bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon density and sequestration in the temperate forests of northern Patagonia, Argentina
Authors: Loguercio Gabriel A. , Simon Alois , Winter Ariel Neri , Ivancich Horacio , Reiter Ernesto J. , Caselli Marina , Heinzle Facundo G. , Leuschner Christoph , Walentowski Helge
Published: April 2024

Introduction

Forests are a crucial part of the global carbon cycle and their proper management is of high relevance for mitigating climate change. There is an urgent need to compile for each region reference data on the carbon (C) stock density and C sequestration rate of its principal forest types to support evidence-based conservation and management decisions in terms of climate change mitigation and adaptation. In the Andean Mountains of northern Patagonia, extensive areas of temperate forest have developed after massive anthropogenic fires since the beginning of the last century.

Methods

We used a plot design along belt transects to determine reference values of carbon storage and annual C sequestration in total live (above- and belowground biomass) and deadwood mass, as well as in the soil organic layer and mineral soil (to 20 cm depth) in different forest types dominated by Nothofagus spp. and Austrocedrus chilensis.

Results

Average total carbon stock densities and C sequestration rates range from a minimum of 187 Mg.ha−1 and 0.7 Mg.ha−1.year−1 in pure and mixed N. antarctica shrublands through pure and mixed A. chilensis forests taller than 7 m and pure N. pumilio forests to a maximum in pure N. dombeyi forests with 339 Mg.ha−1 and 2.2 Mg.ha−1.year−1, respectively. Deadwood C represents between 20 and 33% of total wood mass C and is related to the amount of live biomass, especially for the coarse woody debris component. The topsoil contains between 33 and 57% of the total estimated ecosystem carbon in the tall forests and more than 65% in the shrublands, equaling C stocks of around 100–130 Mg.ha−1 in the different forest types.

Conclusion

We conclude that the northern Patagonian temperate forests actually store fairly high carbon stocks, which must be interpreted in relation to their natural post-fire development and relatively low management intensity. However, the current high stand densities of these forests may well affect their future carbon storage capacity in a warming climate, and they represent a growing threat of high-intensity fires with the risk of a further extension of burned areas in the future.
PD-1 knockout on cytotoxic primary murine CD8+ T cells improves their motility in retrovirus infected mice
Authors: Mittermüller Daniela , Otto Lucas , Kilian Annika Loredana , Schnormeier Ann-Kathrin , Littwitz-Salomon Elisabeth , Hasenberg Anja , Dittmer Ulf , Gunzer Matthias
Published: April 2024

Cytotoxic T lymphocyte (CTL) motility is an important feature of effective CTL responses and is impaired when CTLs become exhausted, e.g. during chronic retroviral infections. A prominent T cell exhaustion marker is programmed cell death protein 1 (PD-1) and antibodies against the interaction of PD-1 and PD-ligand 1 (PD-L1) are known to improve CTL functions. However, antibody blockade affects all PD-1/PD-L1-expressing cell types, thus, the observed effects cannot be attributed selectively to CTLs. To overcome this problem, we performed CRISPR/Cas9 based knockout of the PD-1 coding gene PDCD1 in naïve Friend Retrovirus (FV)-specific CTLs. We transferred 1,000 of these cells into mice where they proliferated upon FV-infection. Using intravital two-photon microscopy we visualized CTL motility in the bone marrow and evaluated cytotoxic molecule expression by flow cytometry. Knockout of PDCD1 improved the CTL motility at 14 days post infection and enhanced the expression of cytotoxicity markers. Our data show the potential of genetic tuning of naive antiviral CTLs and might be relevant for future designs of improved T cell-mediated therapies.
Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response
Authors: Gao Shuo , Zuo Wenfeng , Kang Chao , Zou Zhong , Zhang Kaiqi , Qiu Jun , Shang Xiaomin , Li Jingjing , Zhang Yuanfeng , Zuo Qi , Zhao Ya , Jin Meilin
Published: April 2024

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens—KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L— induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.
Imatinib-induced dermatomyositis sine dermatitis - a rare case report
Authors: Silva Augusto , Romão Vasco C. , Campanilho-Marques Raquel
Published: April 2024

