bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the influence of coral-reef-derived dimethylsulfide on the atmosphere of the Great Barrier Reef, Australia
Authors: Jackson Rebecca L. , Woodhouse Matthew T. , Gabric Albert J. , Cropp Roger A. , Swan Hilton B. , Deschaseaux Elisabeth S. M. , Trounce Haydn
Published: August 2022

Marine dimethylsulfide (DMS) is an important source of natural sulfur to the atmosphere, with potential implications for the Earth’s radiative balance. Coral reefs are important regional sources of DMS, yet their contribution is not accounted for in global DMS climatologies or in model simulations. This study accounts for coral-reef-derived DMS and investigates its influence on the atmosphere of the Great Barrier Reef (GBR), Australia, using the Australian Community Climate and Earth System Simulator Atmospheric Model version 2 (ACCESS-AM2). A climatology of seawater surface DMS (DMSw) concentration in the GBR and an estimate of direct coral-to-air DMS flux during coral exposure to air at low tide are incorporated into the model, increasing DMS emissions from the GBR region by 0.02 Tg yr-1. Inclusion of coral-reef-derived DMS increased annual mean atmospheric DMS concentration over north-eastern Australia by 29%, contributing to an increase in gas-phase sulfate aerosol precursors of up to 18% over the GBR. The findings suggest that the GBR is an important regional source of atmospheric sulfur, with the potential to influence local-scale aerosol-cloud processes. However, no influence on sulfate aerosol mass or number concentration was detected, even with a reduction in anthropogenic sulfur dioxide emissions, indicating that DMS may not significantly influence the regional atmosphere at monthly, annual or large spatial scales. Further research is needed to improve the representation of coral-reef-derived DMS in climate models and determine its influence on local, sub-daily aerosol-cloud processes, for which observational studies suggest that DMS may play a more important role.
A Multivariable Empirical Algorithm for Estimating Particulate Organic Carbon Concentration in Marine Environments From Optical Backscattering and Chlorophyll-a Measurements
Authors: Koestner Daniel , Stramski Dariusz , Reynolds Rick A.
Published: August 2022

Accurate estimates of the oceanic particulate organic carbon concentration (POC) from optical measurements have remained challenging because interactions between light and natural assemblages of marine particles are complex, depending on particle concentration, composition, and size distribution. In particular, the applicability of a single relationship between POC and the spectral particulate backscattering coefficient bbp(λ) across diverse oceanic environments is subject to high uncertainties because of the variable nature of particulate assemblages. These relationships have nevertheless been widely used to estimate oceanic POC using, for example, in situ measurements of bbp from Biogeochemical (BGC)-Argo floats. Despite these challenges, such an in situbased approach to estimate POC remains scientifically attractive in view of the expanding global-scale observations with the BGC-Argo array of profiling floats equipped with optical sensors. In the current study, we describe an improved empirical approach to estimate POC which takes advantage of simultaneous measurements of bbp and chlorophyll-a fluorescence to better account for the effects of variable particle composition on the relationship between POC and bbp. We formulated multivariable regression models using a dataset of field measurements of POC, bbp, and chlorophyll-a concentration (Chla), including surface and subsurface water samples from the Atlantic, Pacific, Arctic, and Southern Oceans. The analysis of this dataset of diverse seawater samples demonstrates that the use of bbp and an additional independent variable related to particle composition involving both bbp and Chla leads to notable improvements in POC estimations compared with a typical univariate regression model based on bbp alone. These multivariable algorithms are expected to be particularly useful for estimating POC with measurements from autonomous BGC-Argo floats operating in diverse oceanic environments. We demonstrate example results from the multivariable algorithm applied to depth-resolved vertical measurements from BGC-Argo floats surveying the Labrador Sea.
Field investigation of steel pipe pile under lateral loading in extensively soft soil
Authors: Yi Shixuan , Liu Jianmei
Published: August 2022

The construction of railway and highway embankments has a significant influence on the behavior of existing pile foundations, especially in the situation of high embankments and extensively soft soils, which are commonly encountered in coastal areas. A high embankment might produce large lateral movement and bending moment to the existing adjacent piles, which would cause the failure of the pile if the surcharge loading is not properly considered. A field test was designed and performed to investigate the effect of lateral surcharge loading on the existing adjacent pile in extensively soft soils. A 4 m high embankment was constructed in five lifts and was close to the existing adjacent steel pipe pile with a length of 35 m. The deformation of the pile and the soft soils, the excess pore water pressure, and lateral earth pressures were measured during the surcharge loading test. The test results showed that the lateral displacement of the steel pipe pile at the ground surface exceeded 229.9 mm and could not maintain constant due to the surcharge loading. The lateral displacement decreased along with the pile depth and was relatively small when the pile depth exceeded 10 m. Large lateral displacements were observed in the soft soils at different locations. The surcharge loading zone showed obvious downward displacements, while the soft soils close to the loading zone showed upward displacements. The excess pore water pressure changed regularly with the construction of the embankment, and its maximum value reached 53.6 kPa. The lateral earth pressures that acted on the pile continuously increased with the increase in the embankment height, which caused large deformation of the pile.
Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation
Authors: El-Domiaty Heba F. , Sweed Eman , Kora Mona A. , Zaki Nader G. , Khodir Suzan A.
Published: August 2022

Background

Metabolic syndrome (MetS) is an independent risk factor for chronic kidney disease (CKD) through many mechanisms, including activation of the renin–angiotensin system. The deleterious effects of angiotensin II (Ang II) can be counterbalanced by angiotensin-converting enzyme 2 (ACE2). Diminazene aceturate (DIZE), an anti-trypanosomal drug, can activate ACE2.

