bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons
Authors: Hyeon Bobae , Lee Heeyoung , Kim Nury , Heo Won Do 
Published: July 2023

AbstractRET (REarranged during Transfection) is a receptor tyrosine kinase that transduces various external stimuli into biological functions, such as survival and differentiation, in neurons. In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET, combining the cytosolic region of human RET with a blue-light–inducible homo-oligomerizing protein. By varying the duration of photoactivation, we were able to dynamically modulate RET signaling. Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation. By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma and trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation. Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain. Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
Role of protein tyrosine phosphatase receptor type M in epithelial ovarian cancer progression
Authors: Li Xiao , Ding Wei , Rao Yang , Qu Pengpeng 
Published: July 2023

Abstract
Background
Epithelial ovarian cancer (EOC) is often diagnosed at advanced stages with low survival rates. Protein tyrosine phosphatase receptor type M (PTPRM) is involved in cancer development and progression; however, its role in EOC remains unclear. In this study,we aimed to detect PTPRM expression in ovarian epithelial tumors, analyze its relationship with the clinicopathological features and survival prognosis of patients with EOC, and provide a theoretical basis for new targets for EOC treatment. Fifty-seven patients with EOC treated at our hospital between January 2012–January 2014 were included; along with 18 borderline and 30 benign epithelial ovarian tumors and 15 normal ovarian and uterine tube tissue samples from patients surgically treated at our hospital during the same period. PTPRM expression was immunohistochemically detected, and we analyzed its relationship with clinicopathological features and prognosis. Associations between PTPRM expression and survival prognosis of patients with EOC were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter databases.

Results
PTPRM had the highest expression rates in normal ovarian and uterine tube tissues, followed by benign and borderline epithelial ovarian tumors; the lowest positive expression rate was observed in EOC tumors. PTPRM expression differed significantly among groups (P < 0.05). The positive PTPRM expression rate significantly decreased with age, progressing clinical stage, and tumor recurrence, and the larger the mass diameter, the higher the positive PTPRM expression rate. PTPRM expression was significantly lower in ovarian cancer compared with that in normal tissues in the GEPIA database (P < 0.05). The overall survival (OS) and disease-free survival(DFS) rates were higher in the PTPRM high-expression group, with statistically significant (P < 0.05) and insignificant (P > 0.05) differences, respectively. The OS rate of the high-expression group compared with the low-expression group in the Kaplan–Meier Plotter database was higher, although without statistical significance (P > 0.05), and progression-free survival(PFS) was higher with statistical significance (P < 0.05).

Conclusion
PTPRM expression was low in patients with EOC, and the PTPRM positive-expression rate significantly decreased with progressing stages of EOC and tumor recurrence, suggesting that PTPRM acts as a tumor suppressor in EOC progression. Negative PTPRM expression may predict poor clinical outcomes in patients with EOC.
Characterization of large-scale genomic differences in the first complete human genome
Authors: Yang Xiangyu , Wang Xuankai , Zou Yawen , Zhang Shilong , Xia Manying , Fu Lianting , Vollger Mitchell R. , Chen Nae-Chyun , Taylor Dylan J. , Harvey William T. , Logsdon Glennis A. , Meng Dan , Shi Junfeng , McCoy Rajiv C. , Schatz Michael C. , Li Weidong , Eichler Evan E. , Lu Qing , Mao Yafei 
Published: July 2023

Abstract
Background
The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet.

Results
Here, in addition to the previously reported “non-syntenic” regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region—the KLRC gene cluster—show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution.

Conclusion
Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.
Agreement between questions about physical activity and sitting time, and device-based measures, used in Swedish targeted health dialogues in the context of primary health care
Authors: Johansson Lisbeth M. , Lingfors Hans , Golsäter Marie , Rolander Bo , Fransson Eleonor I. 
Published: July 2023

