bluuebunny/crossref_metadata_2025 huggingface dataset:
Materials Within a Digitalized Production Environment
Authors: Broeckmann Christoph , Bührig-Polaczek Andreas , Hallstedt Bengt , Krupp Ulrich , Rajaei Ali , Rom Michael , Rudack Maximilian , Schmitz Georg J. , Wesselmecking Sebastian
Published: June 2023

Materials serve as the foundation of the technical framework on which modern society relies every day. Generations have developed new materials, tried to understand the origins of their properties, and found ways to predict them. Modern computational tools have vastly expanded our capabilities to make predictions, not only of material properties but also of component properties and of the component health status over its life cycle. Integrated Computational Materials Engineering (ICME) aims at simulating the material and component properties along the complete process chain and across the length scales from microstructure to component scale. In this way a digital twin of the material or component can be generated, which can be leveraged to facilitate gains in productivity and service life of technical systems. By reducing the complexity of models for the digital twin where necessary, combining them with in-process data using innovative sensor technology and suitable mathematically driven approximation procedures such as machine learning, it is possible to conceive a digital material shadow that resolves elements of the dilemma between data granularity, data volume, and processing speed to enable process monitoring and control for materials processing. To enable communication between humans and machines it is necessary to create a strictly defined language in the form of ontologies. Ontologies are typically domain-specific, but care must be taken to make them consistent across domains. Integrated Structural Health Engineering (ISHE) aims at predicting and monitoring the health state of components over their entire life cycle, enabling timely replacement of components and avoiding costly and possibly life-threatening failures. In particular when components are subjected to cyclic loading, their structural health does not primarily depend on the average material properties, but on the presence of more or less statistically distributed defects. These defects are intrinsic to materials processing, cannot be completely avoided, and evolve during various stages of the production process. The objective of ISHE is to predict their formation and evolution during the production process and their impact on the component structural health during its life cycle. It is clear that the material and component properties are strongly dependent on the process by which they are produced. Therefore, many of the topics discussed in this part have relational counterparts in Part IV: Production.
Loss of functional peroxisomes leads to increased mitochondrial biogenesis and reduced autophagy that preserve mitochondrial function
Authors: Chi Lijun , Lee Dorothy , Leung Sharon , Hu Guanlan , Wen Bijun , Delgado-Olguin Paul , Vissa Miluska , Li Ren , Brumell John H. , Kim Peter K. , Bandsma Robert H. J.
Published: June 2023

Peroxisomes are essential for mitochondrial health, as the absence of peroxisomes leads to altered mitochondria. However, it is unclear whether the changes in mitochondria are a function of preserving cellular function or a response to cellular damage caused by the absence of peroxisomes. To address this, we developed conditional hepatocyte-specific Pex16 deficient (Pex16 KO) mice that develop peroxisome loss and subjected them to a low-protein diet to induce metabolic stress. Loss of PEX16 in hepatocytes led to increased biogenesis of small mitochondria and reduced autophagy flux but with preserved capacity for respiration and ATP capacity. Metabolic stress induced by low protein feeding led to mitochondrial dysfunction in Pex16 KO mice and impaired biogenesis. Activation of PPARα partially corrected these mitochondrial disturbances, despite the absence of peroxisomes. The findings of this study demonstrate that the absence of peroxisomes in hepatocytes results in a concerted effort to preserve mitochondrial function, including increased mitochondrial biogenesis, altered morphology, and modified autophagy activity. Our study underscores the relationship between peroxisomes and mitochondria in regulating the hepatic metabolic responses to nutritional stressors.
DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway
Authors: García-Moreno Juan F. , Lacerda Rafaela , da Costa Paulo J. , Pereira Marcelo , Gama-Carvalho Margarida , Matos Paulo , Romão Luísa
Published: June 2023

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3’end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.
Multidisciplinary structural optimization of novel high-aspect ratio composite aircraft wings
Authors: Kilimtzidis Spyridon , Kostopoulos Vassilis
Published: June 2023

