bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Progress on the Synergistic Antitumor Effect of a Borneol-Modified Nanocarrier Drug Delivery System
Authors: Li Jinxiu , Xie Qian , Ma Rong , Li Yong , Yuan Jianmei , Ren Mihong , Li Hongyan , Wang Jiajun , Lu Danni , Xu Zhuo , Wang Jian
Published: November 2021

Borneol, a traditional Chinese medicine, can enhance therapeutic efficacy by guiding the active ingredients to the target site. Reportedly, borneol improves the penetration capacity of the nasal, cornea, transdermal, intestinal, and blood-brain barriers. Although nanotechnology dramatically changed the face of oncology by targeting tumor sites, the efficiency of nanoparticles delivered to tumor sites is very low, with only 0.7% of the total particles delivered. Thus, based on the penetration ability and the inhibition drug efflux of borneol, it was expected to increase the targeting and detention efficacy of drugs into tumor sites in nanocarriers with borneol modification. Borneol modified nanocarriers used to improve drug-targeting has become a research focus in recent years, but few studies in this area, especially in the antitumor application. Hence, this review summarizes the recent development of nanocarriers with borneol modification. We focus on the updated works of improving therapeutic efficacy, reducing toxicity, inhibiting tumor metastasis, reversing multidrug resistance, and enhancing brain targeting to expand their application and provide a reference for further exploration of targeting drug delivery systems for solid tumor treatment.
The Prenatal Diagnosis and Clinical Outcomes of Fetuses With 15q11.2 Copy Number Variants: A Case Series of 36 Patients
Authors: Kang Jessica , Lee Chien-Nan , Su Yi-Ning , Lin Ming-Wei , Tai Yi-Yun , Hsu Wen-Wei , Huang Kuan-Ying , Chen Chi-Ling , Hung Chien-Hui , Lin Shin-Yu
Published: November 2021

Prenatal genetic counseling of fetuses diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1–BP2 region is difficult due to limited information and controversial opinion on prognosis. In total, we collected the data of 36 pregnant women who underwent prenatal microarray analysis from 2010 to 2017 and were assessed at National Taiwan University Hospital. Comparison of the maternal characteristics, prenatal ultrasound findings, and postnatal outcomes among the different cases involving the 15q11.2 BP1–BP2 region were presented. Out of the 36 fetuses diagnosed with CNVs involving the BP1–BP2 region, five were diagnosed with microduplications and 31 with microdeletions. Among the participants, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its low pathogenicity. In our study, the prenatal abnormal ultrasound findings were recorded in 12 participants and were associated with 15q11.2 deletions. No obvious developmental delay or neurological disorders were detected in early childhood.
The Power of Music to Prevent and Control Emerging Infectious Diseases
Authors: Benavides Julio A. , Caparrós Cristina , da Silva Ramiro Monã , Lembo Tiziana , Tem Dia Philip , Hampson Katie , Dos Santos Feliciano
Published: November 2021

Music is a powerful approach to engage communities and disseminate information. Specifically, health campaigns employing music have been used to promote behaviors that can prevent emerging infectious diseases (EIDs). For example, hip hop artists supported campaigns to prevent acquired immunodeficiency syndrome in the 70s in the United States, while Brazilian funk promoted vaccination to mitigate the ongoing COVID-19 pandemic. Similarly, we broadcast musical messages in local languages to increase community awareness and support prevention measures in Guinea and Liberia in response to the recent Ebola outbreak in 2021. Given the potential of music to promote both individual and population-level behavioral changes to prevent transmission, there is a need to consolidate information on music-based health interventions, and on how we can measure their effectiveness. In this perspective, we provide examples of relevant initiatives, discussing challenges and solutions associated with implementing interventions based on our experience with the 2021 Ebola outbreak. We recommend four steps for a successful music-based health intervention including (1) establishing a task force, (2) compose a “catchy” song including critical preventive measures, (3) deliver the song to the target audience, and (4) evaluate the campaign effectiveness. We argue that close interactions between scientists and musicians can produce rapid musical content for disease prevention. We also identify and discuss several methodological frameworks for testing the effectiveness of such interventions. We conclude that support from public health authorities, government media departments, and international agencies, is necessary to deliver wide outreach and long-term sustainability of musical messaging toward effective EID prevention.
Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD
Authors: Casas-Recasens Sandra , Mendoza Nuria , López-Giraldo Alejandra , Garcia Tamara , Cosio Borja G. , Pascual-Guardia Sergi , Acosta-Castro Ady , Borras-Santos Alicia , Gea Joaquim , Garrabou Gloria , Agusti Alvar , Faner Rosa
Published: November 2021

