bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulated lipid metabolism in colorectal cancer
Authors: Coleman Olivia , Ecker Miriam , Haller Dirk 
Published: December 2021

Purpose of review
Lipid metabolism presents a targetable metabolic vulnerability in colorectal cancer (CRC). Lipid signatures and cancer-cell lipid requirements may serve as noninvasive diagnostic and prognostic biomarkers and as a therapeutic target, respectively.

Recent findings
A growing body of new studies highlight the complexity of lipid metabolism in CRC. Cancer cells are able to utilize an alternative fatty acid desaturation pathway, underlining the metabolic plasticity of tumors. CRC tissue shows a robust triglyceride-species signature with prognostic value in CRC patients. Lipidomic analyses in germfree and colonized mice identify a unique lipid signature and suggest that bacteria inhibit metabolism of polyunsaturated fatty acids by blocking desaturase and elongase activities. Cellular stress responses, particularly the well characterized unfolded protein response, are involved in regulating lipid synthesis and homeostasis, and contribute to adaptation of the lipid environment. Together, lipid metabolism, the intestinal microbiota and cellular stress responses unarguably play crucial roles in CRC.

Summary
A number of recent advances in our understanding of dysregulated lipid metabolism in CRC underline the importance of this research field. An improved knowledge of the complex interplay between lipid metabolism, cellular stress and the intestinal microbiota in the context of CRC may lead to novel therapeutic strategies.
Macrophages in cholangiopathies
Authors: Bruneau Alix , Guillot Adrien , Tacke Frank 
Published: December 2021

Purpose of review
Cholangiopathies are a heterogeneous class of liver diseases where cholangiocytes are the main targets of liver injury. Although available and emerging therapies mainly target bile acids (ursodeoxycholic acid/UDCA, 24-Norursodeoxycholic acid/norUDCA) and related signaling pathways (obeticholic acid, fibrates, FXR, and PPAR agonists), the mechanisms underlying inflammation, ductular reaction and fibrosis in cholestatic liver diseases remain poorly understood.

Recent findings
Data from patients with cholestatic diseases, such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) as well as mouse models of biliary injury emphasize the role of immune cells in the pathogenesis of cholestatic disorders and indicate diverse functions of hepatic macrophages. Their versatile polarization phenotypes and their capacity to interact with other cell types (e.g. cholangiocytes, other immune cells) make macrophages central actors in the progression of cholangiopathies.

Summary
In this review, we summarize recent findings on the response of hepatic macrophages to cholestasis and biliary injury and their involvement in the progression of cholangiopathies. Furthermore, we discuss how recent discoveries may foster the development of innovative therapies to treat patients suffering from cholestatic liver diseases, in particular, treatments targeting macrophages to limit hepatic inflammation.
Management of long-term cardiovascular risk factors post organ transplant
Authors: de la Fuente-Mancera Juan Carlos , Forado-Bentar Ilana , Farrero Marta 
Published: December 2021

Purpose of review
Cardiovascular disease is one of the leading causes of death in solid organ transplant (SOT) recipients. Early identification of cardiovascular risk factors and their adequate management in this population is key for prevention and improved outcomes.

Recent findings
Approximately 80% of SOT present one or more cardiovascular risk factors, with increasing prevalence with time posttransplantation. They are due to the interplay of pretransplant conditions and metabolic consequences of immunosuppressive agents, mainly corticosteroids and calcineurin inhibitors. Among the pharmacological management strategies, statins have shown an important protective effect in SOT.

Summary
Strict surveillance of cardiovascular risk factors is recommended in SOT due to their high prevalence and prognostic implications. Further studies on the best managements strategies in this population are needed.
Spontaneous Multiple Arterial Dissection in a COVID-19–Positive Decedent
Authors: James Christine , Peterson Diane C. 
Published: December 2021