Novel high-aspect ratio airframe designs pave the way for a more sustainable aviation future. Such configurations enhance the aerodynamic efficiency of an aircraft through induced drag reduction mechanisms. Further performance gains, mainly in terms of structural mass, are accomplished via composite materials airframes. Nevertheless, undesired phenomena such as geometric nonlinearities and aeroelastic couplings due to elevated flexibility may often rise, rendering the design and optimization of such airframes extremely intricate and prohibitive in terms of computational cost. Low-fidelity tools, often preferred on the early design stages, accelerate the design process, albeit suffering from reduced accuracy and ability to capture higher-order phenomena. Contrastingly, high-fidelity computational methods incur excessive computational cost and are therefore utilized at the later, detailed design stages. There arises, therefore, the need for a combination of the various fidelities involved in a cost-effective manner, in order to drive the design towards optimal configurations without significant performance losses. In our approach, variable fidelity analyses are initially conducted in order to shed light on their effect on the structural response of a high-aspect ratio composite materials reference wing. An optimization framework combining low and high-fidelity tools in a sequential manner is then proposed, aiming at attaining a minimum mass configuration subject to multidisciplinary design constraints. As demonstrated, reasonable mass reduction was obtained for a future aircraft wing configuration.
Clinical relevance of joint line obliquity after high tibial osteotomy for medial knee osteoarthritis remains controversial: a systematic review
Authors: Xie Tianshun , Brouwer Reinoud W. , van den Akker‐Scheek Inge , van der Veen Hugo C.
Published: June 2023

Purpose

To systematically review the literature on the association between knee joint line obliquity (KJLO) and clinical outcome after high tibial osteotomy (HTO) for medial knee osteoarthritis and summarize the KJLO cut‐off value used when studying this association.

Methods

A systematic search was conducted in three databases(PubMed, Embase, and Web of Science) on September 2022, updated on February 2023. Eligible studies describing postoperative KJLO in relation to clinical outcome after HTO for medial knee osteoarthritis were included. Nonpatient studies and conference abstracts without full‐text were excluded. Two independent reviewers assessed title, abstract and full‐text based on the inclusion and exclusion criteria. The modified Downs and Black checklist was used to assess the methodological quality of each included study.

Results

Of the seventeen studies included, three had good methodological quality, thirteen fair quality, and one had poor quality. Conflicting findings were shown on the associations between postoperative KJLO and patient‐reported outcome, medial knee cartilage regeneration, and 10‐year surgical survival in sixteen studies. Three good‐quality studies found no significant differences in lateral knee cartilage degeneration between postoperative medial proximal tibial angle > 95° and < 95°. Joint line orientation angles by the tibial plateau of 4° and 6°, joint line orientation angle by the middle knee joint space of 5°, medial proximal tibial angles of 95° and 98°, and Mikulicz joint line angle of 94° were KJLO cut‐off values used in the included studies.

Conclusion

Based on current evidence, the actual association between postoperative KJLO and clinical consequences after HTO for medial knee osteoarthritis cannot be ascertained. The clinical relevance of KJLO after HTO remains controversial.

Level of evidence

IV.
The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula
Authors: Gawrys Olga , Husková Zuzana , Škaroupková Petra , Honetschlägerová Zuzana , Vaňourková Zdeňka , Kikerlová Soňa , Melenovský Vojtěch , Bačová Barbara Szeiffová , Sykora Matúš , Táborský Miloš , Červenka Luděk
Published: June 2023

Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210 days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60 days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109 ± 28 nnmol/12 h), but the ACE inhibitor decreased it (-63 ± 21 nnmol/12 h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117 ± 3; day 2: 108 ± 1; day 14: 124 ± 2 mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.
Effect of lithium administration on brain activity under an emotion regulation paradigm in healthy participants: a functional magnetic resonance imaging study
Authors: Artiach Hortelano Pilar , Martens Marieke A. G. , Pringle Abigail , Harmer Catherine J
Published: June 2023

Rationale

Emotion regulation (ER) difficulties have been previously described in bipolar disorder (BD). Whilst lithium has been shown to be effective in the treatment of BD, the mechanisms underlying lithium’s effect on mood stabilisation remain unclear.

