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Use of alternative medicine among the public has increased rapidly over the last few decades. Studies on alternative health care have been conducted on the general public and on major ethnic groups, but not on Korean Americans, who are one of the fastest growing Asian populations in the United States. This study was a cross-sectional survey of 143 Korean Americans in the Greater New York Metropolitan area; all of them were users of alternative medicine. Inter-correlations of hypothetical demographic predictors and preferences for alternative medicine were obtained. Multiple logistic regression analyses were used to identify factors influencing alternative medicine preferences. Most of the respondents answered that they preferred alternative medicine because of philosophical congruence, i.e. they found alternative therapies compatible with their values, world views, spiritual/religious philosophies, and beliefs regarding the nature and meaning of health and illness. The results show that younger, well-educated respondents, with significant acculturation level, and have stayed in the US for a relatively short period of time preferred alternative medicine. The information derived from this and similar studies may be of potential value to the biomedical community, governmental agencies, insurance companies and managed care organizations. [ABSTRACT FROM AUTHOR]

Most of the existing literature on nutrition and health of Korean Americans has been scattered across the various journals in the social, behavioral, psychological, nutrition, and health sciences. A major contribution of this review article is that it is a comprehensive summary of the literature, discussion of research needs, and recommendations for future research. The review of the relevant literature is divided into three sections: food consumption patterns, health status, and acculturation. Copyright © 2000 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

Matthew MK Chan,1,2 Katrin M Sjoquist,1,3 John R Zalcberg4 1NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; 2Department of Medical Oncology, Central Coast Cancer Centre, Gosford Hospital, Gosford, NSW, Australia; 3Cancer Care Centre, St George Hospital, Sydney, NSW, Australia; 4School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia Abstract: Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer. Keywords: ramucirumab, IMC-1121B, gastric cancer, vascular endothelial growth factor receptor-2, angiogenesis, targeted therapy

Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic 'signal-recording' gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior-posterior axis and structures resembling the mammalian primitive streak and tailbud. We find that cell sorting rearranges patchy domains of Wnt activity into a single pole that defines the gastruloid anterior-posterior axis. We also trace the emergence of Wnt domains to earlier heterogeneity in Nodal activity even before Wnt activity is detectable. Our study defines a mechanism through which aggregates of stem cells can form a patterning axis even in the absence of external spatial cues., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors., Design: This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data., Setting and Cases: Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively., Measurements: Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts., Findings: Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence., Conclusions: US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts., (© 2024 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

During development, mulitpotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is an active area of research spanning traditional single marker lineage studies to data-driven trajectory inference methods on single-cell RNA-seq data. Recent high-throughput lineage tracing technologies profile lineages and cell types at scale, but current methods to infer cell differentiation maps from these data rely on simple models with restrictive assumptions about the developmental process. We introduce a mathematical framework for cell differentiation maps based on the concept of potency, and develop an algorithm, Carta , that infers an optimal cell differentiation map from single-cell lineage tracing data. The key insight in Carta is to balance the trade-off between the complexity of the cell differentiation map and the number of unobserved cell type transitions on the lineage tree. We show that Carta more accurately infers cell differentiation maps on both simulated and real data compared to existing methods. In models of mammalian trunk development and mouse hematopoiesis, Carta identifies important features of development that are not revealed by other methods including convergent differentiation of specialized cell types, progenitor differentiation dynamics, and the refinement of routes of differentiation via new intermediate progenitors., Competing Interests: Competing Interests The authors declare no competing interests.

