bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro-Resolving Factor Administration Limits Cancer Progression by Enhancing Immune Response Against Cancer Cells
Authors: Wetzel Audrey , Bonnefoy Francis , Chagué Cécile , Vetter Mathieu , Couturier Mélanie , Baffert Blandine , Adotévi Olivier , Saas Philippe , Perruche Sylvain
Published: January 2022

Cancers are consequences of cellular dysfunction leading to an aberrant cellular multiplication and proliferation, subsequently yielding metastasis formation. Inflammatory reaction, with immune cell recruitment, is the main defense against precancerous lesions. However, an inflammatory environment also favors cancer cell progression, with cancer cell evasion from immune surveillance, leading to cancer development. Current therapeutic strategies enhance this natural immune response in order to restore immunosurveillance. The variety of these strategies is a predominant source of inflammatory mediators used by cancer cells to grow, differentiate, and migrate, therefore encouraging metastasis formation. For this reason, during cancer progression, limiting inflammation appears to be an innovative strategy to avoid the escape of cancer cells and potentially enhance the efficacy of antitumor therapies. Thus, this study aims to investigate the impact of administering pro-resolving factors (SuperMApo® drug candidate), which are inducers of inflammation resolution, in the framework of cancer treatment. We have observed that administering pro-resolving mediators issued from apoptotic cell efferocytosis by macrophages controlled peritoneal cancer progression by limiting cancer cell dissemination to the blood and mesenteric lymph nodes. This observation has been linked to an increase of macrophage mobilization in both peritoneal cavity and mesenteric lymph nodes. This control is associated to a restricted immunosuppressive myeloid cell circulation and to an IFN-γ-specific anti-tumor T-cell response. Altogether, these results suggest that administering proresolving factors could provide a new additional therapeutic alternative to control cancer progression.
Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
Authors: Fasano Rossella , Malerba Eleonora , Prete Marcella , Solimando Antonio Giovanni , Buonavoglia Alessio , Silvestris Nicola , Leone Patrizia , Racanelli Vito
Published: January 2022

The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH.
Rituximab in the Treatment of Interstitial Lung Diseases Related to Anti-Melanoma Differentiation-Associated Gene 5 Dermatomyositis: A Systematic Review
Authors: He Chenjia , Li Wenyu , Xie Qibing , Yin Geng
Published: January 2022

Objective

The effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only in isolated case reports and small series. This paper aims to review the current evidence regarding rituximab (RTX) use in the treatment of ILD related to anti-MDA5 DM (anti-MDA5 DM-ILD).

Methods

We conducted a review by searching PubMed, Web of Science, Embase, and Cochrane for articles with information on patients with anti-MDA5 DM and RTX treatment, published until August 2021, in English language. The selected studies listed variation in chest high-resolution computed tomography (HRCT) and/or pulmonary function test (PFT) as a primary outcome, in patients with anti-MDA5 DM-related ILD after using RTX.

Results

Of the 145 potentially eligible articles, 17 were selected. The information gathered from a total of 35 patients with anti-MDA5 DM-ILD was reviewed, including 13 men and 22 women. Patient age at onset was 47.60 ± 13.72 years old. A total of 11.43% (4/35) of the patients were found to have chronic ILD (C-ILD) and 88.57% (31/30) exhibited rapidly progressive ILD (RP-ILD). Most patients (29/30) had typical DM rashes. Prior to RTX administration, the majority of patients (27/35) were treated with medium- or high-dose glucocorticoids and at least one additional immunotherapeutic agent. With regard to RTX efficacy for ILD in anti-MDA5 DM, 71.43% (25/35) of the patients responded to treatment. Skin rash also improved in more than half of the patients after RTX treatment. The most common side effects were infections, reported by 37.14% (13/35) of the patients after using RTX.

Conclusion

As a CD20 targeting drug, RTX is a promising therapeutic tool for anti-MDA5 DM-ILD, although the risk of infections should be considered before treatment. Further prospective controlled studies are required to evaluate the optimal RTX treatment regimen.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289714, identifier CRD42021289714.
Effects of Selenium as a Dietary Source on Performance, Inflammation, Cell Damage, and Reproduction of Livestock Induced by Heat Stress: A Review
Authors: Zheng Yuhui , Xie Tian , Li Shengli , Wang Wei , Wang Yajing , Cao Zhijun , Yang Hongjian
Published: January 2022

