bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-dependent development of the body’s touch receptors
Authors: Santiago Celine , Sharma Nikhil , Africawala Nusrat , Siegrist Julianna , Handler Annie , Tasnim Aniqa , Anjum Rabia , Turecek Josef , Lehnert Brendan P. , Renauld Sophia , Nolan-Tamariz Michael , Iskols Michael , Magee Alexandra R. , Paradis Suzanne , Ginty David D. 
Published: September 2023

SummaryWe report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end organ structures and altered somatosensory neuron central targeting. Single cell RNA sequencing ofPiezo2conditional mutants revealed changes in gene expression in the sensory neurons activated by light mechanical forces, whereas other neuronal classes were less affected. To further test the role of activity in mechanosensory end organ development, we genetically deleted the voltage-gated sodium channel Nav1.6 (Scn8a) in somatosensory neurons throughout development and found thatScn8amutants also have disrupted somatosensory neuron morphologies and altered electrophysiological responses to mechanical stimuli. Together, these findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of the mechanosensory end organs that underlie our sense of gentle touch.
Differential effects of aneuploidy on growth and differentiation in human intestinal stem cells
Authors: Johnson Blake A. , Liu Albert Z. , Bi Tianhao , Dong Yi , Li Taibo , Zhou Dingjingyu , Narkar Akshay , Wu Yufei , Sun Sean X. , Larman Tatianna C. , Zhu Jin , Li Rong 
Published: September 2023

SummaryAneuploidy, a near ubiquitous genetic feature of tumors, is a context-dependent driver of cancer evolution; however, the mechanistic basis of this role remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigate how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Single-cell RNA sequencing reveals that the gene expression signature across over 100 unique aneuploid karyotypes is enriched with p53 responsive genes. The primary driver of p53 activation is karyotype complexity. Complex aneuploid cells with multiple unbalanced chromosomes activate p53 and undergo G1 cell-cycle arrest, independent of DNA damage and without evidence of senescence. By contrast, simple aneuploid cells with 1-3 chromosomes gained or lost continue to proliferate, demonstrated by single cell tracking in colonoids. Notably, simple aneuploid cells exhibit impaired differentiation when niche factors are withdrawn. These findings suggest that while complex aneuploid cells are eliminated from the normal epithelium due to p53 activation, simple aneuploid cells can escape this checkpoint and may contribute to niche factor-independent growth of cancer-initiating cells.
Engineering antigen-specific tolerance to an artificial protein hydrogel
Authors: Rapp Peter B. , Baccile Joshua A. , Galimidi Rachel P. , Vielmetter Jost 
Published: September 2023

ABSTRACTArtificial protein hydrogels are an emerging class of biomaterials with numerous prospective applications in tissue engineering and regenerative medicine. These materials are likely to be immunogenic due their frequent incorporation of novel amino acid sequence domains, which often serve a functional role within the material itself. We engineered injectable “self” and “non-self” artificial protein hydrogels which were predicted to have divergent immune outcomesin vivoon the basis of their primary amino acid sequence. Following implantation in mouse, the non-self gels raised significantly higher anti-gel antibody titers than the corresponding self gels. Prophylactic administration of a fusion antibody targeting the non-self hydrogel epitopes to DEC-205, an endocytic receptor involved in Treginduction, fully suppressed the elevated antibody titer against the non-self gels. These results suggest that the clinical immune response to artificial protein biomaterials, including those that contain highly antigenic sequence domains, can be tuned through the induction of antigen-specific tolerance.
High-resolution dissection of human cell type-specific enhancers incisandtransactivities
Authors: Wang Meng , Yang Xiaoxu , Wu Qixi 
Published: September 2023

