bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson’s disease
Authors: Geibl Fanni F. , Henrich Martin T. , Xie Zhong , Zampese Enrico , Ueda Jun , Tkatch Tatiana , Wokosin David L. , Nasiri Elena , Grotmann Constantin A. , Dawson Valina L. , Dawson Ted M. , Chandel Navdeep S. , Oertel Wolfgang H. , Surmeier D. James 
Published: October 2024

Abstract
Background
Pathological accumulation of aggregated α-synuclein (aSYN) is a common feature of Parkinson’s disease (PD). However, the mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. A potentially relevant target of aSYN is the mitochondrion. To test this hypothesis, genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain.

Methods
aSYN PFFs were stereotaxically injected into the SNc or PPN of mice. Twelve weeks later, mice were studied using a combination of approaches, including immunocytochemical analysis, cell-type specific transcriptomic profiling, electron microscopy, electrophysiology and two-photon-laser-scanning microscopy of genetically encoded sensors for bioenergetic and redox status.

Results
In addition to inducing a significant neuronal loss, SNc injection of PFFs induced the formation of intracellular, phosphorylated aSYN aggregates selectively in dopaminergic neurons. In these neurons, PFF-exposure decreased mitochondrial gene expression, reduced the number of mitochondria, increased oxidant stress, and profoundly disrupted mitochondrial adenosine triphosphate production. Consistent with an aSYN-induced bioenergetic deficit, the autonomous spiking of dopaminergic neurons slowed or stopped. PFFs also up-regulated lysosomal gene expression and increased lysosomal abundance, leading to the formation of Lewy-like inclusions. Similar changes were observed in PPN cholinergic neurons following aSYN PFF exposure.

Conclusions
Taken together, our findings suggest that disruption of mitochondrial function, and the subsequent bioenergetic deficit, is a proximal step in the cascade of events induced by aSYN pathology leading to dysfunction and degeneration of neurons at-risk in PD.
Heparin-enriched plasma proteome is significantly altered in Alzheimer’s disease
Authors: Guo Qi , Ping Lingyan , Dammer Eric B. , Duong Duc M. , Yin Luming , Xu Kaiming , Shantaraman Anantharaman , Fox Edward J. , Golde Todd E , Johnson Erik C.B. , Roberts Blaine R. , Lah James J. , Levey Allan I. , Seyfried Nicholas T. 
Published: October 2024

Abstract
Introduction
Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to β-amyloid (Aβ) and tau pathology in Alzheimer’s disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches.

Methods
We employed heparin-affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to enrich HBPs from plasma obtained from AD (n = 62) and control (n = 47) samples. These profiles were then correlated to Aβ, tau and phosphorylated tau (pTau) CSF biomarkers and plasma pTau181 from the same individuals, as well as a consensus brain proteome network to assess the overlap with AD brain pathophysiology.

Results
Heparin enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundant proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude in abundance, were measured across 109 samples. Compared to the consensus AD brain protein co-expression network, we observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, highlighting the complex interplay between the two compartments. Elevated proteins in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate with Aβ deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and the APOE4 proteoform. Additionally, heparin-enriched proteins in plasma demonstrated significant correlations with conventional AD CSF biomarkers, including Aβ, total tau, pTau, and plasma pTau181. A panel of five plasma proteins classified AD from control individuals with an area under the curve (AUC) of 0.85. When combined with plasma pTau181, the panel significantly improved the classification performance of pTau181 alone, increasing the AUC from 0.93 to 0.98. This suggests that the heparin-enriched plasma proteome captures additional variance in cognitive dementia beyond what is explained by pTau181.

Conclusion
These findings support the utility of a heparin-affinity approach coupled with TMT-MS for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain.
Visualizing scRNA-Seq data at population scale with GloScope
Authors: Wang Hao , Torous William , Gong Boying , Purdom Elizabeth 
Published: October 2024

AbstractIncreasingly, scRNA-Seq studies explore cell populations across different samples and the effect of sample heterogeneity on organism’s phenotype. However, relatively few bioinformatic methods have been developed which adequately address the variation between samples for such population-level analyses. We propose a framework for representing the entire single-cell profile of a sample, which we call a GloScope representation. We implement GloScope on scRNA-Seq datasets from study designs ranging from 12 to over 300 samples and demonstrate how GloScope allows researchers to perform essential bioinformatic tasks at the sample-level, in particular visualization and quality control assessment.
Effects and mechanisms of supramaximal high-intensity interval training on extrapulmonary manifestations in people with and without chronic obstructive pulmonary disease (COPD-HIIT): study protocol for a multi-centre, randomized controlled trial
Authors: Jakobsson Johan , Burtin Chris , Hedlund Mattias , Boraxbekk Carl-Johan , Westman Jonas , Karalija Nina , Stål Per , Sandström Thomas , Ruttens David , Gosker Harry R. , De Brandt Jana , Nyberg André 
Published: October 2024

Abstract
Background
Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls.

