bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19
Authors: Schagatay Felix , Diamant Klara , Lidén Mats , Edin Alicia , Athlin Simon , Hultgren Olof , Ahlm Clas , Forsell Mattias N. E. , Savilampi Johanna , Normark Johan , Lange Anna , Cajander Sara
Published: July 2022

Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.

Aim

To investigate if the concentration of extracellular CIRP (eCIRP) in serum associates with respiratory failure and lung involvement by chest computed tomography (CT) in COVID-19.

Methods

Herein we report a prospective observational study of patients with COVID-19 included at two University Hospitals in Sweden between April 2020 and May 2021. Serum from hospitalized patients in Örebro (N=97) were used to assess the association between eCIRP and the level of respiratory support and its correlation with pulmonary involvement on chest CT and inflammatory biomarkers. A cohort of hospitalized and non-hospitalized patients from Umeå (N=78) was used as an external validation cohort. The severity of disease was defined according to the highest degree of respiratory support; mild disease (no oxygen), non-severe hypoxemia (conventional oxygen or high-flow nasal oxygen, HFNO <50% FiO2), and severe hypoxemia (HFNO ≥50% FiO2, mechanical ventilation). Unadjusted and adjusted linear regression was used to evaluate peak eCIRP day 0-4 in respect to severity, age, sex, Charlson comorbidity score, symptom duration, and BMI.

Results

Peak eCIRP concentrations were higher in patients with severe hypoxemia and were independently associated with the degree of respiratory support in both cohorts (Örebro; p=0.01, Umeå; p<0.01). The degree of pulmonary involvement measured by CT correlated with eCIRP, rs=0.30, p<0.01 (n=97).

Conclusion

High serum levels of eCIRP are associated with acute respiratory failure in COVID-19. Experimental studies are needed to determine if treatments targeting eCIRP reduces the risk of acute respiratory failure in COVID-19.
The role of neutrophil extracellular traps in acute lung injury
Authors: Scozzi Davide , Liao Fuyi , Krupnick Alexander S. , Kreisel Daniel , Gelman Andrew E.
Published: July 2022

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability of digesting NET DNA scaffold. Moreover, recent advances in neutrophil biology led to the development of selective NET inhibitors, which also appear to reduce ALI in experimental models. Here we provide an overview of the role of NETs in different forms of ALI discussing existing gaps in our knowledge and novel therapeutic approaches to modulate their impact on lung injury.
Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension
Authors: Sanges Sébastien , Guerrier Thomas , Duhamel Alain , Guilbert Lucile , Hauspie Carine , Largy Alexis , Balden Maïté , Podevin Céline , Lefèvre Guillaume , Jendoubi Manel , Speca Silvia , Hachulla Éric , Sobanski Vincent , Dubucquoi Sylvain , Launay David
Published: July 2022

Introduction

Soluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.

Methods

1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.

Results

In a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.

Conclusion

Soluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.
FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation
Authors: Yero Alexis , Shi Tao , Routy Jean-Pierre , Tremblay Cécile , Durand Madeleine , Costiniuk Cecilia T. , Jenabian Mohammad-Ali
Published: July 2022

Objectives

Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.

Methods

Subsets of FoxP3+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21).

Results

Acute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP3+ CD8 T-cells. We observed an increase in FoxP3+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals.

Conclusions

Although early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cell, which may contribute to immune dysfunction.
Toll-like receptor-mediated innate immunity orchestrates adaptive immune responses in HBV infection
Authors: Du Yanqin , Wu Jun , Liu Jia , Zheng Xin , Yang Dongliang , Lu Mengji
Published: July 2022

Chronic hepatitis B virus (HBV) infection remains to be a substantial global burden, especially for end-stage liver diseases. It is well accepted that HBV-specific T and B cells are essential for controlling HBV infection. Toll-like receptors (TLRs) represent one of the major first-line antiviral defenses through intracellular signaling pathways that induce antiviral inflammatory cytokines and interferons, thereby shaping adaptive immunity. However, HBV has evolved strategies to counter TLR responses by suppressing the expression of TLRs and blocking the downstream signaling pathways, thus limiting HBV-specific adaptive immunity and facilitating viral persistence. Recent studies have stated that stimulation of the TLR signaling pathway by different TLR agonists strengthens host innate immune responses and results in suppression of HBV replication. In this review, we will discuss how TLR-mediated responses shape HBV-specific adaptive immunity as demonstrated in different experimental models. This information may provide important insight for HBV functional cure based on TLR agonists as immunomodulators.
Size Dependent Transport of Floating Plastics Modeled in the Global Ocean
Authors: Klink Doug , Peytavin Axel , Lebreton Laurent
Published: July 2022

