bluuebunny/crossref_metadata_2025 huggingface dataset:
Projected Shifts in 21st Century Sardine Distribution and Catch in the California Current
Authors: Fiechter Jerome , Pozo Buil Mercedes , Jacox Michael G. , Alexander Michael A. , Rose Kenneth A.
Published: July 2021

Predicting changes in the abundance and distribution of small pelagic fish species in response to anthropogenic climate forcing is of paramount importance due to the ecological and socioeconomic importance of these species, especially in eastern boundary current upwelling regions. Coastal upwelling systems are notorious for the wide range of spatial (from local to basin) and temporal (from days to decades) scales influencing their physical and biogeochemical environments and, thus, forage fish habitat. Bridging those scales can be achieved by using high-resolution regional models that integrate global climate forcing downscaled from coarser resolution earth system models. Here, “end-to-end” projections for 21st century sardine population dynamics and catch in the California Current system (CCS) are generated by coupling three dynamically downscaled earth system model solutions to an individual-based fish model and an agent-based fishing fleet model. Simulated sardine population biomass during 2000–2100 exhibits primarily low-frequency (decadal) variability, and a progressive poleward shift driven by thermal habitat preference. The magnitude of poleward displacement varies noticeably under lower and higher warming conditions (500 and 800 km, respectively). Following the redistribution of the sardine population, catch is projected to increase by 50–70% in the northern CCS and decrease by 30–70% in the southern and central CCS. However, the late-century increase in sardine abundance (and hence, catch) in the northern CCS exhibits a large ensemble spread and is not statistically identical across the three downscaled projections. Overall, the results illustrate the benefit of using dynamical downscaling from multiple earth system models as input to high-resolution regional end-to-end (“physics to fish”) models for projecting population responses of higher trophic organisms to global climate change.
RETRACTED: Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial
Authors: McCoy John , Goren Andy , Cadegiani Flávio Adsuara , Vaño-Galván Sergio , Kovacevic Maja , Situm Mirna , Shapiro Jerry , Sinclair Rodney , Tosti Antonella , Stanimirovic Andrija , Fonseca Daniel , Dorner Edinete , Onety Dirce Costa , Zimerman Ricardo Ariel , Wambier Carlos Gustavo
Published: July 2021

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03–0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.
Case Report: Regulatory T Cell-Independent Induction of Remission in a Patient With Collagenous Colitis
Authors: Honjo Hajime , Watanabe Tomohiro , Tomooka Mizuki , Matsubara Takuya , Kono Masashi , Sekai Ikue , Hara Akane , Kurimoto Masayuki , Yoshikawa Keisuke , Masuta Yasuhiro , Otsuka Yasuo , Takada Ryutaro , Yoshikawa Tomoe , Kamata Ken , Minaga Kosuke , Matsui Shigenaga , Kimura Masatomo , Kudo Masatoshi
Published: July 2021

Collagenous colitis (CC), a prototypical microscopic colitis, is a chronic inflammatory disorder of the colon. The diagnosis of CC depends on the pathological examination. The colonic mucosa of patients with CC is characterized by the presence of a substantially thickened collagen band (>10μm) under the surface epithelium. In addition, intraepithelial and lamina propria lymphocytes are markedly increased in patients with CC. However, the roles played by the lymphocytes accumulating in the colonic mucosa of patients with CC are poorly defined. Recent studies indicate that T cells infiltrating the colonic mucosa of patients with CC are mainly represented by CD4+ T cells, CD8+ T cells, and forkhead box P3 (FOXP3)+ regulatory T cells (Tregs). Given that activation of CD4+/CD8+ T cells and FOXP3+ Tregs usually mediates pro-inflammatory and anti-inflammatory responses, respectively, alterations in the colonic numbers of these adaptive T cells might be related to the resolution of colitis in patients with CC. We determined alterations in the composition of colonic T cells by extensive immunohistochemical (IHC) analyses in a case of CC successfully treated with budesonide and metronidazole. Colonic lamina propria immune cells mainly comprised CD3+ T cells, CD4+ T cells, CD8+ T cells, CD68+ macrophages, and FOXP3+ Tregs, but not CD20+ B cells or myeloperoxidase (MPO)+ granulocytes in the active phase. During remission, the numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages did not change significantly in the colonic lamina propria, whereas FOXP3+ Tregs were markedly decreased, suggesting that induction of remission was achieved in a Treg-independent manner. Thus, our study indicates that accumulation of FOXP3+ Tregs in the colonic mucosa of patients with CC might be a counter-regulatory mechanism reflecting persistent inflammation and that induction of remission might be achieved without activation of Tregs.
Ultrasound Biomicroscopy Might Predict the Outcome of Phacoemulsification-Visco Dissection in Medically Controlled Primary Angle-Closure Glaucoma Eye With Extensive Peripheral Anterior Synechia
Authors: Gong Haijun , Dong Xu , Zheng Bingru , Gao Xinbo , Chen Liming , Zhang Simin , Zuo Chengguo , Lin Mingkai
Published: July 2021

