bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal Aortic Aneurysm: Can the Anaconda™ Custom-Made Device Deliver? An International Perspective
Authors: Jubouri Matti , Surkhi Abedalaziz O. , Tan Sven Z. C. P. , Bailey Damian M. , Williams Ian M. , Bashir Mohamad
Published: July 2022

Introduction

Since the introduction of endovascular aortic repair (EVAR), it has demonstrated excellent clinical outcomes and has replaced open surgical repair (OSR) in the treatment of abdominal aortic aneurysms (AAA). AAA is a life-threatening abnormal dilation of the abdominal aorta to 1.5 times its normal diameter. Several commercial EVAR devices exist on the global market, with the Terumo Aortic Fenestrated Anaconda™ graft showing superiority. In this study, we sought to provide an international perspective using multicenter-multinational data on the Anaconda™ device characteristics, design, and delivery, and discuss relevant literature.

Materials and Methods

This study represents a cross-sectional international analysis of custom-made fenestrated Anaconda™ device. Ethical and legal approval for data collection was obtained from each of the local authorities. For the statistical analysis, SPSS 28 for Windows and R were utilized. Pearson’s chi-square analysis was used to assess differences in cumulative distribution frequencies between select variables. Statistical significance for all two-tailed tests was set at p < 0.05.

Results

A total of 5,030 Anaconda™ devices were implanted during the 9-year study period in 27 countries spanning 6 continents. The predominant device category was bifurcate (83.6%), whereas the most common proximal ring stent configuration being standard (64.5%). All devices were delivered within 8 weeks of diagnosis, with most being implanted within 6–8 weeks (55.4%). The Anaconda™ was indicated in the 3,891 (77.4%) patients due to competitor rejection/inability to treat unsuitable/complex aortic anatomy. In the remaining 1,139 (22.6%) patients, it was utilized based on surgeon preference. Almost all devices (95%) were delivered along with a prototype. Of the total 5,030 Anaconda™ devices, 438 (8.7%) used 0–1 fenestrations, 2,349 (46.7%) used 2–3, while 2,243 (44.6%) utilized 4, 5, or 6 fenestrations.

Discussion

The Terumo Aortic Fenestrated Anaconda™ device features a highly unique and innovative design that enables it to treat highly complex aortic anatomy while achieving excellent results. The Anaconda™’s custom-made approach allows it to be tailored to individual patient anatomy, in addition to the device prototype provided by Terumo Aortic optimize clinical outcomes. Finally, the fenestrated Anaconda™ is a highly versatile device offering a wide range of device categories, configurations, and sizes.
Ethics of AI in Radiology: A Review of Ethical and Societal Implications
Authors: Goisauf Melanie , Cano Abadía Mónica
Published: July 2022

Artificial intelligence (AI) is being applied in medicine to improve healthcare and advance health equity. The application of AI-based technologies in radiology is expected to improve diagnostic performance by increasing accuracy and simplifying personalized decision-making. While this technology has the potential to improve health services, many ethical and societal implications need to be carefully considered to avoid harmful consequences for individuals and groups, especially for the most vulnerable populations. Therefore, several questions are raised, including (1) what types of ethical issues are raised by the use of AI in medicine and biomedical research, and (2) how are these issues being tackled in radiology, especially in the case of breast cancer? To answer these questions, a systematic review of the academic literature was conducted. Searches were performed in five electronic databases to identify peer-reviewed articles published since 2017 on the topic of the ethics of AI in radiology. The review results show that the discourse has mainly addressed expectations and challenges associated with medical AI, and in particular bias and black box issues, and that various guiding principles have been suggested to ensure ethical AI. We found that several ethical and societal implications of AI use remain underexplored, and more attention needs to be paid to addressing potential discriminatory effects and injustices. We conclude with a critical reflection on these issues and the identified gaps in the discourse from a philosophical and STS perspective, underlining the need to integrate a social science perspective in AI developments in radiology in the future.
Spermatozoa Develop Molecular Machinery to Recover From Acute Stress
Authors: Starovlah Isidora M. , Radovic Pletikosic Sava M. , Tomanic Tamara M. , Medar Marija LJ. , Kostic Tatjana S. , Andric Silvana A.
Published: July 2022