Idiopathic Inflammatory Myopathies are rare conditions with several heterogeneous disease subtypes. They can range from limited muscle or skin involvement to severe, systemic, life-threatening disease. Although the etiology is unknown, some evidence suggests a role for external agents, particularly drugs. Herein, we present a case of a 71-year-old woman with chronic myeloid leukemia who developed imatinib-induced dermatomyositis sine dermatitis. The presentation was predominantly muscular, characterized by proximal muscle weakness and myalgia of the lower limbs, with positive anti-Mi2a antibodies. Spontaneous recovery was observed after drug discontinuation, without the need for immunosuppressive therapy. This is the first confirmed description of an imatinib-induced dermatomyositis sine dermatitis. It reflects the importance of a high awareness from rheumatologists and hematologists to accurately anticipate and identify similar situations.
Habitat associations of marine predators in the northern California Current during the low productivity downwelling season
Authors: Bliss Laura M. , Zamon Jeannette E. , Davoren Gail K. , Hanson M. Bradley , Noren Dawn P. , Emmons Candice , Holt Marla M.
Published: April 2024

Introduction

Eastern Boundary Upwelling Systems are some of the most productive marine ecosystems in the world. Little is known about habitat associations and spatial distributions of marine predators during seasonal periods of low productivity because there are few at-sea surveys during this period. During low productivity or prey scarcity, predators consuming similar prey in the same time and space may compete for limited resources, or they may avoid competition by exploiting different habitats or occupying separate spaces (i.e. niche partitioning). In this study, we examined habitat associations and niche partitioning of marine predators during the low-productivity winter downwelling season of the northern California Current Ecosystem (CCE).

Methods

Seabird and marine mammal counts were continuously collected during systematic at-sea surveys during February–March/April in the northern California Current across four years (2006, 2008, 2009, and 2012). We examined seabird and marine mammal distributions in relation to seven habitat characteristics [i.e., sea surface temperature (°C), salinity, depth (m), seafloor slope (%), distance from shore (km), and distance from the 100 m and 200 m isobaths (km)]. We used a non-parametric multivariate analysis [i.e. canonical correspondence analysis (CCA)] to quantify species’ habitat associations and directional distribution ellipses to explore overlap in species core winter habitat.

Results

Results show 49 seabird and ten marine mammal species inhabit the CCE during this low productivity period, including endangered southern resident killer whales (Orcinus orca). Seabirds and marine mammals exhibited significant but low overlap in habitat associations (i.e. weak niche partitioning) and similar habitat associations to summer studies.

Discussion

We also found that some species with similar foraging strategies showed asymmetrical spatial range overlap (i.e. common murre (Uria aalge) and parakeet auklet (Aethia psittacula)), which may mean that expected increased competition due to climate change can negatively affect some species more than others. Given that climate change is leading to increased frequencies, intensities, and durations of marine heat waves during winter months, addressing the winter ecology knowledge gap will be important to understanding how climate change is going to affect species that reside in or migrate through the northern California Current during the low productivity downwelling season.
Development and validation of a nomogram for predicting poor operative visibility during FESS in Chinese adult patients with CRS
Authors: Sun Deping , Liang Yalan , Yang Fuwei , Liu Lan , Mao Xuemei , Xu Xiaoli
Published: April 2024

Objective

The purpose of this study is to develop and evaluate a nomogram that is capable of predicting poor operative visibility during functional endoscopic sinus surgery.

Method

To identify potential risk factors, patients with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS) between January 2019 and December 2022 were selected from our hospital’s electronic medical record system. Data on general patient information, clinical manifestations, clotting-related test indices, Lund-Machay score of sinuses CT scanning, Lund-kennedy score of nasal endoscopies, anesthesia methods, intraoperative blood pressure and heart rate, and Boezaart bleeding score were collected. Minimum absolute convergence and selection operator (LASSO) regression, as well as multivariate logistic regression, were used to determine the risk factors. A nomogram was developed in order to predict poor operating visibility during FESS, and its performance was evaluated utilizing both the training and verification datasets via various measures including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, calibration curve, and decision curve analysis.

Results

Of the 369 patients who met the inclusion criteria, 88 of them exhibited POV during FESS. By deploying LASSO and multivariate logistic regression analyses, six risk factors were identified and used to construct a nomogram for predicting POV during FESS. These factors include prothrombin time (PT), prothrombin activity (PTA), Lund-Mackay score (LMS), Lund-Kennedy score (LKS), anesthetic method, and intraoperative hypertension. The AUC of the training set was found to be 0.820 while that of the verification set was 0.852. The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis revealed good consistency between predicted and actual probabilities. Also, the decision curve demonstrated that the nomogram had a high degree of clinical usefulness and net benefit.