Objectives

Unravelling lithium’s effect on psychological processes impaired in BD, such as ER, could address this translational gap and inform the development of new treatments.

Methods

This study investigated the neural effects of lithium (800mg) on ER in 33 healthy volunteers in a double-blind between-groups design, randomised to lithium (n=17) or placebo (n=16) for 11 days. At treatment completion, participants underwent 3-Tesla fMRI scan whilst performing an ER task.

Results

Reappraisal reduced negative affect across groups and led to the expected increase in frontal brain activity. Participants receiving lithium showed (1) decreased activation in prefrontal and posterior parietal cortices and connectivity between the fronto-limbic network (Z>2.3, p<0.05 corrected); and (2) increased activity in the right superior temporal gyrus (Z>3.1, p<0.05 corrected) and connectivity between the right medial temporal gyrus (MTG) and left middle frontal gyrus (Z>2.3, p<0.05 corrected) during reappraisal. Further effects of lithium were found in response to negative picture presentation, whereby an anticorrelation was found between the left amygdala and the frontal cortex, and greater connectivity between the right MTG and the bilateral medial prefrontal cortex extending into the paracingulate gyrus, compared to placebo (Z>2.3, p < 0.05 corrected).

Conclusions

These results show a potential effect of lithium on ER through its effects on activity and connectivity, and further elaborate the neural underpinnings of cognitive reappraisal. Future work should investigate longer term effects of lithium on ER in BD, ultimately benefitting the development of novel and more effective treatments.
Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles
Authors: Carlsson Josefine , Åström Tim , Östman Conny , Nilsson Ulrika
Published: June 2023

The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.

Graphical abstract
[18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?
Authors: Jannusch Kai , Morawitz Janna , Schweiger Bernd , Weiss Daniel , Schimmöller Lars , Minko Peter , Herrmann Ken , Fendler Wolfgang P. , Quick Harald H. , Antoch Gerald , Umutlu Lale , Kirchner Julian , Bruckmann Nils-Martin
Published: June 2023

Objectives

Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination.

Methods

A total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin’s Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests.

Results

In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2.

Conclusions

The use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent–free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients.

Clinical relevance statement

This study gives a scientific baseline switching to a contrast agent–free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients.

Key Points

• No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging

• Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast–free [18F]FDG PET/MRI
Site-dependent control of polaritons in the Jaynes–Cummings–Hubbard model with trapped ions
Authors: Muralidharan Silpa , Toyoda Kenji
Published: June 2023

We demonstrate the site-dependent control of polaritons in the Jaynes–Cummings–Hubbard (JCH) model with trapped ions. When a linear ion crystal is illuminated with optical beams which are nearly resonant to the red-sideband (RSB) transition for the radial vibrational direction, quasiparticles called polaritonic excitations or polaritons can exist as conserved particles. Here, each polariton is a superposition of one internal excitation and one vibrational quantum (phonon). Polaritons can freely hop between ion sites in a homogeneous configuration, while their motion can be externally controlled by modifying the parameters for the optical beams site-dependently. We demonstrate the blockade of polariton hopping in a system of two ions by the individual control of the frequency of the optical beams illuminating each ion. A JCH system consisting of polaritons in a large number of ion sites can be considered an artificial many-body system of interacting particles and the technique introduced here can be used to exert fine local control over such a system, enabling detailed studies of both its quasi-static and dynamic properties.
Effectiveness of endourological management of ureteral stenosis in kidney transplant patients: EAU-YAU kidney transplantation working group collaboration
Authors: Territo Angelo , Bravo-Balado Alejandra , Andras Iulia , Campi Riccardo , Pecoraro Alessio , Hevia Vital , Prudhomme Thomas , Baboudjian Michael , Gallioli Andrea , Verri Paolo , Charbonnier Mathieu , Boissier Romain , Breda Alberto
Published: June 2023

Purpose

Ureteral stenosis (US) in kidney transplant (KT) recipients is associated with poorer long-term graft survival. Surgical repair is the standard of care, and endoscopic treatment represents an alternative for stenosis < 3 cm. We aimed to determine the effectiveness and safety of endourological management of US in KT patients and predictors of failure.