Objective: The treatment procedures of primary angle-closure glaucoma (PACG) with extensive peripheral anterior synechia (PAS) is a subject of debate. This study is to investigate the clinical features of phacoemulsification (Phaco)-visco dissection in medically controlled PACG patients with PAS > 180° and evaluate the predictability of Ultrasound Biomicroscopy (UBM) parameters on postoperative intraocular pressure (IOP).

Methods: 48 eyes (48 patients) with acute angle-closure glaucoma (AACG) and 30 eyes (30 patients) with chronic angle-closure glaucoma (CACG) were prospectively included. All patients underwent phaco-viscogoniolysis and foldable lens implantation and were followed for 1 year after surgery. We analyzed preoperative and postoperative IOP, the numbers of anti-glaucoma medicine, the visual field value, the extent of PAS, and UBM parameters alterations, and evaluated the correlation between preoperative UBM parameters and one-year postoperative IOP.

Results: IOP reduced significantly from 16.24 ± 4.33 to 14.49 ± 3.69 mmHg in AACG group and from 16.16 ± 3.69 mmHg to 14.31 ± 4.12 mmHg in CACG group, and PAS decreased significantly from 270 ± 60.33 to 171 ± 56.44° in AACG group and from 285 ± 70.46 to 168 ± 61.32° in CACG group, and the number of anti-glaucoma drugs decreased significantly in both groups. Several UBM parameters, including anterior chamber depth, trabecular iris angle, and peripheral iris thickness 500 increased while iris convex reduced considerably in the two groups, and angle opening distance 500 and trabecular-meshwork ciliary process angle increased significantly only in AACG group. One-year postoperative IOP correlated with preoperative angle opening distance 500 and trabecular iris angle negatively and iris convex positively.

Conclusion: Phaco-visco dissection can effectively reduce IOP, the numbers of glaucomatous medications, and PAS in medically controlled PACG patients with extensive PAS. UBM parameters might be valuable for analyzing postoperative anterior segment structure and predicting postoperative IOP of Phaco-visco dissection in PACG patients with extensive PAS.
Biodegradation of Deoxynivalenol by Nocardioides sp. ZHH-013: 3-keto-Deoxynivalenol and 3-epi-Deoxynivalenol as Intermediate Products
Authors: Zhang Honghai , Zhang Heng , Qin Xing , Wang Xiaolu , Wang Yuan , Bin Yao , Xie Xiangming , Zheng Fei , Luo Huiying
Published: July 2021

Deoxynivalenol (DON) is one of the most devastating and notorious contaminants in food and animal feed worldwide. A novel DON-degrading strain, Nocardioides sp. ZHH-013, which exhibited complete mineralization of DON, was isolated from soil samples. The intermediate products of DON generated by this strain were identified by high-performance liquid chromatography and ultra-performance liquid chromatography tandem mass spectrometry analyses. It was shown that, on an experimental level, 3-keto-DON was a necessary intermediate product during the conversion from DON to 3-epi-DON. Furthermore, the ZHH-013 strain could also utilize 3-epi-DON. This DON degradation pathway is a safety concern for food and feed. The mechanism of DON and 3-epi-DON elimination will be further studied, so that new enzymes for DON degradation can be identified.
CRISPR Typing Increases the Discriminatory Power of Streptococcus agalactiae Typing Methods
Authors: Beauruelle Clémence , Treluyer Ludovic , Pastuszka Adeline , Cochard Thierry , Lier Clément , Mereghetti Laurent , Glaser Philippe , Poyart Claire , Lanotte Philippe
Published: July 2021

