bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted extracellular matrix and cell cycle genes in autism-associated Shank3 deficiency are targeted by lithium
Authors: Ioannidis Valentin , Pandey Rakshita , Bauer Helen Friedericke , Schön Michael , Bockmann Jürgen , Boeckers Tobias M. , Lutz Anne-Kathrin 
Published: December 2023

AbstractThe Shank3 gene encodes the major postsynaptic scaffolding protein SHANK3. Its mutation causes a syndromic form of autism spectrum disorder (ASD): Phelan-McDermid Syndrome (PMDS). It is characterized by global developmental delay, intellectual disorders (ID), ASD behavior, affective symptoms, as well as extra-cerebral symptoms. Although Shank3 deficiency causes a variety of molecular alterations, they do not suffice to explain all clinical aspects of this heterogenic syndrome. Since global gene expression alterations in Shank3 deficiency remain inadequately studied, we explored the transcriptome in vitro in primary hippocampal cells from Shank3∆11(−/−) mice, under control and lithium (Li) treatment conditions, and confirmed the findings in vivo. The Shank3∆11(−/−) genotype affected the overall transcriptome. Remarkably, extracellular matrix (ECM) and cell cycle transcriptional programs were disrupted. Accordingly, in the hippocampi of adolescent Shank3∆11(−/−) mice we found proteins of the collagen family and core cell cycle proteins downregulated. In vitro Li treatment of Shank3∆11(−/−) cells had a rescue-like effect on the ECM and cell cycle gene sets. Reversed ECM gene sets were part of a network, regulated by common transcription factors (TF) such as cAMP responsive element binding protein 1 (CREB1) and β-Catenin (CTNNB1), which are known downstream effectors of synaptic activity and targets of Li. These TFs were less abundant and/or hypo-phosphorylated in hippocampi of Shank3∆11(−/−) mice and could be rescued with Li in vitro and in vivo. Our investigations suggest the ECM compartment and cell cycle genes as new players in the pathophysiology of Shank3 deficiency, and imply involvement of transcriptional regulators, which can be modulated by Li. This work supports Li as potential drug in the management of PMDS symptoms, where a Phase III study is ongoing.
Risk factors of major complications after flap surgery in the treatment of stage III and IV pressure injury in people with spinal cord injury/disorder: a retrospective cohort study
Authors: Fähndrich Carina , Gemperli Armin , Baumberger Michael , Harder Michael , Roth Bianca , Schaefer Dirk J. , Wettstein Reto , Scheel-Sailer Anke 
Published: December 2023

Abstract
Study design
Retrospective cohort study.

Objectives
To identify risk factors associated with major complications after flap surgery in people with spinal cord injury or disorder (SCI/D) and stage III and IV pressure injury (PI).

Setting
Swiss hospital specialized in the treatment of people with SCI/D using the Basel Decubitus Approach.

Methods
We examined 60 risk factors for major postoperative complications in PIs over sacrum/coccyx, ischium or trochanter between 01/2016 and 12/2021. We performed descriptive analysis and computed global p-values using likelihood ratio tests adjusted for clustering of PIs in individuals.

Results
We included 220 PI treatment procedure from 149 individuals. The study population consisted of 163 (74%) men, 133 (60%) traumatic SCI, 136 (58%) stage IV PI, 198 (90%) individuals with paraplegia, 93 (42%) with osteomyelitis, and 85 (39%) with recurrent PI. Major complications 42 (19%) occurred more often in individuals with stage IV PI (p < 0.01), individuals without osteomyelitis (p < 0.03), and individuals with pathological blood concentrations of cystatin c (p < 0.028), calcium (p < 0.048), and vitamin B12 (p < 0.0049) as well as normal blood concentrations of HbA1c (p < 0.033). Immobilization (p < 0.0089) and hospital stay (p < 0.0001) of individuals with major complications was longer.

Conclusion
In the Basel Decubitus Approach, stage IV PI, absence of osteomyelitis, reduced vitamin B12 and calcium, elevated cystatin c, and normal HbA1c should be addressed to reduce major complications.
Stroma AReactive Invasion Front Areas (SARIFA) improves prognostic risk stratification of perioperative chemotherapy treated oesophagogastric cancer patients from the MAGIC and the ST03 trial
Authors: Grosser Bianca , Emmerson Jake , Reitsam Nic G. , Cunningham David , Nankivell Matthew , Langley Ruth E. , Allum William H. , Trepel Martin , Märkl Bruno , Grabsch Heike I. 
Published: December 2023

Abstract
Background
Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The clinical utility of the SARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown.

