bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal Reduction Could Improve but Not Completely Reverse the Pregnancy Outcomes of Multiple Pregnancies: Experience From a Single Center
Authors: Yimin Zhu , Minyue Tang , Yanling Fu , Huanmiao Yan , Saijun Sun , Qingfang Li , Xiaoling Hu , Lanfeng Xing
Published: June 2022

Objective

To investigate the effectiveness and limitations of multifetal pregnancy reduction (MFPR) on the improvement of pregnancy outcomes of triplet or twin pregnancies conceived by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Methods

We performed a cohort study of women undergoing IVF or ICSI from 2002–2016 in reproductive center, women’s hospital, Zhejiang University School of Medicine. The cohort included 502 women who underwent MFPR and 9641 non-reduced women. Pregnancy outcomes were gestational age (GA) at delivery, pregnancy loss, preterm delivery, low birth weight (LBW), very low birth weight (VLBW), and small for gestational age (SGA). Multiple linear regression and logistic regression models were used to compare pregnancy outcomes between groups.

Results

Triplets reduced to singletons had a longer median GA (39.07 vs 37.00, P<0.001), and lower rates of LBW (8.9% vs 53.2%, P<0.001) and SGA (17.8% vs 44.7%, P=0.001) than triplets reduced to twins, with a similar pregnancy loss rate (6.7% vs 6.6%, P=0.701). Twins reduced to singletons had a comparable pregnancy loss rate (4.8% vs. 6.5%, P=0.40), a longer median GA (38.79 vs. 37.00, P<0.001), and lower rates of LBW (13.5% vs. 47.0%, P<0.001) and SGA (13.5% vs. 39.6%, P<0.001) than primary twins. Triplets reduced to twins had higher rates of LBW (53.2% vs. 47.0%, P=0.028) and SGA (44.7% vs. 39.6%, P=0.040) than primary twins, with a similar pregnancy loss rate (6.6% vs. 6.5%, P=0.877). Singletons reduced from triplets/twins had higher rates of preterm delivery (15.8% vs. 7.3%, P<0.001), LBW (12.3% vs. 4.32%, P<0.001), VLBW (2.3% vs. 0.4%, P=0.002), and SGA (14.6% vs.6.6%, P<0.001) than primary singletons, with a comparable pregnancy loss rate (5.3% vs. 5.4%, P=0.671).

Conclusions

This study suggests that the pregnancy loss rate is similar between reduction and non-reduction groups. MFPR improves pregnancy outcomes, including the risk of preterm delivery, LBW, and SGA, but still could not completely reverse the adverse pregnancy outcomes of multiple pregnancies.
N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling
Authors: Zeng Qinghe , Xu Rui , Ling Houfu , Zhao Shan , Wang Xu , Yuan Wenhua , Gu Mancang , Xu Taotao , Wang Pinger , Ruan Hongfeng , Jin Hongting , Qu Hangbo , Ye Fusheng , Chen Jiali
Published: June 2022

Postmenopausal Osteoporosis (PMOP) is the most prevalent primary osteoporosis, attributable to an imbalance in osteoblast and osteoclast activity. Modified You-Gui-Yin (MYGY), a traditional Chinese herbal formula, is able to effectively treat PMOP, while the critical components and pharmacological mechanisms of MYGY are still unclear. In this study, we aimed to investigate the therapeutic effects and underlying mechanisms of N-butanol extract of MYGY (MYGY-Nb) in ovariectomized (OVX)-induced osteoporosis mice. Histological staining and micro-computed tomography (μCT) analysis showed that MYGY-Nb was more effective in the suppression of OVX-induced bone loss than MYGY original formula. Subsequently, liquid chromatography and mass spectrometry analysis identified 16 critical compounds of MYGY-Nb and some of them are reported to affect osteoclast functions. Furthermore, in vivo and in vitro experiments demonstrated that MYGY-Nb significantly attenuated osteoclastogenesis by down-regulating RANKL-mediated NF-κB signaling. In conclusion, our study indicated that MYGY-Nb suppresses NF-κB signaling and osteoclast formation to mitigate bone loss in PMOP, implying that MYGY-Nb and its compounds are potential candidates for development of anti-PMOP drugs.
Effects of Precursor Structure on First-Generation Photo-Oxidation Organic Aerosol Formation
Authors: Sofio D. , Long D. , Kohls T. , Kunz J. , Wentzel M. , Hanson D.
Published: June 2022

