bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Digital Speech Assessments to Detect Early Signs of Cognitive Impairment
Authors: Robin Jessica , Xu Mengdan , Kaufman Liam D. , Simpson William
Published: October 2021

Detecting early signs of cognitive decline is crucial for early detection and treatment of Alzheimer's Disease. Most of the current screening tools for Alzheimer's Disease represent a significant burden, requiring invasive procedures, or intensive and costly clinical testing. Recent findings have highlighted changes to speech and language patterns that occur in Alzheimer's Disease, and may be detectable prior to diagnosis. Automated tools to assess speech have been developed that can be used on a smartphone or tablet, from one's home, in under 10 min. In this study, we present the results of a study of older adults who completed a digital speech assessment task over a 6-month period. Participants were grouped according to those who scored above (N = 18) or below (N = 18) the recommended threshold for detecting cognitive impairment on the Montreal Cognitive Assessment (MoCA) and those with diagnoses of mild cognitive impairment (MCI) or early Alzheimer's Disease (AD) (N = 14). Older adults who scored above the MoCA threshold had better performance on speech composites reflecting language coherence, information richness, syntactic complexity, and word finding abilities. Those with MCI and AD showed more rapid decline in the coherence of language from baseline to 6-month follow-up, suggesting that this score may be useful both for detecting cognitive decline and monitoring change over time. This study demonstrates that automated speech assessments have potential as sensitive tools to detect early signs of cognitive impairment and monitor progression over time.
Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study
Authors: Vogel Frederick , Braun Leah , Rubinstein German , Zopp Stephanie , Oßwald Andrea , Schilbach Katharina , Schmidmaier Ralf , Bidlingmaier Martin , Reincke Martin
Published: October 2021

Context

Glucocorticoid excess exhibits multiple detrimental effects by its catabolic properties. Metformin was recently suggested to protect from adverse metabolic side-effects of glucocorticoid treatment. Whether metformin is beneficial in patients with endogenous glucocorticoid excess has not been clarified.

Objective

To evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.

Patients and Methods

As part of the German Cushing’s Registry we selected from our prospective cohort of 96 patients all 10 patients who had been on pre-existing metformin treatment at time of diagnosis (CS-MET). These 10 patients were matched for age, sex and BMI with 16 patients without metformin treatment (CS-NOMET). All patients had florid CS at time of diagnosis. We analyzed body composition, metabolic parameters, bone mineral density and bone remodeling markers, muscle function and quality of life.

Results

As expected, diabetes was more prevalent in the CS-MET group, and HbA1c was higher. In terms of comorbidities and the degree of hypercortisolism, the two groups were comparable. We did not observe differences in terms of muscle function or body composition. In contrast, bone mineral density in metformin-treated patients was superior to the CS-NOMET group at time of diagnosis (median T-Score -0.8 versus -1.4, p = 0.030). CS-MET patients showed decreased β-CTX levels at baseline (p = 0.041), suggesting reduced bone resorption under metformin treatment during glucocorticoid excess.

Conclusion

This retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.
A Novel Missense Variant of HOXD13 Caused Atypical Synpolydactyly by Impairing the Downstream Gene Expression and Literature Review for Genotype–Phenotype Correlations
Authors: Guo Ruiji , Fang Xia , Mao Hailei , Sun Bin , Zhou Jiateng , An Yu , Wang Bin
Published: October 2021

