bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Change Will Fragment Florida Stone Crab Communities
Authors: Alaerts Lauranne , Dobbelaere Thomas , Gravinese Philip M. , Hanert Emmanuel
Published: July 2022

Many marine species have been shown to be threatened by both ocean acidification and ocean warming which are reducing survival, altering behavior, and posing limits on physiology, especially during earlier life stages. The commercially important Florida stone crab, Menippe mercenaria, is one species that is affected by reduced seawater pH and elevated seawater temperatures. In this study, we determined the impacts of reduced pH and elevated temperature on the distribution of the stone crab larvae along the West Florida Shelf. To understand the dispersion of the larvae, we coupled the multi-scale ocean model SLIM with a larval dispersal model. We then conducted a connectivity study and evaluated the impacts of climate stressors by looking at four different scenarios which included models that represented the dispersion of stone crab larvae under: 1) present day conditions as modelled by SLIM for the temperature and NEMO-PISCES for the pH, 2) SSP1-2.6 scenario (-0.037 reduction in pH and +0.5°C compared to present-day conditions), 3) SSP2-4.5 scenario(-0.15 reduction in pH and +1.5°C) and 4) SSP5-8.5 scenario (-0.375 reduction in pH and +3.5°C). Our results show a clear impact of these climate change stressors on larval dispersal and on the subsequent stone crab distribution. Our results indicate that future climate change could result in stone crabs moving north or into deeper waters. We also observed an increase in the number of larvae settling in deeper waters (defined as the non-fishing zone in this study with depths exceeding 30 m) that are not typically part of the commercial fishing zone. The distance travelled by larvae, however, is likely to decrease, resulting in an increase of self-recruitment and decrease of the size of the sub-populations. A shift of the spawning period, to earlier in the spring, is also likely to occur. Our results suggest that habitats in the non-fishing zone cannot serve as a significant source of larvae for the habitats in the fishing zone (defined as water depth< 30 m) since there is very little exchange (< 5% of all exchanges) between the two zones. These results indicate that the stone crab populations in Florida may be susceptible to community fragmentation and that the management of the fishery should consider the potential impacts of future climate change scenarios.
Acoustic Classification of Juvenile Pacific Salmon (Oncorhynchus spp) and Pacific Herring (Clupea pallasii) Schools Using Random Forests
Authors: Rousseau Shani , Gauthier Stéphane , Neville Chrys , Johnson Stewart , Trudel Marc
Published: July 2022

Acoustic surveys are the standard approach for evaluating many fish stocks around the world. The analysis of such survey data requires the accurate echo-classification of target species. This classification is often challenging as many organisms exhibit overlapping characteristics in terms of shape, acoustic amplitude, and behavior. In this study, a random forest approach was used to distinguish juvenile Pacific salmon (Oncorhynchus spp) from Pacific herring (Clupea pallasii) aggregations using the acoustic and morphological characteristics of their echo traces. The acoustic data was collected with an autonomous, multi-frequency echosounder deployed on the seafloor in the Discovery Islands, British Columbia from May to September 2015. The model was able to differentiate juvenile Pacific salmon from Pacific herring with a 98% accuracy. School depth and school mean volume backscattering strength were the most important predictors in determining the school classification. This study supports other publications suggesting that random forests represent a promising approach to acoustic target classification in fisheries science.
A Photovoltaic Power Predicting Model Using the Differential Evolution Algorithm and Multi-Task Learning
Authors: Pang Senshen , Liu Jiefeng , Zhang Zhenhao , Fan Xianhao , Zhang Yiyi , Zhang Dongdong , Hwang Goh Hui
Published: July 2022

The rapid growth of photovoltaic installed capacity exacerbates the power management challenges faced by photovoltaic power stations, emphasizing the importance of accurate and stable photovoltaic generation forecasting. As a result, researchers conducted research and developed several photovoltaic power prediction models. However, many prediction models focus exclusively on the algorithm structure in order to improve model accuracy, oblivious to how the dataset is constructed and divided for the prediction model. This paper proposes a comprehensive model to address this gap. To be more precise, the differential evolution algorithm is constantly looking for optimal values between different populations and determining the best way to construct datasets for prediction tasks. Multi-task learning enables the transfer of knowledge between related tasks via parameter sharing layers, referring to the accuracy and stability of prediction models. Overall, the proposed model achieves high prediction accuracy and stability. The prediction error of the proposed model is less than 450W in RMSE, NRMSE is less than 2.5%, and R-Square is greater than 99% in multiple prediction tasks. Additionally, when compared to other single-task prediction models with an R-Square greater than 96%, the proposed model further reduces the root mean squared error by an average of 28% and the standard deviation of root mean squared error by 54%.
Subcutaneous Enoxaparin for Systemic Anticoagulation of COVID-19 Patients During Extracorporeal Life Support
Authors: Wiegele Marion , Laxar Daniel , Schaden Eva , Baierl Andreas , Maleczek Mathias , Knöbl Paul , Hermann Martina , Hermann Alexander , Zauner Christian , Gratz Johannes
Published: July 2022

Background

Extracorporeal membrane oxygenation, with an inherent requirement for anticoagulation to avoid circuit thrombosis, is a key element in the treatment of respiratory failure associated with COVID-19. Anticoagulation remains challenging, the standard of care being intravenous continuous administration of unfractionated heparin. Yet regimens vary. Some intensive care units in our center have successfully used enoxaparin subcutaneously in recent years and throughout the pandemic.

