bluuebunny/crossref_metadata_2025 huggingface dataset:
Extremism and Terrorism: Rebel Goals and Tactics in Civil Wars
Authors: Joyce Renanah Miles , Fortna Virginia Page
Published: May 2024

Extremism and terrorism are thought to go hand in hand in civil wars. Yet do they? Are rebel groups with more extreme goals more likely than moderate ones to use terrorism, as commonly assumed? Arguments linking extremism to terrorism are often circular: groups are tagged as extremist because they do extreme things. Our article addresses this problem by articulating a novel conceptualization of extremism as the distance of group goals from the status quo. Understanding the relationship between what groups want and how they try to achieve it has obvious theoretical and policy implications. We theorize mechanisms that might connect extremist goals to terrorism and use new data on rebel group aims in civil wars from 1970 to 2013 to examine the empirical relationship between extremism and terrorism in a nontautological way. The results show that some extremist goals are associated with terrorism but not others. Groups with goals that involve changing the political ideology of the state or transforming political power across identity groups are more likely to use terrorism or to use more of it. Secessionist groups, however, are no more likely to produce terrorism than are those with less extreme territorial aims such as autonomy.
Socialized mitochondria: mitonuclear crosstalk in stress
Authors: Kim Kyung Hwa , Lee Cho Bi
Published: May 2024

Traditionally, mitochondria are considered sites of energy production. However, recent studies have suggested that mitochondria are signaling organelles that are involved in intracellular interactions with other organelles. Remarkably, stressed mitochondria appear to induce a beneficial response that restores mitochondrial function and cellular homeostasis. These mitochondrial stress-centered signaling pathways have been rapidly elucidated in multiple organisms. In this review, we examine current perspectives on how mitochondria communicate with the rest of the cell, highlighting mitochondria-to-nucleus (mitonuclear) communication under various stresses. Our understanding of mitochondria as signaling organelles may provide new insights into disease susceptibility and lifespan extension.
Stress-induced epinephrine promotes hepatocellular carcinoma progression via the USP10-PLAGL2 signaling loop
Authors: Wang Chen , Ni Jiaping , Zhai Dongqing , Xu Yanchao , Wu Zijie , Chen Yuyuan , Liu Ning , Du Juan , Shen Yumeng , Liu Guilai , Yang Yong , You Linjun , Hu Weiwei
Published: May 2024

Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.
Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches
Authors: Ji Zhongyin , Li Jie , Tao Siyue , Li Hui , Kong Xiangxi , Huang Bao , Feng Zhenhua , Wei Xiaoan , Zheng Zeyu , Chen Jian , Chen Binhui , Liu Junhui , Zhao Fengdong
Published: May 2024

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KITW-SH/W-SH) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.
Factors that determine patients considering medication for the disease of obesity: an IMI2 SOPHIA study
Authors: Craig H. C. , Alsaeed D. , Heneghan H. , Al-Najim W. , Al Ozairi E. , le Roux C. W.
Published: May 2024

Objective

Obesity-related problems can now be managed with effective nutritional therapy, pharmacotherapy, and surgeries that achieve >10% weight loss. Assessing patient preferences, treatment choices, and factors affecting patients can improve treatment compliance and efficacy. Our aim was to identify factors affecting patient preference and subsequent choice of pharmacotherapy among those seeking treatment for obesity-related disorders.

Methods

A participatory action study using purposeful sampling recruited 33 patients with obesity complications. They were referred to specialist clinics in non-alcoholic fatty liver disease, diabetes mellitus, hypertension, and chronic kidney disease. Sixteen males and seventeen females aged 18–70 years, with BMI > 35 kg/m2 were recruited. Before the interview, participants watched a 60-minute video explaining nutritional therapy, pharmacotherapy, and surgery in equipoise. Data were collected in semi-structured interviews; Reflective thematic analysis was used. This sub study focuses only on patients who expressed specific attitudes (positive or negative) towards pharmacotherapy.

Results

Ten (30%) patients expressed a view on pharmacotherapy. Eight (24%) patients chose pharmacotherapy alone, whereas two (6%) patients chose pharmacotherapy combined with nutritional therapy. In this sub study focusing on pharmacotherapy, five themes were identified related to choosing whether or not to take medication: (1) attitudes towards pharmacotherapy, (2) attitudes toward size of obesity and its complications, (3) weighing the benefits and risks of treatment, (4) knowledge and reassurance of health professionals, and (5) costs associated with drug therapy.