Plastic has been detected in the ocean in most locations where scientists have looked for it. While ubiquitous in the environment, plastic pollution is heterogeneous, and plastics of varying composition, shape, and size accumulate differently in the global ocean. Many physical and biological processes influence the transport of plastics in the marine environment. Here we focus on physical processes and how they can naturally sort floating plastics at the ocean surface and within its interior. We introduce a new open-source GPU-accelerated numerical model, ADVECT, which simulates the three-dimensional dispersal of large arrays of modelled ocean plastics with varying size, shape, and density. We use this model to run a global simulation and find that buoyant particles are sorted in the ocean according to their size, both at the surface due to wind-driven drift and in the water column due to their rising velocity. Finally, we compare our findings with recent literature reporting the size distribution of plastics in the ocean and discuss which observations can and cannot be explained by the physical processes encoded in our model.
Controlling factors of large-scale harmful algal blooms with Karenia selliformis after record-breaking marine heatwaves
Authors: Takagi Satomi , Kuroda Hiroshi , Hasegawa Natsuki , Watanabe Tsuyoshi , Unuma Tatsuya , Taniuchi Yukiko , Yokota Takashi , Izumida Daisuke , Nakagawa Toru , Kurokawa Tadahide , Azumaya Tomonori
Published: July 2022

Unprecedented, large-scale harmful algal blooms (HABs) dominated by Karenia selliformis occurred off the southeastern coast of Hokkaido, Japan, from late September to early November 2021, about a month after intense and extensive marine heatwaves (MHWs) had subsided. The aims of the present study were to understand the mechanism of development, maintenance, and decay of the HABs as well as to investigate the effect of the MHWs on the HABs. We developed a one-dimensional, lower trophic-level ecosystem model (NEMURO+) to simulate the HABs. The model successfully simulated the 2021 HABs and indicated that their development, maintenance, and decay were controlled primarily by changes of water temperature. Nitrate supply from subsurface layers by seasonal vertical diffusion in autumn also helped to maintain the HABs. Vertical diffusion following MHWs in 2021 contributed to the long duration of the preferred temperature for K. selliformis and the occurrence of pre-bloom of K. selliformis, resulting in preconditioning and accelerating the HABs. However, simulations for normal years (i.e., the climatological mean during 2003–2018) showed that HABs could have occurred, even in the absence of MHWs. The simulations indicated that massive blooms of other phytoplankton species (e.g., diatoms) would not have occurred in 2021, even in the absence of a K. selliformis bloom. The implication was that the HABs in 2021 were the species-specific responses of K. selliformis. The proposed mechanism of the HABs was peculiar to our study area and differed from that previously reported for other K. selliformis blooms. Specifically, the preferred temperature for the HABs of K. selliformis was clearly lower than the previously reported preferred temperature of K. selliformis; thus, the physiological characteristics of the K. selliformis that bloomed in our study area differed from those of other K. selliformis strains. These discoveries provide the first evidence to explain how MHWs affect HABs, and to understand how inter-regional dissimilarities of K. selliformis can lead to large-scale, devastating outbreaks under different oceanographic conditions.
Optimisation of at-sea culture and harvest conditions for cultivated Macrocystis pyrifera: yield, biofouling and biochemical composition of cultured biomass
Authors: Biancacci C. , Visch W. , Callahan D. L. , Farrington G. , Francis D. S. , Lamb P. , McVilly A. , Nardelli A. , Sanderson J. C. , Schwoerbel J. , Hurd C. L. , Evans B. , Macleod C. , Bellgrove A.
Published: July 2022