Heat stress as a result of global warming has harmful consequences for livestock and is thus becoming an urgent issue for animal husbandry worldwide. Ruminants, growing pigs, and poultry are very susceptible to heat stress because of their fast growth, rapid metabolism, high production levels, and sensitivity to temperature. Heat stress compromises the efficiency of animal husbandry by affecting performance, gastrointestinal health, reproductive physiology, and causing cell damage. Selenium (Se) is an essential nutritional trace element for livestock production, which acts as a structural component in at least 25 selenoproteins (SELs); it is involved in thyroid hormone synthesis, and plays a key role in the antioxidant defense system. Dietary Se supplementation has been confirmed to support gastrointestinal health, production performance, and reproductive physiology under conditions of heat stress. The underlying mechanisms include the regulation of nutrient digestibility influenced by gastrointestinal microorganisms, antioxidant status, and immunocompetence. Moreover, heat stress damage to the gastrointestinal and mammary barrier is closely related to cell physiological functions, such as the fluidity and stability of cellular membranes, and the inhibition of receptors as well as transmembrane transport protein function. Se also plays an important role in inhibiting cell apoptosis and reducing cell inflammatory response induced by heat stress. This review highlights the progress of research regarding the dietary supplementation of Se in the mitigation of heat stress, addressing its mechanism and explaining the effect of Se on cell damage caused by heat stress, in order to provide a theoretical reference for the use of Se to mitigate heat stress in livestock.
Seasonality and Annual Utilization Patterns of Antibacterials at Muhimbili National Hospital, Dar es Salaam, Tanzania: A 2015 Monthly Survey
Authors: Sangeda Raphael Zozimus , Urassa Mariki I. , Buma Deus , Musiba George Nyamanda , Chiwanga Faraja S. , Chambuso Mhina , Horumpende Pius Gerald
Published: January 2022

Introduction

Antibacterial utilization studies can help identify areas of intervention of antimicrobial stewardship programs (ASP) to facilitate rational use and prevent the emergence of antimicrobial resistance (AMR). Assessment and comparison of antibacterial utilization depend on the Anatomical Therapeutic Chemical (ATC) classification system and Defined Daily Dose (DDD) recommended by the World Health Organization (WHO) collaborative center for international drug monitoring. This study aimed to determine the DDD of each prescribed antibacterial group and the proportions of wide-spectrum antibacterials used at Muhimbili National Hospital (MNH) in Tanzania to allow baseline data for hospital ASPs.

Methods

A retrospective analytical study using data collected from 1st January 2015 to 31st December 2015 was undertaken at MNH. Data on antibacterials prescribed and dispensed were obtained from the MNH database. The ATC/DDD system was used to classify and quantify the antibacterial utilization patterns.

Results

A total of 10,643.1 DDDs were used in thirteen ward units at the Kibasila, Mwaisela and Sewahaji blocks of the MNH. Eighteen different antibacterials were prescribed and dispensed to 1496 patients. Capsules were the most dispensed dosage form. The drug ciprofloxacin was the leading antibacterial prescribed, with a DDD of about 3780 (35.5%) per year. This was followed by metronidazole and amoxicillin. The proportion of wide-spectrum antibacterials was as high as 66%. Utilization peaks were noted in April, July and September. There was a significant monthly increase in antibacterials utilization between January and December 2015 (p-value = 0.002, R-square = 0.64). The trends forecasted increased through June 2016.

Conclusions

Utilization trends indicated a significant monthly increase in 2015 at MNH wards in Tanzania. The use of wide-spectrum antibacterials was widespread. This calls for continued antibacterial utilization surveillance and implementation of hospital-based ASP to mitigate the rapidly rising global threat of AMR.
Grant-Making Criteria for Developing Useful and Usable Marine Science: A Philanthropic Perspective
Authors: Landrum Jason P. , Hudson Charlotte G. , Close Sarah L. , Knight Emily , Paquin Rachel-Marie , Bell Victoria , Ripple Kayla
Published: January 2022

Decades of scholarship and practice highlight the need for scientific research that informs individuals on the front lines of decision-making. Funding organizations can play an important role in supporting useful and usable research by discussing the criteria and processes they use to guide the development and review of funded projects. However, practical examples of how funders can engage with grantees on the design of research efforts are not widely available. In this article, we respond to calls for more information in this area by presenting one example of evaluation criteria and guidance questions used by a philanthropic grant-making program that is focused on user-driven research. We describe this process through the lens of a funded research project that was designed to inform improvements in coastal habitat restoration. We hope that a closer look at an example of how to evaluate project ideas for their potential to provide critical information to decision-makers can be useful for other funders and researchers trying to produce useful and usable science.
Long-Term Outcomes and Prognostic Factors of Superficial Esophageal Cancer in Patients Aged ≥ 65 Years
Authors: Chang Jin Won , Jung Da Hyun , Huh Cheal Wung , Park Jun Chul , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan
Published: January 2022

Background

The number of elderly patients with superficial esophageal cancer (SEC) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing endoscopic submucosal dissection (ESD) or surgical resection for SEC.

Methods

Between January 2001 and May 2020, 290 patients aged ≥65 years who underwent ESD or surgical resection for SEC were evaluated. Their clinical outcomes and prognosis were assessed, and independent risk factors for OS were identified.

Results

The mean patient age (269 men and 21 women) was 70.9 years (range 65–90 years). En bloc, R0, and curative resections were achieved in 94.5%, 90.0%, and 73.4% of the patients, respectively. During the follow-up [mean: 54.6 months (range: 1–210 months)], 79 patients died. The 3-, 5-, and 10-year OS rates were 82.5, 73.1, and 59.7%, respectively. In multivariate analysis, cancer history of the other organs, American Society of Anesthesiologists performance status, and presence of lymphovascular involvement (hazard ratio = 1.852, 1.656, and 1.943, respectively; all P < 0.05) were independent risk factors for poor OS. The high-risk group (≥2 risk factors) showed a significantly lower OS than the low-risk group (≤ 1 risk factor) (P < 0.001).