The effect of precursor molecular structural features on secondary organic aerosol (SOA) growth was investigated for a number of precursor functional groups. SOA yields were determined for straight chain alkanes, some oxygenated, up to highly functionalized hydrocarbons, the largest being β-caryophyllene. Organic SOA yield was determined by comparing to standard particle size changes with SO2 in a photolytic flow reactor. SOA formation was initiated with OH radicals from HONO photolysis and continued with NO and NO2 present at single-digit nmol/mol levels. Seed particles of ∼10 nm diameter grew by condensation of SOA material and growth was monitored with a nanoparticle sizing system. Cyclic compounds dominate as the highest SOA yielding structural feature, followed by C-10 species with double bonds, with linear alkanes and isoprene most ineffective. Carbonyls led to significant increases in growth compared to the alkanes while alcohols, triple-bond compounds, aromatics, and epoxides were only slightly more effective than alkanes at producing SOA. When more than one double bond is present, or a double bond is present with another functional group as seen with 1, 2-epoxydec-9-ene, SOA yield is notably increased. Placement of the double bond is important as well with β-pinene having an SOA yield approximately 5 times that of α-pinene. In our photolytic flow reactor, first-generation oxidation products are presumed to be the primary species contributing to SOA thus the molecular structure of the precursor is determinant. We also conducted proton-transfer mass spectrometry measurements of α-pinene photooxidation and significant signals were observed at masses for multifunctional nitrates and possibly peroxy radicals. The mass spectrometer measurements were also used to estimate a HONO photolysis rate.
Response of Soil Microbial Community Structure to Phosphate Fertilizer Reduction and Combinations of Microbial Fertilizer
Authors: Liu Hang , Li Songsong , Qiang Ruowen , Lu Enjia , Li Cuilan , Zhang Jinjing , Gao Qiang
Published: June 2022

The excessive application of phosphorus (P) fertilizer is becoming a major agricultural problem, which reduces the utilization rate of the P fertilizer and degrades soil quality. The following five P fertilizer treatments were investigated to know how they affect soil properties, enzyme activity, bacterial and fungal community structure. 1) no P fertilizer (P0); 2) farmers’ traditional P fertilization scheme (FP); 3) 30% reduction in P fertilizer application (P1, microbial blended fertilizer as base fertilizer); 4) 30% reduction in P fertilizer application (P2, diammonium phosphate as starting fertilizer); 5) 30% reduction in P fertilizer application (P3, microbial inoculum seed dressing). The P fertilizer reduction combined with microbial fertilizer significantly increased soil organic matter (SOM), total phosphorus (TP), available phosphorus (AP) available potassium (AK) contents, and acid phosphatase activity (ACP), however, soil urease activity was significantly reduced. Moreover, the P fertilizer reduction combined with microbial fertilizer significantly increased the relative abundance of a potential beneficial genus (i.e., Bacillus, Pseudomonas, Penicillium, and Acremonium) and potentially pathogenic genus (i.e., Fusarium, Gibberella, and Drechslera). The structural equation model (SEM) revealed that different P fertilizer reduction systems had significant indirect effects on bacterial and fungal community structures. The results suggested that the P fertilizer reduction combined with microbial fertilizer systems regulated the pathogenic and beneficial genus which created a microbial community that is favorable for maize growth. Moreover, the findings highlighted the importance of soil properties in determining the soil bacterial and fungal community structure.
Analysis of Agricultural Production Potential and Enhancement Strategy in the Qaidam Basin Based on the Agro-Ecological Zone Method
Authors: Yu Hui , Huang Min , Zhao Tao , Wang Jianping , Li Zihan , Chen Dianpeng , Li Pengshan , Luo Yong , Wang Haoyu , Jing Zhao , Mou Dongyang , Zhang Dan , Wang Xiao
Published: June 2022

The Qaidam Basin has an arid plateau continental climate, with climatic factors strongly influencing agricultural production potential. In the present study, the agro-ecological zone method was applied to study the effects of rainfall, temperature and soil on crop yield, with climatic factors as the main common influencer. By assessing the land production potential, suitable zones for grain production were identified in the Qaidam Basin, and the reasonable current input level was determined, thus, evaluating the population carrying capacity. Strategies for improving crop productivity in these regions were proposed to provide a basis for decision-making by the local government. The results showed that: 1) The photosynthetic and light-temperature production potential was high in Mangya city and the autonomous region; however, the climate production potential was low in Golmud city and the eastern part of Mangya city. After correction based on soil availability, the land production potentials of spring wheat and highland barley were greatly attenuated, and only 15.85 and 16.74% of the photosynthetic production potential, respectively. 2) The current population carrying capacity of the land resources is 595,900 people, which is in a state of human–food balance when the correction coefficient of artificial input is approximately 1.1. If the artificial input can be strengthened to achieve a correction coefficient of 1.2, the population carrying capacity could reach 676,100 people. 3) The suitable area for agricultural production was mainly located in the northeast and west of the Qaidam Basin. These areas can be used as a backup arable land resource. The temperature increase leading to evaporation increase negatively affected the yield per unit area of grain crops in Qaidam Basin. Strengthening water-saving irrigation technology and improving the utilisation rate of chemical fertilisers are good enhancement strategies for the green-oriented agricultural technology system, which would help improve the agricultural productivity potential in the Qaidam Basin.
Rapid Shifts in Visible Carolina Grasshopper (Dissosteira carolina) Coloration During Flights
Authors: Martin Ezekiel , Steinmetz Henry L. , Baek Seo Young , Gilbert Frederick R. , Brandley Nicholas C.
Published: June 2022

