bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered empathy processing in frontotemporal dementia A task-based fMRI study
Authors: Lindberg Olof , Li Tie-Qiang , Lind Cecilia , Vestberg Susanna , Almkvist Ove , Stiernstedt Mikael , Ericson Anita , Bogdanovic Nenad , Hansson Oskar , Harper Luke , Westman Eric , Graff Caroline , Tsevis Theofanis , Mannfolk Peter , Fischer Håkan , Nilsonne Gustav , Petrovic Predrag , Nyberg Lars , Wahlund Lars-Olof , Santillo Alexander F ,   the Swedish FTD initiative
Published: March 2024

AbstractA lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the control’s activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The control’s rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informant’s ratings of the patient’s empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient’s self- ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patient’s capacity to experience affective empathy.
Flight performance, activity and behaviour of breeding pied flycatchers in the wild, revealed with accelerometers and machine learning
Authors: Yu Hui , Liang Shujie , Muijres Florian T. , te Lindert Jan Severin , de Knegt Henrik J. , Hedenström Anders , Lamers Koosje P. , Henningsson Per 
Published: March 2024

AbstractFlight behaviours have been extensively studied from different angles such as their kinematics, aerodynamics and more general their migration pattern. Nevertheless, much is still unknown about the daily flight activity of birds, in terms of their performance, behaviour and the potential differences between males and females. The recent development of miniaturized accelerometers allows us a glimpse into the daily life of a songbird. Here, we tagged 26 pied flycatchers (Ficedula hypoleuca) with accelerometers and analysed using machine learning approaches their flight performance, activity and behaviour during their chick rearing period. We found that during two hours of foraging chick-rearing pied flycatchers were flying 13.7% of the time. Almost all flights (>99%) were short flights lasting less than 10s. Flight activity changed throughout the day and was highest in the morning and lowest in the early afternoon. Male pied flycatcher had lower wing loading than females, and peak flight accelerations were inversely correlated with wing loading. Despite this, we found no significant differences in flight activity and performance between sexes. This suggests that males possess a higher potential flight performance, which they not fully utilized during foraging flights. Our results thus suggest that male and female pied flycatcher invest equally in parental care, but that this comes at a reduced cost by the male, due to their higher flight performance potential.
ParabrachialCalcaneurons mediate second-order conditioning
Authors: Park Sekun , Zhu Anqi , Cao Feng , Palmiter Richard 
Published: March 2024

AbstractLearning to associate cues, both directly and indirectly, with biologically significant events is essential for survival. Second-order conditioning (SOC) involves forming an association between a previously reinforced conditioned stimulus (CS1) and a new conditioned stimulus (CS2) without the presence of an unconditioned stimulus (US). The neural substrates mediating SOC, however, remain unclear. In the parabrachial nucleus,Calcagene-expressing neurons, which react to the noxious US, also respond to a CS after its pairing with a US. This observation led us to hypothesize their involvement in SOC. To explore this possibility, we established an aversive SOC behavioral paradigm in mice and monitoredCalcaneuron activity via single-cell calcium imaging during SOC and subsequent recall phases. These neurons were activated not only by CS1 following its association with the US but also by CS2 after SOC. Chemogenetically inhibiting these neurons during second-order associations attenuated SOC. These findings suggest that activating the US pathway in response to a learned CS plays an important role in forming the association between the old and a new CS, promoting the formation of second-order memories.
Seeing the piles of the velvet bending under our finger sliding over a tactile stimulator improves the perception of the fabric
Authors: Mouchnino Laurence , Camillieri Brigitte , Faucheu Jenny , Juganaru Mihaela , Moinon Alix , Blouin Jean , Bueno Marie-Ange 
Published: March 2024

AbstractUsing friction modulation to simulate fabrics with a tactile stimulator (i.e. virtual surface) is not sufficient to render fabric touch and even more so for hairy fabrics. We hypothesized that seeing the pile of the velvet darken or lighten depending on changes in the finger movement direction on the virtual surface should improve the velvet fabric rendering. Participants actively rubbed a tactile device or a velvet fabric looking at a screen that showed a synthesized image of a velvet which either remained static (V-static) or darkening/lightening with the direction of touch (V-moving). We showed that in V-moving condition, the touched surface was always perceived rougher, which is a descriptor of a real velvet (Experiment 1). Using electroencephalography and sources localization analyses, we found greater theta band [5-7 Hz] oscillation power in the left inferior posterior parietal lobule (PPC) in the Virtual velvet/V-moving condition as compared to both Real velvet/ V-static and Virtual velvet/V-static conditions(Experiment 2). This result is consistent with studies that give a crucial role to the left PPC for visuo-tactile binding. The greater activity of the lateral occipital area found in the Virtual velvet/V-moving condition could have contributed to the emergence of a velvet more realistic representation.
The refinement paradox and cumulative cultural evolution: collective improvement in knowledge favors conformity, blind copying and hyper-credulity
Authors: Miu Elena , Rendell Luke , Bowles Sam , Boyd Rob , Cownden Daniel , Enquist Magnus , Eriksson Kimmo , Feldman Marcus W. , Lillicrap Timothy , McElreath Richard , Murray Stuart , Ounsley James , Lala Kevin N. 
Published: March 2024