Lay Abstract: Autistic features are commonly observed in children and adolescents with first-episode psychosis, but they are sometimes overlooked by clinicians and caregivers. By comprehensively examining the clinical profiles of 103 children and adolescents (below 18 years old) with first-episode psychosis and conducting the Autism Diagnostic Interview-Revised (the 'gold standard' autism diagnostic tool) with their primary caregivers, we showed that around 28% of patients with first-episode psychosis had a comorbid autism diagnosis, and boys were 3.57 times more likely to have first-episode psychosis-autism spectrum disorder comorbidity than girls. After administering the Autism Diagnostic Interview-Revised, we also observed that an additional 30% of patients with first-episode psychosis met the autism spectrum disorder diagnostic cut-off; their autism spectrum disorder symptoms were probably overshadowed by prodromal psychotic symptoms and left undetected before this study. The co-occurrence of autism and first-episode psychosis might be more common than we previously thought. Careful autism screening and assessment is highly recommended for clinicians working with patients with psychosis.

BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.3% of cases, a qualifying potentially disease-causing rare variant in an established gene was found. There was an enrichment of rare coding, splicing, and structural variants in known CyKD genes, with statistically significant gene-based signals in COL4A3 and (monoallelic) PKHD1. Quantification of disease risk for each gene (with replication in the separate UK Biobank study) revealed substantially lower risk associated with genes more recently associated with autosomal dominant polycystic kidney disease, with odds ratios for some below what might usually be regarded as necessary for classical Mendelian inheritance. Meta-analysis of common variants did not reveal significant associations, but suggested this category of variation contributes 3%-9% to the heritability of CyKD across European ancestries.CONCLUSIONBy providing unbiased quantification of risk effects per gene, this research suggests that not all rare variant genetic contributors to CyKD are equally likely to manifest as a Mendelian trait in families. This information may inform genetic testing and counseling in the clinic.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by infiltration of monocyte-derived macrophages (MdMs) into the liver; however, the function of these macrophages is largely unknown. We previously demonstrated that a population of MdMs, referred to as hepatic lipid-associated macrophages (LAMs), assemble into aggregates termed hepatic crown-like structures in areas of liver fibrosis. Intriguingly, decreasing MdM recruitment resulted in increased liver fibrosis, suggesting that LAMs contribute to antifibrotic pathways in MASH. In this study, we determined that hepatic crown-like structures are characterized by intimate interactions between activated hepatic stellate cells (HSCs) and macrophages in a collagen matrix in a mouse model of MASH. MASH macrophages displayed collagen-degrading capacities, and HSCs derived from MASH livers promoted expression of LAM marker genes and acquisition of a collagen-degrading phenotype in naive macrophages. These data suggest that crosstalk between HSCs and macrophages may contribute to collagen degradation MASH., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows., Competing Interests: Declaration of interests Z.D.S. and A.M. are co-founders and scientific advisors of Harbinger Health. D.Y. is a co-founder of and scientific advisor for DEM Biopharma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous research on cool-hot executive function (EF) interactions has examined the effects of motivation and emotional distraction on cool EF separately, focusing on one EF component at a time. Although both incentives and emotional distractors have been shown to modulate attention, how they interact and affect cool EF processes is still unclear. Here, we used an experimental paradigm that manipulated updating, inhibition, and shifting demands to determine the interactions of motivation and emotional distraction in the context of cool EF. Forty-five young adults (16 males, 29 females) completed the go/no-go (inhibition), two-back (updating), and task-switching (shifting) tasks. Monetary incentives were implemented to manipulate motivation, and task-irrelevant threatening or neutral faces were presented before the target stimulus to manipulate emotional distraction. We found that incentives significantly improved no-go accuracy, two-back accuracy, and reaction time (RT) switch cost. While emotional distractors had no significant effects on overall task performance, they abolished the incentive effects on no-go accuracy and RT switch cost. Altogether, these findings suggest that motivation and emotional distraction interact in the context of cool EF. Specifically, transient emotional distraction disrupts the upregulation of control activated by incentives. The present investigation has advanced knowledge about the relationship between cool and hot EF and highlights the importance of considering motivation-emotion interactions for a fuller understanding of control., (© 2024. The Author(s).)