Synpolydactyly (SPD) is a hereditary congenital limb malformation with distinct syndactyly designated as SPD1, SPD2, and SPD3. SPD1 is caused by mutations of HOXD13, which is a homeobox transcription factor crucial for limb development. More than 143 SPD patients have been reported to carry HOXD13 mutations, but there is a lack of genotype–phenotype correlation. We report a novel missense mutation of c. 925A > T (p.I309F) in an individual with atypical synpolydactyly inherited from her father with mild clinodactyly and three other different alanine insertion mutations in HOXD13 identified by whole exome sequencing (WES) in 12 Chinese SPD families. Unlike polyalanine extension, which tends to form α-helix and causes protein aggregation in the cytoplasm as shown by molecular simulation and immunofluorescence, the c. 925A > T mutation impairs downstream transcription of EPHA7. We compiled literature findings and analyzed genotype–phenotype features in 173 SPD individuals of 53 families, including 12 newly identified families. Among the HOXD13-related individuals, mutations were distributed in three regions: polyalanine, homeobox, and non-homeobox. Polyalanine extension was the most common variant (45%), followed by missense mutations (32%) mostly in the homeobox compared with the loss-of-function (LOF) variants more likely in non-homeobox. Furthermore, a more severe degree and classic SPD were associated with polyalanine mutations although missense variants were associated with brachydactyly and syndactyly in hands and feet and LOF variants with clinodactyly in hands. Our study broadens the HOXD13 mutation spectrum and reveals the profile of three different variants and their severity of SPD, the genotype–phenotype correlation related to the HOXD13 mutation site provides clinical insight, including for genetic counseling.
Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation
Authors: Lou Bin , Ma Guanghua , LV Feifei , Yuan Quan , Xu Fanjie , Dong Yuejiao , Lin Sha , Tan Yajun , Zhang Jie , Chen Yu
Published: October 2021

Objective

Hepatitis B virus (HBV) reinfection is a serious complication that arise in patients who undergo hepatitis B virus related liver transplantation. We aimed to use biomarkers to evaluate the HBV reinfection in patients after orthotopic liver transplantation.

Methods

Seventy-nine patients who underwent liver transplantation between 2009 and 2015 were enrolled, and levels of biomarkers were analyzed at different time points. Cox regression and receiver operating characteristic (ROC) curves of different markers at baseline were used to analyze sustained hepatitis B surface antigen (HBsAg) loss. The Kaplan-Meier method was used to compare the levels of the biomarkers.

Results

Among the 79 patients, 42 sustained HBsAg loss with a median time of 65.2 months (12.0-114.5, IQR 19.5) after liver transplantation and 37 patients exhibited HBsAg recurrence with a median time of 8.8 (0.47-59.53, IQR 19.47) months. In the ROC curve analysis, at baseline, 4.25 log10 IU/mL qHBcAb and 2.82 log10 IU/mL qHBsAg showed the maximum Youden’s index values with area under the curves (AUCs) of 0.685and 0.651, respectively. The Kaplan-Meier method indicated that qHBsAg and quantitative antibody against hepatitis B core antigen (qHBcAb) levels in the two groups were significantly different (p = 0.031 and 0.006, respectively). Furthermore, the Cox regression model confirmed the predictive ability of qHBcAb at baseline (AUC = 0.685).

Conclusion

Lower pretransplantation qHBcAb is associated with HBV infection. The baseline concentration of qHBcAb is a promising predictor for the recurrence of HBV in patients undergoing liver transplantation and can be used to guide antiviral treatment for HBV infection.
The Role of HDAC6 in Autophagy and NLRP3 Inflammasome
Authors: Chang Panpan , Li Hao , Hu Hui , Li Yongqing , Wang Tianbing
Published: October 2021

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.
Patterns of Consumption Across a Caribbean Seascape: Roles of Habitat and Consumer Species Composition Through Time
Authors: Ritter Carmen J. , Harper Leah M. , Lefcheck Jonathan S. , Paul Valerie J. , Whippo Ross , Jones Scott , Ogburn Matthew B. , Duffy J. Emmett
Published: October 2021

Herbivores, omnivores, and predators transfer energy and structure the communities of many coastal marine ecosystems, and the intensity with which they consume prey and contribute to ecosystem functioning varies substantially among habitats over short time periods. Whether generalities across habitats might emerge for longer time series and using standard methods remains largely untested. Here, we deployed standardized assays of consumption using dried squid (“squidpops”) and five common macrophytes (“weedpops”) to quantify consumption across coral fore reef and patch reefs, mangroves, seagrass meadows, and bare sand from 2015 to 2019 around Carrie Bow Cay, Belize. We also used video in 2017 to identify the species responsible for consumption. We found that both squid- and weedpop consumption were consistently highest on patch and fore reef habitats, moderate in mangroves, and lowest in seagrass and sand across all years of the survey. Videos showed that the majority of consumption on the reefs in 2017 could be attributed to < 5 fish species, and the identity of the dominant consumers differed among habitats. This study validates a key but implicit assumption in marine ecology that relative patterns in consumption across habitats are consistent through space and time in tropical nearshore environments, and reveals that high consumption rates may be the consequence of one or few species in each location.
Using Bayesian Models to Estimate Humpback Whale Entanglements in the United States West Coast Sablefish Pot Fishery
Authors: Jannot Jason E. , Ward Eric J. , Somers Kayleigh A. , Feist Blake E. , Good Thomas P. , Lawson Dan , Carretta James V.
Published: October 2021