Some brightly colored structures are only visible when organisms are moving, such as parts of wings that are only visible in flight. For example, the primarily brown Carolina grasshopper (Dissosteira carolina) has contrasting black-and-cream hindwings that appear suddenly when it takes off, then oscillate unpredictably throughout the main flight before disappearing rapidly upon landing. However, the temporal dynamics of hindwing coloration in motion have not previously been investigated, particularly for animals that differ from humans in their temporal vision. To examine how quickly this coloration appears to a variety of non-human observers, we took high-speed videos of D. carolina flights in the field. For each of the best-quality takeoffs and landings, we performed a frame-by-frame analysis on how the relative sizes of the different-colored body parts changed over time. We found that in the first 7.6 ± 1.5 ms of takeoff, the hindwings unfurled to encompass 50% of the visible grasshopper, causing it to roughly double in size. During the main flight, the hindwings transitioned 6.4 ± 0.4 times per second between pauses and periods of active wing-beating (31.4 ± 0.5 Hz), creating an unstable, confusing image. Finally, during landings, the hindwings disappeared in 11.3 ± 3.0 ms, shrinking the grasshopper to 69 ± 9% of its main flight size. Notably, these takeoffs and landings occurred faster than most recorded species are able to sample images, which suggests that they would be near-instantaneous to a variety of different viewers. We therefore suggest that D. carolina uses its hindwings to initially startle predators (deimatic defense) and then confuse them and disrupt their search images (protean defense) before rapidly returning to crypsis.
Seasonal Variation Characteristics of C, N, and P Stoichiometry and Water Use Efficiency of Messerschmidia sibirica and Its Relationship With Soil Nutrients
Authors: Li Tian , Zhang Zehao , Sun Jingkuan , Fu Zhanyong , Zhao Yinghan , Xu Wenjing
Published: June 2022

The seasonal dynamic characteristics of C, N, and P stoichiometry and water use efficiency (WUE) of Messerschmidia sibirica and the soil in the Yellow River Delta (YRD) were studied. The correlations of stoichiometric characteristics and WUE between organs of M. sibirica and soil were analyzed. The results showed that: (1) the contents of C, N, and P and their stoichiometric ratios in various organs of M. sibirica varied with seasons. The seasonal dynamics of leaf N:P showed that the degree of nutrient restriction by N decreased in July and increased in September. (2) The contents of C, N, and P, as well as their stoichiometric ratio, showed a high correlation throughout the growing season, with N:P showing a significantly positive correlation among organs and the lowest stoichiometric correlation between leaf and root. (3) C13 stable isotope analysis showed that the WUE of M. sibirica in May was significantly higher than that of other months (July and September). The WUE had a significantly positive correlation with leaf C and N content and a significantly negative correlation with leaf C:N, indicating that M. sibirica can compensate for the decline in N use efficiency through the improvement of WUE. The structural equation model (SEM) showed that the leaf N and P contents were affected by the joint effect of season and WUE, and the leaf C content was mainly directly affected by WUE. (4) Redundancy analysis (RDA) analysis showed that soil P content and soil N:P were the main factors affecting the variation of stoichiometry and WUE in various organs of M. sibirica. This study is helpful to deeply understand the adaptive mechanism of plant nutrient and water use, which provides a theoretical basis for vegetation protection and restoration in the study area.
Social Isolation, Loneliness and Health: A Descriptive Study of the Experiences of Migrant Mothers With Young Children (0–5 Years Old) at La Maison Bleue
Authors: Lim Mona , Van Hulst Andraea , Pisanu Sarah , Merry Lisa
Published: June 2022

Background

Migrant women with young children, including asylum seekers and refugees, have multiple vulnerability factors that put them at increased risk of social isolation and loneliness, which are associated with negative health outcomes. This study explored the experiences of social isolation and loneliness among migrant mothers with children aged 0–5 years as well as their perceptions on possible health impacts.

Methods

A qualitative descriptive study was conducted at La Maison Bleue, a non-profit organization providing perinatal health and social services to vulnerable women in Montreal, Canada. Recruitment and data collection occurred concurrently during the COVID-19 pandemic, between November and December 2020. Eleven women participated in individual semi-structured interviews and provided socio-demographic information. Interview data were thematically analyzed.

Results

Migrant women in this study described social isolation as the loss of family support and of their familiar social/cultural networks, and loneliness as the feelings of aloneness that stemmed from being a mother in a new country with limited support. Multiple factors contributed to women's and children's social isolation and loneliness, including migration status, socioeconomic circumstances, language barriers, and being a single mother. Women expressed that the COVID-19 pandemic exacerbated pre-existing experiences of social isolation and loneliness. Mothers' experiences affected their emotional and mental health, while for children, it reduced their social opportunities outside the home, especially if not attending childcare. However, the extent to which mothers' experiences of social isolation and loneliness influenced the health and development of their children, was less clear.