AbstractBackgroundIt is important that easy-to-use measures like subjective questions about physical activity (PA) and sedentary behaviour are valid and reliable providing accurate measures, when they are used in health promotion work aiming to support people to improve their lifestyle habits such as PA. The aim of this study was to evaluate the concurrent validity of a structured interview form estimating self-reported PA and a question about sitting time used in Swedish targeted health dialogues in the context of primary health care.MethodThe study was conducted in the southern part of Sweden. To evaluate concurrent validity of the interview form, time spent in moderate-to-vigorous physical activities (MVPA) and energy expenditure related to MVPA estimated by an interview form was compared with the same measures assessed by an ActiGraph GT3X-BT accelerometer. To evaluate a question about sitting time, the Swedish School of Sport and Health Sciences’ single-item question about sitting time (SED-GIH) was compared with measures from an activPAL inclinometer. Statistical analyses included deriving Bland‒Altman plots and calculating Spearman’s rank correlation coefficients.ResultBland‒Altman plots indicated lower absolute variation in the difference between self-reported and device-based PA measures for lower PA levels, both for energy expenditure and time spent in MVPA. No systematic over- or underestimation was observed. The Spearman’s correlation coefficient between self-reported and device-based PA measures was 0.27 (p = 0.014) for time spent in MVPA and 0.26 (p = 0.022) for energy expenditure. The correlation coefficient between the single item question and device-based sitting time measures was 0.31 (p = 0.002). Sitting time was underestimated by 74% of the participants.ConclusionThe PA interview form and the SED-GIH question on sitting time may be of value in targeted health dialogues in primary health care with the intention to support sedentary and insufficiently physically active persons in increasing their physical activity and limiting their sitting time. The questionnaires are easy to use and are more cost effective than device-based measures, especially regarding population-based interventions conducted in primary health care for thousands of participants such as targeted health dialogues.Clinical trial registrationNot applicable.
Evaluation of the performance of the IFN-γ release assay in bovine tuberculosis free herds from five European countries
Authors: Gomez-Buendia Alberto , Romero Beatriz , Bezos Javier , Saez José Luis , Archetti Ivonne , Pacciarini Maria Lodovica , Boschiroli Maria Laura , Girard Sébastien , Gutu Emanuela , Barbuceanu Florica , Karaoulani Ourania , Stournara Athanasia , de Juan Lucia , Alvarez Julio 
Published: July 2023

AbstractThe diagnostic methods for granting and maintenance of the official tuberculosis-free (OTF) status and for intra-Community movement of cattle are the tuberculin skin tests (single or comparative) and the interferon-γ (IFN-γ) release assay (IGRA). However, until now, IGRAs have been primarily applied in infected farms in parallel to the skin test to maximize the number of infected animals detected. Therefore, an evaluation of the performance of IGRAs in OTF herds to assess whether if their specificity is equal to or higher than that of the skin tests is needed. For this, a panel of 4365 plasma samples coming from 84 OTF herds in six European regions (five countries) was assembled and analysed using two IGRA kits, the ID Screen® Ruminant IFN-g (IDvet) and the Bovigam™ TB Kit (Bovigam). Results were evaluated using different cut-offs, and the impact of herd and animal-level factors on the probability of positivity was assessed using hierarchical Bayesian multivariable logistic regression models. The percentage of reactors ranged from 1.7 to 21.0% (IDvet: S/P ≥ 35%), and 2.1–26.3% (Bovigam: ODbovis–ODPBS ≥ 0.1 and ODbovis–ODavium ≥ 0.1) depending on the region, with Bovigam disclosing more reactors in all regions. The results suggest that specificity of IGRAs can be influenced by the production type, age and region of origin of the animals. Changes in the cut-offs could lead to specificity values above 98–99% in certain OTF populations, but no single cut-off yielding a sufficiently high specificity (equal or higher than that of skin tests) in all populations was identified. Therefore, an exploratory analysis of the baseline IFN-γ reactivity in OTF populations could help to assess the usefulness of this technique when applied for the purpose of maintaining OTF status.
Tolerance of clinical vancomycin-resistant Enterococcus faecium isolates against UV-C light from a mobile source
Authors: Knobling B. , Franke G. , Belmar Campos C. , Büttner H. , Christner M. , Klupp E. M. , Maurer P. M. , Knobloch J. K. 
Published: July 2023

Abstract
Background
Admission to a room previously occupied by patients carrying environmentally robust pathogens implies an increased risk of acquiring those pathogens. Therefore, ‘No-touch’ automated room disinfection systems, including devices based on UV-C irradiation, are discussed to improve terminal cleaning. It is still unclear if clinical isolates of relevant pathogens behave differently under UV-C irradiation compared to laboratory strains used in the approval process of disinfection procedures. In this study we analysed the susceptibility of well characterized clonally divergent vancomycin-resistant enterococci (VRE) strains, including a linezolid-resistant isolate, against UV-C radiation.

