bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apache is a neuronal player in autophagy required for retrograde axonal transport of autophagosomes
Authors: Parisi Barbara , Esposito Alessandro , Castroflorio Enrico , Bramini Mattia , Pepe Sara , Marte Antonella , Guarnieri Fabrizia C. , Valtorta Flavia , Baldelli Pietro , Benfenati Fabio , Fassio Anna , Giovedì Silvia 
Published: October 2024

AbstractNeurons are dependent on efficient quality control mechanisms to maintain cellular homeostasis and function due to their polarization and long-life span. Autophagy is a lysosomal degradative pathway that provides nutrients during starvation and recycles damaged and/or aged proteins and organelles. In neurons, autophagosomes constitutively form in distal axons and at synapses and are trafficked retrogradely to the cell soma to fuse with lysosomes for cargo degradation. How the neuronal autophagy pathway is organized and controlled remains poorly understood. Several presynaptic endocytic proteins have been shown to regulate both synaptic vesicle recycling and autophagy. Here, by combining electron, fluorescence, and live imaging microscopy with biochemical analysis, we show that the neuron-specific protein APache, a presynaptic AP-2 interactor, functions in neurons as an important player in the autophagy process, regulating the retrograde transport of autophagosomes. We found that APache colocalizes and co-traffics with autophagosomes in primary cortical neurons and that induction of autophagy by mTOR inhibition increases LC3 and APache protein levels at synaptic boutons. APache silencing causes a blockade of autophagic flux preventing the clearance of p62/SQSTM1, leading to a severe accumulation of autophagosomes and amphisomes at synaptic terminals and along neurites due to defective retrograde transport of TrkB-containing signaling amphisomes along the axons. Together, our data identify APache as a regulator of the autophagic cycle, potentially in cooperation with AP-2, and hypothesize that its dysfunctions contribute to the early synaptic impairments in neurodegenerative conditions associated with impaired autophagy.
Alternated cross-laminated timber (aCLT) panels: development and mechanical characterization
Authors: Santos P. , Cardoso L. , Dias A. M. P. G. 
Published: October 2024

AbstractA novel type of wood-based panel for structural applications is presented. Such panel named as alternated cross-laminated timber (aCLT) is based on the cross-laminated timber (CLT) panel concept but with a modified internal architecture, in which the cross-layers are replaced by hybrid layers composed of the traditional cross-lamellas alternated with in-line lamellas—as in glued laminated timber (GLT). Such modification aims to improve stiffness and strength in the main direction of the panel in comparison to the traditional CLT concept. To study the referred panel concept and its behavior, a series of panel stripes specimens (beams) of the new panel concept, as well as of CLT and GLT, were produced with 3 and 5 layers. An experimental campaign was performed to determine: (i) the Young`s modulus of the lamellas; (ii) the shear modulus and strength of the cross/hybrid layers of the panels and; (iii) the force vs. deflection of the beams in bending for the determination of bending and shear stiffness and strength. The data obtained in (i) and (ii) was inputted into a developed finite element (FE) model and the results from (iii) were used to validate the models. The FE model was later used to compare the performance of CLT and aCLT of equivalent thickness for a practical case. The results revealed a slight reduction in deflection (between 2 and 11%) and normal stress (1–7%) and a more substantial reduction in shear stress (between 28 and 94%) against the CLT solutions.
Should sports professionals consider their adversary’s strategy? A case study of match play in golf
Authors: Wajge Nishad , Stauffer Gautier 
Published: October 2024

AbstractThis study explores strategic considerations in professional golf’s Match Play format. Leveraging Professional Golfers’ Association Tour data, we investigate the impact of factoring in an adversary’s strategy. Our findings suggest that while slight strategy adjustments can be advantageous in specific scenarios, the overall benefit of considering an opponent’s strategy remains modest. This confirms the common wisdom in golf, reinforcing the recommendation to adhere to optimal stroke-play strategies due to challenges in obtaining precise opponent statistics. The methodology employed here is generic and could offer valuable insights into whether opponents’ performances should also be considered in other two-player or team sports, such as tennis, darts, soccer, volleyball, etc. We hope that this research will pave the way for new avenues of study in these areas.
Inverse demand tracking in transportation networks
Authors: Göttlich Simone , Mehlitz Patrick , Schillinger Thomas 
Published: October 2024

