bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons
Authors: Bracha Shahar , Johnson Hannah J. , Pranckevicius Nicole A. , Catto Francesca , Economides Athena E. , Litvinov Sergey , Hassi Karoliina , Rigoli Marco Tullio , Cheroni Cristina , Bonfanti Matteo , Valenti Alessia , Stucchi Sarah , Attreya Shruti , Ross Paul D. , Walsh Daniel , Malachi Nati , Livne Hagay , Eshel Reut , Krupalnik Vladislav , Levin Doron , Cobb Stuart , Koumoutsakos Petros , Caporale Nicolò , Testa Giuseppe , Aguzzi Adriano , Koshy Anita A. , Sheiner Lilach , Rechavi Oded 
Published: July 2024

AbstractDelivering macromolecules across biological barriers such as the blood–brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS), can deliver proteins to host cells. Here we engineered T. gondii’s endogenous secretion systems, the rhoptries and dense granules, to deliver multiple large (>100 kDa) therapeutic proteins into neurons via translational fusions to toxofilin and GRA16. We demonstrate delivery in cultured cells, brain organoids and in vivo, and probe protein activity using imaging, pull-down assays, scRNA-seq and fluorescent reporters. We demonstrate robust delivery after intraperitoneal administration in mice and characterize 3D distribution throughout the brain. As proof of concept, we demonstrate GRA16-mediated brain delivery of the MeCP2 protein, a putative therapeutic target for Rett syndrome. By characterizing the potential and current limitations of the system, we aim to guide future improvements that will be required for broader application.
A modular DNA origami nanocompartment for engineering a cell-free, protein unfolding and degradation pathway
Authors: Huang J. , Jaekel A. , van den Boom J. , Podlesainski D. , Elnaggar M. , Heuer-Jungemann A. , Kaiser M. , Meyer H. , Saccà B. 
Published: July 2024

AbstractWithin the cell, chemical reactions are often confined and organized through a modular architecture. This facilitates the targeted localization of molecular species and their efficient translocation to subsequent sites. Here we present a cell-free nanoscale model that exploits compartmentalization strategies to carry out regulated protein unfolding and degradation. Our synthetic model comprises two connected DNA origami nanocompartments (each measuring 25 nm × 41 nm × 53 nm): one containing the protein unfolding machine, p97, and the other housing the protease chymotrypsin. We achieve the unidirectional immobilization of p97 within the first compartment, establishing a gateway mechanism that controls substrate recruitment, translocation and processing within the second compartment. Our data show that, whereas spatial confinement increases the rate of the individual reactions by up to tenfold, the physical connection of the compartmentalized enzymes into a chimera efficiently couples the two reactions and reduces off-target proteolysis by almost sixfold. Hence, our modular approach may serve as a blueprint for engineering artificial nanofactories with reshaped catalytic performance and functionalities beyond those observed in natural systems.
Exerting pulling forces in fluids by directional disassembly of microcrystalline fibres
Authors: Pantaleone L. C. , Calicchia E. , Martinelli J. , Stuart M. C. A. , Lopatina Y. Y. , Browne W. R. , Portale G. , Tych K. M. , Kudernac T. 
Published: July 2024

AbstractBiomolecular polymerization motors are biochemical systems that use supramolecular (de-)polymerization to convert chemical potential into useful mechanical work. With the intent to explore new chemomechanical transduction strategies, here we show a synthetic molecular system that can generate forces via the controlled disassembly of self-organized molecules in a crystal lattice, as they are freely suspended in a fluid. An amphiphilic monomer self-assembles into rigid, high-aspect-ratio microcrystalline fibres. The assembly process is regulated by a coumarin-based pH switching motif. The microfibre crystal morphology determines the monomer reactivity at the interface, resulting in anisotropic etching. This effect exerts a directional pulling force on microscopic beads adsorbed on the crystal surface through weak multivalent interactions. We use optical-tweezers-based force spectroscopy to extract mechanistic insights into this process, quantifying a stall force of 2.3 pN (±0.1 pN) exerted by the ratcheting mechanism produced by the disassembly of the microfibres.
Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry
Authors: Lun Xiao-Kang , Sheng Kuanwei , Yu Xueyang , Lam Ching Yeung , Gowri Gokul , Serrata Matthew , Zhai Yunhao , Su Hanquan , Luan Jingyi , Kim Youngeun , Ingber Donald E. , Jackson Hartland W. , Yaffe Michael B. , Yin Peng 
Published: July 2024