Conclusion

Migrant mothers' experiences of social isolation and loneliness are intricately linked to their status as migrants and mothers. Going forward, it is critical to better document pandemic and post-pandemic consequences of social isolation and loneliness on young children of migrant families. Supportive interventions for migrant mothers and their young children should not only target social isolation but should also consider mothers' feelings of loneliness and foster social connectedness and belongingness. To address social isolation and loneliness, interventions at the individual, community and policy levels are needed.
Cytokines and Lipid Mediators of Inflammation in Lungs of SARS-CoV-2 Infected Mice
Authors: Dubuc Isabelle , Prunier Julien , Lacasse Émile , Gravel Annie , Puhm Florian , Allaeys Isabelle , Archambault Anne-Sophie , Gudimard Leslie , Villano Rosaria , Droit Arnaud , Flamand Nicolas , Boilard Éric , Flamand Louis
Published: June 2022

Coronavirus disease 19 (COVID-19) is the clinical manifestation of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. A hallmark of COVID-19 is a lung inflammation characterized by an abundant leukocyte infiltrate, elevated levels of cytokines/chemokines, lipid mediators of inflammation (LMI) and microthrombotic events. Animal models are useful for understanding the pathophysiological events leading to COVID-19. One such animal model is the K18-ACE2 transgenic mice. Despite their importance in inflammation, the study of LMI in lung of SARS-CoV-2 infected K18-ACE2 mice has yet to be studied to our knowledge. Using tandem mass spectrometry, the lung lipidome at different time points of infection was analyzed. Significantly increased LMI included N-oleoyl-serine, N-linoleoyl-glycine, N-oleoyl-alanine, 1/2-linoleoyl-glycerol, 1/2-docosahexaenoyl-glycerol and 12-hydroxy-eicosapenatenoic acid. The levels of prostaglandin (PG) E1, PGF2α, stearoyl-ethanolamide and linoleoyl-ethanolamide were found to be significantly reduced relative to mock-infected mice. Other LMI were present at similar levels (or undetected) in both uninfected and infected mouse lungs. In parallel to LMI measures, transcriptomic and cytokine/chemokine profiling were performed. Viral replication was robust with maximal lung viral loads detected on days 2-3 post-infection. Lung histology revealed leukocyte infiltration starting on day 3 post-infection, which correlated with the presence of high concentrations of several chemokines/cytokines. At early times post-infection, the plasma of infected mice contained highly elevated concentration of D-dimers suggestive of blood clot formation/dissolution. In support, the presence of blood clots in the lung vasculature was observed during infection. RNA-Seq analysis of lung tissues indicate that SARS-CoV-2 infection results in the progressive modulation of several hundred genes, including several inflammatory mediators and genes related to the interferons. Analysis of the lung lipidome indicated modest, yet significant modulation of a minority of lipids. In summary, our study suggests that SARS-CoV-2 infection in humans and mice share common features, such as elevated levels of chemokines in lungs, leukocyte infiltration and increased levels of circulating D-dimers. However, the K18-ACE2 mouse model highlight major differences in terms of LMI being produced in response to SARS-CoV-2 infection. The potential reasons and impact of these differences on the pathology and therapeutic strategies to be employed to treat severe COVID-19 are discussed.
Monocytic-Myeloid Derived Suppressor Cells Suppress T-Cell Responses in Recovered SARS CoV2-Infected Individuals
Authors: Beliakova-Bethell Nadejda , Maruthai Kathirvel , Xu Ruijie , Salvador Liliana C. M. , Garg Ankita
Published: June 2022

Coronavirus disease 2019 (COVID-19) caused by SARS Coronavirus 2 (CoV2) is associated with massive immune activation and hyperinflammatory response. Acute and severe CoV2 infection is characterized by the expansion of myeloid derived suppressor cells (MDSC) because of cytokine storm, these MDSC suppress T cell functions. However, the presence of MDSC and its effect on CoV2 antigen specific T cell responses in individuals long after first detection of CoV2 and recovery from infection has not been studied. We and others have previously shown that CD11b+CD33+CD14+HLA-DR-/lo monocytic MDSC (M-MDSC) are present in individuals with clinical recovery from viral infection. In this study, we compared the frequency, functional and transcriptional signatures of M-MDSC isolated from CoV2 infected individuals after 5-months of the first detection of the virus (CoV2+) and who were not infected with CoV2 (CoV2-). Compared to CoV2- individuals, M-MDSC were present in CoV2+ individuals at a higher frequency, the level of M-MDSC correlated with the quantity of IL-6 in the plasma. Compared to CoV2-, increased frequency of PD1+, CD57+ and CX3CR1+ T effector memory (TEM) cell subsets was also present in CoV2+ individuals, but these did not correlate with M-MDSC levels. Furthermore, depleting M-MDSC from peripheral blood mononuclear cells (PBMC) increased T cell cytokine production when cultured with the peptide pools of immune dominant spike glycoprotein (S), membrane (M), and nucleocapsid (N) antigens of CoV2. M-MDSC suppressed CoV2 S- antigen-specific T cell in ROS, Arginase, and TGFβ dependent manner. Our gene expression, RNA-seq and pathway analysis studies further confirm that M-MDSC isolated from CoV2+ individuals are enriched in pathways that regulate both innate and adaptive immune responses, but the genes regulating these functions (HLA-DQA1, HLA-DQB1, HLA-B, NLRP3, IL1β, CXCL2, CXCL1) remained downregulated in M-MDSC isolated from CoV2+ individuals. These results demonstrate that M-MDSC suppresses recall responses to CoV2 antigens long after recovery from infection. Our findings suggest M-MDSC as novel regulators of CoV2 specific T cell responses, and should be considered as target to augment responses to vaccine.
Identification and Verification of Necroptosis-Related Gene Signature With Prognosis and Tumor Immune Microenvironment in Ovarian Cancer
Authors: Wang Zitao , Chen Ganhong , Dai Fangfang , Liu Shiyi , Hu Wei , Cheng Yanxiang
Published: June 2022

