bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Salt-Bridge Electroflocculation Technology for Harvesting Microalgae
Authors: Hou Yuyong , Liu Chenfeng , Liu Zhiyong , Han Tong , Hao Nahui , Guo Zhile , Wang Weijie , Chen Shulin , Zhao Lei , Safavi Maliheh , Ji Xiang , Chen Fangjian
Published: June 2022

Microalgae biomass, as a promising alternative feedstock, can be refined into biodiesel, pharmaceutical, and food productions. However, the harvesting process for quality biomass still remains a main bottleneck due to its high energy demand. In this study, a novel technique integrating alkali-induced flocculation and electrolysis, named salt-bridge electroflocculation (SBEF) with non-sacrificial carbon electrodes is developed to promote recovery efficiency and cost savings. The results show that the energy consumption decreased to 1.50 Wh/g biomass with a high harvesting efficiency of 90.4% under 300 mA in 45 min. The mean particle size of algae flocs increased 3.85-fold from 2.75 to 10.59 µm, which was convenient to the follow-up processing. Another major advantage of this method is that the salt-bridge firmly prevented cells being destroyed by the anode’s oxidation and did not bring any external contaminants to algal biomass and flocculated medium, which conquered the technical defects in electro-flocculation. The proposed SBEF technology could be used as a low cost process for efficient microalgae harvest with high quality biomass.
Techno-Economic Analysis as a Driver for Optimisation of Cellobiose Lipid Fermentation and Purification
Authors: Oraby Amira , Rupp Steffen , Zibek Susanne
Published: June 2022

Cellobiose lipids (CL) are glycolipids synthesized by Ustilaginaceae species with potential application as detergents or in cosmetics. This study identified process optimisation potential for CL fermentation based on process modelling and techno-economic analysis. Using a stoichiometric equation based on laboratory data, we calculated the maximum possible CL yield YP/S of 0.45 gCL·gglucose−1 at the biomass yield of 0.10 gBiomass·gglucose−1 with an Ustilago maydis strain. Due to substrate inhibition that may occur at high glucose concentrations, a fed-batch process to increase biomass and CL concentrations was considered in our model. Simulation of different process scenarios showed that the choice of aeration units with high oxygen transfer rates and adaptation of power input to oxygen uptake can significantly decrease electricity consumption. We further assessed scenarios with different fermentation media and CL purification methods, suggesting additional process optimisation potential. Here the omission of vitamins from the fermentation medium proved to be a possible mean to enhance process economy, without compromising CL productivity.
Assessing Wave Attenuation With Rising Sea Levels for Sustainable Oyster Reef-Based Living Shorelines
Authors: Salatin Reza , Wang Hongqing , Chen Qin , Zhu Ling
Published: June 2022

In densely populated coastal areas with sea-level rise (SLR), protecting the shorelines against erosion due to the wave impact is crucial. Along with many engineered structures like seawalls and breakwaters, there are also green structures like constructed oyster reefs (CORs) that can not only attenuate the incident waves but also grow and maintain pace with SLR. However, there is a lack of data and understanding of the long-term wave attenuation capacity of the living shoreline structures under SLR. In this study, we used the phase-resolving Boussinesq model, FUNWAVE-TVD, to examine the hydrodynamics including wave height and wave-induced currents around the CORs in the Gandys Beach living shoreline project area in the upper Delaware Bay, United States. Waves were measured at six locations (offshore to onshore, with and without CORs) in the Gandys Beach living shoreline project area for two winter months, during which four nor’easters occurred. We selected three cases that represent prevailing wind, wave, and tide conditions to examine the fine spatial and temporal changes in wave height and current velocity by the construction of the reefs. Wave heights and wave energy spectra generated from FUNWAVE-TVD were then validated with field observations. It is found that FUNWAVE-TVD is capable of simulating waves and associated hydrodynamic processes that interact with CORs. The model results show that wave attenuation rates vary with the incident wave properties and water depth, and wave-induced circulation patterns are affected by the CORs. The wave attenuation capacity of CORs over the next 100 years was simulated with the incorporation of the oyster reef optimal growth zone. Our study found that sustainable wave attenuation capacity can only be achieved when suitable habitat for COR is provided, thus it can vertically grow with SLR. Suitable habitat includes optimal intertidal inundation duration, current velocity for larval transport and settlement, on-reef oyster survival and growth, and other environmental conditions including salinity, temperature, and nutrient availability. Furthermore, the model results suggest that it would take CORs approximately 9 years after construction to reach and maintain the maximum wave attenuation capacity in sustainable living shorelines.
First Study of Bacteremia Caused by Herbaspirillum huttiense in China: A Brief Research Report and Literature Review
Authors: Li Xiangyun , Bao Xundi , Qiao Guanhua , Wang Lianzi , Shi Cuixiao , Chen Shuyi , Xu Yuanhong , Zheng Meijuan , Wang Zhongxin
Published: June 2022

