bluuebunny/crossref_metadata_2025 huggingface dataset:
RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer
Authors: Muoio M. G. , Pellegrino M. , Rapicavoli V. , Talia M. , Scavo G. , Sergi V. , Vella V. , Pettinato S. , Galasso M. G. , Lappano R. , Scordamaglia D. , Cirillo F. , Pulvirenti A. , Rigiracciolo D. C. , Maggiolini M. , Belfiore A. , De Francesco E. M.
Published: July 2023

The receptor for advanced glycation end products (RAGE) is implicated in diabetes and obesity complications, as well as in breast cancer (BC). Herein, we evaluated whether RAGE contributes to the oncogenic actions of Insulin, which plays a key role in BC progression particularly in obese and diabetic patients. Analysis of the publicly available METABRIC study, which collects gene expression and clinical data from a large cohort (n = 1904) of BC patients, revealed that RAGE and the Insulin Receptor (IR) are co-expressed and associated with negative prognostic parameters. In MCF-7, ZR75 and 4T1 BC cells, as well as in patient-derived Cancer-Associated Fibroblasts, the pharmacological inhibition of RAGE as well as its genetic depletion interfered with Insulin-induced activation of the oncogenic pathway IR/IRS1/AKT/CD1. Mechanistically, IR and RAGE directly interacted upon Insulin stimulation, as shown by in situ proximity ligation assays and coimmunoprecipitation studies. Of note, RAGE inhibition halted the activation of both IR and insulin like growth factor 1 receptor (IGF-1R), as demonstrated in MCF-7 cells KO for the IR and the IGF-1R gene via CRISPR-cas9 technology. An unbiased label-free proteomic analysis uncovered proteins and predicted pathways affected by RAGE inhibition in Insulin-stimulated BC cells. Biologically, RAGE inhibition reduced cell proliferation, migration, and patient-derived mammosphere formation triggered by Insulin. In vivo, the pharmacological inhibition of RAGE halted Insulin-induced tumor growth, without affecting blood glucose homeostasis. Together, our findings suggest that targeting RAGE may represent an appealing opportunity to blunt Insulin-induced oncogenic signaling in BC.
Identifying and quantifying isoforms from accurate full-length transcriptome sequencing reads with Mandalorion
Authors: Volden Roger , Schimke Kayla D. , Byrne Ashley , Dubocanin Danilo , Adams Matthew , Vollmers Christopher
Published: July 2023

In this manuscript, we introduce and benchmark Mandalorion v4.1 for the identification and quantification of full-length transcriptome sequencing reads. It further improves upon the already strong performance of Mandalorion v3.6 used in the LRGASP consortium challenge. By processing real and simulated data, we show three main features of Mandalorion: first, Mandalorion-based isoform identification has very high precision and maintains high recall even in the absence of any genome annotation. Second, isoform read counts as quantified by Mandalorion show a high correlation with simulated read counts. Third, isoforms identified by Mandalorion closely reflect the full-length transcriptome sequencing data sets they are based on.
LILRB4 regulates the function of decidual MDSCs via the SHP-2/STAT6 pathway during Toxoplasma gondii infection
Authors: Li Yuantao , Guo Jingjing , Zhang Haixia , Li Zhidan , Ren Yushan , Jiang Yuzhu , Liu Xianbing , Hu Xuemei
Published: July 2023

Background

Toxoplasma gondii infection can cause adverse pregnancy outcomes, such as recurrent abortion, fetal growth restriction and infants with malformations, among others. Decidual myeloid-derived suppressor cells (dMDSCs) are a novel immunosuppressive cell type at the fetal-maternal interface which play an important role in sustaining normal pregnancy that is related to their high expression of the inhibitory molecule leukocyte immunoglobulin-like receptor B4 (LILRB4). It has been reported that the expression of LILRB4 is downregulated on decidual macrophages after T. gondii infection, but it remains unknown whether T. gondii infection can induce dMDSC dysfunction resulting from the change in LILRB4 expression.

Methods

LILRB4-deficient (LILRB4−/−) pregnant mice infected with T. gondii with associated adverse pregnancy outcomes, and anti-LILRB4 neutralized antibodies-treated infected human dMDSCs were used in vivo and in vitro experiments, respectively. The aim was to investigate the effect of LILRB4 expression on dMDSC dysfunction induced by T. gondii infection.

Results

Toxoplasma gondii infection was observed to reduce STAT3 phosphorylation, resulting in decreased LILRB4 expression on dMDSCs. The levels of the main functional molecules (arginase-1 [Arg-1], interleukin-10 [IL-10]) and main signaling molecules (phosphorylated Src-homology 2 domain-containing protein tyrosine phosphatase [p-SHP2], phosphorylated signal transducer and activator of transcription 6 [p-STAT6]) in dMDSCs were all significantly reduced in human and mouse dMDSCs due to the decrease of LILRB4 expression induced by T. gondii infection. SHP-2 was found to directly bind to STAT6 and STAT6 to bind to the promoter of the Arg-1 and IL-10 genes during T. gondii infection.

