bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion
Authors: Longchamp Alban , Fontan Fermin M. , Aburawi Mohamed M. , Eymard Corey , Karimian Negin , Detelich Danielle , Pendexter Casie , Cronin Stephanie , Agius Thomas , Nagpal Sonal , Banik Peony Dutta , Tessier Shannon N. , Ozer Sinan , Delmonico Francis L. , Uygun Korkut , Yeh Heidi , Markmann James F. 
Published: March 2024

Background.
Brief normothermic machine perfusion is increasingly used to assess and recondition grafts before transplant. During normothermic machine perfusion, metabolic activity is typically maintained using red blood cell (RBC)–based solutions. However, the utilization of RBCs creates important logistical constraints. This study explored the feasibility of human kidney normothermic perfusion using William’s E–based perfusate with no additional oxygen carrier.

Methods.
Sixteen human kidneys declined for transplant were perfused with a perfusion solution containing packed RBCs or William’s E medium only for 6 h using a pressure-controlled system. The temperature was set at 37 °C. Renal artery resistance, oxygen extraction, metabolic activity, energy metabolism, and histological features were evaluated.

Results.
Baseline donor demographics were similar in both groups. Throughout perfusion, kidneys perfused with William’s E exhibited improved renal flow (P = 0.041) but similar arterial resistance. Lactic acid levels remained higher in kidneys perfused with RBCs during the first 3 h of perfusion but were similar thereafter (P = 0.95 at 6 h). Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding oxygen consumption (P = 0.41) and reconstitution of ATP tissue concentration (P = 0.55). Similarly, nicotinamide adenine dinucleotide levels were preserved during perfusion. There was no evidence of histological damage caused by either perfusate.

Conclusions.
In human kidneys, William’s E medium provides a logistically convenient, off-the-shelf alternative to packed RBCs for up to 6 h of normothermic machine perfusion.
The role of nutrition in the pathogenesis of neglected tropical diseases: systematic review and meta-analysis
Authors: Loglo Aloysius , Aniagyei Wilfred , Vivekanandan Monika Mira , Agbanyo Abigail , Asamoah Evans Adu , Phillips Richard Odame , Annan Reginald , Engel Barbara , Simmonds Rachel E 
Published: March 2024

Background: According to the WHO, neglected tropical diseases (NTDs) affect over 2 billion people worldwide. While the links between nutrition and many diseases have become clear over recent decade, NTDs have lagged behind and the linkage with nutrition is largely unknown. We conducted this systematic review with meta-analysis to determine the current status of research on the role of diet in the pathogenesis of NTDs.
Methodology: PubMed, Embase, Scopus and African Journal online databases were searched using predefined search terms. We included all original articles with a case-control design and at least one NTD. The studies had to compare the nutritional parameters between the infected and uninfected. Articles that did not report original data were excluded. The quality of the studies was assessed using the Newcastle-Ottawa scale. Pooled estimates were conducted using the random-effects model. The publication bias of studies was determined by funnel plots. Q and I2 statistics were used to assess the heterogeneity of the studies.
Results: After screening 1294 articles, only 16 qualified for the systematic review and 12 for meta-analysis. These predominately had a focus on soil-transmitted helminthiasis (ascariasis, hookworm diseases, trichuriasis) and schistosomiasis, with a minority concerning leishmaniasis and leprosy. Pooled estimates showed an association between intestinal parasites and stunting in children (OR= 1.38, 95%CI: 1.14-1.66, I2 = 0%). We also identified a moderate association established between blood iron deficiency (OR=4.67, 95%CI: 1.91-11.44) and intestinal parasites.
Conclusions/Significance: Of the 20 NTDs, the links between diet and disease have been explored only for a very few. There is a paucity of data from low and middle-income countries and least developed countries where the NTD burden is high. Therefore, more research into the role of nutrition in NTD infection is recommended.
Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study
Authors: Moor Jeanne , Toepfner Nicole , von Meißner Wolfgang C G , Berner Reinhard , Moor Matthias B. , Kublickiene Karolina , Strumann Christoph , Chao Cho-Ming 
Published: March 2024