Objective

This study aimed to investigate the possible reno-protective effects of DIZE in MetS rats with elucidation of related mechanisms.

Materials and methods

Thirty adult male Wistar albino rats were divided equally into control, MetS, and MetS + DIZE groups. Body weight, systolic blood pressure (SBP), and urinary albumin levels were measured. Serum levels of fasting blood glucose (FBG), insulin, uric acid, lipid profile, urea, and creatinine were measured. Homeostasis Model Assessment Index (HOMA-IR) was estimated. Subsequently, renal levels of ACE2, Ang II, malondialdehyde (MDA), reduced glutathione (GSH), and tumor necrosis factor-α (TNF-α) were measured with histopathological and immunohistochemical assessment of TLR4 and NF-κB in renal tissues.

Results

MetS caused dyslipidemia with significant increases in body weight, SBP, FBG, serum insulin, HOMA-IR, uric acid, urea, creatinine, urinary albumin, and renal levels of Ang II, MDA, and TNF-α, whereas renal ACE2 and GSH were significantly decreased. Renal TLR4 and NF-κB immunoreactivity in MetS rats was upregulated. DIZE supplementation of MetS rats induced significant improvements in renal function parameters; this could be explained by the ability of DIZE to activate renal ACE2 and decrease renal Ang II levels with downregulation of renal TLR4 and NF-κB expression.

Conclusion

DIZE exerts a reno-protective effect in MetS, mainly by downregulating renal TLR4 and NF-κB levels.
Drosophila melanogaster diabetes models and its usage in the research of anti-diabetes management with traditional Chinese medicines
Authors: Miao Yaodong , Chen Rui , Wang Xiaolu , Zhang Jie , Tang Weina , Zhang Zeyu , Liu Yaoyuan , Xu Qiang
Published: August 2022

The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide, but the underlying molecular mechanisms of disease development have not been elucidated, and the current popular anti-diabetic approaches still have non-negligible limitations. In the last decades, several different DM models were established on the classic model animal, the fruit fly (Drosophila melanogaster), which provided a convenient way to study the mechanisms underlying diabetes and to discover and evaluate new anti-diabetic compounds. In this article, we introduce the Drosophila Diabetes model from three aspects, including signal pathways, established methods, and pharmacodynamic evaluations. As a highlight, the progress in the treatments and experimental studies of diabetes with Traditional Chinese Medicine (TCM) based on the Drosophila Diabetes model is reviewed. We believe that the values of TCMs are underrated in DM management, and the Drosophila Diabetes models can provide a much more efficient tool to explore its values of it.
Iodixanol density gradients as an effective phytoplasma enrichment approach to improve genome sequencing
Authors: Rodrigues Jardim Bianca , Tran-Nguyen Lucy T. T. , Gambley Cherie , Rodoni Brendan , Constable Fiona E.
Published: August 2022

Obtaining complete phytoplasma genomes is difficult due to the lack of a culture system for these bacteria. To improve genome assembly, a non-ionic, low- and iso-osmotic iodixanol (Optiprep™) density gradient centrifugation method was developed to enrich for phytoplasma cells and deplete plant host tissues prior to deoxyribonucleic acid (DNA) extraction and high-throughput sequencing (HTS). After density gradient enrichment, potato infected with a ‘Candidatus Phytoplasma australasia’-related strain showed a ∼14-fold increase in phytoplasma HTS reads, with a ∼1.7-fold decrease in host genomic reads compared to the DNA extracted from the same sample without density gradient centrifugation enrichment. Additionally, phytoplasma genome assemblies from libraries equalized to 5 million reads were, on average, ∼15,000 bp larger and more contiguous (N50 ∼14,800 bp larger) than assemblies from the DNA extracted from the infected potato without enrichment. The method was repeated on capsicum infected with Sweet Potato Little Leaf phytoplasma (‘Ca. Phytoplasma australasia’-related strain) with a lower phytoplasma titer than the potato. In capsicum, ∼threefold more phytoplasma reads and ∼twofold less host genomic reads were obtained, with the genome assembly size and N50 values from libraries equalized to 3.4 million reads ∼137,000 and ∼4,000 bp larger, respectively, compared to the DNA extracted from infected capsicum without enrichment. Phytoplasmas from potato and capsicum were both enriched at a density of 1.049–1.058 g/ml. Finally, we present two highly contiguous ‘Ca. Phytoplasma australasia’ phytoplasma reference genomes sequenced from naturally infected Solanaceae hosts in Australia. Obtaining high-quality phytoplasma genomes from naturally infected hosts will improve insights into phytoplasma taxonomy, which will improve their detection and disease management.
Analysis of circulating respiratory syncytial virus A strains in Shanghai, China identified a new and increasingly prevalent lineage within the dominant ON1 genotype
Authors: Zhao Xue , Wang Chun , Jiang Hui , Zhang Hong , Fang Fanghao , Chen Min , Yuan Zhengan , Teng Zheng , Liu Jing , Zhang Xi
Published: August 2022