Methods

A retrospective multicenter study was conducted in four European referral centers, including all KT patients with US managed endoscopically between 2009 and 2021. Clinical success was defined as the absence of upper urinary tract catheterization, surgical repair or transplantectomy during follow-up.

Results

A total of 44 patients were included. The median time to US onset was 3.5 months (IQR 1.9–10.8), the median length of stricture was 10 mm (IQR 7–20). Management of US involved balloon dilation and laser incision in 34 (79.1%) and 6 (13.9%) cases, respectively, while 2 (4.7%) received both. Clavien–Dindo complications were infrequent (10%); only one Clavien ≥ III complication was reported. Clinical success was 61% at last follow-up visit (median = 44.6 months). In the bivariate analysis, duckbill-shaped stenosis (vs. flat/concave) was associated with treatment success (RR = 0.39, p = 0.04, 95% CI 0.12–0.76), while late-onset stenosis (> 3 months post KT) with treatment failure (RR = 2.00, p = 0.02, 95% CI 1.01–3.95).

Conclusions

Considering the acceptable long-term results and the safety of these procedures, we believe that the endoscopic treatment should be offered as a first-line therapy for selected KT patients with US. Those with a short and duckbill-shaped stenosis diagnosed within 3 months of KT seem to be the best candidates.
The 100 most-cited manuscripts in epilepsy epigenetics: a bibliometric analysis
Authors: Fan Lijuan , Liu Lu , Rao Xueyi , Wang Xiaoqian , Luo Huan , Gan Jing
Published: June 2023

Purpose

The top citation article reflects the developmental milestone of a given field. The purpose of this bibliometric analysis was to identify and assess the 100 most-cited (T100) articles on the epigenetics mechanism of epilepsy.

Methods

The Web of Science Core Collection (WoSCC) database was used to investigate, and search terms related to epilepsy epigenetics were compiled. Results were ranked according to citation number. The publication year, citation density, authorship, journal, country, institution, manuscript type, theme, and clinical topics were further evaluated.

Results

The Web of Science search returned a total of 1231 manuscripts. The number of citations for a manuscript ranges from 739 to 75. The greatest number of manuscripts in the top 100 was published in the Human Molecular Genetics and Neurobiology of Disease (n = 4). The journal with the highest 2021 impact factor was Nature Medicine (IF = 87.244). The most-cited paper by Aid et al. reported a new nomenclature for mouse and rat BDNF gene and its expression profiles. Most manuscripts were original articles (n = 69), of which 52 (75.4%) report findings of basic scientific work. The most prevalent theme was microRNA (n = 29), and the most popular clinical topic was temporal lobe epilepsy (n = 13).

Conclusions

The research on the epigenetics mechanism of epilepsy was in its infancy but full of potential. The developmental history and current achievements of hot themes, including microRNA, DNA methylation, and temporal lobe epilepsy, were overviewed. This bibliometric analysis provides useful information and insight for researchers when launching new projects.
Orthonasal and retronasal odor identification in patients with parosmia
Authors: Li Shubin , Boscolo-Rizzo Paolo , Uderzo Francesco , Tirelli Giancarlo , Whitcroft Katherine L. , Hummel Thomas
Published: June 2023

Objective

To compare retronasal and orthonasal perception in parosmic COVID-19 patients, in order to determine whether COVID-19 has a differential effect on these functions.

Methods

Using the Sniffin Sticks test battery orthonasal function was examined for odor threshold, discrimination and identification. Retronasal function was assessed using 20 tasteless aromatized powders. Gustatory function was measured using the Taste Strips test.

Results

This study included 177 patients (127 women, 50 men; mean age 45 years), of whom 127 (72%) were hyposmic and 50 (28%) normosmic. Compared to patients without parosmia, parosmic patients performed worse in odor identification for both orthonasal (F = 4.94, p = 0.03) and retronasal tests (F = 11.95, p < 0.01). However, an interaction effect between route of odor identification (orthonasal or retronasal) and parosmia status was found (F = 4.67, p = 0.03): patients with parosmia had relatively lower retronasal scores than patients without parosmia.