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3' ends of CRISPR-Cas guide RNAs 1 . To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La. Further investigation revealed that La promotes prime editing across approaches (PE2, PE3, PE4 and PE5), edit types (substitutions, insertions and deletions), endogenous loci and cell types but has no consistent effect on genome-editing approaches that rely on standard, unextended guide RNAs. Previous work has shown that La binds polyuridine tracts at the 3' ends of RNA polymerase III transcripts 2 . We found that La functionally interacts with the 3' ends of polyuridylated prime editing guide RNAs (pegRNAs). Guided by these results, we developed a prime editor protein (PE7) fused to the RNA-binding, N-terminal domain of La. This editor improved prime editing with expressed pegRNAs and engineered pegRNAs (epegRNAs), as well as with synthetic pegRNAs optimized for La binding. Together, our results provide key insights into how prime editing components interact with the cellular environment and suggest general strategies for stabilizing exogenous small RNAs therein., (© 2024. The Author(s).)

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6 + macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206 + LYVE1 + cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206 + macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c + CD14 + CD64 + peritoneal cells, which, in turn, resembled human peritoneal CD1c + CD14 - CD64 - cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans., (© 2023. Springer Nature America, Inc.)

We investigated the COVID-19 pandemic's impact on values and religiosity in multi-ethnic Malaysia. Values were measured as changes in values, daily activities, and life priorities using a 5-point Likert scale (-2 to +2). Centrality of Religiosity Scale measured changes in religiosity. Around 176 predominantly female (66.5%), Chinese (68.2%) respondents, aged 35.5 ± 14.1 completed the survey. Most life values changed positively: a sense of security at home (2, interquartile range [IQR]: 1-2), connection with family (1, 1-2), and contribution to society (1, 1-2). Certain life priorities' importance increased: health (2, IQR 2-2), family (2, 2-2), and happiness (2, 1-2); except power and money. These significant positive changes in values and religiosity varied between genders and ethnicities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lay Abstract: Currently available pharmacological and behavioral interventions for adolescents and young adults with autism spectrum disorder (ASD) yield only modest effect in alleviating their core behavioral and cognitive symptoms, and some of these treatment options are associated with undesirable side effects. Hence, developing effective treatment protocols is urgently needed. Given emerging evidence shows that the abnormal connections of the frontal brain regions contribute to the manifestations of ASD behavioral and cognitive impairments, noninvasive treatment modalities that are capable in modulating brain connections, such as transcranial direct current stimulation (tDCS), have been postulated to be potentially promising for alleviating core symptoms in ASD. However, whether tDCS can reduce behavioral symptoms and enhance cognitive performance in ASD remains unclear. This randomized controlled trial involving 105 adolescents and young adults with ASD showed that multiple sessions of a tDCS protocol, which was paired up with computerized cognitive training, was effective in improving social functioning in adolescents and young adults with ASD. No prolonged and serious side effects were observed. With more future studies conducted in different clinical settings that recruit participants from a wider age range, this tDCS protocol may be potentially beneficial to a broad spectrum of individuals with autism., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear., Methods: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue., Results: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells and monocyte-derived macrophages (MdMs). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14 + monocyte/macrophage number correlated with the degree of steatosis. Using mouse models of early liver steatosis, we demonstrate that recruitment of MdMs precedes Kupffer cell loss and liver damage. Electron microscopy of isolated macrophages revealed increased lipid accumulation in MdMs, and ex vivo lipid transfer experiments suggested that MdMs may serve a distinct role in lipid uptake during MAFLD., Conclusions: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans. MdMs appear to participate in lipid uptake during early stages of MALFD., Impact and Implications: Metabolic dysfunction associated fatty liver disease (MAFLD) is extremely common; however, the early inflammatory responses that occur in human disease are not well understood. In this study, we investigated macrophage heterogeneity in human livers during early MAFLD and demonstrated that similar shifts in macrophage subsets occur in human disease that are similar to those seen in preclinical models. These findings are important as they establish a translational link between mouse and human models of disease, which is important for the development and testing of new therapeutic approaches for MAFLD., Competing Interests: BF is a member of the Scientific Advisory Board and owns stock in Cirius Therapeutics, which is developing an MPC inhibitor for clinical use in treating NASH. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Inherited diseases are a frequent cause of end-stage kidney disease and often seen in the kidney clinic. Clinical genomic testing is increasingly available in the UK and eligible patients in England can be referred through the NHS Genomic Medicine Service. Testing is useful for diagnosis, prognostication and management of conditions such as autosomal dominant polycystic kidney disease (ADPKD), Alport syndrome, autosomal dominant tubulointerstitial kidney disease (ADTKD) and focal segmental glomerulosclerosis (FSGS). As more patients undergo genomic testing and newer technologies such as whole genome sequencing are applied, we are developing a greater appreciation of the full phenotypic spectrum of inherited kidney diseases and the challenges associated with the interpretation of clinically significant variants., (© Royal College of Physicians 2023. All rights reserved.)