Methods
COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated.

Discussion
The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease.

Trial registration
Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28.
Evaluation of urinary podocin and nephrin as markers of podocyturia in dogs with leishmaniosis
Authors: Pantaleo Valeria , Furlanello Tommaso , Carli Erika , Ventura Laura , Solano-Gallego Laia 
Published: October 2024

Abstract
Background
Renal disease is the main cause of death in canine leishmaniosis. Detection of an active glomerular injury is important to identify early renal damage and to prevent the development of chronic kidney disease. Podocyturia can indicate renal injury, and podocyte-associated molecules such as podocin and nephrin can be used to identify podocyturia. The purpose of the study was to evaluate urinary podocin and nephrin concentrations in dogs with leishmaniosis as markers of podocyturia.

Methods
A total of 35 healthy dogs and 37 dogs with leishmaniosis were enrolled in the study. Dogs with leishmaniosis were classified according to the staging of the International Renal Interest Society (IRIS). Urinary podocin and nephrin concentrations were measured in all dogs with a validated enzyme-linked immunosorbent assay test and normalized to creatinine (uPoC and uNeC, respectively). The demographic, clinical, and laboratory data from both groups were analyzed and compared. Subsequently, the laboratory results were analyzed and compared according to IRIS staging in dogs in IRIS stage I and dogs in IRIS stage II + III + IV. The Pearson’s correlation test evaluated the relationship between urinary markers of podocyturia.

Results
Compared with healthy dogs, lower urinary podocin [median values (IQR): 15.10 (11.75–17.87) ng/ml versus 8.63 (7.08–13.56) ng/ml; P < 0.01] and nephrin [median values (IQR): 3.2 (3.62–5.43) ng/ml versus 2.67 (2.06–3.44) ng/ml; P < 0.01] were found in infected sick dogs. No significant differences were observed in the uPoC and uNeC between the two groups. Urinary nephrin and podocin concentrations were higher in healthy dogs and in dogs in IRIS stage I (both P < 0.05) compared with dogs in IRIS stages II + III + IV. No significant differences were found for uPoC and uNeC between healthy dogs and dogs with leishmaniosis in different IRIS clinical stages.

Conclusions
Dogs with leishmaniosis had a low concentration of podocin and nephrin in more advanced IRIS clinical stages, when kidney disease was more severe compared with healthy dogs and dogs in IRIS stage I with mild disease. Urinary nephrin was detectable for the first time in healthy non-infected dogs.

Graphical Abstract
Data-driven room acoustic modeling via differentiable feedback delay networks with learnable delay lines
Authors: Mezza Alessandro Ilic , Giampiccolo Riccardo , De Sena Enzo , Bernardini Alberto 
Published: October 2024

AbstractOver the past few decades, extensive research has been devoted to the design of artificial reverberation algorithms aimed at emulating the room acoustics of physical environments. Despite significant advancements, automatic parameter tuning of delay-network models remains an open challenge. We introduce a novel method for finding the parameters of a feedback delay network (FDN) such that its output renders target attributes of a measured room impulse response. The proposed approach involves the implementation of a differentiable FDN with trainable delay lines, which, for the first time, allows us to simultaneously learn each and every delay-network parameter via backpropagation. The iterative optimization process seeks to minimize a perceptually motivated time-domain loss function incorporating differentiable terms accounting for energy decay and echo density. Through experimental validation, we show that the proposed method yields time-invariant frequency-independent FDNs capable of closely matching the desired acoustical characteristics and outperforms existing methods based on genetic algorithms and analytical FDN design.
The state of hand rub dispensers in healthcare settings – a multicenter assessment in 19 German healthcare facilities
Authors: Herzer Christiane , Berg Torsten , Hegemann Christine , Gebhardt Tobias , Niesalla Heide , Senges Christoph 
Published: October 2024

Abstract
Background
Hand hygiene is one of the most important hygiene measures to prevent healthcare-associated infections. Well-functioning hand rub dispensers are the foundation of hand hygiene but are often overlooked in research. As the point of origin for hand hygiene, dispensers not only promote compliance through ease of use, but also strongly influence the amount of hand rub used per disinfection. This work investigates how dispenser types and conditions affect dispensed volumes and usability.

