bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links
Authors: Marini Victoria , Nikulenkov Fedor , Samadder Pounami , Juul Sissel , Knudsen Birgitta R. , Krejci Lumir 
Published: May 2023

Abstract
Background
DNA-protein cross-links (DPCs) are one of the most deleterious DNA lesions, originating from various sources, including enzymatic activity. For instance, topoisomerases, which play a fundamental role in DNA metabolic processes such as replication and transcription, can be trapped and remain covalently bound to DNA in the presence of poisons or nearby DNA damage. Given the complexity of individual DPCs, numerous repair pathways have been described. The protein tyrosyl-DNA phosphodiesterase 1 (Tdp1) has been demonstrated to be responsible for removing topoisomerase 1 (Top1). Nevertheless, studies in budding yeast have indicated that alternative pathways involving Mus81, a structure-specific DNA endonuclease, could also remove Top1 and other DPCs.

Results
This study shows that MUS81 can efficiently cleave various DNA substrates modified by fluorescein, streptavidin or proteolytically processed topoisomerase. Furthermore, the inability of MUS81 to cleave substrates bearing native TOP1 suggests that TOP1 must be either dislodged or partially degraded prior to MUS81 cleavage. We demonstrated that MUS81 could cleave a model DPC in nuclear extracts and that depletion of TDP1 in MUS81-KO cells induces sensitivity to the TOP1 poison camptothecin (CPT) and affects cell proliferation. This sensitivity is only partially suppressed by TOP1 depletion, indicating that other DPCs might require the MUS81 activity for cell proliferation.

Conclusions
Our data indicate that MUS81 and TDP1 play independent roles in the repair of CPT-induced lesions, thus representing new therapeutic targets for cancer cell sensitisation in combination with TOP1 inhibitors.
Increasing emergency number utilisation is not driven by low-acuity calls: an observational study of 1.5 million emergency calls (2018–2021) from Berlin
Authors: Herr David , Bhatia Sangeeta , Breuer Florian , Poloczek Stefan , Pommerenke Christopher , Dahmen Janosch 
Published: May 2023

Abstract
Background
The Emergency Medical Service (EMS) in Germany is increasingly challenged by strongly rising demand. Speculations about a greater utilisation for minor cases have led to intensive media coverage, but empirical evidence is lacking. We investigated the development of low-acuity calls from 2018 to 2021 in the federal state of Berlin and its correlations with sociodemographic characteristics.

Methods
We analysed over 1.5 million call documentations including medical dispatch codes, age, location and time using descriptive and inferential statistics and multivariate binary logistic regression. We defined a code list to classify low-acuity calls and merged the dataset with sociodemographic indicators and data on population density.

Results
The number of emergency calls (phone number 112 in Germany) increased by 9.1% from 2018 to 2021; however, the proportion of low-acuity calls did not increase. The regression model shows higher odds of low-acuity for young to medium age groups (especially for age 0–9, OR 1.50 [95% CI 1.45–1.55]; age 10–19, OR 1.77 [95% CI 1.71–1.83]; age 20–29, OR 1.64 [95% CI 1.59–1.68] and age 30–39, OR 1.40 [95% CI 1.37–1.44]; p < 0.001, reference group 80–89) and for females (OR 1.12 [95% CI 1.1–1.13], p < 0.001). Odds were slightly higher for calls from a neighbourhood with lower social status (OR 1.01 per index unit increase [95% CI 1.0–1.01], p < 0.05) and at the weekend (OR 1.02 [95% CI 1.0–1.04, p < 0.05]). No significant association of the call volume with population density was detected.

Conclusions
This analysis provides valuable new insights into pre-hospital emergency care. Low-acuity calls were not the primary driver of increased EMS utilisation in Berlin. Younger age is the strongest predictor for low-acuity calls in the model. The association with female gender is significant, while socially deprived neighbourhoods play a minor role. No statistically significant differences in call volume between densely and less densely populated regions were detected. The results can inform the EMS in future resource planning.
Implications of CRNDE in prognosis, tumor immunity, and therapeutic sensitivity in low grade glioma patients
Authors: Yang Chen , Jiang Yingchuan , Hu Fan , Li Qiuping , Qi Biao 
Published: May 2023

Abstract
Background
Colorectal tumor differentially expressed (CRNDE) is specifically expressed in human brains and is the most highly expressed lncRNA in gliomas. Nevertheless, its implications in low grade glioma (LGG) are still indistinct. This study presented systematic analyses of CRNDE in LGG biology.

