bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies
Authors: Nido Gonzalo S , Castelli Martina , Mostafavi Sepideh , Rubiolo Anna , Shadad Omnia , Alves Guido , Tysnes Ole-Bjørn , Dölle Christian , Tzoulis Charalampos 
Published: November 2024

Abstract
α-synucleinopathies are progressive neurodegenerative disorders characterized by intracellular aggregation of α-synuclein, yet their molecular pathogenesis remains unknow. Here, we explore cell-specific changes in gene expression across different α-synucleinopathies. We perform single-nucleus RNA sequencing on nearly 300,000 nuclei from the prefrontal cortex of individuals with idiopathic Parkinson’s disease (iPD, n = 20), Parkinson’s disease caused by LRRK2 mutations (LRRK2-PD, n = 7), multiple system atrophy (MSA, n = 6) and healthy controls (n = 13).
iPD and LRRK2-PD exhibit a largely overlapping cell type-specific signature, which is distinct from that of MSA, and includes an overall decrease of the transcriptional output in neurons. Notably, most of the differential expression signal in iPD and LRRK2-PD is concentrated in a specific deep cortical neuronal subtype expressing adrenoceptor alpha 2A. While most differentially expressed genes are highly cell type- and disease-specific, PDE10A is found consistently downregulated in most cortical neurons, and across all three diseases. Finally, exploiting the variable presence and/or severity of α-synuclein pathology in LRRK2-PD and iPD, we identify cell type-specific signatures associated with α-synuclein pathology, including a neuronal upregulation of the SNCA gene itself, encoding α-synuclein.
Our findings provide novel insights into the cell-specific transcriptional landscape of the α-synucleinopathy spectrum.
Synthesis of bisphenol-A- and bio-based polyarylates via amorphous solid-state polymerization with fluoroalkyl diesters
Authors: Taniguchi Taihei , Okazoe Takashi , Matsuoka Shin-ichi , Suzuki Masato 
Published: November 2024

Abstract
Amorphous solid-sate polymerization was efficiently synthesized using bisphenol-A-based polyarylate and isosorbide- or isomannide-based polyarylates, which represent promising super engineering plastics. The prepolymers were synthesized through the solution polymerization of bis(1,1,1,3,3,3-hexafluoro-2-propyl) terephthalate and isophthalate with bisphenol-A, isosorbide, or isomannide, using 1,8-diazabicyclo[5.4.0]-7-undecene and 1,5-diazabicyclo[4.3.0]-5-nonene as catalysts. The obtained prepolymers were then heated incrementally from 40 to 180 °C in the solid state under vacuum conditions. The bisphenol-A-based polyarylate product derived from a mixture of bis(1,1,1,3,3,3-hexafluoro-2-propyl) terephthalate (25%) and bis(1,1,1,3,3,3-hexafluoro-2-propyl) isophthalate (75%) was amorphous, exhibiting a molecular weight of 63,000 and a glass transition temperature of 208 °C. Meanwhile, isomannide-based polyarylate, a novel bio-derived amorphous polymer prepared using a similar approach, exhibited the highest glass transition temperature of 179 °C among known isosorbide-based polymers. Overall, our amorphous solid-sate polymerization method proved to be more efficient compared with conventional solid-sate polymerization, which involves crystallization.
Electrocatalytic oxygen reduction on nitrogen-doped porous carbon spheres prepared with resorcinol–phenolsulfonic acid–formaldehyde mixed resins
Authors: Sakamoto Keisuke , Kinoshita Keisuke , Shiraishi Yasuhiro , Yoshida Koki , Hiramatsu Wataru , Tanaka Shunsuke , Hirai Takayuki 
Published: November 2024

Abstract
Resorcinol–phenolsulfonic acid–formaldehyde (RxPS1–xF) mixed resin spheres were prepared by using high-temperature hydrothermal synthesis. Pyrolysis of the resin spheres under a NH3 atmosphere produced small, porous, conductive N-doped carbon spheres. These carbon spheres promoted an electrocatalytic oxygen reduction reaction with almost 100% four-electron reduction selectivity and their performance was comparable to that of the state-of-the-art Pt/C catalyst.
Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks
Authors: Rosen Linzy V , Thielking Acadia M , Dugdale Caitlin M , Montepiedra Grace , Kalk Emma , Kim Soyeon , LaCourse Sylvia M , Mathad Jyoti S , Freedberg Kenneth A , Horsburgh C Robert , Paltiel A David , Wood Robin , Ciaranello Andrea L , Reddy Krishna P 
Published: November 2024

Abstract

Background
Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH.

Methods
We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW.