We explored the relevance of a Clustered regularly interspaced short palindromic repeats (CRISPR)-based genotyping tool for Streptococcus agalactiae typing and we compared this method to current molecular methods [multi locus sequence typing (MLST) and capsular typing]. To this effect, we developed two CRISPR marker schemes (using 94 or 25 markers, respectively). Among the 255 S. agalactiae isolates tested, 229 CRISPR profiles were obtained. The 94 and 25 markers made it possible to efficiently separate isolates with a high diversity index (0.9947 and 0.9267, respectively), highlighting a high discriminatory power, superior to that of both capsular typing and MLST (diversity index of 0.9017 for MLST). This method has the advantage of being correlated with MLST [through analysis of the terminal direct repeat (TDR) and ancestral spacers] and to possess a high discriminatory power (through analysis of the leader-end spacers recently acquired, which are the witnesses of genetic mobile elements encountered by the bacteria). Furthermore, this “one-shot” approach presents the benefit of much-reduced time and cost in comparison with MLST. On the basis of these data, we propose that this method could become a reference method for group B Streptococcus (GBS) typing.
Beyond Taxonomic Identification: Integration of Ecological Responses to a Soil Bacterial 16S rRNA Gene Database
Authors: Jones Briony , Goodall Tim , George Paul B. L. , Gweon Hyun S. , Puissant Jeremy , Read Daniel S. , Emmett Bridget A. , Robinson David A. , Jones Davey L. , Griffiths Robert I.
Published: July 2021

High-throughput sequencing 16S rRNA gene surveys have enabled new insights into the diversity of soil bacteria, and furthered understanding of the ecological drivers of abundances across landscapes. However, current analytical approaches are of limited use in formalizing syntheses of the ecological attributes of taxa discovered, because derived taxonomic units are typically unique to individual studies and sequence identification databases only characterize taxonomy. To address this, we used sequences obtained from a large nationwide soil survey (GB Countryside Survey, henceforth CS) to create a comprehensive soil specific 16S reference database, with coupled ecological information derived from survey metadata. Specifically, we modeled taxon responses to soil pH at the OTU level using hierarchical logistic regression (HOF) models, to provide information on both the shape of landscape scale pH-abundance responses, and pH optima (pH at which OTU abundance is maximal). We identify that most of the soil OTUs examined exhibited a non-flat relationship with soil pH. Further, the pH optima could not be generalized by broad taxonomy, highlighting the need for tools and databases synthesizing ecological traits at finer taxonomic resolution. We further demonstrate the utility of the database by testing against geographically dispersed query 16S datasets; evaluating efficacy by quantifying matches, and accuracy in predicting pH responses of query sequences from a separate large soil survey. We found that the CS database provided good coverage of dominant taxa; and that the taxa indicating soil pH in a query dataset corresponded with the pH classifications of top matches in the CS database. Furthermore we were able to predict query dataset community structure, using predicted abundances of dominant taxa based on query soil pH data and the HOF models of matched CS database taxa. The database with associated HOF model outputs is released as an online portal for querying single sequences of interest (https://shiny-apps.ceh.ac.uk/ID-TaxER/), and flat files are made available for use in bioinformatic pipelines. The further development of advanced informatics infrastructures incorporating modeled ecological attributes along with new functional genomic information will likely facilitate large scale exploration and prediction of soil microbial functional biodiversity under current and future environmental change scenarios.
Stage-Dependent Within-Individual Comparison Reveals SIV-Specific Activation/Exhaustion Shift in Rhesus Macaques
Authors: Tong Ling , Cong Zhe , Tian Long , Zhang Jingjing , Lu Jiahan , Lu Qiuhan , Chen Ting , Wang Yuhong , Wei Qiang , Xue Jing
Published: July 2021