Protected species bycatch can be rare, making it difficult for fishery managers to develop unbiased estimates of fishing-induced mortality. To address this problem, we use Bayesian time-series models to estimate the bycatch of humpback whales (Megaptera novaeangliae), which have been documented only twice since 2002 by fishery observers in the United States West Coast sablefish pot fishery, once in 2014 and once in 2016. This model-based approach minimizes under- and over-estimation associated with using ratio estimators based only on intra-annual data. Other opportunistic observations of humpback whale entanglements have been reported in United States waters, but, because of spatio-temporal biases in these observations, they cannot be directly incorporated into the models. Notably, the Bayesian framework generates posterior predictive distributions for unobserved entanglements in addition to estimates and associated uncertainty for observed entanglements. The United States National Marine Fisheries Service began using Bayesian time-series to estimate humpback whale bycatch in the United States West Coast sablefish pot fishery in 2019. That analysis resulted in estimates of humpback whale bycatch in the fishery that exceeded the previously anticipated bycatch limits. Those results, in part, contributed to a review of humpback whale entanglements in this fishery under the United States Endangered Species Act. Building on the humpback whale example, we illustrate how the Bayesian framework allows for a wide range of commonly used distributions for generalized linear models, making it applicable to a variety of data and problems. We present sensitivity analyses to test model assumptions, and we report on covariate approaches that could be used when sample sizes are larger. Fishery managers anywhere can use these models to analyze potential outcomes for management actions, develop bycatch estimates in data-limited contexts, and guide mitigation strategies.
Clinical Characteristics of Pediatric Coats' Disease With Retinal Cyst Using Wide-Angle Fluorescein Angiography
Authors: Liu Jing-Hua , Deng Guangda , Ma Jing , Li Liang , Fang Yuxin , Li Songfeng , Lu Hai
Published: October 2021

Purpose: To assess the demographic and treatment features of pediatric patients of Coats' disease with retinal cyst using wide-angle FA.

Design: A retrospective, hospital based, cross-sectional study.

Participants: Pediatric patients of Coats' disease underwent wide-angle FA.

Methods: A retrospective review of pediatric patients of Coats' disease who underwent wide-angle FA at a single center from January 2015 to July 2020. Demographic and treatment features were compared between patients with or without retinal cyst.

Main Outcome Measures: Demographic and treatment outcomes.

Results: There were 123 pediatric Coats' patients in our study, and 18.70% (23/123) of the patients developed complications with retinal cyst, 73.9% (17/23) of the retinal cysts were located in the inferior-temporal quadrant and 82.6% (19/23) of the retinal cysts were located in the peripheral retina anterior to the vortex veins. Compared with patients without retinal cyst, patients with retinal cyst had more clock-hours of telangiectasia on FA (7.32 vs. 5.41, p = 0.031), and may need more total treatments (7.47 vs. 3.53, p = 0.023) including laser photocoagulation (4.08 vs. 2.31, p = 0.019) or intravitreal anti-VEGF (3.13 vs. 2.23, p = 0.039), and also required a longer time for telangiectasia resolution (22.33 vs. 18.53 months, p = 0.043).

