bluuebunny/crossref_metadata_2025 huggingface dataset:
The buccal corridor as a possible morphological risk indicator for sleep disordered breathing
Authors: Kois Dean E. , Kois John C.
Published: May 2023

Objective

To explore a possible morphological relationship between buccal corridor, gingival display, transpalatal molar width, palatal height, and a cephalometric measurement (PV‐A Line) as a risk indicator for sleep‐disordered breathing.

Materials and Methods

Thirty subjects were enrolled. Full face maximum smile images and CBCT scans were taken. A Pearson correlation coefficient was used to identify any relationships between the variables.

Results

No correlations were identified between any of the variables investigated in this study as they relate to risk factors for sleep‐disordered breathing.

Conclusions

The amount of buccal corridor space in relation to a patient's smile and the amount of gingival display does not appear to be a reliable metric in identifying certain morphological risk factors for sleep‐disordered breathing.

Clinical Significance

Assessing the amount of buccal corridor space in relation to a smile does not appear to be a reliable predictor of morphological risk for certain risk factors of sleep‐disordered breathing. In addition, utilizing the amount of gingival display in a patient's maximum smile does not appear to relate directly to risks in sleep‐disordered breathing. Other tests and discovery may be necessary to identify these types of patients.
“It is like a pet in a way”: The self‐management experiences of people with cystic fibrosis diabetes
Authors: Collins Sarah , Jones Andrew , Woodward Sue , Sturt Jackie
Published: May 2023

Background

Cystic fibrosis diabetes (CFD) is a very common co‐morbidity affecting the lives of people with cystic fibrosis. Surprisingly, minimal research has been undertaken to understand the experiences of people with CFD and how they self‐mange this condition.

Methods

Using interpretative phenomenological analysis, the present study examined the self‐management experiences of people with CFD. In‐depth semi‐structure interviews were conducted with eight people who had CFD.

Results

The following three superordinate themes were identified: forming a relationship with CFD, balancing the CFD self‐management triad, and the unmet need for information and support.

Conclusions

The findings suggest that the management of CFD is challenging and, although people with CFD experience many adaptation and management processes similar to people with type 1 diabetes, they struggle with the additional complexity of balancing CF and CFD. The provision of appropriate education, support and person‐centred care needs to be addressed.
Fundamental neurochemistry review: Old brain stories ‐ Influence of age and sex on the neurodegeneration‐associated lipid changes
Authors: Cuenca‐Bermejo Lorena , Prinetti Alessandro , Kublickiene Karolina , Raparelli Valeria , Kautzky‐Willer Alexandra , Norris Colleen M. , Pilote Louise ,   the GOING‐FWD Consortium, Herrero María Trinidad
Published: May 2023

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age‐associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age‐related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non‐biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age‐related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid‐related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid‐lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid‐reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach.

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miR‐140 and miR‐200 regulate the migratory heterogeneity of location‐specific Schwann cell population
Authors: Chen Qianqian , Miao Yang , Xu Zhipeng , Zhang Ruirui , Yi Sheng
Published: May 2023

Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR‐140 and miR‐200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR‐140 and miR‐200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.

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Comparison of different ways of handling consumer segments using L‐shape data
Authors: Nguyen Quoc Cuong , Asioli Daniele , Varela Paula , Næs Tormod
Published: May 2023

Different approaches for handling consumer segments in L‐shape data are compared in a study conducted in Norway. Consumers evaluated eight different yoghurt samples with profiles varying in three intrinsic attributes following a full factorial design. Three blocks of data were collected including sensory properties, liking ratings, and consumer attributes. Data were analyzed using two different approaches. In approach one, the one‐step simultaneous L‐Partial Least Square (L‐PLS) Regression with average consumer liking to represent the segments was used, while approach two was based on a two‐step procedure (TSP) based on Partial Least Square (PLS) Regression using dummy variables to represent the segments. The methods were compared in terms of interpretations, flexibility, and outcomes. Methodological implications, recommendations, and future research avenues are discussed.

Practical Applications

This manuscript has been devoted to two different ways of handling segmentation in L‐shape data of consumer liking, sensory properties, and consumer attributes. Overall, both L‐PLS and TSP approaches provide similar interpretation of results. The TSP approach, however, has the advantage of interpretating the horizontal and vertical direction in the L separately using standard regression methods. It is of interest of product development and marketing activities to identify which food product characteristics are important for consumer preferences and to better understand the characteristics of the consumers (e.g., socio‐demographics) that drive the consumer acceptance of the different products.
A study protocol to develop and test an e‐health intervention in follow‐up service for intensive care survivors' relatives
Authors: van Mol Margo M. C. , Kompanje Erwin J. O. , van Bommel Jasper , Latour Jos M. ,   the ICNaVEN‐study group
Published: May 2023

Background

The negative impact on long‐term health‐related outcomes among relatives of critically ill patients in the intensive care unit (ICU) has been well described. High‐quality ICU specialized follow‐up care, which is easily accessible with digital innovation and which is designed by and with relevant stakeholders (i.e., ICU patients' relatives and nurses), should be considered to reduce these impairments in the psychological and social domains.