Results
Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a &lt;4% or &lt;20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, &lt;2%–22% and &lt;11%–120%, respectively).

Conclusions
If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.
Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis
Authors: Rettl René , Duca Franz , Kronberger Christina , Binder Christina , Willixhofer Robin , Ermolaev Nikita , Poledniczek Michael , Hofer Felix , Nitsche Christian , Hengstenberg Christian , Eslam Roza Badr , Kastner Johannes , Bergler-Klein Jutta , Hacker Marcus , Calabretta Raffaella , Kammerlander Andreas A 
Published: November 2024

Abstract

Aims
Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Methods and results
Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n = 50; high DPD uptake: &gt;5.4, n = 50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r = 0.366, P &lt; 0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r = 0.316, P = 0.002), LV diastolic function (E/e′ average: r = 0.304, P = 0.013), NT-proBNP (r = 0.332, P &lt; 0.001), troponin T (r = 0.233, P = 0.022), 6 min walk distance (6MWD: r = −0.222, P = 0.033), and National Amyloidosis Centre (NAC) stage (r = 0.294, P = 0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: P = 0.012, RV-FW-LS: P = 0.036), LV diastolic function (E/e′ average: P = 0.035), cardiac biomarkers (NT-proBNP: P = 0.012, troponin T: P = 0.044), exercise capacity (6MWD: P = 0.035), and disease stage (NAC stage I: P = 0.045, III: P = 0.006), and experienced adverse outcomes compared with the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95% CI: 1.439–5.737), P = 0.003; DPD retention index: adjusted HR 1.221 (95% CI: 1.078–1.383), P = 0.002].

Conclusion
In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.
Microfluidics for studying the deep underground biosphere: from applications to fundamentals
Authors: Morais Sandy , Vidal Emeline , Cario Anaïs , Marre Samuel , Ranchou-Peyruse Anthony 
Published: November 2024

Abstract
In this review, selected examples are presented to demonstrate how microfluidic approaches can be utilized for investigating microbial life from deep geological environments, both from practical and fundamental perspectives. Beginning with the definition of the deep underground biosphere and the conventional experimental techniques employed for these studies, the use of microfluidic systems for accessing critical parameters of deep life in geological environments at the microscale is subsequently addressed (high pressure, high temperature, low volume). Microfluidics can simulate a range of environmental conditions on a chip, enabling rapid and comprehensive studies of microbial behavior and interactions in subsurface ecosystems, such as simulations of porous systems, interactions among microbes/microbes/minerals, and gradient cultivation. Transparent microreactors allow real-time, noninvasive analysis of microbial activities (microscopy, Raman spectroscopy, FTIR microspectroscopy, etc.), providing detailed insights into biogeochemical processes and facilitating pore-scale analysis. Finally, the current challenges and opportunities to expand the use of microfluidic methodologies for studying and monitoring the deep biosphere in real time under deep underground conditions are discussed.
Communicating State Repression to the International Community: A Case Study of How China Frames Its Policies in Xinjiang Online
Authors: Villegas-Cruz Angel M 
Published: November 2024

Abstract
Regimes and their proxies seek to legitimize overt state repression abroad to avoid economic and reputational costs. Yet, few scholars have studied the international dimension of repression image management. I examine how countries communicate their repressive actions to the international community depending on the audience. Framing repression as a legitimate response to a credible threat (threat strategy) is more likely when communicating with countries facing higher levels of domestic threat. But due to in-group favoritism, when addressing in-group audiences of the repressed, governments are more likely to frame repression as necessary to protect the repressed (benevolent rule strategy). To test these claims, I collect 82,011 tweets about activities in Xinjiang published by eighty-eight Chinese diplomatic accounts from 2014 to 2020. The results suggest that regimes change their repression image management strategies depending on the audience. Chinese government accounts in countries with higher levels of domestic conflict are more likely to use the threat strategy than those in countries with lower levels of conflict, while those in countries with a similar in-group to Xinjiang (Muslim countries) are more likely to use the benevolent rule strategy than those in out-group states. This expands our understanding of the communication strategies of human rights-abusing regimes.
Establishment of a locally adaptive allele in multidimensional continuous space
Authors: Sakamoto Takahiro 
Published: November 2024

