAS analysis identified eight loci. Among these, QTN_11.3 had the largest effect and a rare allele increased grain Zn concentrations by 15%. A genomic prediction model was developed from the above training set to predict Zn concentrations of 3000 sequenced rice accessions. Predicted concentrations ranged from 17.1 to 40.2 ppm with a prediction accuracy of 0.51. An independent confirmation with 61 gene bank seed samples provided high correlations (r = 0.74) between measured and predicted values. Accessions from the aus sub-species had the highest predicted grain Zn concentrations and these were confirmed in additional field experiments, with one potential donor having more than twice the grain Zn compared to a local check variety. We conclude utilizing donors from the aus sub-species and employing genomic selection during the breeding process is the most promising approach to raise grain Zn concentrations in rice.
RETRACTED ARTICLE: Calcium-dependent transcriptional changes in human pancreatic islet cells reveal functional diversity in islet cell subtypes
Authors: Yoon Ji Soo , Sasaki Shugo , Velghe Jane , Lee Michelle Y. Y. , Winata Helena , Nian Cuilan , Lynn Francis C.
Published: May 2022

Aims/hypothesis

Pancreatic islets depend on cytosolic calcium (Ca2+) to trigger the secretion of glucoregulatory hormones and trigger transcriptional regulation of genes important for islet response to stimuli. To date, there has not been an attempt to profile Ca2+-regulated gene expression in all islet cell types. Our aim was to construct a large single-cell transcriptomic dataset from human islets exposed to conditions that would acutely induce or inhibit intracellular Ca2+ signalling, while preserving biological heterogeneity.

Methods

We exposed intact human islets from three donors to the following conditions: (1) 2.8 mmol/l glucose; (2) 16 mmol/l glucose and 40 mmol/l KCl to maximally stimulate Ca2+ signalling; and (3) 16 mmol/l glucose, 40 mmol/l KCl and 5 mmol/l EGTA (Ca2+ chelator) to inhibit Ca2+ signalling, for 1 h. We sequenced 68,650 cells from all islet cell types, and further subsetted the cells to form an endocrine cell-specific dataset of 59,373 cells expressing INS, GCG, SST or PPY. We compared transcriptomes across conditions to determine the differentially expressed Ca2+-regulated genes in each endocrine cell type, and in each endocrine cell subcluster of alpha and beta cells.

Results

Based on the number of Ca2+-regulated genes, we found that each alpha and beta cell cluster had a different magnitude of Ca2+ response. We also showed that polyhormonal clusters expressing both INS and GCG, or both INS and SST, are defined by Ca2+-regulated genes specific to each cluster. Finally, we identified the gene PCDH7 from the beta cell clusters that had the highest number of Ca2+-regulated genes, and showed that cells expressing cell surface PCDH7 protein have enhanced glucose-stimulated insulin secretory function.

Conclusions/interpretation

Here we use our large-scale, multi-condition, single-cell dataset to show that human islets have cell-type-specific Ca2+-regulated gene expression profiles, some of them specific to subpopulations. In our dataset, we identify PCDH7 as a novel marker of beta cells having an increased number of Ca2+-regulated genes and enhanced insulin secretory function.

Data availability

A searchable and user-friendly format of the data in this study, specifically designed for rapid mining of single-cell RNA sequencing data, is available at https://lynnlab.shinyapps.io/Human_Islet_Atlas/. The raw data files are available at NCBI Gene Expression Omnibus (GSE196715).

Graphical abstract
Contingency analysis for gas transport networks with hydrogen injection
Authors: Clees Tanja
Published: May 2022

Novel methods for contingency analysis of gas transport networks are presented. They are motivated by the transition of our energy system where hydrogen plays a growing role. The novel methods are based on a specific method for topological reduction and so-called supernodes. Stationary Euler equations with advanced compressor thermodynamics and a gas law allowing for gas compositions with up to 100$$\%$$%hydrogen are used. Several measures and plots support an intuitive comparison and analysis of the results. In particular, it is shown that the newly developed methods can estimate locations and magnitudes of additional capacities (injection, buffering, storage etc.) with a reasonable performance for networks of relevant composition and size.
Does the smell of alcohol make it harder to resist? The impact of olfactory cues on inhibitory control and attentional bias
Authors: Monk R. L. , Qureshi A. , Wernham G. , Heim D.
Published: May 2022

Background

It is well known that, owing to associative processing, olfactory cues can impact memory, emotion and behaviour. Research also points to a link between the smells of particular substances and craving. Yet, to date, little research has investigated how smell may impact other cognitive processes that are known to drive alcohol consumption.