Abstract
Spontaneous multiple arterial dissection (SMAD) is a rarely reported phenomenon and has been previously linked to connective tissue diseases and specifically the genetic mutations in SMAD3 and COL3A1. Herein we describe a case of SMAD with scattered thrombi in a COVID-19–positive patient with a history of unspecified mitochondrial myopathy. Vasculopathy involved the splenic artery, inferior mesenteric artery, internal mammary arteries, omental arteries, mesenteric arteries, and small renal arteries. Dissections were confirmed by histology in the splenic artery, inferior mesenteric artery, and bilateral renal medullary arteries. Genetic studies were done to rule out SMAD3 and COL3A1 mutations. Because the Smad3 protein has been previously implicated in COVID-19–associated tissue fibrosis, it may play a role in endothelial dysfunction as well.
Cervical Epidural Abscess
Authors: McCarthy Sinead , Milne David , O'Connor Kate , Tse Rexson , Garland Jack 
Published: December 2021

Abstract
Spinal epidural abscess is an uncommon condition, which may have serious complications, including neurological sequelae and death. Classical symptoms include spinal pain, fever, and neurological deficit; however, diagnosis is difficult and requires a high degree of clinical suspicion. Antemortem magnetic resonance imaging (MRI) scanning is the gold-standard diagnostic tool. Computed tomography (CT) is less sensitive and as such, postmortem CT may miss the diagnosis. We report a case of Staphylococcus aureus cervical epidural abscess presenting as neck pain and causing flaccid paralysis and subsequently death. Antemortem MRI showed a small epidural collection, spinal cord edema, and fluid in the adjacent cervical disc and facet joints; however, these findings could not be appreciated on postmortem CT. Postmortem examination, guided by the antemortem imaging, was able to confirm a cervical spinal epidural abscess; however, similar deaths may occur before medical presentation. This case demonstrates a limitation of postmortem imaging in diagnosing spinal epidural abscess and highlights that such cases may be missed.
Intubation During Pediatric Cardiac Arrest in the Emergency Department Is Associated With Reduced First-Pass Success
Authors: Pacheco Garrett S. , Patanwala Asad E. , Leetch Aaron N. , Mendelson Jenny S. , Hurst Nicholas B. , Sakles John C. 
Published: December 2021

Background
Airway compromise and respiratory failure are leading causes of pediatric cardiac arrest making advanced airway management central to pediatric resuscitation. Previous literature has demonstrated that achieving first-pass success (FPS) is associated with fewer adverse events. In cardiac arrest for adult patients, increasing number of intubation attempts is associated with lower likelihood of return of spontaneous circulation (ROSC) and favorable neurologic outcome. There is limited evidence regarding advanced airway management for pediatric out-of-hospital cardiac arrest (OHCA) in the emergency department (ED). The purpose of this study was to compare FPS in pediatric OHCA and non–cardiac arrest patients in the ED.

Methods
This is an analysis of pediatric intubations prospectively recorded into a continuous quality improvement database in an academic pediatric ED over a 12-year period. Between July 1, 2007, and June 30, 2019, physicians recorded all intubations performed in the pediatric ED. The database included patient demographics and detailed information about each intubation such as age of the patient, reason for intubation, number of intubation attempts, and outcome of each attempt. All patients younger than 18 years who underwent intubation in the ED were eligible for inclusion in the study. The primary outcome was FPS for pediatric patients in cardiac arrest compared with those not in cardiac arrest. A logistic regressions analysis was performed to identify characteristics associated with FPS in OHCA patients.

Results
Six hundred eight pediatric patients were intubated during the study period. One hundred three pediatric patients had OHCA compared with 459 non–cardiac arrest patients who underwent rapid sequence intubation. In patients with OHCA, 47.6% had FPS (95% confidence interval [CI], 38.2%–57.1%), 33% required 2 attempts (95% CI, 24.7%–42.6%), and 19.4% required 3 or more attempts (95% CI, 12.9%–28.2%). In patients without OHCA, 75.4% had FPS (95% CI, 75.4%–79.1%), 15% required 2 attempts (95% CI, 12.0%–18.6%), and 9.6% required 3 or more attempts (95% CI, 7.2%–12.6%). Cardiac arrest was associated with a reduction in FPS adjusted odds ratio 0.44 (95% CI, 0.26–0.77).