Accelerated ageing is implicated in the pathogenesis of respiratory diseases as chronic obstructive pulmonary disease (COPD), but recent evidence indicates that the COPD can have roots early in life. Here we hypothesise that the accelerated ageing markers might have a role in the pathobiology of young COPD. The objective of this study was to compare two hallmarks of ageing, telomere length (TL), and mitochondrial DNA copy number (mtDNA-CN, as a surrogate marker of mitochondrial dysfunction) in young (≤ 50 years) and old (>50 years) smokers, with and without COPD. Both, TL and mtDNA-CN were measured in whole blood DNA by quantitative PCR [qPCR] in: (1) young ever smokers with (n = 81) or without (n = 166) COPD; and (2) old ever smokers with (n = 159) or without (n = 29) COPD. A multivariable linear regression was used to assess the association of TL and mtDNA-CN with lung function. We observed that in the entire study population, TL and mtDNA-CN decreased with age, and the former but not the latter related to FEV1/FVC (%), FEV1 (% ref.), and DLCO (% ref.). The short telomeres were found both in the young and old patients with severe COPD (FEV1 <50% ref.). In addition, we found that TL and mtDNA-CN were significantly correlated, but their relationship was positive in younger while negative in the older patients with COPD, suggesting a mitochondrial dysfunction. We conclude that TL, but not mtDNA-CN, is associated with the lung function impairment. Both young and old patients with severe COPD have evidence of accelerated ageing (shorter TL) but differ in the direction of the correlation between TL and mtDNA-CN in relation to age.
Chronic Kidney Disease and Arterial Stiffness: A Two-Way Path
Authors: Inserra Felipe , Forcada Pedro , Castellaro Agustina , Castellaro Carlos
Published: November 2021

The kidney-heart relationship has raised interest for the medical population since its vast and complex interaction significantly impacts health. Chronic kidney disease (CKD) generates vascular structure and function changes, with significant hemodynamic effects. The early arterial stiffening in CKD patients is a consequence of the interaction between oxidative stress and chronic vascular inflammation, leading to an accelerated deterioration of left ventricular function and alteration in tissue perfusion. CKD amplifies the inflammatory cascade's activation and is responsible for altering the endothelium function, increasing the vascular tone, wall thickening, and favors calcium deposits in the arterial wall. Simultaneously, the autonomic imbalance, and alteration in other hormonal systems, also favor the overactivation of inflammatory and fibrotic mediators. Thus, hormonal disarrangement also contributes to structural and functional lesions throughout the arterial wall. On the other hand, a rise in arterial stiffening and volume overload generates high left ventricular afterload. It increases the left ventricular burden with consequent myocardial remodeling, development of left ventricular hypertrophy and, in turn, heart failure. It is noteworthy that reduction in glomerular mass of renal diseases generates a compensatory glomerular filtration overdriven associated with large-arteries stiffness and high cardiovascular events. Furthermore, we consider that the consequent alterations of the arterial system's mechanical properties are crucial for altering tissue perfusion, mainly in low resistance. Thus, increasing the knowledge of these processes may help the reader to integrate them from a pathophysiological perspective, providing a comprehensive idea of this two-way path between arterial stiffness and renal dysfunction and their impact at the cardiovascular level.
A Proposal of a Combined Convergence Regulatory Strategy Applied to Post-approval Changes by Latin American Countries, Reducing Workload and Allowing Continuous Improvement to Guarantee the Quality, Safety, and Efficacy of Medicines
Authors: Rodriguez Heraclio , De Lucia Maria Lucia
Published: November 2021

In recent years, post-approval changes (PACs) for medicinal products have increased faster than the national regulatory agencies can attend to without causing any negative impact. This study presents a proposal for regulatory management based on our analysis of the data available from the national regulatory agencies of Latin America on the total post-approval changes evaluated, and the time spent in the process. A retrospective search on the official websites of competent national regulatory authorities (NRAs) of 14 Latin American countries (México, Guatemala, Nicaragua, Honduras, El Salvador, Panamá, Costa Rica, Venezuela, Colombia, Ecuador, Peru, Argentina, Chile and Brazil) was conducted to collect data on post-approval changes in the last 4–6 years, up to January 2021. The NRAs considered were Brazil, México, Colombia, and Costa Rica. Our analysis was focused on the post-approval changes that required approval before implementation, those that were submitted, and those that were submitted and approved for small molecules, biologics, and biotechnological products. The results indicated differences in the regulatory processes and procedures applied by the different agencies. We also found that the implementation of the PACs was directly impacted by limited resources, which puts the medication supply for chronic treatments at risk resulting in serious consequences for patients. For local decision-making, Latin American NRAs should implement regulatory pathways already made by regulatory agencies included in the World Health Organization Listed Authorities on PAC approval to optimize their resources and to ensure the continuity of medicine supply for their patients.
Construction and Application of an Intelligent Response System for COVID-19 Voice Consultation in China: A Retrospective Study
Authors: Shi Jinming , Gao Jinghong , Zhai Yunkai , Ye Ming , Lu Yaoen , He Xianying , Cui Fangfang , Ma Qianqian , Zhao Jie
Published: November 2021

Background: The outbreak of novel coronavirus disease 2019 (COVID-19) has led to tremendous individuals visit medical institutions for healthcare services. Public gatherings and close contact in clinics and emergency departments may increase the exposure and cross-infection of COVID-19.