Conclusions

The downregulation of LILRB4 expression on dMDSCs induced by T. gondii infection could regulate the expression of Arg-1 and IL-10 via the SHP-2/STAT6 pathway, resulting in the dysfunction of dMDSCs, which might contribute to adverse outcomes during pregnancy by T. gondii infection.

Graphical abstract
Ancestry-driven metabolite variation provides insights into disease states in admixed populations
Authors: Reynolds Kaylia M. , Horimoto Andrea R. V. R. , Lin Bridget M. , Zhang Ying , Kurniansyah Nuzulul , Yu Bing , Boerwinkle Eric , Qi Qibin , Kaplan Robert , Daviglus Martha , Hou Lifang , Zhou Laura Y. , Cai Jianwen , Shaikh Saame Raza , Sofer Tamar , Browning Sharon R. , Franceschini Nora
Published: July 2023

Background

Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.

Methods

We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.

Results

By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.

Conclusions

Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
Tuberculosis and Takayasu arteritis: a case report
Authors: Ferjani Maryem , El Euch Mounira , Boumediene Mariem , Jrad Mariem , Hamida Fethi Ben , Turki Sami , Gargah Tahar
Published: July 2023

Background

Takayasu arteritis is a rare and chronic granulomatous vasculitis that affects the large vessels. Takayasu arteritis targets the aorta and its branches and is still of unknown etiology. It often affects female patients under 50 years of age. A relationship between Takayasu arteritis and tuberculosis has been suggested for a long time.

Case presentation

We report a severe case of Takayasu arteritis in a 10-year-old Tunisian child revealed by renovascular hypertension with concomitant pulmonary tuberculosis.

Conclusions

Our patient is among only a few cases of Takayasu arteritis published worldwide affecting young infants and adolescents, which underlines the strong relationship between Takayasu arteritis and tuberculosis.
E-mental health in Germany — what is the current use and what are experiences of different types of health care providers for patients with mental illnesses?
Authors: Weitzel Elena Caroline , Schwenke Maria , Schomerus Georg , Schönknecht Peter , Bleckwenn Markus , Mehnert-Theuerkauf Anja , Riedel-Heller Steffi G. , Löbner Margrit
Published: July 2023

Background

As a new and effective support option, e-mental health interventions can be useful in complementing treatment in mental health care. To date, little is known about how health care providers use these programs to treat patients with mental illnesses in Germany. The present study aims to examine the use of and experiences with e-mental health interventions from the point of view of different types of health care providers for patients with mental illnesses.

Methods

Data from a cross-sectional survey of routine care health care providers in Germany in 2021 were analysed. In this survey, data were collected from n = 107 general practitioners (GPs), n = 114 specialist doctors, n = 102 psychotherapists, and n = 102 inpatient clinicians. Assessments included professional use of digital media, as well as knowledge, use and experiences regarding e-mental health interventions in care of people with mental illness.

Results

In the total sample of n = 425, 65.6% (n = 279) were female. The study participants had an average age of 47.7 years (SD = 11.0) and their average work experience was 20.0 years (SD = 11.1). Overall, the majority (83.8%, n = 353) had heard of e-mental health interventions, but few felt well informed. Only 28.5% (n = 121) had already used e-mental health interventions for treatment support. The most commonly recommended e-mental health interventions in the sample were deprexis (39.7%, n = 48), moodgym (24.8%, n = 30), and iFightDepression (22.3%, n = 27). The use was predominantly considered to be helpful and satisfactory. Insufficient knowledge about e-mental health interventions and lack of informational materials for patients were reported as relevant barriers to the use of e-mental health interventions.

Conclusions

E-mental health interventions can be a useful support option, but they are rarely used in the treatment of patients with mental illnesses. There is a need to disseminate information specific to the various types of health care providers. Tailored implementation strategies need to be developed in order to capitalize on the potential of effective e-mental health interventions and to improve health care for patients with mental illnesses.
Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer
Authors: Lee Ning-Yuan , Hum Melissa , Zihara Sabna , Wang Lanying , Myint Matthew K. , Lim Darren Wan-Teck , Toh Chee-Keong , Skanderup Anders , Samol Jens , Tan Min-Han , Ang Peter , Lee Soo-Chin , Tan Eng-Huat , Lai Gillianne G. Y. , Tan Daniel S. W. , Yap Yoon-Sim , Lee Ann S. G.
Published: July 2023

Background

Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung.

Methods

Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case–control association analyses were performed.

Results

Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such asBRCA2, TP53,andRAD51D;but also lesser known cancer genesEXT2,WWOX,GATA2, andGPC3.Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations.