This study was designed to search for the possible mechanism(s) of male (in/sub)fertility by following the molecular response of spermatozoa on acute psychological stress (the most common stress in human society) and on a 20-h time-dependent recovery period. To mimic in vivo acute stress, the rats were exposed to immobilization once every 3 h. The recovery periods were as follows: 0 (immediately after stress and 3 h after the light is on—ZT3), 8 (ZT11), 14 (ZT17), and 20 (ZT23) h after stress. Results showed that acute stress provoked effects evident 20 h after the end of the stress period. Numbers of spermatozoa declined at ZT17 and ZT23, while functionality decreased at ZT3 and ZT11, but recovered at ZT17 and ZT23. Transcriptional profiles of 91% (20/22) of tracked mitochondrial dynamics and functionality markers and 91% (20/22) of signaling molecules regulating both mitochondrial dynamics and spermatozoa number/functionality were disturbed after acute stress and during the recovery period. Most of the changes presented as increased transcription or protein expression at ZT23. The results of the principal component analysis (PCA) showed the clear separation of acute stress recovery effects during active/dark and inactive/light phases. The physiological relevance of these results is the recovered positive-acrosome-reaction, suggesting that molecular events are an adaptive mechanism, regulated by acute stress response signaling. The results of the PCA confirmed the separation of the effects of acute stress recovery on gene expression related to mitochondrial dynamics, cAMP, and MAPK signaling. The transcriptional patterns were different during the active and inactive phases. Most of the transcripts were highly expressed during the active phase, which is expected given that stress occurred at the beginning of the inactive phase. To the best of our knowledge, our results provide a completely new view and the first presentation of the markers of mitochondrial dynamics network in spermatozoa and their correlation with signaling molecules regulating both mitochondrial dynamics and spermatozoa number and functionality during recovery from acute stress. Moreover, the interactions between the proteins important for spermatozoa homeostasis and functionality (MFN2 and PRKA catalytic subunit, MFN2 and p38MAPK) are shown for the first time. Since the existing literature suggests the importance of semen quality and male fertility not only as the fundamental marker of reproductive health but also as the fundamental biomarkers of overall health and harbingers for the development of comorbidity and mortality, we anticipate our result to be a starting point for more investigations considering the mitochondrial dynamics markers or their transcriptional profiles as possible predictors of (in/sub)fertility.
Diagnostic Performance of Sex-Specific Modified Metabolite Patterns in Urine for Screening of Prediabetes
Authors: Li Zaifang , Zhang Yanhui , Hoene Miriam , Fritsche Louise , Zheng Sijia , Birkenfeld Andreas , Fritsche Andreas , Peter Andreas , Liu Xinyu , Zhao Xinjie , Zhou Lina , Luo Ping , Weigert Cora , Lin Xiaohui , Xu Guowang , Lehmann Rainer
Published: July 2022

Aims/Hypothesis

Large-scale prediabetes screening is still a challenge since fasting blood glucose and HbA1c as the long-standing, recommended analytes have only moderate diagnostic sensitivity, and the practicability of the oral glucose tolerance test for population-based strategies is limited. To tackle this issue and to identify reliable diagnostic patterns, we developed an innovative metabolomics-based strategy deviating from common concepts by employing urine instead of blood samples, searching for sex-specific biomarkers, and focusing on modified metabolites.

Methods

Non-targeted, modification group-assisted metabolomics by liquid chromatography–mass spectrometry (LC-MS) was applied to second morning urine samples of 340 individuals from a prediabetes cohort. Normal (n = 208) and impaired glucose-tolerant (IGT; n = 132) individuals, matched for age and BMI, were randomly divided in discovery and validation cohorts. ReliefF, a feature selection algorithm, was used to extract sex-specific diagnostic patterns of modified metabolites for the detection of IGT. The diagnostic performance was compared with conventional screening parameters fasting plasma glucose (FPG), HbA1c, and fasting insulin.