Ovarian cancer is the most lethal heterogeneous disease among gynecological tumors with a poor prognosis. Necroptosis, the most studied way of death in recent years, is different from apoptosis and pyroptosis. It is a kind of regulated programmed cell death and has been shown to be closely related to a variety of tumors. However, the expression and prognosis of necroptosis-related genes in ovarian cancer are still unclear. Our study therefore firstly identified the expression profiles of necroptosis-related genes in normal and ovarian cancer tissues. Next, based on differentially expressed necroptosis-related genes, we clustered ovarian cancer patients into two subtypes and performed survival analysis. Subsequently, we constructed a risk model consisting of 5 genes by LASSO regression analysis based on the differentially expressed genes in the two subtypes, and confirmed the strong prognostic ability of the model and its potential as an independent risk factor via survival analysis and independent risk factor analysis. Based on this risk model, patients were divided into high and low risk groups. By exploring differentially expressed genes, enrichment functions and tumor immune microenvironment in patients in high and low risk groups, the results showed that patients in the low risk group were significantly enriched in immune signaling pathways. Besides, immune cells content, immune function activity was significantly better than the high-risk group. Eventually, we also investigated the sensitivity of patients with different risk groups to ICB immunotherapy and chemotherapy drugs. In conclusion, the risk model could effectively predict the survival and prognosis of patients, and explore the tumor microenvironment status of ovarian cancer patients to a certain extent, and provide promising and novel molecular markers for clinical diagnosis, individualized treatment and immunotherapy of patients.
Tumor-Infiltrated CD8+ T Cell 10-Gene Signature Related to Clear Cell Renal Cell Carcinoma Prognosis
Authors: Wang Jie , Huang Feifan , Zhao Jingjie , Huang Peng , Tan Junhua , Huang Meiying , Ma Ruiying , Xiao Yu , He Siyuan , Wang Zechen , Shen Jiajia , Lu Heming , Meng Lingzhang
Published: June 2022

Clear cell renal cell carcinoma (ccRCC) usually affects multiple organs (e.g., bone and brain), and patient prognosis is usually poor. Although it is known that CD8+ T cell infiltration can potentially alleviate ccRCC progression, few studies have concentrated on the correlation between CD8+ T cell infiltration and ccRCC prognosis. In this study, ten genes expressed by infiltrated CD8+ T cells (i.e., AMD1, CCSER2, CIB1, DRAP1, HMGB2, HMGN1, NPIPB5, PTP4A2, RORA, and SAP18) were suggested as potential ccRCC prognostic biomarkers, by using next-generation sequencing (i.e. bulk sequencing and single-cell sequencing) of ccRCC, papillary renal cell carcinoma (papRCC), and control kidney biopsies. Specifically, we identified four genes (i.e., CCSER2, DRAP1, NPIPB5, and SAP18) as potential novel prognostic biomarkers for ccRCC. It is noteworthy that SAP18 derived from CD8+ T cells negatively correlates to Atg7+ neutrophils in ccRCC, compared with papRCC, indicating a potential decreased neutrophil metabolic function in autophagy and fatty acids. This study elucidated the protective role of infiltrated CD8+ T cells in ccRCC and identified ten candidate genes related to an improved prognosis in patients with ccRCC.
Trophic Requirements of the Sea Urchin Paracentrotus lividus Varies at Different Life Stages: Comprehension of Species Ecology and Implications for Effective Feeding Formulations
Authors: Grosso Luca , Rakaj Arnold , Fianchini Alessandra , Tancioni Lorenzo , Vizzini Salvatrice , Boudouresque Charles-François , Scardi Michele
Published: June 2022

Investigations on trophic requirements of different life cycle stages of Paracentrotus lividus are crucial for the comprehension of species ecology and for its artificial rearing. The future success of echinoculture depends heavily on the development of suitable and cost-effective diets that are specifically designed to maximize somatic growth during the early life stages and gonadal production in the later stages. In this context, a considerable number of studies have recommended animal sources as supplements in sea urchin diets. However, with the exception of Fernandez and Boudouresque (2000), no studies have investigated the dietary requirements over the different life stages of the sea urchin. In the present study, the growth and nutrition of three life stages of P. lividus (juveniles: 15-25 mm; subadults: 25-35 mm; adults: 45-55 mm) were analyzed over a 4-month rearing experiment. Three experimental diets, with 0%, 20% and 40% of animal sourced enrichments, were tested in parallel in sea urchin three size classes. The food conversion ratio, somatic and gonadal growth were assessed in each condition in order to evaluate the optimal level of animal-sourced supplements for each life stage. A general growth model covering the full post-metamorphic P. lividus life cycle was defined for each condition. During the juvenile stage P. lividus requires higher animal supply (40%), while a feeding requirement shift takes place toward lower animal supply (20%) in sub-adult and adult stages. Our results evidenced that the progressive increase in size after the metamorphosis led to a consequent variation of trophic requirements and food energy allocation in the sea urchin P. lividus. Macronutrient requirements varied widely during the different life stages, in response to changes in the energy allocation from somatic growth to reproductive investment. This study sheds light on P. lividus trophic ecology, broadening our basic knowledge of the dietary requirements of juveniles, sub-adults and adults as a function of their behavior also in the natural environment.
Submarine Optical Fiber Sensing System for the Real-Time Monitoring of Depth, Vibration, and Temperature
Authors: Liu Zhengyong , Zhang Shengqi , Yang Chengkun , Chung Weng-Hong , Li Zhaohui
Published: June 2022