Methods
The SARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03). The relationship between SARIFA status, clinicopathological factors, overall survival (OS) and treatment was analysed.

Results
The SARIFA status was positive in 42% MAGIC trial S patients, 28% MAGIC and 48% ST03 patients after pre-operative chemotherapy. SARIFA status was related to OS in MAGIC trial S patients and was an independent prognostic biomarker in ST03 trial patients (HR 1.974, 95% CI 1.555–2.507, p < 0.001). ST03 patients with lymph node metastasis (ypN + ) and SARIFA-positive tumours had poorer OS than patients with ypN+ and SARIFA-negative tumours (plogrank < 0.001).

Conclusions
The SARIFA status has clinical utility as prognostic biomarker in oesophagogastric cancer patients irrespective of treatment modality. Whilst underlying biological mechanisms warrant further investigation, the SARIFA status might be used to identify new drug targets, potentially enabling repurposing of existing drugs targeting lipid metabolism.
Role of Fra-2 in cancer
Authors: Rampioni Vinciguerra Gian Luca , Capece Marina , Scafetta Giorgia , Rentsch Sydney , Vecchione Andrea , Lovat Francesca , Croce Carlo M. 
Published: December 2023

AbstractFos-related antigen-2 (Fra-2) is the most recently discovered member of the Fos family and, by dimerizing with Jun proteins, forms the activator protein 1 (AP-1) transcription factor. By inducing or repressing the transcription of several target genes, Fra-2 is critically involved in the modulation of cell response to a variety of extracellular stimuli, stressors and intracellular changes. In physiological conditions, Fra-2 has been found to be ubiquitously expressed in human cells, regulating differentiation and homeostasis of bone, muscle, nervous, lymphoid and other tissues. While other AP-1 members, like Jun and Fos, are well characterized, studies of Fra-2 functions in cancer are still at an early stage. Due to the lack of a trans-activating domain, which is present in other Fos proteins, it has been suggested that Fra-2 might inhibit cell transformation, eventually exerting an anti-tumor effect. In human malignancies, however, Fra-2 activity is enhanced (or induced) by dysregulation of microRNAs, oncogenes and extracellular signaling, suggesting a multifaceted role. Therefore, Fra-2 can promote or prevent transformation, proliferation, migration, epithelial-mesenchymal transition, drug resistance and metastasis formation in a tumor- and context-dependent manner. Intriguingly, recent data reports that Fra-2 is also expressed in cancer associated cells, contributing to the intricate crosstalk between neoplastic and non-neoplastic cells, that leads to the evolution and remodeling of the tumor microenvironment. In this review we summarize three decades of research on Fra-2, focusing on its oncogenic and anti-oncogenic effects in tumor progression and dissemination.
Large mechanical properties enhancement in ceramics through vacancy-mediated unit cell disturbance
Authors: Chen Zhuo , Huang Yong , Koutná Nikola , Gao Zecui , Sangiovanni Davide G. , Fellner Simon , Haberfehlner Georg , Jin Shengli , Mayrhofer Paul H. , Kothleitner Gerald , Zhang Zaoli 
Published: December 2023

AbstractTailoring vacancies is a feasible way to improve the mechanical properties of ceramics. However, high concentrations of vacancies usually compromise the strength (or hardness). We show that a high elasticity and flexural strength could be achieved simultaneously using a nitride superlattice architecture with disordered anion vacancies up to 50%. Enhanced mechanical properties primarily result from a distinctive deformation mechanism in superlattice ceramics, i.e., unit-cell disturbances. Such a disturbance substantially relieves local high-stress concentration, thus enhancing deformability. No dislocation activity involved also rationalizes its high strength. The work renders a unique understanding of the deformation and strengthening/toughening mechanism in nitride ceramics.
Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology
Authors: Montenegro-Navarro Nieves , García-Báez Claudia , García-Caballero Melissa 
Published: December 2023