Methods

We retrospectively analyzed adult COVID-19 patients with respiratory failure who had been systemically anticoagulated using either enoxaparin or unfractionated heparin. The choice of anticoagulant therapy was based on the standard of the intensive care unit. Defined thromboembolic and hemorrhagic events were analyzed as study endpoints.

Results

Of 98 patients, 62 had received enoxaparin and 36 unfractionated heparin. All hazard ratios for the thromboembolic (3.43; 95% CI: 1.08–10.87; p = 0.04), hemorrhagic (2.58; 95% CI: 1.03–6.48; p = 0.04), and composite (2.86; 95% CI: 1.41–5.92; p = 0.007) endpoints favored enoxaparin, whose efficient administration was verified by peak levels of anti-factor Xa (median: 0.45 IU ml−1; IQR: 0.38; 0.56). Activated partial thromboplastin time as well as thrombin time differed significantly (both p<0.001) between groups mirroring the effect of unfractionated heparin.

Conclusions

This study demonstrates the successful use of subcutaneous enoxaparin for systemic anticoagulation in patients with COVID-19 during extracorporeal membrane oxygenation. Our findings are to be confirmed by future prospective, randomized, controlled trials.
Diagnostic Utility of Non-invasive Tests for Inflammatory Bowel Disease: An Umbrella Review
Authors: Shi Jin-Tong , Zhang Yuexin , She Yuehan , Goyal Hemant , Wu Zhi-Qi , Xu Hua-Guo
Published: July 2022

Background

This study aims to consolidate evidence from published systematic reviews and meta-analyses evaluating the diagnostic performances of non-invasive tests for inflammatory bowel disease (IBD) in various clinical conditions and age groups.

Methods

Two independent reviewers systematically identified and appraised systematic reviews and meta-analyses assessing the diagnostic utility of non-invasive tests for IBD. Each association was categorized as adults, children, and mixed population, based on the age ranges of patients included in the primary studies. We classified clinical scenarios into diagnosis, activity assessment, and predicting recurrence.

Results

In total, 106 assessments from 43 reviews were included, with 17 non-invasive tests. Fecal calprotectin (FC) and fecal lactoferrin (FL) were the most sensitive for distinguishing IBD from non-IBD. However, anti-neutrophil cytoplasmic antibodies (ANCA) and FL were the most specific for it. FC and FL were the most sensitive and specific tests, respectively, to distinguish IBD from irritable bowel syndrome (IBS). Anti-Saccharomyces cerevisiae antibodies (ASCA), IgA, were the best test to distinguish Crohn’s disease (CD) from ulcerative colitis (UC). Interferon-γ release assay was the best test to distinguish CD from intestinal tuberculosis (ITB). Ultrasound (US) and magnetic resonance enterography (MRE) were both sensitive and specific for disease activity, along with the high sensitivity of FC. Small intestine contrast ultrasonography (SICUS) had the highest sensitivity, and FC had the highest specificity for operative CD recurrence.

Conclusion

In this umbrella review, we summarized the diagnostic performance of non-invasive tests for IBD in various clinical conditions and age groups. Clinicians can use the suggested non-invasive test depending on the appropriate clinical situation in IBD patients.
Emerging Therapies in Cutaneous Lupus Erythematosus
Authors: Sprow Grant , Dan Joshua , Merola Joseph F. , Werth Victoria P.
Published: July 2022

Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can occur with or without underlying systemic lupus erythematosus (SLE) and often has a profoundly negative impact on patient quality of life. There is substantial need for new and more effective therapies to treat CLE. CLE has a multifactorial pathogenesis that involves several key immune cells and pathways, including abnormalities in innate (e.g., type 1 interferon pathways) and adaptive immune responses (e.g., B and T cell autoreactivity), presenting multiple opportunities for more targeted therapies that do not require immunosuppression. Here we review several emerging therapies and their efficacy in CLE. Anifrolumab and belimumab have both been approved for the treatment of SLE in recent years, and clinical trial evidence suggests some forms of CLE may improve with these agents. Therapies currently in development that are being evaluated with CLE-specific outcome measures include BIIB059 and VIB7734, which target plasmacytoid dendritic cells (pDCs), and iberdomide, a cereblon modulator. These novel therapies all have previously demonstrated clinical benefit in some forms of CLE. Other therapies which target molecules believed to play a role in CLE pathogenesis, such as Janus kinases (JAKs), spleen tyrosine kinase (SYK), interferon γ (IFNγ), IL-12, and IL-23, have been evaluated in lupus clinical trials with skin-specific outcomes but failed to meet their primary endpoints.
Machine Learning Prediction of Nitrification From Ammonia- and Nitrite-Oxidizer Community Structure
Authors: Lee Conard , Amini Fatemeh , Hu Guiping , Halverson Larry J.
Published: July 2022