Aim

To assess how exposure to alcohol-related (vodka) relative to neutral (citrus) olfactory cues impacts inhibitory control and attentional bias.

Method

Participants took part in a go/no-go (Study 1) and Stroop task (Study 2) while wearing masks that were pre-treated with vodka or citrus oil of equivalent intensity.

Study 1 results

Response error rates were higher in participants in the alcohol-related (versus neutral) olfactory condition, with no interaction between olfactory and visual cue.

Study 2 results

Responses to alcohol-related versus neutral words were similar, while performance appeared significantly impaired among participants wearing alcohol (relative to citrus) infused masks. Conclusion

The smell of alcohol may impair signal detection performance on the go/no-go and Stroop task. As inhibitory control and attentional processes are known to be associated with decisions to drink or exercise restraint, these results may have implications for our understanding of alcohol consumption and for tailoring interventions.
Dextran as internal calibrant for N-glycan analysis by liquid chromatography coupled to ion mobility-mass spectrometry
Authors: Manz Christian , Götze Michael , Frank Clemens , Zappe Andreas , Pagel Kevin
Published: May 2022

LC–MS is one of the most important tools for the comprehensive characterization of N-glycans. Despite many efforts to speed up glycan analysis via optimized sample preparation (e.g., faster enzyme digestion in combination with instant or rapid labeling dyes), a major bottleneck remains the rather long measurement times of HILIC chromatography. Further complication arises from the necessity to concomitantly calibrate with an external standard to allow for accurate retention times and the conversion into more robust GU values. Here we demonstrate the use of an internal calibration strategy for HILIC chromatography to speed up glycan analysis. By reducing the number of utilized dextran oligosaccharides, the calibrant can be spiked directly into the sample such that external calibration runs are no longer required. The minimized dextran ladder shows accurate GU calibration with a minor deviation of well below 1% and can be applied without modifications in sample preparation or data processing. We further demonstrate the simultaneous use of the minimized dextran ladder as calibrant for the estimation of CCS values in traveling wave ion mobility spectrometry. In both cases, the minimized dextran ladder enables the measurement of calibrant and sample in a single HPLC run without losing information or accuracy.

Graphical abstract
A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene
Authors: Hofstaetter Jochen G. , Atkins Gerald J. , Kato Hajime , Kogawa Masakazu , Blouin Stéphane , Misof Barbara M. , Roschger Paul , Evdokiou Andreas , Yang Dongqing , Solomon Lucian B. , Findlay David M. , Ito Nobuaki
Published: May 2022

Osteopetrosis is a heterogeneous group of rare hereditary diseases characterized by increased bone mass of poor quality. Autosomal-dominant osteopetrosis type II (ADOII) is most often caused by mutation of theCLCN7gene leading to impaired bone resorption. Autosomal recessive osteopetrosis (ARO) is a more severe form and is frequently accompanied by additional morbidities. We report an adult male presenting with classical clinical and radiological features of ADOII. Genetic analyses showed no amino-acid-converting mutation inCLCN7but an apparent haploinsufficiency and suppression ofCLCN7mRNA levels in peripheral blood mononuclear cells. Next generation sequencing revealed low-frequency intronic homozygous variations inCLCN7, suggesting recessive inheritance. In silico analysis of an intronic duplication c.595-120_595-86dup revealed additional binding sites for Serine- and Arginine-rich Splicing Factors (SRSF), which is predicted to impairCLCN7expression. Quantitative backscattered electron imaging and histomorphometric analyses revealed bone tissue and material abnormalities. Giant osteoclasts were present and additionally to lamellar bone, and abundant woven bone and mineralized cartilage were observed, together with increased frequency and thickness of cement lines. Bone mineralization density distribution (BMDD) analysis revealed markedly increased average mineral content of the dense bone (CaMeanT-score + 10.1) and frequency of bone with highest mineral content (CaHighT-score + 19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except for an unusually circular shape. Together, our findings suggest that the reduced expression ofCLCN7mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture. While the skeletal phenotype and medical history were suggestive of ADOII, genetic analysis revealed that this is a possible mild case of ARO due to deep intronic mutation.
Imaging PARP with [18F]rucaparib in pancreatic cancer models
Authors: Chan Chung Ying , Chen Zijun , Destro Gianluca , Veal Mathew , Lau Doreen , O’Neill Edward , Dias Gemma , Mosley Michael , Kersemans Veerle , Guibbal Florian , Gouverneur Véronique , Cornelissen Bart
Published: May 2022

Purpose

Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types ofBRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report thein vitroandin vivoevaluation of [18F]rucaparib in human pancreatic cancer models.