Technological advances have led to the emergence of lineage tracers, but signal recorders for mammalian systems have remained elusive. Kempton et al. have developed a Cas12a base-editing signal recorder capable of capturing diverse signals and operating in various experimental designs. The recorder enables new opportunities to chronicle cellular history., (Copyright © 2022. Published by Elsevier Ltd.)

Adipocytes transfer mitochondria to macrophages in white and brown adipose tissues to maintain metabolic homeostasis. In obesity, adipocyte-to-macrophage mitochondria transfer is impaired, and instead, adipocytes release mitochondria into the blood to induce a protective antioxidant response in the heart. We found that adipocyte-to-macrophage mitochondria transfer in white adipose tissue is inhibited in murine obesity elicited by a lard-based high-fat diet, but not a hydrogenated-coconut-oil-based high-fat diet, aging, or a corn-starch diet. The long-chain fatty acids enriched in lard suppress mitochondria capture by macrophages, diverting adipocyte-derived mitochondria into the blood for delivery to other organs, such as the heart. The depletion of macrophages rapidly increased the number of adipocyte-derived mitochondria in the blood. These findings suggest that dietary lipids regulate mitochondria uptake by macrophages locally in white adipose tissue to determine whether adipocyte-derived mitochondria are released into systemic circulation to support the metabolic adaptation of distant organs in response to nutrient stress., Competing Interests: Declaration of interests J.R.B. has a pending patent application related to intercellular mitochondria transfer for the treatment of mitochondrial disorders, is a consultant for DeciBio and Flagship Pioneering, and is a scientific advisor to LUCA Science, Inc., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression., Competing Interests: Declaration of interests J.S.W. declares outside interest in 5 AM Venture, Amgen, Chroma Medicine, KSQ Therapeutics, Maze Therapeutics, Tenaya Therapeutics, and Tessera Therapeutics. T.J. is a member of the Board of Directors of Amgen and Thermo Fisher Scientific, is a co-founder of Dragonfly Therapeutics and T2 Biosystems, and is the president of Break Through Cancer. T.J. serves on the Scientific Advisory Board of Dragonfly Therapeutics, SQZ Biotech, and Skyhawk Therapeutics. None of these affiliations represent a conflict of interest with respect to this study. T.G.B. is an advisor to Array BioPharma, Revolution Medicines, Novartis, AstraZeneca, Takeda, Springworks, Jazz Pharmaceuticals, Relay Therapeutics, Rain Therapeutics, and Engine Biosciences and receives research funding from Novartis, Strategia, Kinnate, and Revolution Medicines. J.M.R. consults for Maze Therapeutics and Waypoint Bio. Z.J.G. is an equity holder in Scribe Biosciences and Provenance bio and a member of the SAB of Serotiny Bio., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Percutaneous biliary and gallbladder drainage is routinely performed by interventional radiology. These pathologies and techniques are well described in the literature and in this issue. The purpose of this review is to focus on the recognition and management of complications. Percutaneous biliary drains can have a variety of complications which can range from minor skin issues to more serious and complex bleeding issues. Advancements in imaging and techniques improve the safety profile of percutaneous biliary and gallbladder interventions., (Thieme. All rights reserved.)