AbstractThis paper deals with the reconstruction of the desired demand in an optimal control problem, stated over a tree-shaped transportation network which is governed by a linear hyperbolic conservation law. As desired demands typically undergo fluctuations due to seasonality or unexpected events making short-term adjustments necessary, such an approach can exemplary be used for forecasting from past data. We suggest to model this problem as a so-called inverse optimal control problem, i.e., a hierarchical optimization problem whose inner problem is the optimal control problem and whose outer problem is the reconstruction problem. In order to guarantee the existence of solutions in the function space framework, the hyperbolic conservation law is interpreted in weak sense allowing for control functions in Lebesgue spaces. For the computational treatment of the model, we transfer the hierarchical problem into a nonsmooth single-level one by plugging the uniquely determined solution of the inner optimal control problem into the outer reconstruction problem before applying techniques from nonsmooth optimization. Some numerical experiments are presented to visualize various features of the model including different types of noise in the demand and strategies of how to observe the network in order to obtain good reconstructions of the desired demand.
On the non-uniqueness of linear Markov perfect equilibria in linear-quadratic differential games: a geometric approach
Authors: Eigruber Markus , Wirl Franz 
Published: October 2024

AbstractAlthough the possibility of multiple nonlinear equilibria in linear-quadratic differential games is extensively discussed, the literature on models with multiple linear Markov perfect equilibria (LMPEs) is scarce. Indeed, almost all papers confined to a single state (the vast majority of the application of differential games to economic problems) find a unique LMPE. This paper explains this finding and derives conditions for multiplicity based on the analysis of the phase plane in the state and the derivative of the value function. The resulting condition is applied to derive additional pathways different from the (two) known ones. All these examples, more precisely, their underlying pathways or the resulting outcomes, contradict usual assumptions in economic models. However, by extending the state space, we provide an economic setting (learning by doing) that gives rise to multiple LMPEs.
Determination of double bond positions in unsaturated fatty acids by pre-column derivatization with dimethyl and dipyridyl disulfide followed by LC-SWATH-MS analysis
Authors: Olfert Matthias , Knappe Cornelius , Sievers-Engler Adrian , Masberg Benedikt , Lämmerhofer Michael 
Published: October 2024

AbstractComprehensive in-depth structural characterization of free mono-unsaturated and polyunsaturated fatty acids often requires the determination of carbon-carbon double bond positions due to their impact on physiological properties and relevance in biological samples or during impurity profiling of pharmaceuticals. In this research, we report on the evaluation of disulfides as suitable derivatization reagents for the determination of carbon-carbon double bond positions of unsaturated free fatty acids by UHPLC-ESI-QTOF-MS/MS analysis and SWATH (sequential windowed acquisition of all theoretical mass spectra) acquisition. Iodine-catalyzed derivatization of C = C double bonds with dimethyl disulfide (DMDS) enabled detection of characteristic carboxy-terminal MS2 fragments for various fatty acids in ESI negative mode. The determination of double bond positions of fatty acids with up to three double bonds, the transfer of the method to plasma samples, and its limitations have been shown. To achieve charge-switching for positive ion mode MS-detection, derivatization with 2,2′-dipyridyldisulfide (DPDS) was investigated. It enabled detection of both corresponding characteristic omega-end- and carboxy-end-fragments for fatty acids with up to two double bonds in positive ion mode. It provides a straightforward strategy for designing MRM transitions for targeted LC–MS/MS assays. Both derivatization techniques represent a simple and inexpensive way for the determination of double bond positions in fatty acids with low number of double bonds. No adaptation of MS hardware is required and the specific isotopic pattern of resulting sulfur-containing products provides additional structural confirmation. This reaction scheme opens up the avenue of structural tuning of disulfide reagents beyond DMDS and DPDS using reagents like cystine and analogs to achieve enhanced performance and sensitivity.
Graphical Abstract
An electrochemical proximity assay (ECPA) for antibody detection incorporating flexible spacers for improved performance
Authors: Kurian Amanda S. N. , Mazumder Mainul Islam , Gurukandure Asanka , Easley Christopher J. 
Published: October 2024