Respiratory syncytial virus A (RSV-A) is one of the commonest pathogens causing acute respiratory tract infections in infants and children globally. The currently dominant circulating genotype of RSV-A, ON1, was first detected in Shanghai, China in 2011, but little data are available regarding its subsequent circulation and clinical impact here. In this work, we analyzed RSV-A infection in a cohort of patients hospitalized for acute respiratory infections in Shanghai Children’s Hospital, and RSV-A was detected in ~10% of these cases. RSV-A G gene sequencing revealed that all successfully sequenced strains belonged to ON1 genotype, but in phylogenetic analysis, the majority of these sequences formed a clade separate from the four previously established lineages within ON1. The new lineage, denoted ON1-5, was supported by phylogenetic analyses using additional G gene sequences from RSV-A strains isolated in Shanghai and elsewhere. ON1-5 first appeared in 2015 in China and the Netherlands, and has since spread to multiple continents and gained dominance in Asia. In our cohort, ON1-5 was not associated with markedly different clinical presentations compared to other ON1 lineages. ON1-5 strains are characterized by four amino acid variations in the two mucin-like regions of G protein, and one variation (N178G) within the highly conserved CCD domain that is involved in receptor binding. These data highlight the continuous evolution of RSV-A, and suggest the possibility of the virus acquiring variations in domains traditionally considered to be conserved for fitness gain.
Comparative genomics provides insights into the potential biocontrol mechanism of two Lysobacter enzymogenes strains with distinct antagonistic activities
Authors: Xu Shuai , Zhang Ziyu , Xie Xuewen , Shi Yanxia , Chai Ali , Fan Tengfei , Li Baoju , Li Lei
Published: August 2022

Lysobacter enzymogenes has been applied as an abundant beneficial microorganism to control plant disease; however, most L. enzymogenes strains have been mainly reported to control fungal diseases, not bacterial diseases. In this study, two L. enzymogenes strains were characterized, of which CX03 displayed a broad spectrum of antagonistic activities toward multiple bacteria, while CX06 exhibited a broad spectrum of antagonistic activities toward diverse fungi and oomycete, and the whole genomes of the two strains were sequenced and compared. The genome annotation showed that the CX03 genome comprised a 5,947,018 bp circular chromosome, while strain CX06 comprised a circular 6,206,196 bp chromosome. Phylogenetic analysis revealed that CX03 had a closer genetic relationship with L. enzymogenes ATCC29487T and M497-1, while CX06 was highly similar to L. enzymogenes C3. Functional gene annotation analyses of the two L. enzymogenes strains showed that many genes or gene clusters associated with the biosynthesis of different secondary metabolites were found in strains CX03 and CX06, which may be responsible for the different antagonistic activities against diverse plant pathogens. Moreover, comparative genomic analysis revealed the difference in bacterial secretory systems between L. enzymogenes strains CX03 and CX06. In addition, numerous conserved genes related to siderophore biosynthesis, quorum sensing, two-component systems, flagellar biosynthesis and chemotaxis were also identified in the genomes of strains CX03 and CX06. Most reported L. enzymogenes strains were proven mainly to suppress fungi, while CX03 exhibited direct inhibitory activities toward plant bacterial pathogens and showed an obvious role in managing bacterial disease. This study provides a novel understanding of the biocontrol mechanisms of L. enzymogenes, and reveals great potential for its application in plant disease control.
Retinal ganglion cell desensitization is mitigated by varying parameter constant excitation pulse trains
Authors: Li Wennan , Haji Ghaffari Dorsa , Misra Rohit , Weiland James D.
Published: August 2022

Retinal prostheses partially restore vision in patients blinded by retinitis pigmentosa (RP) and age-related macular degeneration (AMD). One issue that limits the effectiveness of retinal stimulation is the desensitization of the retina response to repeated pulses. Rapid fading of percepts is reported in clinical studies. We studied the retinal output evoked by fixed pulse trains vs. pulse trains that have variable parameters pulse-to-pulse. We used the current clamp to record RGC spiking in the isolated mouse retina. Trains of biphasic current pulses at different frequencies and amplitudes were applied. The main results we report are: (1) RGC desensitization was induced by increasing stimulus frequency, but was unrelated to stimulus amplitude. Desensitization persisted when the 20 Hz stimulation pulses were applied to the retinal ganglion cells at 65 μA, 85 μA, and 105 μA. Subsequent pulses in the train evoked fewer spikes. There was no obvious desensitization when 2 Hz stimulation pulse trains were applied. (2) Blocking inhibitory GABAA receptor increased spontaneous activity but did not reduce desensitization. (3) Pulse trains with constant charge or excitation (based on strength-duration curves) but varying pulse width, amplitude, and shape increased the number of evoked spikes/pulse throughout the pulse train. This suggests that retinal desensitization can be partially overcome by introducing variability into each pulse.
Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin
Authors: Hoelz Amanda Garcia , Bernardes Danielle , Cartarozzi Luciana Politti , Oliveira Alexandre Leite Rodrigues de
Published: August 2022