Accurately modeling nitrification and understanding the role specific ammonia- or nitrite-oxidizing taxa play in it are of great interest and importance to microbial ecologists. In this study, we applied machine learning to 16S rRNA sequence and nitrification potential data from an experiment examining interactions between cropping systems and rhizosphere on microbial community assembly and nitrogen cycling processes. Given the high dimensionality of microbiome datasets, we only included nitrifers since only a few taxa are capable of ammonia and nitrite oxidation. We compared the performance of linear and nonlinear algorithms with and without qPCR measures of bacterial and archaea ammonia monooxygenase subunit A (amoA) gene abundance. Our feature selection process facilitated the identification of taxons that are most predictive of nitrification and to compare habitats. We found that Nitrosomonas and Nitrospirae were more frequently identified as important predictors of nitrification in conventional systems, whereas Thaumarchaeota were more important predictors in diversified systems. Our results suggest that model performance was not substantively improved by incorporating additional time-consuming and expensive qPCR data on amoA gene abundance. We also identified several clades of nitrifiers important for nitrification in different cropping systems, though we were unable to detect system- or rhizosphere-specific patterns in OTU-level biomarkers for nitrification. Finally, our results highlight the inherent risk of combining data from disparate habitats with the goal of increasing sample size to avoid overfitting models. This study represents a step toward developing machine learning approaches for microbiome research to identify nitrifier ecotypes that may be important for distinguishing ecotypes with defining roles in different habitats.
In vitro and in vivo Characterization of Host–Pathogen Interactions of the L3881 Candida albicans Clinical Isolate
Authors: Sucupira Pedro H. F. , Moura Tauany R. , Gurgel Isabella L. S. , Pereira Tassia T. P. , Padovan Ana C. B. , Teixeira Mauro M. , Bahia Diana , Soriani Frederico M.
Published: July 2022

Candida albicansis a human commensal fungus and the etiologic agent of nosocomial infections in immunocompromised individuals.Candidaspp. is the most studied human fungal pathogen, and the mechanisms by which this fungus can evade the immune system affecting immunosuppressed individuals have been extensively studied. Most of these studies focus on different species ofCandida, and there is much to be understood in virulence variability among lineages, specifically differentC. albicansclinical isolates. To better understand the main mechanisms of its virulence variability modulated inC. albicansclinical isolates, we characterized L3881 lineage, which has been previously classified as hypovirulent, and SC5314 lineage, a virulent wild-type control, by using bothin vitroandin vivoassays. Our findings demonstrated that L3881 presented higher capacity to avoid macrophage phagocytosis and higher resistance to oxidative stress than the wild type. These characteristics prevented higher mortality rates for L3881 in the animal model of candidiasis. Conversely, L3881 has been able to induce an upregulation of pro-inflammatory mediators bothin vitroandin vivo. These results indicated thatin vitroandin vivofunctional characterizations are necessary for determination of virulence in different clinical isolates due to its modulation in the host–pathogen interactions.
Use of Whole-Genome Sequencing to Unravel the Genetic Diversity of a Prevalent Mycobacterium bovis Spoligotype in a Multi-Host Scenario in Spain
Authors: Pozo Pilar , Lorente-Leal Victor , Robbe-Austerman Suelee , Hicks Jessica , Stuber Tod , Bezos Javier , de Juan Lucia , Saez Jose Luis , Romero Beatriz , Alvarez Julio ,   on behalf of the Spanish Network on Surveillance Monitoring of Animal Tuberculosis
Published: July 2022

Despite the efforts invested in the eradication of bovine tuberculosis in Spain, herd prevalence has remained constant in the country during the last 15 years (~1.5–1.9%) due to a combination of epidemiological factors impairing disease control, including between-species transmission. Here, our aim was to investigate the molecular diversity of Mycobacterium bovis isolates belonging to the highly prevalent SB0339 spoligotype in the cattle-wildlife interface in different regions of Spain using whole-genome sequencing (WGS). Genomic data of 136 M. bovis isolates recovered from different animal species (cattle, wild boar, fallow deer, and red deer) and locations between 2005 and 2018 were analyzed to investigate between- and within-species transmission, as well as within-herds. All sequenced isolates differed by 49–88 single nucleotide polymorphisms from their most recent common ancestor. Genetic heterogeneity was geographic rather than host species-specific, as isolates recovered from both cattle and wildlife from a given region were more closely related compared to isolates from the same species but geographically distant. In fact, a strong association between the geographic and the genetic distances separating pairs of M. bovis isolates was found, with a significantly stronger effect when cattle isolates were compared with wildlife or cattle-wildlife isolates in Spain. The same results were obtained in Madrid, the region with the largest number of sequenced isolates, but no differences depending on the host were observed. Within-herd genetic diversity was limited despite the considerable time elapsed between isolations. The detection of closely related strains in different hosts demonstrates the complex between-host transmission dynamics present in endemic areas in Spain. In conclusion, WGS results a valuable tool to track bTB infection at a high resolution and may contribute to achieve its eradication in Spain.
RETRACTED: Microbiome-Based Hypothesis on Ivermectin’s Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity
Authors: Hazan Sabine
Published: July 2022

Ivermectin is an anti-parasitic agent that has gained attention as a potential COVID-19 therapeutic. It is a compound of the type Avermectin, which is a fermented by-product of Streptomyces avermitilis. Bifidobacterium is a member of the same phylum as Streptomyces spp., suggesting it may have a symbiotic relation with Streptomyces. Decreased Bifidobacterium levels are observed in COVID-19 susceptibility states, including old age, autoimmune disorder, and obesity. We hypothesize that Ivermectin, as a by-product of Streptomyces fermentation, is capable of feeding Bifidobacterium, thereby possibly preventing against COVID-19 susceptibilities. Moreover, Bifidobacterium may be capable of boosting natural immunity, offering more direct COVID-19 protection. These data concord with our study, as well as others, that show Ivermectin protects against COVID-19.
Effect of pH on Diclofenac–Lysozyme Interaction: Structural and Functional Aspect
Authors: Basheeruddin Mohd , Khan Sheeza , Ahmed Neesar , Jamal Shazia
Published: July 2022