Conclusions

The three risk factors could be useful in predicting the long-term prognosis of elderly patients with SEC.
Application of Machine Learning Algorithms to Predict Lymph Node Metastasis in Early Gastric Cancer
Authors: Tian HuaKai , Ning ZhiKun , Zong Zhen , Liu Jiang , Hu CeGui , Ying HouQun , Li Hui
Published: January 2022

Objective

This study aimed to establish the best early gastric cancer lymph node metastasis (LNM) prediction model through machine learning (ML) to better guide clinical diagnosis and treatment decisions.

Methods

We screened gastric cancer patients with T1a and T1b stages from 2010 to 2015 in the Surveillance, Epidemiology and End Results (SEER) database and collected the clinicopathological data of patients with early gastric cancer who were treated with surgery at the Second Affiliated Hospital of Nanchang University from January 2014 to December 2016. At the same time, we applied 7 ML algorithms—the generalized linear model (GLM), RPART, random forest (RF), gradient boosting machine (GBM), support vector machine (SVM), regularized dual averaging (RDA), and the neural network (NNET)—and combined them with patient pathological information to develop the best prediction model for early gastric cancer lymph node metastasis. Among the SEER set, 80% were randomly selected to train the models, while the remaining 20% were used for testing. The data from the Second Affiliated Hospital were considered as the external verification set. Finally, we used the AUROC, F1-score value, sensitivity, and specificity to evaluate the performance of the model.

Results

The tumour size, tumour grade, and depth of tumour invasion were independent risk factors for early gastric cancer LNM. Comprehensive comparison of the prediction model performance of the training set and test set showed that the RDA model had the best prediction performance (F1-score = 0.773; AUROC = 0.742). The AUROC of the external validation set was 0.73.

Conclusions

Tumour size, tumour grade, and depth of tumour invasion were independent risk factors for early gastric cancer LNM. ML predicted LNM risk more accurately, and the RDA model had the best predictive performance and could better guide clinical diagnosis and treatment decisions.
Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension
Authors: Basuli Debargha , Parekh Rohan Umesh , White Acacia , Thayyil Abdullah , Sriramula Srinivas
Published: January 2022

Despite many readily available therapies, hypertensive kidney disease remains the second most prevalent cause of end-stage renal disease after diabetes, and continues to burden patient populations and escalate morbidity and mortality rates. Kinin B1 receptor (B1R) activation has been shown to have a role in the development of hypertension, one of the major etiologies for chronic kidney disease. However, the role of B1R in hypertension induced renal injury and remodeling remains unexplored. Using a DOCA-salt-induced hypertensive mouse model, we investigated whether B1R deficiency reduces hypertensive renal injury and fibrosis. To further recognize the translational role of B1R, we examined the expression of B1R and its correlation with collagen deposition in renal biopsies from control and hypertensive kidney disease patients. Our data indicates that renal B1R expression was upregulated in the kidneys of DOCA-salt hypertensive mice. Genetic ablation of B1R protected the mice from DOCA-salt-induced renal injury and fibrosis by preventing inflammation and oxidative stress in the kidney. Cultured human proximal tubular epithelial cells expressed B1R and stimulation of B1R with an agonist resulted in increased oxidative stress. In human kidney biopsy samples, we found that the B1R immunoreactivity was not only significantly increased in hypertensive patients compared to normotensive patients, but also there is a positive correlation between B1R expression and renal fibrosis levels. Taken together, our results identify a critical role of B1R in the development of inflammation and fibrosis of the kidney in hypertension.
Protective Effects of Appropriate Amount of Nuts Intake on Childhood Blood Pressure Level: A Cross-Sectional Study
Authors: Feng Ye , Bi Yang , Tang Xian , Zhang Ping , Tong Jishuang , Peng Xin , Tian Jie , Liang Xiaohua
Published: January 2022

Objective

Increased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) in adults. Regular consumption of nuts may improve some BP in adults whereas evidence in children is relatively lacking. This study aimed to determine the efficacy of nuts intake on BP in children.

Methods

Stratified cluster sampling was performed to include a total of 15,268 primary school children aged 6–12 years in urban and rural areas in Southwest China. The daily nuts intake dosage was collected by questionnaires, and generalized linear model (GLM) and logistic regression were used to analyze the relationship between nuts intake and BP.

Results

For the total subjects, 11,130 (72.9%) participants consumed <35 g/day of nuts, 1,145 (7.5%) participants consumed 35 g/day ≤ nut <50 g/day of nuts, 2,053 (13.4%) participants consumed 50~100 g/day of nuts, and 940 (6.2%) participants consumed over 100 g/day of nut. For sex subgroup, 1,074 (13.53%) boys and 979 (13.35%) girls consumed 50~100 g/day of nuts. Compared with the 50~100 g/day of nuts intake group, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were significantly different in <35 g/day, 35g/day ≤ nut <50 g/day, and >100 g/day nuts intake groups (all p < 0.001). The logistic regression showed that compared with the 50~100 g/day group, the other three groups are more likely associated with childhood hypertension (all p < 0.001). Therefore, a U-shaped relationship between nuts intake and BP level was identified.