It is challenging to trace the complicated individual-based variations of HIV-specific immunocompetence shift during the successful antiretroviral therapy (ART) era. Using eight rhesus monkeys simulating a longitudinal stage-dependent cohort (baseline-SIV acute infection-SIV suppression by ART-ART withdrawal), baseline immunocompetence monitoring for 28 days (SIV-negative stage, SN) was compared with host immunocompetence undergoing 90-day ART treatment (SIV-suppressed stage, SS) to reveal the SIV-specific immunity shift aroused by undetectable individual viral replication. During acute SIV infection for 98 days (SIV-emerged stage, SE), immune activation was compared with re-immune activation post ART for 49-day follow-up (SIV-rebounded stage, SR) to reveal the SIV-specific immune activation variation aroused by detectable individual viral replication. Individual immunocompetence was measured by co-expression of CD4, CD8, CD38, HLA-DR, CCR7, CD45RA, and PD-1 on T cells and a cytokine panel. Compared with SN, mild immune activation/exhaustion was characterized by increased CD38+ HLA-DR– CD4+/CD8+ T-cell subsets and PD-1+ memory CD4+/CD8+ T-cell subsets with three elevated cytokines (MIP-1β, IL-8, and IL-10) significantly emerged in SS. Compared with SE, SR produced more exhaustion characterized by increased PD-1+ CD4+ TCM cells and decreased PD-1+ CD4+ TEM cells with four elevated pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, and TNF-α). By such individualized stage-dependent comparison, the sustainable immune activation was found from activation/exhaustion shifted into exhaustion during the longitudinal viral persistence. Further, validated SIV accelerates host immunosenescence continuously independent of viral replication.
Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients
Authors: Moreira-Rosário André , Marques Cláudia , Pinheiro Hélder , Araújo João Ricardo , Ribeiro Pedro , Rocha Rita , Mota Inês , Pestana Diogo , Ribeiro Rita , Pereira Ana , de Sousa Maria José , Pereira-Leal José , de Sousa José , Morais Juliana , Teixeira Diana , Rocha Júlio César , Silvestre Marta , Príncipe Nuno , Gatta Nuno , Amado José , Santos Lurdes , Maltez Fernando , Boquinhas Ana , de Sousa Germano , Germano Nuno , Sarmento Gonçalo , Granja Cristina , Póvoa Pedro , Faria Ana , Calhau Conceição
Published: July 2021

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale—mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19—ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09–7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33–8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.
Exomer Is Part of a Hub Where Polarized Secretion and Ionic Stress Connect
Authors: Moro Sandra , Moscoso-Romero Esteban , Poddar Abhishek , Mulet Jose M. , Perez Pilar , Chen Qian , Valdivieso M.-Henar
Published: July 2021

Plasma membrane and membranous organelles contribute to the physiology of the Eukaryotic cell by participating in vesicle trafficking and the maintenance of ion homeostasis. Exomer is a protein complex that facilitates vesicle transport from the trans-Golgi network to the plasma membrane, and its absence leads to the retention of a set of selected cargoes in this organelle. However, this retention does not explain all phenotypes observed in exomer mutants. The Schizosaccharomyces pombe exomer is composed of Cfr1 and Bch1, and cfr1Δ and bch1Δ were sensitive to high concentrations of potassium salts but not sorbitol, which showed sensitivity to ionic but not osmotic stress. Additionally, the activity of the plasma membrane ATPase was higher in exomer mutants than in the wild-type, pointing to membrane hyperpolarization, which caused an increase in intracellular K+ content and mild sensitivity to Na+, Ca2+, and the aminoglycoside antibiotic hygromycin B. Moreover, in response to K+ shock, the intracellular Ca2+ level of cfr1Δ cells increased significantly more than in the wild-type, likely due to the larger Ca2+ spikes in the mutant. Microscopy analyses showed a defective endosomal morphology in the mutants. This was accompanied by an increase in the intracellular pools of the K+ exporting P-type ATPase Cta3 and the plasma membrane Transient Receptor Potential (TRP)-like Ca2+ channel Pkd2, which were partially diverted from the trans-Golgi network to the prevacuolar endosome. Despite this, most Cta3 and Pkd2 were delivered to the plasma membrane at the cell growing sites, showing that their transport from the trans-Golgi network to the cell surface occurred in the absence of exomer. Nevertheless, shortly after gene expression in the presence of KCl, the polarized distribution of Cta3 and Pkd2 in the plasma membrane was disturbed in the mutants. Finally, the use of fluorescent probes suggested that the distribution and dynamics of association of some lipids to the plasma membrane in the presence of KCl were altered in the mutants. Thus, exomer participation in the response to K+ stress was multifaceted. These results supported the notion that exomer plays a general role in protein sorting at the trans-Golgi network and in polarized secretion, which is not always related to a function as a selective cargo adaptor.
Prevalence and Predictors of Prolonged Cognitive and Psychological Symptoms Following COVID-19 in the United States
Authors: Frontera Jennifer A. , Lewis Ariane , Melmed Kara , Lin Jessica , Kondziella Daniel , Helbok Raimund , Yaghi Shadi , Meropol Sharon , Wisniewski Thomas , Balcer Laura , Galetta Steven L.
Published: July 2021

Background/Objectives

Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19.

Methods

We solicited 1000 adult United States residents for an online survey conducted February 3–5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics.