As a nonsteroidal antiinflammatory drug, diclofenac (DCF) is used in the treatment of a variety of human ailments. It has already been reported that the use of this class of drugs for a longer duration is associated with numerous side effects such as cardiovascular implications, reno-medullary complications, etc. In the present study, the effect of DCF on the structure, stability, and function of lysozyme was studied. The study was designed to examine the effect of DCF only at various pH values. Heat-induced denaturation of lysozyme was analyzed in the presence and absence of various molar concentrations of DCF at different pH values. The values of thermodynamic parameters, the midpoint of denaturation (Tm), enthalpy change at Tm (ΔHm), constant pressure heat capacity change (ΔCp), and Gibbs energy change at 25°C (ΔGDo), thus obtained under a given set of conditions (pH and molar concentration of DCF), demonstrated the following 1) DCF destabilized lysozyme with respect of Tm and ΔGDo at all the pH values, 2) the magnitude of protein destabilization is lesser at acidic pH than at physiological pH, 3) structural changes in lysozyme are less projecting at pH 2.0 than at pH 7.0, and 4) quenching is observed at both pH values. Furthermore, the process of protein destabilization in the presence of DCF is entropically driven.
Essential Roles and Risks of G-Quadruplex Regulation: Recognition Targets of ALS-Linked TDP-43 and FUS
Authors: Ishiguro Akira , Ishihama Akira
Published: July 2022

A non-canonical DNA/RNA structure, G-quadruplex (G4), is a unique structure formed by two or more guanine quartets, which associate through Hoogsteen hydrogen bonding leading to form a square planar arrangement. A set of RNA-binding proteins specifically recognize G4 structures and play certain unique physiological roles. These G4-binding proteins form ribonucleoprotein (RNP) through a physicochemical phenomenon called liquid-liquid phase separation (LLPS). G4-containing RNP granules are identified in both prokaryotes and eukaryotes, but extensive studies have been performed in eukaryotes. We have been involved in analyses of the roles of G4-containing RNAs recognized by two G4-RNA-binding proteins, TDP-43 and FUS, which both are the amyotrophic lateral sclerosis (ALS) causative gene products. These RNA-binding proteins play the essential roles in both G4 recognition and LLPS, but they also carry the risk of agglutination. The biological significance of G4-binding proteins is controlled through unique 3D structure of G4, of which the risk of conformational stability is influenced by environmental conditions such as monovalent metals and guanine oxidation.
Course of Preexisting Migraine Following Spontaneous Subarachnoid Hemorrhage
Authors: Valdueza José Manuel , Dreier Jens Peter , Woitzik Johannes , Dohmen Christian , Sakowitz Oliver , Platz Johannes , Leistner-Glaess Stefanie , Witt Victoria Dorothea
Published: July 2022

Background

Our objective was to observe the course of preexisting migraine following subarachnoid hemorrhage (SAH) in patients with and without craniotomy.

Methods

We designed an exploratory analysis and hypothesis-generating study of prospectively collected data starting by recruiting patients suffering from SAH with the Hunt and Hess scale score of ≤ 4. Out of 994 cases, we identified 46 patients with preexisting active migraine defined by at least four attacks in the year before SAH. According to the treatment, we subdivided the patients into two groups: the first group included patients with surgical aneurysm clipping with transection of the middle meningeal artery (MMA) and accompanying trigeminal nerve branches and the second group included patients with endovascular aneurysm coiling or without any interventional treatment. During the follow-up, we recorded the course of migraine frequency, duration, intensity, and character.

Results

For both groups (craniotomy n = 31, without craniotomy n = 15), a significant improvement regarding the preexisting migraine during a mean follow-up of 46 months (min. 12 months, max. 114 months) was seen regarding complete remission or at least >50% reduction in migraine attacks (p < 0.001 and p = 0.01). On comparing the groups, this effect was significantly more pronounced in patients with craniotomy (for no recurrence of migraine: p = 0.049). After craniotomy, 77.4% of the patients had no further attacks of migraine headache and 19.4% showed a reduction of >50% while only 2.2% did not report any relevant change. In the non-surgical group, 46.7% had no further migraine attacks, 20% had a reduction of >50%, while no change was noted in 33.3%.

Conclusions

Our study provides evidence that the dura mater might be related to migraine headaches and that transection of the MMA and accompanying trigeminal dural nerve branches might disrupt the pathway leading to a reduction of migraine attacks. However, coiling alone ameliorated migraine complaints.
Simultaneous Dual Recordings From Vestibular Hair Cells and Their Calyx Afferents Demonstrate Multiple Modes of Transmission at These Specialized Endings
Authors: Contini Donatella , Holstein Gay R. , Art Jonathan J.
Published: July 2022

In the vestibular periphery, transmission via conventional synaptic boutons is supplemented by post-synaptic calyceal endings surrounding Type I hair cells. This review focusses on the multiple modes of communication between these receptors and their enveloping calyces as revealed by simultaneous dual-electrode recordings. Classic orthodromic transmission is accompanied by two forms of bidirectional communication enabled by the extensive cleft between the Type I hair cell and its calyx. The slowest cellular communication low-pass filters the transduction current with a time constant of 10–100 ms: potassium ions accumulate in the synaptic cleft, depolarizing both the hair cell and afferent to potentials greater than necessary for rapid vesicle fusion in the receptor and potentially triggering action potentials in the afferent. On the millisecond timescale, conventional glutamatergic quantal transmission occurs when hair cells are depolarized to potentials sufficient for calcium influx and vesicle fusion. Depolarization also permits a third form of transmission that occurs over tens of microseconds, resulting from the large voltage- and ion-sensitive cleft-facing conductances in both the hair cell and the calyx that are open at their resting potentials. Current flowing out of either the hair cell or the afferent divides into the fraction flowing across the cleft into its cellular partner, and the remainder flowing out of the cleft and into the surrounding fluid compartment. These findings suggest multiple biophysical bases for the extensive repertoire of response dynamics seen in the population of primary vestibular afferent fibers. The results further suggest that evolutionary pressures drive selection for the calyx afferent.
Case Report: Paraneoplastic Tumefactive Demyelination Associated With Seminoma
Authors: Shiraishi Wataru , Umemura Takeru , Nakayama Yuuki , Yamada Yui , Shijo Masahiro , Hashimoto Tetsuya
Published: July 2022