Methods
Susceptibility against UV-C of ten clonally divergent clinical isolates of VRE was determined in comparison to the commonly used test organism Enterococcus hirae ATCC 10541. Ceramic tiles contaminated with 105 to 106 colony forming units/25 cm² of the different enterococci were positioned at a distance of 1.0 and 1.5 m and irradiated for 20 s, resulting in a UV-C dose of 50 and 22 mJ/cm², respectively. Reduction factors were calculated after quantitative culture of the bacteria recovered from treated and untreated surfaces.

Results
Susceptibility to UV-C varied considerably among the strains studied, with the mean value of the most robust strain being up to a power of ten lower compared to the most sensitive strain at both UV-C doses. The two most tolerant strains belonged to MLST sequence types ST80 and ST1283. The susceptibility of the laboratory strain E. hirae ATCC 10541 ranged between the most sensitive and most tolerant isolates for both irradiation doses. However, for UV-C dose of 22 mJ/cm², the reduction of the most tolerant isolate of ST1283 was statistically significantly lower compared to E. hirae ATCC 10541. The most susceptible strains belonged to the MLST sequence types ST117 and ST203.

Conclusions
These results indicate that UV-C doses reported in the literature are sufficient for the reduction of commonly used reference strains of enterococci but could be insufficient for the reduction of tolerant patient VRE-isolates in a hospital setting. Therefore, for future studies, the most tolerant clinical isolates should be used to validate automated UV-C devices or longer exposure times should be expected to ensure efficacy in the real world.
Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas
Authors: Chang Ya-Sian , Tu Siang-Jyun , Chen Hong-Da , Chung Chin-Chun , Hsu Ming-Hon , Chou Yu-Pao , Lee Ya-Ting , Yen Ju-Chen , Jeng Long-Bin , Chang Jan-Gowth 
Published: July 2023

Abstract
Background
Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses.

Methods
We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence.

Results
The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment.

Conclusions
This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.
Peer counselling as an approach to improve complementary feeding practices: a narrative review
Authors: Haque Nabila Binte , Mihrshahi Seema , Haider Rukhsana 
Published: July 2023

AbstractBackgroundAppropriate complementary feeding can help reduce the risk of malnutrition and is especially important in Asian and African countries. Peer counselling has been used as an approach to improve complementary feeding practices and is often combined with other interventions, like food fortification or supplements, or as a part of broader nutrition education program. The aim of this narrative review is to assess the effectiveness of peer counselling on improving complementary feeding practices in Asian and African countries.MethodsWe searched through seven electronic databases: CINAHL, MEDLINE (OVID), PubMed, Embase, Web of Science, the Cochrane Library and WHO Global Health library from 2000 to April 2021, and had the following inclusion criteria. Studies were included if they were community- or hospital-based, had infants aged 5–24 months old, had individual or group peer counselling, and the effects of peer counselling on complementary feeding practices were measured. Methodological quality was assessed using the Joanna Briggs Institute’s critical appraisal checklist for evidence studies.ResultsOut of 6 studies that met the above criteria, 3 studies were randomised controlled trials and 3 were quasi-experimental studies. In Bangladesh, India, Nepal and Somalia, peer counselling was found to be effective in improving timely initiation of complementary feeding, minimum meal frequency and minimum dietary diversity in all of our selected studies. In addition, improvement in breastfeeding practices, complementary foods preparation, hygiene, psychological stimulation for cognitive development of children and mothers’ understanding of hunger cues were observed in some of our selected studies.ConclusionsThis review evaluates the effectiveness of peer counselling to improve complementary feeding practices in Asian and African countries. Peer counselling improves timely complementary feeding and ensures the correct proportions and consistency of foods including adequate amounts of food is given. Other important complementary feeding indicators like minimum dietary diversity, minimum meal frequency and minimum acceptable diet can also be increased through peer-counselling interventions. Peer counselling is well known to enhance the rate of breastfeeding practices, but this review suggests it is also effective for complementary feeding and may inform future nutrition programs to extend the length of peer counselling for mothers.
A comparison between incremental lines of cementum and aspartic acid racemization in age estimation: histological and biochemical study
Authors: Moawed Dena Mohamed Naguib Abdel , Ibrahim Nadia Mohsen Ali , Eid Ibrahim Mohamed , Soliman Amir , Mostafa Heba El-Sayed 
Published: July 2023

Abstract
Background
Age estimation is a vital aspect of the identification of an individual in forensic science. Teeth are one of the toughest structures in the human body and generally survive postmortem destruction. So, they can therefore be used more reliably than any other morphological or histological trait of the adult skeleton for estimating age.