AbstractSocial learning is common in nature, yet cumulative culture (where knowledge and technology increase in complexity and diversity over time) appears restricted to humans. To understand why, we organized a computer tournament in which programmed entries specified when to learn new knowledge and when to refine (i.e. improve) existing knowledge. The tournament revealed a ‘refinement paradox’: refined behavior afforded higher payoffs as individuals converged on a small number of successful behavioral variants, but refining did not generally pay. Paradoxically, entries that refined only in certain conditions did best during behavioral improvement, while simple copying entries thrived when refinement levels were high. Cumulative cultural evolution may be rare in part because sophisticated strategies for improving knowledge and technology are initially advantageous, yet complex culture, once achieved, favors conformity, blind imitation and hyper-credulity.
Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response
Authors: Höfer Stefanie , Frasch Larissa , Putzker Kerstin , Lewis Joe , Sakhteman Amirhossein , The Matthew , Bayer Florian P. , Müller Julian , Hamood Firas , Kuster Bernhard 
Published: March 2024

AbstractThe DNA-damaging agent gemcitabine (GEM) is a first-line treatment for pancreatic cancer but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs including kinase inhibitors but the experimental evidence for such rational is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 140 clinical kinase inhibitors and observed strong synergy for the ATR inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway including phosphorylated pS468 of CHEK1 as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.
Self-organization of vascularized skeletal muscle from bovine embryonic stem cells
Authors: Sanaki-Matsumiya Marina , Villava Casandra , Rappez Luca , Haase Kristina , Wu Jun , Ebisuya Miki 
Published: March 2024

AbstractCultured beef holds promising potential as an alternative to traditional meat options. While adult stem cells are commonly used as the cell source for cultured beef, their proliferation and differentiation capacities are limited. To produce cultured beef steaks, current manufacturing plans often require the separate preparation of multiple cell types and intricate engineering for assembling them into structured tissues. In this study, we propose and report the co-induction of skeletal muscle, neuronal, and endothelial cells from bovine embryonic stem cells (ESCs) and the self-organization of tissue structures in 2- and 3-dimensional cultures. Bovine myocytes were induced in a stepwise manner through the induction of presomitic mesoderm (PSM) from bovine ESCs. Muscle fibers with sarcomeres appeared within 15 days, displaying calcium oscillations responsive to inputs from co-induced bovine spinal neurons. Bovine endothelial cells were also co-induced via PSM, forming uniform vessel networks inside tissues. Our serum-free, rapid co-induction protocols represent a milestone toward self-organizing beef steaks with integrated vasculature and innervation.
Transcriptomics and trans-organellar complementation reveal a limited signaling capacity of 12-cis-oxo-phytodienoic acid in wounded Arabidopsis
Authors: Mekkaoui Khansa , Baral Ranjit , Smith Fiona , Klein Moritz , Feussner Ivo , Hause Bettina 
Published: March 2024

Abstract12-cis-Oxo-phytodienoic acid (OPDA), the main precursor of the key plant growth and defense hormone jasmonoyl-isoleucine (JA-Ile), is believed to have distinct signaling roles in plant’s responses to stress. In Arabidopsis, insights into OPDA functions have been gained from studying a mutant, which is affected in the conversion of OPDA by missing OPDA REDUCTASE3 (OPR3).opr3mutants, however, accumulate JA-Ile through a cytosolic bypass mediated by OPR2. Therefore, wound-induced transcriptome ofopr2opr3in comparison to wild-type andallene oxide synthasemutant was analyzed to unravel OPDA signaling. Results showed that OPDA lacked a distinct transcriptional signature, whereas known OPDA-response genes were wound-induced independently of OPDA. The application of OPDA toopr2opr3resulted in a distinct transcriptional response compared to the endogenous rise of OPDA in the same mutant, with the activation of the sulfur assimilation pathway genes occurring only with the external application of the compound. These findings suggested a compartmentalization of endogenously produced OPDA, investigated further through trans-organellar complementation. OPR3 complementedopr2opr3mutants in fertility and wound-induced JA-Ile production regardless of its localization. Sincein vitroenzymatic studies revealed OPR3’s activity on both OPDA and 4,5-ddh-JA, conclusions on translocation of OPDA were not unequivocal. Dissecting the conversion of either OPDA or 4,5-ddh-JA by OPR2 and OPR1 organelle variants pointed, however, to a strong OPDA compartmentalization supporting its lacking signaling function.
Shifting Geographical Transmission Patterns: Characterizing the 2023 Fatal Dengue Outbreak in Bangladesh
Authors: Hasan Mohammad Nayeem , Rahman Mahbubur , Uddin Meraj , Ashrafi Shah Ali Akbar , Rahman Kazi Mizanur , Paul Kishor Kumar , Sarker Mohammad Ferdous Rahman , Haque Farhana , Sharma Avinash , Papakonstantinou Danai , Paudyal Priyamvada , Asaduzzaman Md , Zumla Alimuddin , Haider Najmul 
Published: March 2024