Abstract
Local adaptation is widely seen when species adapt to spatially heterogeneous environments. Although many theoretical studies have investigated the dynamics of local adaptation using 2-population models, there remains a need to extend the theoretical framework to continuous space settings, reflecting the real habitats of species. In this study, we use a multidimensional continuous space model and mathematically analyze the establishment process of local adaptation, with a specific emphasis on the relative roles of mutation and migration. First, the role of new mutations is evaluated by deriving the establishment probability of a locally adapted mutation using a branching process and a diffusion approximation. Next, the contribution of immigrants from a neighboring region with similar environmental conditions is considered. Theoretical predictions of the local adaptation rate agreed with the results of Wright–Fisher simulations in both mutation-driven and migration-driven cases. Evolutionary dynamics depend on several factors, including the strength of migration and selection, population density, habitat size, and spatial dimensions. These results offer a theoretical framework for assessing whether mutation or migration predominantly drives convergent local adaptation in spatially continuous environments in the presence of patchy regions with similar environmental conditions.
Allopolyploidy expanded gene content but not pangenomic variation in the hexaploid oilseed Camelina sativa
Authors: Bird Kevin A , Brock Jordan R , Grabowski Paul P , Harder Avril M , Healy Adam L , Shu Shengqiang , Barry Kerrie , Boston LoriBeth , Daum Christopher , Guo Jie , Lipzen Anna , Walstead Rachel , Grimwood Jane , Schmutz Jeremy , Lu Chaofu , Comai Luca , McKay John K , Pires J Chris , Edger Patrick P , Lovell John T , Kliebenstein Daniel J 
Published: November 2024

Abstract
Ancient whole-genome duplications are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent whole-genome duplications may contribute to evolvability within recent polyploids. Hybridization accompanying some whole-genome duplications may combine divergent gene content among diploid species. Some theory and evidence suggest that polyploids have a greater accumulation and tolerance of gene presence–absence and genomic structural variation, but it is unclear to what extent either is true. To test how recent polyploidy may influence pangenomic variation, we sequenced, assembled, and annotated 12 complete, chromosome-scale genomes of Camelina sativa, an allohexaploid biofuel crop with 3 distinct subgenomes. Using pangenomic comparative analyses, we characterized gene presence–absence and genomic structural variation both within and between the subgenomes. We found over 75% of ortholog gene clusters are core in C. sativa and &lt;10% of sequence space was affected by genomic structural rearrangements. In contrast, 19% of gene clusters were unique to one subgenome, and the majority of these were Camelina specific (no ortholog in Arabidopsis). We identified an inversion that may contribute to vernalization requirements in winter-type Camelina and an enrichment of Camelina-specific genes with enzymatic processes related to seed oil quality and Camelina's unique glucosinolate profile. Genes related to these traits exhibited little presence–absence variation. Our results reveal minimal pangenomic variation in this species and instead show how hybridization accompanied by whole-genome duplication may benefit polyploids by merging diverged gene content of different species.
Association of Low Muscle Strength With Incident Pneumonia in Older Patients With Heart Failure
Authors: Yamaguchi Kenta , Konishi Masaaki , Kagiyama Nobuyuki , Kasai Takatoshi , Kamiya Kentaro , Saito Hiroshi , Saito Kazuya , Maekawa Emi , Kitai Takeshi , Iwata Kentaro , Jujo Kentaro , Wada Hiroshi , Shinoda Satoru , Akiyama Eiichi , Momomura Shin-Ichi , Hibi Kiyoshi , Matsue Yuya 
Published: November 2024

Abstract

Background
Patients with heart failure (HF) are at an increased risk of developing pneumonia, leading to a high mortality. A decrease in muscle strength due to aging or concomitant disease may contribute to the development of pneumonia in older adults. We sought to investigate the relationship between low muscle strength and pneumonia incidence in older patients hospitalized for worsening HF.

Methods
We carried out a subanalysis of the FRAGILE-HF, a prospective multicenter observational study, including 1 266 consecutive older (≥65 years) patients hospitalized with HF (mean age 80.2 ± 7.8 years; 57.4% male; left ventricular ejection fraction 46% ± 17%) and information of incident pneumonia observed after discharge. Patients were followed up for 2 years post-discharge.

Results
A total of 88 patients (7.0%) developed pneumonia after discharge, with an incidence of 42.7 per 1 000 person-years. A total of 893 patients with low muscle strength, defined as handgrip strength &lt;28 kg for men and &lt;18 kg for women according to international criteria, were more likely to develop pneumonia than those with normal muscle strength (p &lt; .001; log-rank test). Low muscle strength was a significant predictor of incident pneumonia (adjusted hazard ratio with 95% confidence interval: 2.65 [1.31–5.35], p = .007). Furthermore, the mortality rates were 43.2% in patients who developed pneumonia and 19.3% in those who did not, indicating a heightened risk of death following the onset of pneumonia (adjusted hazard ratio: 4.25 [2.91–6.19], p &lt; .001).