Aim of the study
The present work aimed to compare cementum incremental lines and aspartic acid racemization in age estimation among Egyptian subjects.

Methods
Sixty-four subjects were assigned to two groups: males and females (each with 32 cases) to determine the effect of sex as a possible factor that might affect age estimation. For each group, in all subjects, age was estimated using histologic examination of ground, unstained section teeth by light and polarized microscopes, in addition to estimating the rate of aspartic acid racemization in the collagen of dentin by using the HPLC method.

Results
There was a statistically significant correlation between each method of age estimation and chronological age. However, the strongest degree of correlation was observed for the racemization method, with a correlation coefficient of r = 0.99 (95% CI 0.98 to 0.99), followed by the light method, r = 0.94 (95% CI 0.90 to 0.96), and the polarized method, r = 0.93 (95% CI 0.88 to 0.95).

Conclusions
Both methods, cementum incremental lines and aspartic acid racemization, could help in age estimation, but aspartic acid racemization is more reliable and accurate.
Inter-row cropping and rootstock genotype selection in a UK cider orchard to combat apple replant disease
Authors: Cook Chris , Magan Naresh , Xu Xiangming 
Published: July 2023

AbstractApple rootstock genotypes confer different levels of tolerance to apple replant disease (ARD) and vigour to a newly replanted apple tree. A hybrid management system of rotating the rootstock genotype planted between successive generations and inter-row planting in the alleyways of orchards may minimise the severity of ARD symptoms. High-throughput sequencing of the fungal ITS and bacterial 16S rDNA regions was used to investigate the diversity, and differential taxa present in soils displaying symptoms of ARD. Candidate pathogens and beneficial microorganisms were correlated with the above-ground establishment of each rootstock genotype in a UK cider orchard. Our results suggest that the same rootstock or rootstock with closely related parentage to the previous rootstock had more severe ARD symptoms. Planting in the alleyway appeared an effective strategy to minimise the severity of symptoms irrespective of rootstock genotype. The planting location effect had a higher contribution to the variation in the rhizosphere microbiome than that of the rootstock genotype. No predicted causal agents for ARD could be identified to a taxonomic level to predict their function but two species associated with mycorrhizae, Pteridiospora spinosispora and Paraglomus laccatum were identified as inversely correlated with ARD severity and could be candidate beneficial species for apple, warranting further investigation and research. Our findings suggest that planting in the alleyways and planting rootstocks genetically dissimilar to the previously planted rootstock can be beneficial for tree establishment. We have also identified species inversely associated with ARD severity, making candidates for future research to test the antagonistic effect of the species against ARD pathogens in apple roots.
Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells
Authors: Zhang Kevin R. , Jankowski Connor S. R. , Marshall Rayna , Nair Rohini , Más Gómez Néstor , Alnemri Ahab , Liu Yingrui , Erler Elizabeth , Ferrante Julia , Song Ying , Bell Brent A. , Baumann Bailey H. , Sterling Jacob , Anderson Brandon , Foshe Sierra , Roof Jennifer , Fazelinia Hossein , Spruce Lynn A. , Chuang Jen-Zen , Sung Ching-Hwa , Dhingra Anuradha , Boesze-Battaglia Kathleen , Chavali Venkata R. M. , Rabinowitz Joshua D. , Mitchell Claire H. , Dunaief Joshua L. 
Published: July 2023

ABSTRACT
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1). In a liver-specific Hepc (Hamp) knockout murine model of systemic iron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes and ceramides. The proteolytic enzyme cathepsin D (CTSD) had impaired maturation. A large proportion of lysosomes were galectin-3 (Lgals3) positive, suggesting cytotoxic lysosomal membrane permeabilization. Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.