Conclusion

The primary concerns regarding pharmacotherapy for intentional weight loss were efficacy, side effects, lifelong dosing, pharmacokinetics, and cost. Providing access to information about all the pharmacotherapies and the benefits is likely to result in greater penetrance of treatment.
The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression
Authors: Flinkenflügel Kira , Gruber Marius , Meinert Susanne , Thiel Katharina , Winter Alexandra , Goltermann Janik , Usemann Paula , Brosch Katharina , Stein Frederike , Thomas-Odenthal Florian , Wroblewski Adrian , Pfarr Julia-Katharina , David Friederike S. , Beins Eva C. , Grotegerd Dominik , Hahn Tim , Leehr Elisabeth J. , Dohm Katharina , Bauer Jochen , Forstner Andreas J. , Nöthen Markus M. , Jamalabadi Hamidreza , Straube Benjamin , Alexander Nina , Jansen Andreas , Witt Stephanie H. , Rietschel Marcella , Nenadić Igor , van den Heuvel Martijn P. , Kircher Tilo , Repple Jonathan , Dannlowski Udo
Published: May 2024

Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients. Processing speed performance of n = 284 acutely depressed, n = 177 partially and n = 198 fully remitted patients, and n = 743 healthy controls (HC) was estimated based on five neuropsychological tests. Network-based statistic was used to identify a brain network associated with processing speed. We employed general linear models to examine the association between TNF-α PGS and processing speed. We investigated whether network connectivity mediates the association between TNF-α PGS and processing speed. We identified a structural network positively associated with processing speed in the whole sample. We observed a significant negative association between TNF-α PGS and processing speed in acutely depressed patients, whereas no association was found in remitted patients and HC. The mediation analysis revealed that brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD. The present study provides evidence that TNF-α PGS is associated with decreased processing speed exclusively in patients with acute depression. This association was partially mediated by structural brain connectivity. Using multimodal data, the current findings advance our understanding of cognitive dysfunction in MDD and highlight the involvement of genetic-immunological processes in its pathomechanisms.
New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity
Authors: Ruan Yuan , Yuan Ruolan , He Jiaqi , Jiang Yutong , Chu Shifeng , Chen Naihong
Published: May 2024

Depression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine and psilocybin gained attention as potential sustained antidepressants. Review of recent studies highlights that synaptic plasticity changes as key events of downstream long-lasting changes in sustained antidepressant effect. This underscores the significance of synaptic plasticity in sustained antidepressant effect. Moreover, neurexins, key molecules involved in the regulation of synaptic plasticity, act as critical links between synaptic plasticity and sustained antidepressant effects, involving mechanisms including protein level, selective splicing, epigenetics, astrocytes, positional redistribution and protein structure. Based on the regulation of synaptic plasticity by neurexins, several drugs with potential for sustained antidepressant effect are also discussed. Focusing on neurexins in regulating synaptic plasticity promises much for further understanding underlying mechanisms of sustained antidepressant and the next step in new drug development. This research represents a highly promising future research direction.
Mixed-methods evaluation of an enhanced asthma biologics clinical pathway in the West Midlands UK
Authors: Damery Sarah , Jones Janet , Idris Elfatih , Cooper Angela , Minshall Holly , Clowes Chris , Jolly Kate
Published: May 2024

