bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective
Authors: Nguyen Tram T. T. , Kim Yoon Tae , Jeong Geunyeol , Jin Mirim 
Published: March 2024

AbstractSecondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries
Authors: Lübke Johannes , Christen Deborah , Schwaab Juliana , Kaiser Anne , Naumann Nicole , Shoumariyeh Khalid , Jentzsch Madlen , Sockel Katja , Schaffrath Judith , Ayuk Francis A. , Stelljes Matthias , Hilgendorf Inken , Sala Elisa , Kaivers Jennifer , Schönland Stefan , Wittke Christoph , Hertenstein Bernd , Radsak Markus , Kaiser Ulrich , Brückl Valeska , Kröger Nicolaus , Brümmendorf Tim H. , Hofmann Wolf-Karsten , Klein Stefan , Jost Edgar , Reiter Andreas , Panse Jens 
Published: March 2024

AbstractWe identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999–2021. Median overall survival (OS) of ASM/SM-AHN (n = 30, 45%), SM-AML (n = 28, 39%) and MCL ± AHN (n = 13, 19%) was 9.0, 3.3 and 0.9 years (P = 0.007). Improved median OS was associated with response of SM (17/41, 41%; HR 0.4 [0.2–0.9], P = 0.035) and/or of AHN (26/43, 60%, HR 0.3 [0.1–0.7], P = 0.004) prior to alloHCT. Adverse predictors for OS included absence of KIT D816V (10/61, 16%, HR 2.9 [1.2–6.5], P < 0.001) and a complex karyotype (9/60, 15%, HR 4.2 [1.8–10.0], P = 0.016). HLA-match, conditioning type or transplantation at centers reporting above-average alloHCTs (≥7) had no impact on OS. Taking into account competing events at years 1, 3 and 5, relapse-related mortality and non-relapse mortality rate were 15%/23%, 20%/30% and 23%/35%, respectively. Irrespective of subtype, subsequent treatment response was achieved in 13/30 (43%) patients and was highest on midostaurin/avapritinib (7/9, 78%). We conclude that outcome of alloHCT in AdvSM is more affected by disease phenotype and treatment response prior to transplant than by transplant characteristics.
Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1
Authors: Xie Xiong , Lan Qiaoshuai , Zhao Jinyi , Zhang Sulin , Liu Lu , Zhang Yumin , Xu Wei , Shao Maolin , Peng Jingjing , Xia Shuai , Zhu Yan , Zhang Keke , Zhang Xianglei , Zhang Ruxue , Li Jian , Dai Wenhao , Ge Zhen , Hu Shulei , Yu Changyue , Wang Jiang , Ma Dakota , Zheng Mingyue , Yang Haitao , Xiao Gengfu , Rao Zihe , Lu Lu , Zhang Leike , Bai Fang , Zhao Yao , Jiang Shibo , Liu Hong 
Published: March 2024

AbstractRespiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.
Impact of dental visiting patterns on oral health: A systematic review of longitudinal studies
Authors: Mohd Khairuddin Aina Najwa , Bogale Birke , Kang Jing , Gallagher Jennifer E. 
Published: March 2024

Abstract
Aim
To systematically review longitudinal studies investigating the impact of dental visiting patterns on oral health across the life course.

Methods
Five databases (MEDLINE, Embase, Scopus, Web of Science, CINAHL) were searched up to March 2023. Results were screened based on eligibility criteria in a two-stage process: title and abstract, and full-text review. A backward search of reference lists and a forward search of citations of the included papers was also conducted. The quality of the included papers was assessed using the Newcastle-Ottawa Scale. Key study information was extracted and a narrative synthesis of the findings was performed.

Results
Eleven papers from five longitudinal studies in five countries (Australia, Brazil, China, New Zealand, Sweden) met the inclusion criteria. Studies of moderate to high quality consistently reported that regular dental attendance was associated with having less dental caries experience, fewer missing teeth and better oral health-related quality of life. Inconsistent findings were observed for decayed teeth, and no association was found for periodontal condition.

