bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implantation of CRT pacemaker during pregnancy: estimated fetal radiation dose
Authors: Manninen Anna-Leena , Järvinen Jukka , Sierpowska Joanna , Mäkelä Timo J , Rissanen Tuomas T 
Published: September 2024

Abstract
The benefits of a cardiac resynchronization therapy (CRT) implantation are known in severe heart failure and its implantation may also be considered during pregnancy to ensure safe pregnancy and delivery for both the mother and the fetus. This study on a patient case aimed to estimate the absorbed dose (AD) to the fetus during the CRT implantation of 21st week of the pregnant woman. AD measurement was done using anthropomorphic phantom, radiophotoluminescence dosemeters and Monte Carlo simulation utilizing kerma area product (KAP) of the procedures. The measured AD for a phantom’s uterus and heart was 0.116 and 14.7 mGy with total KAP of 27.9 Gycm2. The estimated actual AD to the fetus and the mother’s heart was 0.004 and 1.2 mGy, with total KAP of 1.5 Gycm2. The dose to the fetus can be minimized with the optimized procedure.
Radiation exposure to patients undergoing percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography: an advanced phantom study
Authors: Tunçman Duygu , Özgür Eren , Nayci Ali Emre , Günay Osman , Kesmezacar Fahrettin Fatih , Karaçam Songül Çavdar , Üzüm Güngör , Demir Mustafa , Akkuş Baki , Elshami Wiam , Almisned Ghada , Tekin Huseyin Ozan 
Published: September 2024

Abstract
Fluoroscopic examinations like Endoscopic Retrograde Cholangiopancreatography (ERCP) and Percutaneous Transhepatic Cholangiography (PTC) are fundamental in diagnosing and treating hepatobiliary diseases. However, these procedures expose patients to significant radiation, highlighting the need for a detailed assessment of the radiation doses received by critical organs. The study’s primary objective is to determine the experimental doses received by critical organs in patients undergoing these procedures. This study utilized an Alderson RANDO phantom outfitted with Thermoluminescent Dosemeters (TLDs) to experimentally measure the radiation doses received by various organs during ERCP and PTC procedures. This method provided direct and accurate data on organ-specific radiation exposure, contrasting with the traditional approach of relying on theoretical simulations. The analysis revealed that PTC generally results in higher radiation doses to organs compared to ERCP. Critical organs, such as the thyroid, spleen, liver, pancreas, ovaries, and uterus, were exposed to varying levels of radiation, with the thyroid and spleen receiving particularly high doses in PTC. The study also demonstrated that the per-minute radiation exposure was consistently higher in PTC across all examined organs. The study’s findings underscore the significant radiation exposure associated with ERCP and PTC, with PTC posing a greater risk. Understanding these exposure levels is crucial for clinical decision-making, particularly when considering patients’ pre-existing conditions and sensitivity to radiation. The study highlights the need for clinicians to carefully weigh the benefits of ERCP and PTC against the potential radiological risks. It suggests a preference for ERCP in situations where radiation exposure needs to be minimized. Furthermore, the findings advocate for ongoing advancements in medical imaging techniques to reduce radiation exposure, emphasizing the importance of patient safety in fluoroscopic examinations. This research contributes significantly to informed clinical decision-making, ensuring that the selection of diagnostic and therapeutic procedures aligns with the best interest of patient health and safety.
Towards sustainable antimicrobial therapies for Staphylococcus aureus skin infections
Authors: Lang Julia C , Shahata Mariam , Melican Keira 
Published: September 2024

Abstract
Skin and soft tissue infections (SSTIs) are a major economic and clinical burden. With the emergence of increasing antimicrobial resistance, novel treatment options, as well as advanced drug delivery systems will be essential to fight these infections and meet the UN Sustainability Development Goals (SDGs). SSTIs are commonly caused by Staphylococcus aureus, including the infamous MRSA (methicillin-resistant S. aureus). In this short review, we discuss new antimicrobial therapies with potential to combat skin infections caused by S. aureus. This includes discussion of antimicrobial strategies originating from both the host and microbiota. Adapting immunotherapy-type approaches to infection is also discussed, giving examples of cellular targets of interest. We examine the difficulties of therapeutic delivery into a barrier tissue such as skin and discuss exciting new developments in interdisciplinary approaches that may help overcome these challenges.
Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson’s disease
Authors: Eubanks Elena , VanderSleen Katelyn , Mody Jiya , Patel Neha , Sacks Benjamin , Farahani Mahsa Darestani , Wang Jinying , Elliott Jordan , Jaber Nora , Akçimen Fulya , Bandres-Ciga Sara , Helweh Fadel , Liu Jun , Archakam Sanjana , Kimelman Robert , Sharma Bineet , Socha Philip , Guntur Ananya , Bartels Tim , Dettmer Ulf , Mouradian M. Maral , Bahrami Amir Houshang , Dai Wei , Baum Jean , Shi Zheng , Hardy John , Kara Eleanna 
Published: September 2024

ABSTRACTAlpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson’s disease and forms intraneuronal inclusions called Lewy Bodies. While the mechanism underlying the dysregulation of αSyn in Parkinson’s disease is unclear, it is thought that prionoid cell-to-cell propagation of αSyn has an important role. Through a high throughput screen, we recently identified 38 genes whose knock down modulates αSyn propagation. Follow up experiments were undertaken for two of those genes,TAX1BP1andADAMTS19, to study the mechanism with which they regulate αSyn homeostasis. We used a recently developed M17D neuroblastoma cell line expressing triple mutant (E35K+E46K+E61K) “3K” αSyn under doxycycline induction. 3K αSyn spontaneously forms inclusions that show ultrastructural similarities to Lewy Bodies. Experiments using that cell line showed thatTAX1BP1andADAMTS19regulate how αSyn interacts with lipids and phase separates into inclusions, respectively, adding to the growing body of evidence implicating those processes in Parkinson’s disease. Through RNA sequencing, we identified several genes that are differentially expressed after knock-down ofTAX1BP1orADAMTS19. Burden analysis revealed that those differentially expressed genes (DEGs) carry an increased frequency of rare risk variants in Parkinson’s disease patients versus healthy controls, an effect that was independently replicated across two separate cohorts (GP2 and AMP-PD). Weighted gene co-expression network analysis (WGCNA) showed that the DEGs cluster within modules in regions of the brain that develop high degrees of αSyn pathology (basal ganglia, cortex). We propose a novel model for the genetic architecture of sporadic Parkinson’s disease: increased burden of risk variants across genetic networks dysregulates pathways underlying αSyn homeostasis, thereby leading to pathology and neurodegeneration.
Ultrastructural and transcriptional changes during a giant virus infection of a green alga
Authors: Gajigan Andrian P. , Schvarcz Christopher R. , Conaco Cecilia , Edwards Kyle F. , Steward Grieg F. 
Published: September 2024

AbstractThe complete genome sequence of theOceanusvirus kaneohensestrain (Tetraselmis virus 1; TetV-1) was previously reported, but little is known about the virus infection cycle. Using a permissiveTetraselmisisolate (UHM1315), we estimated the eclipse period (4–8 hours), latent period (16 hrs), and burst size (800–1000) of the virus and documented ultrastructural and transcriptional changes in the host during infection. Putative viral factories and electron-dense inclusion bodies appeared in the cytoplasm of infected cells by 8 and 16 h post-infection, respectively. The nucleus and chloroplasts appeared to remain intact but reduced in size after 8 h. Transcriptome sequencing suggests that the viral genome codes for 830 transcripts. Those expressed early in infection (eclipse period at 0.25 and 4 hr) were related to the initiation of transcription, DNA synthesis, translation, and host immune repression. During the later, post-eclipse period (8, 12, 16 hr), virus structural genes were expressed. For the algal host, transcripts related to lipid metabolism and endocytosis were upregulated during the early phase, while those for protein modification/ turnover/ transport were downregulated. In the later period, host transcripts associated with basic cellular processes were upregulated, while genes related to morphogenesis/development were downregulated. Many of the most highly expressed virus and host genes were of unknown function, highlighting a need for additional functional studies.
Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling
Authors: Kigar Stacey L. , Lynall Mary-Ellen , DePuyt Allison E. , Atkinson Robert , Sun Virginia H. , Samuels Joshua D. , Eassa Nicole E. , Poffenberger Chelsie N. , Lehmann Michael L. , Listwak Samuel J. , Livak Ferenc , Elkahloun Abdel G. , Clatworthy Menna R. , Bullmore Edward T. , Herkenham Miles 
Published: September 2024