Aim

The programme's aim is to develop and test an e‐health intervention in a follow‐up service to support ICU patients' relatives. Here, the protocol for the overall study programme will be described.

Study Design

The overall study comprises a mixed‐methods, multicentre research design with qualitative and quantitative study parts. The study population is ICU patients' adult relatives and ICU nurses. The main outcomes are the experiences of these stakeholders with the newly developed e‐health intervention. There will be no predefined selection based on age, gender, and level of education to maximize diversity throughout the study programme. After the participants provide informed consent, data will be gathered through focus groups (n = 5) among relatives and individual interviews (n = 20) among nurses exploring the needs and priorities of a digital follow‐up service. The findings will be explored further for priority considerations among members of the patient/relative organization (aiming n = 150), which will serve as a basis for digital prototypes of the e‐health intervention. Assessment of the intervention will be followed during an iterative process with investigator‐developed questionnaires. Finally, symptoms of anxiety and depression will be measured with the 14‐item Dutch version of the ‘Hospital Anxiety and Depression Scale’, and symptoms of posttraumatic stress will be measured with the 21‐item Dutch version of the ‘Impact of Events Scale‐Revised’ to indicate the effectiveness of digital support among ICU patients' relatives.

Relevance to Clinical Practice

The e‐health intervention to be developed during this research programme can possibly bridge the gap in integrated ICU follow‐up care by providing relevant information, self‐monitoring and stimulating self‐care among ICU patients' relatives.
Lycopene ε‐cyclase mediated transition of α‐carotene and β‐carotene metabolic flow in carrot fleshy root
Authors: Wang Ya‐Hui , Zhang Yu‐Qing , Zhang Rong‐Rong , Zhuang Fei‐Yun , Liu Hui , Xu Zhi‐Sheng , Xiong Ai‐Sheng
Published: May 2023

The accumulation of carotenoids, such as xanthophylls, lycopene, and carotenes, is responsible for the color of carrot (Daucus carota subsp. sativus) fleshy roots. The potential role of DcLCYE, encoding a lycopene ε‐cyclase associated with carrot root color, was investigated using cultivars with orange and red roots. The expression of DcLCYE in red carrot varieties was significantly lower than that in orange carrots at the mature stage. Furthermore, red carrots accumulated larger amounts of lycopene and lower levels of α‐carotene. Sequence comparison and prokaryotic expression analysis revealed that amino acid differences in red carrots did not affect the cyclization function of DcLCYE. Analysis of the catalytic activity of DcLCYE revealed that it mainly formed ε‐carotene, while a side activity on α‐carotene and γ‐carotene was also observed. Comparative analysis of the promoter region sequences indicated that differences in the promoter region may affect the transcription of DcLCYE. DcLCYE was overexpressed in the red carrot ‘Benhongjinshi’ under the control of the CaMV35S promoter. Lycopene in transgenic carrot roots was cyclized, resulting in the accumulation of higher levels of α‐carotene and xanthophylls, while the β‐carotene content was significantly decreased. The expression levels of other genes in the carotenoid pathway were simultaneously upregulated. Knockout of DcLCYE in the orange carrot ‘Kurodagosun’ by CRISPR/Cas9 technology resulted in a decrease in the α‐carotene and xanthophyll contents. The relative expression levels of DcPSY1, DcPSY2, and DcCHXE were sharply increased in DcLCYE knockout mutants. The results of this study provide insights into the function of DcLCYE in carrots, which could serve as a basis for creating colorful carrot germplasms.
Trend of blood donors entering the coronavirus pandemic era and challenges: Age‐period‐cohort analysis using 75.5 million all blood donations data during 2006–2020 in Japan
Authors: Imada Hirohito , Akita Tomoyuki , Sugiyama Aya , Tanaka Junko
Published: May 2023

Background

In Japan, “Blood Donation Promotion 2025,” a blood donation target, was established based on a predicted blood donation rate of 5.7% in 2025, which was calculated by the Blood Donation Promotion Study Group (BD research group) of the Ministry of Health, Labor and Welfare using nationwide blood donation data through 2018. However, COVID‐19 since 2020 may affect the blood donation rate in Japan.

Method

Data from 75.5 million blood donations from 2006 to 2020 was used. The age‐period‐cohort model (APC model) was applied to estimate age, period, and birth cohort factors on blood donation rate and to predict the age‐specific blood donation rates from 2021 to 2035.