AbstractA clever approach for biosensing is to leverage the concept of the proximity effect, where analyte binding to probes can be coupled to a second, controlled binding event such as short DNA strands. This analyte-dependent effect has been exploited in various sensors with optical or electrochemical readouts. Electrochemical proximity assays (ECPA) are more amenable to miniaturization and adaptation to the point-of-care, yet ECPA has been generally targeted toward protein sensing with antibody-oligonucleotide probes. Antibodies themselves are also important as biomarkers, since they are produced in bodily fluids in response to various diseases or infections, often in low amounts. In this work, by using antigen-DNA conjugates, we targeted an ECPA method for antibody sensing and showed that the assay performance can be greatly enhanced using flexible spacers in the DNA conjugates. After adding flexible polyethylene glycol (PEG) spacers at two distinct positions, the spacers ultimately increased the antibody-dependent current by a factor of 4.0 without significant background increases, similar to our recent work using thermofluorimetric analysis (TFA). The optimized ECPA was applied to anti-digoxigenin antibody quantification at concentrations ranging over two orders of magnitude, from the limit of detection of 300 pM up to 50 nM. The assay was functional in 90% human serum, where increased ionic strength was used to counteract double-layer repulsion effects at the electrode. This flexible-probe ECPA methodology should be useful for sensing other antibodies in the future with high sensitivity, and the mechanism for signal improvement with probe flexibility may be applicable to other DNA-based electrochemical sensor platforms.
Graphical Abstract
Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas
Authors: Silver Luke W. , McLennan Elspeth A. , Beaman Julian , da Silva Karen Burke , Timms Peter , Hogg Carolyn J. , Belov Katherine 
Published: October 2024

AbstractConservation genomics can greatly improve conservation outcomes of threatened populations, including those impacted by disease. Understanding diversity within immune gene families, including the major histocompatibility complex (MHC) and toll-like receptors (TLR), is important due to the role they play in disease resilience and susceptibility. With recent advancements in sequencing technologies and bioinformatic tools, the cost of generating high-quality sequence data has significantly decreased and made it possible to investigate diversity across entire gene families in large numbers of individuals compared to investigating only a few genes or a few populations previously. Here, we use the koala as a case study for investigating functional diversity across populations. We utilised previous target enrichment data and 438 whole genomes to firstly, determine the level of sequencing depth required to investigate MHC diversity and, secondly, determine the current level of diversity in MHC genes in koala populations. We determined for low complexity, conserved genes such as TLR genes 10 × sequencing depth is sufficient to reliably genotype more than 90% of variants, whereas for complex genes such as the MHC greater than 20 × and preferably 30 × sequencing depth is required. We used whole genome data to identify 270 biallelic SNPs across 24 MHC genes as well as copy number variation (CNV) within class I and class II genes and conduct supertype analysis. Overall, we have provided a bioinformatic workflow for investigating variation in a complex immune gene family from whole genome sequencing data and determined current levels of diversity within koala MHC genes.
Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome
Authors: Huls Gerwin , Chitu Dana A. , Tick Lidwine , Boersma Rinske , Breems Dimitri , Herbers Alexandra , Klein Saskia K. , de Jonge Suzan , Westerweel Peter E. , Cruijsen Marjan , Hoogendoorn Mels , Cuijpers Marlous , Deeren Dries , Bailly Benjamin , Visser Otto , van Rhenen Anna , Posthuma Eduard F. M. , Valk Peter J. M. , Cloos Jacqueline , Ammatuna Emanuele , Refos Jeannine M. , Fakkert R. , Löwenberg Bob , Ossenkoppele Gert J. 
Published: October 2024

AbstractThe treatment of older patients with acute myeloid leukemia (AML) considered unfit for receiving intensive chemotherapy is challenging. Based on the hypothesis that addition of the broad tyrosine kinase inhibitor (TKI) midostaurin could improve the response to hypomethylating agents, irrespective of FLT3 gene mutational status, we conducted a randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to a 10-day schedule of decitabine in unfit (i.e. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≥ 3) AML and higher risk myelodysplasia (MDS) patients (HOVON155 trial). In total, 140 eligible patients were randomly (1:1) assigned to treatment with 10-days of decitabine alone (N = 70) or combined with midostaurin (50 mg bid;starting the day following the last dose of decitabine), (N = 70). Addition of midostaurin was well tolerated and the number of AEs was comparable for both treatment arms. Early death rates (< 30 days) were similar as well (10%). In the decitabine plus midostaurin arm 24% reached CR/CRi, the median OS was 4.8 months and 1-yrs OS was 31% which compared with 34% CR/CRi, median OS of 7.4 months and 1-yrs OS of 37% for the decitabine alone group (NS). Thus, while the addition of midostaurin appears safe, it does not enhance therapeutic efficacy of decitabine in unfit AML patients.
Cryptofaunal communities are influenced by benthic cover and fish abundance in a large Caribbean coral reef system
Authors: Armenteros Maickel , Díaz-Delgado Yarima , Marzo-Pérez Diana , Pérez-García José A. , Hernández-Fernández Leslie , González de Zayas Roberto , Navarro-Martínez Zenaida M. , Apprill Amy 
Published: October 2024