Dysregulated microglia and astrocytes have been associated with progressive neurodegeneration in multiple sclerosis (MS), highlighting the need for strategies that additionally target intrinsic inflammation in the central nervous system (CNS). The objective of the present study was to investigate the glial response in experimental autoimmune encephalomyelitis (EAE)-induced mice treated with a combination of dimethyl fumarate (DMF) and pregabalin (PGB). For that, 28 C57BL/6J mice were randomly assigned to the five experimental groups: naïve, EAE, EAE-DMF, EAE-PGB, and EAE-DMF + PGB. Pharmacological treatments were initiated with the beginning of clinical signs, and all animals were euthanized at 28 dpi for the lumbar spinal cord evaluation. The results demonstrated a stronger attenuation of the clinical presentation by the combined approach. DMF alone promoted the downregulation of Iba-1 (microglia/macrophages marker) in the ventral horn compared with the non-treated EAE animals (P < 0.05). PGB treatment was associated with reduced Iba-1 immunofluorescence in both the dorsal (P < 0.05) and ventral horn (P < 0.05) compared to EAE vehicle-treated counterparts. However, the combined approach reduced the Iba-1 marker in the dorsal (P < 0.05) and ventral (P < 0.01) horns compared to non-treated EAE animals and further reduced Iba-1 in the ventral horn compared to each drug-alone approach (P < 0.05). In addition, the combination of DMF and PGB reduced activated astrocytes (GFAP) in both the dorsal and ventral horns of the spinal cord to a naïve-like level and upregulated Nrf-2 expression. Taken together, the data herein suggest robust attenuation of the glial response in EAE mice treated with DMF and PGB.
History of development of the life-saving drug “Nusinersen” in spinal muscular atrophy
Authors: Qiu Jiaying , Wu Liucheng , Qu Ruobing , Jiang Tao , Bai Jialin , Sheng Lei , Feng Pengchao , Sun Junjie
Published: August 2022

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with an incidence of 1/6,000–1/10,000 and is the leading fatal disease among infants. Previously, there was no effective treatment for SMA. The first effective drug, nusinersen, was approved by the US FDA in December 2016, providing hope to SMA patients worldwide. The drug was introduced in the European Union in 2017 and China in 2019 and has so far saved the lives of several patients in most parts of the world. Nusinersen are fixed sequence antisense oligonucleotides with special chemical modifications. The development of nusinersen progressed through major scientific discoveries in medicine, genetics, biology, and other disciplines, wherein several scientists have made substantial contributions. In this article, we will briefly describe the pathogenesis and therapeutic strategies of SMA, summarize the timeline of important scientific findings during the development of nusinersen in a detailed, scientific, and objective manner, and finally discuss the implications of the development of nusinersen for SMA research.
Multifocal brain abscesses caused by invasive Streptococcus intermedia: A case report
Authors: Yao Lin , Chen Sansong , Yu Zuan , Yu Tao
Published: August 2022

Multifocal brain abscesses caused by invasive Streptococcus intermedia are relatively rare. Here, we present a 67-year-old male was admitted to the hospital for unconsciousness and fever. The computed tomography (CT) examination showed multiple intracranial space-occupying and “cavity-like” changes in the right lower lung. The examination of cerebrospinal fluid (CSF) was consistent with typical bacterial meningitis, CSF analyses revealed leukocytosis (10,300 × 106/L), elevated protein levels (140.39 mg/dL), decreased glucose levels (0.27 mmol/L), and normal chloride concentration level (120.2 mmol/L), however, pathogens were not detected in the cultures. Then, the CSF and sputum samples were analyzed using meta-genomic next-generation sequencing (mNGS), and S. intermedia was detected in both samples. We adjusted the use of antibiotics according to the results of mNGS in time. After anti-infective treatment, the patient achieved good treatment results in a very short time. This case highlights the mNGS can identify pathogens of brain abscess, and provide strong evidence for clinical diagnosis and treatment strategy.
Ultra-early endovascular treatment improves prognosis in High grade aneurysmal subarachnoid hemorrhage: A single-center retrospective study
Authors: Wu Botao , Huang Zhe , Liu Huan , He Jiayao , Ju Yan , Chen Ziwei , Zhang Taiwei , Yi Fuxin
Published: August 2022

Background

The long-term survival prognosis of patients with high-grade (Hunt-Hess grade IV–V or World Federation of Neurosurgical Societies grade IV–V) aneurysmal subarachnoid hemorrhage (aSAH) is generally poor, and the association between endovascular treatment timing and the prognosis of high-grade aSAH has not been explored in depth. This retrospective cohort study aimed to determine whether endovascular treatment within 24 h of high-grade aSAH is associated with a better prognosis.