Conclusion

The constructed nomogram has a strong ability to predict the poor intraoperative field in patients with chronic rhinosinusitis, which can help preoperative judgment of high-risk patients and provide evidence for perioperative management and preoperative plan formulation.
Transformer-based framework for multi-class segmentation of skin cancer from histopathology images
Authors: Imran Muhammad , Islam Tiwana Mohsin , Mohsan Mashood Mohammad , Alghamdi Norah Saleh , Akram Muhammad Usman
Published: April 2024

Introduction

Non-melanoma skin cancer comprising Basal cell carcinoma (BCC), Squamous cell carcinoma (SCC), and Intraepidermal carcinoma (IEC) has the highest incidence rate among skin cancers. Intelligent decision support systems may address the issue of the limited number of subject experts and help in mitigating the parity of health services between urban centers and remote areas.

Method

In this research, we propose a transformer-based model for the segmentation of histopathology images not only into inflammation and cancers such as BCC, SCC, and IEC but also to identify skin tissues and boundaries that are important in decision-making. Accurate segmentation of these tissue types will eventually lead to accurate detection and classification of non-melanoma skin cancer. The segmentation according to tissue types and their visual representation before classification enhances the trust of pathologists and doctors being relatable to how most pathologists approach this problem. The visualization of the confidence of the model in its prediction through uncertainty maps is also what distinguishes this study from most deep learning methods.

Results

The evaluation of proposed system is carried out using publicly available dataset. The application of our proposed segmentation system demonstrated good performance with an F1 score of 0.908, mean intersection over union (mIoU) of 0.653, and average accuracy of 83.1%, advocating that the system can be used as a decision support system successfully and has the potential of subsequently maturing into a fully automated system.

Discussion

This study is an attempt to automate the segmentation of the most occurring non-melanoma skin cancer using a transformer-based deep learning technique applied to histopathology skin images. Highly accurate segmentation and visual representation of histopathology images according to tissue types by the proposed system implies that the system can be used for skin-related routine pathology tasks including cancer and other anomaly detection, their classification, and measurement of surgical margins in the case of cancer cases.
Transcriptomic insights into the dominance of two phototrophs throughout the water column of a tropical hypersaline-alkaline crater lake (Dziani Dzaha, Mayotte)
Authors: Duperron Sébastien , Halary Sébastien , Bouly Jean-Pierre , Roussel Théotime , Hugoni Myléne , Bruto Maxime , Oger Philippe M. , Duval Charlotte , Woo Anthony , Jézéquel Didier , Ader Magali , Leboulanger Christophe , Agogué Hélène , Grossi Vincent , Troussellier Marc , Bernard Cécile
Published: April 2024

Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one such lake characterized by the stable co-dominance of the cyanobacterium Limnospira platensis and the picoeukaryote Picocystis salinarum throughout its water column. Despite light penetrating only into the uppermost meter, the prevailing co-dominance of these species persists even in light- and oxygen-deprived zones. Here, a depth profile of phototrophs metatranscriptomes, annotated using genomic data from isolated strains, is employed to identify expression patterns of genes related to carbon processing pathways including photosynthesis, transporters and fermentation. The findings indicate a prominence of gene expression associated with photosynthesis, with a peak of expression around 1 m below the surface, although the light intensity is very low and only red and dark red wavelengths can reach it, given the very high turbidity linked to the high biomass of L. platensis. Experiments on strains confirmed that both species do grow under these wavelengths, at rates comparable to those obtained under white light. A decrease in the expression of photosynthesis-related genes was observed in L. platensis with increasing depth, whereas P. salinarum maintained a very high pool of psbA transcripts down to the deepest point as a possible adaptation against photodamage, in the absence and/or very low levels of expression of genes involved in protection. In the aphotic/anoxic zone, expression of genes involved in fermentation pathways suggests active metabolism of reserve or available dissolved carbon compounds. Overall, L. platensis seems to be adapted to the uppermost water layer, where it is probably maintained thanks to gas vesicles, as evidenced by high expression of the gvpA gene. In contrast, P. salinarum occurs at similar densities throughout the water column, with a peak in abundance and gene expression levels which suggests a better adaptation to lower light intensities. These slight differences may contribute to limited inter-specific competition, favoring stable co-dominance of these two phototrophs.
Revolutionizing orthopedic healthcare: a systematic review unveiling recombinant antimicrobial peptides
Authors: Pennone Vincenzo , Rosini Elena , Mascheroni Elena , Gianola Silvia , Castellini Greta , Bargeri Silvia , Lovati Arianna B.
Published: April 2024