Paraneoplastic tumefactive demyelination (TD) is a rare disorder of the central nervous system that can be challenging to diagnose. Here, we describe a 32-year-old Japanese man with a TD associated with testicular seminoma. He presented with symptoms of right-sided motor and sensory impairment 2 days after vaccination for coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) showed a high-intensity lesion in the left internal capsule. He had a 3-year history of enlargement of the left testicle. Blood examination showed tumor marker elevation and the presence of anti-amphiphysin antibodies. Whole-body computed tomography (CT) revealed mass lesions in the left testicle and enlargement of the retroperitoneal lymph nodes. Radical orchiectomy was performed. As the pathology showed testicular seminoma, chemotherapy was administered. After surgery, his neurological symptoms deteriorated. MRI revealed that the brain lesion had enlarged and progressed to a tumefactive lesion without gadolinium enhancement. The cerebrospinal fluid (CSF) examination was normal without pleocytosis or protein elevation. Steroid pulse therapy was added; however, his symptoms did not improve. A brain stereotactic biopsy was performed and the sample showed demyelinating lesions without malignant cells. As the initial corticosteroid therapy was ineffective, gamma globulin therapy was administered in parallel with chemotherapy, and the clinical symptoms and imaging findings were partially ameliorated. TD seldom appears as a paraneoplastic neurological syndrome. In addition, there are few reports of COVID-19 vaccination-associated demyelinating disease. Clinicians should recognize paraneoplastic TD, and the further accumulation of similar cases is needed.
The Structured Mind at Rest: Low-Frequency Oscillations Reflect Interactive Dynamics Between Spontaneous Brain Activity and a Common Architecture for Task Control
Authors: Sibert Catherine , Hake Holly Sue , Stocco Andrea
Published: July 2022

The Common Model of Cognition (CMC) has been proposed as a high level framework through which functional neuroimaging data can be predicted and interpreted. Previous work has found the CMC is capable of predicting brain activity across a variety of tasks, but it has not been tested on resting state data. This paper adapts a previously used method for comparing theoretical models of brain structure, Dynamic Causal Modeling, for the task-free environment of resting state, and compares the CMC against six alternate architectural frameworks while also separately modeling spontaneous low-frequency oscillations. For a large sample of subjects from the Human Connectome Project, the CMC provides the best account of resting state brain activity, suggesting the presence of a general purpose structure of connections in the brain that drives activity when at rest and when performing directed task behavior. At the same time, spontaneous brain activity was found to be present and significant across all frequencies and in all regions. Together, these results suggest that, at rest, spontaneous low-frequency oscillations interact with the general cognitive architecture for task-based activity. The possible functional implications of these findings are discussed.
β-Hydroxybutyrate Attenuates Painful Diabetic Neuropathy via Restoration of the Aquaporin-4 Polarity in the Spinal Glymphatic System
Authors: Wang Fei-xiang , Xu Chi-liang , Su Can , Li Jiang , Lin Jing-yan
Published: July 2022

Waste removal is essential for maintaining homeostasis and the normal function of the central nervous system (CNS). The glymphatic system based on aquaporin-4 (AQP4) water channels on the endfeet of astrocytes is recently discovered as the excretion pathway for metabolic waste products of CNS. In the CNS, α-syntrophin (SNTA1) directly or indirectly anchors AQP4 in astrocyte membranes facing blood vessels. Studies have indicated that β-hydroxybutyrate (BHB) can raise the expression of SNTA1 and thus restoring AQP4 polarity in mice models with Alzheimer’s disease. The study aims to evaluate the neuroprotective mechanism of BHB in rats with painful diabetic neuropathy (PDN). PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. Magnetic resonance imaging (MRI) was applied to observe the clearance of contrast to indicate the functional variability of the spinal glymphatic system. Mechanical allodynia was assessed by paw withdrawal threshold. The expressions of SNTA1 and AQP4 were tested, and the polarity reversal of AQP4 protein was measured. As demonstrated, PDN rats were manifested with deceased contrast clearance of the spinal glymphatic system, enhanced mechanical allodynia, lower expression of SNTA1, higher expression of AQP4, and reversed polarity of AQP4 protein. An opposite change in the above characteristics was observed in rats being treated with BHB. This is the first study that demonstrated the neuroprotective mechanism of BHB to attenuate PDN via restoration of the AQP4 polarity in the spinal glymphatic system and provides a promising therapeutic strategy for PDN.
Involvement of White Matter Language Tracts in Glioma: Clinical Implications, Operative Management, and Functional Recovery After Injury
Authors: Aabedi Alexander A. , Young Jacob S. , Chang Edward F. , Berger Mitchel S. , Hervey-Jumper Shawn L.
Published: July 2022