AbstractAnimal models of stress and stress-related disorders are also associated with blood neutrophilia. The mechanistic relevance of this to symptoms or behavior is unclear. We used cytometry, immunohistochemistry, whole tissue clearing, and single-cell sequencing to characterize the meningeal immune response to chronic social defeat (CSD) stress in mice. We find that chronic, but not acute, stress causes meningeal neutrophil accumulation, and CSD increases neutrophil trafficking in vascular channels emanating from skull bone marrow (BM). Transcriptional analysis suggested CSD increases type I interferon (IFN-I) signaling in meningeal neutrophils. Blocking this pathway via the IFN-I receptor (IFNAR) protected against the anhedonic and anxiogenic effects of CSD stress, potentially through reduced infiltration of IFNAR+neutrophils into the meninges from skull BM. Our identification of IFN-I signaling as a putative mediator of meningeal neutrophil recruitment may facilitate development of new therapies for stress-related disorders.One sentence summaryType I interferon sensing neutrophils accumulate in meninges of psychosocially stressed mice via skull bone marrow channels and are associated with the negative behavioral sequelae of stress; blockade of this pathway inhibits neutrophil trafficking and improves behavioral outcomes.
LexicMap: efficient sequence alignment against millions of prokaryotic genomes
Authors: Shen Wei , Iqbal Zamin 
Published: September 2024

AbstractAlignment against a database of genomes is a fundamental operation in bioinformatics, popularized by BLAST. However, the rate at which microbial genomes are sequenced has continued to increase, and there are now datasets in the millions, far beyond the abilities of existing alignment tools. We introduce LexicMap, a nucleotide sequence alignment tool for efficiently querying moderate length sequences (> 500 bp) such as a gene, plasmid or long read against up to millions of prokaryotic genomes. A key innovation is to construct a small set of probek-mers (e.g. n = 40,000) which “window-cover” the entire database to be indexed, in the sense that every 500 bp window of every database genome contains multiple seedk-mers each with a shared prefix with one of the probes. Storing these seeds, indexed by the probes with which they agree, in a hierarchical index enables fast and low-memory variable-length seed matching, pseudoalignment, and then full alignment. We show that LexicMap is able to align with higher sensitivity than Blastn as the query divergence drops from 90% to 80% for queries ≥ 1 kb, and then benchmark on small (GTDB) and large (AllTheBacteria and Genbank+RefSeq) databases. We show that LexicMap achieves higher sensitivity and speed and lower memory compared to the state-of-the-art approaches. Alignment of a single gene against 2.34 million prokaryotic genomes from GenBank and RefSeq takes 36 seconds (rare gene) to 15 minutes (16S rRNA gene). LexicMap produces output in standard formats including that of BLAST and is available under MIT license athttps://github.com/shenwei356/LexicMap.
Insulin-Independent Regulation of Type 1 Diabetes via Brown Adipocyte-Secreted Proteins and the Novel Glucagon Regulator Nidogen-2
Authors: Lee Jeongmin , Ustione Alessandro , Wilkerson Emily M , Balakrishnan Rekha , Thurmond Debbie C. , Goldfarb Dennis , Piston David W. 
Published: September 2024

SUMMARYCurrent treatments for type 1 diabetes (T1D) focus on insulin replacement. We demonstrate the therapeutic potential of a secreted protein fraction from embryonic brown adipose tissue (BAT), independent of insulin. The large molecular weight secreted fraction mediates insulin receptor-dependent recovery of euglycemia in a T1D animal model, nonobese diabetic (NOD) mice, by suppressing glucagon secretion. This fraction also promotes white adipocyte differentiation and browning, maintains healthy BAT, and enhances glucose uptake in adipose tissue, skeletal muscle, and liver. From this fraction, we identify nidogen-2 as a critical BAT-secreted protein that reverses hyperglycemia in NOD mice, inhibits glucagon secretion from pancreatic α-cells, and mimics other actions of the entire secreted fraction. These findings confirm that BAT transplants affect physiology and demonstrate that BAT-secreted peptides represent a novel therapeutic approach to diabetes management. Furthermore, our research reveals a novel signaling role for nidogen-2, beyond its traditional classification as an extracellular matrix protein.HIGHLIGHTSThe large molecular weight brown adipocyte-secreted protein fraction suppresses glucagon secretion and normalizes glycemia in mouse models of type 1 diabetes (T1D), independent of insulin, offering a novel therapeutic strategy for disease management.Nidogen-2, a critical component of this fraction, is identified as an inhibitor of glucagon secretion in pancreatic α-cells by regulating intracellular messenger activities.The large-secreted protein fraction prevents T1D-related whitening of brown adipose tissue, promotes adipocyte differentiation, and enhances browning of inguinal white adipose tissue.This fraction enhances glucose uptake in adipose tissue, skeletal muscle, and liver through an insulin receptor-dependent pathway.
Developing Biosensors for Specific Assessment ofTrans-translation inPseudomonas aeruginosa
Authors: L’Hermitte Bastien , Chauvet Thomas , Georgeault-Daguenet Sylvie , Yondre Nicolas Le , Jehan Philippe , Gillet Reynald , Baysse Christine 
Published: September 2024