Methods

We retrospectively analyzed the clinical data of patients with high-grade aSAH who were admitted to our institution between January 2018 and January 2021. The Modified Rankin Scale score was used to assess the 6-month prognosis of patients. Univariate and multivariate logistic regression analyses were used to identify the factors associated with prognosis. The area under the receiver operating characteristic (ROC) curve was used to assess the model's discriminatory ability.

Results

Eighty-six patients were included in the study. In the multivariate analysis, the timing of endovascular treatment (odds ratio = 7.003 [1.800–27.242], P = 0.005) was an independent risk factor for prognosis. The ROC curve showed that the predictive power of the timing of endovascular treatment was 0.744, the best cut-off value was 12.5 h, and the corresponding sensitivity and specificity were 71.4 and 70.5%, respectively. Hydrocephalus (P = 0.005) and pulmonary infection (P = 0.029) were also associated with prognosis. In addition, cerebrospinal fluid drainage immediately after endovascular treatment had a significant effect on reducing hydrocephalus formation.

Conclusions

Endovascular therapy within 24 h is feasible and improves the prognosis of patients with high-grade aSAH.
Neuroprotection in neurodegenerations of the brain and eye: Lessons from the past and directions for the future
Authors: Levin Leonard A. , Patrick Christopher , Choudry Nozhat B. , Sharif Najam A. , Goldberg Jeffrey L.
Published: August 2022

Background

Neurological and ophthalmological neurodegenerative diseases in large part share underlying biology and pathophysiology. Despite extensive preclinical research on neuroprotection that in many cases bridges and unifies both fields, only a handful of neuroprotective therapies have succeeded clinically in either.

Main body

Understanding the commonalities among brain and neuroretinal neurodegenerations can help develop innovative ways to improve translational success in neuroprotection research and emerging therapies. To do this, analysis of why translational research in neuroprotection fails necessitates addressing roadblocks at basic research and clinical trial levels. These include optimizing translational approaches with respect to biomarkers, therapeutic targets, treatments, animal models, and regulatory pathways.

Conclusion

The common features of neurological and ophthalmological neurodegenerations are useful for outlining a path forward that should increase the likelihood of translational success in neuroprotective therapies.
Applying functional near-infrared spectroscopy and eye-tracking in a naturalistic educational environment to investigate physiological aspects that underlie the cognitive effort of children during mental rotation tests
Authors: da Silva Soares Raimundo , Ambriola Oku Amanda Yumi , Barreto Cândida S. F. , Ricardo Sato João
Published: August 2022

Spatial cognition is related to academic achievement in science, technology, engineering, and mathematics (STEM) domains. Neuroimaging studies suggest that brain regions’ activation might be related to the general cognitive effort while solving mental rotation tasks (MRT). In this study, we evaluate the mental effort of children performing MRT tasks by measuring brain activation and pupil dilation. We use functional near-infrared spectroscopy (fNIRS) concurrently to collect brain hemodynamic responses from children’s prefrontal cortex (PFC) and an Eye-tracking system to measure pupil dilation during MRT. Thirty-two healthy students aged 9–11 participated in this experiment. Behavioral measurements such as task performance on geometry problem-solving tests and MRT scores were also collected. The results were significant positive correlations between the children’s MRT and geometry problem-solving test scores. There are also significant positive correlations between dorsolateral PFC (dlPFC) hemodynamic signals and visuospatial task performances (MRT and geometry problem-solving scores). Moreover, we found significant activation in the amplitude of deoxy-Hb variation on the dlPFC and that pupil diameter increased during the MRT, suggesting that both physiological responses are related to mental effort processes during the visuospatial task. Our findings indicate that children with more mental effort under the task performed better. The multimodal approach to monitoring students’ mental effort can be of great interest in providing objective feedback on cognitive resource conditions and advancing our comprehension of the neural mechanisms that underlie cognitive effort. Hence, the ability to detect two distinct mental states of rest or activation of children during the MRT could eventually lead to an application for investigating the visuospatial skills of young students using naturalistic educational paradigms.
The associations between specific-type sedentary behaviors and cognitive flexibility in adolescents
Authors: Cui Jie , Li Lin , Dong Chao
Published: August 2022

Background: The prevalence of sedentary behavior in adolescents has aroused social attention. The association between sedentary behavior and cognitive flexibility remains unclear, and it may vary depending on the type of sedentary behavior. This study aimed to investigate the associations between specific-type sedentary behaviors and cognitive flexibility in adolescents.

Method: A total of 700 Chinese adolescents aged 10–15 years were recruited. The self-report questionnaire was used to assess total sedentary time, recreational screen-based sedentary time, and educational sedentary time. The More-odd shifting task was used to assess cognitive flexibility.

Results: The correlation analysis showed that recreational screen-based sedentary time was negatively correlated with cognitive flexibility, whereas educational sedentary time was positively correlated with cognitive flexibility. The regression analysis also further revealed that a significantly negative association between recreational screen-based sedentary time and cognitive flexibility, while a significantly positive association existed between educational sedentary time and cognitive flexibility.