Objectives: The purpose of this study was to develop and deploy an intelligent response system for COVID-19 voice consultation, to provide suggestions of response measures based on actual information of users, and screen COVID-19 suspected cases.

Methods: Based on the requirements analysis of business, user, and function, the physical architecture, system architecture, and core algorithms are designed and implemented. The system operation process is designed according to guidance documents of the National Health Commission and the actual experience of prevention, diagnosis and treatment of COVID-19. Both qualitative (system construction) and quantitative (system application) data from the real-world healthcare service of the system were retrospectively collected and analyzed.

Results: The system realizes the functions, such as remote deployment and operations, fast operation procedure adjustment, and multi-dimensional statistical report capability. The performance of the machine-learning model used to develop the system is better than others, with the lowest Character Error Rate (CER) 8.13%. As of September 24, 2020, the system has received 12,264 times incoming calls and provided a total of 11,788 COVID-19-related consultation services for the public. Approximately 85.2% of the users are from Henan Province and followed by Beijing (2.5%). Of all the incoming calls, China Mobile contributes the largest proportion (66%), while China Unicom and China Telecom are accounted for 23% and 11%. For the time that users access the system, there is a peak period in the morning (08:00–10:00) and afternoon (14:00–16:00), respectively.

Conclusions: The intelligent response system has achieved appreciable practical implementation effects. Our findings reveal that the provision of inquiry services through an intelligent voice consultation system may play a role in optimizing the allocation of healthcare resources, improving the efficiency of medical services, saving medical expenses, and protecting vulnerable groups.
Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection
Authors: Wang Jiayi , Du Lingyao , Tang Hong
Published: November 2021

Chronic hepatitis B virus (CHB) infection remains a major global public health issue for which there is still lacking effective curative treatment. Interferon-α (IFN-α) and its pegylated form have been approved as an anti-HBV drug with the advantage of antiviral activity and host immunity against HBV infection enhancement, however, IFN-α treatment failure in CHB patients is a challenging obstacle with 70% of CHB patients respond poorly to exogenous IFN-α treatment. The IFN-α treatment response is negatively regulated by both viral and host factors, and the role of viral factors has been extensively illustrated, while much less attention has been paid to host negative factors. Here, we summarized evidence of host negative regulators and parameters involved in IFN-α therapy failure, review the mechanisms responsible for these effects, and discuss the possible improvement of IFN-based therapy and the rationale of combining the inhibitors of negative regulators in achieving an HBV cure.
Changes in Anterior and Posterior Corneal Elevation in Patients With Allergic Conjunctivitis
Authors: Wang Qian , Yu Fei , Feng Ziqing , Li Weihua , Li Naiyang , Du Xinyue , Zhao Xuan , Li Saiqun , Yuan Jin
Published: November 2021

Purpose: To evaluate corneal elevation changes in patients with allergic conjunctivitis (AC) and to analyze their correlations with ocular allergy signs and corneal biomechanical alterations.

Methods: Thirty patients (30 eyes) with AC and twenty normal subjects (20 eyes) were included in this prospective study. All participants underwent a complete ocular examination, including corneal tomography by Pentacam and corneal biomechanics evaluation by Corvis ST. AC patients were evaluated for their eye rubbing frequency and ocular allergic signs.

Results: The elevation at the thinnest location (TE) and the central location (CE), the elevation difference at the thinnest location (TED) and the central location (CED), and the mean value of elevation difference in the central 4 mm zoom (MED) of both the anterior and posterior corneal surface were significantly higher in the AC group than in the normal group (p < 0.05 for all). In AC patients, only anterior corneal elevation parameters were positively correlated with eye rubbing frequency and ocular allergy sign severity (p < 0.05 for all), while the tomography and biomechanical index (TBI) was positively correlated with the elevation parameters of both the anterior and posterior corneal surfaces (p < 0.05 for all).

Conclusion: AC patients carry an increased risk of corneal ectasia. Posterior corneal elevation parameters are sensitive and reliable predictors of keratoconus (KC) risk in AC patients.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04299399, identifier [NCT04299399].
Dry Eye Disease Among Mongolian and Han Older Adults in Grasslands of Northern China: Prevalence, Associated Factors, and Vision-Related Quality of Life
Authors: Wu Jianhua , Wu Xiaomei , Zhang Han , Zhang Xiaoguang , Zhang Jie , Liu Yanqiu , Liu Jun , Lu Lu , Zhang Song , Zhang Guisen , Liu Lei
Published: November 2021

Purpose: Dry eye disease (DED) is projected to have increasing public health burden in China with the aging population. No published studies on the epidemiology of DED have been found in grasslands. We estimated DED prevalence among older adults living in grasslands of northern China and investigated its associated factors and impact on vision-related quality of life (VR-QoL).