The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic surgeries carry a risk of infection, especially in patients with comorbidities. The rise of antibiotic resistance exacerbates this issue, necessitating alternatives like in vitro bioengineered antimicrobial peptides (AMPs), offering broad-spectrum activity and multiple action mechanisms. This review aimed to assess the prevalence of antimicrobial potential and the yield after purification among recombinant AMP families. The antimicrobial potential was evaluated using the Minimum Inhibitory Concentration (MIC) values against the most common bacteria involved in clinical infections. This systematic review adhered to PRISMA guidelines, focusing on in vitro studies of recombinant AMPs. The search strategy was run on PubMed, Scopus and Embase up to 30th March 2023. The Population, Exposure and Outcome model was used to extract the data from studies and ToxRTool for the risk of bias analysis. This review included studies providing peptide production yield data and MIC values against pathogenic bacteria. Non-English texts, reviews, conference abstracts, books, studies focusing solely on chemical synthesis, those reporting incomplete data sets, using non-standard MIC assessment methods, or presenting MIC values as ranges rather than precise concentrations, were excluded. From 370 publications, 34 studies on AMPs were analyzed. These covered 46 AMPs across 18 families, with Defensins and Hepcidins being most common. Yields varied from 0.5 to 2,700 mg/L. AMPs were tested against 23 bacterial genera, with MIC values ranging from 0.125 to >1,152 μg/mL. Arenicins showed the highest antimicrobial activity, particularly against common orthopedic infection pathogens. However, AMP production yields varied and some AMPs demonstrated limited effectiveness against certain bacterial strains. This systematic review emphasizes the critical role of bioengineered AMPs to cope infections and antibiotic resistance. It meticulously evaluates recombinant AMPs, focusing on their antimicrobial efficacy and production yields. The review highlights that, despite the variability in AMP yields and effectiveness, Arenicins and Defensins are promising candidates for future research and clinical applications in treating antibiotic-resistant orthopedic infections. This study contributes significantly to the understanding of AMPs in healthcare, underscoring their potential in addressing the growing challenge of antibiotic resistance.

Systematic review registration:https://osf.io/2uq4c/.
Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus
Authors: Yang Can , Chen Jing , Zhou Huifen , Zeng Di , Wan Haitong , Yang Jiehong
Published: April 2024

Objective

In this study, we examined the therapeutic effects of Yinhuapinggan granules (YHPGs) in influenza-infected mice. We also examined how YHPGs affect the composition of the intestinal flora and associated metabolites.

Methods

We used the nasal drip method to administer the influenza A virus (IAV) H1N1 to ICR mice. Following successful model construction, the mice were injected with 0.9% sterile saline and low (5.5 g/kg), medium (11 g/kg), and high (22 g/kg) doses of YHPGs. The pathological changes in the lungs and intestines were evaluated by gavage for 5 consecutive days. Detection of sIgA, IL-6, TNF-α, INF-γ, and TGF-β cytokine levels in serum by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to measure the mRNA and protein expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in the colon. To assess the influence of YHPGs on the intestinal microbiota, feces were obtained from the mice for 16s rRNA sequencing, and short-chain fatty acids (SCFAs) were measured in the feces.

Results

By reducing the production of pro-inflammatory cytokines and increasing the relative expression of claudin-1, occludin, and ZO-1 in colon tissues, YHPGs had a protective effect in tissues from the lungs and colon. When YHPGs were administered to mice with IAV infection, the relative abundance of Lactobacillus, Coprobacillus, Akkermansia, Prevotella, Oscillospira, and Ruminococcus increased, whereas the relative abundance of Desulfovibrio decreased.