Conclusion: The findings shown that the association between recreational screen-based sedentary behavior and cognitive flexibility differs from educational sedentary behavior in adolescents, providing new ideas for a more comprehensive understanding of the association between sedentary behavior and cognitive flexibility in adolescents.
Maturational trajectory of fusiform gyrus neural activity when viewing faces: From 4 months to 4 years old
Authors: Chen Yuhan , Allison Olivia , Green Heather L. , Kuschner Emily S. , Liu Song , Kim Mina , Slinger Michelle , Mol Kylie , Chiang Taylor , Bloy Luke , Roberts Timothy P. L. , Edgar J. Christopher
Published: August 2022

Infant and young child electrophysiology studies have provided information regarding the maturation of face-encoding neural processes. A limitation of previous research is that very few studies have examined face-encoding processes in children 12–48 months of age, a developmental period characterized by rapid changes in the ability to encode facial information. The present study sought to fill this gap in the literature via a longitudinal study examining the maturation of a primary node in the face-encoding network—the left and right fusiform gyrus (FFG). Whole-brain magnetoencephalography (MEG) data were obtained from 25 infants with typical development at 4–12 months, and with follow-up MEG exams every ∼12 months until 3–4 years old. Children were presented with color images of Face stimuli and visual noise images (matched on spatial frequency, color distribution, and outer contour) that served as Non-Face stimuli. Using distributed source modeling, left and right face-sensitive FFG evoked waveforms were obtained from each child at each visit, with face-sensitive activity identified via examining the difference between the Non-Face and Face FFG timecourses. Before 24 months of age (Visits 1 and 2) the face-sensitive FFG M290 response was the dominant response, observed in the left and right FFG ∼250–450 ms post-stimulus. By 3–4 years old (Visit 4), the left and right face-sensitive FFG response occurred at a latency consistent with a face-sensitive M170 response ∼100–250 ms post-stimulus. Face-sensitive left and right FFG peak latencies decreased as a function of age (with age explaining greater than 70% of the variance in face-sensitive FFG latency), and with an adult-like FFG latency observed at 3–4 years old. Study findings thus showed face-sensitive FFG maturational changes across the first 4 years of life. Whereas a face-sensitive M290 response was observed under 2 years of age, by 3–4 years old, an adult-like face-sensitive M170 response was observed bilaterally. Future studies evaluating the maturation of face-sensitive FFG activity in infants at risk for neurodevelopmental disorders are of interest, with the present findings suggesting age-specific face-sensitive neural markers of a priori interest.
The hand motor hotspot for seed-based functional connectivity of hand motor networks at rest
Authors: Bonzano Laura , Bortoletto Marta , Zazio Agnese , Iester Costanza , Stango Antonietta , Gasparotti Roberto , Miniussi Carlo , Bove Marco
Published: August 2022

In the seed-based method for studying functional connectivity (FC), seed selection is relevant. Here, we propose a new methodological approach for resting-state FC analysis of hand motor networks using the individual hand motor hotspot (hMHS) as seed. Nineteen right-handed healthy volunteers underwent a transcranial magnetic stimulation (TMS) session and resting-state fMRI. For each subject, the hMHS in both hemispheres was identified by TMS with the contralateral abductor pollicis brevis muscle as the target, the site eliciting the highest and most reliable motor-evoked potentials. Seed regions were built on coordinates on the cortex corresponding to the individual left and right hMHSs. For comparison, the left and right Brodmann’s area 4 (BA4) masks extracted from a standard atlas were used as seed. The left and right hMHSs showed FC patterns at rest mainly including sensorimotor regions, with a bilateral connectivity only for the left hMHS. The statistical contrast BA4 > hMHS for both hemispheres showed different extension and lateralization of the functionally connected cortical regions. On the contrary, no voxels survived the opposite contrast (hMHS > BA4). This suggests that detection of individual hand motor seeds by TMS allows to identify functionally connected motor networks that are more specific with respect to those obtained starting from the a priori atlas-based identification of the primary motor cortex.
Exploring the role of sex differences in Alzheimer's disease pathogenesis in Down syndrome
Authors: Andrews Elizabeth J. , Martini Alessandra C. , Head Elizabeth
Published: August 2022

Women are disproportionately affected by Alzheimer's disease (AD), yet little is known about sex-specific effects on the development of AD in the Down syndrome (DS) population. DS is caused by a full or partial triplication of chromosome 21, which harbors the amyloid precursor protein (APP) gene, among others. The majority of people with DS in their early- to mid-40s will accumulate sufficient amyloid-beta (Aβ) in their brains along with neurofibrillary tangles (NFT) for a neuropathological diagnosis of AD, and the triplication of the APP gene is regarded as the main cause. Studies addressing sex differences with age and impact on dementia in people with DS are inconsistent. However, women with DS experience earlier age of onset of menopause, marked by a drop in estrogen, than women without DS. This review focuses on key sex differences observed with age and AD in people with DS and a discussion of possible underlying mechanisms that could be driving or protecting from AD development in DS. Understanding how biological sex influences the brain will lead to development of dedicated therapeutics and interventions to improve the quality of life for people with DS and AD.
Triplanar U-Net with lesion-wise voting for the segmentation of new lesions on longitudinal MRI studies
Authors: Hitziger Sebastian , Ling Wen Xin , Fritz Thomas , D'Albis Tiziano , Lemke Andreas , Grilo Joana
Published: August 2022