Bacteremia caused by Herbaspirillum huttiense (H. huttiense) is relatively rare in positive blood cultures. H. huttiense is an opportunistic bacterium in patients with cancer and cirrhosis and has also been described in immunocompromised hosts. In this study, H. huttiense was isolated from a patient with repeated chest tightness and chest pain. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing and Next-Generation Sequencing (NGS). Antibiotic sensitivity was assessed by agar dilution. Almost all publications on H. huttiense infections in the PubMed/ScienceDirect/EBSCO databases were reviewed and summarized. Blood sample culturing yielded white, gelatinous, and slightly raised colonies without hemolytic rings. The bacilli were found to be Gram-negative, and MS results showed 99.2% homology with H. huttiense. This was confirmed by 16S rRNA gene sequencing, phylogenetic tree analysis and NGS all of which were homologous with H. huttiense in GenBank. Antibiotic susceptibility tests were performed to determine the minimum inhibitory concentrations (MICs) of imipenem, meropenem, piperacillin-tazobactam, and levofloxacin. A comprehensive literature review revealed that H. huttiense was an emergent pathogen. After medical treatment, the patient’s body temperature returned to normal. This is the first report of bacteremia caused by H. huttiense in China. The findings could improve the awareness and attention of the rare pathogenic microorganisms in China.
Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease
Authors: Chancharoenthana Wiwat , Kamolratanakul Supitcha , Ariyanon Wassawon , Thanachartwet Vipa , Phumratanaprapin Weerapong , Wilairatana Polrat , Leelahavanichkul Asada
Published: June 2022

Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.
Comprehensive Analysis of Gut Microbiota and Fecal Bile Acid Profiles in Children With Biliary Atresia
Authors: Yang Ting , Yang Shen , Zhao Jiawei , Wang Peize , Li Siqi , Jin Yuyan , Liu Zhaozhou , Zhang Xinyue , Zhang Yanan , Zhao Yong , Liao Junmin , Li Shuangshuang , Hua Kaiyun , Gu Yichao , Wang Dingding , Huang Jinshi
Published: June 2022

Background

Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Herein, we aimed at characterizing the gut microbiota and fecal bile acid profiles of BA patients, defining the correlations between them, and evaluating the relationship between the clinical pathogenesis and changes in the gut microbiota and bile acid profiles.

Methods

A total of 84 fecal samples from BA patients (n = 46) and matched healthy controls (HCs, n = 38) were subjected to sequencing by 16S rRNA gene amplification, and fecal bile acid were analyzed by targeted metabolomics.

Findings

Compared with the controls, a structural separation of the intestinal flora of BA patients was uncovered, which was accompanied by changes in the composition of fecal bile acids. In the BA group, Actinobacillus, Monoglobus, and Agathobacter were enriched in patients without cholangitis (p < 0.05). Selenomonadaceae and Megamonas were more abundant in patients without recurrent cholangitis episodes (p < 0.05), while Lachnospiraceae and Ruminococcaceae were enriched in patients with multiple recurrences of cholangitis (p < 0.05). Postoperative jaundice clearance was associated with Campylobacter and Rikenellaceae (p < 0.05), and tauroursodeoxycholic acid was associated with jaundice clearance (p < 0.001).