AbstractIn 2023, Bangladesh experienced its largest and deadliest outbreak of Dengue virus (DENV), reporting the highest-ever recorded annual cases and deaths. We aimed to characterize the geographical transmission of the DENV in Bangladesh. From 1 Jan – 31 Dec 2023, we extracted and analyzed daily data on dengue cases and deaths from the national Management Information System (MIS). We performed a generalized linear mixed model to identify the associations between division-wise daily dengue counts and various geographical and meteorological covariates. The number of Dengue cases reported in 2023 was 1.3 times higher than the total number recorded in the past 23 years (321,179 vs. 244,246), with twice as many deaths than the total fatalities recorded in the past 23 years (1705 vs. 849). Of the 1705 deaths in 2023, 67.4% (n=1015) expired within one day after hospital admission. The divisions southern to Dhaka had a higher dengue incidence/1000 population (2.30 vs. 0.50, p<0,0.01), and higher mean annual temperatures (27.46 vs. 26.54 °C) than the northern divisions. The average daily temperature (IRR: 1.13, 95% CI: 1.11-1.14), urban and rural population ratio of the divisions (IRR: 1.04, 95% CI: 1.03-1.04), showed a positive, and rainfall (IRR: 0.99, 95% CI: 0.98-0.99) showed a negative association with dengue cases in each division. We observed a major geographical shift of Dengue cases from the capital city Dhaka to different districts of Bangladesh with a higher incidence of dengue in the southern division of Bangladesh, influenced by temperature and urbanization.
Enhancing patient stratification and interpretability through class-contrastive and feature attribution techniques
Authors: Olowu Sharday , Lawrence Neil , Banerjee Soumya 
Published: March 2024

AbstractA crucial component of the treatment of genetic disorders is identifying and characterising the genes and gene modules that drive disease processes. Recent advances in Next-Generation Sequencing (NGS) improve the prospects for achieving this goal. However, many machine learning techniques are not explainable and fail to account for gene correlations. In this work, we develop a comprehensive set of explainable machine learning techniques to perform patient stratification for inflammatory bowel disease. We focus on Crohn’s disease (CD) and its subtypes: CD with deep ulcer, CD without deep ulcer and IBD-controls. We produce an interpretable probabilistic model over disease subtypes using Gaussian Mixture Modelling. We then apply class-contrastive and feature-attribution techniques to identify potential target genes and modules. We modify the widely used kernelSHAP (Shapley Additive Explanations) algorithm to account for gene correlations. We obtain relevant gene modules for each disease subtype. We develop a class-contrastive technique to visually explain why a particular patient is predicted to have a particular subtype of the disease. We show that our results are relevant to the disease through Gene Ontology enrichment analysis and a review of the literature. We also uncover some novel findings, including currently uncharacterised genes. These approaches maybe beneficial, in personalised medicine, to inform decision-making regarding the diagnosis and treatment of genetic disorders. Our approach is model-agnostic and can potentially be applied to other diseases and domains where explainability and feature correlations are important.
Quality of Care at childbirth during the COVID-19 pandemic: findings of the IMAgiNE EURO study in Belgium
Authors: Galle Anna , D’Hauwers Silke , Berghman Helga , Vaerewijck Nele , Valente Emanuelle Pessa , Mariani Ilaria , Bomben Arianna , Vedove Stefano delle , Lazzerini Marza ,   the IMAgiNE EURO Study Group
Published: March 2024

