bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathy
Authors: Meftah Soraya , Cavallini Annalisa , Murray Tracey K , Jankowski Lukasz , Bose Suchira , Ashby Michael C , Brown Jonathan T , Witton Jonathan 
Published: April 2024

Abstract
Synapse loss is currently the best biological correlate of cognitive decline in Alzheimer’s disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function related to the progression of tauopathy and neurodegeneration. We used the well-characterized rTg4510 mouse model of tauopathy at 5–6 months and 7–8 months of age, respectively, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly, in vitro whole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5–6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching proximal to the soma in rTg4510 neurons. Therefore, in vivo whole-cell patch clamp recordings were utilized to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding these compensatory processes could identify targets to help delay symptomatic onset of dementia.
Tissue-level evidence of fibroblast activation protein inhibitor imaging in hypertrophic obstructive cardiomyopathy: a case series
Authors: Li Lina , Gao Jie , Liu Xin , Chen Bi-Xi , Su Pixiong , Xie Boqia 
Published: April 2024

Abstract

Background
Myocardial fibrosis is a key pathological factor for the occurrence of ventricular arrhythmias in hypertrophic obstructive cardiomyopathy (HOCM).

Case summary
This case series reports on two patients diagnosed with HOCM who underwent 18F-fibroblast activation protein inhibitor (FAPI) positron-emission tomography/computed tomography imaging and Morrow myotomy procedure. The collected myocardial tissue was examined histopathologically. Both patients exhibited intense and heterogeneous 18F-FAPI uptake in the septum, with significant number of activated fibroblasts.

Discussion
Enhanced 18F-FAPI uptake was observed before irreversible fibrosis, and the degree of 18F-FAPI uptake was higher in tissue with greater fibrosis. 18F-FAPI imaging may provide a promising tool for guiding surgical strategy in HOCM, and further research is needed to fully explore its potential in clinical practice.
Remote rhythm monitoring using a photoplethysmography smartphone application after cardioversion for atrial fibrillation
Authors: Calvert Peter , Mills Mark T , Howarth Kelly , Aykara Sini , Lunt Lindsay , Brewer Helen , Green David , Green Janet , Moore Simon , Almutawa Jude , Linz Dominik , Lip Gregory Y H , Todd Derick , Gupta Dhiraj 
Published: April 2024

Abstract

Aims
Direct current cardioversion (DCCV) is a commonly utilized rhythm control technique for atrial fibrillation. Follow-up typically comprises a hospital visit for 12-lead electrocardiogram (ECG) two weeks post-DCCV. We report the feasibility, costs, and environmental benefit of remote photoplethysmography (PPG) monitoring as an alternative.

Methods and results
We retrospectively analysed DCCV cases at our centre from May 2020 to October 2022. Patients were stratified into those with remote PPG follow-up and those with traditional 12-lead ECG follow-up. Monitoring type was decided by the specialist nurse performing the DCCV at the time of the procedure after discussing with the patient and offering them both options if appropriate. Outcomes included the proportion of patients who underwent PPG monitoring, patient compliance and experience, and cost, travel, and environmental impact. Four hundred sixteen patients underwent 461 acutely successful DCCV procedures. Two hundred forty-six underwent PPG follow-up whilst 214 underwent ECG follow-up. Patient compliance was high (PPG 89.4% vs. ECG 89.8%; P &gt; 0.999) and the majority of PPG users (90%) found the app easy to use. Sinus rhythm was maintained in 71.1% (PPG) and 64.7% (ECG) of patients (P = 0.161). Twenty-nine (11.8%) PPG patients subsequently required an ECG either due to non-compliance, technical failure, or inconclusive PPG readings. Despite this, mean healthcare costs (£47.91 vs. £135 per patient; P &lt; 0.001) and median cost to the patient (£0 vs. £5.97; P &lt; 0.001) were lower with PPG. Median travel time per patient (0 vs. 44 min; P &lt; 0.001) and CO2 emissions (0 vs. 3.59 kg; P &lt; 0.001) were also lower with PPG. No safety issues were identified.