Methods
We retrospectively retrieved TCGA, CGGC and GSE16011 LGG cohorts. Survival analysis was conducted for evaluating the prognostic significance of CRNDE in LGG. A CRNDE-based nomogram was established, and its predictive performance was verified. Signaling pathways underlying CRNDE were analyzed through ssGSEA and GSEA approaches. The abundance of immune cells and activity of cancer-immunity cycle were estimated with ssGSEA approach. Immune checkpoints, HLAs, chemokines, and immunotherapeutic response indicators (TIDE, and TMB) was quantified. U251 and SW1088 cells were transfected with specific shRNAs of CRNDE, and flow cytometry (apoptosis) and western blot (β-catenin and Wnt5a) assays were conducted.

Results
Up-regulated CRNDE was found in LGG, and was linked to unfavorable clinical outcomes. The CRNDE-based nomogram enabled to accurately predict patients’ prognosis. High CRNDE expression was linked to more genomic variations, activity of tumorigenic pathways, tumor immunity (increase in infiltration of immune cells, expression of immune checkpoints, HLAs and chemokines, and cancer-immunity cycle), and therapeutic sensitivity. CRNDE knockdown mitigated malignant phenotypes of LGG cells.

Conclusions
Our study determined CRNDE as a novel predictor for patient prognosis, tumor immunity and therapeutic response in LGG. Assessment of CRNDE expression is a promising approach for predicting the therapeutic benefits of LGG patients.
Longitudinal trends (2011–2020) of premature mortality and years of potential life loss (YPLL) and associated covariates of the 62 New York State counties
Authors: Roldós Maria Isabel , Orazem John , Fortunato-Tavares Talita 
Published: May 2023

Abstract
Background
New York State (NYS) is the 27th largest state and the 4th most populous state in the U.S., with close to 20 million people in 62 counties. Territories with diverse populations present the best opportunity to study health outcomes and associated covariates, and how these differ across different populations and groups. The County Health Ranking and Roadmaps (CHR&R) ranks counties by linking the population’s characteristics and health outcomes and contextual factors in a synchronic approach.

Methods
The goal of this study is to analyze the longitudinal trends in NYS counties of age-adjusted premature mortality rate and years of potential life loss rate (YPLL) from 2011–2020 using (CHR&R) data to identify similarities and trends among the counties of the state. This study used a weighted mixed regression model to analyze the longitudinal trend in health outcomes as a function of the time-varying covariates and clustered the 62 counties according to the trend over time in the covariates.

Results
Four clusters of counties were identified. Cluster 1, which represents 33 of the 62 counties in NYS, contains the most rural counties and the least racially and ethnically diverse counties. Clusters 2 and 3 mirror each other in most covariates and Cluster 4 is comprised of 3 counties (Bronx, Kings/Brooklyn, Queens) representing the most urban and racial and ethnic diverse counties in the state.

Conclusion
The analysis clustered counties according to the longitudinal trends of the covariates, and by doing so identified clusters of counties that shared similar trends among the covariates, to later examine trends in the health outcomes through a regression model. The strength of this approach lies in the predictive feature of what is to come for the counties by understanding the covariates and setting prevention goals.
Origin and functional role of antisense transcription in endogenous and exogenous retroviruses
Authors: Romerio Fabio 
Published: May 2023