Conclusion

The therapeutic mechanism of YHPGs against IAV infection in mice may be underpinned by modulation of the structural composition of colonic bacteria and regulation of SCFA production.
Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability
Authors: Sharma Shikha , Chauhan Abhishek , Ranjan Anuj , Mathkor Darin Mansor , Haque Shafiul , Ramniwas Seema , Tuli Hardeep Singh , Jindal Tanu , Yadav Vikas
Published: April 2024

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.
Tafazzin deficiency causes substantial remodeling in the lipidome of a mouse model of Barth Syndrome cardiomyopathy
Authors: Hachmann Malte , Gülcan Güntas , Rajendran Ranjithkumar , Höring Marcus , Liebisch Gerhard , Bachhuka Akash , Kohlhaas Michael , Maack Christoph , Ergün Süleyman , Dudek Jan , Karnati Srikanth
Published: April 2024

Barth Syndrome (BTHS) is a rare X-linked disease, characterized clinically by cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the phospholipid acyltransferase tafazzin (Gene: TAFAZZIN, TAZ). Tafazzin catalyzes the final step in the remodeling of cardiolipin (CL), a glycerophospholipid located in the inner mitochondrial membrane. As the phospholipid composition strongly determines membrane properties, correct biosynthesis of CL and other membrane lipids is essential for mitochondrial function. Mitochondria provide 95% of the energy demand in the heart, particularly due to their role in fatty acid oxidation. Alterations in lipid homeostasis in BTHS have an impact on mitochondrial membrane proteins and thereby contribute to cardiomyopathy. We analyzed a transgenic TAFAZZIN-knockdown (TAZ-KD) BTHS mouse model and determined the distribution of 193 individual lipid species in TAZ-KD and WT hearts at 10 and 50 weeks of age, using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Our results revealed significant lipid composition differences between the TAZ-KD and WT groups, indicating genotype-dependent alterations in most analyzed lipid species. Significant changes in the myocardial lipidome were identified in both young animals without cardiomyopathy and older animals with heart failure. Notable alterations were found in phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC) and plasmalogen species. PC species with 2–4 double bonds were significantly increased, while polyunsaturated PC species showed a significant decrease in TAZ-KD mice. Furthermore, Linoleic acid (LA, 18:2) containing PC and PE species, as well as arachidonic acid (AA, 20:4) containing PE 38:4 species are increased in TAZ-KD. We found higher levels of AA containing LPE and PE-based plasmalogens (PE P-). Furthermore, we are the first to show significant changes in sphingomyelin (SM) and ceramide (Cer) lipid species Very long-chained SM species are accumulating in TAZ-KD hearts, whereas long-chained Cer and several hexosyl ceramides (HexCer) species accumulate only in 50-week-old TAZ-KD hearts These findings offer potential avenues for the diagnosis and treatment of BTHS, presenting new possibilities for therapeutic approaches.
Association between loneliness and cognitive function, and brain volume in community-dwelling elderly
Authors: Lee Hunju , Yong Sang Yeol , Choi Hyowon , Yoon Ga Young , Koh Sangbaek
Published: April 2024

Introduction

We investigated the relationship between loneliness, cognitive impairment, and regional brain volume among elderly individuals residing in the Korean community.

Methods

Data from the ARIRANG aging-cognition sub-cohort, collected between 2020 and 2022, were utilized for the present study. Loneliness was assessed using the UCLA-Loneliness Scale (UCLA-LS) questionnaire and the relevant item from Center for Epidemiologic Studies Depression Scale Korean version (CES-D-K). Cognitive impairment was measured through Mini-Mental State Examination (K-MMSE-2) and Seoul Neuropsychological Screening Battery (SNSB-C), with five sub-categories: attention, memory, visuospatial function, language, and executive function. Logistic regression was employed for prevalence ratios related to cognitive impairment, while linear regression was used for regional brain volume including white matter hyperintensity (WMH) and cortical thickness.

Results

Our analysis involved 785 participants (292 men and 493 women). We observed increased cognitive impairment assessed by K-MMSE-2 [UCLA-LS: odds ratio (OR) 3.133, 95% confidence interval (CI) 1.536–6.393; loneliness from CES-D: OR 2.823, 95% CI 1.426–5.590] and SNSB-C total score (UCLA-LS: OR 2.145, 95% CI 1.304–3.529) in the lonely group compared to the non-lonely group. Specifically, the lonely group identified by UCLA-LS showed an association with declined visuospatial (OR 1.591, 95% CI 1.029–2.460) and executive function (OR 1.971, 95% CI 1.036–3.750). The lonely group identified by CES-D-K was associated with impaired memory (OR 1.577, 95% CI 1.009–2.466) and executive function (OR 1.863, 95% CI 1.036–3.350). In the regional brain volume analysis, loneliness was linked to reduced brain volume in frontal white matter (left: −1.24, 95% CI −2.37 ∼−0.12; right: −1.16, 95% CI −2.31 ∼ −0.00), putamen (left: −0.07, 95% CI −0.12 ∼−0.02; right: −0.06, 95% CI −0.11 ∼−0.01), and globus pallidus (−15.53, 95% CI −30.13 ∼−0.93). There was no observed association in WMH and cortical thickness.