Seaweed cultivation is gaining interest world-wide for both food and non-food applications. Global seaweed aquaculture production currently exceeds 32 Mt WW per annum but is dominated (86% of total) by Asian countries. To meet future demand for seaweed products, regions beyond Asia with aquaculture production potential are being explored. The goal of this study was to assess the suitability of the native kelp Macrocystis pyrifera (Phaeophyceae, Laminariales), for aquaculture in Tasmania, south-eastern Australia. M. pyrifera was cultivated on seeded twine on loops (1 – 5 m depth) along 100-m longlines at two sites (Okehampton Bay and Great Taylor Bay) from April-November 2020. Temporal and spatial variability in (1) yield (kg m-1, WW), (2) biofouling (% coverage), and (3) biochemical composition (including proximate composition, fatty acids, dietary minerals, heavy metal profiling, C, N, H, S concentrations and C:N ratio, antioxidants (phenolic compounds), and pigments (Chl-a, Chl-c, fucoxanthin)) was compared amongst the two cultivation sites, at two depths (1 and 5 m) from harvests between July – November 2020. Yield (kg m-1, WW) did not significantly change across harvest times, but was greater at a depth of 1 m compared to 5 m. Biofouling on the kelp blades increased significantly in early spring (September). The biochemical composition of the cultured biomass varied over time, between sites and with depth for most of the compounds analysed. Higher lipid, protein and ash content was reported for cultures cultivated at Okehampton Bay compared to Great Taylor Bay and at 5 m compared to 1 m depth, and levels of these macronutrients decreased during the harvest period. The iodine content was slightly above the tolerable content for dried seaweed products in Australia and New Zealand. The combined results of yield, biofouling, and biochemical composition suggest that, for an April deployment at the sites investigated, M. pyrifera should be harvested in July-August (mid to late winter) to optimise yield and quality of the cultured kelp biomass. These findings provide a better understanding of the variation in growth and quality of cultivated M. pyrifera biomass in the region, and inform future management and development of kelp aquaculture in south-eastern Australia and in a global context.
Temperature Upshift Mostly but not Always Enhances the Growth of Vibrio Species: A Systematic Review
Authors: Sheikh H. I. , Najiah M. , Fadhlina A. , Laith A. A. , Nor M. M. , Jalal K. C. A. , Kasan Nor Azman
Published: July 2022

The spread of Vibrio spp. and the prevalence of vibriosis around the world are often correlated with global warming, especially an increase in sea surface temperature. However, many ecological and virulence factors also trigger the spread of Vibrio species, while vibriosis occurs at both low and high temperatures. Recent studies that focused on a single factor (e.g. temperature) and one species (e.g. V. vulnificus) also showed that single factors such as temperature were insufficient to explain the pathogenicity and virulence of Vibrio spp. In this review, we have compiled and discussed the existing literature on the effect of temperature on different growth and pathogenicity of Vibrio spp. A systematic literature search was conducted using Web of Science (WoS) and SCOPUS databases up to 1st January 2022. After applying the selection criteria, a final list of 111 articles was included in this review. We have found that only certain Vibrio spp. are positively impacted by the increase in temperature. The results showed that 47% of the articles reported an increase in growth with the increase in temperature, while 38% showed that the relationship is complex. Reduced growth (6%) and no effect (9%) were also reported. These results showed that most but not all Vibrio spp. were positively impacted by an increase in temperature. The results indicated that V. alginolyticus, V. cholerae, V. parahaemolyticus, and V. vulnificus are the biggest threats to human and animal wellbeing.
13C-sucrose breath test for the non-invasive assessment of environmental enteropathy in Zambian adults
Authors: Schillinger Robert J. , Mwakamui Simutanyi , Mulenga Chola , Tembo Mizinga , Hodges Phoebe , Besa Ellen , Chandwe Kanta , Owino Victor O. , Edwards Christine A. , Kelly Paul , Morrison Douglas J.
Published: July 2022

Objectives

Environmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE.

Methods

We optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE.

Results

Fully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height (r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies.

Conclusion

A 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.
The bacterial and fungal microbiomes of ectomycorrhizal roots from stone oaks and Yunnan pines in the subtropical forests of the Ailao Mountains of Yunnan
Authors: Zeng Qingchao , Man Xiaowu , Lebreton Annie , Dai Yucheng , Martin Francis M.
Published: July 2022

Ectomycorrhizal (ECM) symbioses play an important role in tree biology and forest ecology. However, little is known on the composition of bacterial and fungal communities associated to ECM roots. In the present study, we surveyed the bacterial and fungal microbiome of ECM roots from stone oaks (Lithocarpus spp.) and Yunnan pines (Pinus yunnanensis) in the subtropical forests of the Ailao Mountains (Yunnan, China). The bacterial community was dominated by species pertaining to Rhizobiales and Acidobacteriales, whereas the fungal community was mainly composed of species belonging to the Russulales and Thelephorales. While the bacterial microbiome hosted by ECM roots from stone oaks and Yunnan pines was very similar, the mycobiome of these host trees was strikingly distinct. The microbial networks for bacterial and fungal communities showed a higher complexity in Lithocarpus ECM roots compared to Pinus ECM roots, but their modularity was higher in Pinus ECM roots. Seasonality also significantly influenced the fungal diversity and their co-occurrence network complexity. Our findings thus suggest that the community structure of fungi establishing and colonizing ECM roots can be influenced by the local soil/host tree environment and seasonality. These results expand our knowledge of the ECM root microbiome and its diversity in subtropical forest ecosystems.
Recent progress on harm, pathogen classification, control and pathogenic molecular mechanism of anthracnose of oil-tea
Authors: Chen Xinggang , Chen Xingzhou , Tan Qian , Mo Xiuli , Liu Junang , Zhou Guoying
Published: July 2022