AbstractThe spatiotemporal specific gene expression is regulated by cell type-specific regulatory elements including enhancers, silencers and insulators etc. The massively parallel reporter assay (MPRA) methods like STARR-seq facilitate the systematic study of DNA sequence intrinsic enhancer activities in a large scale. However, when applied to human cells, it remains challenging to identify and quantify cell type-specific active enhancers in the genome-wide scale with high-resolution, due to the large size of human genome. In this study, we selected the H3K4me1 associated dinucleosome with the linker DNA sequences as candidate enhancer sequences in two different human cell lines and performed ChIP-STARR-seq to quantify the cell type-specific enhancer activities with high-resolution in a genome-wide scale. Furthermore, we investigated how the activity landscape of enhancer repository would change when transferred from native cells (cisactivity) to another cell lines (transactivity). Using ChIP-STARR-seq of the candidate enhancers in native cells and another type of cells, we obtained enhancerscisactivity maps andtransactivity maps in two different cell lines. Thecisandtransactivity maps enabled us to identify cell type-specific active enhancers, with enrichment of motifs of differentially expressed TFs. Comparisons between thecisandtransactivity maps revealed general consistent regulatory property with different levels of activity in the two cell types, suggesting the sequence intrinsic regulatory properties keep similar in different type of cells. This study provides a new perspective of sequence intrinsic enhancer activities in different types of cells.
Interactions with a phage gene underlie costs of a β-lactamase
Authors: Lai Huei-Yi , Cooper Tim F. 
Published: September 2023

AbstractThe fitness cost of an antibiotic resistance gene (ARG) can differ across host strains creating refuges that allow maintenance of an ARG in the absence of direct selection for its resistance phenotype. Despite the importance of such ARG-host interactions for predicting ARG dynamics, the basis of ARG fitness costs and their variability between hosts are not well understood. We determined the genetic basis of a host-dependent cost of a β-lactamase,blaTEM-116*, that conferred a significant cost in oneEscherichia colistrain but was close to neutral in 11 otherEscherichia spp.strains. Selection of ablaTEM-116*encoding plasmid in the strain in which it initially had a high cost resulted in rapid and parallel compensation to that cost through mutations in a P1 phage gene,relAP1. When the wildtyperelAP1gene was added to a strain in which it was not present and in whichblaTEM-116*was neutral, it caused the ARG to become costly. Thus,relAP1is both necessary and sufficient to explainblaTEM-116*costs in at least some host backgrounds. To our knowledge, these findings represent the first demonstrated case of the cost of an ARG being influenced by a genetic interaction with a phage gene. The interaction between a phage gene and a plasmid-borne ARG highlights the complexity of selective forces determining the maintenance and spread of ARGs, and, by extension, encoding phage and plasmids, in natural bacterial communities.
Hand2 represses non-cardiac cell fates through chromatin remodeling atcis-regulatory elements
Authors: Komatsu Valerie , Cooper Brendon , Yim Paul , Chan Kira , Gong Wesley , Wheatley Lucy , Rohs Remo , Fraser Scott E. , Trinh Le A. 
Published: September 2023

AbstractDevelopmental studies have revealed the importance of the transcription factor Hand2 in cardiac development. Hand2 promotes cardiac progenitor differentiation and epithelial maturation, while repressing other tissue types. The mechanisms underlying the promotion of cardiac fates are far better understood than those underlying the repression of alternative fates. Here, we assess Hand2-dependent changes in gene expression and chromatin remodeling in cardiac progenitors of zebrafish embryos. Cell-type specific transcriptome analysis shows a dual function for Hand2 in activation of cardiac differentiation genes and repression of pronephric pathways. We identify functionalcis-regulatory elements whose chromatin accessibility are increased inhand2mutant cells. These regulatory elements associate with non-cardiac gene expression, and drive reporter gene expression in tissues associated with Hand2-repressed genes. We find that functional Hand2 is sufficient to reduce non-cardiac reporter expression in cardiac lineages. Taken together, our data support a model of Hand2-dependent coordination of transcriptional programs, not only through transcriptional activation of cardiac and epithelial maturation genes, but also through repressive chromatin remodeling at the DNA regulatory elements of non-cardiac genes.
Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised Blood-Brain Barrier integrity
Authors: Bassi Ivan , Grunspan Moshe , Hen Gideon , Ravichandran Kishore A. , Moshe Noga , Safriel Stav R. , Chen Amitai , Ruiz de Almodovar Carmen , Yaniv Karina 
Published: September 2023