Methods: A multistage cluster random sampling technique was used to select Mongolian and Han participants aged over 40 from November 2020 to May 2021 in this area. An assessment of DED was performed with Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's I test (ST), and Tear film break up time (TBUT). All the participants completed the Chinese version of National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) assessing VR-QoL.

Results: Of the 1,400 enumerated residents, 1,287 were examined. The overall age and gender standardized prevalence of DED was 34.5%, of which, 32.6% of Mongolian and 35.4% of Han had DED. In a multivariate model, statistically significant associations were found with advancing age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02–1.04], female gender (OR 1.32, 95% CI 1.04–1.68), smoking (OR 0.7, 95% CI 0.5–0.98), anti-fatigue eye-drop use (OR 0.56, 95% CI 0.41–0.77), milk product intake (OR 0.55, 95% CI 0.39–0.77), number of household members (OR 0.8, 95% CI 0.72–0.88). DED was associated with lower scores on VR-QoL (β= −0.14, P < 0.01). Similar results were observed when analyses were stratified by ethnicity.

Conclusions: The novelty-associated factors for DED in the grasslands area were anti-fatigue eye drop use, milk product intake, and number of household members. DED and its components were associated with VR-QoL. Further prospective studies are needed to confirm these findings.
The Digital Way to Intercept Psoriatic Arthritis
Authors: Giovannini Ivan , Bosch Philipp , Dejaco Christian , De Marco Gabriele , McGonagle Dennis , Quartuccio Luca , De Vita Salvatore , Errichetti Enzo , Zabotti Alen
Published: November 2021

Psoriasis (PsO) and Psoriatic Arthritis (PsA) are chronic, immune-mediated diseases that share common etiopathogenetic pathways. Up to 30% of PsO patient may later develop PsA. In nearly 75% of cases, skin psoriatic lesions precede arthritic symptoms, typically 10 years prior to the onset of joint symptoms, while PsO diagnosis occurring after the onset of arthritis is described only in 15% of cases. Therefore, skin involvement offers to the rheumatologist a unique opportunity to study PsA in a very early phase, having a cohort of psoriatic “risk patients” that may develop the disease and may benefit from preventive treatment. Progression from PsO to PsA is often characterized by non-specific musculoskeletal symptoms, subclinical synovio-entheseal inflammation, and occasionally asymptomatic digital swelling such as painless toe dactylitis, that frequently go unnoticed, leading to diagnostic delay. The early diagnosis of PsA is crucial for initiating a treatment prior the development of significant and permanent joint damage. With the ongoing development of pharmacological treatments, early interception of PsA has become a priority, but many obstacles have been reported in daily routine. The introduction of digital technology in rheumatology may fill the gap in the physician-patient relationship, allowing more targeted monitoring of PsO patients. Digital technology includes telemedicine, virtual visits, electronic health record, wearable technology, mobile health, artificial intelligence, and machine learning. Overall, this digital revolution could lead to earlier PsA diagnosis, improved follow-up and disease control as well as maximizing the referral capacity of rheumatic centers.
Contrasting Community Assembly Forces Drive Microbial Structural and Potential Functional Responses to Precipitation in an Incipient Soil System
Authors: Sengupta Aditi , Volkmann Till H. M. , Danczak Robert E. , Stegen James C. , Dontsova Katerina , Abramson Nate , Bugaj Aaron S. , Volk Michael J. , Matos Katarena A. , Meira-Neto Antonio A. , Barberán Albert , Neilson Julia W. , Maier Raina M. , Chorover Jon , Troch Peter A. , Meredith Laura K.
Published: November 2021

Microbial communities in incipient soil systems serve as the only biotic force shaping landscape evolution. However, the underlying ecological forces shaping microbial community structure and function are inadequately understood. We used amplicon sequencing to determine microbial taxonomic assembly and metagenome sequencing to evaluate microbial functional assembly in incipient basaltic soil subjected to precipitation. Community composition was stratified with soil depth in the pre-precipitation samples, with surficial communities maintaining their distinct structure and diversity after precipitation, while the deeper soil samples appeared to become more uniform. The structural community assembly remained deterministic in pre- and post-precipitation periods, with homogenous selection being dominant. Metagenome analysis revealed that carbon and nitrogen functional potential was assembled stochastically. Sub-populations putatively involved in the nitrogen cycle and carbon fixation experienced counteracting assembly pressures at the deepest depths, suggesting the communities may functionally assemble to respond to short-term environmental fluctuations and impact the landscape-scale response to perturbations. We propose that contrasting assembly forces impact microbial structure and potential function in an incipient landscape; in situ landscape characteristics (here homogenous parent material) drive community structure assembly, while short-term environmental fluctuations (here precipitation) shape environmental variations that are random in the soil depth profile and drive stochastic sub-population functional dynamics.
Soil Bacteria in Urban Community Gardens Have the Potential to Disseminate Antimicrobial Resistance Through Horizontal Gene Transfer
Authors: Mafiz Abdullah Ibn , He Yingshu , Zhang Wei , Zhang Yifan
Published: November 2021