Ocean observation becomes increasingly important as the ocean climate changes diversely and the marine disasters (such as tsunamis, typhoon, and earthquakes) occur frequently, which typically requires widespread and reliable monitoring techniques. In such a scenario, this paper presents a submarine optical fiber sensing system to realize real-time monitoring of the environmental parameters. The system consists of an undersea optical interrogation module together with multiple fiber Bragg grating (FBG)-based sensors, particularly for the measurement of depth, vibration, and temperature. The experimentally demonstrated sensitivities of the pressure, temperature, and vibration sensors are -1.993 nm/MPa, 0.08 nm/°C, and 0.139 nm/g (g = 9.8 m/s2), corresponding to the resolutions of 0.25 kPa, 0.006°C, and 0.004 g, respectively, based on the interrogation resolution of ~0.5 pm. To verify the feasibility and reliability of the proposed submarine sensing system, a prototype was developed and a proof test under the sea was conducted in an area close to Pearl River Estuary in China. The achieved results from the sea test show promising accuracy that is comparable to the commercially available electric-based sensors. Good characteristics of the surface water wave were observed by conducting the fast Fourier transform of the measured depth change, which shows a dominant frequency of ~0.25 Hz. The system provides the flexibility of replacing various optical fiber sensors easily and the capability of real-time monitoring in a remote way. The demonstrated submarine sensing system could find potential applications in real-time monitoring of the undersea ecosystem and the environmental evolution where multiparameter sensing is in demand.
The Extent of Inflammatory Cell Infiltrate and Fibrosis in Lungs of Telomere- and Surfactant-Related Familial Pulmonary Fibrosis
Authors: van Batenburg Aernoud A. , van Oosterhout Matthijs F. M. , Knoppert Sebastiaan N. , Kazemier Karin M. , van der Vis Joanne J. , Grutters Jan C. , Goldschmeding Roel , van Moorsel Coline H. M.
Published: June 2022

Familial pulmonary fibrosis (FPF) is a monogenic disease most commonly involving telomere- (TERT) or surfactant- (SFTP) related mutations. These mutations have been shown to alter lymphocytic inflammatory responses, and FPF biopsies with histological lymphocytic infiltrates have been reported. Recently, a model of a surfactant mutation in mice showed that the disease initially started with an inflammatory response followed by fibrogenesis. Since inflammation and fibrogenesis are targeted by different drugs, we investigated whether the degree of these two features co-localize or occur independently in different entities of FPF, and whether they influence survival. We quantified the number of lymphocyte aggregates per surface area, the extent of diffuse lymphocyte cell infiltrate, the number of fibroblast foci per surface area, and the percentage of fibrotic lung surface area in digitally scanned hematoxylin and eosin (H&E) sections of diagnostic surgical biopsies of patients withTERT-related FPF (TERT-PF;n= 17),SFTP-related FPF (SFTP-PF;n= 7), and sporadic idiopathic pulmonary fibrosis (sIPF;n= 10). For comparison, we included biopsies of patients with cellular non-specific interstitial pneumonia (cNSIP;n= 10), an inflammatory interstitial lung disease with high lymphocyte influx and usually responsive to immunosuppressive therapy. The degree of inflammatory cell infiltrate and fibrosis in TERT-PF and SFTP-PF was not significantly different from that in sIPF. In comparison with cNSIP, the extent of lymphocyte infiltrates was significantly lower in sIPF and TERT-PF, but not in SFTP-PF. However, in contrast with cNSIP, in sIPF, TERT-PF, and SFTP-PF, diffuse lymphocyte cell infiltrates were predominantly present and lymphocyte aggregates were only present in fibrotic areas (p < 0.0001). Furthermore, fibroblast foci and percentage of fibrotic lung surface were associated with survival (p= 0.022 andp= 0.018, respectively), while this association was not observed for lymphocyte aggregates or diffuse lymphocytic infiltration. Inflammatory cells in diagnostic lung biopsies of TERT-PF, SFTP-PF, and sIPF were largely confined to fibrotic areas. However, based on inflammation and fibrosis, no differences were found between FPF and sIPF, substantiating the histological similarities between monogenic familial and sporadic disease. Furthermore, the degree of fibrosis, rather than inflammation, correlates with survival, supporting that fibrogenesis is the key feature for therapeutic targeting of FPF.
The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective
Authors: Zanotti Sofia , Boot Gina F. , Coto-Llerena Mairene , Gallon John , Hess Gabriel F. , Soysal Savas D. , Kollmar Otto , Ng Charlotte K. Y. , Piscuoglio Salvatore
Published: June 2022