ObjectivesTo examine quality of maternal and newborn care (QMNC) around childbirth in facilities in Belgium during the COVID-19 pandemic and trends over time.DesignA cross-sectional observational study.SettingData of the IMAgiNE EURO study in Belgium. ParticipantsWomen giving birth in a Belgian facility from March 1, 2020, to May 1, 2023, responded a validated online questionnaire based on 40 WHO standards-based quality measures organised in four domains: provision of care, experience of care, availability of resources, and organizational changes related to COVID-19.Primary and secondary outcome measuresQuantile regression analysis was performed to assess predictors of QMNC; trends over time were tested with the Mann-Kendall test.Results897 women were included in the analysis, 67%(n=601) with spontaneous vaginal birth, 13.3%(n=119) with instrumental vaginal birth and 19.7%(n=177) with cesarean section. We found high QMNC scores but also specific gaps in all domains of QMNC. On provision of care, 21.0%(n=166) of women who experienced labor and 14.7%(n=26) of women with a cesarean reported inadequate pain relief; 64.7%(n=74) of women with an instrumental birth reported fundal pressure and 72.3% (n=86) reported that forceps or vacuum cup was used without their consent. On experience of care, 31.1%(n=279) reported unclear communication, 32.9%(n=295) reported that they were not involved in choices,11.5%(n=104) stated not being treated with dignity and 8.1%(n=73) experienced abuse. Related to resources, almost half of the women reported an inadequate number of healthcare professionals (46.2%, n=414). The multivariable analyses showed significantly lower QMNC scores for women with an instrumental vaginal birth. Over time there was a significant increase in QMNC score for ‘experience of care’ and ‘key organizational changes due to COVID-19’.Conclusions and relevanceAlthough overall QMNC scores were high, findings also suggest gaps in QMNC. Underlying causes of these gaps should be explored to design appropriate interventions and policies.
Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition
Authors: Thoumas Jean-Louis , Cavaroc Amandine , Sery Damien , Leulier François , Vadder Filipe De 
Published: March 2024

AbstractBackgroundEarly life, particularly after weaning, is the most rapid period of growth in mammals, and this growth is highly dependent on adequate nutrition. Protein-energy malnutrition (PEM) during this critical window can lead to stunting and wasting, which have long-term health consequences.ObjectiveThis study aimed to develop a mouse model of juvenile PEM to assess the effects of refeeding with various diets and interventions on growth recovery, including the impact of probiotic supplementation and suboptimal refeeding diets.MethodsJuvenile C57Bl/6J mice were fed a low-protein diet (LPD, 5% kcal from protein) starting at postnatal day 14 (P14) to induce malnutrition. Following weaning, both male and female mice were refed an optimal diet (Altromin 1310, 27% kcal from protein) at different times ranging from P28 to P56. In a second intervention, male mice were supplemented during refeeding withLactiplantibacillus plantarumWJL (LpWJL), a probiotic known to stimulate growth in malnourished conditions. A final group of malnourished male mice were refed with a Western diet (WD, 34.5% kcal from fat; 15.3% kcal from protein) or a modified Western diet (MWD, 34.2% kcal from fat; 7.5% kcal from protein) to model suboptimal refeeding.ResultsRefeeding with an optimal diet fully restored growth in female mice, but male mice exhibited persistent stunting despite nutritional rehabilitation. LpWJLtreatment during refeeding did not enhance systemic growth in males. In contrast, refeeding with WD or MWD restored body length but impaired glucose metabolism, particularly in mice refed MWD after PEM. LpWJLexacerbated glucose intolerance in the suboptimal refeeding groups.ConclusionSex-dependent differences exist in the recovery from early-life malnutrition, with males showing incomplete growth recovery despite optimal refeeding. Suboptimal diets, while compensating for stunting, impair glucose metabolism, especially when protein intake is insufficient. Probiotic supplementation with LpWJLdid not improve growth outcomes.
Profiling trace organic chemical biotransformation genes, enzymes and associated bacteria in microbial model communities
Authors: Cao Lijia , Garcia Sarahi L. , Wurzbacher Christian 
Published: March 2024

AbstractMicrobial biotransformation of trace organic chemicals (TOrCs) is an essential process in wastewater treatment for eliminating environmental pollution. Understanding of TOrC biotransformation mechanisms, especially at their original concentrations, is important to optimize treatment performance, whereas our current knowledge is limited. Here we investigated the biotransformation of seven TOrCs by 24 model communities. The genome-centric analyses unraveled the biotransformation drivers concerning functional genes and enzymes and responsible bacteria. We obtained efficient model communities for complete removal on ibuprofen, caffeine and atenolol, and the transformation efficiencies for sulfamethoxazole, carbamazepine, trimethoprim and gabapentin were 0-45%. Biotransformation performance was not fully reflected by the presence of known biotransformation genes and enzymes. However, functional similar homologs to existing biotransformation genes and enzymes (e.g., long-chain-fatty-acid-CoA ligase encoded byfadDandfadD13gene, acyl-CoA dehydrogenase encoded byfadE12gene) could play critical roles in TOrC metabolism. Finally, we identified previously undescribed degrading strains, e.g.,Rhodococcus qingshengiifor caffeine, carbamazepine, sulfamethoxazole and ibuprofen biotransformation, and potential transformation enzymes, e.g., SDR family oxidoreductase targeting sulfamethoxazole and putative hypothetical proteins for caffeine, atenolol and gabapentin biotransformation.