Results

The APC model was highly reproducible for blood donation rates (modified R2 = 0.99). The blood donation rate in 2020 was 6.0% (5.04 million), an increase compared to 2019. Comparing this study with the BD research group, the predicted blood donation rates in 2025 for those 16–19 years old and in 20s are lower (4.8% vs. 5.2% and 5.3% vs. 5.5%) but those among 50s and 60s are higher (7.9% vs. 7.5% and 4.2% vs. 3.9%, respectively).

Discussion

The number of blood donations in 2020 increased despite COVID‐19 and it proved that the blood donation promotion was effective. The different age‐specific blood donation rates between our study and the report of BD research group infers the effect of COVID‐19 on blood donation were differed by age and suggested the need for different approaches to blood donation promotion by generation.
A remote fluorescein staining and photography protocol for monitoring of ulcerative keratitis in small animal patients: A pilot study
Authors: Li Puma Margaret C. , Diehl Kathryn A. , Myrna Kathern E.
Published: May 2023

Objective

To describe a protocol for corneal ulcer monitoring utilizing daily fluorescein staining and evaluation of owner‐acquired anterior segment images.

Animal studied

Nine client‐owned small animal patients (eight dogs, one cat) diagnosed with superficial corneal ulcers at the University of Georgia Veterinary Hospital.

Procedure(s)

In addition to routine ulcer therapy, patients were discharged with supplies to perform daily fluorescein staining including a Quikvue® cobalt blue light camera adapter. Fluorescein staining was performed daily, photographs and/or videos were acquired at home by the patient's owner(s), and images were analyzed daily by trained personnel. In‐house examinations were performed weekly and within 24 h after the ulcer had appeared healed on photographs.

Results

All (9/9) owners were able to take interpretable photographs. The majority (6/9) of patients had images successfully detailing their ulcer healing progress. One (1/9) patient appeared healed on images, but on subsequent examination had persistent ulceration covered by third eyelid elevation. Two (2/9) patients had persistent ulceration, consistent on both images and examination, but exited the study prematurely prior to ulcer healing.

Conclusions

Remote fluorescein staining and image evaluation can be considered as an adjunct for monitoring ulcer healing but should not be used alone or as a substitute for ophthalmic examinations. Ulcers under the third eyelid have potential to be missed on image evaluation alone.
Analysis of furnace contamination on superconducting radio frequency niobium using secondary-ion mass spectrometry
Authors: Angle Jonathan W. , Lechner Eric M. , Reece Charles E. , Stevie Fred A. , Kelley Michael J.
Published: May 2023

Detection of surface contamination on niobium materials used in superconducting radio frequency (SRF) applications is difficult due to quantitative sensitivity and near-atomic depth resolution needed. Inspection of samples known to have experienced surface contamination was found to have inconsistent nitride coverage after high-temperature nitrogen gas exposure (“doping”). We compare contaminating species found on samples treated in several different vacuum furnaces, both “exposed” directly in the chamber and “protected” by containment shielding from evaporative sources with “furnace caps.” Typically, furnace caps are used to impede contamination from reaching the interior surface of cavities during the high-temperature vacuum bake that immediately precedes exposure to nitrogen gas. Although, to date, little is known about the effectiveness of these caps, SIMS results showed that they were effective in limiting contamination arising from the furnace environment. Inspection of sample surfaces by SEM showed a lack of nitrides present on contaminated specimens. TEM with energy dispersive spectroscopy performed on these samples revealed that a carbon-rich layer now existed, indicating that a relatively high contaminant load prevents the nucleation and growth of surface nitrides, while thus inhibiting interstitial nitrogen uptake. Except in extreme cases, subsequent removal of the top several micrometers of the surface via electropolishing appears to effectively eliminate any strong influence on the subsequent SRF cavity performance. With the absence of furnace cleaning, carbon contamination was found to be nearly 10× higher for protected nitrogen-doped and electropolished samples, with minimal metallic contamination detected for both processes. SIMS analysis was also performed to compare the cleanliness of samples fully prepared by such nitrogen “doping” with those prepared by a related process, involving the dissolution of niobium surface oxide and diffusion of oxygen into the surface. This oxygen doping or alloying process offers attractive advantages.
Physiological and Energetic Demands During Still-Rings Routines of Elite Artistic Gymnasts
Authors: Seemann-Sinn Alexander , Rüdrich Peter , Gorges Tom , Naundorf Falk , Wolfarth Bernd
Published: May 2023