AbstractBackgroundSex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany.MethodsThis is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines.ResultsThe dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3µg BNT162b2, no sex differences were noted, but after a first dose of 5 or 10µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms.ConclusionsSex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies.(German Clinical Trials Register ID: DRKS00028759).
3D culture of pancreatic cancer cellsin vitrorecapitulates an aberrant mitochondrial oxidative phosphorylation genotype observedin vivo
Authors: Kuś Krzysztof , Mark Treherne J. , Earnshaw David L. , Krzykawska Renata , Biesaga Beata , Statkiewicz Małgorzata , Unrug-Bielawska Katarzyna , Sandowska-Markiewicz Zuzanna , Mikula Michal , Alfaro Javier Antonio , Krzykawski Marcin Przemyslaw 
Published: March 2024

AbstractThe treatment of many aggressive cancers remains a significant unmet medical need. An aberrant dependence of tumors on mitochondrial oxidative phosphorylation pathways has been well characterized in mediating the progression of pancreatic cancers, as well as some other malignancies. However, the discovery and development of new therapeutic strategies targeting or manipulating this pathway in pancreatic tumors has been relatively slow when compared with other cancers, limiting the current options for treating patients. One key technical challenge in discovering new therapies has been the limited ability of cancer cell lines when grown in 2D conditions to recapitulate the mitochondrial oxidative phosphorylation pathways in vitro that have been observed in vivo. In part, this is because 2D cultures fail to mimic the extracellular 3D tumoral environment. More generally, the translation of data based on 2D pancreatic cancer cell culture systems have also been constraining options for discovering new therapies. Conversely, 3D cultures can provide an improved technology platform in which pathologically relevant pathways in tumors can be recapitulated and analyzed in vitro. In this study, we have demonstrated in 3D cultures the reconstruction of the mitochondrial oxidative phosphorylation genotype in vitro, which more closely resembles that observed in vivo. Our study highlights the value of using transcriptomic readouts as a method to demonstrate the relevance and utility of 3D preclinical modelsin vitro, when grown in a more physiological extracellular environment. This key technological advance can now better enable the discovery and subsequent development of new therapeutic strategies targeting disease-relevant pathways found in pancreatic and other tumors.
ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF
Authors: Magnitov Mikhail D. , Maresca Michela , Saiz Noemí Alonso , Teunissen Hans , Braccioli Luca , de Wit Elzo 
Published: March 2024

SummaryGene expression is orchestrated by transcription factors, which function within the context of a three-dimensional genome. Zinc finger protein 143 (ZNF143/ZFP143) is a transcription factor that has been implicated in both gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, we generated a ZNF143/ZFP143 degron line. Our results show that ZNF143/ZFP143 depletion has no effect on chromatin looping. Systematic analysis of ZNF143/ZFP143 occupancy data revealed that a commonly used antibody cross-reacts with CTCF, leading to its incorrect association with chromatin loops. Nevertheless, ZNF143/ZFP143 specifically activates nuclear-encoded mitochondrial genes and its loss leads to severe mitochondrial dysfunction. Using anin vitroembryo model, we find that ZNF143/ZFP143 is an essential regulator of organismal development. Our results establish ZNF143/ZFP143 as a conserved transcriptional regulator of cell proliferation and differentiation by safeguarding mitochondrial activity.HighlightsAcute degradation of ZFP143 leads to rapid and specific loss of gene transcription.Molecular consequences of ZFP143 loss are inconsistent with a role in chromatin looping.ZFP143 is a conserved transcriptional regulator of nuclear-encoded mitochondrial proteins.ZFP143 regulation of mitochondrial homeostasis is critical for multicellular organismal development.Graphical Abstract
Emergence of Orientation Pinwheels in a Self-Evolving Spiking Neural Network: Enhancing Visual Coding Efficiency and Reliability
Authors: Zhong Haixin , Wang Haoyu , Huang Mingyi , Dai Wei P , Huang Yuchao , An Mengyao , Roe Anna Wang , Yu Yuguo 
Published: March 2024