Conclusions
In older patients hospitalized for HF, low muscle strength was associated with incident pneumonia after discharge.
Two dimensions of product modularity and innovation: the case of R&D teams
Authors: Martinez Martin Daniel , de Leeuw Tim , Haefliger Stefan 
Published: November 2024

Abstract
This study investigates the relationship between product modularity and innovation in 101 research and development (R&D) teams. The key contribution and the departure from prior empirical work consists in bringing into relation multidimensional operationalizations of these two concepts. Product modularity is composed of standardization and reconfigurability and innovation of novelty and efficiency. The literature provides arguments for both negative and positive relationships between standardization and the two types of innovation, while positive relationships are argued for product reconfigurability. The empirical findings corroborate most of the theorizing, although negative relationships are found for standardization. This study contributes to the literature by unpacking the understanding of the concept of product modularity in R&D organizations since the multidimensional approach resolves some of the ambiguity from previous studies. The modularity literature long called for studies to empirically investigate product modularity in more than one dimension implying a number of theoretical implications discussed here.
Elucidating the augmented resistance profile of Scedosporium/Lomentospora species to azoles in a cystic fibrosis mimic environment
Authors: Mello Thaís P , Ramos Lívia S , Andrade Valter V , Torres-Santos Eduardo Caio , Lackner Michaela , Branquinha Marta H , Santos André L S 
Published: November 2024

Abstract

Background
Scedosporium/Lomentospora species are ranked as the second most frequently isolated filamentous fungi from cystic fibrosis (CF) patients. Previously, we demonstrated that the minimum inhibitory concentration (MIC) for voriconazole and posaconazole increased when performed on a mucin-containing synthetic CF sputum medium (SCFM) compared to the standard medium, RPMI-1640. In this study, we have expanded the MIC comparison to four additional azoles and investigated characteristics linked to azole resistance in Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans.

Methods
MIC was assayed by CLSI protocol, efflux pump activity was assessed by rhodamine 6G and sterols were analysed by gas chromatography-mass spectrometry (GC-MS).

Results
Overall, MICs for fluconazole, itraconazole, voriconazole, posaconazole, miconazole and ketoconazole increased by least 2-fold when susceptibility tests were performed using SCFM compared to RPMI. The activity of efflux pumps was similar in both media; however, in RPMI, but not in SCFM, the activity was induced by voriconazole and fluconazole. Additionally, MICs for those antifungals decreased more noticeably in SCFM than in RPMI in the presence of the efflux pump inhibitor PaβN. The SCFM-grown cells presented fewer sterols in their composition, and consequently higher membrane fluidity, than RPMI-grown cells. GC-MS analysis demonstrated a remodulation in the sterol profile in SCFM- compared to RPMI-grown cells. Accordingly, when the MIC assay was performed in the presence of the membrane stressor NaCl (3%), the susceptibility to voriconazole and fluconazole increased more in SCFM- than RPMI-grown cells.

Conclusions
Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.
Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study
Authors: Tumbarello Mario , Giuliano Gabriele , Criscuolo Marianna , Del Principe Maria Ilaria , Papayannidis Cristina , Fracchiolla Nicola Stefano , Dargenio Michela , Cefalo Mariagiovanna , Nadali Gianpaolo , Candoni Anna , Buquicchio Caterina , Marchesi Francesco , Picardi Marco , Lessi Federica , Piedimonte Monica , Prezioso Lucia , Piccini Matteo , Cattaneo Chiara , Busca Alessandro , Brunetti Sara , Buzzatti Elisa , Dedola Alessandra , Sciumé Mariarita , Di Renzo Nicola , Cesini Laura , Vatteroni Alessandra , Raffaelli Francesca , Pagano Livio 
Published: November 2024

Abstract

Objectives
To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs).

Methods
We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset. Secondary endpoints included the development of in vitro ceftazidime/avibactam resistance, adverse reactions and infection relapse.

Results
Of 198 patients enrolled, 66 had fever of unknown origin and 132 had microbiologically proven infections (MPIs). Enterobacterales were responsible for 98 MPIs, with KPC producers accounting for 75% of these, and carbapenem-resistant Pseudomonas aeruginosa caused 25% of MPIs. The overall 30-day mortality rate was 17.7%. Infection relapse occurred in four patients with MPI. Patients who died within 30 days of infection onset tended to have pre-existing cerebrovascular diseases, a Charlson Comorbidity Index &gt; 4 and septic shock at infection onset and had received inadequate initial antibiotic therapy. Thirty-day mortality was independently associated with septic shock at infection onset and inappropriate initial antibiotic therapy.

Conclusions
Our study provides further evidence about the effectiveness of ceftazidime/avibactam in treating infections in patients with HMs.