Conclusion

Loneliness is associated with cognitive decline and volumetric reduction in the frontal white matter, putamen, and globus pallidus.
Unveiling the vulnerability of the human abducens nerve: insights from comparative cranial base anatomy in mammals and primates
Authors: Rotenstreich Liat , Eran Ayelet , Siegler Yoav , Grossman Rachel , Edery Nir , Cohen Roni , Marom Assaf
Published: April 2024

The topographic anatomy of the abducens nerve has been the subject of research for more than 150 years. Although its vulnerability was initially attributed to its length, this hypothesis has largely lost prominence. Instead, attention has shifted toward its intricate anatomical relations along the cranial base. Contrary to the extensive anatomical and neurosurgical literature on abducens nerve anatomy in humans, its complex anatomy in other species has received less emphasis. The main question addressed here is why the human abducens nerve is predisposed to injury. Specifically, we aim to perform a comparative analysis of the basicranial pathway of the abducens nerve in mammals and primates. Our hypothesis links its vulnerability to cranial base flexion, particularly around the sphenooccipital synchondrosis. We examined the abducens nerve pathway in various mammals, including primates, humans (N = 40; 60% males; 40% females), and human fetuses (N = 5; 60% males; 40% females). The findings are presented at both the macroscopic and histological levels. To associate our findings with basicranial flexion, we measured the cranial base angles in the species included in this study and compared them to data in the available literature. Our findings show that the primitive state of the abducens nerve pathway follows a nearly flat (unflexed) cranial base from the pontomedullary sulcus to the superior orbital fissure. Only the gulfar segment, where the nerve passes through Dorello’s canal, demonstrates some degree of variation. We present evidence indicating that the derived state of the abducens pathway, which is most pronounced in humans from an early stage of development, is characterized by following the significantly more flexed basicranium. Overall, the present study elucidates the evolutionary basis for the vulnerability of the abducens nerve, especially within its gulfar and cavernous segments, which are situated at the main synchondroses between the anterior, middle, and posterior cranial fossae—a unique anatomical relation exclusive to the abducens nerve. The principal differences between the pathways of this nerve and those of other cranial nerves are discussed. The findings suggest that the highly flexed human cranial base plays a pivotal role in the intricate anatomical relations and resulting vulnerability of the abducens nerve.
Effects of transcranial alternating current stimulation to the supplementary motor area on motor learning
Authors: Yamamoto Shunpei , Miyaguchi Shota , Ogawa Takuma , Inukai Yasuto , Otsuru Naofumi , Onishi Hideaki
Published: April 2024

Transcranial alternating current stimulation (tACS) is a noninvasive method for brain stimulation that artificially modulates oscillatory brain activity in the cortical region directly beneath the electrodes by applying a weak alternating current. Beta (β) oscillatory activity in the supplementary motor area (SMA) is involved in motor planning and maintenance, whereas gamma (γ) oscillatory activity is involved in the updating of motor plans. However, the effect of applying tACS to the SMA on motor learning has not yet been investigated. This study assessed the effects of applying tACS to the SMA on motor learning. Forty-two right-handed healthy adults (age 20.6 ± 0.5 years, 24 men and 18 women) were included. Motor learning was assessed using a visuomotor tracking task with pinch tension of the right thumb and right forefinger. Each trial lasted 60 s, and the error rates were measured. Conductive rubber electrodes were attached to the SMA and the left shoulder for tACS. Stimulation was applied at an intensity of 1.0 mA and frequencies of 70 and 20 Hz in the γ-tACS and β-tACS treatment groups, respectively. The sham group was only administered a fade-in/out. The visuomotor tracking task was performed for 10 trials before tACS and 10 trials after tACS. Two trials were conducted on the following day to determine motor skill retention. The average deviation measured during 60 s was considered the error value. Pre-stimulation learning rate was calculated as the change in error rate. Post-stimulation learning rate and retention rate were calculated as the change in error rate after stimulation and on the day after stimulation, respectively. In both the stimulation groups, differences in pre-stimulation learning, post-stimulation learning, and retention rates were not significant. However, in the γ-tACS group, baseline performance and pre-stimulation learning rate were positively correlated with post-stimulation learning rate. Therefore, applying γ-tACS to the SMA can increase post-stimulation learning rate in participants exhibiting low baseline performance and high pre-stimulation learning rate. Our findings suggest that motor learning can be effectively enhanced by applying γ-tACS to the SMA based on an individual’s motor and learning abilities.
Rate of atrial fibrillation by Holter-Stroke Risk Analysis in undetermined TIA/rapidly improving stroke symptoms patients
Authors: Cannizzaro F , Izquierdo A , Cocho D
Published: April 2024