Conclusion

BA patients are characterized by different compositions of gut microbiota and bile acids, and their interaction is involved in the process of liver damage in BA, which may be closely related to the occurrence of postoperative cholangitis and jaundice clearance.
Multimodal Prominence Marking in Semi-Spontaneous YouTube Monologs: The Interaction of Intonation and Eyebrow Movements
Authors: Berger Stephanie , Zellers Margaret
Published: June 2022

Both facial expressions like eyebrow movements and prosodic characteristics like pitch height and the position of the pitch accent relative to the prominent syllable play an important role in prominence marking, which in turn is used by YouTubers and other public speakers alike to engage their audience. We analyze the co-occurrence of eyebrow movements and pitch accents of differing prominence levels produced by a sample of English-speaking YouTubers, and the height and position of those pitch accents. We annotated pitch accents, and analyzed videos using OpenFace 2.0, using three different eyebrow movement measures: eyebrow landmarks, distance between eyebrow and eye landmarks, and Action Units (facial expressions). We found that pitch height and eyebrow movements are positively correlated for at least some of the measures for all speakers. We also found that it is more likely for a medial or late pitch accent to arise at the time of an Action Unit connected to the eyebrows than an early accent, while there was no effect of the prominence level. However, we did not find evidence for a close temporal coordination of pitch movement and eyebrow movement. Finally, we found speaker-individual differences in the use of eyebrow movements and pitch accents, but also some slight indications of an effect for geographical origin of the speaker.
Devising Trainings to Enhance the Capabilities of Children With Autism Spectrum Disorder to Cope With Metaphor: A Review of the Literature
Authors: Melogno Sergio , Pinto Maria Antonietta
Published: June 2022

This article reviews the literature reporting on the trainings implemented with children with Autism Spectrum Disorder (ASD) without intellectual disability to enhance their capability to cope with metaphor comprehension. The studies in this review can be classified into two main strands of thought, behavioral-analytic and psycholinguistic, respectively. Beyond some basic similarities all these studies share in their attempt at training children to consider the semantic features of metaphors, the mental pathways activated by those trainings are based on different cognitive and linguistic processes. The trainings based on the behavioral-analytic perspective teach the meaning of metaphors by making an extensive use of prompts: iconic, echoic, and textual. In the trainings based on the psycholinguistic perspective, instead, a wide range of activities are devised to stimulate children's analytical abilities to cope with semantic relations in metaphors. A significant part of these activities are jointly conducted between adult and children, and aimed at promoting the child's autonomy. Among the most interesting theoretical challenges stemming from the abovementioned studies, this review considers the spontaneous creation of original metaphors in children with ASD when solicited to understand metaphorical expressions. This unexpected reaction highlights the complexity of the relationships between metaphor comprehension and production in children with ASD.
The Association Between Remnant Cholesterol and the Estimated 10-Year Risk of a First Hard Cardiovascular Event
Authors: Yang Zhen , Yang Kuo , Shi Junhe , Yang Qiaoning , Zhang Ying , Gao Jie , Shi Dazhuo , Qu Hua
Published: June 2022

Background

Remnant cholesterol (Remnant-C), rather than TG, is believed to increase the risk of atherosclerotic cardiovascular disease. We evaluated whether Remnant-C is associated with an estimated 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Methods

This cross-sectional study was performed on 2,048 participants (1,130 men and 918 women), aged 40 to 79 years, from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The independent variable was Remnant-C; the dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular disease event (defined as non-fatal myocardial infarction, coronary heart disease death, or stroke, over a 10-year period among people free from atherosclerotic cardiovascular disease at the beginning of the period). The other variables, such as smoking behavior, hypertension, diabetes etc., were considered as the potential effect modifiers. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event. Subgroup analyses stratified by gender and race were also performed.

Results

A positive association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event was demonstrated in the fully adjusted model (β = 0.078, [95%CI: 0.061–0.094], P < 0.001). The 10-year risk was increased by 0.078% for each 1 mg/dl increase in Remnant-C. In the subgroup analysis for gender, this association remained in both men (β = 0.128, [95%CI: 0.108–0.148], P < 0.001) and women (β = 0.043, [95%CI: 0.016–0.070], P = 0.00179). However, in the subgroup analysis for race, the association between Remnant-C and the 10-year risk reached an inflection point at remnant-C 38 mg/dL, where a positive association was not as obvious for the non-Hispanic Black population as for other racial groups.