AbstractLymphangiogenesis refers to the generation of new lymphatic vessels from pre-existing ones. During development and particular adult states, lymphatic endothelial cells (LEC) undergo reprogramming of their transcriptomic and signaling networks to support the high demands imposed by cell proliferation and migration. Although there has been substantial progress in identifying growth factors and signaling pathways controlling lymphangiogenesis in the last decades, insights into the role of metabolism in lymphatic cell functions are just emerging. Despite numerous similarities between the main metabolic pathways existing in LECs, blood ECs (BEC) and other cell types, accumulating evidence has revealed that LECs acquire a unique metabolic signature during lymphangiogenesis, and their metabolic engine is intertwined with molecular regulatory networks, resulting in a tightly regulated and interconnected process. Considering the implication of lymphatic dysfunction in cancer and lymphedema, alongside other pathologies, recent findings hold promising opportunities to develop novel therapeutic approaches. In this review, we provide an overview of the status of knowledge in the molecular and metabolic network regulating the lymphatic vasculature in health and disease.
Disproportionate declines of formerly abundant species underlie insect loss
Authors: van Klink Roel , Bowler Diana E. , Gongalsky Konstantin B. , Shen Minghua , Swengel Scott R. , Chase Jonathan M. 
Published: December 2023

AbstractStudies have reported widespread declines in terrestrial insect abundances in recent years1–4, but trends in other biodiversity metrics are less clear-cut5–7. Here we examined long-term trends in 923 terrestrial insect assemblages monitored in 106 studies, and found concomitant declines in abundance and species richness. For studies that were resolved to species level (551 sites in 57 studies), we observed a decline in the number of initially abundant species through time, but not in the number of very rare species. At the population level, we found that species that were most abundant at the start of the time series showed the strongest average declines (corrected for regression-to-the-mean effects). Rarer species were, on average, also declining, but these were offset by increases of other species. Our results suggest that the observed decreases in total insect abundance2 can mostly be explained by widespread declines of formerly abundant species. This counters the common narrative that biodiversity loss is mostly characterized by declines of rare species8,9. Although our results suggest that fundamental changes are occurring in insect assemblages, it is important to recognize that they represent only trends from those locations for which sufficient long-term data are available. Nevertheless, given the importance of abundant species in ecosystems10, their general declines are likely to have broad repercussions for food webs and ecosystem functioning.
Cryo-EM structures of PP2A:B55–FAM122A and PP2A:B55–ARPP19
Authors: Padi Sathish K. R. , Vos Margaret R. , Godek Rachel J. , Fuller James R. , Kruse Thomas , Hein Jamin B. , Nilsson Jakob , Kelker Matthew S. , Page Rebecca , Peti Wolfgang 
Published: December 2023

AbstractProgression through the cell cycle is controlled by regulated and abrupt changes in phosphorylation1. Mitotic entry is initiated by increased phosphorylation of mitotic proteins, a process driven by kinases2, whereas mitotic exit is achieved by counteracting dephosphorylation, a process driven by phosphatases, especially PP2A:B553. Although the role of kinases in mitotic entry is well established, recent data have shown that mitosis is only successfully initiated when the counterbalancing phosphatases are also inhibited4. Inhibition of PP2A:B55 is achieved by the intrinsically disordered proteins ARPP195,6 and FAM122A7. Despite their critical roles in mitosis, the mechanisms by which they achieve PP2A:B55 inhibition is unknown. Here, we report the single-particle cryo-electron microscopy structures of PP2A:B55 bound to phosphorylated ARPP19 and FAM122A. Consistent with our complementary NMR spectroscopy studies, both intrinsically disordered proteins bind PP2A:B55, but do so in highly distinct manners, leveraging multiple distinct binding sites on B55. Our extensive structural, biophysical and biochemical data explain how substrates and inhibitors are recruited to PP2A:B55 and provide a molecular roadmap for the development of therapeutic interventions for PP2A:B55-related diseases.
Protracted neuronal recruitment in the temporal lobes of young children
Authors: Nascimento Marcos Assis , Biagiotti Sean , Herranz-Pérez Vicente , Santiago Samara , Bueno Raymund , Ye Chun J. , Abel Taylor J. , Zhang Zhuangzhi , Rubio-Moll Juan S. , Kriegstein Arnold R. , Yang Zhengang , Garcia-Verdugo Jose Manuel , Huang Eric J. , Alvarez-Buylla Arturo , Sorrells Shawn F. 
Published: December 2023

AbstractThe temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1–4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer’s disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.
Multiomic spatial landscape of innate immune cells at human central nervous system borders
Authors: Sankowski Roman , Süß Patrick , Benkendorff Alexander , Böttcher Chotima , Fernandez-Zapata Camila , Chhatbar Chintan , Cahueau Jonathan , Monaco Gianni , Gasull Adrià Dalmau , Khavaran Ashkan , Grauvogel Jürgen , Scheiwe Christian , Shah Mukesch Johannes , Heiland Dieter Henrik , Schnell Oliver , Markfeld-Erol Filiz , Kunze Mirjam , Zeiser Robert , Priller Josef , Prinz Marco 
Published: December 2023