Oil tea (Camellia oleifera), mainly used to produce high-quality edible oil, is an important cash crop in China. Anthracnose of oil tea is a considerable factor that limits the yield of tea oil. In order to effectively control the anthracnose of oil tea, researchers have worked hard for many years, and great progress has been made in the research of oil tea anthracnose. For instance, researchers isolated a variety of Colletotrichum spp. from oil tea and found that Colletotrichum fructicola was the most popular pathogen in oil tea. At the same time, a variety of control methods have been explored, such as cultivating resistant varieties, pesticides, and biological control, etc. Furthermore, the research on the molecular pathogenesis of Colletotrichum spp. has also made good progress, such as the elaboration of the transcription factors and effector functions of Colletotrichum spp. The authors summarized the research status of the harm, pathogen types, control, and pathogenic molecular mechanism of oil tea anthracnose in order to provide theoretical support and new technical means for the green prevention and control of oil tea anthracnose.
A clinical Pseudomonas juntendi strain with blaIMP−1 carried by an integrative and conjugative element in China
Authors: Zheng Lin , Zhang Xinfang , Zhu Lingwei , Lu Gejin , Guan Jiayao , Liu Mingwei , Jing Jie , Sun Shiwen , Wang Ying , Sun Yang , Ji Xue , Jiang Bowen , Chen Jun , Liu Jun , Chen Ping , Guo Xuejun
Published: July 2022

Objective

To precisely determine the species of a carbapenem-resistant Pseudomonas strain 1809276 isolated from the urine of a Chinese patient and analyze its integrative and conjugative element (ICE) 1276 formation mechanism.

Methods

Single-molecule real-time (SMRT) sequencing was carried out on strain 18091276 to obtain the complete chromosome and plasmid (pCN1276) sequences, and average nucleotide identity (ANI) was used for precise species identification. The ICEs in GenBank with the same integrase structure as ICE 1276 were aligned. At the same time, the transfer ability of blaIMP−1 and the antibiotic sensitivity of Pseudomonas juntendi 18091276 were tested.

Results

This bacterium was P. juntendi, and its drug resistance mechanism is the capture of the accA4' gene cassette by the Tn402-like type 1 integron (IntI1-blaIMP−1) to form In1886 before its capture by the ΔTn4662a-carrying ICE 1276. The acquisition of blaIMP−1 confers carbapenem resistance to P. juntendi 18091276.

Conclusion

The formation of blaIMP−1-carrying ICE 1276, its further integration into the chromosomes, and transposition and recombination of other elements promote bacterial gene accumulation and transmission.
Secretion of poly-γ-glutamic acid by Bacillus atrophaeus NX-12 enhanced its root colonization and biocontrol activity
Authors: Xue Jian , Tong Tong , Wang Rui , Qiu Yibin , Gu Yian , Sun Liang , Xu Hong , Lei Peng
Published: July 2022

Bacilli are used as biocontrol agents (BCAs) against phytopathogens and most of them can produce poly-γ-glutamic acid (γ-PGA) as one of the major extracellular polymeric substances (EPSs). However, the role of γ-PGA in plant biocontrol is still unclear. In this study, Bacillus atrophaeus NX-12 (γ-PGA yield: 16.8 g/l) was screened, which formed a strong biofilm and has been proved to be a promising BCA against Cucumber Fusarium wilt. Then, the γ-PGA synthesis gene cluster pgsBCA was knocked out by CRISPR-Cas9n. Interestingly, the antifungal ability of γ-PGA synthetase-deficient strain NX-12Δpgs (γ-PGA yield: 1.65 g/l) was improved in vitro, while the biocontrol ability of NX-12Δpgs was greatly diminished in situ. Data proved that γ-PGA produced by NX-12 contributes to the biofilm formation and rhizosphere colonization, which effectively improved biocontrol capability. Taken together, these findings prove that the mechanism of γ-PGA promotes the colonization of NX-12 and thus assists in controlling plant diseases, which highlight the key role of γ-PGA produced by BCA in biocontrol.
The influence of metabolic syndrome on age-related hearing loss from the perspective of mitochondrial dysfunction
Authors: Guo Dongye , Zhang Andi , Zou Tianyuan , Ding Rui , Chen Kaili , Pan Yi , Ji Peilin , Ye Bin , Xiang Mingliang
Published: July 2022