Hepatocellular carcinoma (HCC) typically develops from a background of cirrhosis resulting from chronic inflammation. This inflammation is frequently associated with chronic liver diseases (CLD). The advent of next generation sequencing has enabled extensive analyses of molecular aberrations in HCC. However, less attention has been directed to the chronically inflamed background of the liver, prior to HCC emergence and during recurrence following surgery. Hepatocytes within chronically inflamed liver tissues present highly activated inflammatory signaling pathways and accumulation of a complex mutational landscape. In this altered environment, cells may transform in a stepwise manner toward tumorigenesis. Similarly, the chronically inflamed environment which persists after resection may impact the timing of HCC recurrence. Advances in research are allowing an extensive epigenomic, transcriptomic and proteomic characterization of CLD which define the emergence of HCC or its recurrence. The amount of data generated will enable the understanding of oncogenic mechanisms in HCC from the CLD perspective and provide the possibility to identify robust biomarkers or novel therapeutic targets for the treatment of primary and recurrent HCC. Importantly, biomarkers defined by the analysis of CLD tissue may permit the early detection or prevention of HCC emergence and recurrence. In this review, we compile the current omics based evidence of the contribution of CLD tissues to the emergence and recurrence of HCC.
Seeking the Light in Intensive Care Unit Sedation: The Optimal Sedation Strategy for Critically Ill Patients
Authors: Gitti Nicola , Renzi Stefania , Marchesi Mattia , Bertoni Michele , Lobo Francisco A. , Rasulo Frank A. , Goffi Alberto , Pozzi Matteo , Piva Simone
Published: June 2022

The clinical approach to sedation in critically ill patients has changed dramatically over the last two decades, moving to a regimen of light or non-sedation associated with adequate analgesia to guarantee the patient’s comfort, active interaction with the environment and family, and early mobilization and assessment of delirium. Although deep sedation (DS) may still be necessary for certain clinical scenarios, it should be limited to strict indications, such as mechanically ventilated patients with Acute Respiratory Distress Syndrome (ARDS), status epilepticus, intracranial hypertension, or those requiring target temperature management. DS, if not indicated, is associated with prolonged duration of mechanical ventilation and ICU stay, and increased mortality. Therefore, continuous monitoring of the level of sedation, especially when associated with the raw EEG data, is important to avoid unnecessary oversedation and to convert a DS strategy to light sedation as soon as possible. The approach to the management of critically ill patients is multidimensional, so targeted sedation should be considered in the context of the ABCDEF bundle, a holistic patient approach. Sedation may interfere with early mobilization and family engagement and may have an impact on delirium assessment and risk. If adequately applied, the ABCDEF bundle allows for a patient-centered, multidimensional, and multi-professional ICU care model to be achieved, with a positive impact on appropriate sedation and patient comfort, along with other important determinants of long-term patient outcomes.
Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism
Authors: Sun Luyan , Jiang Yiran , Xie Jing , Zhu Hongyuan , Wu Luming , Zhong Xu , Zhou Weiwei , Su Tingwei , Wang Weiqing
Published: June 2022

Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism.

Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients’ sections using immunohistochemistry technology and the relationship with clinical data was assessed.

Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis.

Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism.
Targeting Triple Negative Breast Cancer With Oncolytic Adenoviruses
Authors: Green-Tripp Gabriela , Nattress Callum , Halldén Gunnel
Published: June 2022

Breast cancer (BC) is the most common cancer globally, accounting for 685,000 deaths in 2020. Triple-negative breast cancers (TNBC) lack oestrogen (ER) and progesterone (PR) hormone receptor expression and HER2 overexpression. TNBC represent 10–15% of all BC with high incidence in women under 50-years old that have BRCA mutations, and have a dismal prognosis. African American and Hispanic women are at higher risk partly due to the common occurrence of BRCA mutations. The standard treatment for TNBC includes surgery, radiotherapy, and chemotherapy although, resistance to all standard-of-care therapies eventually develops. It is crucial to identify and develop more efficacious therapeutics with different mechanisms of action to improve on survival in these women. Recent findings with oncolytic adenoviruses (OAds) may generate a new strategy to improve on the outcomes for women afflicted by TNBC and other types of BC. OAds are genetically engineered to selectively lyse, eliminate and recruit the host antitumour immune responses, leaving normal cells unharmed. The most common modifications are deletions in the early gene products including the E1B55 KDa protein, specific regions of the E1A protein, or insertion of tumour-specific promoters. Clinical trials using OAds for various adenocarcinomas have not yet been sufficiently evaluated in BC patients. Preclinical studies demonstrated efficacy in BC cell lines, including TNBC cells, with promising novel adenoviral mutants. Here we review the results reported for the most promising OAds in preclinical studies and clinical trials administered alone and in combination with current standard of care or with novel therapeutics. Combinations of OAds with small molecule drugs targeting the epidermal growth factor receptor (EGFR), androgen receptor (AR), and DNA damage repair by the novel PARP inhibitors are currently under investigation with reported enhanced efficacy. The combination of the PARP-inhibitor Olaparib with OAds showed an impressive anti-tumour effect. The most promising findings to date are with OAds in combination with antibodies towards the immune checkpoints or expression of cytokines from the viral backbone. Although safety and efficacy have been demonstrated in numerous clinical trials and preclinical studies with cancer-selective OAds, further developments are needed to eliminate metastatic lesions, increase immune activation and intratumoural viral spread. We discuss shortcomings of the OAds and potential solutions for improving on patient outcomes.
Effects of Tempeh Probiotics on Elderly With Cognitive Impairment
Authors: Handajani Yvonne Suzy , Turana Yuda , Yogiara Yogiara , Sugiyono Sagita Pratiwi , Lamadong Vincent , Widjaja Nelly Tina , Christianto Geovannie Audrey Moniqe , Suwanto Antonius
Published: June 2022