Biologic treatments can alleviate severe asthma symptoms and reduce health service use. However, service capacity limits and low referral rates from primary care indicate unmet patient need. We report a mixed-methods evaluation of an enhanced severe asthma pathway implemented in Staffordshire and Stoke-on-Trent, UK which aimed to optimise primary care referrals through training/education, and increased capacity in specialist clinics. Quantitative analysis assessed patient wait times between pathway stages, prescribing changes, exacerbations, hospital admissions and asthma control. Interviews with 12 stakeholders evaluated perceptions of the enhanced pathway across settings. In 12 months, 564 patients from 28 general practices were reviewed for biologics eligibility, of whom 125 (22.2%) were referred for specialist assessment. Wait times were significantly lower under the enhanced pathway when compared against historic patients following the standard pathway, and reduced overall from a mean of 76.4 to 26.7 weeks between referral and biologics initiation (p < 0.001). Patients commencing biologics (n = 46) showed significantly reduced reliever inhaler prescribing rates (p = 0.037), 60% lower oral steroid use (p < 0.001), significantly reduced exacerbation rates (p < 0.001) and fewer hospital admissions (p < 0.001) compared with the 12 months pre-treatment. Mean asthma control scores reduced from 3.13 pre-initiation to 1.89 post-initiation (p < 0.001) – a clinically significant improvement. Interviewees viewed the enhanced pathway positively, although ongoing issues related to difficulties engaging primary care amid concerns around increased workloads and pathway capacity. The large number of referrals generated from a comparatively small number of general practices confirms substantial unmet need that an enhanced severe asthma pathway could help address if implemented routinely.
Frequent disturbances enhanced the resilience of past human populations
Authors: Riris Philip , Silva Fabio , Crema Enrico , Palmisano Alessio , Robinson Erick , Siegel Peter E. , French Jennifer C. , Jørgensen Erlend Kirkeng , Maezumi Shira Yoshi , Solheim Steinar , Bates Jennifer , Davies Benjamin , Oh Yongje , Ren Xiaolin
Published: May 2024

The record of past human adaptations provides crucial lessons for guiding responses to crises in the future1–3. To date, there have been no systematic global comparisons of humans’ ability to absorb and recover from disturbances through time4,5. Here we synthesized resilience across a broad sample of prehistoric population time–frequency data, spanning 30,000 years of human history. Cross-sectional and longitudinal analyses of population decline show that frequent disturbances enhance a population’s capacity to resist and recover from later downturns. Land-use patterns are important mediators of the strength of this positive association: farming and herding societies are more vulnerable but also more resilient overall. The results show that important trade-offs exist when adopting new or alternative land-use strategies.
Multimodal decoding of human liver regeneration
Authors: Matchett K. P. , Wilson-Kanamori J. R. , Portman J. R. , Kapourani C. A. , Fercoq F. , May S. , Zajdel E. , Beltran M. , Sutherland E. F. , Mackey J. B. G. , Brice M. , Wilson G. C. , Wallace S. J. , Kitto L. , Younger N. T. , Dobie R. , Mole D. J. , Oniscu G. C. , Wigmore S. J. , Ramachandran P. , Vallejos C. A. , Carragher N. O. , Saeidinejad M. M. , Quaglia A. , Jalan R. , Simpson K. J. , Kendall T. J. , Rule J. A. , Lee W. M. , Hoare M. , Weston C. J. , Marioni J. C. , Teichmann S. A. , Bird T. G. , Carlin L. M. , Henderson N. C.
Published: May 2024

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3–5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut–liver barrier may advance new areas of therapeutic discovery in regenerative medicine.
A body–brain circuit that regulates body inflammatory responses
Authors: Jin Hao , Li Mengtong , Jeong Eric , Castro-Martinez Felipe , Zuker Charles S.
Published: May 2024

The body–brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4–6. Here we show that a peripheral immune insult strongly activates the body–brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body–brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.
Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors
Authors: Mondragón-González Sirenia Lizbeth , Schreiweis Christiane , Burguière Eric
Published: May 2024

Compulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming—a behavioral metric of compulsive-like behavior—in male Sapap3 knockout mice (Sapap3-KO). Continuous optogenetic activation of PVIs in striatal areas receiving input from the lateral orbitofrontal cortex reduced self-grooming events in Sapap3-KO mice to wild-type levels. Aiming to shorten the critical time window for PVI recruitment, we then provided real-time closed-loop optogenetic stimulation of striatal PVIs, using a transient power increase in the 1–4 Hz frequency band in the orbitofrontal cortex as a predictive biomarker of grooming onsets. Targeted closed-loop stimulation at grooming onsets was as effective as continuous stimulation in reducing grooming events but required 87% less stimulation time, paving the way for adaptive stimulation therapeutic protocols.
Mannose-binding lectin gene sequence data in Kelantan population
Authors: Zahidin Muhamad Aidil , Mohd Noor Noor Haslina , Johan Muhammad Farid , Abdullah Abu Dzarr , Zulkafli Zefarina , Edinur Hisham Atan
Published: May 2024