With the increase in life expectancy in the global population, aging societies have emerged in many countries, including China. As a common sensory defect in the elderly population, the prevalence of age-related hearing loss and its influence on society are increasing yearly. Metabolic syndrome is currently one of the main health problems in the world. Many studies have demonstrated that metabolic syndrome and its components are correlated with a variety of age-related diseases of the peripheral sensory system, including age-related hearing loss. Both age-related hearing loss and metabolic syndrome are high-prevalence chronic diseases, and many people suffer from both at the same time. In recent years, more and more studies have found that mitochondrial dysfunction occurs in both metabolic syndrome and age-related hearing loss. Therefore, to better understand the impact of metabolic syndrome on age-related hearing loss from the perspective of mitochondrial dysfunction, we reviewed the literature related to the relationship between age-related hearing loss and metabolic syndrome and their components to discern the possible role of mitochondria in both conditions.
Systematic review of the therapeutic use of Schwann cells in the repair of peripheral nerve injuries: Advancements from animal studies to clinical trials
Authors: Vallejo Frederic A. , Diaz Anthony , Errante Emily L. , Smartz Taylor , Khan Aisha , Silvera Risset , Brooks Adriana E. , Lee Yee-Shuan , Burks Stephen Shelby , Levi Allan D.
Published: July 2022

Objective

To systematically evaluate the literature on the therapeutic use of Schwann cells (SC) in the repair of peripheral nerve injuries.

Methods

The Cochrane Library and PubMed databases were searched using terms [(“peripheral nerve injury” AND “Schwann cell” AND “regeneration”) OR (“peripheral nerve injuries”)]. Studies published from 2008 to 2022 were eligible for inclusion in the present study. Only studies presenting data from in-vivo investigations utilizing SCs in the repair of peripheral nerve injuries qualified for review. Studies attempting repair of a gap of ≥10 mm were included. Lastly, studies needed to have some measure of quantifiable regenerative outcome data such as histomorphometry, immunohistochemical, electrophysiology, or other functional outcomes.

Results

A search of the PubMed and Cochrane databases revealed 328 studies. After screening using the abstracts and methods, 17 studies were found to meet our inclusion criteria. Good SC adherence and survival in conduit tubes across various studies was observed. Improvement in morphological and functional outcomes with the use of SCs in long gap peripheral nerve injuries was observed in nearly all studies.

Conclusion

Based on contemporary literature, SCs have demonstrated clear potential in the repair of peripheral nerve injury in animal studies. It has yet to be determined which nerve conduit or graft will prove superior for delivery and retention of SCs for nerve regeneration. Recent developments in isolation and culturing techniques will enable further translational utilization of SCs in future clinical trials.
The role of gamma oscillations in central nervous system diseases: Mechanism and treatment
Authors: Guan Ao , Wang Shaoshuang , Huang Ailing , Qiu Chenyue , Li Yansong , Li Xuying , Wang Jinfei , Wang Qiang , Deng Bin
Published: July 2022

Gamma oscillation is the synchronization with a frequency of 30–90 Hz of neural oscillations, which are rhythmic electric processes of neuron groups in the brain. The inhibitory interneuron network is necessary for the production of gamma oscillations, but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this network to malfunction. Gamma oscillations specifically control the connectivity between different brain regions, which is crucial for perception, movement, memory, and emotion. Studies have linked abnormal gamma oscillations to conditions of the central nervous system, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Evidence suggests that gamma entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses the function of gamma oscillations in advanced brain activities from both a physiological and pathological standpoint, and it emphasizes gamma entrainment as a potential therapeutic approach for a range of neuropsychiatric diseases.
Tension-type headache and low back pain reconsidered
Authors: Astrup Jens , Gyntelberg Finn
Published: July 2022

The natural history and clinical course of tension-type headache and non-specific low back pain are reconsidered. By closer examination, these two conditions appear to share several specific clinical features. Both are muscular pain conditions along the spine, they have a preponderance in women, they may occur spontaneously or follow a trivial traumatic incident, and they both have a high risk of chronicity. The affected muscles are tender with tender points. EMG indicates diffuse hyperactivity and abnormal activation pattern, and motor control of the affected muscles and adjacent muscle groups is discoordinated. These shared features suggest analogous pathophysiology involving the neuromotor control of affected and adjacent muscle groups in the cervical and lumbar regions, respectively. As recently suggested for the whiplash disease, we suggest the term spinal dyssynergia for this specific pattern of pathology. This suggestion provides a new perspective for the understanding of these diseases by placing their cause within the central nervous system and not in the spine or spinal musculature. This perspective warrants further clinical, neurophysiological, and neuropharmacological studies of this ‘family’ of common yet poorly understood clinical muscular pain conditions along the spine.
Diagnosis and prognostic value of circDLGAP4 in acute ischemic stroke and its correlation with outcomes
Authors: Bai Ying , Ren Hui , Zhu Yi , Chen Xufeng , Yang Li , Xia Jiangyan , Shu Guofang , Han Bing
Published: July 2022

Rationale and aims

Circular RNAs are a subclass of noncoding RNAs in mammalian cells and highly expressed in the central nervous system. Although their physiological functions are not yet completely defined, they are thought to promise as stroke biomarkers because of their stability in peripheral blood.