Conclusions

Remnant-C positively correlates with a 10-year risk of a first hard atherosclerotic cardiovascular disease event.
Arterial Stiffness, Subendocardial Impairment, and 30-Day Readmission in Heart Failure Older Patients
Authors: Fantin Francesco , Giani Anna , Franconi Arianna , Zoico Elena , Urbani Silvia , Rossi Andrea P. , Mazzali Gloria , Zamboni Mauro
Published: June 2022

Arterial stiffness and subendocardial perfusion impairment may play a significant role in heart failure (HF) outcomes. The aim of the study was to examine the main predictors of 30-day readmission in geriatric patients, hospitalized with HF, explore hemodynamical parameters, arterial stiffness indexes, and subendocardial viability ratio (SEVR). In total, 41 hospitalized patients, affected by HF, were included; they underwent clinical evaluation, routine laboratory testing, and echocardiography. At the time of admission, after the achievement of clinical stability (defined as switching from intravenous to oral diuretic therapy), and at discharge, arterial tonometry was performed to evaluate carotid-femoral pulse wave velocity (PWVcf) and SEVR (then corrected for hemoglobin concentration and oxygen saturation). Through the evaluations, a significant progressive decrease in PWVcf was described (17.79 ± 4.49, 13.54 ± 4.54, and 9.94 ± 3.73 m/s), even after adjustment for age, gender, mean arterial pressure (MAP) variation, and left ventricular ejection fraction (LVEF). A significant improvement was registered for both SEVR (83.48 ± 24.43, 97.94 ± 26.84, and 113.29 ± 38.02) and corrected SEVR (12.74 ± 4.69, 15.71 ± 5.30, and 18.55 ± 6.66) values, and it was still significant when adjusted for age, gender, MAP variation, and LVEF. After discharge, 26.8% of patients were readmitted within 30 days. In a multivariate binary logistic regression analysis, PWVcf at discharge was the only predictor of 30-day readmission (odds ratio [OR] 1.957, 95% CI 1.112–3.443). In conclusion, medical therapy seems to improve arterial stiffness and subendocardial perfusion in geriatric patients hospitalized with heart failure. Furthermore, PWVcf is a valid predictor of 30-day readmission. Its feasibility in clinical practice may provide an instrument to detect patients with HF at high risk of rehospitalization.
It Is Necessary to Re-understand the Low-Voltage Area in Atrial Fibrillation Patients
Authors: Liu Wei , Li Shijie , Han Bing
Published: June 2022

The presence of a low-voltage areas (LVAs) is a major feature of the progression of atrial fibrillation. Typically, the LVA is determined by invasive left atrial voltage mapping. In addition to pulmonary vein electrical isolation, Voltage-guided substrate modification by targeting LVAs in addition to PVI has been shown to be superior to conventional PVI “only” approaches regarding freedom from AF recurrences after ablation. Recent studies have found Atrial wall thickness correlates with low voltage areas, and the degree of atrial myocardial fibrosis can be better assessed by CT or MRI in combination with voltage mapping, which might help reduce the recurrence of AF after catheter ablation.
Electrocardiographic Markers Indicating Right Ventricular Outflow Tract Conduction Delay as a Predictor of Major Arrhythmic Events in Patients With Brugada Syndrome: A Systematic Review and Meta-Analysis
Authors: Iqbal Mohammad , Putra Iwan Cahyo Santosa , Pranata Raymond , Budiarso Michael Nathaniel , Pramudyo Miftah , Goenawan Hanna , Akbar Mohammad Rizki , Kartasasmita Arief Sjamsulaksan
Published: June 2022

Introduction

Risk stratification in Brugada Syndrome (BrS) patients is still challenging due to the heterogeneity of clinical presentation; thus, some additional risk markers are needed. Several studies investigating the association between RVOT conduction delay sign on electrocardiography (ECG) and major arrhythmic events (MAE) in BrS patients showed inconclusive results. This meta-analysis aims to evaluate the association between RVOT conduction delay signs presented by aVR sign and large S wave in lead I, and MAE in BrS patients.

Methods

The literature search was performed using several online databases from the inception to March 16th, 2022. We included studies consisting of two main components, including ECG markers of RVOT conduction delay (aVR sign and large S wave in lead I) and MAE related to BrS (syncope/VT/VF/SCD/aborted SCD/appropriate ICD shocks)

Results

Meta-analysis of eleven cohort studies with a total of 2,575 participants showed RVOT conduction delay sign was significantly associated with MAE in BrS patients [RR = 1.87 (1.35, 2.58); p < 0.001; I2= 52%, Pheterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I2= 0%, Pheterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I2= 60%, Pheterogeneity = 0.01] were significantly associated with MAE. Summary receiver operating characteristics analysis revealed the aVR sign [AUC: 0.77 (0.73–0.80)] and large S wave in lead I [AUC: 0.69 (0.65–0.73)] were a good predictor of MAE in BrS patients.