AbstractTrans-translation is a crucial bacterial process and a target for new antibiotics. We developed twoPseudomonas aeruginosabiosensor strains that detecttrans-translation inhibitors by exploiting the bacterium’s natural red fluorescence, linked to protoporphyrin IX accumulation. The first biosensor monitors tmRNA-SmpB-mediated tagging, while the second serves as control for biosensor 1 by keeping track of ClpP1-related proteolysis and porphyrin biosynthesis. Validation through gene deletions and complementation confirmed their specificity. These biosensors were effective in screening antibiotics and designed inhibitors, demonstrating their potential for high-throughput identification oftrans-translation inhibitors in drug-resistantP. aeruginosa.
Population-level age effects on the white matter structure subserving cognitive flexibility in the human brain
Authors: Wolfe Tatiana , Gassel Alexandra , Calvert Maegan L. , Isaac Lee , James G. Andrew , Kosick Timothy R. , Kilts Clint D. 
Published: September 2024

AbstractCognitive flexibility, a cognition crucial for adaptive behavior, involves multi-scale functioning across several neuronal organization levels. While the neural underpinnings of flexibility have been studied for decades, limited knowledge exist about the structure and differentiation of the white matter subserving brain regions implicated in cognitive flexibility. Neural changes that occur over the lifespan have an impact in the brain’s white matter organization and, thereby, may alter cognitive flexibility abilities. This study investigates the population-level relationship between cognitive flexibility and macromolecular properties of white matter across two periods of adulthood, aiming to discern how these associations vary over different life stages and brain tracts. A novel method to study age-effects in the brain’s structure-function associations is proposed. First, the white matter structure implicated in cognitive flexibility was delineated by tracing in the Human Connectome Project tractography template the pathways subserving neural regions derived via meta-analysis of set-shifting. Then, a cohort analysis was performed to characterize related brain features using a subset of the UKBiobank MRI data which has a companion functional/behavioral dataset.1We found that (1)the wiring of cognitive flexibility is defined by specialized tracts, which present undifferentiated features early in adulthood, and significantly differentiated types in later life. (2)These MRI-derived properties are correlated with individual subprocesses of cognition which intimately relate to the latent construct of cognitive flexibility function (switch, inhibition, and updating).2(3)In late life, myelin-related homogeneity of specific white matter tracts implicated in cognitive flexibility declines as a function of chronological age—a phenomenon not observed in early life. Our findings support the age-related differentiation of white matter tracts implicated in cognitive flexibility as a natural substrate of brain adaptive function.Significance StatementCognitive flexibility, a cognition that facilitates adaptation to environmental demands, involves complex brain processes. During the lifespan, brain changes affecting the brain’s structural organization are theorized to impact cognitive flexibility. This study characterizes how the brain’s connectivity is correlated with cognitive flexibility throughout adulthood. By analyzing macromolecular properties of white matter, this study found that certain parts of the brain’s wiring related to cognitive flexibility become more distinct with advanced age. This age-related distinction of the wiring implicated in cognitive flexibility appears as a natural, underlying characteristic of the human brain which may impact specific aspects of thinking, like shifting between tasks or updating information.
An alveolus lung-on-a-chip model ofMycobacterium fortuitumlung infection
Authors: Ektnitphong Victoria , Dias Beatriz R.S. , Campos Priscila C. , Shiloh Michael U. 
Published: September 2024