Purpose: The aim of the study was to analyze physiological and energetic demands of elite gymnasts during still-rings routines (SRRs). Methods: Eleven male gymnasts (mean [SD] 23.6 [3.9] y, 65.9 [5.6] kg, 171.1 [6.7] cm) performed a maximal graded exercise test and an individual SRR, during which respiratory gas and heart rate (HR) were measured using a mobile spiroergometer and a paired HR sensor. Metabolic energy and the energy contribution in terms of aerobic, anaerobic lactic, and anaerobic alactic were determined by oxygen uptake (VO2) during exercise, net lactate production, and the fast component of postexercise VO2 kinetics. Results: Mean routine duration of the SRRs was 48.3 (4.5) seconds. VO2 and HR during SRRs were shown to be 86.9% (5.9%) and 91.0% (3.3%), respectively, of the maximal values measured during the graded exercise test. The anaerobic alactic, aerobic, and anaerobic lactic systems provided 50.9% (6.6%), 28.6% (4.8%), and 20.5% (5.2%), respectively, of the total energy required during SRRs. The energy contribution of the anaerobic lactic system correlated negatively with individual anaerobic threshold (r = −.715) and maximal VO2 (r = −.682). Conclusions: The anaerobic alactic system is the predominant energy source for ATP resynthesis during SRRs. The high relative VO2 and HR values reached during SRRs show that these routines strongly stress the cardiovascular system.
Inverse mechanical-swelling coupling of a highly deformed double-network gel
Authors: Imaoka Chika , Nakajima Tasuku , Indei Tsutomu , Iwata Masaya , Hong Wei , Marcellan Alba , Gong Jian Ping
Published: May 2023

Mechanical behaviors of a polymer gel are coupled with its swelling behavior. It has been known that typical hydrogels display extension-induced swelling and drying-induced stiffening, called normal mechanical-swelling coupling. In this study, we experimentally found that highly extended double-network (DN) hydrogels exhibit abnormal inverse mechanical-swelling coupling such as extension-induced deswelling and drying-induced softening. We established theoretical hyperelastic and swelling models that reproduced all the complicated mechanical and swelling trends of the highly deformed DN hydrogels. From these theoretical analyses, it is considered that the inverse mechanical-swelling coupling of a DN gel is derived from the extreme nonlinear elasticity of its first network at its ultimate deformation state. These findings contribute toward the understanding of the mechanics of rubber-like materials up to their ultimate deformation and fracture limit.
Single-domain antibody–based noninvasive in vivo imaging of α-synuclein or tau pathology
Authors: Jiang Yixiang , Lin Yan , Krishnaswamy Senthilkumar , Pan Ruimin , Wu Qian , Sandusky-Beltran Leslie A. , Liu Mengyu , Kuo Min-Hao , Kong Xiang-Peng , Congdon Erin E. , Sigurdsson Einar M.
Published: May 2023

Intracellular deposition of α-synuclein and tau are hallmarks of synucleinopathies and tauopathies, respectively. Recently, several dye-based imaging probes with selectivity for tau aggregates have been developed, but suitable imaging biomarkers for synucleinopathies are still unavailable. Detection of both of these aggregates early in the disease process may allow for prophylactic therapies before functional impairments have manifested, highlighting the importance of developing specific imaging probes for these lesions. In contrast to the β sheet dyes, single-domain antibodies, found in camelids and a few other species, are highly specific, and their small size allows better brain entry and distribution than whole antibodies. Here, we have developed such imaging ligands via phage display libraries derived from llamas immunized with α-synuclein and tau preparations, respectively. These probes allow noninvasive and specific in vivo imaging of α-synuclein versus tau pathology in mice, with the brain signal correlating strongly with lesion burden. These small antibody derivatives have great potential for in vivo diagnosis of these diseases.
Global crotonylatome and GWAS revealed a
TaSRT1
-
TaPGK
model regulating wheat cold tolerance through mediating pyruvate
Authors: Zhang Ning , Wang Sisheng , Zhao Simin , Chen Daiying , Tian Hongyan , Li Jia , Zhang Lingran , Li Songgang , Liu Lu , Shi Chaonan , Yu Xiaodong , Ren Yan , Chen Feng
Published: May 2023