Conclusions
This review highlights an association between regular dental visiting pattern and improved oral health, notably less dental caries experience and better oral health-related quality of life. Dental attendance emerges as an important predictor of oral health across the life course, underscoring the importance of routine dental care.

Registration information
The PROSPERO registration number is CRD42023396380.
Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas
Authors: Polo-Generelo Salvador , Rodríguez-Mateo Cristina , Torres Belén , Pintor-Tortolero José , Guerrero-Martínez José A. , König Julian , Vázquez Jesús , Bonzón-Kulichenco Elena , Padillo-Ruiz Javier , de la Portilla Fernando , Reyes José C. , Pintor-Toro José A. 
Published: March 2024

AbstractSerine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.
Real-world effects of anti-vascular endothelial growth factor injection frequency on visual outcomes in patients with diabetic macular oedema
Authors: Payne Carter J. , Gupta Urvi , Maatouk Christopher M. , Kuo Blanche L. , Perkins Scott W. , Singh Rishi P. , Talcott Katherine E. 
Published: March 2024

Abstract
Background and objective
Anti-vascular endothelial growth factor (VEGF) injections are often administered less frequently in real-world treatment of diabetic macular oedema (DMO) than what was studied in clinical trials. This study aims to characterise real-world DMO treatment patterns and the effect of treatment intervals on patient outcomes.

Study design/patients and methods
This was a retrospective study of 291 patients with DMO treated with anti-VEGF therapy. 12- and 24-month best visual acuity (BVA) and central subfield thickness (CST) were compared between injection interval groups, which were determined by averaging the two most recent injection intervals. Multiple linear regressions were performed to identify factors associated with injection interval, BVA, and CST.

Results
48.8% of patients received injections less than or equal to every 8 weeks (≤ q8w), 27.5% between every 8 to 12 weeks (q8–12w), and 23.7% greater than every 12 weeks (> q12w). Baseline CST was similar (p = 0.32), but BVA differed significantly in q8–12w patients (p = 0.0095). BVA and CST at 12 months were similar, but q8–12w patients experienced greater 12-month BVA improvement (7.36 ± 12.4 letters) than > q12w patients (1.26 ± 12.3 letters; p = 0.0056). 24-month BVA and CST changes were similar between groups (p = 0.30 and 0.87). Baseline BVA, HbA1c, and sex were associated with 12-month BVA, and baseline BVA and CST were associated with 12-month CST.

Conclusion
Many patients experienced improvements in BVA and CST over 12 months of treatment despite receiving less frequent anti-VEGF therapy than recommended in the pivotal trials. The present study showed that extended treatment intervals with bevacizumab were effective in preserving vision of many individuals with high baseline BVA.
Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency
Authors: Haudiquet Matthieu , Le Bris Julie , Nucci Amandine , Bonnin Rémy A. , Domingo-Calap Pilar , Rocha Eduardo P. C. , Rendueles Olaya 
Published: March 2024