AbstractMass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited. Here, we present a signal amplification technology, termed Amplification by Cyclic Extension (ACE), implementing thermal-cycling-based DNA in situ concatenation in combination with 3-cyanovinylcarbazole phosphoramidite-based DNA crosslinking to enable signal amplification simultaneously on >30 protein epitopes. We demonstrate the utility of ACE in low-abundance protein quantification with suspension mass cytometry to characterize molecular reprogramming during the epithelial-to-mesenchymal transition as well as the mesenchymal-to-epithelial transition. We show the capability of ACE to quantify the dynamics of signaling network responses in human T lymphocytes. We further present the application of ACE in imaging mass cytometry-based multiparametric tissue imaging to identify tissue compartments and profile spatial aspects related to pathological states in polycystic kidney tissues.
Bracing for impact: how shifting precipitation extremes may influence physical climate risks in an uncertain future
Authors: Rahat Saiful Haque , Saki Shah , Khaira Ummul , Biswas Nishan Kumar , Dollan Ishrat Jahan , Wasti Asphota , Miura Yuki , Bhuiyan Md Abul Ehsan , Ray Patrick 
Published: July 2024

AbstractAs extreme precipitation intensifies under climate change, traditional risk models based on the ‘100-year return period’ concept are becoming inadequate in assessing real-world risks. In response, this nationwide study explores shifting extremes under non-stationary warming using high-resolution data across the contiguous United States. Results reveal pronounced variability in 100-year return levels, with Coastal and Southern regions displaying the highest baseline projections, and future spikes are anticipated in the Northeast, Ohio Valley, Northwest, and California. Exposure analysis indicates approximately 53 million residents currently reside in high-risk zones, potentially almost doubling and tripling under 2 °C and 4 °C warming. Drought frequency also rises, with over 37% of major farmland vulnerable to multi-year droughts, raising agricultural risks. Record 2023 sea surface temperature anomalies suggest an impending extreme El Niño event, demonstrating the need to account for natural climate variability. The insights gained aim to inform decision-makers in shaping adaptation strategies and enhancing the resilience of communities in response to evolving extremes.
GIS based geostatistical modelling and trends analysis of groundwater quality for suitable uses in Dhaka division
Authors: Karim Md. Rezaul , Arham Md. Atif , Shorif Md. Jahim Uddin , Ahsan Amimul , Al-Ansari Nadhir 
Published: July 2024

AbstractPreserving the quality of groundwater has become Bangladesh’s primary challenge in recent years. This study explores temporal trend variations in groundwater quality on a broader scale across 18 stations within the Dhaka division over 35 years. The data set encompasses an analysis of 15 distinct water quality parameters. Modified Mann-Kendal, Sens Slope and Mann-Kendal tests were performed to determine the trend’s variation and slope. In addition, the spatial–temporal changes in the quality of groundwater are studied through Geographic Information System (GIS) mapping and Piper diagram was applied to identify the unique hydrochemical properties. This is the first study conducted on this area using various trends analysis and no in-depth study is available highlighting the trends analysis of groundwater quality on a larger magnitude. In contrast, the correlation matrix reveals a high association between Mg2+and SO42−, Na+and Cl−that affects salinity and overall hardness at the majority of sites. The Piper diagram also demonstrates that the groundwater in Madaripur Sadar has major salinity issues. The analysis reveals a distinctive dominance of bicarbonate (HCO3−) ions across all sampling stations, with (HCO3−) equivalent fractions consistently ranging from 0.70 to 0.99 which can cause a significant impact on groundwater uses. This extensive analysis of long-term groundwater quality trends in the Dhaka Division enables researchers to comprehend the overall transition of groundwater quality for hardness related complications in future. Moreover, it can be a baseline study considering the valuable implications and future steps for sustainable water resource management in this region.
Environmental DNA concentrations vary greatly across productive and degradative conditions, with implications for the precision of population estimates
Authors: Parsley Meghan B. , Crespi Erica J. , Rittenhouse Tracy A. G. , Brunner Jesse L. , Goldberg Caren S. 
Published: July 2024