Method

We incorporated the positron-emitting18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models.

Results

Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib.In vivostudies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration).In vitroandin vivostudies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding.

Conclusion

Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers.
Rigorous Analysis and Dynamics of Hibler’s Sea Ice Model
Authors: Brandt Felix , Disser Karoline , Haller-Dintelmann Robert , Hieber Matthias
Published: May 2022

This article develops for the first time a rigorous analysis of Hibler’s model of sea ice dynamics. Identifying Hibler’s ice stress as a quasilinear second-order operator and regarding Hibler’s model as a quasilinear evolution equation, it is shown that a regularized version of Hibler’s coupled sea ice model, i.e., the model coupling velocity, thickness and compactness of sea ice, is locally strongly well-posed within the $$L_q$$

L
q

-setting and also globally strongly well-posed for initial data close to constant equilibria.
Intravesical aminophylline instillation as an alternative for balloon dilatation prior to semi-rigid ureteroscopic management of distal ureteral stones
Authors: Shabayek M. , Osman T. , Wahb M. , Elmoazen M. , Osman D. , Saafan A.
Published: May 2022

Purpose

In a randomized controlled trial, we evaluated the effect of intravesical aminophylline instillation (IVAI) on intraureteral pressure of lower ureter and its use as an alternative to balloon dilatation after failure of advancing semi-rigid ureteroscope through the ureteric orifice without endodilatation.

Methods

Our study included 83 patients with juxta-vesical distal ureteral calculi requiring endodilatation after unsuccessfully introducing the semi-rigid ureteroscope through the ureteric orifice. Patients were randomized into two groups: group A (study group) included 41 patients, where IVAI was used to dilate the ureter and facilitate ureteroscopy (the intraureteral pressure was measured using a pressure transducer connected to an invasive pressure monitor before and 5 min after IVAI), whereas group B (control group) included 42 patients, where balloon dilatation was used prior to ureteroscopy. Perioperative surgical outcomes of ureteroscopy were evaluated in both groups.

Results

A statistically significant decrease in mean intraureteral pressure of intravesical ureter was found after IVAI from 12.34 mmHg ± 1.94 before injection to 8.46 mmHg ± 1.94 after injection (P < 0.001). Ureteral injuries, postoperative pain and hematuria were statistically significantly less among the study group compared to the control group (P < 0.05). We did not find statistically significant differences in operative time, need for DJ ureteral stenting or stone-free rate between both groups and no perioperative side effects were associated with IVAI.

Conclusion

In ureteroscopic management of distal ureteral stones, intravesical aminophylline instillation is safe, inexpensive and effective in reducing intraureteral pressure and achieves comparable outcomes to balloon dilatation with less ureteral injuries, postoperative pain and hematuria.
Coleoptera claws and trichome interlocking
Authors: Salerno Gianandrea , Rebora Manuela , Piersanti Silvana , Saitta Valerio , Gorb Elena , Gorb Stanislav
Published: May 2022

The present study tests the hypothesis that the specialized claws with a basal tooth found in some coccinellid beetles represent an adaptation to interlock with flexible unbranched trichomes of different plants. We compared the attachment ability of three Coleoptera species, Chnootriba elaterii, Harmonia axyridis (both Coleoptera: Coccinellidae), and Chrysolina herbacea (Coleoptera: Chrysomelidae) with claws of different shape. The attachment ability of insect individuals with or without claws to a plant with leaves bearing straight non-branched trichomes (Cucurbita moschata) and to a plant with smooth leaves (Prunus laurocerasus) was measured in traction force experiments. Insect attachment ability was also tested on a resin replica of C. moschata leaf, to variate trichome stiffness, and on glass as a reference surface. Centrifugal force tester experiments were performed to compare the attachment ability of the two ladybird species to glass and to the leaf of C. moschata. Natural and artificial substrates were characterized in cryo-SEM. The collected data reveal that plant trichomes can enhance insect attachment to plant surface compared with smooth glass by increasing insect friction force, but this is directly related to the trichome stiffness. To effectively grasp soft trichomes, insects evolved special claws-associated structures, such as the dentate claws observed in Coccinellidae.
Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett’s esophagus: a matched case–control study
Authors: Helminen Olli , Melkko Jukka , Saarnio Juha , Sihvo Eero , Kuopio Teijo , Ohtonen Pasi , Kauppila Joonas H. , Karttunen Tuomo J. , Huhta Heikki
Published: May 2022