Introduction

Oral consumption of probiotics can alter Gut Microbiota by causing changes in the production of probiotic derivatives. Therefore, by utilizing Gut-Brain-Axis (GBA), probiotics could provide an opportunity for central nervous system (CNS) modulation, including cognitive function. Tempeh is a traditional Indonesian food rich in probiotics and beneficial for cognitive function. However, the type of probiotics that play a role in cognitive improvement and the number of probiotics needed for the benefits of increasing cognitive function was unknown.

Method

This experimental study involved a total of 93 subjects, divided into 3 groups: A, B and C/control (n: 33, 32, and 28), who were provided with probiotic supplementation isolated from tempeh for 12 weeks intervention. Inclusion criteria were age > 60 years, and memory impairment with the third repetition value of Word List Memory Immediate Recall (WLMIR) < 7. Subjects with diabetes were excluded. Cognitive function examinations were carried out before and after treatment. The tempeh-derived probiotics were prepared trough several processes. Genomic isolation, detection of GABA-encoding genes, and species identification using the 16S-rRNA gene encoding were performed.

Results

The probiotics isolate used in the intervention was identified as Limosilactobacillus fermentum. We assigned this isolate as L. fermentum A2.8. The presence of the gene encoding GABA was found on this isolate. There was an increase in the cognitive domains of memory, learning process, and verbal fluency (p < 0.05) in group A (probiotics at concentration of 108 CFU/mL). Memory function, visuospatial, and verbal fluency improved (p < 0.05) in group B (probiotics at concentration of 107 CFU/mL). Only an increase in the memory domain was observed in the control group. Improvement of the learning process occurred only in group A (p = 0.006).

Conclusion

Administration of probiotics derived from L. fermentum A2.8 increased the cognitive domains of memory, language and visuospatial function. However, probiotic supplementation at a concentration of 108 CFU/mL was better in improving the learning process. This study succeeded in detecting Lactic Acid Bacterial isolates L. fermentum A2.8 that enclosed gene encoding glutamate decarboxylase (gad) which is involved in the synthesis of -aminobutyric acid (GABA), a neurotransmitter vital for cognitive function.
The Combined Efficacy of a Two-Year Period of Cybernic Treatment With a Wearable Cyborg Hybrid-Assistive Limb and Leuprorelin Therapy in a Patient With Spinal and Bulbar Muscular Atrophy: A Case Report
Authors: Nakatsuji Hideaki , Ikeda Tetsuhiko , Hashizume Atsushi , Katsuno Masahisa , Sobue Gen , Nakajima Takashi
Published: June 2022

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, slowly progressive, incurable, and hereditary neurodegenerative disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. After extensive review, two treatments for SBMA have recently been approved in Japan; this decision was based on the results of randomized controlled trials: First, anti-androgen therapy using leuprorelin acetate (leuprorelin), a disease-modifying drug that can inhibit the progression of dysphagia but has not yet been proved to improve gait function; second, cybernic treatment with a wearable cyborg hybrid assistive limb (HAL®) (Cyberdyne Inc. Tsukuba, Japan). The HAL is an innovative walking exercise system that has been shown to significantly improve gait function in eight neuromuscular diseases without reduction in muscle function, including SBMA. It is possible that the combination of these two approaches might yield better outcomes. However, the long-term effects of such a combined approach have yet to be clinically evaluated. Here, we describe the case of a 39-year-old male with SBMA who commenced anti-androgen therapy with leuprorelin 1 year previously; this was followed by cybernic treatment with HAL. The duration of walking exercise with HAL was 20–30 min a day in one session. Over 2 weeks, the patient underwent nine sessions (one course). The efficacy of HAL was evaluated by gait function tests before and after one course of cybernic treatment. Then, leuprorelin treatment was combined with cybernic sessions every 2 months for 2 years (13 courses in total). Walking ability, as evaluated by the 2-min walk test, improved by 20.3% in the first course and peaked 10 months after the commencement of combined therapy (a 59.0% improvement). Walking function was maintained throughout the period. Generally, SBMA is characterized by moderately increased serum levels of creatine kinase (CK), reflecting neuromuscular damage; interestingly, the patient's CK levels decreased dramatically with combined therapy, indicating remarkable functional improvement. Long-term combined therapy improved the patient's gait function with a steady reduction in CK levels. The combination of leuprorelin with cybernic treatment can, therefore, improve and maintain gait function without damaging the motor unit and may also suppress disease progression.