Conclusion

Our results suggest that COVID-19 may affect the olfactory mucosa differently along the anterior–posterior axis, thereby possibly contributing to the pathophysiology of parosmia. Patients with parosmia also exhibit a higher degree of impairment when odors are presented through the retronasal route during eating and drinking.
Autoimmune glial fibrillary acidic protein astrocytosis mimicking tuberculous meningitis: a retrospective study
Authors: Liang Yingfang , Wang Gangqi , Li Bixun , Li Guoliang , Zeng Hao
Published: June 2023

Background

This study aimed to summarize the clinical features of Autoimmune Glial Fibrillary Acidic Protein Astrocytosis mimicking tuberculosis meningitis to improve clinicians’ understanding of this disease.

Methods

We retrospectively analyzed the clinical manifestations, cerebrospinal fluid results, and imaging data of five patients with Autoimmune Glial Fibrillary Acidic Protein Astrocytosis mimicking tuberculous meningitis who were admitted to Xiangya Hospital Central South University between October 2021 and July 2022.

Results

Five patients were aged 31–59 years, with a male-to-female ratio of 4:1. Among the cases reviewed, four had a history of prodromal infections manifesting as fever and headache. One patient developed limb weakness and numbness with clinical manifestations of meningitis, meningoencephalitis, encephalomyelitis, or meningomyelitis. Cerebrospinal fluid analysis revealed an increased cell count in five cases, with a lymphocyte majority. All five cases had a CSF protein level > 1.0 g/L, CSF/blood glucose ratio < 0.5, and two patients had CSF glucose < 2.2 mmol/L. Decreased CSF chloride was observed in three cases, while increased ADA was observed in one case. Both serum and cerebrospinal fluid were positive for anti-GFAP antibodies in three cases, while in two cases, only CSF was positive for anti-GFAP antibodies. Additionally, hyponatremia and hypochloremia were observed in three cases. No tumors were detected in any of the five patients during tumor screening, and all five cases had a good prognosis following immunotherapy.

Conclusion

Anti-GFAP antibody testing should be routinely performed in patients with suspected tuberculosis meningitis to avoid misdiagnosis.
Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer
Authors: Karjula Topias , Niskakangas Anne , Mustonen Olli , Puro Iiris , Elomaa Hanna , Ahtiainen Maarit , Kuopio Teijo , Mecklin Jukka-Pekka , Seppälä Toni T. , Wirta Erkki-Ville , Sihvo Eero , Yannopoulos Fredrik , Helminen Olli , Väyrynen Juha P.
Published: June 2023

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48–1.73) or maximum diameter (adjusted HR 0.78, 0.40–1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18–0.87) and maximum diameter (adjusted HR 0.28, 0.11–0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis.
IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes
Authors: Zusi Chiara , Rioda Marco , Maguolo Alice , Emiliani Federica , Unali Ilaria , Costantini Silvia , Corradi Massimiliano , Contreas Giovanna , Morandi Anita , Maffeis Claudio
Published: June 2023

Introduction

Several genetic loci have been associated with diabetic nephropathy; however, the underlying genetic mechanisms are still poorly understood, with no robust candidate genes identified yet.

Aim

We aimed to determine whether two polymorphisms, previously associated with renal decline, influence kidney impairment evaluating their association with markers of renal function in a pediatric population with type 1 diabetes (T1D).

Material and methods

Renal function was evaluated by glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in a cohort of pediatric subjects with T1D (n = 278). Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were assessed. The IGF1 rs35767 and PPARG rs1801282 SNPs were genotyped by TaqMan RT-PCR system. An additive genetic interaction was calculated. Association analysis between markers of renal function and both SNPs or their additive interaction were performed.

Results

Both SNPs showed a significant association with eGFR: the A allele of rs35767 or the C allele of rs1801282 were associated to reduced eGFR compared to G alleles. Multivariate regression analysis adjusted for age, sex, z-BMI, T1D duration, blood pressure and Hba1c values showed that the additive genetic interaction was independently associated with lower eGFR (β = −3.59 [−6.52 to −0.66], p = 0.017). No associations were detected between SNPs, their additive interaction and ACR.