To achieve optimal survival and quality of life outcomes in patients with glioma, the extent of tumor resection must be maximized without causing injury to eloquent structures. Preservation of language function is of particular importance to patients and requires careful mapping to reveal the locations of cortical language hubs and their structural and functional connections. Within this language network, accurate mapping of eloquent white matter tracts is critical, given the high risk of permanent neurological impairment if they are injured during surgery. In this review, we start by describing the clinical implications of gliomas involving white matter language tracts. Next, we highlight the advantages and limitations of methods commonly used to identify these tracts during surgery including structural imaging techniques, functional imaging, non-invasive stimulation, and finally, awake craniotomy. We provide a rationale for combining these complementary techniques as part of a multimodal mapping paradigm to optimize postoperative language outcomes. Next, we review local and long-range adaptations that take place as the language network undergoes remodeling after tumor growth and surgical resection. We discuss the probable cellular mechanisms underlying this plasticity with emphasis on the white matter, which until recently was thought to have a limited role in adults. Finally, we provide an overview of emerging developments in targeting the glioma-neuronal network interface to achieve better disease control and promote recovery after injury.
Brain Neural Underpinnings of Interoception and Decision-Making in Alzheimer's Disease: A Narrative Review
Authors: Sun Weiyi , Ueno Daisuke , Narumoto Jin
Published: July 2022

This study reviews recent literature on interoception directing decision-making in Alzheimer's disease (AD). According to the somatic marker hypothesis, signals from the internal body direct decision-making and involve the ventromedial prefrontal cortex (vmPFC). After reviewing relevant studies, we summarize the brain areas related to interoception and decision-making (e.g., vmPFC, hippocampus, amygdala, hypothalamus, anterior cingulate cortex, and insular cortex) and their roles in and relationships with AD pathology. Moreover, we outline the relationship among interoception, the autonomic nervous system, endocrine system, and AD pathology. We discuss that impaired interoception leads to decreased decision-making ability in people with AD from the perspective of brain neural underpinning. Additionally, we emphasize that anosognosia or reduced self-awareness and metacognition in AD are remarkably congruent with the malfunction of the autonomic nervous system regulating the interoceptive network. Furthermore, we propose that impaired interoception may contribute to a loss in the decision-making ability of patients with AD. However, there still exist empirical challenges in confirming this proposal. First, there has been no standardization for measuring or improving interoception to enhance decision-making ability in patients with AD. Future studies are required to better understand how AD pathology induces impairments in interoception and decision-making.
Nucleus Tractus Solitarius Neurons Activated by Hypercapnia and Hypoxia Lack Mu Opioid Receptor Expression
Authors: Maletz Sebastian N. , Reid Brandon T. , Varga Adrienn G. , Levitt Erica S.
Published: July 2022

Impaired chemoreflex responses are a central feature of opioid-induced respiratory depression, however, the mechanism through which mu opioid receptor agonists lead to diminished chemoreflexes is not fully understood. One brainstem structure involved in opioid-induced impairment of chemoreflexes is the nucleus of the solitary tract (NTS), which contains a population of neurons that express mu opioid receptors. Here, we tested whether caudal NTS neurons activated during the chemoreflex challenge express mu opioid receptors and overlap with neurons activated by opioids. Using genetic labeling of mu opioid receptor-expressing neurons and cFos immunohistochemistry as a proxy for neuronal activation, we examined the distribution of activated NTS neurons following hypercapnia, hypoxia, and morphine administration. The main finding was that hypoxia and hypercapnia primarily activated NTS neurons that did not express mu opioid receptors. Furthermore, concurrent administration of morphine with hypercapnia induced cFos expression in non-overlapping populations of neurons. Together these results suggest an indirect effect of opioids within the NTS, which could be mediated through mu opioid receptors on afferents and/or inhibitory interneurons.
Chloral Hydrate Alters Brain Activation Induced by Methamphetamine-Associated Cue and Prevents Relapse
Authors: Jiang Chenyu , Xu Yunlong , Zhong Jiafeng , Wu Junyan , He Jian , Xu Wei , Zhu Yingjie
Published: July 2022

Methamphetamine is a highly addictive drug and its abuse leads to serious health and social problems. Until now, no effective medications are yet available for the treatment of methamphetamine addiction. Our study reveals that chloral hydrate, a clinical sedative drug, suppresses the seeking desire for methamphetamine. After 5 days of continuous administration (subanesthetic dose 50 mg/kg and 100 mg/kg), methamphetamine-seeking behavior of rats was inhibited in the condition place preference and intravenous self-administration tests. Furthermore, chloral hydrate treatment robustly suppressed cue-induced methamphetamine relapse. The whole brain c-fos immunostaining revealed that chloral hydrate treatment suppressed neuronal activity in the rhomboid thalamic nucleus (Rh), dorsal endopiriform nucleus (dEn), and claustrum (Cl) while enhanced zona incerta (ZI) activity during cue-induced methamphetamine relapse. Therefore, chloral hydrate could remodel neural network activity and serve as a potential medicine to treat methamphetamine addiction.
Bioaccessibility and Antioxidant Capacity of Bioactive Compounds From Various Typologies of Canned Tomatoes
Authors: Izzo Luana , Castaldo Luigi , Lombardi Sonia , Gaspari Anna , Grosso Michela , Ritieni Alberto
Published: July 2022