AbstractSmall-sized invertebrates inhabiting hard substrates in coral reefs (a.k.a. cryptofauna) contribute substantially to reef biodiversity, but their patterns of distribution and ecological controls are poorly understood. Here, we characterized the cryptofauna community and explored “bottom-up” and “top-down” controls by benthic cover and fish abundance, respectively. We sampled the cryptofauna inhabiting the reef terrace from 13 sites along 200 km in Jardines de la Reina (Cuba), a well-preserved and protected area in the Caribbean. We counted 23,959 invertebrates of 14 higher taxa, being the most abundant Copepoda (54%), Nematoda (21%), Mollusca (7%), Ostracoda (5%), Polychaeta (5%), and Amphipoda (3%). Richness, abundance, and community structure varied across the reefs without any geographical gradient of distribution. One-third of the variance occurred at site scale (~ 10 km), and half occurred at quadrat scale (~ 1 m). Algal cover promoted cryptofauna richness and abundance likely providing substrate and food, while live coral cover negatively influenced nematode abundances, potentially due to coral defenses. Relationships between cryptofauna and reef fishes were also present, with invertivores and herbivores negatively affecting cryptofauna abundance likely due to direct or indirect predation pressures. This research highlights the important roles of bottom-up and top-down controls, by algal/coral cover and fishes, respectively, on cryptofauna and in extension to coral reef biodiversity. Current threats by climate change are expected to alter these controls on cryptofauna resulting in changes to diversity, trophodynamics and energy flows of coral reefs.
National centralization of Hirschsprung’s disease in Sweden: a comparison of postoperative outcome
Authors: Söderström Linnea , Graneli Christina , Rossi Daniel , Hagelsteen Kristine , Gunnarsdottir Anna , Oddsberg Jenny , Svensson Pär-Johan , Borg Helena , Bräutigam Matilda , Gustafson Elisabet , Löf Granström Anna , Stenström Pernilla , Wester Tomas 
Published: October 2024

Abstract
Background
In Sweden, surgical treatment of Hirschsprung’s disease (HSCR) was centralized from four to two pediatric surgery centers 1st of July 2018. In adults, centralization of surgical care for complex or rare diseases seems to improve quality of care. There is little evidence supporting centralization of pediatric surgical care. The aim of this study was to assess surgical management and postoperative outcome in HSCR patients following centralization of care.

Methods
This study retrospectively analyzed data of patients with HSCR that had undergone pull-through at a pediatric surgery center in Sweden from 1st of July 2013 to 30th of June 2023. Patients managed from 1st of July 2013 to 30th of June 2018 (before centralization) were compared with patients managed from 1st of July 2018 to 30th of June 2023 (after centralization) regarding surgical treatment, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through as well as complications classified according to Clavien–Madadi up to 30 days after pull-through.

Results
In the 5-year period prior to centralization, 114 individuals from 4 treating centers were included and compared to 83 patients from 2 treating centers in the second period. There was no difference regarding age at pull-through or proportion of patients with a stoma prior to pull-through. An increase of laparoscopically assisted endorectal pull-through (8.8% to 39.8%) was observed (p < 0.001). No significant differences were seen in postoperative hospital stay, unplanned procedures under general anesthesia, or readmissions up to 90 days after pull-through. There was no difference in severe complications (Clavien–Madadi ≥ 3); however, HAEC treated with antibiotics increased following centralization (10.5–24.1%; p = 0.018).

Conclusion
Centralization of care for HSCR does not seem to delay time to pull-through nor reduce severe complications, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through. The increased HAEC rate may be due to increased awareness of mild HAEC.
Level of evidence: Level III.
Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy
Authors: Moser Tobias , Gruber Joachim , Mylonaki Eirini , Böhm Vincent , Schwarzenhofer Daniel , Tröscher Anna R. , Lenzenweger Eva , Krehan Ingomar , Söllradl Eva , Leitinger Markus , Helbok Raimund , Trinka Eugen , von Oertzen Tim J. , Wagner Judith N. 
Published: October 2024

Abstract
Background
Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.

Methods
A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits.

Results
Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433–3274) indicated favorable outcomes in both groups.

Conclusion
This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.