AbstractMost proteins expressed by endogenous and exogenous retroviruses are encoded in the sense (positive) strand of the genome and are under the control of regulatory elements within the 5’ long terminal repeat (LTR). A number of retroviral genomes also encode genes in the antisense (negative) strand and their expression is under the control of negative sense promoters within the 3’ LTR. In the case of the Human T-cell Lymphotropic Virus 1 (HTLV-1), the antisense protein HBZ has been shown to play a critical role in the virus lifecycle and in the pathogenic process, while the function of the Human Immunodeficiency Virus 1 (HIV-1) antisense protein ASP remains unknown. However, the expression of 3’ LTR-driven antisense transcripts is not always demonstrably associated with the presence of an antisense open reading frame encoding a viral protein. Moreover, even in the case of retroviruses that do express an antisense protein, such as HTLV-1 and the pandemic strains of HIV-1, the 3’ LTR-driven antisense transcript shows both protein-coding and noncoding activities. Indeed, the ability to express antisense transcripts appears to be phylogenetically more widespread among endogenous and exogenous retroviruses than the presence of a functional antisense open reading frame within these transcripts. This suggests that retroviral antisense transcripts may have originated as noncoding molecules with regulatory activity that in some cases later acquired protein-coding function. Here, we will review examples of endogenous and exogenous retroviral antisense transcripts, and the ways through which they benefit viral persistence in the host.
Hide or die when the winds bring wings: predator avoidance by activity shift in a mountain snake
Authors: Radovics Dávid , Szabolcs Márton , Lengyel Szabolcs , Mizsei Edvárd 
Published: May 2023

Abstract
Background
Understanding predator–prey relationships is fundamental in many areas of ecology and conservation. In reptiles, basking time often increases the risk of predation and one way to minimise this risk is to reduce activity time and to stay within a refuge. However, this implies costs of lost opportunities for foraging, reproduction, and thermoregulation. We aimed to determine the main potential and observed predators of Vipera graeca, to infer predation pressure by estimating the incidence and the body length and sex distribution of predation events based on body injuries, and to assess whether and how the activity of V. graeca individuals is modified by predation pressure.

Results
We observed n = 12 raptor bird species foraging at the study sites, of which Circaetus gallicus, Falco tinnunculus and Corvus cornix were directly observed as predators of V. graeca. We found injuries and wounds on 12.5% of the studied individuals (n = 319). The occurrence of injuries was significantly positively influenced by the body length of vipers, and was more frequent on females than on males, while the interaction of length and sex showed a significant negative effect. The temporal overlap between predator and viper activity was much greater for the vipers’ potential activity than their realised activity. Vipers showed a temporal shift in their bimodal daily activity pattern as they were active earlier in the morning and later in the afternoon than could be expected based on the thermal conditions.

Conclusion
The time spent being active on the surface has costs to snakes: predation-related injuries increased in frequency with length, were more frequent in females than in males and occurred in shorter length for males than for females. Our results suggest that vipers do not fully exploit the thermally optimal time window available to them, likely because they shift their activity to periods with fewer avian predators.
Diffuse intrapulmonary mesothelioma mimicking pulmonary lepidic adenocarcinoma: a rare case report and review of the literature
Authors: RanYue Wang , ChunYan Wu , Likun Hou , LiPing Zhang , JieLu Lin , ZhengWei Dong 
Published: May 2023

AbstractMesothelioma, with various clinical manifestations, radiological features, and histomorphological types, can be divided into epithelioid, sarcomatoid, and biphasic types, according to their histomorphological characteristics. There is a rare growth pattern of pleural mesothelioma: diffuse intrapulmonary mesothelioma (DIM), with a distinctive pattern of predominantly intrapulmonary growth, has no or minimal pleural involvement, and simulates interstitial lung disease(ILD) clinically and radiologically. A 59-year-old man presented to the hospital with recurrent pleural effusions for 4 years and a history of asbestos exposure. Computed tomography (CT) showed bilateral pure ground-glass opacity lesions, and the tumor cells showed a lepidic growth pattern pathologically. Immunohistochemical staining was positive for CK, WT-1, calretinin, D2-40, CK5/6, and Claudin4, while TTF-1, CEA, EMA, CK7, CK20, and other epithelial markers were negative. BAP1 loss its expression, and MTAP was positive in cytoplasm. CDKN2A was negative tested by Fluorescence in situ hybridization (FISH). The final diagnosis was DIM. In conclusion, we should recognize this rare disease to avoid misdiagnosis and delayed treatment.
Can the F‐Scan in‐shoe pressure system be combined with the GAITRite® temporal and spatial parameter‐recording walkway as a cost‐effective alternative in clinical gait analysis? A validation study
Authors: Speight Stephanie , Reel Sarah , Stephenson John 
Published: May 2023