Conclusions

We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.
HPLC–HR-ESI–MS/MS identification of fluorescent dyes and optical brighteners and their degradation products in daylight fluorescent paints
Authors: Reiß Lukas , Machill Susanne , Lübken Tilo , Herm Christoph
Published: July 2023

Daylight fluorescent paints are luminous colors that are increasingly used in contemporary art. The pigments consist of a synthetic resin in which fluorescent dyes and optical brighteners are embedded. In the recent years, several research articles have been published on the composition of daylight fluorescent pigments. Despite the growing research on the aging behavior of daylight fluorescent paints, little is known to date about the chemical processes involved in aging. In the research presented here, we used dialysis to separate the colorants from the resin. HPLC–HR-ESI–MS/MS was used to extend the elucidation of the dye composition. A variety of rhodamines and coumarins, an aminonaphthalimide dye and another optical brightener were determined. NMR was used to elucidate the structure of an additional hemicyanine dye not listed in the Colour Index. Furthermore, reference substances were artificially aged under visible light and UV radiation and the degradation products were analyzed accordingly. N-deethylation, hydroxylation and higher oxidation processes were found to be the main degradation pathways for all colorants. For most dyes and optical brighteners, there was no difference between aging under visible light and aging under UV radiation. When the results were checked on samples of aged paint mock-ups, it was found that only a few of the degradation products can still be detected in the case of very advanced aging even with the smallest sample quantities.
Automated radiosynthesis and in vivo evaluation of 18F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy
Authors: Kawamura Kazunori , Yamasaki Tomoteru , Fujinaga Masayuki , Kokufuta Tomomi , Zhang Yiding , Mori Wakana , Kurihara Yusuke , Ogawa Masanao , Tsukagoe Kaito , Nengaki Nobuki , Zhang Ming-Rong
Published: July 2023

Background

A family of BF2-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring. Radiolabeled photosensitizers can efficiently address photosensitizer biodistribution, providing helpful information for photodynamic therapy planning. To evaluate the biodistribution of ADPM06 and predict its pharmacokinetics on photodynamic therapy with light irradiation immediately after administration, we synthesized [18F]ADPM06 and evaluated its in vivo properties.

Results

[18F]ADPM06 was automatically synthesized by Lewis acid-assisted isotopic 18F-19F exchange using ADPM06 and tin (IV) chloride at room temperature for 10 min. Radiolabeling was carried out using 0.4 μmol of ADPM06 and 200 μmol of tin (IV) chloride. The radiosynthesis time was approximately 60 min, and the radiochemical purity was > 95% at the end of the synthesis. The decay-corrected radiochemical yield from [18F]F− at the start of synthesis was 13 ± 2.7% (n = 5). In the biodistribution study of male ddY mice, radioactivity levels in the heart, lungs, liver, pancreas, spleen, kidney, small intestine, muscle, and brain gradually decreased over 120 min after the initial uptake. The mean radioactivity level in the thighbone was the highest among all organs investigated and increased for 120 min after injection. Upon co-injection with ADPM06, the radioactivity levels in the blood and brain significantly increased, whereas those in the heart, lung, liver, pancreas, kidney, small intestine, muscle, and thighbone of male ddY mice were not affected. In the metabolite analysis of the plasma at 30 min post-injection in female BALB/c-nu/nu mice, the percentage of radioactivity corresponding to [18F]ADPM06 was 76.3 ± 1.6% (n = 3). In a positron emission tomography study using MDA-MB-231-HTB-26 tumor-bearing mice (female BALB/c-nu/nu), radioactivity accumulated in the bone at a relatively high level and in the tumor at a moderate level for 60 min after injection.

Conclusions

We synthesized [18F]ADPM06 using an automated 18F-labeling synthesizer and evaluated the initial uptake and pharmacokinetics of ADPM06 using biodistribution of [18F]ADPM06 in mice to guide photodynamic therapy with light irradiation.
Unforeseen complications: a case of dengue shock syndrome presenting with multi-organ dysfunction in a subtropical region
Authors: Owais Syed Muhammad , Ansar Farrukh , Saqib Muhammad , Wahid Khatira , Rashid Khalid , Mumtaz Hassan
Published: July 2023

Overview

Dengue fever, a viral illness transmitted by the Aedes mosquito, is capable of causing a range of serious complications, including fulminant hepatic failure, renal dysfunction, encephalitis, encephalopathy, neuromuscular and ophthalmic disorders, seizures, and cardiomyopathy.

Case description

This report details the case of a 30-year-old lactating woman with no notable medical history who presented to the emergency department with symptoms of high-grade fever, altered mental status, and seizures. Upon imaging, bilateral infarcts in the thalami and cerebellar hemispheres were observed, consistent with cerebellitis and dengue encephalitis.

Patient treatment and outcome

The patient was admitted to the intensive care unit and received appropriate treatment. Following a critical phase and successful patient stabilization, she was transferred to a high dependency unit for a week before being discharged with recommendations for follow-up care.