Conclusions

The finding suggests that intake of 50~100 g/day nuts is the recommended dose of nuts intake to control childhood hypertension, as well as for cardioprotection purposes.
Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study
Authors: Mauricio Didac , Vlacho Bogdan , Barrot de la Puente Joan , Mundet-Tudurí Xavier , Real Jordi , Kulisevsky Jaime , Ortega Emilio , Castelblanco Esmeralda , Julve Josep , Franch-Nadal Josep
Published: January 2022

The purpose of this study was to assess the risk of occurrence of Parkinson's disease (PD) among subjects with type 2 diabetes and diabetic retinopathy (DR) in our large primary health care database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated the number of events, time to event, cumulative incidence, and incidence rates of PD for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and PD. In total, 26,453 type 2 diabetic subjects with DR were identified in the database, and 216,250 subjects without DR at inclusion. During the follow-up period, 1,748 PD events occurred. PD incidence rate and cumulative incidence were higher among subjects with DR (16.95 per 10,000 person-years and 0.83%, respectively). In the unadjusted analysis, subjects with DR were at 1.25 times higher risk (hazard ratio: 1.22, 95% confidence interval: 1.06; 1.41) of developing PD during the study period. However, we did not find any statistically significant HR for DR in any models after adjusting for different risk factors (age, sex, duration of diabetes, smoking, body mass index, glycosylated hemoglobin, comorbidities). In conclusion, in our primary health care population database, DR was not associated with an increased risk of PD after adjusting for different risk factors. In our retrospective cohort study, age, male sex, and diabetes duration were independent risk factors for developing PD.
Relationship Between Peripheral Refraction in Different Retinal Regions and Myopia Development of Young Chinese People
Authors: Zheng Xiangyue , Cheng Dejin , Lu Xiaoli , Yu Xiaoyi , Huang Yuting , Xia Yujie , Lin Chuni , Wang Zhao
Published: January 2022

Objective

To observe the associations between regional peripheral refraction and myopia development in young Chinese people.

Methods

Two hundred and forty-one young adult subjects (21 emmetropes, 88 low myopes, 94 moderate myopes, and 38 high myopes) aged 18–28 years were included, and only the right eyes were tested. Eye biometrics were measured before pupil dilation using the Lenstar. Relative peripheral refractive errors (RPRE) were measured after pupil dilation using multispectral refractive topography (MRT), at nine retinal eccentricities: 0–5, 5–10, 10–15, 15–20, 20–25, 25–30, 30–35, 35–40, and 40–45 degrees.

Results

In this study, RPRE increased with eccentricity, and it shows a growing trend with the increase of the degree of myopia among emmetropia, low myopia and moderate myopia groups, and RPRE varied with myopia severity at eccentricities between 20 and 35 degrees only. In addition, axial length (AL) and RPRE were positively correlated between 20 and 45 degrees, and AL was an independent risk factor for RPRE between 20 and 35 degrees.

Conclusion

These findings indicate that the eccentricities between 20 and 35 degrees RPRE may be closely related to refractive development and eye growth in young Chinese people.
The Pass-on Effect of Tetracycline-Induced Honey Bee (Apis mellifera) Gut Community Dysbiosis
Authors: Jia Shuo , Wu Yuqi , Chen Gongwen , Wang Shuai , Hu Fuliang , Zheng Huoqing
Published: January 2022

Gut microbial community plays an important role in the regulation of insect health. Antibiotic treatment is powerful to fight bacterial infections, while it also causes collateral damage to gut microbiome, which may have long-lasting consequences for host health. However, current studies on honey bees mainly focus on the impact of direct exposure to antibiotics on individual bees, and little is known about the impact of social transmission of antibiotic-induced gut community disorder in honey bee colonies. In order to provide insight into the potential pass-on effect of antibiotic-induced dysbiosis, we colonized newly emerged germ-free workers with either normal or tetracycline-treated gut community and analyzed the gut bacteria composition. We also treated workers with low dosage of tetracycline to evaluate its impact on honey bee gut microbiota. Our results showed that the tetracycline-treated gut community caused disruption of gut community in their receivers, while the direct exposure to the low dosage of tetracycline had no significant effect. In addition, no significant difference was observed on the mortality rate of A. mellifera workers with different treatments. These results suggest that though the residue of antibiotic treatment may not have direct effect on honey bee gut community, the gut microbiota dysbiosis caused by high dosage of antibiotic treatment has a cascade effect on the gut community of the nestmates in honeybee colonies.
SARS-CoV-2 Vaccination and Protection Against Clinical Disease: A Retrospective Study, Bouches-du-Rhône District, Southern France, 2021
Authors: Fournier Pierre-Edouard , Houhamdi Linda , Colson Philippe , Cortaredona Sébastien , Delorme Lea , Cassagne Carole , Lagier Jean-Christophe , Chaudet Hervé , Tissot-Dupont Hervé , Giraud-Gatineau Audrey , Fenollar Florence , Million Matthieu , Raoult Didier
Published: January 2022