The human mannose-binding lectin (MBL) gene encodes a polymorphic protein that plays a crucial role in the innate immune response. Human MBL deficiency is associated with immunodeficiencies, and its variants have been linked to autoimmune and infectious diseases. Despite this significance, gene studies concerning MBL sequencing are uncommon in Malaysia. Therefore, we aimed to preliminary described the human MBL sequencing dataset based on the Kelantan population. Blood samples were collected from 30 unrelated individuals and underwent DNA extraction, genotyping, and sequencing. The sequencing data generated 886 bp, which were deposited in GenBank (ON619541-ON619546). Allelic variants were identified and translated into six MBL haplotypes: HYPA, HYPB, LYPB, LXPB, HXPA, and LXPA. An evolutionary tree was constructed using the haplotype sequences. These findings contribute to the expansion of MBL information within the country, providing a valuable baseline for future research exploring the association between the gene and targeted diseases.
Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair
Authors: Zhang Qiang , Zhang Yu , Chen Hui , Sun Lei-Na , Zhang Bin , Yue Dong-Sheng , Wang Chang-Li , Zhang Zhen-Fa
Published: May 2024

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.
Synthesis, characterization, biological potency, and molecular docking of Co2+, Ni2+ and Cu2+ complexes of a benzoyl isothiocyanate based ligand
Authors: Al-Farraj Eida S. , Younis Adel M. , El-Reash Gaber M. I. Abu
Published: May 2024

The primary objective of the present study was to produce metal complexes of H4DAP ligand (N,N'-((pyridine-2,6-diylbis(azanediyl))bis(carbonothioyl))dibenzamide) derived from 2,6-diaminopyridine and benzoyl isothiocyanate with either ML or M2L stoichiometry. There are three distinct coordination complexes obtained with the formulas [Co(H2DAP)]·H2O, [Ni2(H2DAP)Cl2(H2O)2]·H2O, and [Cu(H4DAP)Cl2]·3H2O. The confirmation of the structures of all derivatives was achieved through the utilization of several analytical techniques, including FT-IR, UV–Vis, NMR, GC–MS, PXRD, SEM, TEM analysis, and QM calculations. Aiming to analyze various noncovalent interactions, topological methods such as QTAIM, NCI, ELF, and LOL were performed. Furthermore, the capacity of metal–ligand binding was examined by fluorescence emission spectroscopy. An in vitro investigation showed that the viability of MDA-MB-231 and HepG-2 cells was lower when exposed to the manufactured Cu2+ complex, in comparison to the normal cis-platin medication. The compounds were further evaluated for their in vitro antibacterial activity. The Ni2+ complex has shown promising activity against all tested pathogens, comparable to the reference drugs Gentamycin and Ketoconazole. Furthermore, a computational docking investigation was conducted to further examine the orientation, interaction, and conformation of the recently created compounds on the active site of the Bcl-2 protein.
Forecasting the spread of COVID-19 based on policy, vaccination, and Omicron data
Authors: Han Kyulhee , Lee Bogyeom , Lee Doeun , Heo Gyujin , Oh Jooha , Lee Seoyoung , Apio Catherine , Park Taesung
Published: May 2024