AbstractBackgroundClinical gait analysis is widely used to aid the assessment and diagnosis of symptomatic pathologies. Foot function pressure systems such as F‐scan and analysis of the spatial–temporal parameters of gait using GAITRite® can provide clinicians with a more comprehensive assessment. There are systems however, such as Strideway™ that can measure these parameters simultaneously but can be expensive. F‐Scan in‐shoe pressure data is normally collected whilst the person is walking on a hard floor surface. The effects of the softer Gaitrite® mat upon the F‐Scan in‐shoe sensor pressure data is unknown. This study therefore aimed to assess the agreement between F‐Scan pressure measurements taken from a standard walkway (normal hard floor), and those from a GAITRite® walkway to establish whether these two pieces of equipment (in‐shoe F‐Scan and GAITRite®) can be used simultaneously, as a cost‐effective alternative.MethodTwenty‐three participants first walked on a standard floor and then on a GAITRite® walkway wearing F‐Scan pressure sensor insoles with same footwear. They repeated these walks three times on each surface. Mid gait protocols were utilised by analysing the contact pressure of the first and second metatarsophalangeal joint of the third, fifth and seventh step from each walk. For both joints, 95% Bland–Altman Limits of Agreement was used to determine a level of agreement between the two surfaces, using mean values from pressure data collected from participants who successfully completed all required walks. The intraclass correlation coefficient (ICC) and Lin's concordance correlation coefficient were calculated as indices of reliability.FindingsICC results for the hard surface and the GAITRrite® walkway at the first and second metatarsophalangeal joints were 0.806 and 0.991 respectively. Lin's concordance correlation coefficient for the first and second metatarsophalangeal joints were calculated to be 0.899 and 0.956 respectively. Both sets of statistics indicate very good reproducibility. Bland–Altman plots revealed good repeatability of data at both joints.ConclusionThe level of agreement in F‐Scan plantar pressures observed between walking on a normal hard floor and on a GAITRite® walkway was very high, suggesting that it is feasible to use F‐Scan with GAITRite® together in a clinical setting, as an alternative to other less cost‐effective standalone systems. Although it is assumed combining F‐Scan with GAITRite® does not affect spatiotemporal analysis, this was not validated in this study.
Radiologic-pathologic correlation of prostatic cancer extracapsular extension (ECE)
Authors: Guerra Adalgisa , Flor-de-Lima Beatriz , Freire Gonçalo , Lopes Ana , Cassis João 
Published: May 2023

Abstract
Recent advancements on nerve-sparing robotic prostatectomy allow fewer side effects such as urinary incontinence and sexual dysfunction. To perform such techniques, it is essential for the surgeon to know if the neurovascular bundle is involved. Despite being the gold-standard imaging method for Prostate Cancer (PCa) staging, Magnetic Resonance Imaging (MRI) lacks high specificity for detecting extracapsular extension (ECE). Therefore, it is essential to understand the pathologic aspects of ECE to better evaluate the MRI findings of PCa. We reviewed the normal MRI appearance of the prostate gland and the periprostatic space and correlated them to prostatectomy specimens. The different findings of ECE and neurovascular bundle invasion are exemplified with images of both MRI and histologic specimens.

Graphical abstract
Electromagnetic fields regulate calcium-mediated cell fate of stem cells: osteogenesis, chondrogenesis and apoptosis
Authors: Ma Tian , Ding Qing , Liu Chaoxu , Wu Hua 
Published: May 2023

AbstractElectromagnetic fields (EMF) are increasing in popularity as a safe and non-invasive therapy. On the one hand, it is widely acknowledged that EMF can regulate the proliferation and differentiation of stem cells, promoting the undifferentiated cells capable of osteogenesis, angiogenesis, and chondroblast differentiation to achieve bone repair purpose. On the other hand, EMF can inhibit tumor stem cells proliferation and promote apoptosis to suppress tumor growth. As an essential second messenger, intracellular calcium plays a role in regulating cell cycle, such as proliferation, differentiation and apoptosis. There is increasing evidence that the modulation of intracellular calcium ion by EMF leads to differential outcomes in different stem cells. This review summarizes the regulation of channels, transporters, and ion pumps by EMF-induced calcium oscillations. It furtherly discusses the role of molecules and pathways activated by EMF-dependent calcium oscillations in promoting bone and cartilage repair and inhibiting tumor stem cells growth.
CINC-2 and miR-199a-5p in EVs secreted by transplanted Thy1+ cells activate hepatocytic progenitor cell growth in rat liver regeneration
Authors: Ichinohe Norihisa , Tanimizu Naoki , Ishigami Keisuke , Yoshioka Yusuke , Fujitani Naoki , Ochiya Takahiro , Takahashi Motoko , Mitaka Toshihiro 
Published: May 2023