Recently, it has become evident that macrophage diversity increases in the liver during the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we provide a detailed protocol for the analysis of liver macrophage subsets in mice with non-alcoholic fatty liver disease (NAFLD) and early NASH using flow cytometry and immunofluorescence (IF). These methods can be used to assess the composition and localization of macrophage subsets during NASH. For complete details on the use and execution of this protocol, please refer to Daemen et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Detailed phylogenies of tumor populations can recount the history and chronology of critical events during cancer progression, such as metastatic dissemination. We applied a Cas9-based, single-cell lineage tracer to study the rates, routes, and drivers of metastasis in a lung cancer xenograft mouse model. We report deeply resolved phylogenies for tens of thousands of cancer cells traced over months of growth and dissemination. This revealed stark heterogeneity in metastatic capacity, arising from preexisting and heritable differences in gene expression. We demonstrate that these identified genes can drive invasiveness and uncovered an unanticipated suppressive role for KRT17 We also show that metastases disseminated via multidirectional tissue routes and complex seeding topologies. Overall, we demonstrate the power of tracing cancer progression at subclonal resolution and vast scale., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4 pos Kupffer cells (KCs) decrease in number, while monocyte-derived Tim4 neg macrophages accumulate. In concert, monocyte-derived infiltrating macrophages enter the liver and consist of a transitional subset that expresses Cx3cr1/Ccr2 and a second subset characterized by expression of Trem2, Cd63, Cd9, and Gpmnb; markers ascribed to lipid-associated macrophages (LAMs). The Cx3cr1/Ccr2-expressing macrophages, referred to as C-LAMs, localize to macrophage aggregates and hepatic crown-like structures (hCLSs) in the steatotic liver. In C-motif chemokine receptor 2 (Ccr2)-deficient mice, C-LAMs fail to appear in the liver, and this prevents hCLS formation, reduces LAM numbers, and increases liver fibrosis. Taken together, our data reveal dynamic changes in liver macrophage subsets during the pathogenesis of NASH and link these shifts to pathologic tissue remodeling., Competing Interests: Declaration of Interests A.E.F. is co-inventor on pending and issued patents filed by the Cleveland Clinic and UCSD that refer to the use of biomarkers and therapies in inflammatory and fibrotic disorders. Scientific Founder: Jecure Therapeutics, Elgia Therapeutics. Consultant/Advisory Board: Gilead, GSK, Merck, Ferring Pharmaceutical, Centurion BioPharma, Oppilan Pharma. The remaining authors have no interests to declare., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Metastasis allows cancer cells to spread via circulatory and lymphatic systems; secondary tumorigenesis typically leads to a fatal outcome. Recent experimental evidence suggests that Cancer Stem Cells (CSCs) play a pivotal role in tumor progression. A tumor is heterogeneous and composed of different cell types. CSCs are a subpopulation of tumor cells possessing abilities to self-renew and differentiate., Objective: The aim of this study was to present repurposed drugs, and potential candidates, that can serve as anticancer medications intended to target resistant cancer cells, i.e. CSCs., Methods: Research publications, FDA filings, and patents have been reviewed for repurposed drugs or drug combinations that can act to improve cancer treatment and care., Results: Drugs that act against CSCs include ones approved for treatment of diabetes (metformin & thiazolidinediones), parasitic diseases (chloroquine, niclosamide, mebendazole & pyrvinium), psychotic disorders (thioridazine, clomipramine & phenothiazines), alcoholism (disulfiram), lipid disorder (statins), inflammatory diseases (tranilast, auranofin, acetaminophen & celecoxib), antibiotics (azithromycin), and other disorders. Current research findings advocate the existence of beneficial effects by combining these repurposed drugs, and also through their complementary use with conventional cancer therapies., Conclusion: Repurposing FDA-approved medications towards cancer care, by targeting the resistant CSCs, will allow for a quicker, cheaper development and approval process. A larger drug library available to physicians will allow for increased efficacy during both first-line and recurrent cancer treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: People with neurological disorders are found to have abnormal resting-state functional connectivity (rsFC), which is associated with the persistent functional impairment found in these patients. Recently, transcranial direct current stimulation (tDCS) has been shown to improve rsFC, although the results are inconsistent., Objective: We hope to explore whether tDCS induces rsFC changes among patients with neurological disorders, whether rsFC is clinically relevant and how different tDCS parameters affect rsFC outcome among these individuals., Methods: A systematic review was conducted according to PRISMA guidelines (systematic review registration number: CRD42020168654). Randomized controlled trials that studied the tDCS effects on rsFC between the experimental and sham-controlled groups using either electrophysiological or neuroimaging methods were included., Results: Active tDCS can induce changes in both localized (ie, brain regions under the transcranial electrodes) and diffused (ie, brain regions not directly influenced by the transcranial electrodes) rsFC. Interestingly, fMRI studies showed that the default mode network was enhanced regardless of patients' diagnoses, the stimulation paradigms used or the rsFC analytical methods employed. Second, stimulation intensity, but not total stimulation time, appeared to positively influence the effect of tDCS on rsFC., Limitations and Conclusion: Due to the inherent heterogeneity in rsFC analytical methods and tDCS protocols, meta-analysis was not conducted. We recommend that future studies may investigate the effect of tDCS on rsFC for repeated cathodal stimulation. For clinicians, we suggest anodal stimulation at a higher stimulation intensity within the safety limit may maximize tDCS effects in modulating aberrant functional connectivity of patients with neurological disorders., Competing Interests: Declaration of conflicting interests:The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Case: Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease. Patients typically present with fever, cough, and radiological lung changes. However, a significant proportion of these patients are asymptomatic. To date, we have limited information on the operations performed on these patients. We report our experience of a relatively asymptomatic elderly patient who underwent surgery for a hip fracture and was confirmed postoperatively to have COVID-19., Conclusion: Meticulous hand hygiene and use of surgical mask in daily practice is crucial to protect against asymptomatic and undiagnosed patients.