Conclusion

This case illustrates the broad spectrum of complications that can arise as a result of dengue infection and the importance of timely diagnosis and management in improving patient outcomes. Further investigation is required to better understand the mechanisms underlying these complications and to formulate specific guidelines for the prevention and treatment of dengue shock syndrome.
Contribution of remote sensing to wildfire trend and dynamic analysis in two of Ghana’s ecological zones: Guinea-savanna and Forest-savanna mosaic
Authors: Dahan Kueshi Sémanou , Kasei Raymond Abudu , Husseini Rikiatu
Published: July 2023

Background

Two of Ghana’s ecological zones—Guinea-savanna zone (GSZ) and Forest-savanna mosaic zone (FSZ)—are practically homologous in terms of structure and floristic composition, with some differences. The various sub-ecosystems that make up these areas are being depleted and losing their natural values due to various threats. There is little understanding about the fire trends in these areas due to a lack of data and poor accessibility to existing fire statistics. This study aimed to contribute to the understanding of the trends of area burned and active fire in the Guinea-savanna and Forest-savanna mosaic zones in order to inform policy-makers about sustainable management options. We used the Moderate Resolution Imaging Spectroradiometer (MODIS) daily active fire (MDC14ML) and burned-area (MCD64A1) products to characterize the fire regime in terms of seasonality, intensity, density, burned area, frequency, and trends during the study period of 2001 to 2021.

Results

This study indicated that fire activity started in October and peaked in December (GSZ) and January (FSZ). The mean proportion burned was approximately 39.95% (burned area of 2659.31 km2; FSZ) and 60.05% (burned area of 3996.63 km2: GSZ), while the frequency was approximately 42.87% (1759.95 of active fires; FSZ) and 57.13% (2345.26 of active fires: GSZ). In 2018, GSZ recorded the largest burned area (19 811.2 km2, which represents an average of 825.5 km2of the total area burned from 2001 to 2021) with 4719 active points detected. FSZ recorded its greatest burned area in 2015 (8727.4 km2; which represents an average of 363.6 km2of the total area burned from 2001 to 2021) with 5587 active points recorded. In addition, it was found that specific times of the day (1000 h to 1420 h) recorded the majority of burned areas. In overview, between 2001 and 2021, burned areas increased by an average of 1.4 km2(FSZ) and 4.6 km2(GSZ), and the number of active fires increased by an average of 4.7 (FSZ) and 4.4 (GSZ) active fires per km2.

Conclusions

In conclusion, burned areas and active fires are increasing in both ecological zones. This study demonstrated the relevance of remote sensing to describe spatial and temporal patterns of fire occurrence in Ghana and highlighted the need for fire control and fuel management by the policies and institutions (e.g., Ghana National Fire and Rescue Service) in these important and vulnerable zones (GSZ and FSZ). This is especially true in the Forest-savanna mosaic zone, which is increasingly affected by the disasters of wildfires and records more active fires than GSZ, indicating that this zone is becoming more and more vulnerable. Therefore, rigorous continuous monitoring is essential, and collaboration between organizations fighting for the conservation of natural resources in the field is strongly recommended.
Novel complete methanogenic pathways in longitudinal genomic study of monogastric age-associated archaea
Authors: Feehan Brandi , Ran Qinghong , Dorman Victoria , Rumback Kourtney , Pogranichniy Sophia , Ward Kaitlyn , Goodband Robert , Niederwerder Megan C. , Lee Sonny T. M.
Published: July 2023

Background

Archaea perform critical roles in the microbiome system, including utilizing hydrogen to allow for enhanced microbiome member growth and influencing overall host health. With the majority of microbiome research focusing on bacteria, the functions of archaea are largely still under investigation. Understanding methanogenic functions during the host lifetime will add to the limited knowledge on archaeal influence on gut and host health. In our study, we determined lifelong archaea dynamics, including detection and methanogenic functions, while assessing global, temporal and host distribution of our novel archaeal metagenome-assembled genomes (MAGs). We followed 7 monogastric swine throughout their life, from birth to adult (1–156 days of age), and collected feces at 22 time points. The samples underwent gDNA extraction, Illumina sequencing, bioinformatic quality and assembly processes, MAG taxonomic assignment and functional annotation. MAGs were utilized in downstream phylogenetic analysis for global, temporal and host distribution in addition to methanogenic functional potential determination.