Conclusions
In this study, we found that pediatric OHCA is associated with reduced FPS in the ED. Although additional studies are needed, rescuers should prioritize restoring effective oxygenation and ventilation and optimizing intubation conditions before an advanced airway attempt.
Histopathological Changes In The Intestine Of Infected Pigeons (Columba Livia Domestica) Caused By Helminthes Infection From Al-Qassim, Saudi Arabia
Authors: Aldamigh Mashael A. , Hassan Amaal H. , Alahmadi Ahlam A. 
Published: December 2021

AbstractHelminthes infection causes extensive harm to the pigeon host. The purpose of this study was to observe histopathological changes caused by helminths infection. Thirty-five pigeons (C.L. domestica) were purchased weekly from a bird’s market from Al-Qassim region, Saudi Arabia. Out of the 35 pigeons examined, 9 pigeons (25.71%) were found infected with helminth parasites, which were identified as one cestode (Raillietina sp.), and one nematode (Ascaridia columbae). The infected pigeons suffered from growth retardation, emaciation, weakness, droopiness, and diarrhea. A lot of histopathological changes were seen in the intestine of infected pigeons including atrophy and distortion of villi, infiltration of inflammatory lymphocytic cells, erosion, and loss of the typical structure of the intestine, necrosis in villi, and blood vessels congestion. This study concludes, for the first time in AL-Qassim region-Saudi Arabia, that the infection with helminth parasites caused significant histopathological changes in the intestines of the infected pigeons, and this could lead to increased mortality to the infected pigeons. Further work is necessary in Saudi Arabia to determine the prevalence and biological factors that have a significant impact on the helminth parasites community.
High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effect
Authors: Tong Huawei , Huang Jia , Xiao Qingquan , He Bingbing , Dong Xue , Liu Yuanhua , Yang Xiali , Han Dingyi , Wang Zikang , Ying Wenqin , Zhang Runze , Wei Yu , Wang Xuchen , Xu Chunlong , Zhou Yingsi , Li Yanfei , Cai Minqing , Wang Qifang , Xue Mingxing , Li Guoling , Fang Kailun , Zhang Hainan , Yang Hui 
Published: December 2021

AbstractCRISPR-Cas13 systems have recently been employed for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has imposed a major barrier for their in vivo applications. We designed a dual-fluorescent reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells. Among over 200 engineered variants, several Cas13 variants (including Cas13d and Cas13X) exhibit efficient on-target activity but markedly reduced collateral activity. Furthermore, transcriptome-wide off-targets and cell growth arrest induced by Cas13 are absent for these variants. Importantly, high-fidelity Cas13 variants show comparable RNA knockdown activity with wild-type Cas13 but no detectable collateral damage in transgenic mice and adeno-associated virus-mediated somatic cell targeting. Thus, high-fidelity Cas13 variants with minimal collateral effect are now available for targeted degradation of RNAs in basic research and therapeutic applications.
Pyrethroid insecticides susceptibility of Stomoxys calcitrans (Linnaeus) and Stomoxys indicus Picard (Diptera: Muscidae) from cattle farms in southern Thailand
Authors: Lorn Sokchan , Tainchum Krajana , Nusen Pitunart , Sumarnrote Anchana , Chareonviriyaphap Theeraphap 
Published: December 2021

AbstractThe susceptibility to six pyrethroid insecticides (permethrin, deltamethrin, alpha-cypermethrin, cypermethrin, lambda-cyhalothrin and bifenthrin), each at the recommended concentration, was evaluated for the two stable fly species Stomoxys calcitrans (Linnaeus) and Stomoxys indicus Picard, through tarsal contact using a World Health Organization (WHO) cone bioassay procedure. The field populations of stable flies were collected from three study sites (Songkhla, Phattalung and Satun provinces) in Thailand. The stable flies were exposed to insecticide-treated filter paper for 30 min and their knockdown counts at 30 min and 60 min and mortality counts at 12 hr and 24 hr were recorded. The S. calcitrans and S. indicus in Songkhla and Phattalung populations were moderately susceptible to pyrethroids for 24-hr mortality. Nonetheless, the Satun population of S. indicus was completely susceptible to permethrin with 100% mortality and the lowest susceptible to deltamethrin and bifenthrin. The results indicate a generally low susceptibility of stable flies to pyrethroids in the southern provinces of Thailand.
ePat: extended PROVEAN annotation tool
Authors: Ito Takumi , Yoshitake Kazutoshi , Iwata Takeshi 
Published: December 2021