Barrett’s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett’s metaplasia and low-grade dysplasia. This was a retrospective matched case–control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett’s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett’s metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett’s metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett’s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd’s ratio 6.7, 95% CI 1.8–24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case–control study, p53 expression associated with a high risk of malignant progression in Barrett’s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.
Chondrocyte death involvement in osteoarthritis
Authors: Salucci S. , Falcieri E. , Battistelli M.
Published: May 2022

Chondrocyte apoptosis is known to contribute to articular cartilage damage in osteoarthritis and is correlated to a number of cartilage disorders. Micromass cultures represent a convenient means for studying chondrocyte biology, and, in particular, their death. In this review, we focused the different kinds of chondrocyte death through a comparison between data reported in the literature. Chondrocytes show necrotic features and, occasionally, also apoptotic features, but usually undergo a new form of cell death called Chondroptosis, which occurs in a non-classical manner. Chondroptosis has some features in common with classical apoptosis, such as cell shrinkage, chromatin condensation, and involvement, not always, of caspases. The most crucial peculiarity of chondroptosis relates to the ultimate elimination of cellular remnants. Independent of phagocytosis, chondroptosis may serve to eliminate cells without inflammation in situations in which phagocytosis would be difficult. This particular death mechanism is probably due to the unusual condition chondrocytes both in vivo and in micromass culture. This review highlights on the morpho-fuctional alterations of articular cartilage and focus attention on various types of chondrocyte death involved in this degeneration. The death features have been detailed and discussed through in vitro studies based on tridimensional chondrocyte culture (micromasses culture). The study of this particular mechanism of cartilage death and the characterization of different biological and biochemical underlying mechanisms can lead to the identification of new potentially therapeutic targets in various joint diseases.
Genuinely distributed Byzantine machine learning
Authors: El-Mhamdi El-Mahdi , Guerraoui Rachid , Guirguis Arsany , Hoang Lê-Nguyên , Rouault Sébastien
Published: May 2022

Machine learning (ML) solutions are nowadays distributed, according to the so-called server/worker architecture. One server holds the model parameters while several workers train the model. Clearly, such architecture is prone to various types of component failures, which can be all encompassed within the spectrum of a Byzantine behavior. Several approaches have been proposed recently to tolerate Byzantine workers. Yet all require trusting a central parameter server. We initiate in this paper the study of the “general” Byzantine-resilient distributed machine learning problem where no individual component is trusted. In particular, we distribute the parameter server computation on several nodes. We show that this problem can be solved in an asynchronous system, despite the presence of $$\frac{1}{3}$$

1
3

Byzantine parameter servers (i.e., $$n_{ps} > 3f_{ps}+1$$

n

ps

>
3

f

ps

+
1

) and $$\frac{1}{3}$$

1
3

Byzantine workers (i.e., $$n_w > 3f_w$$

n
w

>
3

f
w

), which is asymptotically optimal. We present a new algorithm, ByzSGD, which solves the general Byzantine-resilient distributed machine learning problem by relying on three major schemes. The first, scatter/gather, is a communication scheme whose goal is to bound the maximum drift among models on correct servers. The second, distributed median contraction (DMC), leverages the geometric properties of the median in high dimensional spaces to bring parameters within the correct servers back close to each other, ensuring safe and lively learning. The third, Minimum-diameter averaging (MDA), is a statistically-robust gradient aggregation rule whose goal is to tolerate Byzantine workers. MDA requires a loose bound on the variance of non-Byzantine gradient estimates, compared to existing alternatives [e.g., Krum (Blanchard et al., in: Neural information processing systems, pp 118-128, 2017)]. Interestingly, ByzSGD ensures Byzantine resilience without adding communication rounds (on a normal path), compared to vanilla non-Byzantine alternatives. ByzSGD requires, however, a larger number of messages which, we show, can be reduced if we assume synchrony. We implemented ByzSGD on top of both TensorFlow and PyTorch, and we report on our evaluation results. In particular, we show that ByzSGD guarantees convergence with around 32% overhead compared to vanilla SGD. Furthermore, we show that ByzSGD’s throughput overhead is 24–176% in the synchronous case and 28–220% in the asynchronous case.
Diet and exercise advice and referrals for cancer survivors: an integrative review of medical and nursing perspectives
Authors: Joseph Ria , Hart Nicolas H. , Bradford Natalie , Agbejule Oluwaseyifunmi Andi , Koczwara Bogda , Chan Alexandre , Wallen Matthew P. , Chan Raymond J.
Published: May 2022