Introduction

Holter-SRA (Stroke Risk Analysis) is an automated analysis of ECG monitoring for Atrial Fibrillation (AF) detection. The aim of this study was to evaluate the rate of AF in undetermined TIA/Rapidly improving stroke symptoms (RISS) patients.

Methods

Prospective study of undetermined TIA/RISS patients who presented to the emergency department. Early vascular studies (angio CT, transthoracic echocardiography and ECG) were performed in emergency department. The Holter-SRA device was placed for 2 h and the patients were classified into: confirmed AF, high risk of AF or low risk of AF. Prolonged ambulatory monitoring (7 days) was carried out every month for patients with a high-risk pattern. The results were evaluated until definitive detection of AF or low-risk pattern. The endpoints were rate of AF and vascular recurrence at 90 days.

Results

Over a period of 24 months, 83 undetermined TIA/RISS patients were enrolled. The mean age was 70 ± 10 years and 61% were men. The median ABCD2 score was 4 points (1–7). After 2 h of monitoring in the emergency department, AF was detected in one patient (1.2%), 51 patients with a low-risk pattern and 31 patients (37.3%) showed a high-risk pattern of AF. During the ambulatory monitoring, of the 31 patients high risk pattern patients, AF was diagnosed to 17 cases and of the 51 patients with a low-risk pattern, one case experienced a recurrent vascular due to undetected AF (1.9% false negative). Three patients (3.6%) suffered a vascular recurrence within the first 90 days, before AF diagnosis.

Conclusions

In our study, AF was detected in 22.9% of the 83 patients with indeterminate TIA/RISS. Holter-SRA has allowed us to increase the detection of AF, especially those patients with a high-risk pattern in the first 3 months.
Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study
Authors: Huang Mingsheng , Liu Yiheng , Peng Jie , Cheng Yuan
Published: April 2024

Background

Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined.

Method

In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis.

Results

After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515–0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L– HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004–2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031–1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma.

Conclusion

Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.
Safety considerations in the treatment with anti-CGRP(R) monoclonal antibodies in patients with migraine
Authors: Van Der Arend Britt W. H. , Van Veelen Nancy , De Ruijter Joëlle E. T. , Olsen Michael H. , MaassenVanDenBrink Antoinette , Terwindt Gisela M.
Published: April 2024

Background

Anti-CGRP-(receptor-)monoclonal antibodies (anti-CGRP(R)-mAbs) represent a novel class of drugs for migraine treatment, but their long-term cerebrovascular and cardiovascular (CV) safety warrants further examination.

Methods

In this observational cohort study we assessed the CV safety for erenumab and fremanezumab in a real-world setting during a follow-up period of at least 1 year. Patients with hypertension or CV history were excluded. We conducted ECGs and collected clinical data at treatment initiation and thereafter every 3 months, including liver and kidney function, lipid-, electrolyte-and glucose levels.

Results

Among patients receiving erenumab (n = 101) or fremanezumab (n = 92), 3.1% (6/193) developed abnormal ECGs or CV adverse events. Of these, three (1.6%) experienced moderate to severe CV adverse events (cerebellar stroke, spontaneous coronary artery dissection, and pericarditis) and discontinued treatment. The remaining three (1.6%) developed non-threatening ECG abnormalities without physical complaints. No significant changes were observed in liver and kidney function, lipid-, electrolyte-, or glucose levels.

Discussion

We observed CV events in 1.6% of patients with 1.5-year follow-up of anti-CGRP(R)-mAbs treatment. We advise awareness regarding CV events in patients with migraine undergoing CGRP-targeted treatment, not as a confirmation of increased risk but as a proactive measure to address potential multifactorial influences.
Activation and functional connectivity of cerebellum during reading and during arithmetic in children with combined reading and math disabilities
Authors: Ashburn Sikoya M. , Matejko Anna A. , Eden Guinevere F.
Published: April 2024

Background

Reading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children’s educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing.