Here, we reported the complete profiling of the crotonylation proteome in common wheat. Through a combination of crotonylation and multi-omics analysis, we identified a TaPGK associated with wheat cold stress. Then, we confirmed the positive role of TaPGK-modulating wheat cold tolerance. Meanwhile, we found that cold stress induced lysine crotonylation of TaPGK. Moreover, we screened a lysine decrotonylase TaSRT1 interacting with TaPGK and found that TaSRT1 negatively regulated wheat cold tolerance. We subsequently demonstrated TaSRT1 inhibiting the accumulation of TaPGK protein, and this inhibition was possibly resulted from decrotonylation of TaPGK by TaSRT1. Transcriptome sequencing indicated that overexpression of TaPGK activated glycolytic key genes and thereby increased pyruvate content. Moreover, we found that exogenous application of pyruvate sharply enhanced wheat cold tolerance. These findings suggest that the TaSRT1-TaPGK model regulating wheat cold tolerance is possibly through mediating pyruvate. This study provided two valuable cold tolerance genes and dissected diverse mechanism of glycolytic pathway involving in wheat cold stress.
A first-in-human study of the fibroblast activation protein–targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors
Authors: Melero Ignacio , Tanos Tamara , Bustamante Mariana , Sanmamed Miguel F. , Calvo Emiliano , Moreno Irene , Moreno Victor , Hernandez Tatiana , Martinez Garcia Maria , Rodriguez-Vida Alejo , Tabernero Josep , Azaro Analia , Ponz-Sarvisé Mariano , Spanggaard Iben , Rohrberg Kristoffer , Guarin Ernesto , Nüesch Eveline , Davydov Iakov I. , Ooi Chiahuey , Duarte José , Chesne Evelyne , McIntyre Christine , Ceppi Maurizio , Cañamero Marta , Krieter Oliver
Published: May 2023

This first-in-human study evaluated RO7122290, a bispecific fusion protein carrying a split trimeric 4-1BB (CD137) ligand and a fibroblast activation protein α (FAP) binding site that costimulates T cells for improved tumor cell killing in FAP-expressing tumors. Patients with advanced or metastatic solid tumors received escalating weekly intravenous doses of RO7122290 as a single agent (
n
= 65) or in combination with a 1200-milligram fixed dose of the anti–programmed death-ligand 1 (anti–PD-L1) antibody atezolizumab given every 3 weeks (
n
= 50), across a tested RO7122290 dose range of 5 to 2000 milligrams and 45 to 2000 milligrams, respectively. Three dose-limiting toxicities were reported, two at different RO7122290 single-agent doses (grade 3 febrile neutropenia and grade 3 cytokine release syndrome) and one for the combination (grade 3 pneumonitis). No maximum tolerated dose was identified. The pharmacokinetic profile of RO7122290 suggested nonlinearity in elimination. The observed changes in peripheral and tissue pharmacodynamic (PD) biomarkers were consistent with the postulated mechanism of action. Treatment-induced PD changes included an increase in proliferating and activated T cells in peripheral blood both in the single-agent and combination arms. Increased infiltration of intratumoral CD8
+
and Ki67
+
CD8
+
T cells was observed for both treatment regimens, accompanied by the up-regulation of T cell activation genes and gene signatures. Eleven patients experienced a complete or partial response, six of whom were confirmed to be immune checkpoint inhibitor naive. These results support further evaluation of RO7122290 in combination with atezolizumab or other immune-oncology agents for the treatment of solid tumors.
Multicenter Clinical Performance Evaluation of Omadacycline Susceptibility Testing of
Enterobacterales
on VITEK 2 Systems
Authors: Csiki-Fejer Edith , Traczewski Maria , Procop Gary W. , Davis Thomas E. , Hackel Meredith , Dwivedi Hari P. , Pincus David H.
Published: May 2023

We present the first performance evaluation results for omadacycline on the VITEK 2 and VITEK 2 Compact Systems (bioMérieux, Inc.). The trial was conducted at four external sites and one internal site.
Lithosphere tearing and foundering during continental subduction: Insights from Oligocene−Miocene magmatism in southern Tibet
Authors: Pan Fabin , Zhang Hongfei , He Xiaobo , Harris Nigel , Dai Hong-Kun , Xiong Qing , Luo Biji , Liu Dong , Kusky Timothy , Sadiq Izhar
Published: May 2023