Results

We generated 1130 non-redundant MAGs, representing 588 unique taxa at the species level, with 8 classified as methanogenic archaea. The taxonomic classifications were as follows: ordersMethanomassiliicoccales(5) andMethanobacteriales(3); generaUBA71(3),Methanomethylophilus(1),MX-02(1), andMethanobrevibacter(3). We recovered the first US swineMethanobrevibacter UBA71 sp006954425andMethanobrevibacter gottschalkiiMAGs. TheMethanobacterialesMAGs were identified primarily during the young, preweaned host whereasMethanomassiliicoccalesprimarily in the adult host. Moreover, we identified our methanogens in metagenomic sequences from Chinese swine, US adult humans, Mexican adult humans, Swedish adult humans, and paleontological humans, indicating that methanogens span different hosts, geography and time. We determined complete metabolic pathways for all three methanogenic pathways: hydrogenotrophic, methylotrophic, and acetoclastic. This study provided the first evidence of acetoclastic methanogenesis in archaea of monogastric hosts which indicated a previously unknown capability for acetate utilization in methanogenesis for monogastric methanogens. Overall, we hypothesized that the age-associated detection patterns were due to differential substrate availability via the host diet and microbial metabolism, and that these methanogenic functions are likely crucial to methanogens across hosts. This study provided a comprehensive, genome-centric investigation of monogastric-associated methanogens which will further improve our understanding of microbiome development and functions.
Rock-physics modeling of elastic properties of multiscale fractured rocks
Authors: Wang Yirong , Zhao Luanxiao , Yang Zhifang , Cao Hong , Guo Junxin , Geng Jianhua
Published: July 2023

Fractures, often existing across various scales, control the mechanical and fluid flow properties of upper crustal rocks. Inferring fracture properties at different scales from multiband geophysical measurements is essential for many fields of earth and energy sciences. Under the framework of multiscale homogenization, we develop a rock-physics model to characterize the elastic and anisotropic properties of multiscale fractured rocks following a certain statistical law. The isotropic differential effective medium theory is used to model the elasticity of randomly oriented microcracks, and the linear slip theory is used to model the elasticity of oriented or randomly oriented macroscale fractures. For a multiscale fractured rock covered by six orders of fracture length (10−4 m to 102 m), it is found that velocity exhibits a decreasing trend with the increment of scale. Nevertheless, the different statistical distribution of multiscale fractures significantly affects the velocity and anisotropy variation pattern with scale. The velocity for the fractal distribution decreases significantly at the seismic scale, whereas, for the log-Gaussian distribution, the dramatic change in velocity occurs more at the ultrasonic and logging scales, depending on the length of the dominant fractures. We apply our methodology to interpret a set of multiscale geophysical data of P-wave velocity in a fractured carbonate formation and estimate that the multiscale fracture is possibly distributed in a log-Gaussian manner. Our elastic and anisotropic modeling strategy has the potential to predict the distribution pattern of fractures, especially by reconciling the multifrequency geophysical measurements (e.g., ultrasonic, logging, and seismic data).
Pseudo-3D cubes from densely spaced subbottom profiles via projection onto convex sets interpolation: An open-source workflow applied to a pockmark field
Authors: Warnke Fynn , Pecher Ingo A. , Hillman Jess I. T. , Davy Bryan , Woelz Susi , Gorman Andrew R. , Strachan Lorna J.
Published: July 2023

High-resolution subbottom profiler (SBP) data are commonly recorded during academic or industrial surveys and analyzed as 2D profiles. However, there is growing interest in 3D imaging of the shallow seafloor subsurface, e.g., site surveys prior to the installation of offshore wind farms. Despite ongoing advancements in 3D systems, SBPs continue to be used mainly for 2D profiling. In other seismic imaging applications, “pseudo-3D” seismic cubes have been successfully generated from dense 2D seismic surveys. We developed a novel open-source Python-based workflow to interpolate densely spaced 2D SBP profiles acquired with a hull-mounted parametric SBP into pseudo-3D cubes. This workflow is applied to a study area on the Chatham Rise east of New Zealand’s South Island, comprising numerous seafloor pockmarks and subsurface paleo-pockmarks. Our workflow consists of two stages: (1) processing of individual 2D profiles to compensate for existing vertical offsets and (2) sparse data interpolation by applying the iterative projection onto convex sets algorithm. We correct the residual static effect caused by the sea state during acquisition, compensate for the varying tidal elevations, and apply vertical time shifts to individual profiles to correct misties at profile intersections. The interpolation of the binned sparse 3D cube is performed in the frequency domain using the fast Fourier transform and executed in parallel processes, which significantly increases the computational efficiency. We validate our workflow by testing different bin sizes, sparse transforms, thresholding approaches, and varying total iterations, which noticeably impact the resulting interpolation quality. Our developed workflow generates pseudo-3D subsurface images from densely spaced SBP profiles, with numerous potential applications for academic and industrial surveys.
Immune Resistance Mechanisms and the Road to Personalized Immunotherapy
Authors: Piper Miles , Kluger Harriet , Ruppin Eytan , Hu-Lieskovan Siwen
Published: July 2023

What does the future of cancer immunotherapy look like and how do we get there? Find out where we've been and where we're headed in A Report on Resistance: The Road to personalized immunotherapy
Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200
Authors: Giantonio Bruce J. , Catalano Paul J. , Meropol Neal J. , O'Dwyer Peter J. , Mitchell Edith P. , Alberts Steven R. , Schwartz Michael A. , Benson Al B.
Published: July 2023

Purpose

Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer.

Patients and Methods

Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity.

Results

The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively ( P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting.