Purpose

To examine the perspectives of medical and nursing health professionals concerning their roles and responsibilities in providing dietary and exercise advice to cancer survivors, and referrals to allied health professionals.

Methods

An integrative review. PubMed, CINAHL, PsycINFO, Embase, Web of Science databases, and bibliographies of relevant studies were searched from December 2011 to June 2021. All studies were eligible for inclusion. The Mixed-Methods Appraisal Tool (MMAT) was used to critically appraise included studies. Data were extracted and synthesised regarding the perspectives of medical and nursing health professionals on their roles, responsibilities, barriers, and facilitators.

Results

Twenty-one studies involving 3401 medical and nursing health professionals and 264 cancer survivors of diverse cancer types were included. Ten quantitative, nine qualitative, and two mixed-methods studies were eligible. All included studies met at least 80% of the quality criteria in the MMAT. Major findings include the following: (1) medical and nursing health professionals were unclear on their roles in providing dietary and exercise advice to cancer survivors but agreed they play a key role in referrals to dietitians and exercise professionals; (2) most cancer survivors valued the involvement of their general practitioner when receiving dietary and exercise advice.

Conclusion

Although medical and nursing health professionals understand that referrals to allied health professionals form part of their role, there is a lack of clarity regarding their roles to provide dietary and exercise advice to cancer survivors. Future studies should address barriers and facilitators of dietary and exercise advice and referral by medical and nursing health professionals.
Population kinetics of homoarginine and optimized supplementation for cardiovascular risk reduction
Authors: Kleist Christine J. , Choe Chi-Un , Atzler Dorothee , Schönhoff Mirjam , Böger Rainer , Schwedhelm Edzard , Wicha Sebastian G.
Published: May 2022

Homoarginine is an endogenous amino acid whose levels are reduced in patients with renal, cardio- and cerebrovascular disease. Moreover, low homoarginine concentrations independently predict morbidity and mortality in these patients. Besides endogenous synthesis, homoarginine is also a constituent of the human diet. The objective of the present study was to analyze the kinetics of orally supplemented homoarginine in human plasma by means of a pharmacometric approach. We developed a pharmacometric model to evaluate different dosing regimens, especially the regimen of 125 mg once weekly, based on a previous clinical study (n = 20). The model was adapted to account for differences in baseline homoarginine plasma concentrations between healthy and diseased individuals. A novel dosing regimen of 25 mg once daily led to higher attainment of homoarginine reference concentrations using clinical trial simulations. With 25 mg/day, the trough concentration of only 6% of the older and 3.8% of the younger population was predicted to be below the target concentration of 2.0–4.1 µmol/L. In synopsis, the new dosing regimen recapitulates the kinetics of homoarginine in healthy individuals optimally.
Efficacy of concentrated growth factor versus collagen membrane in reconstructive surgical therapy of peri-implantitis: 3-year results of a randomized clinical trial
Authors: Isler Sila Cagri , Soysal Fatma , Ceyhanlı Tugce , Bakırarar Batuhan , Unsal Berrin
Published: May 2022

Objectives

To compare the 3-year clinical and radiographic outcomes of two different reconstructive surgical management of peri-implantitis using a bone substitute in combination with either concentrated growth factor (CGF) or collagen membrane (CM).

Material and methods

Fifty-one patients who had at least one implant presenting peri-implantitis with an intrabony defect were filled with a xenogenic bone grafting material and covered either CGF or CM. Clinical and radiographic assessments were carried out at baseline and postoperative years 1 and 3. Three different composite outcomes were defined to evaluate treatment success at a 3-year follow-up. The effects of possible prognostic indicators on treatment success were identified by using multilevel regression analysis.