The distribution of Oligo−Miocene magmatic rocks from southern Tibet in space and time yields critical information on the geometry and deformation of the subducted Indian lithosphere which impacts on plateau growth following the India and Eurasia collision. A growing body of geophysical evidence has shown that the subducted Indian lithosphere beneath the Tibetan Plateau has been torn apart. However, the spatiotemporal distribution and cause of the tearing remain enigmatic. Timing of the post-collisional magmatic rocks in southern Tibet exhibits four patterns of decreasing ages; magmatism began earlier in the west and east Himalayan syntaxis and evolved to two age undulations in the central southern Tibet. Seismic images show that regions of slab window (both 90°E and 84°E) and flattened subducted lithosphere (both 86°E and 81°E) are present at depth of 135 km. Correspondingly, increasing mineral crystallization temperatures (absolute value of 50 °C) were recorded in the Oligo−Miocene ultrapotassic-potassic rocks at 90°E and 84°E, while opposing trends were shown by coeval ultrapotassic-potassic rocks at 86°E and 81°E. Besides, the melting depth of the Oligo−Miocene ultrapotassic-potassic primitive melts decreases from nearly 100 km to 70 km between 81°E and 90°E, probably indicating progressive rising of the lithosphere-asthenosphere boundary. Such variations were possibly the results of the focused flow and upwelling of asthenosphere, which advanced rapidly but diachronously through weakened and torn sectors within the overlying Indian slab. The upwellings probably induced diachronously upward bending of the residual Indian slab and its flattening, which accelerated the tearing of the Indian lithosphere during continental subduction.
Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial
Authors: Gögenur Mikail , Balsevicius Lukas , Bulut Mustafa , Colak Nesibe , Justesen Tobias Freyberg , Fiehn Anne-Marie Kanstrup , Jensen Marianne Bøgevang , Høst-Rasmussen Kathrine , Cappelen Britt , Gaggar Shruti , Tajik Asma , Zahid Jawad Ahmad , Bennedsen Astrid Louise Bjørn , D’Ondes Tommaso Del Buono , Raskov Hans , Sækmose Susanne Gjørup , Hansen Lasse Bremholm , Salanti Ali , Brix Susanne , Gögenur Ismail
Published: May 2023

Background

In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.

Methods

We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.

Results

A total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05).

Conclusions

Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts.

Trial registration number

NCT04591379.
Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners
Authors: Kelly-Reif Kaitlin , Bertke Stephen J , Rage Estelle , Demers Paul A , Fenske Nora , Deffner Veronika , Kreuzer Michaela , Samet Jonathan , Schubauer-Berigan Mary K , Tomasek Ladislav , Zablotska Lydia B , Wiggins Charles , Laurier Dominique , Richardson David B
Published: May 2023

Objectives

Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners.

Methods

The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure.

Results

In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM.

Conclusions

This new large, pooled study confirms and supports a linear exposure–response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.
Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study
Authors: Lindström Ulf , di Giuseppe Daniela , Exarchou Sofia , Alenius Gerd-Marie , Olofsson Tor , Klingberg Eva , Jacobsson Lennart , Askling Johan , Wallman Johan K
Published: May 2023

Introduction

We aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions not having started another DMARD (regardless of methotrexate discontinuation), within 2 years of starting methotrexate, as well as methotrexate effectiveness.

Methods

Patients with DMARD-naïve, newly diagnosed PsA, starting methotrexate 2011–2019, were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA. Proportions remaining on methotrexate and not starting another DMARD were calculated. For patients with disease activity data at baseline and 6 months, response to methotrexate monotherapy was compared through logistic regression, applying non-responder imputation.

Results

In total, 3642/3642 patients with PsA/RA were included. Baseline patient-reported pain and global health were similar, whereas patients with RA had higher 28-joint scores and evaluator-assessed disease activity. Two years after methotrexate start, 71% of PsA vs 76% of patients with RA remained on methotrexate, 66% vs 60% had not started any other DMARD, and 77% vs 74% had not started specifically a biological or targeted synthetic DMARD. At 6 months, the proportions of patients with PsA versus RA achieving pain-scores ≤15 mm were 26% vs 36%; global health ≤20 mm: 32% vs 42%; evaluator-assessed ‘remission’: 20% vs 27%, with corresponding adjusted ORs (PsA vs RA) of 0.63 (95% CI 0.47 to 0.85); 0.57 (95% CI 0.42 to 0.76) and 0.54 (95% CI 0.39 to 0.75).

Discussion

In Swedish clinical practice, methotrexate use is similar in PsA and RA, both regarding initiation of other DMARDs and methotrexate retention. On a group level, disease activity improved during methotrexate monotherapy in both diseases, although more so in RA.
Optimizing the Parton Showers in PYTHIA8 for Xe–Xe collision at 5.44 TeV
Authors: Ul Abidin Zain , Tabassam Uzma
Published: May 2023

We present the doubly differential invariant yield of primary charged particles [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text] in Xe–Xe collisions at [Formula: see text] = 5.44 TeV, as a function of [Formula: see text] in kinematic region of [Formula: see text] and for the pseudorapidity interval of [Formula: see text] by using PYTHIA8 tuned to different Parton Showers like Simple Showers (Time-Like, Space-Like), DIRE and VINCIA Showers. The predictions of hard and soft QCD processes of Parton Showers are then compared with the ALICE data at different centrality classes of 0–5%, 50–60% and 70–80%. The observed deviations are connected with the kinematics involved and are mostly due to the color coherence and soft gluon emission from parton pairs. As PYTHIA8 does not take into account the Cronin effect, thus the deviation at low [Formula: see text] is due to Cronin effect. The nuclear modification factor is constructed and it is observed that the signal is less than unity or suppression is seen which is coming from Parton Showers.
Coupling condition analysis of Bessel–Gaussian beam to few mode fibers
Authors: Liu Renxuan , Juan Wei , Yang Heng , Hu Zhouyi , Li Jiarui , Hu Jun
Published: May 2023