Tomato (Solanum lycopersicum L.) is one of the most consumed vegetables in the world; it contains high amounts of antioxidant phytochemicals and essential nutrients. Although it is commonly consumed fresh, more than 80% of its consumption derives from processed products. Since limited information on changes in the bioaccessibility of bioactive compounds during gastrointestinal digestion was reported, this current study aimed to monitor the antioxidant activity, total polyphenolic and carotenoid content, and bioaccessibility during in vitro gastrointestinal digestion of different typologies (n = 7) of canned tomatoes. A comprehensive evaluation of the polyphenolic profile of digested and not digested samples was ascertained by ultra-high-performance liquid chromatography combined with high-resolution Orbitrap mass spectrometry. The results highlighted a considerable content of rutin (1.191–9.516 mg/100 g), naringenin (0.359–1.452 mg/100 g), chlorogenic acid (1.857–11.236 mg/100 g), and lycopene (50.894–222.061 mg/kg) in the analyzed matrices. After in vitro gastrointestinal digestion, large variability, losses and low recovery were recorded. An appreciable percentage of rutin (30.7%), naringenin (29.6%), chlorogenic acid (25.8%), and lycopene (varied between 9.3 and 20%) remained bioaccessible after the in vitro gastrointestinal digestion. Our study could be a valid support to evaluate which content of bioactive compounds could be really bioaccessible to exercise beneficial effects on human health.
Association Between Dairy Intake and Executive Function in Chinese Children Aged 6–12 Years
Authors: Zeng Xia , Cai Li , Gui Zhaohuan , Shen Tianran , Yang Wenhan , Chen Qingsong , Chen Yajun
Published: July 2022

Association between dairy intake and executive function remains controversial, especially among children, a population with fast-developing executive functions. This study aimed to explore this topic. Additionally, we further distinguished the role of dairy intake types (full- or low-fat milk or yogurt) in this relationship. This survey included 5,138 children aged 6–12 years. Dairy intakes were assessed by validated questionnaires. Executive function was measured by the behavior rating inventory of executive function (BRIEF; Parent Version), and lower T-scores of BRIEF indices indicated superior executive function performance. Results showed that children with higher dairy intake had statistically better performance in Shift (46.58 ± 7.48 vs. 45.85 ± 7.10), Initiate (48.02 ± 8.58 vs. 47.14 ± 8.33), and Working Memory (50.69 ± 8.82 vs. 49.89 ± 8.73). In the analysis of multivariate linear regression, we found that for every one unit increase in full-fat dairy intake, T-scores for Shift (β = −0.350 (95% confidence interval [CI]: (−0.660, −0.039) and Initiate (β = −0.486 (95% CI: (−0.845, −0.127) were decreased and for every one unit increase in low-fat dairy intake, T-score for Organizations of Materials (β = −0.940 (95% CI: (−1.690, −0.189) was decreased. After distinguishing dairy into milk and yogurt, we observed that only milk intake, not yogurt, was significantly associated with better executive function performance in Shift (β = −0.390 (95% CI (−0.745, −0.035) and Initiate (β = −0.509 (95% CI (−0.917, −0.101) after adjusting for potential confounding factors. This study shows that a higher intake of dairy, irrespective of fat content, is related to better executive function performance among children aged 6–12. In addition, a significantly positive relationship between dairy intake and executive function’s indices of Shift and Initiate only was observed in milk, not in yogurt.
The Role of Bioelectrical Impedance Analysis in Predicting COVID-19 Outcome
Authors: Stevanovic Djordje , Zdravkovic Vladimir , Poskurica Mina , Petrovic Marina , Cekerevac Ivan , Zdravkovic Nemanja , Mijailovic Sara , Todorovic Dusan , Divjak Ana , Bozic Dunja , Marinkovic Milos , Jestrovic Aleksandra , Azanjac Anja , Miloradovic Vladimir
Published: July 2022

Background

Published data regarding the impact of obesity on COVID-19 outcomes are inconsistent. However, in most studies, body composition was assessed using body mass index (BMI) alone, thus neglecting the presence and distribution of adipose tissue. Therefore, we aimed to investigate the impact of body and visceral fat on COVID-19 outcomes.

Methods

Observational, prospective cohort study included 216 consecutive COVID-19 patients hospitalized at University Clinical Center Kragujevac (Serbia) from October to December 2021. Body composition was assessed using the BMI, body fat percentage (%BF), and visceral fat (VF) via bioelectrical impedance analysis (BIA). In addition to anthropometric measurements, variables in the research were socio-demographic and medical history data, as well as admission inflammatory biomarkers. Primary end-points were fatal outcomes and intensive care unit (ICU) admission.

Results

The overall prevalence of obesity was 39.3% according to BMI and 50.9% according to % BF, while 38.4% of patients had very high VF levels. After adjusting odds ratio values for cofounding variables and obesity-related conditions, all three anthropometric parameters were significant predictors of primary end-points. However, we note that % BF and VF, compared to BMI, were stronger predictors of both mortality (aOR 3.353, aOR 3.05, and aOR 2.387, respectively) and ICU admission [adjusted odds ratio (aOR) 7.141, aOR 3.424, and aOR 3.133, respectively].