Conclusion

The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.
Polygenic Risk and Chemotherapy-Related Subsequent Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study Report
Authors: Im Cindy , Sharafeldin Noha , Yuan Yan , Wang Zhaoming , Sapkota Yadav , Lu Zhanni , Spector Logan G. , Howell Rebecca M. , Arnold Michael A. , Hudson Melissa M. , Ness Kirsten K. , Robison Leslie L. , Bhatia Smita , Armstrong Gregory T. , Neglia Joseph P. , Yasui Yutaka , Turcotte Lucie M.
Published: July 2023

PURPOSE

Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases.

PATIENTS AND METHODS

SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS quintiles was estimated, along with hazard ratios (HRs) from proportional hazards models.

RESULTS

A total of 1,594 survivors developed SMNs, with basal cell carcinomas (n = 822), breast cancers (n = 235), and thyroid cancers (n = 221) being the most frequent. Although SMN risk associations with the PRS were extremely modest in RT-exposed EUR survivors (HR, 1.22; P = .048; n = 4,630), the increase in 30-year SMN cumulative incidence and HRs comparing top and bottom PRS quintiles was statistically significant among nonirradiated EUR survivors (n = 4,322) treated with alkylating agents (17% v 6%; HR, 2.46; P < .01), anthracyclines (20% v 8%; HR, 2.86; P < .001), epipodophyllotoxins (23% v 1%; HR, 12.20; P < .001), or platinums (46% v 7%; HR, 8.58; P < .01). This PRS also significantly modified epipodophyllotoxin-related SMN risk among nonirradiated AFR survivors (n = 414; P < .01). Improvements in prediction attributable to the PRS were greatest for epipodophyllotoxin-exposed (AUC, 0.71 v 0.63) and platinum-exposed (AUC,0.68 v 0.58) survivors.

CONCLUSION

A pleiotropic cancer PRS has strong potential for improving SMN clinical risk stratification among nonirradiated survivors treated with specific chemotherapies. A polygenic risk screening approach may be a valuable complement to an early screening strategy on the basis of treatments and rare cancer-susceptibility mutations.
Resuming Anticoagulants in Patients With Intracranial Hemorrhage: A Meta-Analysis and Literature Review
Authors: El Naamani Kareem , Abbas Rawad , Ghanem Marc , Mounzer Marc , Tjoumakaris Stavropoula I. , Gooch M. Reid , Rosenwasser Robert H. , Jabbour Pascal M.
Published: July 2023

BACKGROUND AND OBJECTIVES:

Intracerebral hemorrhage (ICH) is one of the most disabling cerebrovascular events. Several studies have discussed oral anticoagulant (OAC)–related ICH; however, the optimal timing of resuming OAC in patients with ICH is still a dilemma. In this literature review/meta-analysis, we will summarize, discuss, and provide the results of studies pertaining to OAC resumption in patients with ICH.

METHODS:

Using PubMed, Ovid Medline, and Web science, a systemic literature review was performed in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement on December 20, 2022. Inclusion criteria for the meta-analysis were all studies reporting mean, median, and standard deviation for the duration of anticoagulants resumption after ICH. Thirteen studies met the above criteria and were included in the meta-analysis.

RESULTS:

Of the 271 articles found in the literature, pooled analysis was performed in 13 studies that included timing of OAC resumption after ICH. The pooled mean duration to OAC resumption after the index ICH was 31 days (95% CI: 13.7-48.3). There was significant variation among the mean duration to OAC resumption reported by the studies as observed in the heterogeneity test (P-value ≈0).

CONCLUSION:

Based on our meta-analysis, the average time of resuming OAC in patients with ICH is around 30 days. Several factors including the type of intracranial hemorrhage, the type of OAC, and the indication for OACs should be taken into consideration for future studies to try and identify the best time to resume OAC in patients with ICH.
Understanding the neurological implications of acute and long COVID using brain organoids
Authors: García-González Laura , Martí-Sarrias Andrea , Puertas Maria C. , Bayón-Gil Ángel , Resa-Infante Patricia , Martinez-Picado Javier , Navarro Arcadi , Acosta Sandra
Published: July 2023

As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.
Dehydrated snakes reduce postprandial thermophily
Authors: Azzolini Jill L. , Roderick Travis B. , DeNardo Dale F.
Published: July 2023