Fifteen soil and 45 vegetable samples from Detroit community gardens were analyzed for potential antimicrobial resistance contamination. Soil bacteria were isolated and tested by antimicrobial susceptibility profiling, horizontal gene transfer, and whole-genome sequencing. High-throughput 16S rRNA sequencing analysis was conducted on collected soil samples to determine the total bacterial composition. Of 226 bacterial isolates recovered, 54 were from soil and 172 from vegetables. A high minimal inhibitory concentration (MIC) was defined as the MIC greater than or equal to the resistance breakpoint of Escherichia coli for Gram-negative bacteria or Staphylococcus aureus for Gram-positive bacteria. The high MIC was observed in 63.4 and 69.8% of Gram-negative isolates from soil and vegetables, respectively, against amoxicillin/clavulanic acid, as well as 97.5 and 82.7% against ampicillin, 97.6 and 90.7% against ceftriaxone, 85.4 and 81.3% against cefoxitin, 65.8 and 70.5% against chloramphenicol, and 80.5 and 59.7% against ciprofloxacin. All Gram-positive bacteria showed a high MIC to gentamicin, kanamycin, and penicillin. Forty of 57 isolates carrying tetM (70.2%) successfully transferred tetracycline resistance to a susceptible recipient via conjugation. Whole-genome sequencing analysis identified a wide array of antimicrobial resistance genes (ARGs), including those encoding AdeIJK, Mex, and SmeDEF efflux pumps, suggesting a high potential of the isolates to become antimicrobial resistant, despite some inconsistency between the gene profile and the resistance phenotype. In conclusion, soil bacteria in urban community gardens can serve as a reservoir of antimicrobial resistance with the potential to transfer to clinically important pathogens, resulting in food safety and public health concerns.
Microbiota Variation Across Life Stages of European Field-Caught Anopheles atroparvus and During Laboratory Colonization: New Insights for Malaria Research
Authors: Birnberg Lotty , Climent-Sanz Eric , Codoñer Francisco M. , Busquets Núria
Published: November 2021

The potential use of bacteria for developing novel vector control approaches has awakened new interests in the study of the microbiota associated with vector species. To set a baseline for future malaria research, a high-throughput sequencing of the bacterial 16S ribosomal gene V3-V4 region was used to profile the microbiota associated with late-instar larvae, newly emerged females, and wild-caught females of a sylvanAnopheles atroparvuspopulation from a former malaria transmission area of Spain. Field-acquired microbiota was then assessed in non-blood-fed laboratory-reared females from the second, sixth, and 10th generations. Diversity analyses revealed that bacterial communities varied and clustered differently according to origin with sylvan larvae and newly emerged females distributing closer to laboratory-reared females than to their field counterparts. Inter-sample variation was mostly observed throughout the different developmental stages in the sylvan population. Larvae harbored the most diverse bacterial communities; wild-caught females, the poorest. In the transition from the sylvan environment to the first time point of laboratory breeding, a significant increase in diversity was observed, although this did decline under laboratory conditions. Despite diversity differences between wild-caught and laboratory-reared females, a substantial fraction of the bacterial communities was transferred through transstadial transmission and these persisted over 10 laboratory generations. Differentially abundant bacteria were mostly identified between breeding water and late-instar larvae, and in the transition from wild-caught to laboratory-reared females from the second generation. Our findings confirmed the key role of the breeding environment in shaping the microbiota ofAn. atroparvus. Gram-negative bacteria governed the microbiota ofAn. atroparvuswith the prevalence of proteobacteria.Pantoea,Thorsellia,Serratia,Asaia, andPseudomonasdominating the microbiota associated with wild-caught females, with the latter two governing the communities of laboratory-reared females. A core microbiota was identified withPseudomonasandSerratiabeing the most abundant core genera shared by all sylvan and laboratory specimens. Overall, understanding the microbiota composition ofAn. atroparvusand how this varies throughout the mosquito life cycle and laboratory colonization paves the way when selecting potential bacterial candidates for use in microbiota-based intervention strategies against mosquito vectors, thereby improving our knowledge of laboratory-rearedAn. atroparvusmosquitoes for research purposes.
Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
Authors: Zhang Ingrid W. , López-Vicario Cristina , Duran-Güell Marta , Clària Joan
Published: November 2021

Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.
Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease
Authors: Seo Nari , Lee Hyunjun , Oh Myung Jin , Kim Ga Hyeon , Lee Sang Gil , Ahn Joong Kyong , Cha Hoon-Suk , Kim Kyoung Heon , Kim Jaehan , An Hyun Joo
Published: November 2021

Behcet’s disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death. Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity. As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted. In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell–cell/pathogen interactions, and tumor progression. Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases. Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans. Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2. Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers. In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD. In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes. Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
Prospective Analysis Between Neutrophil-to-Lymphocyte Ratio on Admission and Development of Delirium Among Older Hospitalized Patients With COVID-19
Authors: Fernández-Jiménez Eduardo , Muñoz-Sanjose Ainoa , Mediavilla Roberto , Martínez-Alés Gonzalo , Louzao Iker I. , Andreo Jorge , Cebolla Susana , Bravo-Ortiz María-Fe , Bayón Carmen
Published: November 2021

Objective: To examine any prospective association between neutrophil-to-lymphocyte ratio (NLR) at hospital admission and subsequent delirium in older COVID-19 hospitalized patients comparing by sex and age groups.

Methods: The sample consisted of 1,785 COVID-19 adult inpatients (minimum sample size required of 635 participants) admitted to a public general hospital in Madrid (Spain) between March 16th and April 15th, 2020. Variables were obtained from electronic health records. Binary logistic regression models were performed between baseline NLR and delirium adjusting for age, sex, medical comorbidity, current illness severity, serious mental illness history and use of chloroquine and dexamethasone. An NLR cut-off was identified, and stratified analyses were performed by age and sex. Also, another biomarker was tested as an exposure (the systemic immune-inflammation index –SII).

Results: 55.3% of the patients were men, with a mean age of 66.8 years. Roughly 13% of the patients had delirium during hospitalization. NLR on admission predicted subsequent delirium development (adjusted OR = 1.02, 95 percent CI: 1.00–1.04, p = 0.024). Patients between 69 and 80 years with NLR values > 6.3 presented a twofold increased risk for delirium (p = 0.004). There were no sex differences in the association between baseline NLR and delirium (p > 0.05) nor SII predicted delirium development (p = 0.341).

Conclusion: NLR is a good predictor of delirium during hospitalization, especially among older adults, independently of medical comorbidity, illness severity, and other covariates. Routine blood tests on admission might provide valuable information to guide the decision-making process to be followed with these especially vulnerable patients.
Effects of Buprenorphine on the Memory and Learning Deficit Induced by Methamphetamine Administration in Male Rats
Authors: Etaee Farshid , Rezvani-Kamran Arezoo , Komaki Somayeh , Asadbegi Masoumeh , Faraji Nafiseh , Raoufi Safoura , Taheri Mohammad , Kourosh-Arami Masoumeh , Komaki Alireza
Published: November 2021

Little is known about the effects of methamphetamine (Meth) and buprenorphine (Bup) on memory and learning in rats. The aim of this investigation was to examine the impact of Meth and Bup on memory and learning. Fourteen male Wistar rats weighing 250–300 g were assigned to four groups: Sham, Meth, Bup, and Meth + Bup and were treated for 1 week. Spatial learning and memory, avoidance learning, and locomotion were assessed using the Morris water maze, passive avoidance learning, and open field tests, respectively. Meth and Bup impaired spatial learning and memory in rats. Co-administration of Meth + Bup did not increase the time spent in the target quadrant compared to Meth alone in the MWM. The Bup and Meh + Bup groups were found with an increase in step-through latency (STLr) and a decrease in the time spent in the dark compartment (TDC). Meth and Bup had no effects on locomotor activity in the open field test. Bup showed a beneficial effect on aversive memory. Since Bup demonstrates fewer side effects than other opioid drugs, it may be preferable for the treatment of avoidance memory deficits in patients with Meth addiction.
Evaluating Convolutional Neural Networks as a Method of EEG–EMG Fusion
Authors: Tryon Jacob , Trejos Ana Luisa
Published: November 2021