Conclusion

RVOT conduction delay sign, presented by aVR sign and large S wave in the lead I, is significantly associated with an increased risk of MAE in BrS patients. Hence, we propose that these parameters may be useful as an additional risk stratification tool to predict MAE in BrS patients.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.
Assessment of Debris Flow Activity in Response to an Earthquake Using the Sediment Connectivity Index
Authors: Li Yanji , Hu Kaiheng , Zhang Xiaopeng , Hu Xudong , Ning Lan , Li Hao
Published: June 2022

Large earthquakes can trigger landslides and collapses, which not only increase the mass of loose solid materials but also change the topography of catchments. Debris flow activity in response to earthquakes is of widespread concern; however, most studies have focused on the material conditions and flow property variations prior to and after earthquakes. In this study, we investigate temporal variations in the debris flow activity in a typical catchment in the Wenchuan Earthquake area via the sediment connectivity index (IC), which reflects the sediment delivery efficiency in the catchment. The IC values in different tributaries and during different time periods were calculated to determine their spatial distribution and temporal variations. The results show that high IC values are distributed in downstream tributaries near the main fault. The IC values decreased significantly following a 2008 Wenchuan Earthquake, indicating a continuous decrease in the sediment transfer ability. The debris flow history and loose solid material amounts were also investigated via field surveys. The debris flow activity is closely related to variations in the solid material source amounts and the IC values in the catchment. This study provides a new insight into the assessment of debris flow activity with respect to its close relationship with the distribution of loose solid materials and the sediment connectivity.
Evaluating Technology-Enhanced, STEAM-Based Remote Teaching With Parental Support in Luxembourgish Early Childhood Education
Authors: Haas Ben , Lavicza Zsolt , Houghton Tony , Kreis Yves
Published: June 2022

During COVID-19 confinement, we observed numerous challenges in using educational technology in early childhood Science–Technology–Engineering–Arts–Mathematics (STEAM) education in Luxembourg. Thus, we designed a conceptual framework on parent-assisted remote teaching with active uses of educational technology supported by cycles of design-based research. After a previous study utilizing computer-aided design (CAD) software and three-dimensional (3D) printing in primary education, we used our initial findings to work with 12 early childhood students (ages 4–6), together with their teachers and parents in the second remote teaching period in Luxembourg. We created a STEAM modeling task with CAD software on robots and collected data through chat responses, messageboards, and online communication channels during a 3-week period. Here, we observed new roles in the parent–child relationship while learning STEAM in remote teaching with technology, and new opportunities in using educational technology overall in early childhood education. In this article, we have described findings that are likely to influence students’ learning and parent-assisted teaching, in particular parents and students’ perceptions and motivations, together with the way in which parents provide technical knowledge and support in remote early childhood STEAM education.
Evaluation of a Virtual Campus Adapted to Web-Based Virtual Reality Spaces: Assessments of Teachers and Students
Authors: Rocha Estrada Francisco Javier , Ruiz-Ramírez Jessica Alejandra , George-Reyes Carlos Enrique , Glasserman-Morales Leonardo David
Published: June 2022

Educational institutions have continuously adapted to new realities in school education, accelerated recently by the COVID-19 pandemic’s transformation of learning modalities. This article analyzes teachers’ and Students’ acceptance of a web-based virtual reality (WebVR) tool called Virtual Campus proposed to overcome the limitations of teaching strategies using video conferencing platforms. To measure the acceptance of the Virtual Campus, we designed an instrument based on the Technology Acceptance Model (TAM) that involves variables related to online contexts, the future perception of using the tool, skills development, and appreciation and recommendation. The results indicate that the participants favorably accepted WebVR technology as an alternative teaching methodology in emerging learning scenarios and intend to use it post-pandemic. The best-valued elements were interactions in the socialization spaces, the simulation of presence, and the environmental dynamics. The principal areas of opportunity for improvement were overcoming technical problems and improving the internet connection quality; however, these did not affect the participants’ recommendations. Future studies should incorporate variables related to analyzing learning mediated by WebVR-based strategies and using different methodological designs to compare the findings.
Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy
Authors: Kim Youngsook , Huh Ji Hye , Lee Minyoung , Kang Eun Seok , Cha Bong-Soo , Lee Byung-Wan
Published: June 2022

Aims

Glucagon‐like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment.

Materials and methods

We retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide.

Results

Of 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin.