Conclusion
Remote PPG monitoring is a viable method of assessing for arrhythmia recurrence post-DCCV. This approach may save patients significant travel time, reduce environmental CO2 emission, and be cost saving in a publicly-funded healthcare system.
Does training beget training over the life course? Cumulative advantage in work-related non-formal training participation in Germany and the UK
Authors: dos Santos Sascha , Dieckhoff Martina , Ehlert Martin , Mertens Antje 
Published: April 2024

AbstractContinuous training participation over the career becomes ever more important. However, most existing research mainly analyzed training at single points in time. This article investigates training dynamics and hence asks the question of whether training begets training. We provide two contributions to the literature: First, we analyze if previous training participation has an effect on later participation, leading to strict cumulative advantages. Second, by comparing Germany and the United Kingdom, we aim to explore whether these processes differ between countries with divergent skill formation systems. Using dynamic random effects probit models, which control for time-constant unobserved factors, and panel data (NEPS and UKHLS), we find that the accumulation of training experiences is mainly determined by initial education as well as job and firm characteristics. Still, previous participation plays a secondary yet noteworthy role, signifying dynamic growth in both countries, with higher effects for the United Kingdom. Thus, we show that only considering worker, job, and firm characteristics when analyzing inequality in training participation neglects a significant further mechanism that is rooted in previous training participation. We come to three main conclusions: (i) There is a potential amplification of early inequalities over time. Individuals who are initially on career paths that promote regular training participation are likely to keep and even enhance their advantage over time. (ii) On the other hand, our results also suggest the potential for individuals to break free from non-participation patterns. (iii) The inequality-generating pathways can be influenced by institutions.
Microbial Diversity and Open Questions about the Deep Tree of Life
Authors: Eme Laura , Tamarit Daniel 
Published: April 2024

Abstract
In this perspective, we explore the transformative impact and inherent limitations of metagenomics and single-cell genomics on our understanding of microbial diversity and their integration into the Tree of Life. We delve into the key challenges associated with incorporating new microbial lineages into the Tree of Life through advanced phylogenomic approaches. Additionally, we shed light on enduring debates surrounding various aspects of the microbial Tree of Life, focusing on recent advances in some of its deepest nodes, such as the roots of bacteria, archaea, and eukaryotes. We also bring forth current limitations in genome recovery and phylogenomic methodology, as well as new avenues of research to uncover additional key microbial lineages and resolve the shape of the Tree of Life.
Evolution of Phenotypic Variance Provides Insights into the Genetic Basis of Adaptation
Authors: Lai Wei-Yun , Nolte Viola , Jakšić Ana Marija , Schlötterer Christian 
Published: April 2024

Abstract
Most traits are polygenic, and the contributing loci can be identified by genome-wide association studies. The genetic basis of adaptation (adaptive architecture) is, however, difficult to characterize. Here, we propose to study the adaptive architecture of traits by monitoring the evolution of their phenotypic variance during adaptation to a new environment in well-defined laboratory conditions. Extensive computer simulations show that the evolution of phenotypic variance in a replicated experimental evolution setting can distinguish between oligogenic and polygenic adaptive architectures. We compared gene expression variance in male Drosophila simulans before and after 100 generations of adaptation to a novel hot environment. The variance change in gene expression was indistinguishable for genes with and without a significant change in mean expression after 100 generations of evolution. We suggest that the majority of adaptive gene expression evolution can be explained by a polygenic architecture. We propose that tracking the evolution of phenotypic variance across generations can provide an approach to characterize the adaptive architecture.
The endosymbiont of Epithemia clementina is specialized for nitrogen fixation within a photosynthetic eukaryote
Authors: Moulin Solène L Y , Frail Sarah , Braukmann Thomas , Doenier Jon , Steele-Ogus Melissa , Marks Jane C , Mills Matthew M , Yeh Ellen 
Published: April 2024

Abstract
Epithemia spp. diatoms contain obligate, nitrogen-fixing endosymbionts, or diazoplasts, derived from cyanobacteria. These algae are a rare example of photosynthetic eukaryotes that have successfully coupled oxygenic photosynthesis with oxygen-sensitive nitrogenase activity. Here, we report a newly-isolated species, E. clementina, as a model to investigate endosymbiotic acquisition of nitrogen fixation. We demonstrate that the diazoplast, which has lost photosynthesis, provides fixed nitrogen to the diatom host in exchange for fixed carbon. To identify the metabolic changes associated with this endosymbiotic specialization, we compared the Epithemia diazoplast with its close, free-living cyanobacterial relative, Crocosphaera subtropica. Unlike C. subtropica, in which nitrogenase activity is temporally separated from photosynthesis, we show that nitrogenase activity in the diazoplast is continuous through the day (concurrent with host photosynthesis) and night. Host and diazoplast metabolism are tightly coupled to support nitrogenase activity: Inhibition of photosynthesis abolishes daytime nitrogenase activity, while nighttime nitrogenase activity no longer requires cyanobacterial glycogen storage pathways. Instead, import of host-derived carbohydrates supports nitrogenase activity throughout the day-night cycle. Carbohydrate metabolism is streamlined in the diazoplast compared to C. subtropica with retention of the oxidative pentose phosphate pathway and oxidative phosphorylation. Similar to heterocysts, these pathways may be optimized to support nitrogenase activity, providing reducing equivalents and ATP and consuming oxygen. Our results demonstrate that the diazoplast is specialized for endosymbiotic nitrogen fixation. Altogether, we establish a new model for studying endosymbiosis, perform a functional characterization of this diazotroph endosymbiosis, and identify metabolic adaptations for endosymbiotic acquisition of a critical biological function.
2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation
Authors: Riess Salomé , Chèze Marjorie , Muckensturm Aurelie , Klinger Nadine , Roussel Olivier , Cirimele Vincent 
Published: April 2024