Wearable robotic exoskeletons have emerged as an exciting new treatment tool for disorders affecting mobility; however, the human–machine interface, used by the patient for device control, requires further improvement before robotic assistance and rehabilitation can be widely adopted. One method, made possible through advancements in machine learning technology, is the use of bioelectrical signals, such as electroencephalography (EEG) and electromyography (EMG), to classify the user's actions and intentions. While classification using these signals has been demonstrated for many relevant control tasks, such as motion intention detection and gesture recognition, challenges in decoding the bioelectrical signals have caused researchers to seek methods for improving the accuracy of these models. One such method is the use of EEG–EMG fusion, creating a classification model that decodes information from both EEG and EMG signals simultaneously to increase the amount of available information. So far, EEG–EMG fusion has been implemented using traditional machine learning methods that rely on manual feature extraction; however, new machine learning methods have emerged that can automatically extract relevant information from a dataset, which may prove beneficial during EEG–EMG fusion. In this study, Convolutional Neural Network (CNN) models were developed using combined EEG–EMG inputs to determine if they have potential as a method of EEG–EMG fusion that automatically extracts relevant information from both signals simultaneously. EEG and EMG signals were recorded during elbow flexion–extension and used to develop CNN models based on time–frequency (spectrogram) and time (filtered signal) domain image inputs. The results show a mean accuracy of 80.51 ± 8.07% for a three-class output (33.33% chance level), with an F-score of 80.74%, using time–frequency domain-based models. This work demonstrates the viability of CNNs as a new method of EEG–EMG fusion and evaluates different signal representations to determine the best implementation of a combined EEG–EMG CNN. It leverages modern machine learning methods to advance EEG–EMG fusion, which will ultimately lead to improvements in the usability of wearable robotic exoskeletons.
Egocentric Gesture Recognition Using 3D Convolutional Neural Networks for the Spatiotemporal Adaptation of Collaborative Robots
Authors: Papanagiotou Dimitris , Senteri Gavriela , Manitsaris Sotiris
Published: November 2021

Collaborative robots are currently deployed in professional environments, in collaboration with professional human operators, helping to strike the right balance between mechanization and manual intervention in manufacturing processes required by Industry 4.0. In this paper, the contribution of gesture recognition and pose estimation to the smooth introduction of cobots into an industrial assembly line is described, with a view to performing actions in parallel with the human operators and enabling interaction between them. The proposed active vision system uses two RGB-D cameras that record different points of view of gestures and poses of the operator, to build an external perception layer for the robot that facilitates spatiotemporal adaptation, in accordance with the human's behavior. The use-case of this work is concerned with LCD TV assembly of an appliance manufacturer, comprising of two parts. The first part of the above-mentioned operation is assigned to a robot, strengthening the assembly line. The second part is assigned to a human operator. Gesture recognition, pose estimation, physical interaction, and sonic notification, create a multimodal human-robot interaction system. Five experiments are performed, to test if gesture recognition and pose estimation can reduce the cycle time and range of motion of the operator, respectively. Physical interaction is achieved using the force sensor of the cobot. Pose estimation through a skeleton-tracking algorithm provides the cobot with human pose information and makes it spatially adjustable. Sonic notification is added for the case of unexpected incidents. A real-time gesture recognition module is implemented through a Deep Learning architecture consisting of Convolutional layers, trained in an egocentric view and reducing the cycle time of the routine by almost 20%. This constitutes an added value in this work, as it affords the potential of recognizing gestures independently of the anthropometric characteristics and the background. Common metrics derived from the literature are used for the evaluation of the proposed system. The percentage of spatial adaptation of the cobot is proposed as a new KPI for a collaborative system and the opinion of the human operator is measured through a questionnaire that concerns the various affective states of the operator during the collaboration.
TLR4 Associated Signaling Disrupters as a New Means to Overcome HERV-W Envelope-Mediated Myelination Deficits
Authors: Göttle Peter , Schichel Kira , Reiche Laura , Werner Luisa , Zink Annika , Prigione Alessandro , Küry Patrick
Published: November 2021

Myelin repair in the adult central nervous system (CNS) is driven by successful differentiation of resident oligodendroglial precursor cells (OPCs) and thus constitutes a neurodegenerative process capable to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis (MS). The human endogenous retrovirus type W (HERV-W) represents an MS-specific pathogenic entity, and its envelope (ENV) protein was previously identified as a negative regulator of OPC maturation—hence, it is of relevance in the context of diminished myelin repair. We here focused on the activity of the ENV protein and investigated how it can be neutralized for improved remyelination. ENV-mediated activation of toll like receptor 4 (TLR4) increases inducible nitric oxide synthase (iNOS) expression, prompts nitrosative stress, and results in myelin-associated deficits, such as decreased levels of oligodendroglial maturation marker expression and morphological alterations. The intervention of TLR4 surface expression represents a potential means to rescue such ENV-dependent deficits. To this end, the rescue capacity of specific substances, either modulating V-ATPase activity or myeloid differentiation 2 (MD2)-mediated TLR4 glycosylation status, such as compound 20 (C20), L48H437, or folimycin, was analyzed, as these processes were demonstrated to be relevant for TLR4 surface expression. We found that pharmacological treatment can rescue the maturation arrest of oligodendroglial cells and their myelination capacity and can prevent iNOS induction in the presence of the ENV protein. In addition, downregulation of TLR4 surface expression was observed. Furthermore, mitochondrial integrity crucial for oligodendroglial cell differentiation was affected in the presence of ENV and ameliorated upon pharmacological treatment. Our study, therefore, provides novel insights into possible means to overcome myelination deficits associated with HERV-W ENV-mediated myelin deficits.
Dynamic Visual Stimulations Produced in a Controlled Virtual Reality Environment Reveals Long-Lasting Postural Deficits in Children With Mild Traumatic Brain Injury
Authors: Romeas Thomas , Greffou Selma , Allard Remy , Forget Robert , McKerral Michelle , Faubert Jocelyn , Gagnon Isabelle
Published: November 2021