Results

Female- and male-specific diagnostic patterns were identified in urine. Only three biomarkers were identical in both. The patterns showed better AUC and diagnostic sensitivity for prediabetes screening of IGT than FPG, HbA1c, insulin, or a combination of FPG and HbA1c. The AUC of the male-specific pattern in the validation cohort was 0.889 with a diagnostic sensitivity of 92.6% and increased to an AUC of 0.977 in combination with HbA1c. In comparison, the AUCs of FPG, HbA1c, and insulin alone reached 0.573, 0.668, and 0.571, respectively. Validation of the diagnostic pattern of female subjects showed an AUC of 0.722, which still exceeded the AUCs of FPG, HbA1c, and insulin (0.595, 0.604, and 0.634, respectively). Modified metabolites in the urinary patterns include advanced glycation end products (pentosidine-glucuronide and glutamyl-lysine-sulfate) and microbiota-associated compounds (indoxyl sulfate and dihydroxyphenyl-gamma-valerolactone-glucuronide).

Conclusions/Interpretation

Our results demonstrate that the sex-specific search for diagnostic metabolite biomarkers can be superior to common metabolomics strategies. The diagnostic performance for IGT detection was significantly better than routinely applied blood parameters. Together with recently developed fully automatic LC-MS systems, this opens up future perspectives for the application of sex-specific diagnostic patterns for prediabetes screening in urine.
Altered Glucose Metabolism and Glucose Transporters in Systemic Organs After Bariatric Surgery
Authors: Oh Ju Hun , Kang Chan Woo , Wang Eun Kyung , Nam Jung Ho , Lee Soohyun , Park Kyeong Hye , Lee Eun Jig , Cho Arthur , Ku Cheol Ryong
Published: July 2022

The Roux-en-Y gastric bypass (RYGB) is highly effective in the remission of obesity and associated diabetes. The mechanisms underlying obesity and type 2 diabetes mellitus remission after RYGB remain unclear. This study aimed to evaluate the changes in continuous dynamic FDG uptake patterns after RYGB and examine the correlation between glucose metabolism and its transporters in variable endocrine organs using 18F-fluoro-2-deoxyglucose positron emission tomography images. Increased glucose metabolism in specific organs, such as the small intestine and various fat tissues, is closely associated with improved glycemic control after RYGB. In Otsuka Long-Evans Tokushima Fatty rats fed with high-fat diets, RYGB operation increases intestine glucose transporter expression and various fat tissues’ glucose transporters, which are not affected by insulin. The fasting glucose decrement was significantly associated with RYGB, sustained weight loss, post-RYGB oral glucose tolerance test (OGTT) area under the curve (AUC), glucose transporter, or glycolytic enzymes in the small bowel and various fat tissues. High intestinal glucose metabolism and white adipose tissue-dependent glucose metabolism correlated with metabolic benefit after RYGB. These findings suggest that the newly developed glucose biodistribution accompanied by increased glucose transporters is a mechanism associated with the systemic effect of RYGB.
Influence of sperm DNA fragmentation on the clinical outcome of in vitro fertilization-embryo transfer (IVF-ET)
Authors: Zhu Chunhui , Chen Fang , Zhang Shengmin , She Hong , Ju Yun , Wen Xidong , Yang Chunxia , Sun Yan , Dong Naijun , Xue Tongmin , Liu Kaifeng , Li Feng , Cui Hengmi
Published: July 2022

Purpose

To evaluate the effect of elevated sperm DNA fragmentation index (DFI) on fresh and frozen embryo transfer cycles.

Methods

A retrospective study was performed with 549 fresh embryo transfer cycles and 1340 frozen embryo transfer cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) from 2016 to 2021.