AbstractOrientation preference maps (OPMs) in the primary visual cortex of primates organize orientation-tuned neurons into columnar structures, forming pinwheel-like patterns. However, lower-level animals like rodents typically exhibit a lack of OPMs, with neurons either randomly distributed or aggregated in small clusters. This distinction prompts an inquiry into whether more structured cortical columns correlate with improved visual computational or coding efficiency. To explore this, we propose a novel self-evolving spiking neural network (SESNN). To the best of our knowledge, the SESNN is the first spiking network, incorporating mechanisms of neural plasticity in forming neural connections without explicit objective functions. We reveal that the emergence of pinwheel structures is primarily driven by sparse coding constraints and local synaptic plasticity as fundamental mechanisms. Second, for higher mammals with expansive iso-orientation domains (IODs), the firing responses in pinwheel structures primarily emanate from pinwheel centers (PCs) and progressively extend toward the periphery, encompassing adjacent IODs. Third, the size and organization of these IODs across species are significantly influenced by the receptive fields’ ability to process overlapping visual information. Lastly, PCs within large IODs demonstrate enhanced robustness and population sparseness in detecting a variety of orientation features. These results indicate that the spatial pinwheel structure facilitates highly efficient and reliable coding performance.
Chloride intracellular channel 4 (CLIC4) is a global regulator of type 1 interferon signaling in Systemic Sclerosis (SSc) epithelial cells
Authors: Wasson Christopher W , Dibb Sophie L , Caballero-Ruiz Begoña , Clavane Eva M , Wells Rebecca , Kakkar Vishal , Lorenzis Enrico De , Ross Rebecca L , Bryon Jessica , Derrett-Smith Emma , Denton Christopher P , Meakin Paul J , Galdo Francesco Del 
Published: March 2024

AbstractObjectivesSystemic sclerosis (SSc) is an autoimmune disease in which an immune-related injury induces fibrosis of the skin, progressing to affect the internal organs in the most serve cases. Type 1 interferon (IFN) signaling plays a major role in SSc disease progression. We have previously shown the chloride intracellular channel 4 (CLIC4) is upregulated in SSc skin fibroblasts and plays an important role in SSc fibrosis. In this study we investigated the role of CLIC4 in SSc keratinocyte biology.Methodshealthy (HC) and SSc skin biopsies were analysed by immunohistochemistry for the expression of CLIC4. The skin keratinocyte cell line Hacats was stimulated with a range of type 1 IFN signaling agonists (POLY I:C, POLY dA:Dt, ODN 2216 and IFN-α). CLIC4 was inhibited with the chloride channel inhibitors NPPB and IAA-94 or siRNA. Conditioned media from HC or SSc fibroblasts was employed for indirect co-culture of Hacats and HUVECs.ResultsSSc skin biopsies showed high levels of CLIC4 in SSc skin fibroblasts, keratinocytes and endothelial cells compared to HC. Co-culture of Hacats and Huvecs with SSc fibroblast media induced CLIC4 expression. CLIC4 played an important role in type 1 IFN signalling in keratinocytes. Inhibition of CLIC4 blocked TLR3, TLR9 and cGAS mediated activation of the type 1 IFN signaling pathway. Additionally, inhibition of CLIC4 prevented SSc fibroblast media from inducing a type 1 IFN response in keratinocytes.ConclusionsThe data presented in this study suggests CLIC4 is a global regulator of type 1 IFN signalling in SSc epithelial cells.Key MessagesWhat is already knownSSc disease progression is driven in part by a Type 1 IFN signature and CLIC4 has previously been implicated in SSc fibroblast activation.What this study addsWe show for the first time CLIC4 is a regulator of type 1 interferon signalling in epithelial cells and plays an important role in the signalling found in SSc skin.How this study might affect researchTargeting CLIC4 in the context of SSc may disrupt the fibrosis and inflammation associated with SSc.
A genetic perspective on the recent demographic history of Ireland and Britain
Authors: Shanmugam Ashwini , Merrigan Michael , O’Reilly Seamus , Molloy Anne M. , Brody Lawrence , Hardiman Orla , McLaughlin Russell , Cavalleri Gianpiero L. , Byrne Ross , Gilbert Edmund 
Published: March 2024