AbstractThe ‘ePat’ (extended PROVEAN annotation tool) is a software tool that extends the functionality of PROVEAN: a software tool for predicting whether amino acid substitutions and indels will affect the biological function of proteins. The ‘ePat’ extends the conventional PROVEAN to enable the following two things, which the conventional PROVEAN could not calculate the pathogenicity of these variants. First is to calculate and score the pathogenicity of indel mutations with frameshift and variants near splice junctions. Second is to use batch processing to calculate the pathogenicity of multiple variants into a variants list (VCF file) in a single step. ePat can help extract variants that affect biological functions by utilizing not only point mutations, and indel mutations that does not cause frameshift, but also frameshift, stop gain, and splice variants. These extended features will increase detection rate and improve diagnostic of inherited diseases or associate specific variant to phenotype.
Long-term non-invasive drug treatments for adult zebrafish
Authors: Lu Yuting , Patton E. Elizabeth 
Published: December 2021

SUMMARYZebrafish embryos are widely used for drug-discovery however administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we develop a drug formulation and administration method for adult zebrafish by producing food-based drug pellets which are consumed voluntarily. We apply this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Short-term, precise, and daily dosing with drug-pellets made with the BRAFV600E inhibitor, vemurafenib, led to tumour regression. On-target drug efficacy was determined by phospho-ERK staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies, and can be widely applied to any adult zebrafish model.SUMMARY STATEMENTThis drug-pellet approach is a precise dosing method to administer short or long-term drug treatments to adult zebrafish, that is stress-free for the fish and requires minimal animal handling. We use this method to develop new drug-resistant models of melanoma in zebrafish, opening new doors for modelling and screening drug treatments in adult zebrafish.
CSF1R inhibition by small molecule affects T-helper cell differentiation independently of microglia depletion
Authors: Lei Fengyang , Cui Naiwen , Zhou Chengxin , Chodosh James , Vavvas Demetrios G. , Paschalis Eleftherios I. 
Published: December 2021

AbstractColony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a specific method for microglia depletion. However, recent work revealed that in addition to microglia, CSF1R inhibition also affects other innate immune cells, such as peripheral monocytes and tissueresident macrophages of the lung, liver, spleen, and peritoneum. Here, we show that this effect is not restricted to innate immune cells only, but extends to the adaptive immune compartment. CSF1R inhibition alters the transcriptional profile of bone marrow cells that control T helper cell activation. In vivo or ex vivo inhibition of CSF1R profoundly changes the transcriptional profile of CD4+ cells and suppresses Th1 and Th2 differentiation in directionally stimulated and unstimulated cells and independently of microglia depletion. Given that T cells also contribute in CNS pathology, these effects may have practical implications in the interpretation of relevant experimental data.Significance statementHere we show that CSF1R inhibition affects not only innate immune cells and microglia, but also the adaptive immune compartment by suppressing Th1/Th2 differentiation of CD4+ cells, independently of microglia depletion.
Genomic diversity and biosynthetic capabilities of sponge-associated chlamydiae
Authors: Dharamshi Jennah E. , Gaarslev Natalia , Steffen Karin , Martin Tom , Sipkema Detmer , Ettema Thijs J. G. 
Published: December 2021