Results

The statistical results of 549 fresh embryo transfer cycles showed that the delivery rate in the normal sperm DFI group (43.9% vs. 27.1%, P = 0.014) was significantly higher than that in the abnormal sperm DFI group, and there were no significant differences in the biochemical pregnancy rate (59.0% vs. 50.8%, P = 0.232), clinical pregnancy rate (53.1% vs. 40.7%, P = 0.072), or miscarriage rate (17.3% vs. 33.3%, P = 0.098) between the two groups. The results of 1340 frozen embryo transfer cycles showed that the biochemical pregnancy rate (57.9% vs. 45.6%, P = 0.006) and clinical pregnancy rate (50.3% vs. 40.7%, P = 0.027) in the normal sperm DFI group were significantly higher than those in the abnormal sperm DFI group. The delivery rate (40.9% vs. 33.3%, P = 0.074) and miscarriage rate (18.6% vs. 18.0%, P = 0.919) were not significantly different between the two groups.

Conclusion

The increase of sperm DFI significantly reduced the delivery rate of fresh embryo transfer cycles and the biochemical pregnancy rate and clinical pregnancy rate of frozen embryo transfer cycles.
Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities
Authors: Chen Long , Chen Fukun , Niu Huatao , Li Jindan , Pu Yongzhu , Yang Conghui , Wang Yue , Huang Rong , Li Ke , Lei Yujie , Huang Yunchao
Published: July 2022

Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.
Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota
Authors: Li Xiaomin , Chen Ting , Wu Xiaofen , Li Zhuobo , Zhang Xin , Jiang Xiao , Luo Peng , Hu Chaoqun , Wong Nai-Kei , Ren Chunhua
Published: July 2022

Heavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicologically modulated by marine metal pollutants such as cadmium (Cd). The processes underpinning Cd’s toxic effects on immune systems in the sea cucumber, Holothuria leucospilota, are still poorly understood. To this end, we cloned and characterized a full-length caspase-9 (Hl-CASP9) cDNA in the sea cucumber, Holothuria leucospilota. Hl-CASP9 mRNA levels evolved dynamically during embryonic development. Coelomocytes, a type of phagocytic immune effectors central to H. leucospilota immunity, were found to express Hl-CASP9 mRNA most abundantly. Hl-CASP9 protein structurally resembles caspases-2 and -9 in both invertebrate and vertebrate species, comprising a CARD domain and a CASc domain. Remarkably, Hl-CASP9 was transcriptionally sensitive to abiotic oxidative stress inducers including hydrogen peroxide (H2O2), nitric oxide (•NO) and cadmium (Cd), but insensitive to immunostimulants including lipopolysaccharide (LPS), and poly(I:C). Overexpression of Hl-CASP9 augmented mitochondria-dependent apoptosis in HEK293T cells, while knock-down of Hl-CASP9 blunted Cd-induced coelomocyte apoptosis in vivo. Overall, we illustrate that an evolutionarily ancient caspase-9-dependent pathway exists to sensitize coelomocytes to premature cell death precipitated by heavy metal pollutants, with important implications for negative modulation of organismal immune response in marine invertebrates.
elk1/miR-462-731 Feedback Loop Regulates Macrophages Polarization and Phagocytosis in Grass Carp (Ctenopharyngodon idella)
Authors: He Yan , Liu Yuting , Yang Yuyue , Liu Yang , Jia Xuewen , Shen Yubang , Xu Xiaoyan , Li Jiale
Published: July 2022

MicroRNA clusters are microRNAs (miRNAs) that are distributed in close proximity on chromosomes. In this study, we report a miRNA cluster identified from grass carp (Ctenopharyngodon idella), miR-462-731, which plays a positive role in host antibacterial immunity. The expression of miR-462-731 was disrupted after infection by Aeromonas hydrophila. Transcription factor ETS transcription factor ELK1 was identified to bind to the promoter of the miR-462-731 cluster and suppress its expression. In addition, miR-731 negatively regulates the expression of elk1, forms an elk1/miR-462-731 double negative feedback loop. In addition, we found that miR-731 directly targets ezrin a (ezra), participates in inducing PI3K/AKT signaling in macrophage, to induce macrophage polarization to the M1 phenotype with stronger phagocytosis. Our results demonstrate a novel elk1/miR-462-731 feedback loop. The data deepen our understanding of the relationship between macrophage polarization and phagocytosis in teleost fish.
CRISPR/Cas Genome Editing—Can It Become a Game Changer in Future Fisheries Sector?
Authors: Roy Suvra , Kumar Vikash , Behera Bijay Kumar , Parhi Janmejay , Mohapatra Sipra , Chakraborty Tapas , Das Basanta Kumar
Published: July 2022