Transient thermophily in ectothermic animals is a common response during substantial physiological events. For example, ectotherms often elevate body temperature after ingesting a meal. In particular, the increase in metabolism during the postprandial response of pythons – known as specific dynamic action – is supported by a concurrent increase in preferred temperature. The objective of this study was to determine whether hydration state influences digestion-related behavioral thermophily. Sixteen (8 male and 8 female) Children's pythons (Antaresia childreni) with surgically implanted temperature data loggers were housed individually and provided with a thermal gradient of 25–45°C. Body temperature was recorded hourly beginning 6 days prior to feeding and for 18 days post-feeding, thus covering pre-feeding, postprandial and post-absorptive stages. Each snake underwent this 24 day trial twice, once when hydrated and once when dehydrated. Our results revealed a significant interaction between temperature preference, digestive stage and hydration state. Under both hydrated and dehydrated conditions, snakes similarly increased their body temperature shortly after consuming a meal, but during the later days of the postprandial stage, snakes selected significantly lower (∼1.5°C) body temperature when they were dehydrated compared with when they were hydrated. Our results demonstrate a significant effect of hydration state on postprandial thermophily, but the impact of this dehydration-induced temperature reduction on digestive physiology (e.g. passage time, energy assimilation) is unknown and warrants further study.
Phase-separated ribosome-nascent chain complexes in genotoxic stress response
Authors: Németh-Szatmári Orsolya , Nagy-Mikó Bence , Györkei Ádám , Varga Dániel , Kovács Bálint Barna H. , Igaz Nóra , Bognár Bence , Rázga Zsolt , Nagy Gábor , Zsindely Nóra , Bodai László , Papp Balázs , Erdélyi Miklós , Kiricsi Mónika , Blastyák András , Collart Martine A. , Boros Imre M. , Villányi Zoltán
Published: July 2023

Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered amino-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits ofSaccharomyces cerevisiaeprotein complexes according to their amino-terminal disorder propensity. The results revealed that gene products involved in DNA repair are enriched among the top candidates. The Sgs1 DNA helicase was chosen for experimental validation. We found that indeed nascent chains of Sgs1 form EDTA-resistant RNP condensates, assemblysomes by definition. Moreover, upon exposure to UV,SGS1mRNA shifted from assemblysomes to polysomes, suggesting that external stimuli are regulators of assemblysome dynamics. We extended our studies to human cell lines. The BLM helicase, ortholog of yeast Sgs1, was identified upon sequencing assemblysome-associated RNAs from the MCF7 human breast cancer cell line, and mRNAs encoding DNA repair proteins were overall enriched. Using the radiation-resistant A549 cell line, we observed by transmission electron microscopy that 1,6-hexanediol, an agent known to disrupt phase-separated condensates, depletes ring ribosome structures compatible with assemblysomes from the cytoplasm of cells and makes the cells more sensitive to X-ray treatment. Taken together, these findings suggest that assemblysomes may be a component of the DNA damage response from yeast to human.
Social and health indicators in an academic community: enteroparasites, nutritional, allergic and clinical aspects
Authors: Santos Junior Edemilton Ribeiro , Andrade Raoni dos Santos , Souza Passos Aldery , Santos Raíssa da Silva , Andrade dos Santos Glauber , Soares de Almeida Mariana , Bomfim Érica Santos , Dos Santos de Matos Paulo José , Araújo de Lima Luana Brunelly , Sampaio de Carvalho Karine , Rossi Rebeca Correia , Araújo de Albuquerque Wesley , Correia Manuella Silva , Ribeiro Lívia Sousa , Amor Ana Lúcia Moreno
Published: July 2023

Objective: this study aimed to associate enteroparasitic infection with nutritional, allergic, and clinical repercussions and the sociodemographic aspects in an academic community in Santo Antônio de Jesus, Bahia, Brazil. Methods: the cross-sectional research was carried out between February 2018 and March 2020, with 121 participants. Spontaneous sedimentation and Rugai techniques were used for the parasitological diagnosis of fecal samples. Allergies and clinical issues and the sociodemographic aspects were studied via a questionnaire, and the nutritional status was obtained from the assessment of body mass index and arm and abdominal circumferences. Results: there was 38.2% positivity for intestinal parasites; 65.9% for female participants; with the majority of eutrophic, between 18-27 years old; heteronormative, and single. Besides, the Endolimax nana (78.7%) and Giardia duodenalis (21.3%) were the predominant species. Statistical significance was found between obesity rates and the presence of intestinal parasites and those with allergic aspects. Nervousness, headache, and back and abdominal pains were the most common symptoms. Conclusions: this study contributes to obtaining data on epidemiological and public health surveys in the Bahian territory, providing a reference for other researchers. The statistical association of these with nutritional and allergic aspects can support future research on this population.
Διαγνωστική και κλινική σημασία ανοσοβιολογικών δεικτών στον καρκίνο της ωοθήκης
Authors: Παπαδόπουλος Βασίλειος
Published: July 2023