Results

The changes in probing depth (PD) and radiographic vertical defect depth (VDD) between baseline and year 1 and baseline and year 3 presented significantly greater decreases for the CM group in comparison with the CGF group (p < 0.05). No significant differences between the two treatment modalities were demonstrated regarding treatment success outcomes. History of periodontitis, VDD at baseline, and the number of intrabony defect walls revealed significant impacts on treatment success (p = 0.033; OR = 3.50,p = 0.039; OR = 0.975, andp = 0.024; OR = 7.0 andp = 0.019;OR = 6.0, respectively).

Conclusions

CM in combination with a bone substitute seems to have slightly better outcomes compared to the CGF membranes in reconstructive surgical therapy of peri-implantitis. The history of periodontitis, baseline VDD, and peri-implant bone defect configuration could be possible predictors influencing treatment success.

Trial registration

ClinicalTrials.gov NCT04769609.

Clinical relevance

For the reconstruction of peri-implant bone defects, using a bone substitute in combination with a collagen membrane may show more favorable outcomes.
A meta-analytic review of the impact of ADHD medications on anxiety and depression in children and adolescents
Authors: Bryant Annie , Schlesinger Hope , Sideri Athina , Holmes Joni , Buitelaar Jan , Meiser-Stedman Richard
Published: May 2022

Anxiety and depression are listed as common side effects for medications licensed for treating ADHD in children and adolescents. This meta-analytic review of randomised controlled trials aimed to explore the effect of medications on symptoms of anxiety and depression in children and adolescents with ADHD. A meta-analytic review of ADHD drug trials in children and adolescents was conducted. Random effects meta-analyses were conducted on anxiety and depression outcomes measured by validated psychological scales or side effect rating scales. Only 11% of eligible trials in this review reported anxiety and/or depression as an outcome or side effect, limiting the conclusions of the meta-analyses. Relative to placebo control, no significant effect of medication was found for symptoms of anxiety or depression in randomised controlled trials of ADHD medication in children and adolescents. This review highlights the systemic lack of mental health outcome reporting in child and adolescent ADHD drug trials. The importance of widespread implementation of standardised measurement of mental health outcomes in future trials is discussed.
Morphological and histological changes in the urethra after intraurethral nonablative erbium YAG laser therapy: an experimental study in beagle dogs
Authors: Xu Sheng-fei , Abulikim Kuerbanjiang , Wu Xiao-yu , Cheng Yu , Ling Qing , Rao Ke , Cui Kai , Chen Zhong , Du Guang-hui , Yuan Xiao-yi
Published: May 2022

The purpose of this study was to investigate the morphological and histological changes in the urethra in beagle dogs after intraurethral Er:YAG laser irradiation in nonablative mode to confirm the safety of this therapy. Six 2-year-old healthy female virgin beagle dogs (13 ± 1.51 kg) were used in this study. The animals were divided into 2 groups: the sham group, which received sham treatment (n = 3) involving insertion of an intraurethral cannula and laser delivery handpiece into the urethra without laser irradiation, and the experimental group (n = 3), which received intraurethral Er:YAG laser irradiation. The laser irradiation parameters were set according to clinical criteria (4 mm spot size, 1.5 J/cm2, 1.4 Hz, and 4 pulses) in nonablative mode. All animals received three sequential sessions at 4-week intervals. Urethrography and urethroscopy were performed in the 12th week and 13th week, respectively, after the first treatment. After urethroscopy, the animals were sacrificed, and urethral tissue was harvested for histological investigations. All procedures were performed under general anesthesia (40 mg/kg 3% sodium pentobarbital, i.v.). Transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression levels were measured to evaluate the biochemical characteristics of the scar. Urethral stricture was not found by urethrography or urethroscopy in either group. Urethral epithelium thickness and collagen expression under the urethral mucosa were significantly increased in the experimental group compared with the sham group. However, there were no significant differences in TGF-β1 and α-SMA expression between the experimental group and sham group (p > 0.05). Urethral stricture is not found in beagle dogs after clinically relevant intraurethral nonablative mode Er:YAG laser irradiation. Proliferation of urethral collagen and the urethral mucosa may be one of the mechanisms by which urine leakage symptoms can be improved.
Assessing the reliability and validity of an FRAM model: the case of driving in an overtaking scenario
Authors: Grabbe Niklas , Arifagic Almin , Bengler Klaus
Published: May 2022