In this paper, the theoretical model of the coupling efficiency of BG beams to few-mode fibers (FMFs) in the case of perfect alignment, lateral or vertical offsets, and random angular jitter is investigated and compared with that of sew-mode fibers (SMFs). Under the same conditions, FMF obtains a higher coupling efficiency with the BG beam and flatter response characteristics to deviations from ideal conditions compared with SMF. At the same time, the effects of the half-cone angle and topological charge of the BG beam on the coupling efficiency and response characteristics during nonideal conditions are studied. According to the precision of the coupling system, a higher coupling efficiency can be obtained by adjusting the half-cone angle, topological charge, and focal length. That makes them a more practical choice for information transmissions, such as mobile platform communication and the transmission of pedestrian data collected during transportation. The research results could help apply the BG beam and other orbital angular momentum (OAM) beams coupled with FMF.
COVID-Attention: Efficient COVID19 Detection Using Pre-trained Deep Models Based on Vision Transformers and X-ray Images
Authors: Haouli Imed-Eddine , Hariri Walid , Seridi-Bouchelaghem Hassina
Published: May 2023

COVID19 is becoming more and more threatening to human life since the appearance of many variants like Alpha, Omicron and Delta. These variants have dozens of mutations that can make their diagnosis more challenging. Despite the recent success of Convolutional Neural Networks (CNN) to detect COVID19 automatically using transfer learning techniques, they are not the most robust to accomplish this task since some translation, scale and hyperparameter variations can affect the accuracy. Newly, Vision Transformers (ViT) are becoming increasingly popular to handle similar tasks and to deal with the aforementioned variations. In this paper, we propose an enhanced ViT architecture for COVID19 detection referred to as COVID-Attention. The proposed ViT-based models are robust due to their capability to capture long-range dependencies within images thanks to the attention mechanism, which is the core of the transformer block. We compare the efficiency of our proposed method to top-performing CNN baselines using two different transfer learning modes. We further show in our experiments that adding a convolution block to the top of the ViT model (i.e. as an initial block) can avoid the collapse issue and enhance the ViT performance using the recent ViTC model. We finally show that ViT-based models give more explainable visualization compared to CNN models using the Grad-CAM technique in order to highlight the attention map that affects the classification decision. Our experiments have been conducted on two recent databases of X-ray images and show high performance compared to the state-of-the-art methods in three-class classifications.
Nonlinear Stability of Three-Layer Circular Shallow Arches with Elastic Interlayer Bonding
Authors: Adam Christoph , Paulmichl Ivan , Furtmüller Thomas
Published: May 2023

In this paper, stability-prone circular shallow arches composed of three symmetrically arranged flexibly bonded layers with fixed and hinged supports at both ends are examined. Based on the differential equations of equilibrium and a series expansion of the governing kinematic variables, analytical expressions for the limit points and bifurcation points are derived. Solutions for the nonlinear equilibrium path are also provided. Comparison with the results of much more complex numerical analyses with 2D finite continuum elements show high accuracy of these analytical expressions. The application examples indicate the importance of considering the flexibility of the interlayers in the stability analysis. With the assumption of a rigid bond between the layers, the stability limit is overestimated by up to 100% in the examples considered.
Drug synergy model for malignant diseases using deep learning
Authors: Rani Pooja , Dutta Kamlesh , Kumar Vijay
Published: May 2023

Drug synergy has emerged as a viable treatment option for malignancy. Drug synergy reduces toxicity, improves therapeutic efficacy, and overcomes drug resistance when compared to single-drug doses. Thus, it has attained significant interest from academics and pharmaceutical organizations. Due to the enormous combinatorial search space, it is impossible to experimentally validate every conceivable combination for synergistic interaction. Due to advancement in artificial intelligence, the computational techniques are being utilized to identify synergistic drug combinations, whereas prior literature has focused on treating certain malignancies. As a result, high-order drug combinations have been given little consideration. Here, DrugSymby, a novel deep-learning model is proposed for predicting drug combinations. To achieve this objective, the data is collected from datasets that include information on anti-cancer drugs, gene expression profiles of malignant cell lines, and screening data against a wide range of malignant cell lines. The proposed model was developed using this data and achieved high performance with f1-score of 0.98, recall of 0.99, and precision of 0.98. The evaluation results of DrugSymby model utilizing drug combination screening data from the NCI-ALMANAC screening dataset indicate drug combination prediction is effective. The proposed model will be used to determine the most successful synergistic drug combinations, and also increase the possibilities of exploring new drug combinations.
Towards Optimal Moment Estimation in Streaming and Distributed Models
Authors: Jayaram Rajesh , Woodruff David P.
Published: May 2023