Conclusion

Obesity is linked with COVID-19 mortality and ICU admission, with BIA measurements being stronger predictors of outcome compared to BMI use alone.
Improvement of Storage Stability of Zein-Based Pickering Emulsions by the Combination of Konjac Glucomannan and L-Lysine
Authors: Song Teng , Liu Hui , Monto Abdul Razak , Shi Tong , Yuan Li , Gao Ruichang
Published: July 2022

In this work, L-lysine (Lys) was employed together with konjac glucomannan (KGM) to fabricate zein colloidal particles (ZCPs) aimed at enhancing the storage stability of Pickering emulsions. With the addition of Lys, zein-Lys colloidal particles (ZLCPs) and zein-Lys-KGM (ZLKCPs) exhibited smaller particle size (133.64 ± 1.43, 162.54 ± 3.51 nm), polydispersity index (PDI) (0.10 ± 0.029, 0.13 ± 0.022), π value, and more adsorbed protein. Meanwhile, KGM underwent deamidation in an alkaline solution, so the emulsions stabilized by ZLKCPs exhibited a solid gel-like structure with higher storage modulus (G′) and loss modulus (G′′), leading to lower fluidity and better stability. The synergistic effects of Lys and KGM improved the stability of the emulsion. Hydrophobic interactions and hydrogen bonds were the main driving forces forming colloidal particles, which were determined by driving force analysis.
CD147 Mediates 5-Fluorouracil Resistance in Colorectal Cancer by Reprogramming Glycolipid Metabolism
Authors: Dong Shuohui , Li Songhan , Wang Xiaoyan , Liang Shuo , Zhang Wenjie , Li Linchuan , Xu Qian , Shi Bowen , Cheng Zhiqiang , Zhang Xiang , Zhong Mingwei , Zhang Guangyong , Hu Sanyuan
Published: July 2022

Chemoresistance against 5-fluorouracil (5-FU) is a major issue for colorectal cancer (CRC) patients. Increasing evidence for the roles of CD147 in glycolipid metabolic reprogramming and chemoresistance of tumor cells has emerged in recent years. However, whether CD147 contributes to 5-FU resistance in CRC and the role of abnormal glycolipid metabolism in this process remain poorly understood. We analyzed CD147 expression in primary tumor samples of CRC patients and found that upregulated CD147 correlated with decreased 5-FU chemosensitivity and an unfavorable prognosis of CRC patients. Moreover, in vivo and in vitro experiments confirmed that CD147 regulates glycolipid metabolism through two separate pathways. Mechanistically, CD147 upregulates HIF-1α-mediated glycolysis by activating the PI3K/AKT/mTOR pathway and CD147 also attenuates PPARα-mediated fatty acid oxidation by activation of the MAPK pathway. Most importantly, we found that CD147 confers 5-FU resistance in CRC via these glycolipid metabolic signatures. Our results demonstrated that CD147 is a potential 5-FU resistance biomarker for CRC patients and a candidate therapeutic target to restore 5-FU sensitivity of 5-FU-resistant CRC by remodeling glycolipid metabolism.
Deciphering Prognostic Value of TTN and Its Correlation With Immune Infiltration in Lung Adenocarcinoma
Authors: Chen Jianing , Wen Yaokai , Su Hang , Yu Xin , Hong Ruisheng , Chen Chang , Su Chunxia
Published: July 2022

Background

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for around 40%. Despite achievements in the treatment approach, the prognosis is still dismal, with overall survival of fewer than five years. Thus, novel prognostic biomarkers are needed to predict the clinical outcomes of individual patients better. TTN has a high mutation rate in the LUAD, which encodes a large abundant protein of striated muscle. However, the value of TTN in prognosis and the immune environment are poorly understood.

Methods

We investigated the clinicopathological characteristics, transcriptional and protein level, prognostic value, biological function, and its relationship with immune infiltration of TTN gene in LUAD patients through bioinformatics analysis.

Results

TTN expression was significantly lower in LUAD than that in normal lung tissue. Lower TTN expression was associated with worse survival. Besides, TTN is highly expressed in alveolar type 2 cells which were surmised as the origin of LUAD.

Conclusion

Our findings indicated the potential prognostic value of TTN and its role as a biomarker for determining the immune infiltration levels in patients with LUAD.
The Deubiquitinase USP13 Maintains Cancer Cell Stemness by Promoting FASN Stability in Small Cell Lung Cancer
Authors: Wang Juhong , Lin Weihao , Li Renda , Cheng Hong , Sun Sijin , Shao Fei , Yang Yannan , Zhang Lin , Feng Xiaoli , Gao Shugeng , Gao Yibo , He Jie
Published: July 2022

USP13 is significantly amplified in over 20% of lung cancer patients and critical for tumor progression. However, the functional role of USP13 in small cell lung cancer (SCLC) remains largely unclear. In this study, we found that the deubiquitinase USP13 is highly expressed in SCLC tumor samples and positively associated with poor prognosis in multiple cohorts. In vitro and in vivo depletion of USP13 inhibited SCLC cancer stem cells (CSCs) properties and tumorigenesis, and this inhibitory effect was rescued by reconstituted expression of wide type (WT) USP13 but not the enzyme-inactive USP13 mutant. Mechanistically, USP13 interacts with fatty acid synthase (FASN) and enhances FASN protein stability. FASN downregulation suppresses USP13-enhanced cell renewal regulator expression, sphere formation ability, and de novo fatty acids biogenesis. Accordingly, we found FASN expression is upregulated in surgical resected SCLC specimens, positively correlated with USP13, and associated with poor prognosis of SCLC patients. More importantly, the small molecule inhibitor of FASN, TVB-2640, significantly inhibits lipogenic phenotype and attenuates self-renewal ability, chemotherapy resistance and USP13-mediated tumorigenesis in SCLC. Thus, our study highlights a critical role of the USP13-FASN-lipogenesis axis in SCLC cancer stemness maintenance and tumor growth, and reveals a potential combination therapy for SCLC patients.