Results

Among 999 respondents, the average age was 45 years (range 18–84), 49% were male, 76 (7.6%) had a history of COVID-19 and 19/76 (25%) COVID-19 positive participants reported prolonged symptoms lasting a median of 4 months (range 1–13). Prolonged COVID-19 participants were more often younger, female, Hispanic, and had a history of depression/mood/thought disorder (all P < 0.05). They experienced significantly higher rates of unemployment and financial insecurity, and their symptoms created greater interference with work and household activities compared to other COVID-19 status groups (all P < 0.05). After adjusting for demographics, past medical history and stressor covariates in multivariable logistic regression analysis, COVID-19 status was independently predictive of worse Neuro-QoL cognitive dysfunction scores (adjusted OR 11.52, 95% CI 1.01–2.28, P = 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep.

Conclusion

Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.
Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease
Authors: Wang Dong , Chen Fanglian , Han Zhaoli , Yin Zhenyu , Ge Xintong , Lei Ping
Published: July 2021

Amyloid-β (Aβ) is the predominant pathologic protein in Alzheimer’s disease (AD). The production and deposition of Aβ are important factors affecting AD progression and prognosis. The deposition of neurotoxic Aβ contributes to damage of the blood–brain barrier. However, the BBB is also crucial in maintaining the normal metabolism of Aβ, and dysfunction of the BBB aggravates Aβ deposition. This review characterizes Aβ deposition and BBB damage in AD, summarizes their interactions, and details their respective mechanisms.
Value of Dual-Energy Dual-Layer CT After Mechanical Recanalization for the Quantification of Ischemic Brain Edema
Authors: Steffen Paul , Austein Friederike , Lindner Thomas , Meyer Lukas , Bechstein Matthias , Rümenapp Johanna , Klintz Tristan , Jansen Olav , Gellißen Susanne , Hanning Uta , Fiehler Jens , Broocks Gabriel
Published: July 2021

Background and Purpose: Ischemic brain edema can be measured in computed tomography (CT) using quantitative net water uptake (NWU), a recently established imaging biomarker. NWU determined in follow-up CT after mechanical thrombectomy (MT) has shown to be a strong predictor of functional outcome. However, disruption of the blood–brain barrier after MT may also lead to contrast staining, increasing the density on CT scans, and hence, directly impairing measurements of NWU. The purpose of this study was to determine whether dual-energy dual-layer CT (DDCT) after MT can improve the quantification of NWU by measuring NWU in conventional polychromatic CT images (CP-I) and virtual non-contrast images (VNC-I). We hypothesized that VNC-based NWU (vNWU) differs from NWU in conventional CT (cNWU).

Methods: Ten patients with middle cerebral artery occlusion who received a DDCT follow-up scan after MT were included. NWU was quantified in conventional and VNC images as previously published and was compared using paired sample t-tests.

Results: The mean cNWU was 3.3% (95%CI: 0–0.41%), and vNWU was 11% (95%CI: 1.3–23.4), which was not statistically different (p = 0.09). Two patients showed significant differences between cNWU and vNWU (Δ = 24% and Δ = 36%), while the agreement of cNWU/vNWU in 8/10 patients was high (difference 2.3%, p = 0.23).

Conclusion: NWU may be quantified precisely on conventional CT images, as the underestimation of ischemic edema due to contrast staining was low. However, a proportion of patients after MT might show significant contrast leakage resulting in edema underestimation. Further research is needed to validate these findings and investigate clinical implications.
Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats
Authors: Kale Rajas P. , Nguyen Thanh Thanh L. , Price J. Blair , Yates Nathanael J. , Walder Ken , Berk Michael , Sillitoe Roy V. , Kouzani Abbas Z. , Tye Susannah J.
Published: July 2021

The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippocampus of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH; 100 μg/day; 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg). Portable microdevices provided continuous bilateral NAc DBS (130 Hz, 200 μA, 90 μs) for 7 days. A control sham electrode group was included, together with ACTH- and saline-treated control groups. Home cage monitoring, open field, sucrose preference, and, forced swim behavioral tests were performed. Post-mortem levels of GSK3 and mTOR, total and phosphorylated, were determined with Western blot. As previously reported, ACTH treatment blocked the immobility-reducing effects of imipramine in the forced swim test. In contrast, treatment with either active DBS or sham electrode placement in the NAc significantly reduced forced swim immobility time in ACTH-treated animals. This was associated with increased homecage activity in the DBS and sham groups relative to ACTH and saline groups, however, no differences in locomotor activity were observed in the open field test, nor were any group differences seen for sucrose consumption across groups. The antidepressant-like actions of NAc DBS and sham electrode placements were associated with an increase in levels of IL and vHIP phospho-GSK3β and phospho-mTOR, however, no differences in these protein levels were observed in the dHIP region. These data suggest that early response to electrode placement in the NAc, irrespective of whether active DBS or sham, has antidepressant-like effects in the ACTH-model of antidepressant resistance associated with distal upregulation of phospho-GSK3β and phospho-mTOR in the IL and vHIP regions of the mood network.
Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?
Authors: Gastelum Gilberto , Veena Mysore , Lyons Kylee , Lamb Christopher , Jacobs Nicole , Yamada Alexandra , Baibussinov Alisher , Sarafyan Martin , Shamis Rebeka , Kraut Jeffry , Frost Patrick
Published: July 2021