AbstractPopulation size is an important metric to inform the conservation and management of species. For aquatic species, environmental DNA (eDNA) concentration has been suggested for non-invasively estimating population size. However, many biotic and abiotic factors simultaneously influence the production and degradation of eDNA which can alter the relationship between population size and eDNA concentration. We investigated the influence of temperature, salinity, and ranavirus infection on eDNA concentrations using tadpole mesocosms. Using linear regression models, we tested the influence of each experimental treatment on eDNA concentrations at three time points before and during epidemics. Prior to infection, elevated temperatures lowered eDNA concentrations, indicating that degradation was the driving force influencing eDNA concentrations. During early epidemics, no treatments strongly influenced eDNA concentrations and in late epidemics, productive forces dominated as ranavirus intensity and dead organisms increased eDNA concentrations. Finally, population size was only an important predictor of eDNA concentration in late epidemics and we observed high levels of variation between samples of replicate mesocosms. We demonstrate the complexities of several interacting factors influencing productive and degradative forces, variation in influences on eDNA concentration over short time spans, and examine the limitations of estimating population sizes from eDNA with precision in semi-natural conditions.
An efficient PanAir integrated framework for automated analysis
Authors: Shahid Tahura , Gürkan Ceren 
Published: July 2024

AbstractThe work proposed here is an automated pre and post-processor integrated to PanAir that is is a high-order aerodynamic panel method-based software for flow analysis developed in 70s but still in active use especially for preliminary aircraft design. With the integrated environment proposed in this work, manipulation of input and output data to and from PanAir is bypassed successfully that is otherwise requires manual manipulations and use of third party software. The integrated environment is validated over a Cessna 210 aircraft with a modified NLF (1)-0414 airfoil. The flow around the aircraft is analyzed using PanAir together with the integrated environment and results show that pre and post processing times reduced and ease in PanAir use is increased significantly.
Adsorptive removal of phosphate from water with biochar from acacia tree modified with iron and magnesium oxides
Authors: Manawi Yehia , Al-Gaashani Rashad , Simson Simjo , Tong Yongfeng , Lawler Jenny , Kochkodan Viktor 
Published: July 2024

AbstractA novel biochar (BC) from Acaciatortilis trees pruning waste was synthesized and tested for the removal of phosphate from aqueous solutions. The BC was prepared by calcination at 600 °C and doped with Fe3O4 and MgO by hydrothermal process. The presence of iron and magnesium ions in the modified BC was confirmed by EDS analysis and X-ray diffraction (XRD) methods. Both unmodified and doped BCs were tested for phosphate removal from synthetic 1–500 ppm aqueous solutions. While the unmodified BC did not show any significant removal of phosphate from aqueous solutions, the modified BC almost completely removed phosphate from water. The enhancement in removal efficiency is due to an increase in the overall surface charge and surface area of BC as a result of doping with Fe3O4 and MgO salts. The average porosity and BET surface area corresponding to the plain BC increased by more than 20% from 322 to 394 m2/g after modification by impregnation with iron oxide and magnesium oxide. The modificaiton of BC with Fe3O4 and MgO nanoparticles was observed to increase the point of zero electric charge (PZC) from pH 3.4 (corresponding to plain BC) to pH 5.3 (corresponding to modified BC). The adsorption process was very fast and a phosphate removal value of 82.5% was reached only after 30 min of adsorption, while the removal efficiency after 4 h of adsorption was 97.5%. The rapid removal efficiency in short contact time is attributed to the high surface area of BC and strong bonding between the modified BC surface and PO43− ions. The highest adsorption capacity was observed to correspond to 98.5 mg/g which was achieved at PO43− concentration of 500 ppm and pH 8.5. Moreover, after fitting the adsorption data onto four of the most widely used adsorption isotherm models, the adsorption of PO43− onto BC can be better described by the Langmuir isotherm model.
Majority of Treponema pallidum ssp. pallidum MLST allelic profiles in the Czech Republic (2004–2022) belong to two SS14-like clusters
Authors: Vrbová Eliška , Pospíšilová Petra , Dastychová Eliška , Kojanová Martina , Kreidlová Miluše , Rob Filip , Vašků Vladimír , Mosio Petra , Strnadel Radim , Faustmannová Olga , Kuklová Ivana , Heroldová Monika Dvořáková , Zákoucká Hana , Šmajs David 
Published: July 2024