We present a deep learning method for the segmentation of new lesions in longitudinal FLAIR MRI sequences acquired at two different time points. In our approach, the 3D volumes are processed slice-wise across the coronal, axial, and sagittal planes and the predictions from the three orientations are merged using an optimized voting strategy. Our method achieved best F1 score (0.541) among all participating methods in the MICCAI 2021 challenge Multiple sclerosis new lesions segmentation (MSSEG-2). Moreover, we show that our method is on par with the challenge's expert neuroradiologists: on an unbiased ground truth, our method achieves results comparable to those of the four experts in terms of detection (F1 score) and segmentation accuracy (Dice score).
Bimodal EEG-fNIRS in Neuroergonomics. Current Evidence and Prospects for Future Research
Authors: Bourguignon Nicolas J. , Bue Salvatore Lo , Guerrero-Mosquera Carlos , Borragán Guillermo
Published: August 2022

Neuroergonomics focuses on the brain signatures and associated mental states underlying behavior to design human-machine interfaces enhancing performance in the cognitive and physical domains. Brain imaging techniques such as functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) have been considered key methods for achieving this goal. Recent research stresses the value of combining EEG and fNIRS in improving these interface systems' mental state decoding abilities, but little is known about whether these improvements generalize over different paradigms and methodologies, nor about the potentialities for using these systems in the real world. We review 33 studies comparing mental state decoding accuracy between bimodal EEG-fNIRS and unimodal EEG and fNIRS in several subdomains of neuroergonomics. In light of these studies, we also consider the challenges of exploiting wearable versions of these systems in real-world contexts. Overall the studies reviewed suggest that bimodal EEG-fNIRS outperforms unimodal EEG or fNIRS despite major differences in their conceptual and methodological aspects. Much work however remains to be done to reach practical applications of bimodal EEG-fNIRS in naturalistic conditions. We consider these points to identify aspects of bimodal EEG-fNIRS research in which progress is expected or desired.
Sensorimotor impairments during spaceflight: Trigger mechanisms and haptic assistance
Authors: Weber Bernhard , Stelzer Martin
Published: August 2022

In a few years, manned space missions are planned in which the sensorimotor performance of humans will be of outstanding importance. However, research has repeatedly shown that human sensorimotor function can be impaired under conditions of microgravity. One way to compensate for these impairments is haptic feedback provided by the human-machine interface. In the current series of studies, sensorimotor performance was measured in basic aiming and tracking tasks. These tasks had to be performed using a force feedback joystick with different haptic settings (three spring stiffnesses, two dampings, two virtual masses, and no haptics). In two terrestrial studies, we investigated (1) the effects of cognitive load on performance in a dual-task paradigm (N = 10) and (2) which learning effects can be expected in these tasks in a longitudinal study design (N = 20). In the subsequent space study (N = 3 astronauts), the influence of microgravity and haptic settings of the joystick were investigated. For this purpose, three mission sessions after 2, 4, and 6 weeks on board the International Space Station (ISS), as well as terrestrial pre- and post-flight sessions, were conducted. The results of the studies indicated that (1) additional cognitive load led to longer reaction times during aiming and increased tracking error while aiming precision was not affected. (2) Significant learning effects were evident for most measures in the study on time effects. (3) Contrary to the expected learning trend, microgravity impaired the aiming precision performance of all astronauts in the initial phase of adaptation (2 weeks in space). No other significant effects were found. Intriguingly, these performance decrements could be compensated for with low to medium spring stiffness and virtual mass. The general result pattern provides further evidence that distorted proprioception during early adaptation to microgravity conditions is one main mechanism underlying sensorimotor impairment.
Circulating trace elements status in COVID-19 disease: A meta-analysis
Authors: Li Yunhui , Luo Weihe , Liang Bin
Published: August 2022