Sample Size Estimate: 222 participants.

Methods and design

The plasma of patients with acute ischemic stroke (AIS) (n = 111) and non-stroke controls (n = 111) from November 2017 to February 2019 were enrolled in our research. The expression of circDLGAP4 in plasma was evaluated using real-time PCR.

Study outcomes

In patients with AIS, circDLGAP4 was significantly decreased in comparison with non-stroke controls. The CircDLGAP4 level had a significant AUC of 0.7896 with 91.72% sensitivity and 64.83% specificity in diagnosing AIS. Furthermore, the circDLGAP4 level was related to smoking history and previous transient ischemic attack/stroke/myocardial infarction in all samples. The change rate in circDLGAP4 within the first 7 days showed an AUC curve of 0.960 in predicting an stroke outcome.

Conclusion

circDLGAP4 could serve as biomarker for AIS diagnosis and prediction of stroke outcomes.
Effects of repetitive transcranial magnetic stimulation on upper-limb and finger function in stroke patients: A systematic review and meta-analysis of randomized controlled trials
Authors: Chen Gengbin , Lin Tuo , Wu Manfeng , Cai Guiyuan , Ding Qian , Xu Jiayue , Li Wanqi , Wu Cheng , Chen Hongying , Lan Yue
Published: July 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for stroke rehabilitation. Several studies have demonstrated the effectiveness of rTMS in restoring motor function. This meta-analysis aimed to summarize the current evidence of the effect of rTMS in improving upper limb function and fine motor recovery in stroke patients.

Methods

Three online databases (Web of Science, PubMed, and Embase) were searched for relevant randomized controlled trials. A total of 45 studies (combined n = 2064) were included. Random effects model was used for meta-analysis and effect size was reported as standardized mean difference (SMD).

Results

rTMS was effective in improving fine motor function in stroke patients (SMD, 0.38; 95% CI 0.19–0.58; P = 0). On subgroup analyses, for post-stroke functional improvement of the upper extremity, bilateral hemisphere stimulation was more effective than unilateral stimulation during the acute phase of stroke, and a regimen of 20 rTMS sessions produced greater improvement than <20 sessions. In the subacute phase of stroke, affected hemispheric stimulation with a 40-session rTMS regimen was superior to unaffected hemispheric stimulation or bilateral hemispheric stimulation with <40 sessions. Unaffected site stimulation with a 10-session rTMS regimen produced significant improvement in the chronic phase compared to affected side stimulation and bilateral stimulation with >10 rTMS sessions. For the rTMS stimulation method, both TBS and rTMS were found to be significantly more effective in the acute phase of stroke, but TBS was more effective than rTMS. However, rTMS was found to be more effective than TBS stimulation in patients in the subacute and chronic phases of stroke. rTMS significantly improved upper limb and fine function in the short term (0–1-month post-intervention) and medium term (2–5 months), but not for upper limb function in the long term (6 months+). The results should be interpreted with caution due to significant heterogeneity.

Conclusions

This updated meta-analysis provides robust evidence of the efficacy of rTMS treatment in improving upper extremity and fine function during various phases of stroke.

Systematic Review Registration

https://inplasy.com/inplasy-2022-5-0121/, identifier: INPLASY202250121.
Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage
Authors: Cliteur Maaike P. , Sondag Lotte , Wolsink Axel , Rasing Ingeborg , Meijer F. J. A. , Jolink Wilmar M. T. , Wermer Marieke J. H. , Klijn Catharina J. M. , Schreuder Floris H. B. M.
Published: July 2022

Objective

Blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.

Methods

We selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.

Results

We included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1–19). Median ICH volume was 17.0 mL (IQR 1.4–88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = −0.003, 95% CI −0.003–0.03, p = 0.83), nor for any of the individual radiological cSVD markers.