Methods
Data from 5,014 wall-mounted or point-of-care dispensers was collected from 19 German healthcare facilities during installation of an electronic hand hygiene monitoring system, including dispenser type and dispensed hand rub volumes. Of these dispensers, 56.2% were metal dispensers, and the majority (89.5%) were wall-mounted. For one hospital, 946 wall-mounted dispensers were analyzed in detail regarding pump material, damages, functionality, cleanliness, and filling levels.

Results
Dispensed volumes varied across and within dispenser types, ranging from 0.4 mL to 4.4 mL per full actuation, with the largest volumes generally dispensed by plastic dispensers with a preset of 1.0 to 3.0 mL per actuation. In general, most dispensers dispense more hand rub per full actuation than specified by the manufacturer. When different types of dispensers are used within a healthcare facility, vastly different volumes can be dispensed, making reliable and reproducible disinfection difficult for healthcare workers. In the detailed analysis of 946 dispensers, 27.1% had cosmetic defects, reduced performance, or were unusable, with empty disinfectant being the most common reason. Only 19.7% of working dispensers delivered their maximum volume on the first full actuation.

Conclusion
Even though several studies addressed the variability in dispensed volumes of hand hygiene dispensers, studies dealing with dispenser types and functionality are lacking, promoting the common but false assumption that different dispensers may be equivalent and interchangeable. Variability in dispensed volumes, coupled with frequent dispenser defects and maintenance issues, can be a major barrier to hand hygiene compliance. To support healthcare workers, more attention should be paid to ‘dispenser compliance’, selecting dispensers with similar volume ranges and proper maintenance.
A prediction of mutations in infectious viruses using artificial intelligence
Authors: Choi Won Jong , Park Jongkeun , Seong Do Young , Chung Dae Sun , Hong Dongwan 
Published: October 2024

AbstractMany subtypes of SARS-CoV-2 have emerged since its early stages, with mutations showing regional and racial differences. These mutations significantly affected the infectivity and severity of the virus. This study aimed to predict the mutations that occur during the evolution of SARS-CoV-2 and identify the key characteristics for making these predictions. We collected and organized data on the lineage, date, clade, and mutations of SARS-CoV-2 from publicly available databases and processed them to predict the mutations. In addition, we utilized various artificial intelligence models to predict newly emerging mutations and created various training sets based on clade information. Using only mutation information resulted in low performance of the learning models, whereas incorporating clade differentiation resulted in high performance in machine learning models, including XGBoost (accuracy: 0.999). However, mutations fixed in the receptor-binding motif (RBM) region of Omicron resulted in decreased predictive performance. Using these models, we predicted potential mutation positions for 24C, following the recently emerged 24A and 24B clades. We identified a mutation at position Q493 in the RBM region. Our study developed effective artificial intelligence models and characteristics for predicting new mutations in continuously evolving infectious viruses.
Bridging early life trauma to difficult-to-treat depression: scoping review
Authors: Paganin Walter , Signorini Sabrina , Sciarretta Antonio 
Published: October 2024

Aims and method
Accumulating evidence suggests that early life trauma (ELT) initiates and perpetuates a cycle of depression, leading to challenges in management and achieving remission. This scoping review aimed to examine the intricate relationship between ELT and difficult-to-treat depression (DTD). An extensive literature search from 1 January 2013 to 21 October 2023 was conducted using the Cochrane Library, PubMed, Scopus, PsycINFO and OpenGrey.

Results
Our review identified scientific literature illustrating the multifaceted link between ELT and DTD, highlighting the dual impact of ELT on therapeutic resistance and clinical complexity.

Clinical implications
This complexity hampers management of patients with DTD, who are characterised by limited pharmacological responsiveness and heightened relapse risk. While exploring the ELT–DTD nexus, the review revealed a paucity of literature on the impact of ELT within DTD. Findings underscore the profound link between ELT and DTD, which is essential for comprehensive understanding and effective management. Tailoring treatments to address ELT could enhance therapeutic outcomes for patients with DTD. Future studies should use larger samples and well-defined diagnostic criteria and explore varied therapeutic approaches.
Controversies in trauma- and stress-related disorders
Authors: Maercker Andreas , Brewin Chris R 
Published: October 2024

SummaryThe release of ICD-11 has resulted in an expansion of diagnostic entities for trauma- and stress-related disorders. This resulted, at least temporarily, in discrepancies with the DSM-5. This situation is outlined and a look is taken at the potential diagnosis of ‘continuous traumatic stress reaction’.
Maternal mental disorders and neonatal outcomes: Danish population-based cohort study
Authors: Momen Natalie C. , Chatwin Hannah , Holde Katrine , Liu Xiaoqin , Munk-Olsen Trine , Madsen Kathrine Bang , Petersen Liselotte Vogdrup 
Published: October 2024