ABSTRACTSponge microbiomes contribute to host health, nutrition, and defense through the production of secondary metabolites. Chlamydiae, a phylum of obligate intracellular bacteria ranging from animal pathogens to endosymbionts of microbial eukaryotes, are frequently found associated with sponges. However, sponge-associated chlamydial diversity has not yet been investigated at the genomic level and host-interactions remain thus far unexplored. Here, we sequenced the microbiomes of three sponge species and found high, though variable, Chlamydiae relative abundances of up to 21.2% of bacterial diversity. Using genome-resolved metagenomics 18 high-quality sponge-associated chlamydial genomes were reconstructed, covering four chlamydial families. Among these, Sorochlamydiaceae shares a common ancestor with Chlamydiaceae animal pathogens, suggesting long-term co-evolution with animals. Sponge-associated chlamydiae genomes mostly resembled environmental chlamydial endosymbionts, but not pathogens, and encoded genes for degrading diverse compounds associated with sponges, such as taurine. Unexpectedly, we identified widespread genetic potential for secondary metabolite biosynthesis across Chlamydiae, which may represent an explored reservoir of novel natural products. This finding suggests that chlamydiae may partake in defensive symbioses and that secondary metabolites play a wider role in mediating intracellular interactions. Furthermore, sponge-associated chlamydiae relatives were found in other marine invertebrates, pointing towards wider impacts of this phylum on marine ecosystems.
Estimating cell-type-specific gene co-expression networks from bulk gene expression data with an application to Alzheimer’s disease
Authors: Su Chang , Zhang Jingfei , Zhao Hongyu 
Published: December 2021

AbstractInferring and characterizing gene co-expression networks has led to important insights on the molecular mechanisms of complex diseases. Most co-expression analyses to date have been performed on gene expression data collected from bulk tissues with different cell type compositions across samples. As a result, the co-expression estimates only offer an aggregate view of the underlying gene regulations and can be confounded by heterogeneity in cell type compositions, failing to reveal gene coordination that may be distinct across different cell types. In this paper, we describe a flexible framework for estimating cell-type-specific gene co-expression networks from bulk sample data, without making specific assumptions on the distributions of gene expression profiles in different cell types. We develop a novel sparse least squares estimator, referred to as CSNet, that is efficient to implement and has good theoretical properties. Using CSNet, we analyzed the bulk gene expression data from a cohort study on Alzheimer’s disease and identified previously unknown cell-type-specific co-expressions among Alzheimer’s disease risk genes, suggesting cell-type-specific disease pathology for Alzheimer’s disease.
Correlated STORM-homoFRET Imaging: Applications to the Study of Membrane Receptor Self-Association and Clustering
Authors: Driouchi Amine , Gray-Owen Scott D. , Yip Christopher M. 
Published: December 2021

AbstractMapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. We report here on a correlated STORM/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Live cell homoFRET imaging of CEACAM1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, revealed highly heterogenous diffraction-limited structures on the surface of HeLa cells. Correlated super-resolved STORM imaging revealed that these structures comprised a complex mixture and spatial distribution of self-associated CEACAM1 molecules. This correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function.
From mass spectral features to molecules in molecular networks: a novel workflow for untargeted metabolomics
Authors: Olivier-Jimenez Damien , Bouchouireb Zakaria , Ollivier Simon , Mocquard Julia , Allard Pierre-Marie , Bernadat Guillaume , Chollet-Krugler Marylène , Rondeau David , Boustie Joël , van der Hooft Justin J.J. , Wolfender Jean-Luc 
Published: December 2021

AbstractIn the context of untargeted metabolomics, molecular networking is a popular and efficient tool which organizes and simplifies mass spectrometry fragmentation data (LC-MS/MS), by clustering ions based on a cosine similarity score. However, the nature of the ion species is rarely taken into account, causing redundancy as a single compound may be present in different forms throughout the network. Taking advantage of the presence of such redundant ions, we developed a new method named MolNotator. Using the different ion species produced by a molecule during ionization (adducts, dimers, trimers, in-source fragments), a predicted molecule node (or neutral node) is created by triangulation, and ultimately computing the associated molecule’s calculated mass. These neutral nodes provide researchers with several advantages. Firstly, each molecule is then represented in its ionization context, connected to all produced ions and indirectly to some coeluted compounds, thereby also highlighting unexpected widely present adduct species. Secondly, the predicted neutrals serve as anchors to merge the complementary positive and negative ionization modes into a single network. Lastly, the dereplication is improved by the use of all available ions connected to the neutral nodes, and the computed molecular masses can be used for exact mass dereplication. MolNotator is available as a Python library and was validated using the lichen database spectra acquired on an Orbitrap, computing neutral molecules for >90% of the 156 molecules in the dataset. By focusing on actual molecules instead of ions, MolNotator greatly facilitates the selection of molecules of interest.Abstract Figure