Over the past two decades, systemic-based risk assessment methods have garnered more attention, and their use and popularity are growing. In particular, the functional resonance analysis method (FRAM) is one of the most widely used systemic methods for risk assessment and accident analysis. FRAM has been progressively evolved since its starting point and is considered to be the most recent and promising step in understanding socio-technical systems. However, there is currently a lack of any formal testing of the reliability and validity of FRAM, something which applies to Human Factors and Ergonomics research as a whole, where validation is both a particularly challenging issue and an ongoing concern. Therefore, this paper aims to define a more formal approach to achieving and demonstrating the reliability and validity of an FRAM model, as well as to apply this formal approach partly to an existing FRAM model so as to prove its validity. At the same time, it hopes to evaluate the general applicability of this approach to potentially improve the performance and value of the FRAM method. Thus, a formal approach was derived by transferring both the general understanding and definitions of reliability and validity as well as concrete methods and techniques to the concept of FRAM. Consequently, predictive validity, which is the highest maxim of validation, was assessed for a specific FRAM model in a driving simulator study using the signal detection theory. The results showed that the predictive validity of the FRAM model is limited and a generalisation with changing system conditions is impossible without some adaptations of the model. The applicability of the approach is diminished because of several methodological limitations. Therefore, the reliability and validity framework can be utilised to calibrate rather than validate an FRAM model.
Maximum Entropy Technique and Regularization Functional for Determining the Pharmacokinetic Parameters in DCE-MRI
Authors: Amini Farsani Zahra , Schmid Volker J
Published: May 2022

This paper aims to solve the arterial input function (AIF) determination in dynamic contrast-enhanced MRI (DCE-MRI), an important linear ill-posed inverse problem, using the maximum entropy technique (MET) and regularization functionals. In addition, estimating the pharmacokinetic parameters from a DCE-MR image investigations is an urgent need to obtain the precise information about the AIF–the concentration of the contrast agent on the left ventricular blood pool measured over time. For this reason, the main idea is to show how to find a unique solution of linear system of equations generally in the form of$$y=Ax+b,$$y=Ax+b,named an ill-conditioned linear system of equations after discretization of the integral equations, which appear in different tomographic image restoration and reconstruction issues. Here, a new algorithm is described to estimate an appropriate probability distribution function for AIF according to the MET and regularization functionals for the contrast agent concentration when applying Bayesian estimation approach to estimate two different pharmacokinetic parameters. Moreover, by using the proposed approach when analyzing simulated and real datasets of the breast tumors according to pharmacokinetic factors, it indicates that using Bayesian inference—that infer the uncertainties of the computed solutions, and specific knowledge of the noise and errors—combined with the regularization functional of the maximum entropy problem, improved the convergence behavior and led to more consistent morphological and functional statistics and results. Finally, in comparison to the proposed exponential distribution based on MET and Newton’s method, or Weibull distribution via the MET and teaching–learning-based optimization (MET/TLBO) in the previous studies, the family of Gamma and Erlang distributions estimated by the new algorithm are more appropriate and robust AIFs.
LncRNA ENSMUST_147219 mediates the progression of ischemic acute kidney injury by targeting the miR-221-5p/IRF6 axis
Authors: Liu Jing , Li Xiaozhou , Yang Jurong , Zhang Dongshan
Published: May 2022

Although previous studies have revealed that long noncoding RNAs (lncRNAs) regulate the progression of ischemic acute kidney injury (AKI), the exact role and mechanism of lncRNA ENSMUST_147219 in ischemic AKI are not clear. In the present study, lncRNA ENSMUST_147219 was induced by ischemic injury in vitro and in vivo. Functionally, lncRNA ENSMUST_147219 mediated apoptosis in mouse proximal tubule‐derived cell line (BUMPT). Mechanistically, lncRNA ENSMUST_147219 sponged the microRNA (miR)-221-5p to upregulate the expression of interferon regulatory factor 6 (IRF6) to drive apoptosis. Finally, knockdown of lncRNA ENSMUST_147219 markedly attenuated the ischemic AKI by targeting the miR-221-5p/IRF6 axis. Collectively, our data demonstrated that lncRNA ENSMUST_147219 promoted the development of ischemic AKI by regulating the miR-221-5p/IRF6 pathway, which could be considered a new therapeutic target for ischemic AKI.