AbstractSyphilis is a multistage sexually transmitted disease caused by Treponema pallidum ssp. pallidum. In the Czech Republic, there are around 700–800 new syphilis cases annually, continuously increasing since 2012. This study analyzed a total of 1228 samples from 2004 to 2022. Of the PCR-positive typeable samples (n = 415), 68.7% were fully-typed (FT), and 31.3% were partially-typed. Most of the identified isolates belonged to the SS14-clade and only 6.3% were the Nichols-like cluster. While in the beginning of sample collection isolates have been macrolide-susceptible, recent isolates are completely resistant to macrolides. Among the FT samples, 34 different allelic profiles (APs) were found. Most of the profiles (n = 27) appeared just once in the Czech population, while seven profiles were detected more than twice. The most frequent APs belonged to two separate groups of SS14-like isolates, including group of 1.3.1 (ST 1) and 1.26.1 (ST 25) profiles, and the second group containing 1.1.8 (ST 3), 1.1.1 (ST 2), and 1.1.3 (ST 11) (representing 57.5%, and 25.3% of all detected APs, respectively). Both groups consistently differed in 6 nucleotide positions in five genes (TP0150, TP0324, TP0515, TP0548, and TP0691) coding amino-acid replacements suggesting that one or more of these differences could be involved in the higher success of the first group.
Impact of ocean heat transport on sea ice captured by a simple energy balance model
Authors: Aylmer Jake R. , Ferreira David , Feltham Daniel L. 
Published: July 2024

AbstractFuture projections of Arctic and Antarctic sea ice suffer from uncertainties largely associated with inter-model spread. Ocean heat transport has been hypothesised as a source of this uncertainty, based on correlations with sea ice extent across climate models. However, a physical explanation of what sets the sea ice sensitivity to ocean heat transport remains to be uncovered. Here, we derive a simple equation using an idealised energy-balance model that captures the emergent relationship between ocean heat transport and sea ice in climate models. Inter-model spread of Arctic sea ice loss depends strongly on the spread in ocean heat transport, with a sensitivity set by compensation of atmospheric heat transport and radiative feedbacks. Southern Ocean heat transport exhibits a comparatively weak relationship with Antarctic sea ice and plays a passive role secondary to atmospheric heat transport. Our results suggest that addressing ocean model biases will substantially reduce uncertainty in projections of Arctic sea ice.
Endothelial LATS2 is a suppressor of bone marrow fibrosis
Authors: Sivaraj Kishor K. , Majev Paul-Georg , Dharmalingam Backialakshmi , Schröder Silke , Banjanin Bella , Stehling Martin , Zeuschner Dagmar , Nordheim Alfred , Schneider Rebekka K. , Adams Ralf H. 
Published: July 2024

AbstractMyelofibrosis and osteosclerosis are fibrotic diseases disrupting bone marrow function that occur in various leukemias but also in response to non-malignant alterations in hematopoietic cells. Here we show that endothelial cell–specific inactivation of the Lats2 gene, encoding Hippo kinase large tumor suppressor kinase 2, or overexpression of the downstream effector YAP1 induce myofibroblast formation and lead to extensive fibrosis and osteosclerosis, which impair bone marrow function and cause extramedullary hematopoiesis in the spleen. Mechanistically, loss of LATS2 induces endothelial-to-mesenchymal transition, resulting in increased expression of extracellular matrix and secreted signaling molecules. Changes in endothelial cells involve increased expression of serum response factor target genes, and, strikingly, major aspects of the LATS2 mutant phenotype are rescued by inactivation of the Srf gene. These findings identify the endothelium as a driver of bone marrow fibrosis, which improves understanding of myelofibrotic and osteosclerotic diseases, for which drug therapies are currently lacking.
Künstliche Intelligenz als Gamechanger
Authors: Hantl-Merget Judith 
Published: July 2024

ZusammenfassungKI ist längst im Gesundheitswesen angekommen: Wie sich die RoMed Kliniken der Technologie annähern und
lernen, sie für sich zu nutzen, erklärt hier Pflegedirektorin Hantl-Merget M.A.
Roboter und KI am Krankenbett: Vision oder Wirklichkeit?
Authors: Heeser Alexandra 
Published: July 2024