Motor control deficits outlasting self-reported symptoms are often reported following mild traumatic brain injury (mTBI). The exact duration and nature of these deficits remains unknown. The current study aimed to compare postural responses to static or dynamic virtual visual inputs and during standard clinical tests of balance in 38 children between 9 and 18 years-of-age, at 2 weeks, 3 and 12 months post-concussion. Body sway amplitude (BSA) and postural instability (vRMS) were measured in a 3D virtual reality (VR) tunnel (i.e., optic flow) moving in the antero-posterior direction in different conditions. Measures derived from standard clinical balance evaluations (BOT-2, Timed tasks) and post-concussion symptoms (PCSS-R) were also assessed. Results were compared to those of 38 healthy non-injured children following a similar testing schedule and matched according to age, gender, and premorbid level of physical activity. Results highlighted greater postural response with BSA and vRMS measures at 3 months post-mTBI, but not at 12 months when compared to controls, whereas no differences were observed in post-concussion symptoms between mTBI and controls at 3 and 12 months. These deficits were specifically identified using measures of postural response in reaction to 3D dynamic visual inputs in the VR paradigm, while items from the BOT-2 and the 3 timed tasks did not reveal deficits at any of the test sessions. PCSS-R scores correlated between sessions and with the most challenging condition of the BOT-2 and as well as with the timed tasks, but not with BSA and vRMS. Scores obtained in the most challenging conditions of clinical balance tests also correlated weakly with BSA and vRMS measures in the dynamic conditions. These preliminary findings suggest that using 3D dynamic visual inputs such as optic flow in a controlled VR environment could help detect subtle postural impairments and inspire the development of clinical tools to guide rehabilitation and return to play recommendations.
Longitudinal Quantitative MRI Evaluation of Muscle Involvement in Amyotrophic Lateral Sclerosis
Authors: Paoletti Matteo , Diamanti Luca , Muzic Shaun I. , Ballante Elena , Solazzo Francesca , Foppoli Lia , Deligianni Xeni , Santini Francesco , Figini Silvia , Bergsland Niels , Pichiecchio Anna
Published: November 2021

Background: Biomarkers of disease progression and outcome measures are still lacking for patients with amyotrophic lateral sclerosis (ALS). Muscle MRI can be a promising candidate to track longitudinal changes and to predict response to the therapy in clinical trials.

Objective: Our aim is to apply quantitative muscle MRI in the evaluation of disease progression, focusing on thigh and leg muscles of patients with ALS, and to explore the correlation between radiological and clinical scores.

Methods: We enrolled newly diagnosed patients with ALS, longitudinally scored using the ALS Functional Rating Scale-Revised (ALSFRS-R), who underwent a 3T muscle MRI protocol including a 6-point Dixon gradient-echo sequence and multi-echo turbo spin echo (TSE) T2-weighted sequence for quantification of fat fraction (FF), cross-sectional area (CSA), and water T2 (wT2). A total of 12 muscles of the thigh and six muscles of the leg were assessed by the manual drawing of 18 regions of interest (ROIs), for each side. A group of 11 age-matched healthy controls (HCs) was enrolled for comparison.

Results: 15 patients (M/F 8/7; mean age 62.2 years old, range 29–79) diagnosed with possible (n = 2), probable (n = 12), or definite (n = 1) ALS were enrolled. Eleven patients presented spinal onset, whereas four of them had initial bulbar involvement. All patients performed MRI at T0, nine of them at T1, and seven of them at T2. At baseline, wT2 was significantly elevated in ALS subjects compared to HCs for several muscles of the thigh and mainly for leg muscles. By contrast, FF was elevated in few muscles, and mainly at the level of the thigh. The applied mixed effects model showed that FF increased significantly in the leg muscles over time (mainly in the triceps surae) and that wT2 decreased significantly in line with worsening in the leg subscore of ALSFRS-R, mainly at the leg level and in the anterior and medial compartment of the thigh.

Conclusions: Quantitative MRI represents a non-invasive tool that is able to outline the trajectory of pathogenic modifications at the muscle level in ALS. In particular, wT2 was found to be increased early in the clinical history of ALS and also tended to decrease over time, also showing a positive correlation with leg subscore of ALSFRS-R.