Abstract
Background
Small hepatocyte-like progenitor cells (SHPCs) are hepatocytic progenitor cells that transiently form clusters in rat livers treated with retrorsine (Ret) that underwent 70% partial hepatectomy (PH). We previously reported that transplantation of Thy1+ cells obtained from d-galactosamine-treated livers promotes SHPC expansion, thereby accelerating liver regeneration. Extracellular vesicles (EVs) secreted by Thy1+ cells induce sinusoidal endothelial cells (SECs) and Kupffer cells (KCs) to secrete IL17B and IL25, respectively, thereby activating SHPCs through IL17 receptor B (RB) signaling. This study aimed to identify the inducers of IL17RB signaling and growth factors for SHPC proliferation in EVs secreted by Thy1+ cells (Thy1-EVs).

Methods
Thy1+ cells isolated from the livers of rats treated with d-galactosamine were cultured. Although some liver stem/progenitor cells (LSPCs) proliferated to form colonies, others remained as mesenchymal cells (MCs). Thy1-MCs or Thy1-LSPCs were transplanted into Ret/PH-treated livers to examine their effects on SHPCs. EVs were isolated from the conditioned medium (CM) of Thy1-MCs and Thy1-LSPCs. Small hepatocytes (SHs) isolated from adult rat livers were used to identify factors regulating cell growth in Thy1-EVs.

Results
The size of SHPC clusters transplanted with Thy1-MCs was significantly larger than that of SHPC clusters transplanted with Thy1-LSPCs (p = 0.02). A comprehensive analysis of Thy1-MC-EVs revealed that miR-199a-5p, cytokine-induced neutrophil chemoattractant-2 (CINC-2), and monocyte chemotactic protein 1 (MCP-1) were candidates for promoting SHPC growth. Additionally, miR-199a-5p mimics promoted the growth of SHs (p = 0.02), whereas CINC-2 and MCP-1 did not. SECs treated with CINC-2 induced Il17b expression. KCs treated with Thy1-EVs induced the expression of CINC-2, Il25, and miR-199a-5p. CM derived from SECs treated with CINC-2 accelerated the growth of SHs (p = 0.03). Similarly, CM derived from KCs treated with Thy1-EVs and miR-199a-5p mimics accelerated the growth of SHs (p = 0.007). In addition, although miR-199a-overexpressing EVs could not enhance SHPC proliferation, transplantation of miR-199a-overexpressing Thy1-MCs could promote the expansion of SHPC clusters.

Conclusion
Thy1-MC transplantation may accelerate liver regeneration owing to SHPC expansion, which is induced by CINC-2/IL17RB signaling and miR-199a-5p via SEC and KC activation.

Graphical Abstract
Food, cooking and potteries in the Neolithic Mijiaya site, Guanzhong area, North China, revealed by multidisciplinary approach
Authors: Qu Yating , Zhu Junxiao , Yang Han , Zhou Longlong 
Published: May 2023

Abstract
Investigating the coevolutions in human food resources, cooking technologies and pottery functions will provide a vital perspective for understanding the driving force of social development in Neolithic China. Here, we preliminarily present a multianalytical study on the plant microfossils of pottery residues, the stable isotopic compositions and radiocarbon dating of animal bones, and the characteristics of pottery vessels (including their types, textures and smoked traces) from the Mijiaya site. The results indicate that the Mijiaya people (ca. 3093‒1961 cal. BC) probably relied on the various food resources consisting of the diversified crops, livestock and some foraging food; Mijiaya people had refined the pottery functions by changing their types, textures and assemblages, and they also used some auxiliary tools for increasing the cooking efficiency and obtaining the complex foodstuff. Integrated with agricultural development and technological innovation during Neolithic China, the foodways at the Mijiaya site also shed light on its inherited social tradition and social organization in the Late Neolithic period.