Conclusions

A considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.
Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer
Authors: Yang Tianli , Yang Yuanyuan , Zhang Qiong , Liu Donge , Liu Nenghui , Li Yumei , Yao Zhongyuan , Zhang Yeqing , Tian Fen , Zhao Jing , Li Yanping
Published: June 2022

Objective

To evaluate the associations between homeostatic model assessment for insulin resistance (HOMA-IR) and pregnancy outcomes in non-dyslipidemic infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).

Materials and Methods

This is a retrospective study involving 3,615 non-dyslipidemic infertile women who attend to the Reproductive Medicine Center of Xiangya Hospital, Central South University (CSU) between January 2014 and October 2021. Eligible participants were divided into three groups according to the quartiles of HOMA-IR: Group 1 (HOMA-IR <1.46), Group 2 (1.46 to <2.71) and Group 3 (HOMA-IR ≥2.71). Baseline data, clinical characteristics during the assisted reproductive technology (ART) procedure, pregnancy, and neonatal outcomes were compared among the three groups. Subgroup analysis based on presence or absence of the polycystic ovary syndrome (PCOS) status was also performed to analyze the effects of HOMA-IR among non-PCOS populations.

Results

The late miscarriage rate and percentage of macrosomia increased with the HOMA-IR group (for late miscarriage rate: 2.23% vs. 3.04% vs. 7.35%, P<0.001; for macrosomia: 0.21% vs. 1.70% vs. 3.23%, P=0.002). Increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.50, 95% CI 1.64-7.47, P=0.001; adjusted OR 3.56, 95% CI 1.56-8.15, P=0.003). In the subgroup analysis, there were 3,165 participants in the non-PCOS group and 450 were assigned to the PCOS group. Late miscarriage rate increased with the HOMA-IR group among non-PCOS populations (2.20% vs. 3.03% vs. 7.67%, P<0.001). Late miscarriage rate of PCOS women were comparable among the three HOMA-IR groups (2.50% vs. 3.06% vs. 5.71%, P=0.634). Among non-PCOS women, increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.71, 95% CI 1.66-8.30, P=0.001; adjusted OR 3.82, 95% CI 1.59-9.17, P=0.003).

Conclusions

Late miscarriage rate and prevalence of macrosomia increased with the HOMA-IR index. Preconception HOMA-IR is an independent risk factor for late miscarriage in normolipidemic women undergoing IVF/ICSI-ET. Controlling insulin resistance before ART might prevent the occurrence of late miscarriage and macrosomia.
Antidepressants as Endocrine Disrupting Compounds in Fish
Authors: Thompson William Andrew , Vijayan Mathilakath M.
Published: June 2022

As antidepressant usage by the global population continues to increase, their persistent detection in aquatic habitats from municipal wastewater effluent release has led to concerns of possible impacts on non-target organisms, including fish. These pharmaceuticals have been marketed as mood-altering drugs, specifically targeting the monoaminergic signaling in the brain of humans. However, the monoaminergic systems are highly conserved and involved in the modulation of a multitude of endocrine functions in vertebrates. While most studies exploring possible impact of antidepressants on fish have focused on behavioural perturbations, a smaller spotlight has been placed on the endocrine functions, especially related to reproduction, growth, and the stress response. The purpose of this review is to highlight the possible role of antidepressants as endocrine disruptors in fish. While studies linking the effects of environmentally relevant levels of antidepressant on the endocrine system in fish are sparse, the emerging evidence suggests that early-life exposure to these compounds have the potential to alter the developmental programming of the endocrine system, which could persist as long-term and multigenerational effects in teleosts.
Neural Network Acceleration of Genetic Algorithms for the Optimization of a Coupled Fast/Thermal Nuclear Experiment
Authors: Pevey John , Sobes Vlad , Hines Wes. J.
Published: June 2022

Genetic algorithms (GA) are used to optimize the Fast Neutron Source (FNS) core fuel loading to maximize a multiobjective function. The FNS has 150 material locations that can be loaded with one of three different materials resulting in over 3E+71 combinations. The individual designs are evaluated with computationally intensive calls to MCNP. To speed up the optimization, convolutional neural networks (CNN) are trained as surrogate models and used to produce better performing candidates that will meet the design constraints before they are sent to the costly MCNP evaluations. A major hurdle in training neural networks of all kinds is the availability of robust training data. In this application, we use the data produced by the GA as training data for the surrogate models which combine geometric features of the system to predict the objectives and constraint objectives. Utilizing the surrogate models, the accelerated algorithm produced more viable designs that significantly improved the objective function utilizing the same computational resources.
Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice
Authors: Yang Liqin , Xia Zhixiong , Feng Jianhua , Zhang Menghuan , Miao Pu , Nie Yingjie , Zhang Xiangyan , Hao Zijian , Hu Ronggui
Published: June 2022