Multiple myeloma (MM) is an incurable cancer arising from malignant plasma cells that engraft in the bone marrow (BM). The physiology of these cancer cells within the BM microenvironment (TME) plays a critical role in MM development. These processes may be similar to what has been observed in the TME of other (non-hematological) solid tumors. It has been long reported that within the BM, vascular endothelial growth factor (VEGF), increased angiogenesis and microvessel density, and activation of hypoxia-induced transcription factors (HIF) are correlated with MM progression but despite a great deal of effort and some modest preclinical success the overall clinical efficacy of using anti-angiogenic and hypoxia-targeting strategies, has been limited. This review will explore the hypothesis that the TME of MM engrafted in the BM is distinctly different from non-hematological-derived solid tumors calling into question how effective these strategies may be against MM. We further identify other hypoxia-mediated effectors, such as hypoxia-mediated acidification of the TME, oxygen-dependent metabolic changes, and the generation of reactive oxygen species (ROS), that may prove to be more effective targets against MM.
Ductal Flow Ratio as Measure of Transition in Preterm Infants After Birth: A Pilot Study
Authors: Brouwer Emma , Knol Ronny , Hahurij Nathan D. , Hooper Stuart B. , Te Pas Arjan B. , Roest Arno A. W.
Published: July 2021

Background: Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth.

Aim: Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth.

Methods: Echocardiography was performed in preterm infants born <32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO2, SpO2, and SpO2/FiO2 (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared.

Results: Measurements from 16 infants were analysed (median [IQR] GA 29 [27–30] weeks; birthweight 1,176 [951–1,409] grams). R-L DA shunting was 16 [17–27] ml/kg/min and L-R was 110 [81–124] ml/kg/min. The DA flow ratio was 0.18 [0.11–0.28], SpO2 94 [93–96]%, FiO2 was 23 [21–28]% and SF ratio 4.1 [3.3–4.5]. There was a moderate correlation between DA flow ratio and SpO2 [correlation coefficient (CC) −0.415; p = 0.110], FiO2 (CC 0.384; p = 0.142) and SF ratio (CC −0.356; p = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed.

Conclusion: In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.
Fraction B From Catfish Epidermal Secretions Kills Pancreatic Cancer Cells, Inhibits CD44 Expression and Stemness, and Alters Cancer Cell Metabolism
Authors: Al-Hassan Jassim M. , Wei Daoyan , Chakraborty Sharmistha , Conway Tara , Rhea Patrea , Wei Bo , Tran Megan , Gagea Mihai , Afzal Mohammad , Oommen Sosamma , Nair Divya , Paul Bincy M. , Yang Peiying
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in western countries. The successful treatment of PDAC remains limited. We investigated the effect of Fraction B, which is a fraction purified from catfish (Arius bilineatus, Val.) skin secretions containing proteins and lipids, on PDAC biology both in-vivo and in-vitro. We report here that Fraction B potently suppressed the proliferation of both human and mouse pancreatic cancer cells in vitro and significantly reduced the growth of their relevant xenograft (Panc02) and orthotopic tumors (human Panc-1 cells) (p < 0.05). The Reverse Phase Protein Array (RPPA) data obtained from the tumor tissues derived from orthotopic tumor bearing mice treated with Fraction B showed that Fraction B altered the cancer stem cells related pathways and regulated glucose and glutamine metabolism. The down-regulation of the cancer stem cell marker CD44 expression was further confirmed in Panc-1 cells. CBC and blood chemistry analyses showed no systemic toxicity in Fraction B treated Panc-1 tumor bearing mice compared to that of control group. Our data support that Fraction B is a potential candidate for PDAC treatment.
Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats
Authors: Qin Chufeng , Luo Lichuan , Cui Yusheng , Jiang Li , Li Beilei , Lou Yijie , Weng Zhuofan , Lou Jingwen , Liu Chenxin , Weng Cuiting , Wang Zhaojun , Ji Yunxi
Published: July 2021

Background and Aims: Zhi Gan prescription (ZGP) has been clinically proven to exert a favorable therapeutic effect on nonalcoholic steatohepatitis (NASH). This study purpose to reveal the underlying molecular mechanisms of ZGP action in NASH.