From January 18th to August 13th, 2021, 13,804 unvaccinated and 1,156 patients who had received at least one COVID-19 vaccine dose were tested qPCR-positive for SARS-CoV-2 in our center. Among vaccinated patients, 949, 205 and 2 had received a single, two or three vaccine doses, respectively. Most patients (80.3%) had received the Pfizer-BioNTech vaccine. The SARS-CoV-2 variants infecting vaccinated patients varied over time, reflecting those circulating in the Marseille area, with a predominance of the Marseille-4/20A.EU2 variant from weeks 3 to 6, of the Alpha/20I variant from weeks 7 to 25, and of the Delta/21A variant from week 26. SARS-CoV-2 infection was significantly more likely to occur in the first 13 days post-vaccine injection in those who received a single dose (48.9%) than two doses (27.4%, p< 10–3). Among 161 patients considered as fully vaccinated, i.e., >14 days after the completion of the vaccinal scheme (one dose for Johnson and Johnson and two doses for Pfizer/BioNTech, Moderna and Sputnik vaccines), 10 (6.2%) required hospitalization and four (2.5%) died. Risks of complications increased with age in a nonlinear pattern, with a first breakpoint at 54, 33, and 53 years for death, transfer to ICU, and hospitalization, respectively. Among patients infected by the Delta/21A or Alpha/20I variants, partial or complete vaccination exhibited a protective effect with a risk divided by 3.1 for mortality in patients ≥ 55 years, by 2.8 for ICU transfer in patients ≥ 34 years, and by 1.8 for hospitalization in patients ≥ 54 years. Compared to partial vaccination, complete vaccination provided an even stronger protective effect, confirming effectiveness to prevent severe forms of COVID-19.
Development and Electromyographic Validation of a Compliant Human-Robot Interaction Controller for Cooperative and Personalized Neurorehabilitation
Authors: Dalla Gasperina Stefano , Longatelli Valeria , Braghin Francesco , Pedrocchi Alessandra , Gandolla Marta
Published: January 2022

Background

Appropriate training modalities for post-stroke upper-limb rehabilitation are key features for effective recovery after the acute event. This study presents a cooperative control framework that promotes compliant motion and implements a variety of high-level rehabilitation modalities with a unified low-level explicit impedance control law. The core idea is that we can change the haptic behavior perceived by a human when interacting with the rehabilitation robot by tuning three impedance control parameters.

Methods

The presented control law is based on an impedance controller with direct torque measurement, provided with positive-feedback compensation terms for disturbances rejection and gravity compensation. We developed an elbow flexion-extension experimental setup as a platform to validate the performance of the proposed controller to promote the desired high-level behavior. The controller was first characterized through experimental trials regarding joint transparency, torque, and impedance tracking accuracy. Then, to validate if the controller could effectively render different physical human-robot interaction according to the selected rehabilitation modalities, we conducted tests on 14 healthy volunteers and measured their muscular voluntary effort through surface electromyography (sEMG). The experiments consisted of one degree-of-freedom elbow flexion/extension movements, executed under six high-level modalities, characterized by different levels of (i) corrective assistance, (ii) weight counterbalance assistance, and (iii) resistance.

Results

The unified controller demonstrated suitability to promote good transparency and render both compliant and stiff behavior at the joint. We demonstrated through electromyographic monitoring that a proper combination of stiffness, damping, and weight assistance could induce different user participation levels, render different physical human-robot interaction, and potentially promote different rehabilitation training modalities.

Conclusion

We proved that the proposed control framework could render a wide variety of physical human-robot interaction, helping the user to accomplish the task while exploiting physiological muscular activation patterns. The reported results confirmed that the control scheme could induce different levels of the subject's participation, potentially applicable to the clinical practice to adapt the rehabilitation treatment to the subject's progress. Further investigation is needed to validate the presented approach to neurological patients.
Synergies of Multiple Zeitgebers Tune Entrainment
Authors: Grabe Saskia , Mahammadov Elmir , Olmo Marta Del , Herzel Hanspeter
Published: January 2022

Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth’s solar day via different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops. However, circadian rhythms are exposed to multiple coexisting zeitgebers in nature. Therefore, we study synergistic effects of two coexisting zeitgebers on different components of the circadian clock. We investigate the induction of period genes by light together with modulations of nuclear receptor activities by drugs and metabolism. Our results show that the entrainment of a circadian rhythm to two coexisting zeitgebers depends strongly on the phase difference between the two zeitgebers. Synergistic interactions of zeitgebers can strengthen diurnal rhythms to reduce detrimental effects of shift-work and jet lag. Medical treatment strategies which aim for stable circadian rhythms should consider interactions of multiple zeitgebers.
Olfactory Dysfunction in Patients With Coronavirus Disease 2019: A Review
Authors: Wei Guoli , Gu Jialin , Gu Zhancheng , Du Cheng , Huang Xiaofei , Xing Haiyan , Li Lingchang , Zhang Aiping , Hu Xingxing , Huo Jiege
Published: January 2022