Background: It is vital to develop a better understanding of the use of different modalities for enteral feeding and its associated complications, given differences in funding support, community resources and infrastructure available to support home enteral feeding in an acute care tertiary hospital., Aim: To provide a description of the clinical characteristics of patients on long-term enteral feeding and incidence of associated complications., Methods: A retrospective case records review study design was adopted. Medical records of patients discharged from a tertiary hospital with long-term nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG) feeding for the first time during the period of January 2010 to June 2017 were reviewed. Data collected include patient's demographics, reason for enteral feeding, morbidity and nutritional status upon initiation of NGT and PEG feeding, readmission episodes and documented complications (associated with enteral feeding) within one-year post discharge., Results: Records of 120 NGT and 118 PEG patients were analysed. Significant age and gender differences were found with older patients being more likely to be placed on NGT [NGT (Mean 79.1, SD 11.3) vs. PEG (Mean 67.1, SD 12.6)] and higher number of females in the NGT group as compared to the PEG group (NGT 59.2% vs. PEG 31.4%). Majority of patients were fed by caregivers in the NGT (99.2%) as compared to the PEG (51.7%) group. Patients with cancer were more likely to be on PEG feeding (NGT 5%, PEG 70.3%), whereas patients with stroke-related diagnoses were more likely to be on NGT feeding (NGT 48% vs. PEG 8.5%). The total Charlson Comorbidity score was also significantly different between the NGT (mean = 5.7; SD = 1.5) and PEG (mean = 4.5; SD = 2.0) groups. A higher number of patients with PEG feeding had no complications (47.5%) as compared to the NGT group (8.3%). Patients who received NGT feeding were more likely experience tube blockage [OR 0.03, 95% CI (0.001-0.72), p = 0.03], secondary displacement of tube [OR 0.04, 95% CI (0.002-0.72), p = 0.03] and accidental tube removal [OR 0.03, 95% CI (0.004-0.21), p < 0.001]., Conclusion: Overall, patients who received NGT feeding experienced more complications than those who had PEG feeding. The choice for NGT or PEG feeding may be influenced by patient related factors as well as the presence of caregivers, which need to be considered in the improvement of enteral nutrition services in the local context., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The treatment paradigm of several cancers has dramatically changed in recent years with the introduction of immunotherapy. Most oncology trials involving immune checkpoint inhibitors (ICIPs) have routinely excluded patients with HIV infection and chronic viral hepatitis B (HBV) and C (HCV) due to concerns about viral reactivation, fears of increased toxicity, and the potential lack of efficacy in these patient subgroups. However, with current antiviral therapies, HIV and HBV infections have become chronic diseases and HCV infections can even be cured. Broadening cancer trial eligibility criteria in order to include cancer patients with chronic viral infections can maximize the ecological validity of study results and the ability to understand the ICPIs' benefit-risk profile in patients with these comorbidities. In this review, we examined the evidence on the efficacy and safety of using ICPIs in cancer patients with concurrent chronic viral infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia.