Abstract
2-Fluorodeschloroketamine (2-FDCK) is a new psychoactive substance (NPS), close to the ketamine structure. Few cases of 2-FDCK intake are described in the forensic literature, especially concerning death cases. We report here a case of self-mutilation (Case 1) and two forensic deaths linked to 2-FDCK consumption. The second case involved a man found dead in the street, having been stabbed. The third case was a man found dead following a suspected overdose and in an advanced state of putrefaction. For all three cases, biological fluids such as blood and urine were analyzed, as was hair for the two fatal cases. The aim of this study was to identify and quantify 2-FDCK and its main metabolites in different matrices. Biological fluids and hair were analyzed by liquid chromatography coupled with tandem mass spectrometry after decontamination and extraction. Seized products were analyzed by gas chromatography–mass spectrometry and assayed, when possible, by ultra-performance liquid chromatography with diode-array detection. 2-FDCK was detected and quantified in the peripheral blood of Cases 1, 2 and 3 (457, 758 and 5885 µg/L, respectively), as were its main metabolites nor-2-FDCK, dihydro-nor-2-FDCK and dihydro-2-FDCK. In the 1 cm long hair of Cases 2 and 3, 2-FDCK was also detected (approximately 4149 and 79824 pg/mg, respectively). Deschloroketamine (DCK) was found in the biological fluids of Cases 1, 2 and 3 (10, 8 and 350 µg/L, respectively), as well as in hair of Cases 2 and 3 (65 and around 8119 pg/mg, respectively). In Case 3, as a small bag containing DCK powder was seized from his home, we can assume that DCK was taken. On the contrary, to our knowledge, it has not been established that Case 2 took DCK alone, so we can assume that it may be the first case to report DCK from 2-FDCK metabolism in fluids as well as in hair.
RANKL signaling drives skeletal muscle into the oxidative profile
Authors: Cavalcanti de Araújo Paulo Henrique , Cezine Maria Eduarda Ramos , Vulczak Anderson , Vieira Luiz Carlos , Matsuo Flávia Sayuri , Remoto Júlia Maranghetti , Santos Audrei dos Reis , Miyabara Elen Haruka , Alberici Luciane Carla , Osako Mariana Kiomy 
Published: April 2024

Abstract
The bone–muscle unit refers to the reciprocal regulation between bone and muscle by mechanical interaction and tissue communication via soluble factors. The RANKL stimulation induces mitochondrial biogenesis and increases the oxidative capacity in osteoclasts and adipocytes. RANKL may bind to the membrane bound RANK or to osteoprotegerin (OPG), a decoy receptor that inhibits RANK–RANKL activation. RANK is highly expressed in skeletal muscle, but the contribution of RANKL to healthy skeletal muscle fiber remains elusive. Here we show that RANKL stimulation in C2C12-derived myotubes induced activation of mitochondrial biogenesis pathways as detected by RNA-seq and western blot. RANKL expanded the mitochondrial reticulum, as shown by mitochondrial DNA quantification and MitoTracker staining, and boosted the spare respiratory capacity. Using MEK and MAPK inhibitors, we found that RANKL signals via ERK and p38 to induce mitochondrial biogenesis. The soleus from OPG−/− and OPG+/− mice showed higher respiratory rates compared to C57BL6/J WT mice, which correlates with high serum RANKL levels. RANKL infusion using a mini-osmotic pump in WT mice increased the number of mitochondria, boosted the respiratory rate, increased succinate dehydrogenase activity in skeletal muscle, and improved the fatigue resistance of gastrocnemius. Therefore, our findings reveal a new role of RANKL as an osteokine-like protein that impacts muscle fiber metabolism.
Decolonization in South African universities: storytelling as subversion and reclamation
Authors: Davids Nuraan 
Published: April 2024