The COVID-19 pandemic caused by the novel SARS-COV-2 virus poses a great risk to the world. During the COVID-19 pandemic, observing and forecasting several important indicators of the epidemic (like new confirmed cases, new cases in intensive care unit, and new deaths for each day) helped prepare the appropriate response (e.g., creating additional intensive care unit beds, and implementing strict interventions). Various predictive models and predictor variables have been used to forecast these indicators. However, the impact of prediction models and predictor variables on forecasting performance has not been systematically well analyzed. Here, we compared the forecasting performance using a linear mixed model in terms of prediction models (mathematical, statistical, and AI/machine learning models) and predictor variables (vaccination rate, stringency index, and Omicron variant rate) for seven selected countries with the highest vaccination rates. We decided on our best models based on the Bayesian Information Criterion (BIC) and analyzed the significance of each predictor. Simple models were preferred. The selection of the best prediction models and the use of Omicron variant rate were considered essential in improving prediction accuracies. For the test data period before Omicron variant emergence, the selection of the best models was the most significant factor in improving prediction accuracy. For the test period after Omicron emergence, Omicron variant rate use was considered essential in deciding forecasting accuracy. For prediction models, ARIMA, lightGBM, and TSGLM generally performed well in both test periods. Linear mixed models with country as a random effect has proven that the choice of prediction models and the use of Omicron data was significant in determining forecasting accuracies for the highly vaccinated countries. Relatively simple models, fit with either prediction model or Omicron data, produced best results in enhancing forecasting accuracies with test data.
Transcriptome analysis of cardiac endothelial cells after myocardial infarction reveals temporal changes and long-term deficits
Authors: Basu Chitra , Cannon Presley L. , Awgulewitsch Cassandra P. , Galindo Cristi L. , Gamazon Eric R. , Hatzopoulos Antonis K.
Published: May 2024

Endothelial cells (ECs) have essential roles in cardiac tissue repair after myocardial infarction (MI). To establish stage-specific and long-term effects of the ischemic injury on cardiac ECs, we analyzed their transcriptome at landmark time points after MI in mice. We found that early EC response at Day 2 post-MI centered on metabolic changes, acquisition of proinflammatory phenotypes, initiation of the S phase of cell cycle, and activation of stress-response pathways, followed by progression to mitosis (M/G2 phase) and acquisition of proangiogenic and mesenchymal properties during scar formation at Day 7. In contrast, genes involved in vascular physiology and maintenance of vascular tone were suppressed. Importantly, ECs did not return to pre-injury phenotypes after repair has been completed but maintained inflammatory, fibrotic and thrombotic characteristics and lost circadian rhythmicity. We discovered that the highest induced transcript is the mammalian-specific Sh2d5 gene that promoted migration and invasion of ECs through Rac1 GTPase. Our results revealed a synchronized, temporal activation of disease phenotypes, metabolic pathways, and proliferation in quiescent ECs after MI, indicating that precisely-timed interventions are necessary to optimize cardiac tissue repair and improve outcomes. Furthermore, long-term effects of acute ischemic injury on ECs may contribute to vascular dysfunction and development of heart failure.
Age- and sex-related changes in vertebral trabecular bone architecture in Neolithic and Mediaeval populations from Poland
Authors: Galassi Francesco Maria , Lorkiewicz Wiesław , Filipiak Jarosław , Nikodem Anna , Żądzińska Elżbieta
Published: May 2024

This paper investigates trabecular bone ontogenetic changes in two different Polish populations, one prehistoric and the other historical. The studied populations are from the Brześć Kujawski region in Kujawy (north-central Poland), one from the Neolithic Period (4500–4000 BC) and one from the Middle Ages (twelfth-sixteenth centuries AD), in total 62 vertebral specimens (32 males, 30 females). Eight morphometric parameters acquired from microCT scan images were analysed. Two-way ANOVA after Box-Cox transformation and multifactorial regression model were calculated. A significant decrease in percentage bone volume fraction (BV/TV; [%]) with age at death was observed in the studied sample; Tb.N (trabecular number) was also significantly decreased with age; trabecular separation (Tb.Sp) increased with advancing age; connectivity density (Conn.D) was negatively correlated with biological age and higher in the Neolithic population. These data are found to be compatible with data from the current biomedical literature, while no loss of horizontal trabeculae was recorded as would be expected based on modern osteoporosis.
Zika emergence, persistence, and transmission rate in Colombia: a nationwide application of a space-time Markov switching model
Authors: Picinini Freitas Laís , Douwes-Schultz Dirk , Schmidt Alexandra M. , Ávila Monsalve Brayan , Salazar Flórez Jorge Emilio , García-Balaguera César , Restrepo Berta N. , Jaramillo-Ramirez Gloria I. , Carabali Mabel , Zinszer Kate
Published: May 2024

Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika’s emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes-borne diseases.
Computing the effects of temperature and osmotic stress on the seed germination of Helianthus annuus L. by using a mathematical model
Authors: Javid Maryam , Ullah Sami , Amin Fazal , Shah Wadood , Malik Tabarak , Alwahibi Mona S. , Waheed Abdul , Ercisli Sezai , Ali Baber
Published: May 2024