The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on public-health and economic systems worldwide. Among the several neurological symptoms of patients with COVID-19 reported in clinical practice, olfactory dysfunction (OD) is the most common. OD occurs as the earliest or the only clinical manifestation in some patients. Increasing research attention has focused on OD, which is listed as one of the main diagnostic symptoms of severe acute respiratory syndrome-coronavirus-2 infection. Multiple clinical and basic-science studies on COVID-19-induced OD are underway to clarify the underlying mechanism of action. In this review, we summarize the clinical characteristics, mechanisms, evaluation methods, prognosis, and treatment options of COVID-19-induced OD. In this way, we hope to improve the understanding of COVID-19-induced OD to aid early identification and precise intervention.
High Level of the Fibrin Degradation Products at Admission Predicts Parenchymal Hematoma and Unfavorable Outcome of Ischemic Stroke After Intravenous Thrombolysis
Authors: Liu Chang , Zhang Yun , Niu Lingchuan , Li Jiani
Published: January 2022

Background and Purpose

We aim to investigate whether the higher admission fibrin degradation products (FDPs) levels are associated with parenchymal hematomas (PHs) and unfavorable outcome after intravenous thrombolysis (IVT).

Methods

Consecutive patients with acute ischemic stroke treated with IVT were studied. The FDP level was obtained on admission. PH was evaluated 24 h after treatment. The unfavorable outcome was defined as a 90-day modified Rankin Scale >2. The multivariable linear stepwise regression was used to assess independent factors associated with the log-transformed FDP (lgFDP). The receiver operating characteristics (ROCs) curve analysis was used to determine the predictive value of the FDP level for PH and unfavorable outcome. The logistic regression was used to identify independent predictors for PH and unfavorable outcome. The mediation analyses were performed to investigate associations among the FDP level, PH, and outcome.

Results

A total of 181 patients were included in the final analyses [median age, 73 (63–79) years; 102 (56.4%) males; and the median baseline National Institutes of Health Stroke Scale (NIHSS) score, 8 (5–15)]. The lgFDP was independently associated with age (B = 0.011, 95% CI 0.006–0.015, p < 0.001) and the baseline NIHSS score (B = 0.016, 95% CI 0.008–0.025, p < 0.001). The FDP was positively associated with PH [odds ratio (OR) 1.034, 95% CI 1.000–1.069; p = 0.047]. According to the ROC analysis, the best discriminating factor for unfavorable outcome was the FDP ≥3.085 μg/ml. The FDP ≥3.085 μg/ml was an independent predictor of unfavorable outcome (OR 7.086, 95% CI 2.818–17.822; p < 0.001). Mediation analysis revealed that the association of the FDP ≥3.085 μg/ml with unfavorable outcome was not mediated by PH (p = 0.161).

Conclusion

The admission FDP levels can predict PH and unfavorable outcome in patients with acute ischemic stroke after IVT. PH does not mediate the effect of the FDP level on the outcome.
Case Report: Catatonic Stupor in Behavioral Variant Frontotemporal Dementia
Authors: de França Gustavo Campos , Barreto Henrique Carneiro de Barros , Paranhos Thiago , Nunes Julio Cesar , de Oliveira-Souza Ricardo
Published: January 2022

Catatonia is a psychomotor syndrome common to several medical and neuropsychiatric disorders. Here, we report on the case of a 95-year-old woman who underwent a radical change in personality characterized by sexual disinhibition, and physical and verbal aggressiveness. Over several months, she developed verbal stereotypies, gait deterioration, and double incontinence. She eventually developed mutism and an active opposition to all attempts to be fed or cared for. Benzodiazepines, olanzapine and electroconvulsive therapy were of no benefit. Magnetic resonance imaging revealed asymmetric (more severe on the right) frontotemporal, parietal, and upper brainstem atrophy. She died from sepsis without recovering from stupor seven years after the onset of symptoms. We believe that the initial behavioral disinhibition was related to the frontotemporal injury, whereas catatonic stupor reflected the progression of the degenerative process to the parietal cortices. Our case adds to the small number of cases of catatonia as a symptom of degenerative dementia. It also supports the idea that damage to the parietal cortex gives rise to pathological avoidance of which catatonic stupor represents an extreme form.
Towards a Comprehensive Optical Connectome at Single Synapse Resolution via Expansion Microscopy
Authors: Sneve Madison A. , Piatkevich Kiryl D.
Published: January 2022

Mapping and determining the molecular identity of individual synapses is a crucial step towards the comprehensive reconstruction of neuronal circuits. Throughout the history of neuroscience, microscopy has been a key technology for mapping brain circuits. However, subdiffraction size and high density of synapses in brain tissue make this process extremely challenging. Electron microscopy (EM), with its nanoscale resolution, offers one approach to this challenge yet comes with many practical limitations, and to date has only been used in very small samples such as C. elegans, tadpole larvae, fruit fly brain, or very small pieces of mammalian brain tissue. Moreover, EM datasets require tedious data tracing. Light microscopy in combination with tissue expansion via physical magnification—known as expansion microscopy (ExM)—offers an alternative approach to this problem. ExM enables nanoscale imaging of large biological samples, which in combination with multicolor neuronal and synaptic labeling offers the unprecedented capability to trace and map entire neuronal circuits in fully automated mode. Recent advances in new methods for synaptic staining as well as new types of optical molecular probes with superior stability, specificity, and brightness provide new modalities for studying brain circuits. Here we review advanced methods and molecular probes for fluorescence staining of the synapses in the brain that are compatible with currently available expansion microscopy techniques. In particular, we will describe genetically encoded probes for synaptic labeling in mice, zebrafish, Drosophila fruit flies, and C. elegans, which enable the visualization of post-synaptic scaffolds and receptors, presynaptic terminals and vesicles, and even a snapshot of the synaptic activity itself. We will address current methods for applying these probes in ExM experiments, as well as appropriate vectors for the delivery of these molecular constructs. In addition, we offer experimental considerations and limitations for using each of these tools as well as our perspective on emerging tools.
Preceding Postural Control in Forelimb Reaching Movements in Cats
Authors: Takahashi Mirai , Nakajima Toshi , Takakusaki Kaoru
Published: January 2022