Abstract
Underscoring recurrent calls for the decolonization of university curricula in South Africa are underexplored presumptions that by only disrupting theoretical content, universities might release themselves from a colonialist grasp, that continues to dominate and distort higher education discourse. While it might be the case that certain theories hold enormous authoritative, ‘truthful’ sway, as propagated through Western interpretations and norms, there are inherent problems in exclusively approaching the decolonization project as a content-based hurdle, removed from the subjectivities of students’ social, lived, and learning realities. The argument advanced in this article is that until the epistemic harm of colonialism and apartheid are afforded careful recognition and attention—as in focusing on the lived experiences, realities, and stories of individuals—the hard work of delegitimizing coloniality, and its implicit structures of hegemonies and binaries cannot unfold. In addressing these harms, I commence by describing some of the contexts of epistemic harm, promulgated through colonialism and apartheid. This is followed by a consideration of decolonization, both as theory and practice-within-context. Here, I also foreground the #Rhodesmustfall campaign, as a particular moment of painful clarity about why decolonization, as well as transformation, has faltered in higher education in South Africa. In the second half, I focus on the necessity of prioritizing storytelling as a deep manifestation of decolonization. Stories, I maintain, provide access into unknown lives, and can subvert the invisible, normative framings, which dictate how we live in this world. As a manifestation of decolonization, students’ stories hold profound implications for the recognition and affirmation of pluralist identities, histories, knowledge, values, and world-views.
Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study
Authors: Schultz Lauren S , Murphy Mikela A , Donegan Macayla , Knights Jonathan , Baker Justin T , Thompson Matthew F , Waters Andrew J , Roy Michael , Gray Joshua C 
Published: April 2024

ABSTRACT

Introduction
This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges. Exploratory aim 3 sought to leverage data on phone and keyboard interactions to predict if a participant (a) is depressed and (b) has depression that improves over the course of the study.

Materials and Methods
A passive digital phenotyping app (Mindstrong Discovery) functioned in the background of the participants’ smartphones and passively collected phone usage and typing kinematics data.

Results
Fifteen out of 16 participants (93.8%) consented to install the app on their personal smartphone devices. Four participants (26.7%) discontinued the use of the app partway through the study, primarily because of keyboard usability and technical issues. Fourteen out of 15 participants (93.3%) had at least one data transfer, and the median number of days with data was 40 out of a possible 57 days. The exploratory machine learning models predicting depression status and improvement in depression performed better than chance.

Conclusions
The findings of this pilot study suggest that digital phenotyping is acceptable and feasible in a military sample and provides support for future larger investigations of this technology.
Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Up to 3-year results from a postmarketing surveillance study
Authors: Kameda Hideto , Nishida Keiichiro , Nanki Toshihiro , Watanabe Akira , Oshima Yukiya , Momohara Shigeki 
Published: April 2024

ABSTRACT

Objectives
To report up to 3-year safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a postmarketing surveillance study.

Methods
Patients enrolled previously completed 24 weeks of CZP in the 24-week postmarketing surveillance study. Adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes were 28-joint Disease Activity Score with erythrocyte sedimentation rate and European Alliance of Associations for Rheumatology response. Week 24–156 safety and Week 0–52 effectiveness data are reported here.

Results
A total of 781 patients were enrolled, with 735 and 376 patients evaluated for safety and effectiveness, respectively. Within the safety set, 17.8% (131/735) of patients reported ADRs; 9.4% (69/735) reported serious ADRs. Among patients with history of respiratory, thoracic, and mediastinal disorders, 38.4% (28/73) reported ADRs. The most frequent ADRs were infections and infestations (11.8%; 87/735); skin and subcutaneous tissue disorders (1.9%; 14/735); respiratory, thoracic, and mediastinal disorders (1.6%; 12/735). Mean 28-joint Disease Activity Score with erythrocyte sedimentation rate reduced from 4.6 (Week 0) to 2.8 (Week 52). At Week 52, 51.8% (161/311) of patients achieved European Alliance of Associations for Rheumatology Good response.

Conclusions
The long-term safety and effectiveness of CZP in the real-world setting in Japan were consistent with previously reported data; no new safety signals were identified.
The impact of ribosome biogenesis in cancer: from proliferation to metastasis
Authors: Hwang Sseu-Pei , Denicourt Catherine 
Published: April 2024

AbstractThe dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating the adaptation to altered translational demands essential for various aspects of tumor progression. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting dynamic regulation orchestrated by key oncogenic signaling pathways. Recent studies reveal the multifaceted roles of ribosomes, extending beyond protein factories to include regulatory functions in mRNA translation. Dysregulated ribosome biogenesis not only hampers precise control of global protein production and proliferation but also influences processes such as the maintenance of stem cell-like properties and epithelial-mesenchymal transition, contributing to cancer progression. Interference with ribosome biogenesis, notably through RNA Pol I inhibition, elicits a stress response marked by nucleolar integrity loss, and subsequent G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, rendering ribosomal RNA synthesis a potential therapeutic vulnerability. The review further explores targeting ribosome biogenesis vulnerabilities as a promising strategy to disrupt global ribosome production, presenting therapeutic opportunities for cancer treatment.