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.
Comprehensive Evaluation of the m6A Regulator Prognostic Risk Score in the Prediction of Immunotherapy Response in Clear Cell Renal Cell Carcinoma
Authors: Yu Mingke , Liu Xuefei , Xu Han , Shen Sangyu , Wang Fajiu , Chen Dajin , Li Guorong , Wang Zongping , Zuo Zhixiang , Zhao An
Published: June 2022

Background

Clear cell renal cell carcinoma (ccRCC) is known for its high drug resistance. The tumor-immune crosstalk mediated by the epigenetic regulation of N6-methyladenosine (m6A) modification has been demonstrated in recent studies. Therefore, m6A modification-mediated immune cell infiltration characteristics may be helpful to guide immunotherapy for ccRCC.

Methods

This study comprehensively analyzed m6A modifications using the clinical parameters, single-cell RNA sequencing data, and bulk RNA sequencing data from the TCGA-ccRC cohort and 13 external validation cohorts. A series of bioinformatic approaches were applied to construct an m6A regulator prognostic risk score (MRPRS) to predict survival and immunotherapy response in ccRCC patients. Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low-MRPRS groups.

Results

The expressional alteration landscape of m6A regulators was profiled in ccRCC cell clusters and tissue. The 8 regulator genes with minimal lambda were integrated to build an MRPRS, and it was positively correlated with immunotherapeutic response in extent validation cohorts. The clinicopathological features and immune infiltration characteristics could be distinguished by the high- and low-MRPRS. Moreover, the MRPRS-mediated mutation pattern has an enhanced response to immune checkpoint blockade in the ccRCC and pan-cancer cohorts.

Conclusions

The proposed MRPRS is a promising biomarker to predict clinical outcomes and therapeutic responses in ccRCC patients.
Mesenchymal Stem/Stromal Cell Therapy Is More Cost-Effective Than Fecal Diversion for Treatment of Perianal Crohn’s Disease Fistulas
Authors: Johnson Sheeva , Hoch Jeffrey S. , Halabi Wissam J. , Ko Jeffrey , Nolta Jan , Dave Maneesh
Published: June 2022

Crohn’s disease (CD) is an inflammatory bowel disease with increasing incidence and prevalence worldwide. Perianal fistulas are seen in up to 26% of CD patients and are often refractory to medical therapy. Current treatments for CD perianal fistulas (pCD) include antibiotics, biologics, and for refractory cases, fecal diversion (FD) with ileostomy or colostomy. Mesenchymal stem/stromal cell therapy (MSCs) is a new modality that have shown efficacy in treating pCD. MSCs locally injected into pCD can lead to healing, and a phase III clinical trial (ADMIRE-CD) showed 66% clinical response, leading to approval of MSCs (Alofisel, Takeda) in the European Union. It is unclear if MSCs would be more cost-effective than the current standard of FD. We therefore developed a decision tree model to determine the cost-effectiveness of MSCs compared to FD for pCD. Our study showed that both autologous and allogeneic MSCs are more cost-effective than FD in an academic medical center and even in a worst-case scenario with 100% chance of all complications for MSCs treatment and 0% chance of complications for FD, both allogeneic and autologous MSCs are still cost saving compared to FD.
CD137 Costimulation Enhances the Antitumor Activity of Vγ9Vδ2-T Cells in IL-10-Mediated Immunosuppressive Tumor Microenvironment
Authors: Pei Yujun , Xiang Zheng , Wen Kun , Tu Chloe Ran , Wang Xiwei , Zhang Yanmei , Mu Xiaofeng , Liu Yinping , Tu Wenwei
Published: June 2022

Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity has shown success in some cancer patients, the clinical application is limited due to the rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from phosphoantigens and the profoundly immunosuppressive tumor microenvironment (TME). In this study, using a cell culture medium containing human and viral interleukin-10 (hIL-10 and vIL-10) secreted from EBV-transformed lymphoblastoid B cell lines (EBV-LCL) to mimic the immunosuppressive TEM, we found that the antitumor activity of Vγ9Vδ2-T cells was highly suppressed by endogenous hIL-10 and vIL-10 within the TME. CD137 costimulation could provide an anti-exhaustion signal to mitigate the suppressive effects of IL-10 in TME by suppressing IL-10R1 expression on Vγ9Vδ2-T cells. CD137 costimulation also improved the compromised antitumor activity of Vγ9Vδ2-T cells in TME with high levels of IL-10 in Rag2-/- γc-/- mice. In humanized mice, CD137 costimulation boosted the therapeutic effects of aminobisphosphonate pamidronate against EBV-induced lymphoma. Our study offers a novel approach to overcoming the obstacle of the hIL-10 and vIL-10-mediated immunosuppressive microenvironment by costimulating CD137 and enhancing the efficacy of γδ-T cell-based tumor therapy.
Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort
Authors: Mauro Daniele , Ciancio Antonio , Di Vico Claudio , Passariello Luana , Rozza Gelsomina , Pasquale Maria Dora , Pantano Ilenia , Cannistrà Carlo , Bucci Laura , Scriffignano Silvia , Riccio Flavia , Patrone Martina , Scalise Giuseppe , Ruscitti Piero , Montemurro Maria Vittoria , Giordano Antonio , Vietri Maria Teresa , Ciccia Francesco
Published: June 2022

Objective

In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination.

Methods

Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers.

Results

Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age.

Conclusion

The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.
Identification of New Antibodies Targeting Malignant Plasma Cells for Immunotherapy by Next-Generation Sequencing-Assisted Phage Display
Authors: Krohn Steffen , Boje Ammelie Svea , Gehlert Carina Lynn , Lutz Sebastian , Darzentas Nikos , Knecht Henrik , Herrmann Dietrich , Brüggemann Monika , Scheidig Axel J. , Weisel Katja , Gramatzki Martin , Peipp Matthias , Klausz Katja
Published: June 2022

To identify new antibodies for the treatment of plasma cell disorders including multiple myeloma (MM), a single-chain Fragment variable (scFv) antibody library was generated by immunizing mice with patient-derived malignant plasma cells. To enrich antibodies binding myeloma antigens, phage display with cellular panning was performed. After depleting the immune library with leukocytes of healthy donors, selection of antibodies was done with L-363 plasma cell line in two consecutive panning rounds. Monitoring the antibodies’ enrichment throughout the panning by next-generation sequencing (NGS) identified several promising candidates. Initially, 41 unique scFv antibodies evolving from different B cell clones were selected. Nine of these antibodies strongly binding to myeloma cells and weakly binding to peripheral blood mononuclear cells (PBMC) were characterized. Using stably transfected Chinese hamster ovary cells expressing individual myeloma-associated antigens revealed that two antibodies bind CD38 and intercellular adhesion molecule-1 (ICAM-1), respectively, and 7 antibodies target yet unknown antigens. To evaluate the therapeutic potential of our new antibodies, in a first proof-of-concept study the CD38 binding scFv phage antibody was converted into a chimeric IgG1. Further analyses revealed that #5-CD38-IgG1 shared an overlapping epitope with daratumumab and isatuximab and had potent anti-myeloma activity comparable to the two clinically approved CD38 antibodies. These results indicate that by phage display and deep sequencing, new antibodies with therapeutic potential for MM immunotherapy can be identified.
Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis
Authors: Sadeghi Hassanabadi Negar , Broux Bieke , Marinović Sonja , Gotthardt Dagmar
Published: June 2022

Multiple sclerosis (MS) is a highly debilitating autoimmune disease affecting millions of individuals worldwide. Although classically viewed as T-cell mediated disease, the role of innate lymphoid cells (ILC) such as natural killer (NK) cells and ILC 1-3s has become a focal point as several findings implicate them in the disease pathology. The role of ILCs in MS is still not completely understood as controversial findings have been reported assigning them either a protective or disease-accelerating role. Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that ILCs infiltrate the central nervous system (CNS), mediate inflammation, and have a disease exacerbating role by influencing the recruitment of autoreactive T-cells. Elucidating the detailed role of ILCs and altered signaling pathways in MS is essential for a more complete picture of the disease pathology and novel therapeutic targets. We here review the current knowledge about ILCs in the development and progression of MS and preclinical models of MS and discuss their potential for therapeutic applications.