Conclusion

We found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.
An informal logic of feedback-based temporal control
Authors: Tilsen Sam
Published: July 2022

A conceptual framework and mathematical model of the control of articulatory timing are presented, in which feedback systems play a fundamental role. The model applies both to relatively small timescales, such as within syllables, and to relatively large timescales, such as multi-phrase utterances. A crucial distinction is drawn between internal/predictive feedback and external/sensory feedback. It is argued that speakers modulate attention to feedback to speed up and slow down speech. A number of theoretical implications of the framework are discussed, including consequences for the understanding of syllable structure and prosodic phrase organization.
Contrast Sensitivity and Night Driving in Older People: Quantifying the Relationship Between Visual Acuity, Contrast Sensitivity, and Hazard Detection Distance in a Night-Time Driving Simulator
Authors: Jones Pete R. , Ungewiss Judith , Eichinger Peter , Wörner Michael , Crabb David P. , Schiefer Ulrich
Published: July 2022

Purpose

(i) To assess how well contrast sensitivity (CS) predicts night-time hazard detection distance (a key component of night driving ability), in normally sighted older drivers, relative to a conventional measure of high contrast visual acuity (VA); (ii) To evaluate whether CS can be accurately quantified within a night driving simulator.

Materials and Methods

Participants were 15 (five female) ophthalmologically healthy adults, aged 55–81 years. CS was measured in a driving simulator using Landolt Cs, presented under static or dynamic driving conditions, and with or without glare. In the dynamic driving conditions, the participant was asked to simultaneously maintain a (virtual) speed of 60 km/h on a country road. In the with glare conditions, two calibrated LED arrays, moved by cable robots, simulated the trajectories and luminance characteristics of the (low beam) headlights of an approaching car. For comparison, CS was also measured clinically (with and without glare) using a Optovist I instrument (Vistec Inc., Olching, Germany). Visual acuity (VA) thresholds were also assessed at high and low contrast using the Freiburg Visual Acuity Test (FrACT) under photopic conditions. As a measure of driving performance, median hazard detection distance (MHDD) was computed, in meters, across three kinds of simulated obstacles of varying contrast.

Results

Contrast sensitivity and low contrast VA were both significantly associated with driving performance (both P < 0.01), whereas conventional high contrast acuity was not (P = 0.10). There was good correlation (P < 0.01) between CS measured in the driving simulator and a conventional clinical instrument (Optovist I). As expected, CS was shown to decrease in the presence of glare, in dynamic driving conditions, and as a function of age (all P < 0.01).

Conclusion

Contrast sensitivity and low contrast VA predict night-time hazard detection ability in a manner that conventional high contrast VA does not. Either may therefore provide a useful metric for assessing fitness to drive at night, particularly in older individuals. CS measurements can be made within a driving simulator, and the data are in good agreement with conventional clinical methods (Optovist I).
Pharmacotherapeutic management of insomnia and effects on sleep processes, neural plasticity, and brain systems modulating stress: A narrative review
Authors: Palagini Laura , Bianchini Carlotta
Published: July 2022

Introduction

Insomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may contribute to mental and physical disorders. In this framework, assessing and targeting insomnia is of importance.

Aim

Since maladaptive neuroplasticity and allostatic overload are hypothesized to be related to GABAergic alterations, compounds targeting GABA may play a key role. Accordingly, the aim of this review was to discuss the effect of GABAA receptor agonists, short-medium acting hypnotic benzodiazepines and the so called Z-drugs, at a molecular level.

Method

Literature searches were done according to PRISMA guidelines. Several combinations of terms were used such as “hypnotic benzodiazepines” or “brotizolam,” or “lormetazepam” or “temazepam” or “triazolam” or “zolpidem” or “zopiclone” or “zaleplon” or “eszopiclone” and “insomnia” and “effects on sleep” and “effect on brain plasticity” and “effect on stress system”. Given the complexity and heterogeneity of existing literature, we ended up with a narrative review.

Results

Among short-medium acting compounds, triazolam has been the most studied and may regulate the stress system at central and peripheral levels. Among Z-drugs eszopiclone may regulate the stress system. Some compounds may produce more “physiological” sleep such as brotizolam, triazolam, and eszopiclone and probably may not impair sleep processes and related neural plasticity. In particular, triazolam, eszopiclone, and zaleplon studied in vivo in animal models did not alter neuroplasticity.