ZusammenfassungRoboter am Krankenbett? Diese Vorstellung ist nicht so utopisch, wie sie klingt. Künstliche Intelligenz
(KI) ist aus dem Gesundheitswesen nicht mehr wegzudenken. Zahlreiche Arbeitsprozesse, aber auch Therapien
können durch KI und Digitalisierung verbessert und individualisiert werden. Dennoch kann KI nie den
menschlichen Kontakt ersetzen.
Invasive Mykosen – Innovative Therapien
Authors: Mellinghoff Sibylle C. , Cornely Oliver A. , Mammadova Parvin , Sprute Rosanne , Stemler Jannik 
Published: July 2024

ZusammenfassungInvasive Pilzerkrankungen sind schwer zu behandeln und stellen eine erhebliche Bedrohung für immungeschwächte Menschen dar. Die derzeitigen antimykotischen Wirkstoffe stoßen an ihre Grenzen, einschließlich zunehmender Resistenzen gegen Antimykotika und unerwünschter Wirkungen. Diese Übersicht soll einen umfassenden Überblick über neue Behandlungsstrategien geben.
Routine colonoscopy with a surprise in the cecum: It’s a giant appendicolith! A Case report and review of the literature
Authors: Kock am Brink Magnus , Schmidt Christa , Daniels Thies , Lock Guntram 
Published: July 2024

AbstractGiant appendicoliths (defined as appendiceal stones larger than 2 cm in size) are rare findings, with less than 20 well-documented reported cases. Appendicoliths, in general, are linked to an increased risk of appendicitis and associated complications. However, little information is available on the clinical impact of giant appendicoliths. We present a case of a giant appendicolith accidentally discovered during screening colonoscopy. With more than 4 cm, this appendicolith is one of the largest of the few reported so far. In contrast to all other cases of giant appendicoliths, the patient did not exhibit any symptoms. Additionally, we provide an overview of giant appendicolith cases, discussing their clinical features, diagnosis, and treatment.
Peristomal skin lesions – identifying patients at risk
Authors: Dietmaier Louisa , Summa Scarlett , Ronicke Moritz , Erfurt-Berge Cornelia 
Published: July 2024

Abstract
Background and Objectives Diagnosis and therapy of peristomal skin lesions are challenging for the majority of therapists. Established diagnostic tools have not yet been validated. Our objective was to outline the spectrum of and to identify risk factors for skin lesions in ostomy patients. A focus was set on peristomal ulcerations and their differentiation as peristomal pyoderma gangrenosum.
Methods In a retrospective analysis, frequency and character of peristomal skin lesions in patients presenting at two departments were analysed. Patients suffering from peristomal ulcerations were subjected to a more detailed analysis including application of the PARACELSUS score.
Results A total of 565 patients with ostomy were analysed; 40.2% (n = 227) presented with peristomal skin lesions. Moisture-associated skin damage (27.9%) was the most common, while ulcerations (21.9%) and eczematous skin alterations (19.1%) were seen with comparable frequency. Peristomal pyoderma gangrenosum was diagnosed in 7.9% of all observed peristomal lesions. Among patients with inflammatory bowel disease (n = 98), peristomal ulcerations were the leading finding (35.7%), and pyoderma gangrenosum was more frequent in these patients (16.3%).
Conclusions It is necessary to assess and classify peristomal skin lesions. Further studies for the validation of different scores or the development of diagnostic tools are needed.
Pediatric Wrist
Authors: Cantarelli Rodrigues Tatiane , Godoy Ivan Rodrigues Barros , Serfaty Aline 
Published: July 2024

AbstractPediatric wrist injuries pose unique diagnostic challenges due to distinct bone characteristics in children and their diverse injury patterns. The dynamic development of the wrist, marked by changes in bone age and emerging ossification centers, is crucial to evaluate growth and identify potential pathologies. The skeletal composition, rich in cartilage, renders bones relatively weaker yet more elastic, impacting their susceptibility to fracture. Forearm fractures display diverse patterns influenced by torsional forces. Scaphoid fractures, less common in children, differ from those in adults. Conditions like Madelung's deformity and ulnar variance are more common wrist disorders in the pediatric population. In addition, the scarcity and nonspecificity of symptoms in those with tendon injuries and triangular fibrocartilage complex lesions can be diagnostically challenging. This article reviews pediatric wrist injuries, emphasizing ossification patterns, common fracture types, and developmental variants. Grasping these complexities in pediatric wrist development and associated pathologies is essential for precise diagnosis and treatment.