Postural control precedes the goal-directed movement to maintain body equilibrium during the action. Because the environment continuously changes due to one’s activity, postural control requires a higher-order brain function that predicts the interaction between the body and the environment. Here, we tried to elucidate to what extent such a preceding postural control (PPC) predictively offered a posture that ensured the entire process of the goal-directed movement before starting the action. For this purpose, we employed three cats, which we trained to maintain a four-leg standing posture on force transducers to reach the target by either forelimb. Each cat performed the task under nine target locations in front with different directions and distances. As an index of posture, we employed the center of pressure (CVP) and examined CVP positions when the cat started postural alteration, began to lift its paw, and reached the target. After gazing at the target, each cat started PPC where postural alteration was accompanied by a 20–35 mm CVP shift to the opposite side of the forelimb to be lifted. Then, the cat lifted its paw at the predicted CVP position and reached the forelimb to the target with a CVP shift of only several mm. Moreover, each cat had an optimal target location where the relationship between the cat and target minimized the difference in the CVP positions between the predicted and the final. In this condition, more than 80% of the predicted CVP positions matched the final CVP positions, and the time requiring the reaching movement was the shortest. By contrast, the forelimb reaching movement required a greater CVP shift and longer time when the target was far from the cat. In addition, the time during forelimb reaching showed a negative correlation with the speed of the CVP shift during the PPC. These results suggest that the visuospatial information, such as the body-environment interaction, contributes to the motor programming of the PPC. We conclude that the PPC ensures postural stability throughout the action to optimize the subsequent goal-directed movements. Impairments in these processes may disturb postural stability during movements, resulting in falling.
Designing a Clinical Study With Dietary Supplements: It's All in the Details
Authors: Floyd Z. Elizabeth , Ribnicky David M. , Raskin Ilya , Hsia Daniel S. , Rood Jennifer C. , Gurley Bill J.
Published: January 2022

A successful randomized clinical trial of the effect of dietary supplements on a chosen endpoint begins with developing supporting data in preclinical studies while paying attention to easily overlooked details when planning the related clinical trial. In this perspective, we draw on our experience studying the effect of an ethanolic extract from Artemisia dracunculus L. (termed PMI-5011) on glucose homeostasis as a potential therapeutic option in providing resilience to metabolic syndrome (MetS). Decisions on experimental design related to issues ranging from choice of mouse model to dosing levels and route of administration in the preclinical studies will be discussed in terms of translation to the eventual human studies. The more complex considerations in planning the clinical studies present different challenges as these studies progress from testing the safety of the dietary supplement to assessing the effect of the dietary supplement on a predetermined clinical outcome. From the vantage point of hindsight, we will outline potential pitfalls when translating preclinical studies to clinical studies and point out details to address when designing clinical studies of dietary supplements.
Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review
Authors: Cai Xianlei , Li Xueying , Jin Yangli , Zhang Miaozun , Xu Yuan , Liang Chao , Weng Yihui , Yu Weiming , Li Xiuyang
Published: January 2022

Background

Over recent decades, epidemiological studies have shown relationships between vitamins and Helicobacter pylori (H. pylori) infection and eradication, but the results are controversial.

Methods

A comprehensive meta-analysis and systematic review were conducted to clarify the relationships between common types of vitamins and H. pylori. We applied meta-regression, subgroup analysis and sensitivity analysis to obtain available evidence. Articles published from January 1991 to June 2021 in PubMed, EMBASE, and the Cochrane Library were searched.

Results

In total, we identified 48 studies. The results indicate that H. pylori -positive patients had lower serum vitamin B12 [standardized mean difference (SMD) = −0.30; 95% confidence interval (CI): −0.53 – −0.08], folate (SMD = −0.69; 95% CI: −1.34 – −0.04), vitamin C (SMD = −0.37; 95%CI: −0.57 – −0.18) and vitamin D (SMD = −0.34; 95% CI: −0.49 – −0.18) levels than H. pylori-negative patients. Patients in which H. pylori had been successfully eradicated had higher serum vitamin D levels (SMD = 1.37; 95% CI: 0.37–2.38) than in patients in which eradication had been unsuccessful. The serum vitamin B12 levels of H. pylori-positive patients improved after successful H. pylori eradication therapy (SMD = 1.85; 95% CI: 0.81–2.90), and antioxidant vitamin supplementation to an H. pylori eradication regimen improved the eradication rate (risk ratio = 1.22; 95% CI: 1.02–1.44 for per-protocol analysis; risk ratio = 1.25; 95% CI: 1.06–1.47 for intention-to-treat analysis).