BackgroundPrevious studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum.AimsWe aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations.MethodWe included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark. We compared children of mothers with a past (>2 years prior to conception; n = 48 646), recent (2 years prior to conception and during pregnancy; n = 15 899) or persistent (both past and recent; n = 10 905) diagnosis of any mental disorder, with children of mothers with no mental disorder diagnosis before the index delivery (n = 1 057 307). We also considered different types of mental disorders. We calculated odds ratios and 95% CIs of low birthweight, preterm birth, small for gestational age, low Apgar score, Caesarean delivery and neonatal death.ResultsOdds ratios for children exposed to past, recent and persistent maternal mental disorders suggested an increased risk for almost all adverse neonatal outcomes. Estimates were highest for children in the ‘persistent’ group for all outcomes, with the exception of the association between persistent maternal mental disorders and neonatal death (odds ratio 0.96, 0.62–1.48).ConclusionsOur study provides evidence for increased risk of multiple adverse neonatal outcomes among children of mothers with mental disorders, highlighting the need for close monitoring and support for women with mental disorders.
Coherence as maximal imaginarity generated by incoherent operations
Authors: Zhang Linshuai , Li Nan 
Published: October 2024

Abstract
Since both coherence and imaginarity have proven to be fundamental resources in quantum information processing and their definitions are both relative to a given basis, it is natural to investigate the conversion between them. In this work, we prove that a quantum state can be transformed into a state with nonvanishing imaginarity resource by incoherent operations if and only if it has nonvanishing coherence resource. On the other hand, we demonstrate that a quantum state can be transformed into a state with vanishing coherence resource by orthogonal operations if and only if it has vanishing imaginarity resource. Based on these results, we show that for any imaginarity measure, a corresponding coherence measure can be defined as the maximal amount of imaginarity generated by incoherent operations, and that for any coherence quantifier, a corresponding imaginarity quantifier can be defined as the minimal coherence generated by orthogonal operations.
Perioperative Complications and In-Hospital Mortality in Paraplegic Radical Cystectomy Patients
Authors: Di Bello Francesco , Siech Carolin , de Angelis Mario , Rodriguez Peñaranda Natali , Tian Zhe , Goyal Jordan A. , Collà Ruvolo Claudia , Califano Gianluigi , Creta Massimiliano , Saad Fred , Shariat Shahrokh F. , Briganti Alberto , Chun Felix K. H. , Micali Salvatore , Longo Nicola , Karakiewicz Pierre I. 
Published: October 2024

Abstract
Objective
The aim of this study was to test for the association between paraplegia and perioperative complications as well as in-hospital mortality after radical cystectomy (RC) for non-metastatic bladder cancer.

Methods
Perioperative complications and in-hospital mortality were tabulated in RC patients with or without paraplegia in the National Inpatient Sample (2000–2019).

Results
Of 25,527 RC patients, 185 (0.7%) were paraplegic. Paraplegic RC patients were younger (≤70 years of age; 75 vs. 53%), more frequently female (28 vs. 19%), and more frequently harbored Charlson Comorbidity Index ≥3 (56 vs. 18%). Of paraplegic vs. non-paraplegic RC patients, 141 versus 15,112 (76 vs. 60%) experienced overall complications, 38 versus 2794 (21 vs. 11%) pulmonary complications, 36 versus 3525 (19 vs. 14%) genitourinary complications, 33 versus 3087 (18 vs. 12%) intraoperative complications, 21 versus 1035 (11 vs. 4%) infections, and 17 versus 1343 (9 vs. 5%) wound complications, while 62 versus 6267 (34 vs. 25%) received blood transfusions, 47 versus 3044 (25 vs. 12%) received critical care therapy (CCT), and intrahospital mortality was recorded in 13 versus 456 (7.0 vs. 1.8%) patients. In multivariable logistic regression models, paraplegic status independently predicted higher overall CCT use (odds ratio [OR] 2.1, p < 0.001) as well as fourfold higher in-hospital mortality (p < 0.001), higher infection rate (OR 2.5, p < 0.001), higher blood transfusion rate (OR 1.45, p = 0.009), and higher intraoperative (OR 1.56, p = 0.02), wound (OR 1.89, p = 0.01), and pulmonary (OR 1.72, p = 0.004) complication rates.

Conclusion
Paraplegic patients contemplating RC should be counseled about fourfold higher risk of in-hospital mortality and higher rates of other untoward effects.