AbstractThe neurovascular unit (NVU) is a complex structure comprising neurons, glia, and pericytes that interact with specialized endothelial cells to maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. Alterations to NVU formation and function can lead to serious forms of cerebrovascular disease, including cerebral small vessel diseases (CSVDs), a range of pathological changes of cerebral capillaries within the white matter contributing to BBB dysfunction and demyelination.Despite the growing recognition of the pivotal roles played by neuro-vascular and glia-vascular interfaces in NVU formation and functioning, CSVD research has mainly focused on characterizing pericyte and EC dysfunction, leaving our understanding of the contribution of non-vascular cells of the brain parenchyma limited.Here, we use a novel zebrafish mutant to delve into the intricate interplay among NVU components and demonstrate how the compromised specification of a progenitor cell population sets off a cascade of events, ultimately leading to severe cerebrovascular abnormalities. The mutation affects Scavenger Receptor B2 (scarb2)/Lysosomal Membrane Protein 2 (limp2), a highly conserved protein residing in the membrane of late endosomes and lysosomes. We find Scarb2 to be predominantly expressed in Radial Glia Cells (RGCs), a multipotent cell giving rise to neurons and glia in both zebrafish and mammals. Through live imaging and genetic manipulations, we identify impaired Notch3 signaling in RGCs and their glial progeny as the primary consequence of Scarb2a depletion and show that this disruption causes excessive neurogenesis at the expense of glial cell differentiation. We further pinpoint compromised acidification of the endolysosomal compartment in mutant cells as the underlying cause of disrupted Notch3 processing, linking for the first time Notch3 defects in non-vascular cells of the brain parenchyma to CSVD phenotypes.Given the evolutionary conservation of SCARB2 expression and the remarkable recapitulation of CSVD phenotypes,scarb2mutants provide a promising framework for investigating the mechanisms governing Notch3 processing in non-vascular cells and their involvement in the onset of CSVD.
Development and implementation barriers of a new patient‐reported measure: The Radiation therapy‐related Inconvenience Questionnaire (RIQ)
Authors: Shunmugasundaram Chindhu , Sundaresan Puma , White Kate , King Madeleine T , Milross Chris , Rodd Lucinda , Fuller Matthew , Rutherford Claudia 
Published: September 2023

AbstractIntroductionRadiation therapy (RT) can benefit approximately 50% of cancer patients and contribute to 40% of all cancer cures, yet its utilisation in cancer is low globally. Several factors contribute to this including perceived inconvenience related to accessing and utilising RT. To quantitatively assess the latter, a new tool – the Radiation therapy‐related Inconvenience Questionnaire (RIQ) – was developed. This study aimed to pre‐test the RIQ and explore barriers and facilitators to implementing it in routine clinical practice and clinical trials.MethodsSemi‐structured cognitive interviews were conducted with patients undertaking RT, recruited via three hospitals to examine content validity, acceptability, and comprehensibility of the RIQ. Interviews identified inconsistencies, relevance, and clarity of items. Semi‐structured interviews with healthcare professionals involved in the delivery of care to individuals undertaking RT explored barriers and facilitators to routine usage. Thematic analysis was used to identify themes.ResultsPatients (N = 15) identified problems in content, instructions, layout, length, and response options; consequently, 25 items were revised and eight removed, resulting in a final 29‐item questionnaire. Clinicians identified staff‐ and patient‐specific barriers to implementing RIQ in clinical practice. Perceived facilitators included the following: (a) workplace factors, (b) mode of administration, and (c) imparting knowledge.ConclusionThis study demonstrated acceptability and comprehensibility of the 29‐item RIQ amongst cancer patients undertaking RT and treating clinicians. The next phase will evaluate the RIQ's measurement properties in a larger clinical study. The barriers and facilitators identified can guide future implementation of RIQ in clinical practice and clinical trials.
Interventional management of malignant bone tumours
Authors: Cazzato Roberto Luigi , Garnon Julien , Jennings Jack William , Gangi Afshin 
Published: September 2023