Conclusion: Pediatric patients with Coats' disease complicated by retinal cyst presented with more clock-hours of telangiectasia on FA and needed more total treatments and longer time for telangiectasia resolution.
Epidemiology and Prognosis of Invasive Fungal Disease in Chinese Lung Transplant Recipients
Authors: Ju Chunrong , Lian Qiaoyan , Xu Xin , Cao Qingdong , Lan Cong , Chen Rongchang , He Jianxing
Published: October 2021

This study explored the epidemiology, risk factors, and prognosis of invasive fungal disease (IFD) in Chinese lung transplant recipients (LTRs). This retrospective cohort study included patients who received lung transplants at four hospitals in South China between January 2015 and June 2019. The participants were divided into IFD and non-IFD (NIFD) groups. The final analysis included 226 LTRs (83.2% males) aged 55.0 ± 14.2 years old. Eighty-two LTRs (36.3%) developed IFD (proven or probable diagnosis). The most common pathogens were Aspergillus (57.3%), Candida (19.5%), and Pneumocystis jiroveci (13.4%). Multivariate logistic regression revealed that anastomotic disease [odds ratio (OR): 11.86; 95% confidence interval (95%CI): 4.76–29.54; P < 0.001], cytomegalovirus (CMV) pneumonia (OR: 3.85; 95%CI: 1.88–7.91; P = 0.018), and pre-transplantation IFD (OR: 7.65; 95%CI: 2.55–22.96; P < 0.001) were associated with higher odds of IFD, while double-lung transplantation (OR: 0.40; 95%CI: 0.19–0.79; P = 0.009) was associated with lower odds of IFD. Logistic regression analysis showed that anastomotic disease was associated with higher odds of death (OR: 5.01; 95%CI: 1.24–20.20; P = 0.02) and that PJP prophylaxis was associated with lower odds of death (OR: 0.01; 95%CI: 0.001–0.11; P < 0.001). Invasive fungal disease is prevalent among LTRs in southern China, with Aspergillus the most common pathogen. Prophylaxis should be optimized based on likely pathogens.
Lipidomics Analysis of the Tears in the Patients Receiving LASIK, FS-LASIK, or SBK Surgery
Authors: Gao Yan , Qi Yuanyuan , Huang Yue , Li Xiaorong , Zhou Lei , Zhao Shaozhen
Published: October 2021

Purpose: Tear film lipid layer (TFLL) plays a vital role in maintaining the tear film stability and, thus, the lipid composition of the tears could greatly affect the physiological function and biophysical integrity of the tear film. The objective of this study is to assess the tear lipid composition of the patients receiving laser-assisted in situ keratomileusis (LASIK), femtosecond LASIK (FS-LASIK), or sub-Bowman's keratomileusis (SBK) surgery preoperatively and postoperatively.

Methods: Tear samples were collected from the left eye of the patient who receiving LASIK (n = 10), FS-LASIK (n = 10), or SBK (n = 10) surgery in week 0, week 1, week 4, and week 52. A rapid direct injection shotgun lipidomics workflow, MS/MSALL (<2 min/sample), was applied to examine the tear lipidome.

Results: In week 52, the SBK group demonstrated a similar lipidome profile compared to week 0, while the FS-LASIK and LASIK groups shifted away from week 0. Two lipids, ganglioside (GD3) 27:4 and triacylglycerol (TAG) 59:3, were found to be associated with the lipidome changes preoperatively and postoperatively. No statistical significance was found in the overall lipid classes from the FS-LASIK group. The LASIK group showed significant alteration in the phospholipid and sphingolipid over time, while the SBK group demonstrated a significant difference in the (O-acyl)-ω-hydroxy fatty acid (OAHFA) and phospholipid.

Conclusion: LASIK showed the greatest impact on the tear lipidome changes over time, while SBK demonstrated minimal impact among the three types of refractive surgeries after 1 year.
A New Tool for Analyses of Whole Genome Sequences Reveals Dissemination of Specific Strains of Vancomycin-Resistant Enterococcus faecium in a Hospital
Authors: Marbjerg Lis , Stougaard Caroline Louise , Sørensen Sophie-Amalie Grønhøj , Thomsen Amalie Vørs , Wang Lis , Andersen Lise , Andersen Thomas Emil , Kallipolitis Birgitte , Kemp Michael
Published: October 2021