Conclusions

These results provide new insight into the genetic predisposition to renal dysfunction, showing that two polymorphisms in IGF1 and PPARG genes can lead to a reduction in renal filtration rate leading these patients to be exposed to a higher risk of early renal complications.
Untersuchungen zum Wärmetransport in Schneckengetrieben
Authors: Norgauer P. , Kirsch J. , Hein M. , Stahl K.
Published: June 2023

Im Rahmen dieser Veröffentlichung werden Ergebnisse experimenteller Untersuchungen an tauchgeschmierten Schneckengetrieben präsentiert. Ziel dieser Untersuchungen ist die experimentelle Bestimmung des Wärmestroms aus dem Zahnkontakt sowie die Evaliuerung der aktuell verwendeten rechnerischen Wärmestromaufteilung auf Basis der gemessenen Komponententemperaturen.

Weiter wurden im Zuge der durchgeführten Versuche die derzeitigen Einflussfaktoren auf die Temperaturentwicklung innerhalb des Getriebes und den Wärmedurchgang getestet und mit der Normrechnung nach DIN 3996:2019-04 verglichen. Besonderer Fokus liegt hierbei auf der Entwicklung der Ölsumpf‑, Radmassen- sowie der Schneckenmassentemperatur.

Die Ergebnisse zeigen, dass die thermische Berechnung von Getrieben komplex ist, da diese von zahlreichen Parametern beeinflusst wird. Auf Basis der Versuchsergebnisse wird der Einfluss der untersuchten Parameter beurteilt, sodass der aktuelle Stand der Forschung experimentell erweitert und abgesichert wird. Die vorgestellten Ergebnisse bieten darüber hinaus Orientierungswerte für zukünftige Getriebeauslegungen und Forschungsthemen.
Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis
Authors: Takagi Yusuke , Sato Junya , Yamamoto Yoshihiro , Matsunuma Ryo , Watanabe Hiroaki , Mori Masanori , Hasegawa Takaaki , Matsuda Yoshinobu , Kako Jun , Kasahara Yoko , Goya Sho , Kohara Hiroyuki , Nakayama Takeo , Yamaguchi Takashi
Published: June 2023

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference − 0.43, 95% confidence interval [CI] − 0.75 to – 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.
Interior dynamics of fatou sets
Authors: Hu Mi
Published: June 2023

In this paper, we investigate the precise behavior of orbits inside attracting basins. Let f be a holomorphic polynomial of degree $$m\ge 2$$

m
≥
2

in $$\mathbb {C}$$
C
, $$\mathcal {A}(p)$$

A
(
p
)

be the basin of attraction of an attracting fixed point p of f, and $$\Omega _i (i=1, 2, \cdots )$$

Ω
i

(
i
=
1
,
2
,
⋯
)

be the connected components of $$\mathcal {A}(p)$$

A
(
p
)

. Assume $$\Omega _1$$

Ω
1

contains p and $$\{f^{-1}(p)\}\cap \Omega _1\ne \{p\}$$

{

f

-
1

(
p
)

}

∩

Ω
1

≠

{
p
}

. Then there is a constant C so that for every point $$z_0$$

z
0

inside any $$\Omega _i$$

Ω
i

, there exists a point $$q\in \cup _k f^{-k}(p)$$

q
∈

∪
k

f

-
k

(
p
)

inside $$\Omega _i$$

Ω
i

such that $$d_{\Omega _i}(z_0, q)\le C$$

d

Ω
i

(

z
0

,
q
)

≤
C

, where $$d_{\Omega _i}$$

d

Ω
i

is the Kobayashi distance on $$\Omega _i.$$

Ω
i

.