SummaryIn the last few decades, interventional radiology (IR) has significantly increased its role in the management of bone tumours including bone metastases (BM) that represent the most common type of tumour involving the bone. The current IR management of BM is based on the ‘palliative‐curative’ paradigm and relies on the use of consolidative (i.e. osteplasty, osteosynthesis) and/or ablation (i.e. cryoablation, radiofrequency ablation, electrochemotherapy) techniques. The present narrative review will overview the current role of IR for the management of BM.
The percutaneous management of pulmonary metastases
Authors: de Baere Thierry , Bonnet Baptiste , Tselikas Lambros , Deschamps Frederic 
Published: September 2023

SummaryLocal treatment of lung metastases has been in the front scene since late 90s when an international registry of thoracic surgery reported a median overall survival of 35 months in resected patients versus 15 months in non‐resected patients. Today, other local therapies are available for patients with oligometastatic lung disease, including image guided thermal ablation, such as ablation, microwave ablation, and cryoablation. Image‐guided ablation is increasingly offered, and now recommended in guidelines as option to surgery. Today, the size of the target tumour remains the main driver of success and selection of patients with limited tumour size allowing for local tumour control in the range of 90% in most recent and larger series targeting lung metastases up to 3.5 cm. Overall survival exceeding five‐years in large series of thermal ablation for lung metastases from colorectal origin are align with outcome of same patients treated with surgical resection. Moreover, thermal ablation in such population allows for one‐year chemotherapy holidays in all comers and over 18 months in lung only metastatic patients, allowing for improved patient quality of life and preserving further lines of systemic treatment when needed. Tolerance of thermal ablation is excellent and better than surgery with no lost in respiratory function, allowing for repeated treatment when needed. In the future, it is likely that practice of lung surgery for small oligometastatic lung disease will decrease, and that minimally invasive techniques will replace surgery in such indications. Randomized study will be difficult to obtain as demonstrated by discontinuation of many studies testing the hypothesis of surgery versus observation, or surgery versus SBRT.
Private health care, cancer, and the vulnerable middle class in Kenya
Authors: Prince Ruth J. 
Published: September 2023

AbstractA novel terrain of health care is emerging in Kenya at the intersection of a cancer epidemic, expanding medical and health insurance markets, the continued evisceration of public health care, and a middle class that can raise funds from credit, loans, and social networks. As middle‐class cancer patients and their families navigate these landscapes, they find themselves vulnerable both to the “ordinary crisis” of public health care undermined by austerity and neglect, and to an extractive medical marketplace offering state‐of‐the‐art treatment that is just within, or just beyond, financial reach. To analyze this, I build on Lauren Berlant's concept of cruel optimism, which captures how precarity is not only grounded in economic realities but also tied to hopes and expectations that always remain unfulfilled, creating constant anxiety and exhaustion. Further, I examine the double binds of cancer treatment and the entanglements between medical, health, and economic precarities, as families are drawn into private health care while the state disinvests in public services.
Turkey in Turbulence: Heterodoxy or a New Chapter in Neoliberal Peripheral Development?
Authors: Orhangazi Özgür , Erinç Yeldan A. 
Published: September 2023

ABSTRACTWhile global monetary tightening by central banks, led by the US Federal Reserve, has heightened concerns about a slowdown in the world's economy and an increased likelihood of debt crises across developing countries, Turkey has attracted attention for doing the opposite. Indeed, the country's economic policy makers have intensified monetary easing towards credit expansion at the risk of increased exchange rate instability. This article analyses the Turkish case and makes four contributions. First, it establishes a framework through which we can understand and interpret the policy choices of the government. Second, it shows the binding effects of the trilemma in the context of an economy fully integrated in the global economy and discusses how the government tried to tackle these effects through a series of ad hoc policy measures. Third, the article discloses the distributional consequences of such policy manoeuvres and argues that the burden of adjustment fell on the shoulders of wage labour, while various competing rentier interests benefited from these policies. Fourth, the authors analyse these policies from a broader perspective of whether they can be interpreted as a courageous attempt by a peripheral developing economy to claim some policy space, or whether these policy choices in essence only amount to a deepening of neoliberal peripheralization.
The Price (and Costs) of Macroeconomic Stability in Peru: Some Lessons on the Implications of FDI‐driven Growth
Authors: Bibi Samuele , Valdecantos Sebastian 
Published: September 2023