Conclusion

Current models of insomnia may lead us to revise the way in which we use hypnotic compounds in clinical practice. Specifically, compounds should target sleep processes, the stress system, and sustain neural plasticity. In this framework, among the short/medium acting hypnotic benzodiazepines, triazolam has been the most studied compound while among the Z-drugs eszopiclone has demonstrated interesting effects. Both offer potential new insight for treating insomnia.
Age-Dependent Behavioral and Metabolic Assessment of AppNL−G−F/NL−G−F Knock-in (KI) Mice
Authors: Wang Shanshan , Ichinomiya Taiga , Savchenko Paul , Devulapalli Swetha , Wang Dongsheng , Beltz Gianna , Saito Takashi , Saido Takaomi C. , Wagner Steve L. , Patel Hemal H. , Head Brian P.
Published: July 2022

Mitochondria play a crucial role in Alzheimer's disease (AD) onset and progression. Traditional transgenic AD mouse models which were widely used in the past decades share a common limitation: The overexpression of APP and overproduction of amyloid-beta (Aβ) are accompanied by other APP peptide fragments, which could introduce artificial and non-clinically relevant phenotypes. Here, we performed an in-depth and time-resolved behavioral and metabolic characterization of a clinically relevant AD mouse model engineered to express normal physiological levels of APP harboring humanized Swedish (K670N/M671L), Beyreuther/Iberian (I716F), and Arctic (E693G) mutations (AppNL−G−F/NL−G−F), termed APP knock-in (APPKI) mice. Our result showed that APPKI mice exhibited fear learning deficits at 6-m age and contextual memory deficit at 12-m age. Histopathological analysis revealed mild amyloidosis (6E10) accompanied by microgliosis (Iba1) as early as 3 months, which progressed significantly together with significant astrocytosis at 6 and 12 m. We further analyzed hippocampal mitochondrial dysfunction by multiple assays, while 3-m APPKI mice brain mitochondrial function remains a similar level as WT mice. Significant mitochondrial dysfunction characterized by decreased ATP production and higher membrane potential with subsequent overproduction of reactive oxygen species (ROS) was observed in mitochondria isolated from 7-m APPKI mice hippocampal tissue. Morphologically, these mitochondria were larger in volume with a decreased level of mitochondrial fusion protein mitofusin-2 (MFN2). At 12 months, APPKI mice exhibit a significantly decreased total mitochondrial oxygen consumption rate (OCR) in isolated hippocampal mitochondria detected by high-resolution respirometry. These data indicate early mitochondrial dysfunction in the brain at pre-symptomatic age in the AppNL−G−F/NL−G−mice, which may play a key role in the progression of the disease. Moreover, the identified behavioral and bioenergetic alterations in this clinically relevant AD mouse model provide a valuable tool to optimize the temporal component for therapeutic interventions to treat AD.
The effects of whey protein fibrils on the linear and non-linear rheological properties of a gluten-free dough
Authors: Shan Shengyue , Chen Da , Federici Enrico , Jones Owen G. , Campanella Osvaldo H.
Published: July 2022

The increasing awareness of the celiac disease, an autoimmune disorder caused by the consumption of products containing gluten, has led to a growing interest in the development of gluten-free bakery products. In this study, whey protein fibrils (WPFs) were incorporated to mimic the fibrous network of gluten. The rheological properties and microstructure of the developed gluten-free doughs were evaluated and compared with gluten doughs. Protein fibrils were prepared by heating a whey protein isolate (WPI) solution at 80°C in an acidic environment with low salt concentration, and then the fibril lengths were adjusted by leveling up the solution pH to 3.5 and 7. The dimensions of the fibrils were measured by atomic force microscopy (AFM). Rice and potato starches were mixed with fibrils, WPI, gluten, or without protein, to form different doughs for further investigation. Shear tests, including stress sweep, frequency sweep, and creep recovery, were performed to study the viscoelastic properties of doughs under small or large deformation. The strain-hardening properties of doughs under biaxial extension were studied by the lubricated squeezing flow method. The microstructure of the doughs was characterized by cryo-scanning electron microscopy (cryo-SEM). Compared with doughs prepared with WPI and no proteins, doughs incorporating fibrils showed comparable linear viscoelasticity to gluten dough tested with stress sweep, frequency sweep, and creep recovery in the linear viscoelastic region. More differences between the protein fibril doughs were revealed in the rheological properties in the non-linear region. Creep recovery parameters, such as compliance, elastic moduli during the creep, and recovery stages of gluten dough, were like those of WPF pH7 dough, but significantly different from those of the WPF pH3.5 dough. Strain-hardening properties were found in the WPF pH7 dough, although not in WPF pH3.5 dough. Microstructural characterization showed that both fibrils prepared with the different conditions formed a continuous protein phase for the improvement of dough cohesiveness, but the structure of the phase was different between the two fibrils. To summarize, whey protein fibril at pH 7 seemed to have the potential of being used as an ingredient with similar functions to gluten in gluten-free bakery products.