AbstractBacterial evolution is affected by mobile genetic elements like phages and conjugative plasmids, offering new adaptive traits while incurring fitness costs. Their infection is affected by the bacterial capsule. Yet, its importance has been difficult to quantify because of the high diversity of confounding mechanisms in bacterial genomes such as anti-viral systems and surface receptor modifications. Swapping capsule loci between Klebsiella pneumoniae strains allowed us to quantify their impact on plasmid and phage infection independently of genetic background. Capsule swaps systematically invert phage susceptibility, revealing serotypes as key determinants of phage infection. Capsule types also influence conjugation efficiency in both donor and recipient cells, a mechanism shaped by capsule volume and conjugative pilus structure. Comparative genomics confirmed that more permissive serotypes in the lab correspond to the strains acquiring more conjugative plasmids in nature. The least capsule-sensitive pili (F-like) are the most frequent in the species’ plasmids, and are the only ones associated with both antibiotic resistance and virulence factors, driving the convergence between virulence and antibiotics resistance in the population. These results show how traits of cellular envelopes define slow and fast lanes of infection by mobile genetic elements, with implications for population dynamics and horizontal gene transfer.
Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma
Authors: Grandclément C. , Estoppey C. , Dheilly E. , Panagopoulou M. , Monney T. , Dreyfus C. , Loyau J. , Labanca V. , Drake A. , De Angelis S. , Rubod A. , Frei J. , Caro L. N. , Blein S. , Martini E. , Chimen M. , Matthes T. , Kaya Z. , Edwards C. M. , Edwards J. R. , Menoret E. , Kervoelen C. , Pellat-Deceunynck C. , Moreau P. , Mbow M. L. , Srivastava A. , Dyson M. R. , Zhukovsky E. A. , Perro M. , Sammicheli S. 
Published: March 2024

AbstractAntibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.
Integration of graph neural networks and genome-scale metabolic models for predicting gene essentiality
Authors: Hasibi Ramin , Michoel Tom , Oyarzún Diego A. 
Published: March 2024

AbstractGenome-scale metabolic models are powerful tools for understanding cellular physiology. Flux balance analysis (FBA), in particular, is an optimization-based approach widely employed for predicting metabolic phenotypes. In model microbes such as Escherichia coli, FBA has been successful at predicting essential genes, i.e. those genes that impair survival when deleted. A central assumption in this approach is that both wild type and deletion strains optimize the same fitness objective. Although the optimality assumption may hold for the wild type metabolic network, deletion strains are not subject to the same evolutionary pressures and knock-out mutants may steer their metabolism to meet other objectives for survival. Here, we present FlowGAT, a hybrid FBA-machine learning strategy for predicting essentiality directly from wild type metabolic phenotypes. The approach is based on graph-structured representation of metabolic fluxes predicted by FBA, where nodes correspond to enzymatic reactions and edges quantify the propagation of metabolite mass flow between a reaction and its neighbours. We integrate this information into a graph neural network that can be trained on knock-out fitness assay data. Comparisons across different model architectures reveal that FlowGAT predictions for E. coli are close to those of FBA for several growth conditions. This suggests that essentiality of enzymatic genes can be predicted by exploiting the inherent network structure of metabolism. Our approach demonstrates the benefits of combining the mechanistic insights afforded by genome-scale models with the ability of deep learning to infer patterns from complex datasets.
The anti-aromatic dianion and aromatic tetraanion of [18]annulene
Authors: Stawski Wojciech , Zhu Yikun , Rončević Igor , Wei Zheng , Petrukhina Marina A. , Anderson Harry L. 
Published: March 2024

Abstractπ-Conjugated macrocycles behave differently from analogous linear chains because their electronic wavefunctions resemble a quantum particle on a ring, leading to aromaticity or anti-aromaticity. [18]Annulene, (CH)18, is the archetypal non-benzenoid aromatic hydrocarbon. Molecules with circuits of 4n + 2 π electrons, such as [18]annulene (n = 4), are aromatic, with enhanced stability and diatropic ring currents (magnetic shielding inside the ring), whereas those with 4n π electrons, such as the dianion of [18]annulene, are expected to be anti-aromatic and exhibit the opposite behaviour. Here we use 1H NMR spectroscopy to re-evaluate the structure of the [18]annulene dianion. We also show that it can be reduced further to an aromatic tetraanion, which has the same shape as the dianion. The crystal structure of the tetraanion lithium salt confirms its geometry and reveals a metallocene-like sandwich, with five Li+ cations intercalated between two [18]annulene tetraanions. We also report a heteroleptic sandwich, with [18]annulene and corannulene tetraanion decks.
Chimpanzees use social information to acquire a skill they fail to innovate
Authors: van Leeuwen Edwin J. C. , DeTroy Sarah E. , Haun Daniel B. M. , Call Josep 
Published: March 2024