Glucocorticoids (GC) in all its various forms and formulations are likely one of the most commonly used pharmacologic agents in medicine. Their use can be profoundly therapeutic but are also associated with a myriad of acute and chronic side effects. It is fairly well-accepted in the medical community that GC can be life-saving when used in critically ill patients with severe exacerbations of asthma and chronic obstructive pulmonary disease, HIV-associated pneumocystosis, and systemic vasculitides. However, the adjunctive role of GC is much more controversial in acute respiratory distress syndrome (ARDS), septic shock, community-acquired pneumonia, and several other serious medical conditions. Despite such controversies, GC should at least be considered for patients with fulminant manifestations of the following conditions as there is equipoise to indicate that GC may improve outcome with acceptable risks: (i) severe ARDS with refractory hypoxemia despite one to two weeks of state-of-the-art management, (ii) recalcitrant, vasopressor-dependent septic shock, (iii) non-influenza, severe community-acquired pneumonia, and (iv) severe alcoholic hepatitis. The bases for these controversies is likely due to both host factors (e.g., differences in GC resistance and susceptibility to adverse effects) and different phenotypes of any one disease state; e.g., different pathogenesis and pathogens under the rubric of "sepsis." Elucidation of better biomarkers to determine the underlying pathogenic phenotype will significantly advance our understanding and prediction of which critically ill patients will benefit from GC and who would experience a deleterious effect from its use., (Copyright © 2019 Elsevier Inc. All rights reserved.)