ABSTRACTBackgroundWhile subtle yet discrete clusters of genetic identity across Ireland and Britain have been identified, their demographic history is unclear.MethodsUsing genotype data from 6,574 individuals with associated regional Irish or British ancestry, we identified Irish-like and British-like genetic communities using network community detection. We segregated Identity-by-Descent (IBD) and Runs-of-Homozygosity (ROH) segments by length and approximated their corresponding time periods. Through this, we inferred the regional Irish and British demographic histories in these time periods by (1) estimating genetic relatedness between communities, (2) estimating changes in effective population sizes, (3) inferring recent migration rates across Ireland and Britain, and (4) estimating changing affinities to regional European populations. For a subset of the Irish communities, we determined the enrichment/depletion of surnames within the genetic communities.ResultsThrough patterns of IBD-sharing and ROH, we find evidence of recent population bottlenecks in the Orcadian, Manx and Welsh communities. While the structure in Ireland is subtler, the communities share relatively more IBD segments that are shorter in length, and the genetic differences between the Irish communities are more subtle on average, when compared to the British communities. Regional effective population size trajectories indicate a similar demographic history throughout the island of Ireland. Further, we observe a stable migration corridor between north-east Ireland and south-west Scotland while there is a recent migration barrier between South-Eastern Ireland and Western Ireland. We observed an enrichment of Anglo-Norman and English surnames in the Wexford community while within the West Ulster-Argyll community, we saw an enrichment of Gallowglass and Scottish surnames.ConclusionsUsing well-annotated Irish and British reference genotypes, we observed temporal changes in genetic affinities within and between genetic communities in Ireland and Britain. In addition, using effective population size estimates and levels of haplotype-sharing, we detected varying degrees of genetic isolation in some Irish and British genetic communities across time. Using these new insights into the regional demographic history of Ireland and Britain across different time periods, we hope to understand the driving forces of rare allele frequencies and disease risk association within these populations.
Chemotherapy-treated breast cancer cells activate the Wnt signaling pathway to enter a diapause-DTP state
Authors: El Laithy Youssef , Abreu De Oliveira Willy Antoni , Pabba Anirudh , Qualizza Alessandra , Richard François , Athanasouli Paraskevi , Luci Carla Rios , De Wispelaere Wout , Mourao Larissa , Hamer Siân , Moens Stijn , De Jaime-Soguero Anchel , Francesca Baietti Maria , Hutten Stefan J , Jonkers Jos , Sammut Stephen-John , Soenen Stefaan , Scheele Colinda LGJ , Bruna Alejandra , Desmedt Christine , Annibali Daniela , Lluis Frederic 
Published: March 2024

ABSTRACTThe efficacy of chemotherapy is often hindered by the enrichment of a population of cancer cells that enter a drug-tolerant persister (DTP) state, mimicking embryonic diapause, yet the underlying mechanisms of this transition remain poorly understood. This study demonstrates that both parental and chemotherapy-induced Wnt-active (WntHigh) cells in Triple-negative breast cancer exhibit transcriptional and functional properties characteristic of DTP cells, including a diapause transcriptional signature, reduced MYC expression, reversible restricted proliferation, and pronounced chemoresistance. Our findings reveal that thede novoactivation of the Wnt signaling pathway, triggered by the transcriptional upregulation of components essential for canonical Wnt ligand-secretion and -activation, is critical for enriching the diapause-DTP (DTPDiap) population across various chemotherapy regimens. The diapause-DTP/WntHighpopulation can be selectively ablated by concomitant, rather than sequential, pharmacological inhibition of Wnt ligand-secretion alongside chemotherapy, highlighting new vulnerabilities in DTPDiapcell-emergence and potentially yielding a therapeutic opportunity against DTPs. This study shows that activation of Wnt signaling pathway is sufficient and necessary for the induction of a DTPDiapstate and enhances our understanding of the introductory mechanisms driving DTP cell-enrichment upon chemotherapy.
Why models underestimate West African tropical forest productivity
Authors: Zhang-Zheng Huanyuan , Stocker Benjamin , Thomson Eleanor , Aguirre-Gutiérrez Jesús , Deng Xiongjie , Ding Ruijie , Bredu Stephen Adu , Duah-Gyamfi Akwasi , Gvozdevaite Agne , Moore Sam , Oliveras Menor Imma , Prentice I. Colin , Malhi Yadvinder 
Published: March 2024