AbstractThe innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain’s immune system.
A dataset of formulation compositions for self-emulsifying drug delivery systems
Authors: Zaslavsky Jonathan , Allen Christine 
Published: December 2023

AbstractSelf-emulsifying drug delivery systems (SEDDS) are a well-established formulation strategy for improving the oral bioavailability of poorly water-soluble drugs. Traditional development of these formulations relies heavily on empirical observation to assess drug and excipient compatibility, as well as to select and optimize the formulation compositions. The aim of this work was to leverage previously developed SEDDS in the literature to construct a comprehensive SEDDS dataset that can be used to gain insights and advance data-driven approaches to formulation development. A dataset comprised of 668 unique SEDDS formulations encompassing 20 poorly water-soluble drugs was curated. While there are still opportunities to enhance the quality and quantity of data on SEDDS, this research lays the groundwork to potentially simplify the SEDDS formulation development process.
A randomized controlled trial of a proactive analgesic protocol demonstrates reduced opioid use among hospitalized adults with inflammatory bowel disease
Authors: Berry Sameer K. , Takakura Will , Patel Devin , Govalan Rajalakshmi , Ghafari Afsoon , Kiefer Elizabeth , Huang Shao-Chi , Bresee Catherine , Nuckols Teryl K. , Melmed Gil Y. 
Published: December 2023

AbstractMost hospitalized patients with inflammatory bowel disease (IBD) experience pain. Despite the known risks associated with opioids in IBD including risk for misuse, overdose, infection, readmission, and even death, opioid use is more prevalent in IBD than any other chronic gastrointestinal condition. Most hospitalized IBD patients receive opioids; however, opioids have not been shown to improve pain during hospitalization. We conducted a randomized controlled trial in hospitalized patients with IBD to evaluate the impact of a proactive opioid-sparing analgesic protocol. Wearable devices measured activity and sleep throughout their hospitalization. Chronic opioid users, post-operative, and pregnant patients were excluded. The primary endpoint was a change in pain scores from admission to discharge. Secondary endpoints included opioid use, functional activity, sleep duration and quality, and length of stay. Of 329 adults with IBD evaluated for eligibility, 33 were enrolled and randomized to the intervention or usual care. Both the intervention and control group demonstrated significant decreases in pain scores from admission to discharge (− 2.6 ± 2.6 vs. − 3.0 ± 3.2). Those randomized to the intervention tended to have lower pain scores than the control group regardless of hospital day (3.02 ± 0.90 vs. 4.29 ± 0.81, p = 0.059), used significantly fewer opioids (daily MME 11.8 ± 15.3 vs. 30.9 ± 42.2, p = 0.027), and had a significantly higher step count by Day 4 (2330 ± 1709 vs. 1050 ± 1214; p = 0.014). There were no differences in sleep duration, sleep quality, readmission, or length-of-stay between the two groups. A proactive analgesic protocol does not result in worsening pain but does significantly reduce opioid-use in hospitalized IBD patients.Clinical trial registration number: NCT03798405 (Registered 10/01/2019).
Optimizing the ordering of the Hadamard masks of ghost imaging suitable for the efficient face reconstruction using the max-projection method
Authors: Zhang Haipeng , Du Kang , Zhao Changzhe , Tang Jie , Si Shangyu , Jia Wenhong , Xue Lian , Li Zhongliang 
Published: December 2023

AbstractOne crucial component of ghost imaging (GI) is the encoded mask. Higher-quality reconstruction at lower sampling rates is still a major challenge for GI. Inspired by deep learning, max-projection method is proposed in the paper to reorder the Hadamard masks for its efficient and rapid reconstruction. The simulations demonstrated that max-projection ordering with only 20 face training images yielded excellent reconstruction outcomes. In noise-free simulations, at an ultralow sampling rate of 5%, the PSNR of the max-projection ordering was 1.1 dB higher than that of the cake-cutting ordering with the best performance in the reference group. In noisy simulations, at ultralow sampling rates, the retrieved images remained almost identical to their noise-free counterparts. Irrespective of the presence or absence of noise, the max-projection ordering guaranteed the highest fidelity of image reconstruction at ultralow sampling rates. The reconstruction time was reduced to mere milliseconds, thereby enabling swift visualization of dynamic phenomena. Accordingly, the max-projection ordering Hadamard matrix offers a promising solution for real-time GI due to its higher reconstruction quality, stronger noise immunity and millisecond reconstruction time.