"Can I keep my dog while receiving chemotherapy?" "Can my cat sleep on my bed while I'm on treatment?" "What precautions should I take with my pets in order to avoid infections?"" I read that my dog could give me breast cancer, is that true?" "Do you have assistance therapy dogs at your chemotherapy day unit?" These are not uncommon questions from cancer patients in oncology/haematology consultation rooms. The answers to these questions however, are widely unknown among physicians. Pet ownership is thought to provide patients with both emotional and physical health benefits. However, owning pets may also pose health risks to immunocompromised patients through zoonotic transmission of disease. Some studies have also suggested that the ownership of domestic pets may increase the risk of developing some cancers. But what is the evidence behind these claims? This paper presents the results of a literature review of a variety of scientific literature about pet ownership as a potential risk factor for suffering cancer, zoonotic diseases and the immunocompromised, and animal-assisted-therapy in cancer patients., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Aims and Objectives: To explore patients and carers' experience and perceptions of different modalities of long-term enteral feeding., Background: With an ageing population in Singapore, there is a concomitant increase in number of patients with dysphagia and hence increase in prevalence of enteral feeding. It is essential to understand experiences of patients and home carers with long-term home enteral feeding and perceptions of different modalities to better provide support., Design: A qualitative descriptive approach fulfilling the COREQ checklist criteria (See File S1). Nine patients who were receiving long-term enteral feeding and nine carers were recruited over the period of August to December 2017. One-to-one interviews were conducted and audio-recorded. An inductive content analysis approach, with open coding, creation of categories and abstraction of data, was adopted., Results: Three themes were generated: (a) factors influencing choice of mode of enteral feeding; respondents narrated factors such as need to "conceal" illness, need to be independent and previous bad experience with alternative modality (b) identified informational, emotional and physical needs. Respondents reported the need for support in terms of information on the different modalities, and training on how to self-care or provide care and (c) individual perception and attitude towards life with enteral feeding. Most respondents portrayed a positive outlook to life, despite that they could no longer participate in communal eating., Conclusion and Relevance to Clinical Practice: Understanding patients and carers' experience and perceptions will inform the development of strategies to empower future patients and carers in choice of modality for enteral feeding. Patients with percutaneous endoscopic gastrostomy (PEG) found it easier to integrate enteral tube feeding into daily lives. Carers played a pivotal role in choice of modality, as well as in care of patients on enteral feeding., (© 2019 John Wiley & Sons Ltd.)

Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine- N -oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.

The fast and constant evolution of Massive Open Online Courses (MOOCs) has gained the attention of the educational community, achieving widespread popularity among many universities. However, there is very little research on the use and acceptance of MOOCs by students in disciplines such as health and medicine. The principal focus of this study is to explore the behavior of students from a MOOC on Health Emergencies, analyzing the completion and drop-out rates. The data were collected from three self-administered questionnaires; the first identified general demographic information and the students' learning preferences, the second determined the level of MOOC adoption and the level of identification and satisfaction the students had with the course content, and the third measured the completion and drop-out rates. The MOOC had more than 2114 registered participants. The enrolled students showed high levels of commitment and motivation to learn about this topic through a varied of innovative educational resources, such as videos, learning activities, and interactive animations. In general, the participants expressed their desire to continue learning with this type of methodology. However, the results also showed important issues to be considered in the design and development of a MOOC of these characteristics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.

Background: With an aging population, there is a concomitant increase in number of patients with dysphagia; and hence increase in prevalence of enteral feeding. Health care professionals play a critical role in informing decisions of patients and caregivers on their choice of modality for long-term home enteral feeding., Aims: To explore the perceptions of health care professionals on different modalities for enteral feeding and their experiences in initiating long-term enteral feeding among adult patients., Methods: A qualitative explorative descriptive study design with purposive sampling approach was adopted. A total of four speech therapists, fifteen nurses and seven doctors who were ever involved in initiating long term home enteral tube feeding were recruited over a data collection period of August to December 2017. One to one interviews were conducted and audio-recorded. An inductive content analysis approach, with open coding, creation of categories and abstraction of data was adopted., Results: Four main themes were generated: (1) Naso-gastric Tube Feeding (NGT) is health care professionals' first choice of modality; (2) Percutaneous Endoscopic Gastrostomy Tube Feeding (PEG) is regarded as an alternative approach; (3) Perceived better outcomes with PEG; and (4) Identified barriers to promotion of PEG., Conclusion: NGT remained as the modality of choice although health care professionals perceived that patients will have better outcomes with the use of PEG., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57 putative lncRNAs that are activated by TAL1. Many of these transcripts were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One transcript near the ARID5B gene locus was specifically expressed in TAL1-positive T-ALL cases. The other transcript located between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic stem cells and T-cell progenitor cells. In addition, we identified a subset of lncRNAs that were negatively regulated by TAL1 and positively regulated by E-proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3-2:7) located near the RORC gene, which was expressed in normal thymocytes but repressed in TAL1-positive T-ALL cells.