Conclusions

H. pylori infections decrease the serum levels of several types of vitamins, eradication of H. pylori could rescue its adverse effects, and antioxidant vitamin supplementation may improve the H. pylori eradication rate.

Systematic Review Registration

identifier: CRD42021268127.
Dietary Hermetia illucens Larvae Meal Improves Growth Performance and Intestinal Barrier Function of Weaned Pigs Under the Environment of Enterotoxigenic Escherichia coli K88
Authors: Tang Qingsong , Xu E. , Wang Zhikang , Xiao Mingfei , Cao Shuting , Hu Shenglan , Wu Qiwen , Xiong Yunxia , Jiang Zongyong , Wang Fengying , Yang Geling , Wang Li , Yi Hongbo
Published: January 2022

The aim of this study was to evaluate the effect of Hermetia illucens larvae meal (HI) on the growth performance and intestinal barrier function of weaned pigs. To achieve this, 72 weaned pigs [28-day-old, 8.44 ± 0.04 kg body weight (BW)] were randomly assigned to three dietary treatments: basal diet (negative control, NC), zinc oxide-supplemented diet (positive control, PC), and HI-supplemented diet [100% replacement of fishmeal (FM), HI], for 28 days in the presence of enterotoxigenic Escherichia coli (ETEC). The results showed that HI and PC increased (p < 0.05) the average daily gain (ADG) and average daily feed intake (ADFI) of weaned pigs from day 1 to 14, and decreased diarrhea incidence from day 1 to 28. Additionally, HI increased (p < 0.05) claudin-1, occludin, mucin-1 (MUC-1), and MUC-2 expression, goblet cell number, and secretory immunoglobulin A (sIgA) concentration in the intestine of weaned pigs. Compared with NC, HI downregulated (p < 0.05) interleukin-1β (IL-1β) and IL-8 expression, and upregulated IL-10, transforming growth factor-β (TGF-β), antimicrobial peptide [porcine β defensin 1 (pBD1), pBD2, protegrin 1-5 (PG1-5)] expression in the jejunum or ileum. Moreover, HI decreased (p < 0.05) toll-like receptor 2 (TLR2), phosphorylated nuclear factor-κB (p-NF-κB), and phosphorylated mitogen-activated protein kinase (p-MAPK) expression, and increased sirtuin 1 (SIRT1) expression in the ileum. Additionally, HI increased histone deacetylase 3 (HDAC3) expression and acetylation of histone 3 lysine 27 (acH3k27) in the ileum. Furthermore, HI positively influenced the intestinal microbiota composition and diversity of weaned pigs and increased (p < 0.05) butyrate and valerate concentrations. Overall, dietary HI improved growth performance and intestinal barrier function, as well as regulated histone acetylation and TLR2-NF-κB/MAPK signaling pathways in weaned pigs.
Comparable Outcomes and Health-Related Quality of Life for Severe Aplastic Anemia: Haploidentical Combined With a Single Cord Blood Unit vs Matched Related Transplants
Authors: Lei Meiqing , Li Xiaoli , Zhang Yanming , Qu Qi , Jiao Wenjing , Zhou Huifen , Wang Qingyuan , Qiu Huiying , Tang Xiaowen , Han Yue , Fu Chengcheng , Jin Zhengming , Chen Suning , Sun Aining , Miao Miao , Liu Limin , Wu Depei
Published: January 2022

We retrospectively compared the outcomes and health-related quality of life (HRQoL) of severe aplastic anemia (SAA) patients who received haploidentical hematopoietic stem cell transplantation with a single unrelated cord blood unit (Haplo-cord HSCT) (n = 180) or matched related donor (MRD)-HSCT (n = 128). After propensity score matching, we were able to match 88 patients in each group and to compare the outcomes between the two matched-pair groups. Haplo-cord recipients exhibited a longer median days for neutrophil engraftment (12 vs 11, P = 0.001) and for platelet engraftment (15 vs 13, P = 0.003). Haplo-cord recipients a high cumulative incidence of grades II–IV acute graft-versus-host disease (GVHD) (29.8 vs 14.0%, P = 0.006), while similar III–IV acute GVHD, total chronic GVHD, and moderate to severe chronic GVHD at four-year (all P < 0.05). Among the Haplo-cord HSCT and MRD-HSCT groups, the four-year GVHD-free/failure-free survival rates were 73.5% and 66.9% (P = 0.388) respectively, and the overall survival rates were 81.5% and 77.2% (P = 0.484), respectively. Similar comparable results also were observed between the corresponding first-line, older or younger than 40 years old subgroups. The Haplo-cord HSCT group exhibited higher scores in the physical component summary, physical functioning, general health and social functioning than the MRD-HSCT group (all P < 0.05). In the multivariate analysis, young age and Haplo-cord HSCT were favorable factors for HRQoL, while moderate to severe cGVHD was associated with lower HRQoL. These results suggest that for SAA patients, Haplo-cord HSCT could achieve at least comparable efficacy and HRQoL to MRD-HSCT.