Trace elements are a group of essential metals or metalloids, which are necessary for life, and present in minute amounts. Despite substantial researches highlighting the importance of trace elements in Coronavirus disease 2019 (COVID-19) diseases, a thorough evaluation of the levels of circulating trace elements is lacking. Therefore, we conducted a systematic review and meta-analysis to evaluate the trace element status (Zn, Fe, Cu, Mg, and Se) in COVID-19 disease. We also assessed the relationship between circulating trace elements and COVID-19 disease severity and survival status during follow-up. We searched comprehensively MEDLINE, Web of Science, CNKI, and WangFang databases without language restriction, between November 1, 2019 and April 1, 2022. The search identified 1,566 preliminary references. A total of 49 studies met the eligibility criteria and were included in the review, and 42 studies were included in the final meta-analysis. Meta-analysis showed that COVID-19 patients had significantly lower circulating Zn (SMD: −0.83, 95% CI: −1.19 to −0.46, P < 0.001), Fe (SMD: −1.56, 95% CI: −2.90 to −0.21, P = 0.023), and Se (SMD: −0.75, 95% CI: −0.94 to −0.56, P < 0.001) levels than healthy controls, and circulating Zn (SMD: −0.47, 95% CI: −0.75 to −0.18, P = 0.002), Fe (SMD: −0.45, 95% CI: −0.79 to −0.12, P = 0.008), and Se (SMD: −0.27, 95% CI: −0.49 to −0.04, P = 0.020) levels were associated with the presence of severity status in COVID-19 patients. Moreover, circulating Fe levels in non-survivors were significantly lower than survivors in COVID-19 (SMD: −0.28, 95% CI: −0.44 to −0.12, P = 0.001). However, there was no significant difference in Cu and Mg levels between COVID-19 patients and controls, severity and non-severity status, and survivors and non-survivors (all P > 0.05). Taken together, COVID-19 patients displayed lower circulating levels of Zn, Fe, and Se, and their levels were associated with severity status. Moreover, circulating Fe levels may provide part of the explanation for the unfavorable survival status. Therefore, we presumed optimistically that supplements of trace elements might provide an adjutant treatment in the early stages of COVID-19.

Systematic review registration

[https://www.crd.york.ac.uk/prospero], identifier [CRD42022348599].
Eosinophil as a biomarker for diagnosis, prediction, and prognosis evaluation of severe checkpoint inhibitor pneumonitis
Authors: Li Yanlin , Jia Xiaohui , Du Yonghao , Mao Ziyang , Zhang Yajuan , Shen Yuan , Sun Hong , Liu Mengjie , Niu Gang , Wang Jun , Hu Jie , Jiao Min , Guo Hui
Published: August 2022

Introduction

Checkpoint inhibitor pneumonitis (CIP) is a common serious adverse event caused by immune checkpoint inhibitors (ICIs), and severe CIP can be life-threatening. We aimed to investigate the role of peripheral blood cells in diagnosis, prediction, and prognosis evaluation for all and severe CIP.

Materials and methods

Patients with lung cancer receiving ICIs were enrolled in this retrospective study. Baseline was defined as the time of ICI initiation, endpoint was defined as the time of clinical diagnosis of CIP or the last ICI treatment, and follow-up point was defined as 1 week after CIP. Eosinophil percentages at baseline, endpoint, and follow-up point were shortened to “Ebas”, “Eend and “Efol”, respectively.

Results

Among 430 patients included, the incidence of CIP was 15.6%, and severe CIP was 3.7%. The Eend/Ebas value was lower in patients with CIP (p = 0.001), especially severe CIP (p = 0.036). Receiver operating characteristic curves revealed that Eend/Ebas could serve as a biomarker to diagnose CIP (p = 0.004) and severe CIP (p < 0.001). For severe CIP, the eosinophil percentage declined before the symptoms appeared and CT diagnosis. The eosinophil percentage significantly elevated at the follow-up point in the recovery group but not in the non-recovery group. The CIP patients with Efol/Ebas ≥1.0 had significantly prolonged overall survival (p = 0.024) and after-CIP survival (AS) (p = 0.043). The same results were found in severe CIP but without a statistical difference.

Conclusions

Eosinophil percentage was associated with the diagnosis, prediction, and prognosis of CIP and severe CIP.
Gene expression analysis reveals a 5-gene signature for progression-free survival in prostate cancer
Authors: Mou Zhuofan , Spencer Jack , Knight Bridget , John Joseph , McCullagh Paul , McGrath John S. , Harries Lorna W.
Published: August 2022

Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs. benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) (PCBP1, PABPN1, PTPRF, DANCR, and MYC) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64–0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC: 0.71–0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment.
Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway
Authors: Mranda Geofrey Mahiki , Xiang Zhi-Ping , Liu Jun-Jian , Wei Tian , Ding Yinlu
Published: August 2022

Primary liver cancer is the sixth most frequently diagnosed cancer worldwide and the third leading cause of cancer-related death. The majority of the primary liver cancer cases are hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Worldwide, there is an increasing incidence of primary liver cancer cases due to multiple risk factors ranging from parasites and viruses to metabolic diseases and lifestyles. Often, patients are diagnosed at advanced stages, depriving them of surgical curability benefits. Moreover, the efficacy of the available chemotherapeutics is limited in advanced stages. Furthermore, tumor metastases and recurrence make primary liver cancer management exceptionally challenging. Thus, exploring the molecular mechanisms for the development and progression of primary liver cancer is critical in improving diagnostic, treatment, prognostication, and surveillance modalities. These mechanisms facilitate the discovery of specific targets that are critical for novel and more efficient treatments. Consequently, the Hippo signaling pathway executing a pivotal role in organogenesis, hemostasis, and regeneration of tissues, regulates liver cells proliferation, and apoptosis. Cell polarity or adhesion molecules and cellular metabolic status are some of the biological activators of the pathway. Thus, understanding the mechanisms exhibited by the Hippo pathway is critical to the development of novel targeted therapies. This study reviews the advances in identifying therapeutic targets and prognostic markers of the Hippo pathway for primary liver cancer in the past six years.