An extremely important oil crop in the world, Helianthus annuus L. is one of the world's most significant members of the Asteraceae family. The rate and extent of seed germination and agronomic features are consistently affecting  by temperature (T) and changes in water potential (ψ). A broad hydrothermal time model with T and ψ components could explain sunflower responses over suboptimal T and ψ. A lab experiment was performed using the HTT model to discover both T and ψ and their interactive effects on sunflower germination and also to figure  out the cardinal Ts values. The sunflower seeds were germinated at temperatures (15 °C, 20 °C, 25 °C and 30 °C); each Ts had five constant ψs of 0, 0.3, 0.6, 0.9, and 1.2 MPa via PEG 6000 as osmotic stress inducer. The results revealed that highest germination index was found in seed grown at 20 °C in distilled water (0 MPa) and the lowest at 30 °C with osmotic stress of (− 1.2 MPa). The highest value of germination rate index was found in seed grown at 20 °C in distilled water (0 MPa) and the lowest at 15 °C with an osmotic stress of (− 1.2 MPa). In conclusion, water potential, temperature, and their interactions have a considerable impact on seed germination rate, and other metrics (GI, SVI-I, GRI, GE, SVI-II, and MGT). Seeds sown  at 20 °C with zero water potential showed high germination metrics such as GE, GP, GRI, and T50%. The maximum value to TTsub noted at 30 °C in − 0.9 MPa osmotic stress and the minimum value was calculated at 15 °C in − 1.2 MPa osmotic stress. The result of TTsupra recorded highest at 15 °C in  controlled group (0 MPa). Moreover, θH was  highest at 30 °C in controlled condition (0 MPa) and minimum value was observed at  20 °C under − 1.2 MPa osmotic stress. The value of θHTT were  maximum at  30 °C in controlled group (0 MPa) and minimum value was  recorded at 15 °C under − 1.2 MPa osmotic potential. The base, optimum and ceiling temperatures for sunflower germination metrics in this experiment were noted  6.8, 20 and 30 °C respectively.
Structural monitoring data repair based on a long short-term memory neural network
Authors: Panfeng Ba , Songlin Zhu , Hongyu Chai , Caiwei Liu , Pengtao Wu , Lichang Qi
Published: May 2024

As construction technology and project management develop, structural monitoring systems become increasingly important for ensuring large-span spatial structure safety during construction and operation. However, most of the sensors and monitoring equipment in monitoring systems are poorly serviced, resulting in frequent abnormal monitoring data, which directly leads to challenges in data analysis and structural safety assessment. In this paper, a structural response recovery method based on a long short-term memory (LSTM) neural network is proposed by studying the autocorrelation of data and the spatial correlations among data at multiple measurement points. The effectiveness and robustness of the proposed method are verified using the monitored stress data for a grid structure jacking construction process, and the influence of different data loss rates on the recovery accuracy is analysed. The recovery models are compared using a support vector machine and a Multi-Layer Perception (MLP) neural network. The proposed method can effectively restore missing data; notably, the MSE index is 0.6, and the MAPE is below 15%. The data restoration method based on the LSTM neural network is more accurate than the traditional method. Finally, the repair applicability of various types of monitored data is verified using the monitoring data from Hall F of Qingdao Jiao-dong International Airport under typhoon conditions.
High clonal diversity of Staphylococcus aureus isolates from children’s playgrounds in Hungary
Authors: Horváth Andrea , Tormássi Áron , Hajósi-Kalcakosz Szofia , Huber Annamária , Sahin-Tóth Judit , Dobay Orsolya
Published: May 2024