AbstractLung disease due to non-tuberculous mycobacteria (NTM) is rising in incidence. While both two dimensional cell culture and animal models exist for NTM infections, a major knowledge gap is the early responses of human alveolar and innate immune cells to NTM within the human alveolar microenvironment. Here we describe development of a humanized, three-dimensional, alveolus lung-on-a-chip (ALoC) model ofMycobacterium fortuitumlung infection that incorporates only primary human cells such as pulmonary vascular endothelial cells in a vascular channel, and type I and II alveolar cells and monocyte-derived macrophages in an alveolar channel along an air-liquid interface.M. fortuitumintroduced into the alveolar channel primarily infected macrophages, with rare bacteria inside alveolar cells. Bulk-RNA sequencing of infected chips revealed marked upregulation of transcripts for cytokines, chemokines and secreted protease inhibitors (SERPINs). Our results demonstrate how a humanized ALoC system can identify critical early immune and epithelial responses toM. fortuituminfection. We envision potential application of the ALoC to other NTM and for studies of new antibiotics.
Unraveling tumor heterogeneity: Quantitative insights from scRNA-seq analysis in breast cancer subtypes
Authors: Senra Daniela , Guisoni Nara , Diambra Luis 
Published: September 2024

Tumors are complex systems characterized by genetic, transcriptomic, phenotypic, and microenvironmental variations. The complexity of this heterogeneity plays a crucial role in metastasis, tumor progression, and recurrence. In this work, we utilized publicly available single-cell transcriptomics data from human breast cancer samples (ER+, HER2+, and triple-negative) to evaluate key concepts pertinent to cancer biology. Quantitative assessments included measures based on copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and different protein-protein interaction networks (PPINs).We found that entropy and PPIN activity related to the cell cycle delineate cell clusters with notably elevated mitotic activity, particularly elevated in aggressive breast cancer subtypes. Additionally, CNA distributions differentiate between ER+ and HER2+/TN subtypes. Further, we identified positive correlations among the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as basal and mesenchymal cell lines. These scores reveal associations with tumor characteristics, reflecting the known malignancy spectrum across breast cancer subtypes.By bridging the gap between existing literature and a comprehensive quantitative approach, we present a novel framework for quantifying cancer traits from scRNA-seq data by establishing several scores. This approach highlights the potential for deeper insights into tumor biology compared to conventional marker-based approaches.
Wirelessly-Powered Ingestible Electronic Capsule for Non-invasive Gastrointestinal Optogenetics
Authors: Elsherif Mohamed , El-Din Rawan Badr , Makhambetova Zhansaya , Naser Heba , Boitet Maylis , Singh Rahul , Oh Keonghwan , Sukesan Revathi , Ha Sohmyung , Ramadi Khalil B. 
Published: September 2024

AbstractOptogenetics enables the activation and inhibition of neurons with cell specificity. The gut harbors intricate networks of enteric and central neurons. Uncovering these neuronal pathways in vivo is challenging with traditional neuroscience probes due to the highly motile and harsh gut environment. Here we report the development of an ingestible electronic capsule for non-invasive optical gut stimulation (ICOPS) in rodents. ICOPS is powered wirelessly via a transmitter coil, dosed via oral gavage, and safely excreted without causing obstruction. ICOPS permits modular interchangeability of onboard light-emitting diodes (LEDs) for illumination. We exemplify this with optical irradiance at 470 nm, a commonly-used wavelength in optogenetics for activating channelrhodopsin2. ICOPS features a micro-LED (µLED), a 460-turn coil wound around a ferrite core, and a resonating capacitor. We optimized the transmitting and receiving circuits to achieve maximum power transfer at low operating frequencies (45-140 kHz), overcoming challenges like loose coupling and misalignment. The capsule operates effectively at a distance up to 12 cm longitudinally, 9 cm laterally, and 75° rotational angle relative to the magnetic field. Specific absorption rate (SAR) calculations indicate transmitter-induced SAR levels within safe limits for the occupational environment at 6 Armsand 45 and 63 kHz frequencies ICOPS is robust and transits through the rat gastrointestinal (GI) tract in under 20 hours intact. We demonstrate in vivo functionality and viability of ICOPS using IVIS micro-computed tomography (µCT). ICOPS could pave the way for non-invasive optogenetic interfacing of enteric neural circuits towards their use to regulate motility, visceral pain, and other gastrointestinal disorders.