One of the oldest problems in the data stream model is to approximate the
p
th moment

\(\Vert \mathbf {X}\Vert _p^p = \sum _{i=1}^n \mathbf {X}_i^p\)

of an underlying non-negative vector

\(\mathbf {X}\in \mathbb {R}^n\)

, which is presented as a sequence of

\(\mathrm{poly}(n)\)

updates to its coordinates. Of particular interest is when

\(p \in (0,2]\)

. Although a tight space bound of

\(\Theta (\epsilon ^{-2} \log n)\)

bits is known for this problem when both positive and negative updates are allowed, surprisingly, there is still a gap in the space complexity of this problem when all updates are positive. Specifically, the upper bound is

\(O(\epsilon ^{-2} \log n)\)

bits, while the lower bound is only

\(\Omega (\epsilon ^{-2} + \log n)\)

bits. Recently, an upper bound of

\(\tilde{O}(\epsilon ^{-2} + \log n)\)

bits was obtained under the assumption that the updates arrive in a
random order
.

We show that for

\(p \in (0, 1]\)

, the random order assumption is not needed. Namely, we give an upper bound for worst-case streams of

\(\tilde{O}(\epsilon ^{-2} + \log n)\)

bits for estimating

\(\Vert \mathbf {X}\Vert _p^p\)

. Our techniques also give new upper bounds for estimating the empirical entropy in a stream. However, we show that for

\(p \in (1,2]\)

, in the natural coordinator and blackboard distributed communication topologies, there is an

\(\tilde{O}(\epsilon ^{-2})\)

bit max-communication upper bound based on a randomized rounding scheme. Our protocols also give rise to protocols for heavy hitters and approximate matrix product. We generalize our results to arbitrary communication topologies
G
, obtaining an

\(\tilde{O}(\epsilon ^{2} \log d)\)

max-communication upper bound, where
d
is the diameter of
G
. Interestingly, our upper bound rules out natural communication complexity-based approaches for proving an

\(\Omega (\epsilon ^{-2} \log n)\)

bit lower bound for

\(p \in (1,2]\)

for streaming algorithms. In particular, any such lower bound must come from a topology with large diameter.
A Taxonomy and Analysis of Misbehaviour Detection in Cooperative Intelligent Transport Systems: A Systematic Review
Authors: Amanullah Mohamed Ahzam , Loke Seng W. , Baruwal Chhetri Mohan , Doss Robin
Published: May 2023

Cooperative Intelligent Transport Systems (C-ITS) is one of the proposed solutions to improve the safety and efficiency of road transport. However, C-ITS is prone to misbehaviours that can cause devastating effects such as road accidents and potential loss of life. While there are several research studies including technical studies and surveys that discuss misbehaviour detection in C-ITS, they tend to focus on specific aspects of misbehaviour detection and do not provide a comprehensive and unified coverage. With the objective of serving as a reference for future researchers, this study provides a comprehensive survey of misbehaviour detection in C-ITS. It identifies and discusses the key causes of misbehaviour in C-ITS, and the mechanisms used to detect them. Additionally, it proposes a thematic taxonomy on misbehaviour detection based on a comparative analysis of the technical studies. Furthermore, the existing solutions from the state-of-the-art and their shortcomings are also presented. Finally, this study highlights several significant research challenges and discusses future research directions in the area of misbehaviour detection in C-ITS. In doing so, this study contributes to the existing literature in an important field of study.
Virulence and Ecology of Agrobacteria in the Context of Evolutionary Genomics
Authors: Weisberg Alexandra J. , Wu Yu , Chang Jeff H. , Lai Erh-Min , Kuo Chih-Horng
Published: May 2023

Among plant-associated bacteria, agrobacteria occupy a special place. These bacteria are feared in the field as agricultural pathogens. They cause abnormal growth deformations and significant economic damage to a broad range of plant species. However, these bacteria are revered in the laboratory as models and tools. They are studied to discover and understand basic biological phenomena and used in fundamental plant research and biotechnology. Agrobacterial pathogenicity and capability for transformation are one and the same and rely on functions encoded largely on their oncogenic plasmids. Here, we synthesize a substantial body of elegant work that elucidated agrobacterial virulence mechanisms and described their ecology. We review findings in the context of the natural diversity that has been recently unveiled for agrobacteria and emphasize their genomics and plasmids. We also identify areas of research that can capitalize on recent findings to further transform our understanding of agrobacterial virulence and ecology.