Staphylococcus aureus is one of the most important human pathogenic bacteria and environmental surfaces play an important role in the spread of the bacterium. Presence of S. aureus on children’s playgrounds and on toys was described in international studies, however, little is known about the prevalence and characteristics of S. aureus at playgrounds in Europe. In this study, 355 samples were collected from playgrounds from 16 cities in Hungary. Antibiotic susceptibility of the isolates was tested for nine antibiotics. Presence of virulence factors was detected by PCR. Clonal diversity of the isolates was tested by PFGE and MLST. The overall prevalence of S. aureus was 2.81% (10/355) and no MRSA isolates were found. Presence of spa (10), fnbA (10), fnbB (5), icaA (8), cna (7), sea (2), hla (10), hlb (2) and hlg (6) virulence genes were detected. The isolates had diverse PFGE pulsotypes. With MLST, we have detected isolates belonging to ST8 (CC8), ST22 (CC22), ST944 and ST182 (CC182), ST398 (CC398), ST6609 (CC45), ST3029 and ST2816. We have identified a new sequence type, ST6609 of CC45. S. aureus isolates are present on Hungarian playgrounds, especially on plastic surfaces. The isolates were clonally diverse and showed resistance to commonly used antibiotics. These data reinforce the importance of the outdoor environment in the spread for S. aureus in the community.
Global hyperperfusion after successful endovascular thrombectomy is linked to worse outcome in acute ischemic stroke
Authors: Yang Wookjin , Kim Jeong-Min , Sohn Chul-Ho , Chung Matthew , Kim Youngjoon , Ha Jiyeon , Kang Dong-Wan , Lee Eung-Joon , Jeong Han-Yeong , Jung Keun-Hwa , Lee Seung-Hoon
Published: May 2024

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3–132.7] vs. 13.5 [5.0–34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1–4] vs. 2 [0–3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: β = 0.176, p = 0.034; direct effect: β = 0.045, p = 0.64; indirect effect: β = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.
Evaluating carbon stocks in soils of fragmented Brazilian Atlantic Forests (BAF) based on soil features and different methodologies
Authors: Guerrini Iraê Amaral , da Silva Jaqueline Pinheiro , Lozano Sivisaca Deicy Carolina , de Moraes Felipe Góes , Puglla Celso Anibal Yaguana , de Melo Silva Neto Carlos , Barroca Silva Rafael , Pereira Justino Sérvio Túlio , Roder Ludmila Ribeiro , James Jason Nathaniel , Capra Gian Franco , Ganga Antonio
Published: May 2024

Brazil’s Atlantic Forest (BAF) is a highly fragmented, strategic environmental and socio-economic region that represents the fourth biodiversity hotspot while also producing many commodities that are exported globally. Human disturbance plays a pivotal role as a driver of BAF’s soil dynamics and behaviors. The soils under Late Primary and Secondary Semideciduous Seasonal Forests (LPSF and LSSF) were characterized by high to moderate resilience, with improved chemical properties as human disturbance decreased. The Transitional Forest to Cerrado (TFC) had the worst soil conditions. Disturbed Primary and Secondary Semideciduous Seasonal Forests (DPSF and DSSF) represent a transitional stage between LPSF/LSSF and TFC. Accordingly, SOCs stocks increased from TFC << DPSF, DSSF < LPSF, LSSF. In BAF soils, to avoid unreliable data, SOCs measurements should be (i) conducted to at least 1 m soil depth and (ii) quantified with a CHN analyzer. Human disturbance strongly affected the positive feedback between vegetation succession, SOCs, and soil nutrition. Soil development decreased as human disturbance increased, thus negatively affecting SOCs. Soils in the BAF require a long time to recover after the end of human disturbance, thus suggesting that preservation strategies should be prioritized in remnant BAF fragments.
Genetic-based patient stratification in Alzheimer’s disease
Authors: Hernández-Lorenzo Laura , García-Gutiérrez Fernando , Solbas-Casajús Ana , Corrochano Silvia , Matías-Guiu Jordi A. , Ayala Jose L.
Published: May 2024