ABSTRACTIn the period 2000–2019, Peru enjoyed sustained GDP growth and a long period of macroeconomic stability; as a result, poverty was reduced markedly in comparison to the 1980s and early 1990s, when the country faced severe recessions and hyperinflation. This positive economic performance coincided with the implementation of a mainstream macroeconomic framework which, alongside favourable external conditions, allowed for continuous external financing of current account deficits, mainly through foreign direct investment (FDI). Against the background of current debates regarding the resurgence of debt crises and the advocacy of FDI as a way to avoid such crises, this article uses balance of payments and international investment position statistics to assess whether Peru's acquired macroeconomic stability can be deemed sustainable. Drawing on the contributions of the Latin American structuralist school and more recent analyses that have raised concerns, the article shows that Peru's external position has taken on a Ponzi profile, casting doubt on the idea that FDI is a superior way of external financing compared to external debt. It concludes with a discussion of the social and environmental implications of Peru's widely praised macroeconomic framework, highlighting the limits that peripheral economies face when their growth relies excessively on external financing.
Assessing the venous system: Correlation of mean systemic filling pressure with the venous excess ultrasound grading system in cardiac surgery
Authors: Utrilla‐Alvarez Jose Daniel , Gopar‐Nieto Rodrigo , García‐Cruz Edgar , Lazcano‐Díaz Emmanuel , Jiménez‐Rodrìguez Gian Manuel , Rojas‐Velasco Gustavo , Manzur‐Sandoval Daniel 
Published: September 2023

AbstractBackgroundEvaluation of the venous system has long been underestimated as an important component of the circulatory system. As systemic venous pressure increases, the perfusion pressure to the tissues is compromised. During initial resuscitation in cardiac surgery, excessive fluid administration is associated with increased morbidity and mortality.MethodsWe conducted a cross‐sectional study of 60 consecutive adult patients who underwent cardiac surgery and in whom it was possible to obtain the venous excess ultrasound (VExUS) grading system and mean systemic filling pressure (Pmsf) in the postoperative period upon admission, at 24 and 48 h. We then determined the correlation between VExUS grading and Pmsf.ResultsOn admission, patients with VExUS grading 0 predominated, with a progressive increase in venous congestion and an increase in Pmsf over the course of the first 48 h. There was a strong positive correlation between VExUS grading and the invasive measurement of Pmsf at 24 and 48 h after arrival. The presence of grade 2 or grade 3 venous congestion in the postoperative period poses an increased risk of developing acute kidney injury.ConclusionThe VExUS grading system indicates a high degree of systemic venous congestion in the first 48 h of the postoperative period after cardiac surgery and correlates with the Pmsf, which is the best surrogate of stressed circulatory volume.
Smolting in post‐sexually mature male Atlantic salmon (Salmo salar L.) parr in the wild
Authors: Lothian Angus J. , Rodger Jessica , Wilkie Lorna , Walters Marcus , Miller Richard , Conroy Chris , Marshall Shona , MacKenzie Morven , Adams Colin E. 
Published: September 2023

AbstractConflicts can arise in developmental pathways that prevent an individual entering different developmental life stages that result in the expression of different phenotypes within a specific time period. In salmonids, theory suggests that sexual maturation may inhibit subsequent smolting within the same 12‐month period and that this is partly the result of the time and the apparently conflicting physiological changes for these processes to occur, and partly because of the energy requirements for these physiologically taxing processes. This study tested whether sexually mature male Atlantic salmon (Salmo salar L.) parr, caught in the autumn, would subsequently smolt the following spring. Through individual identification using PIT telemetry, minimum estimates of 3.0% (n = 6/203) and 5.9% (n = 1/17) of Atlantic salmon parr that were sexually mature in two river catchments during the autumn were subsequently identified as smolts in the following spring. We therefore suggest that, in line with previous studies on domesticated Atlantic salmon and laboratory‐based experiments, there is no developmental conflict but that life‐history expression is mediated by environmental and genetic processes.