Methods

Here we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex.

Results

The two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity).

Conclusion

These results do not support theories that children’s deficits in reading and math originate in the cerebellum.
Design of urban road fault detection system based on artificial neural network and deep learning
Authors: Lin Ying
Published: April 2024

Introduction

In urban traffic management, the timely detection of road faults plays a crucial role in improving traffic efficiency and safety. However, conventional methods often fail to fully leverage the information from road topology and traffic data.

Methods

To address this issue, we propose an innovative detection system that combines Artificial Neural Networks (ANNs), specifically Graph Convolutional Networks (GCN), Bidirectional Gated Recurrent Units (BiGRU), and self-attention mechanisms. Our approach begins by representing the road topology as a graph and utilizing GCN to model it. This allows us to learn the relationships between roads and capture their structural dependencies. By doing so, we can effectively incorporate the spatial information provided by the road network. Next, we employ BiGRU to model the historical traffic data, enabling us to capture the temporal dynamics and patterns in the traffic flow. The BiGRU architecture allows for bidirectional processing, which aids in understanding the traffic conditions based on both past and future information. This temporal modeling enhances our system's ability to handle time-varying traffic patterns. To further enhance the feature representations, we leverage self-attention mechanisms. By combining the hidden states of the BiGRU with self-attention, we can assign importance weights to different temporal features, focusing on the most relevant information. This attention mechanism helps to extract salient features from the traffic data. Subsequently, we merge the features learned by GCN from the road topology and BiGRU from the traffic data. This fusion of spatial and temporal information provides a comprehensive representation of the road status.

Results and discussions

By employing a Multilayer Perceptron (MLP) as a classifier, we can effectively determine whether a road is experiencing a fault. The MLP model is trained using labeled road fault data through supervised learning, optimizing its performance for fault detection. Experimental evaluations of our system demonstrate excellent performance in road fault detection. Compared to traditional methods, our system achieves more accurate fault detection, thereby improving the efficiency of urban traffic management. This is of significant importance for city administrators, as they can promptly identify road faults and take appropriate measures for repair and traffic diversion.
The role of dietary preferences in osteoarthritis: a Mendelian randomization study using genome-wide association analysis data from the UK Biobank
Authors: Chen Long , Su Yiqi , Li Hui , Yang Zhen , Li Jiao Jiao , Xing Dan
Published: April 2024

Background

To understand the impact of individual preferences for specific dietary items on OA, and to help inform the development of effective and targeted OA prevention and management strategies, we performed a Mendelian randomization analysis between dietary preferences and osteoarthritis.

Methods

This study utilized genetic data from the UK Biobank to investigate the association between OA and 21 different common dietary items. Instrumental variables representing European populations were carefully selected based on their genetic significance and linkage disequilibrium. In cases where a dietary item had few relevant genetic markers, a more lenient selection threshold was applied. To prevent bias, the analysis excluded single nucleotide polymorphisms (SNPs) associated with factors such as body mass index (BMI) and cholesterol. Using inverse-variance weighting (IVW) and Mendelian randomization, significant associations were detected between certain dietary items and OA.

Results

Using Mendelian randomization to examine the relationship between 21 different dietary items and OA, significant associations were found for coffee, peas, watercress, and cheese, where the first two had a promoting effect and the last two an inhibiting effect on OA. Due to heterogeneity in the test results for cheese, a random IVW representation was used. The results of sensitivity analysis showed no significant heterogeneity or horizontal pleiotropy in the selected SNPS, demonstrating the reliability of Mendelian randomization analysis.

Conclusion

This study identified coffee, peas, watercress, and cheese as food items that may have significant dietary effects on osteoarthritis. This information may be useful to consider in the development of OA management strategies.
Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity
Authors: Tamayo-Trujillo Rafael , Ruiz-Pozo Viviana A. , Cadena-Ullauri Santiago , Guevara-Ramírez Patricia , Paz-Cruz Elius , Zambrano-Villacres Raynier , Simancas-Racines Daniel , Zambrano Ana Karina
Published: April 2024

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism. Finally, several clinical trial outcomes are described to show the safety and efficacy of these drugs in obesity management.