AbstractCumulative cultural evolution has been claimed to be a uniquely human phenomenon pivotal to the biological success of our species. One plausible condition for cumulative cultural evolution to emerge is individuals’ ability to use social learning to acquire know-how that they cannot easily innovate by themselves. It has been suggested that chimpanzees may be capable of such know-how social learning, but this assertion remains largely untested. Here we show that chimpanzees use social learning to acquire a skill that they failed to independently innovate. By teaching chimpanzees how to solve a sequential task (one chimpanzee in each of the two tested groups, n = 66) and using network-based diffusion analysis, we found that 14 naive chimpanzees learned to operate a puzzle box that they failed to operate during the preceding three months of exposure to all necessary materials. In conjunction, we present evidence for the hypothesis that social learning in chimpanzees is necessary and sufficient to acquire a new, complex skill after the initial innovation.
DeltaDTM: A global coastal digital terrain model
Authors: Pronk Maarten , Hooijer Aljosja , Eilander Dirk , Haag Arjen , de Jong Tjalling , Vousdoukas Michalis , Vernimmen Ronald , Ledoux Hugo , Eleveld Marieke 
Published: March 2024

AbstractCoastal elevation data are essential for a wide variety of applications, such as coastal management, flood modelling, and adaptation planning. Low-lying coastal areas (found below 10 m +Mean Sea Level (MSL)) are at risk of future extreme water levels, subsidence and changing extreme weather patterns. However, current freely available elevation datasets are not sufficiently accurate to model these risks. We present DeltaDTM, a global coastal Digital Terrain Model (DTM) available in the public domain, with a horizontal spatial resolution of 1 arcsecond (∼30 m) and a vertical mean absolute error (MAE) of 0.45 m overall. DeltaDTM corrects CopernicusDEM with spaceborne lidar from the ICESat-2 and GEDI missions. Specifically, we correct the elevation bias in CopernicusDEM, apply filters to remove non-terrain cells, and fill the gaps using interpolation. Notably, our classification approach produces more accurate results than regression methods recently used by others to correct DEMs, that achieve an overall MAE of 0.72 m at best. We conclude that DeltaDTM will be a valuable resource for coastal flood impact modelling and other applications.
Analytical solutions for the Klein–Gordon equation with combined exponential type and ring-shaped potentials
Authors: Ahmadov A. I. , Nagiyev Sh. M. , Ikot A. N. , Tarverdiyeva V. A. 
Published: March 2024

AbstractIn this study, we have successfully obtained the analytical solutions for the Klein–Gordon equation with new proposed a non-central exponential potential $$V\left( r \right) = D\left[ {1 - \sigma_{0} \coth (\alpha r)} \right]^{2} + (\eta_{1} + \eta_{2} \cos \theta )/r^{2} \sin^{2} \theta$$

V

r

=
D

1
-

σ
0

coth

(
α
r
)

2

+

(

η
1

+

η
2

cos
θ
)

/

r
2

sin
2

θ

. Our approach involves a proper approximation of the centrifugal term, with $${l}{\prime}$$

l
′

representing the generalized orbital angular momentum quantum number, and the utilization of the Nikiforov–Uvarov method. The resulting radial and angular wave functions are expressed in terms of Jacobi polynomials, and the corresponding energy equation is also derived. Our calculations of the eigenvalues for arbitrary quantum numbers demonstrated significant sensitivity to potential parameters and quantum numbers. Additionally, we evaluate the dependence of energy eigenvalues on screening parameter $$\alpha$$
α
for arbitrary quantum numbers $$n_{r}$$

n
r

and $$N$$
N
to establish the accuracy of our findings. Furthermore, we determine the non-relativistic limits of the radial wave function and energy equation, which align with corresponding previous results in the case where $$\eta_{1} = \eta_{2} = 0$$

η
1

=

η
2

=
0

.