In paper Hu (Dynamics inside parabolic basins, 2022), we proved that this result is not valid for parabolic basins.
Paenibacillus plantiphilus sp. nov. from the plant environment of Zea mays
Authors: Kämpfer Peter , Lipski André , Lamothe Lucie , Clermont Dominique , Criscuolo Alexis , McInroy John A. , Glaeser Stefanie P.
Published: June 2023

A Gram-strain positive, aerobic, endospore-forming bacterial strain (JJ-246T) was isolated from the rhizosphere of Zea mays. The 16S rRNA gene sequence similarity comparisons showed a most closely relationship to Paenibacillus oenotherae DT7-4T (98.4%) and Paenibacillus xanthinolyticus 11N27T (98.0%). The pairwise average nucleotide identity and digital DNA-DNA hybridisation values of the JJ-246T genome assembly against publicly available Paenibacillus type strain genomes were below 82% and 33%, respectively. The draft genome of JJ-246T shared many putative plant-beneficial functions contributing (PBFC) genes, related to plant root colonisation, oxidative stress protection, degradation of aromatic compounds, plant growth-promoting traits, disease resistance, drug and heavy metal resistance, and nutrient acquisition. The quinone system of strain JJ-246T, the polar lipid profile and the major fatty acids were congruent with those reported for members of the genus Paenibacillus. JJ-246T was shown to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus plantiphilus sp. nov. is proposed, with JJ-246T (= LMG 32093T = CCM 9089T = CIP 111893T) as the type strain.
Tutorial: Topology, Waves, and the Refractive Index
Authors: Horsley S. A. R.
Published: June 2023

This tutorial is divided into two parts: the first examines the application of topology to problems in wave physics. The origins of the Chern number are reviewed, where it is shown that this counts the number of critical points of a complex tangent vector field on the surface. We then show that this quantity arises naturally when calculating the dispersion of modes in any linear system, and give examples of its ap plication to find one–way propagating interface modes in both continuous and periodic materials. The second part offers a physical interpretation for the Chern number, based on the idea that the critical points which it records can be understood as points where the refractive index vanishes. Using the theory of crystal optics, we show that when the refractive index vanishes in acomplex valueddirection, the wave is forced to circulate in only one sense, and this is the origin of the one–way propagation of topological interface states. We conclude by demonstrating that this idea of ‘zero refractive index in a complex direction’ can be used as a shortcut to find acoustic and electromagnetic materials supporting one–way interface states.
RSDFT-NEGF transport simulations in realistic nanoscale transistors
Authors: Mil’nikov Gennady , Iwata Jun-ichi , Mori Nobuya , Oshiyama Atsushi
Published: June 2023

The paper presents a device simulator for computing transport characteristics from first principles. The developed computer program effectively performs large-scale parallel calculation of quasi-one-dimensional quantum transport in realistic nanoscale devices with thousands of atoms in the cross section area of the device channel. Our simulator is based on the real-space Kohn–Sham Hamiltonian in the density functional theory and improved numerical algorithms for reducing computational burden in non-equilibrium Green’s function (NEGF) method. Several computational improvements have been introduced in constructing a reduced quantum transport model from the original Kohn-Sham Hamiltonian and implementing the R-matrix computational scheme in the NEGF simulations.
REF: A Rapid Exploration Framework for Deploying Autonomous MAVs in Unknown Environments
Authors: Patel Akash , Lindqvist Björn , Kanellakis Christoforos , Agha-mohammadi Ali-akbar , Nikolakopoulos George
Published: June 2023

Exploration and mapping of unknown environments is a fundamental task in applications for autonomous robots. In this article, we present a complete framework for deploying Micro Aerial Vehicles (MAVs) in autonomous exploration missions in unknown subterranean areas. The main motive of exploration algorithms is to depict the next best frontier for the MAV such that new ground can be covered in a fast, safe yet efficient manner. The proposed framework uses a novel frontier selection method that also contributes to the safe navigation of autonomous MAVs in obstructed areas such as subterranean caves, mines, and urban areas. The framework presented in this work bifurcates the exploration problem in local and global exploration. The proposed exploration framework is also adaptable according to computational resources available onboard the MAV which means the trade-off between the speed of exploration and the quality of the map can be made. Such capability allows the proposed framework to be deployed in subterranean exploration and mapping as well as in fast search and rescue scenarios. The performance of the proposed framework is evaluated in detailed simulation studies with comparisons made against a high-level exploration-planning framework developed for the DARPA Sub-T challenge as it will be presented in this article.
Causal pluralism: agent causation without the panicky metaphysics
Authors: Martinez Joseph
Published: June 2023