Alzheimer's disease (AD) shows a high pathological and symptomatological heterogeneity. To study this heterogeneity, we have developed a patient stratification technique based on one of the most significant risk factors for the development of AD: genetics. We addressed this challenge by including network biology concepts, mapping genetic variants data into a brain-specific protein–protein interaction (PPI) network, and obtaining individualized PPI scores that we then used as input for a clustering technique. We then phenotyped each obtained cluster regarding genetics, sociodemographics, biomarkers, fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, and neurocognitive assessments. We found three clusters defined mainly by genetic variants found in MAPT, APP, and APOE, considering known variants associated with AD and other neurodegenerative disease genetic architectures. Profiling of these clusters revealed minimal variation in AD symptoms and pathology, suggesting different biological mechanisms may activate the neurodegeneration and pathobiological patterns behind AD and result in similar clinical and pathological presentations, even a shared disease diagnosis. Lastly, our research highlighted MAPT, APP, and APOE as key genes where these genetic distinctions manifest, suggesting them as potential targets for personalized drug development strategies to address each AD subgroup individually.
Novel applications of Convolutional Neural Networks in the age of Transformers
Authors: Ersavas Tansel , Smith Martin A. , Mattick John S.
Published: May 2024

Convolutional Neural Networks (CNNs) have been central to the Deep Learning revolution and played a key role in initiating the new age of Artificial Intelligence. However, in recent years newer architectures such as Transformers have dominated both research and practical applications. While CNNs still play critical roles in many of the newer developments such as Generative AI, they are far from being thoroughly understood and utilised to their full potential. Here we show that CNNs can recognise patterns in images with scattered pixels and can be used to analyse complex datasets by transforming them into pseudo images with minimal processing for any high dimensional dataset, representing a more general approach to the application of CNNs to datasets such as in molecular biology, text, and speech. We introduce a pipeline called DeepMapper, which allows analysis of very high dimensional datasets without intermediate filtering and dimension reduction, thus preserving the full texture of the data, enabling detection of small variations normally deemed ‘noise’. We demonstrate that DeepMapper can identify very small perturbations in large datasets with mostly random variables, and that it is superior in speed and on par in accuracy to prior work in processing large datasets with large numbers of features.
The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection
Authors: Wang Ao , Dong Shengjun , Liu Baohui , Liu Dianxiao , Zou Mingrui , Han Yuexin , Yang Lijuan , Wang Yujiu
Published: May 2024

The pathogenesis of aortic dissection (AD), an aortic disease associated with high mortality, involves significant vascular inflammatory infiltration. However, the precise relationship between perivascular adipose tissue (PVAT) and aortic dissection remains incompletely understood. The objective of this study is to investigate the role of PVAT inflammation in the pathogenesis of aortic dissection and identify novel therapeutic targets for this disease. The mouse model of aortic dissection was established in this study through intraperitoneal injection of Ang II and administration of BAPN in drinking water. Additionally, control groups were established at different time points including the 2-week group, 3-week group, and 4-week group. qPCR and immunohistochemistry techniques were employed to detect the expression of inflammatory markers and RUNX1 in PVAT surrounding the thoracic aorta in mice. Additionally, an aortic dissection model was established using RUNX1 knockout mice, and the aforementioned indicators were assessed. The 3T3-L1 cells were induced to differentiate into mature adipocytes in vitro, followed by lentivirus transfection for the knockdown or overexpression of RUNX1. The study aimed to investigate the potential cell-to-cell interactions by co-culturing 3T3-L1 cells with A7r5 or RAW264.7 cells. Subsequently, human aortic PVAT samples were obtained through clinical surgery and the aforementioned indicators were detected. In comparison to the control group, the aortic dissection model group exhibited decreased expression of MMP-2 and NF-κB in PVAT, while TNF-α and RUNX1 expression increased. Suppression of RUNX1 expression resulted in increased MMP-2 and NF-κB expression in PVAT, along with decreased TNF-α expression. Overexpression of RUNX1 upregulated the expression levels of NF-Κb, MMP-2, and TNF-α in adipocytes, whereas knockdown of RUNX1 exerted an opposite effect. Macrophages co-cultured with adipocytes overexpressing RUNX1 exhibited enhanced CD86 expression, while vascular smooth muscle cells co-cultured with these adipocytes showed reduced α-SMA expression. In human samples, there was an increase in both RUNX1 and MMP-2 expression levels, accompanied by a decrease in TNF-α and NF-Κb expression. The presence of aortic dissection is accompanied by evident inflammatory alterations in the PVAT, and this phenomenon appears to be associated with the involvement of RUNX1. It is plausible that the regulation of PVAT's inflammatory changes by RUNX1/NF-κB signaling pathway plays a role in the pathogenesis of aortic dissection.