Methods: Systematic network pharmacology was used to identify bioactive components, potential targets, and the underlying mechanism of ZGP action in NASH. High fat (HF)-induced NASH model rats were used to assess the effect of ZGP against NASH, and to verify the possible molecular mechanisms as predicted by network pharmacology.

Results: A total of 138 active components and 366 potential targets were acquired in ZGP. In addition, 823 targets of NASH were also screened. In vivo experiments showed that ZGP significantly improved the symptoms in HF-induced NASH rats. qRT-PCR and western blot analyses showed that ZGP could regulate the hub genes, PTEN, IL-6 and TNF in NASH model rats. In addition, ZGP suppressed mitochondrial autophagy through mitochondrial fusion and fission via the PINK/Parkin pathway.

Conclusion: ZGP exerts its effects on NASH through mitochondrial autophagy. These findings provide novel insights into the mechanisms of ZGP in NASH.
The Role of HSP90α in Methamphetamine/Hyperthermia-Induced Necroptosis in Rat Striatal Neurons
Authors: Liao Lv-shuang , Lu Shuang , Yan Wei-tao , Wang Shu-chao , Guo Li-min , Yang Yan-di , Huang Kai , Hu Xi-min , Zhang Qi , Yan Jie , Xiong Kun
Published: July 2021

Methamphetamine (METH) is one of the most widely abused synthetic drugs in the world. The users generally present hyperthermia (HT) and psychiatric symptoms. However, the mechanisms involved in METH/HT-induced neurotoxicity remain elusive. Here, we investigated the role of heat shock protein 90 alpha (HSP90α) in METH/HT (39.5°C)-induced necroptosis in rat striatal neurons and an in vivo rat model. METH treatment increased core body temperature and up-regulated LDH activity and the molecular expression of canonical necroptotic factors in the striatum of rats. METH and HT can induce necroptosis in primary cultures of striatal neurons. The expression of HSP90α increased following METH/HT injuries. The specific inhibitor of HSP90α, geldanamycin (GA), and HSP90α shRNA attenuated the METH/HT-induced upregulation of receptor-interacting protein 3 (RIP3), phosphorylated RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL. The inhibition of HSP90α protected the primary cultures of striatal neurons from METH/HT-induced necroptosis. In conclusion, HSP90α plays an important role in METH/HT-induced neuronal necroptosis and the HSP90α-RIP3 pathway is a promising therapeutic target for METH/HT-induced neurotoxicity in the striatum.
Heart Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression Associated With Male Sex and Salt-Sensitive Hypertension in the Dahl Rat
Authors: Ytrehus Kirsti , Ludvigsen Stian , Mancusi Costantino , Gerdts Eva , de Simone Giovanni
Published: July 2021

Angiotensin-converting enzyme 2 (ACE 2) in the heart including its sex dependency in the hypertensive heart, has not been much studied compared to ACE. In the present study, we used the Dahl salt-sensitive rat exposed to fructose and salt to model a hypertensive phenotype in males, females, and ovariectomized females. Blood pressure was measured by the tale-cuff technique in the conscious state. Expression of RAS-related genes ACE, ACE2, angiotensin II receptor type 1, Mas1, and CMA1 in the heart were quantified. The results revealed small but significant differences between male and female groups. The main results indicate the presence of a male preponderance for an increase in ACE and ACE2 gene expression. The results are in accordance with the role of androgens or male chromosomal complement in controlling the expression of the two ACE genes.
Discrete Dynamic Model of the Mammalian Sperm Acrosome Reaction: The Influence of Acrosomal pH and Physiological Heterogeneity
Authors: Aldana Andrés , Carneiro Jorge , Martínez-Mekler Gustavo , Darszon Alberto
Published: July 2021