A new easy-to-use online bioinformatic tool analyzing whole genome sequences of healthcare associated bacteria was used by a local infection control unit to retrospectively map genetic relationship of isolates of E. faecium carrying resistance genes to vancomycin in a hospital. Three clusters of isolates were detected over a period of 5 years, suggesting transmission between patients. Individual relatedness between isolates within each cluster was established by SNP analyses provided by the system. Genetic antimicrobial resistance mechanisms to antibiotics other than vancomycin were identified. The results suggest that the system is suited for hospital surveillance of E. faecium carrying resistance genes to vancomycin in settings with access to next Generation Sequencing without bioinformatic expertise for interpretation of the genome sequences.
Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis
Authors: An Yang , Xu Shixue , Liu Yiting , Xu Xiangbo , Philips Cyriac Abby , Chen Jiang , Méndez-Sánchez Nahum , Guo Xiaozhong , Qi Xingshun
Published: October 2021

Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear.

Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model.

Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61–2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62–6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18–2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58–5.60, p = 0.001); but, high expression of galectin-4 and −9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36–0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44–0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19–0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37–0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79–4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23–0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15–2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91–27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57–4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61–9.99, p < 0.001).

Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.
SARS-CoV2 Infection and the Importance of Potassium Balance
Authors: Causton Helen C.
Published: October 2021

SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms associated with COVID-19, the activity of repurposed drugs associated with lower death rates or antiviral activity in vitro and a small number of studies describing interventions, point to the importance of electrolyte, and particularly potassium, homeostasis at both the cellular, and systemic level. Elevated urinary loss of potassium is associated with disease severity, and the response to electrolyte replenishment correlates with progression toward recovery. These findings suggest possible diagnostic opportunities and therapeutic interventions. They provide insights into comorbidities and mechanisms associated with infection by SARS-CoV2 and other RNA viruses that target the ACE2 receptor, and/or activate cytokine-mediated immune responses in a potassium-dependent manner.
Global and Regional Estimates for Subtype-Specific Therapeutic and Prophylactic HIV-1 Vaccines: A Modeling Study
Authors: Elangovan Ramyiadarsini , Jenks Michael , Yun Jason , Dickson-Tetteh Leslie , Kirtley Shona , Hemelaar Joris ,   WHO-UNAIDS Network for HIV Isolation and Characterisation
Published: October 2021

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.
Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein
Authors: Wang Yingchen , Zhang Zhe , Shang Lei , Gao Hong , Du Xiqiao , Li Falong , Gao Ya , Qi Guiyun , Guo Weiyuan , Qu Zhangyi , Dong Tuo
Published: October 2021

Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations.

Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples.

Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults.

Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors.
Pyrolyzed Substrates Induce Aromatic Compound Metabolism in the Post-fire Fungus, Pyronema domesticum
Authors: Fischer Monika S. , Stark Frances Grace , Berry Timothy D. , Zeba Nayela , Whitman Thea , Traxler Matthew F.
Published: October 2021

Wildfires represent a fundamental and profound disturbance in many ecosystems, and their frequency and severity are increasing in many regions of the world. Fire affects soil by removing carbon in the form of CO2 and transforming remaining surface carbon into pyrolyzed organic matter (PyOM). Fires also generate substantial necromass at depths where the heat kills soil organisms but does not catalyze the formation of PyOM. Pyronema species strongly dominate soil fungal communities within weeks to months after fire. However, the carbon pool (i.e., necromass or PyOM) that fuels their rise in abundance is unknown. We used a Pyronema domesticum isolate from the catastrophic 2013 Rim Fire (CA, United States) to ask whether P. domesticum is capable of metabolizing PyOM. Pyronema domesticum grew readily on agar media where the sole carbon source was PyOM (specifically, pine wood PyOM produced at 750°C). Using RNAseq, we investigated the response of P. domesticum to PyOM and observed a comprehensive induction of genes involved in the metabolism and mineralization of aromatic compounds, typical of those found in PyOM. Lastly, we used 13C-labeled 750°C PyOM to demonstrate that P. domesticum is capable of mineralizing PyOM to CO2. Collectively, our results indicate a robust potential for P. domesticum to liberate carbon from PyOM in post-fire ecosystems and return it to the bioavailable carbon pool.
Hydrodynamics Regulate Longitudinal Plankton Community Structure in an Alpine Cascade Reservoir System
Authors: Liu Yang , Li Chengyan , Jian Shenglong , Miao Shiyu , Li Kemao , Guan Hongtao , Mao Yaqi , Wang Zhongyi , Li Changzhong
Published: October 2021