AbstractTropical forests dominate terrestrial photosynthesis, yet there are major contradictions in our understanding due to a lack of field studies, especially outside the tropical Americas. A recent field study indicated that West African forests have among the highest forests gross primary productivity (GPP) yet observed, contradicting models that rank them lower than Amazonian forests. Here, we explore possible reasons for this data-model mismatch. We found the in situ GPP measurements higher than multiple global GPP products at the studied sites in Ghana. The underestimation of GPP by models largely disappears when a standard photosynthesis model is informed by local field-measured values of (a) fractional absorbed photosynthetic radiation (fAPAR), and (b) photosynthetic traits. Satellites systematically underestimate fAPAR in the tropics due to cloud contamination issues. The study highlights the potential widespread underestimation of tropical forests GPP and carbon cycling and hints at the ways forward for model and input data improvement.Related manuscriptThe recent field study mentioned above is a manuscript currently accepted byNature Communications(manuscript id NCOMMS-23-37419), which is available as a preprinthttps://www.researchsquare.com/article/rs-3136892/v1Codes and data availabilityAll data and codes underlying the study are currently shared viaGithub (link here)which will be made available through Zenodo upon acceptance.
A randomized, controlled, two-center preclinical trial assessing the efficacy of a new benzodiazepine–dihydropyridine hybrid molecule (JM-20) in rodent models of ischemic stroke
Authors: Ramírez-Sánchez Jeney , Rex André , McCann Sarah , Schulze Daniel , Wong-Guerra Maylin , Fonseca-Fonseca Luis A , García-Alonso Enrique , Ramírez-Abreu Ailín , Limonta Ricardo , Dopatka Monika , Mosch Larissa , Núñez-Figueredo Yanier , Dirnagl Ulrich 
Published: March 2024

AbstractJM-20 is a novel multifunctional benzodiazepine molecule with potent neuroprotective effects in rat focal cerebral ischemia. To confirm previous results obtained in single laboratories with small sample sizes, and to provide a robust preclinical evidence base for potential clinical development in stroke, we have performed a two-center preclinical trial with sufficiently large group sizes to detect relevant effects, minimizing biases in experimental design as much as possible (randomization, blinding, predefined in- and exclusion criteria) and increasing external and construct validities by performing experimental focal cerebral ischemia by different surgeons in two different laboratories on two continents, including two species (480 mice and 55 rats), different suppliers, young, young adult, and mature adult animals (range 2 -16 months) as well as comorbid animals (diabetes). While JM-20 improved functional outcomes after middle cerebral artery occlusion in young adult mice at day 7 and appeared to reduce mortality (not statistically significant), it had no effect in mature adult or comorbid (STZ-induced diabetes) mice. Effect sizes, where statistically significant, were modest, and much lower than those reported in the previous studies. Meta-analysis of all individual mouse data did not reveal statistically significant different functional outcomes or mortalities between vehicle- and JM-20-treated animals, although neuroscores and survival were slightly better in JM-20-treated animals. In the less severe model of permanent cortical focal cerebral ischemia in rats, JM-20 significantly reduced brain infarction. We conclude that we were able to confirm the neuroprotective potential of JM-20. However, effect sizes were substantially lower as previously described in small, monocentric trials. Further study is needed to determine whether JM-20 could be effective in less severe cases of focal cerebral ischemia or when used in combination with thrombolysis.