The acrosome reaction (AR) is an exocytotic process essential for mammalian fertilization. It involves diverse physiological changes (biochemical, biophysical, and morphological) that culminate in the release of the acrosomal content to the extracellular medium as well as a reorganization of the plasma membrane (PM) that allows sperm to interact and fuse with the egg. In spite of many efforts, there are still important pending questions regarding the molecular mechanism regulating the AR. Particularly, the contribution of acrosomal alkalinization to AR triggering physiological conditions is not well understood. Also, the dependence of the proportion of sperm capable of undergoing AR on the physiological heterogeneity within a sperm population has not been studied. Here, we present a discrete mathematical model for the human sperm AR based on the physiological interactions among some of the main components of this complex exocytotic process. We show that this model can qualitatively reproduce diverse experimental results, and that it can be used to analyze how acrosomal pH (pHa) and cell heterogeneity regulate AR. Our results confirm that a pHa increase can on its own trigger AR in a subpopulation of sperm, and furthermore, it indicates that this is a necessary step to trigger acrosomal exocytosis through progesterone, a known natural inducer of AR. Most importantly, we show that the proportion of sperm undergoing AR is directly related to the detailed structure of the population physiological heterogeneity.
Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder
Authors: Hartmann Phillipp , Lang Sonja , Zeng Suling , Duan Yi , Zhang Xinlian , Wang Yanhan , Bondareva Marina , Kruglov Andrey , Fouts Derrick E. , Stärkel Peter , Schnabl Bernd
Published: July 2021

Background

Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein.

Methods

We studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples.

Results

Patients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease.

Conclusion

In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.
Signaling Peptides Regulating Abiotic Stress Responses in Plants
Authors: Kim Jin Sun , Jeon Byeong Wook , Kim Jungmook
Published: July 2021

As sessile organisms, plants are exposed to constantly changing environments that are often stressful for their growth and development. To cope with these stresses, plants have evolved complex and sophisticated stress-responsive signaling pathways regulating the expression of transcription factors and biosynthesis of osmolytes that confer tolerance to plants. Signaling peptides acting like phytohormones control various aspects of plant growth and development via cell-cell communication networks. These peptides are typically recognized by membrane-embedded receptor-like kinases, inducing activation of cellular signaling to control plant growth and development. Recent studies have revealed that several signaling peptides play important roles in plant responses to abiotic stress. In this mini review, we provide recent findings on the roles and signaling pathways of peptides that are involved in coordinating plant responses to abiotic stresses, such as dehydration, high salinity, reactive oxygen species, and heat. We also discuss recent developments in signaling peptides that play a role in plant adaptation responses to nutrient deficiency stress, focusing on nitrogen and phosphate deficiency responses.
Multiple Hazard Uncertainty Visualization Challenges and Paths Forward
Authors: Padilla Lace , Dryhurst Sarah , Hosseinpour Helia , Kruczkiewicz Andrew
Published: July 2021

Making decisions with uncertainty is challenging for the general public, policymakers, and even highly trained scientists. Nevertheless, when faced with the need to respond to a potential hazard, people must make high-risk decisions with uncertainty. In some cases, people have to consider multiple hazards with various types of uncertainties. Multiple hazards can be interconnected by location, time, and/or environmental systems, and the hazards may interact, producing complex relationships among their associated uncertainties. The interaction between multiple hazards and their uncertainties can have nonlinear effects, where the resultant risk and uncertainty are greater than the sum of the risk and uncertainty associated with individual hazards. Effectively communicating the uncertainties related to such complicated systems should be a high priority because the frequency and variability of multiple hazard events due to climate change continue to increase. However, the communication of multiple hazard uncertainties and their interactions remains largely unexplored. The lack of practical guidance on conveying multiple hazard uncertainties is likely due in part to the field’s vast expanse, making it challenging to identify entry points. Here, we offer a perspective on three critical challenges related to uncertainty communication across various multiple hazard contexts to galvanize the research community. We advocate for systematic considerations of multiple hazard uncertainty communication that focus on trade-offs between complexity and factors, including mental effort, trust, and usability.
Aesthetic Experience of Representational Art: Liking Is Affected by Audio-Information Naming and Explaining Inaccuracies of Historical Paintings
Authors: Knoos Manuel , Glaser Manuela , Schwan Stephan
Published: July 2021

Paintings in museums are often accompanied by additional information, such as titles or audio-texts. Previous research has reported mostly positive effects of additional information on the liking and subjective understanding of a painting. However, some studies have also reported negative effects when additional information introduces inconsistencies between the painting’s content and the represented reality. Therefore, the present study examined the negative effects of naming a painting’s historical inaccuracies, which are inconsistencies between the content of the painting and the real historic event, and whether these negative effects can be compensated by an explanation for the inaccuracies. The results revealed that liking was lower with inaccuracies named and that this effect was compensated by an explanation for the inaccuracies. No significant effects were observed for subjective understanding and aesthetic emotions. The results corroborate parts of the Vienna integrated model of art perception and have practical implications for the design of audio-texts in museums.