Previous studies report significant changes on biotic communities caused by cascade reservoir construction. However, factors regulating the spatial–temporal plankton patterns in alpine cascade reservoir systems have not been fully explored. The current study explored effects of environmental factors on the longitudinal plankton patterns, through a 5-year-long study on the environmental factors and communities of phytoplankton and zooplankton in an alpine cascade reservoir system located upstream of Yellow River region. The findings showed that phytoplankton and zooplankton species numbers in the studied cascade reservoir system were mainly regulated by the hydrological regime, whereas nutrient conditions did not significantly affect the number of species. Abundance and biovolume of phytoplankton in cascade reservoirs were modulated by the hydrological regime and nutrient conditions. The drainage rate, N:P ratio, and sediment content in cascade reservoirs were negatively correlated with abundance and biovolume of phytoplankton. Abundance and biovolume of zooplankton were not significantly correlated with the hydrological regime but showed a strong positive correlation with nutrient conditions in cascade reservoirs. Shannon–Wiener index (H’) and the Pielou index (J) of phytoplankton were mainly regulated by the hydrological regime factors, such as drainage rate and sediment content in cascade reservoirs. However, temperature and nutrient conditions were the main factors that regulated the Shannon–Wiener index (H’) and the Pielou index (J) of zooplankton. Species number, abundance, and biovolume of phytoplankton showed a significant positive correlation with those of zooplankton. Hydrodynamics and nutrient conditions contributed differently in regulating community structure of phytoplankton or zooplankton. These findings provide an understanding of factors that modulate longitudinal plankton community patterns in cascade reservoir systems.
Polyphosphate Kinase 1 Is a Pathogenesis Determinant in Enterohemorrhagic Escherichia coli O157:H7
Authors: Du Yanli , Wang Xiangyu , Han Zongli , Hua Ying , Yan Kaina , Zhang Bao , Zhao Wei , Wan Chengsong
Published: October 2021

Theppk1gene encodes polyphosphate kinase (PPK1), which is the major catalytic enzyme thatEscherichia coliutilizes to synthesize inorganic polyphosphate (polyP). The aim of this study was to explore the role of PPK1 in the pathogenesis of EnterohemorrhagicE. coliO157:H7 (EHEC O157:H7). An isogenic in-frameppk1deletion mutant (Δppk1) andppk1complemented mutant (Cppk1) were constructed and characterized in comparison to wild-type (WT) EHEC O157:H7 strain EDL933w by microscope observation and growth curve analysis. Survival rates under heat stress and acid tolerance, both of which the bacteria would face during pathogenesis, were compared among the three strains. LoVo cells and a murine model of intestinal colitis were used as thein vitroandin vivomodels, respectively, to evaluate the effect of PPK1 on adhesion and invasion during the process of pathogenesis. Real-time reverse-transcription PCR of regulatory generpoS, adhesion geneeae, and toxin genesstx1andstx2was carried out to corroborate the results from thein vitroandin vivomodels. Theppk1deletion mutant exhibited disrupted polyP levels, but not morphology and growth characteristics. The survival rate of the Δppk1strain under stringent environmental conditions was lower as compared with WT andCppk1.Thein vitroassays showed that deletion of theppk1gene reduced the adhesion, formation of attaching and effacing (A/E) lesions, and invasive ability of EHEC O157:H7. Moreover, the virulence of the Δppk1in BALB/c mice was weaker as compared with the other two strains. Additionally, mRNA expression ofrpoS,eae,stx1andstx2were consistent with thein vitroandin vivoresults. In conclusion: EHEC O157:H7 requires PPK1 for both survival under harsh environmental conditions and virulencein vivo.
Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome
Authors: Jiao Zonglin , Cao Shoubo , Li Jianhua , Hu Nan , Gong Yinghui , Wang Linduo , Jin Shi
Published: October 2021

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.

Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.

Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p < 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p < 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p < 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p < 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p < 0.001).

Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.
Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control
Authors: Fauvet Bruno , Rebeaud Mathieu E. , Tiwari Satyam , De Los Rios Paolo , Goloubinoff Pierre
Published: October 2021

Life is a non-equilibrium phenomenon. Owing to their high free energy content, the macromolecules of life tend to spontaneously react with ambient oxygen and water and turn into more stable inorganic molecules. A similar thermodynamic picture applies to the complex shapes of proteins: While a polypeptide is emerging unfolded from the ribosome, it may spontaneously acquire secondary structures and collapse into its functional native conformation. The spontaneity of this process is evidence that the free energy of the unstructured state is higher than that of the structured native state. Yet, under stress or because of mutations, complex polypeptides may fail to reach their native conformation and form instead thermodynamically stable aggregates devoid of biological activity. Cells have evolved molecular chaperones to actively counteract the misfolding of stress-labile proteins dictated by equilibrium thermodynamics. HSP60, HSP70 and HSP100 can inject energy from ATP hydrolysis into the forceful unfolding of stable misfolded structures in proteins and convert them into unstable intermediates that can collapse into the native state, even under conditions inauspicious for that state. Aggregates and misfolded proteins may also be forcefully unfolded and degraded by chaperone-gated endo-cellular proteases, and in eukaryotes also by chaperone-mediated autophagy, paving the way for their replacement by new, unaltered functional proteins. The greater energy cost of degrading and replacing a polypeptide, with respect to the cost of its chaperone-mediated repair represents a thermodynamic dilemma: some easily repairable proteins are better to be processed by chaperones, while it can be wasteful to uselessly try recover overly compromised molecules, which should instead be degraded and replaced. Evolution has solved this conundrum by creating a host of unfolding chaperones and degradation machines and by tuning their cellular amounts and activity rates.
Rehabilitation of Acute Vs. Chronic Patients With Spinal Cord Injury With a Neurologically Controlled Hybrid Assistive Limb Exoskeleton: Is There a Difference in Outcome?
Authors: Zieriacks Amrei , Aach Mirko , Brinkemper Alexis , Koller Daniela , Schildhauer Thomas Armin , Grasmücke Dennis
Published: October 2021

This study aimed to assess the outcome of acute and chronic participants with spinal cord injury (SCI) after 12 weeks of bodyweight supported treadmill training (BWSTT) with a hybrid assistive limb exoskeleton (HAL). Acute participants were defined as ≤12 months between SCI and training, chronic participants >12 months between SCI and training. We assessed whether HAL-assisted BWSTT is advantageous for acute and chronic participants and if length of time post injury impacts the outcome of HAL-assisted BWSTT. As the primary outcome, we assessed the time needed for the 10 meter walk test (10MWT). Hundred and twenty-one individuals participated in a 12-week HAL-assisted BWSTT five times a week. We regularly conducted a 10MWT, a 6 minute walk test (6MWT), and assessed the walking index for spinal cord injury (WISCI II) and lower extremity motor score (LEMS) to evaluate the gait performance without the exoskeleton. Distance and time were recorded by the treadmill while the participant was walking with the exoskeleton. All participants benefit from the 12-week HAL-assisted BWSTT. A significant difference between acute and chronic participants' outcomes was found in 6MWT, LEMS, and WISCI II, though not in 10MWT. Although chronic participants improved significantly lesser than acute participants, they did improve their outcome significantly compared to the beginning. Hybrid assistive limb-assisted BWSTT in the rehabilitation of patients with SCI is advantageous for both acute and chronic patients. We could not define a time related cut-off threshold following SCI for effectiveness of HAL-assisted BWSTT.
Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial
Authors: Chen Yi , Wei Qing-Chuan , Zhang Ming-Zhi , Xie Yun-Juan , Liao Ling-Yi , Tan Hui-Xin , Guo Qi-Fan , Gao Qiang
Published: October 2021

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients.

Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention.

Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group.

Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).
Respiration-Driven Brain Oscillations in Emotional Cognition
Authors: Folschweiller Shani , Sauer Jonas-Frederic
Published: October 2021

Respiration paces brain oscillations and the firing of individual neurons, revealing a profound impact of rhythmic breathing on brain activity. Intriguingly, respiration-driven entrainment of neural activity occurs in a variety of cortical areas, including those involved in higher cognitive functions such as associative neocortical regions and the hippocampus. Here we review recent findings of respiration-entrained brain activity with a particular focus on emotional cognition. We summarize studies from different brain areas involved in emotional behavior such as fear, despair, and motivation, and compile findings of respiration-driven activities across species. Furthermore, we discuss the proposed cellular and network mechanisms by which cortical circuits are entrained by respiration. The emerging synthesis from a large body of literature suggests that the impact of respiration on brain function is widespread across the brain and highly relevant for distinct cognitive functions. These intricate links between respiration and cognitive processes call for mechanistic studies of the role of rhythmic breathing as a timing signal for brain activity.
Monitoring and Evaluation of Emotion Regulation by Aerobic Exercise and Motor Imagery Based on Functional Near-Infrared Spectroscopy
Authors: Ding Peng , Wang Fawang , Li Siyu , Zhang Wei , Li Hongquan , Chen Zhuangfei , Zhao Lei , Gong Anmin , Fu Yunfa
Published: October 2021

Objective: We sought to effectively alleviate the emotion of individuals with anxiety and depression, and explore the effects of aerobic exercise on their emotion regulation. Functional near-infrared spectroscopy (fNIRS) brain imaging technology is used to monitor and evaluate the process of aerobic exercise and imagination that regulates emotion.

Approach:Thirty participants were scored by the state-trait anxiety inventory (STAI) and profile of mood states (POMS), and fNIRS images were collected before, after, and during aerobic exercise and motor imagery. Then, the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (HbT) concentrations and their average value were calculated, and the ratio of HbO concentration in the left and right frontal lobes was determined. Spearman's correlation coefficient was used to calculate the correlation between variations in the average scores of the two scales and in blood oxygen concentrations.

Results: In comparison with motor imagery, STAI, and POMS scores decreased after 20 min of aerobic exercise. The prefrontal cortex had asymmetry and laterality (with the left side being dominant in emotion regulation). The increase in hemoglobin concentration recorded by fNIRS was negatively correlated with STAI and POMS scores. Aerobic exercise has a good effect on emotion regulation.

Significance:The study showed that portable fNIRS could be effectively used for monitoring and evaluating emotion regulation by aerobic exercise. This study is expected to provide ideas for constructing fNIRS-based online real-time monitoring and evaluation of emotion regulation by aerobic exercise.
Alterations in Glycerolipid and Fatty Acid Metabolic Pathways in Alzheimer's Disease Identified by Urinary Metabolic Profiling: A Pilot Study
Authors: Watanabe Yumi , Kasuga Kensaku , Tokutake Takayoshi , Kitamura Kaori , Ikeuchi Takeshi , Nakamura Kazutoshi
Published: October 2021

An easily accessible and non-invasive biomarker for the early detection of Alzheimer's disease (AD) is needed. Evidence suggests that metabolic dysfunction underlies the pathophysiology of AD. While urine is a non-invasively collectable biofluid and a good source for metabolomics analysis, it is not yet widely used for this purpose. This small-scale pilot study aimed to examine whether the metabolic profile of urine from AD patients reflects the metabolic dysfunction reported to underlie AD pathology, and to identify metabolites that could distinguish AD patients from cognitively healthy controls. Spot urine of 18 AD patients (AD group) and 18 age- and sex-matched, cognitively normal controls (control group) were analyzed by mass spectrometry (MS). Capillary electrophoresis time-of-flight MS and liquid chromatography–Fourier transform MS were used to cover a larger range of molecules with ionic as well as lipid characteristics. A total of 304 ionic molecules and 81 lipid compounds of 12 lipid classes were identified. Of these, 26 molecules showed significantly different relative concentrations between the AD and control groups (Wilcoxon's rank-sum test). Moreover, orthogonal partial least-squares discriminant analysis revealed significant discrimination between the two groups. Pathway searches using the KEGG database, and pathway enrichment and topology analysis using Metaboanalyst software, suggested alterations in molecules relevant to pathways of glycerolipid and glycerophospholipid metabolism, thermogenesis, and caffeine metabolism in AD patients. Further studies of urinary metabolites will contribute to the early detection of AD and understanding of its pathogenesis.