An important divide in the free will literature—one that is arguably almost as common as the distinction between compatibilism and incompatibilism—concerns the distinction between event and substance causation. As the story typically goes, event-causalists maintain that an action is free only if it is caused by appropriate mental events, and agent-causalists maintain that an action is free only if it is caused directly by a substance (the agent). This paper argues that this dichotomy is a false one. It does this by introducing a new view called Causal Pluralism, which maintains that free will is compatible with both event and substance causation. Furthermore, it is argued that agent-causalists have good reason to adopt Causal Pluralism, and also that that the view has interesting implications for the free will dialectic.
Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism
Authors: Abril-Parreño Laura , Druart Xavier , Fair Sean , Krogenaes Anette
Published: June 2023

Introduction

Cervical artificial insemination (AI) with frozen-thawed semen in sheep has yielded unacceptably low pregnancy rates. The exception is in Norway where vaginal AI yields non-return rates in excess of 60%, which has been attributed to the ewe breed used.

Objectives and methods

This study aimed to characterise, for the first time, the ovine follicular phase cervical mucus metabolome, with a focus on the amino acid profile. Cervical mucus was collected from four European ewe breeds with known differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk (low fertility), Belclare (medium fertility), Norwegian White Sheep (NWS) and Fur (both high fertility).

Results

A total of 689 metabolites were identified in the cervical mucus of all the four ewe breeds. Of these, 458 metabolites were altered by ewe breed, which had the greatest effect in the dataset (P < 0.05). We detected 194 metabolites involved in the amino acid pathway, of which 133, 56 and 63 were affected by ewe breed, type of cycle and their interaction, respectively (P < 0.05). N-methylhydantoin and N-carbamoylsarcosine (degradation products of creatinine pathway) exhibited the greatest fold change decrease in the Suffolk breed compared to Fur and NWS (P < 0.001). Oxidized metabolites were also decreased in Suffolk compared to high fertility breeds (P < 0.05). In contrast, other metabolites such as 3-indoxyl-sulfate, putrescine, cadaverine were significantly increased in Suffolk at the synchronised cycle.

Conclusion

The suboptimal amino acid profile in the cervical mucus of the low fertility Suffolk breed may have negative consequences for sperm transport.
Veterans Health Administration Outpatient Psychiatry Staffing Model: Longitudinal Analysis on Mental Health Performance
Authors: Smith Clifford , Boden Matthew , Trafton Jodie
Published: June 2023

Background

An adequate supply of mental health (MH) professionals is necessary to provide timely access to MH services. Veterans Health Administration (VHA) continues to prioritize the expansion of the MH workforce to meet increasing demand for services.

Objective

Validated staffing models are essential to ensure timely access to care, to plan for future demand, to ensure delivery of high-quality care, and to balance the demands of fiscal responsibility and strategic priorities.

Design

Longitudinal retrospective cohort of VHA outpatient psychiatry, fiscal years 2016–2021.

Participants

Outpatient VHA psychiatrists.

Main Measures

Quarterly outpatient staff-to-patient ratios (SPRs), defined as the number of full-time equivalent clinically assigned providers per 1000 veterans receiving outpatient MH care, were calculated. Longitudinal recursive partitioning models were created to identify optimal cut-offs for the outpatient psychiatry SPR associated with success on VHA’s measures of quality, access, and satisfaction.

Key Results

Among outpatient psychiatry staff, the root node identified an outpatient SPR of 1.09 for overall performance (p < 0.001). For metrics associated with Population Coverage, a root node identified an SPR of 1.36 (p < 0.001). Metrics associated with continuity of care and satisfaction were associated with a root node of 1.10 and 1.07 (p < 0.001), respectively. In all analyses, the lowest SPRs were associated with the lowest group performance on VHA MH metrics of interest.

Conclusions

Establishing validated staffing models associated with high-quality MH care is critical given the national psychiatry shortage and increasing demand for services. Analyses support VHA’s current recommended minimum outpatient psychiatry-specific SPR of 1.22 as a reasonable target to provide high-quality care, access, and satisfaction.