Ο καρκίνος των ωοθηκών ανήκει στις συχνότερες γυναικολογικές κακοήθειες. Δεν υπάρχουν ειδικοί βιοδείκτες για την πρώιμη διάγνωση του. Το CA125 χρησιμοποιείται για την παρακολούθηση της ανταπόκρισης στη θεραπεία. Τα παρανεοπλασματικά αντισώματα δημιουργούνται εξαιτίας της μη ρυθμισμένης ανοσιακής απόκρισης έναντι καρκινικών αντιγόνων. Η ειδική ανοσο-αντιδραστικότητα έναντι καρκινικών αντιγόνων αποτελεί έναν υποσχόμενο μηχανισμό για την ανάπτυξη πιο εξειδικευμένων βιοδεικτών. Η πρωτεΐνη TRIM21/Ro52 εμπλέκεται στη φλεγμονή, στον καρκίνο και στην αυτοανοσία. Στον καρκίνο έχει διττό ρόλο ανάλογα με τους παράγοντες καρκινογένεσης και τον τύπο του καρκίνου. Αντισώματα έναντι Ro52/TRIM21 ανιχνεύονται συχνά σε ασθενείς με αυτοάνοσες παθήσεις αλλά ακόμη και κακοήθειες. Στη μελέτη μας αναλύθηκαν με έμμεσο ανοσοφθορισμό οροί από 77 ασθενείς με καρκίνο των ωοθηκών ενώ η ομάδα ελέγχου αποτελούνταν από 48 ασθενείς με άλλους τύπους καρκίνου. Θετικότητα βρέθηκε στο 53,2% των ασθενών με καρκίνο των ωοθηκών με τίτλο ≥1/80 και με ένα σημαντικό ποσοστό αυτών να εμφανίζουν ένα κυτταροπλασματικό κοκκιώδες πρότυπο ανοσοφθορισμού. Αντίθετα, στην ομάδα ελέγχου θετικότητα βρέθηκε στο 31,2%. Δεν υπήρξε συσχέτιση με κλινικοεργαστηριακά στοιχεία αλλά ούτε και με την ολική επιβίωση. Ακολούθως, έγινε προσπάθεια ανεύρεσης του πιθανού αντιγόνου στόχου στο κυτταρόπλασμα με ανοσοτύπωση γραμμής αλλά δεν βρέθηκε να είναι κάποιο από τα γνωστά αντιγόνα στόχοι. Στη συνέχεια, μελετήθηκε η παρουσία αντι-Ro52 αντισωμάτων σε 490 ασθενείς με διάφορες κακοήθειες και έγινε προσπάθεια χαρτογράφησης των επιτόπων των Β κυττάρων τους. Θετικότητα βρέθηκε στο 14.3% των ασθενών συνολικά με πιο συχνή την εμφάνιση μεταξύ των ασθενών με καρκίνο ωοθηκών (30%). Βρέθηκε στατιστικά σημαντική συσχέτιση με την ολική επιβίωση. Τέλος, αυτά τα μονοειδικά αντισώματα έχουν διαφορετικό προφίλ επιτόπων σε σχέση με αυτό που παρατηρείται σε αυτοάνοσες ρευματικές παθήσεις. Συμπερασματικά, στον καρκίνο των ωοθηκών παρατηρείται, περισσότερο από άλλους τύπους καρκίνου, απώλεια ανοσολογικής ανοχής έναντι του Ro52. Η μελέτη μας αναδεικνύει την πιθανή προγνωστική αξία του αντι-Ro52 αντισώματος σε ασθενείς με καρκίνο των ωοθηκών, καθιστώντας το ένα πιθανό μελλοντικό βιοδείκτη.
Ανέκδοτη επιστολή του Μητροπολίτη Σμύρνης Ανθμίου προς τον Ειρηναίο Θήρσιο
Authors: Karaoulas Apostolos
Published: July 2023

Η επιστολή που εντοπίσαμε στα αρχεία χειρογράφων της Κρατικής Βαυαρικής Βιβλιοθήκης στο Μόναχο, εντάσσεται στο πλαίσιο της φιλελληνικής δράσης, την περίοδο του Νεοελληνικού Διαφωτισμού καθώς και στην προσπάθεια ίδρυσης και οργάνωσης ικανών διδακτηρίων, αποβλέποντας στη μόρφωση και στη σωτηρία της πατρίδας κατά την προεπαναστατική περίοδο. Η επιστολή υπογράφεται από τον Μητροπολίτη Σμύρνης Άνθιμο, φέρει ημερομηνία την 1η Δεκεμβρίου 1814 και απευθύνεται στον Φρειδερίκο Θήρσιο, καθώς και στα μέλη της Βαυαρικής Ακαδημίας (Παπαδόπουλος, 1962). Η επιστολή είναι εκτενής και γραμμένη με λόγιο ύφος. Ο επιστολογράφος παραθέτει χωρία από τον Όμηρο, τον Ευριπίδη και τον Πλούταρχο, καθώς έμμεσες και άμεσες αναγωγές με μυθολογικό περιεχόμενο και με έντονα στοιχεία της αρχαίας ελληνικής γραμματείας και φιλοσοφίας. Είναι επιστολή απαντητική και ευχαριστήρια σε άκρως επιμελημένο ύφος. Ο Άνθιμος καταβάλλει συνειδητά προσπάθεια να εντυπωσιαστεί ο αποδέκτης της. Το περιεχόμενο της επιστολής δείχνει άνθρωπο με υψηλή μόρφωση και καλλιεργημένο και στο σύνολό της θυμίζει κείμενο της αρχαιοελληνικής γραμματείας.