Fisheries and aquaculture are the fastest-growing food-producing sector and rapidly becoming an important element for the global food security since they are the primary source of seafood and high animal protein in the human diet. Genome editing offers new possibilities such as the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas9) technology, which has the potential to accelerate the sustainable genetic improvement in fisheries and aquaculture. The CRISPR/Cas9 system has four key components, namely, target DNA, Cas9, the protospacer adjacent motif sequence, and the guide RNA or single-guide RNA. CRISPR/Cas is cheaper, easier, and more precise than the other genome editing technologies and can be used as a new breeding technology in fisheries and aquaculture to solve the far-reaching challenges. The attributes like high fecundity, external fertilization, short generation interval, the established method of breeding, and the larval rearing of most aquaculture species have advantages for CRISPR/Cas9 genome editing applications. CRISPR/Cas9 has recently been applied to the traits valued in some aquaculture species (almost >20 species), targeting the main traits of traditional genetic improvement initiatives like growth, disease resistance, reproduction, sterility, and pigmentation. Genome editing can fast forward the breeding process with precision where changes occur in the targeted genes. The probability of desired changes occurring and passing the trait in the next generation is high, so it takes 1-3 generations to establish a breed. Moreover, CRISPR/Cas genome editing rapidly introduces favorable changes by disrupting genes with targeted minor changes, in contrast to transgenesis, which introduces foreign genes into the host genome and thereby alleviates major public concerns on safety. Although the CRISPR/Cas technology has a tremendous potential, there are several technical challenges and regulatory and public issues concerning the applications in fisheries and the aquaculture breeding sector. Nonetheless, the exciting point in the CRISPR/Cas9 genome editing is that two CRISPR-edited fish, namely, red sea bream and tiger puffer developed by the Kyoto-based startup got approval and are now on the market for sale, and another fish, FLT-01 Nile tilapia developed by the AquaBounty, is not classified under genetically modified organism regulatory. However, there is still a way to go before it revolutionizes and becomes viable in commercial aquaculture as the new breeding technology for aquaculture-important traits and species.
Steroids Therapy in Patients With Severe COVID-19: Association With Decreasing of Pneumonia Fibrotic Tissue Volume
Authors: He Jin-wei , Su Ying , Qiu Ze-song , Wu Jiang-jie , Chen Jun , Luo Zhe , Zhang Yuyao
Published: July 2022

Background

We use longitudinal chest CT images to explore the effect of steroids therapy in COVID-19 pneumonia which caused pulmonary lesion progression.

Materials and Methods

We retrospectively enrolled 78 patients with severe to critical COVID-19 pneumonia, among which 25 patients (32.1%) who received steroid therapy. Patients were further divided into two groups with severe and significant-severe illness based on clinical symptoms. Serial longitudinal chest CT scans were performed for each patient. Lung tissue was segmented into the five lung lobes and mapped into the five pulmonary tissue type categories based on Hounsfield unit value. The volume changes of normal tissue and pneumonia fibrotic tissue in the entire lung and each five lung lobes were the primary outcomes. In addition, this study calculated the changing percentage of tissue volume relative to baseline value to directly demonstrate the disease progress.

Results

Steroid therapy was associated with the decrease of pneumonia fibrotic tissue (PFT) volume proportion. For example, after four CT cycles of treatment, the volume reduction percentage of PFT in the entire lung was −59.79[±12.4]% for the steroid-treated patients with severe illness, and its p-value was 0.000 compared to that (−27.54[±85.81]%) in non-steroid-treated ones. However, for the patient with a significant-severe illness, PFT reduction in steroid-treated patients was −41.92[±52.26]%, showing a 0.275 p-value compared to −37.18[±76.49]% in non-steroid-treated ones. The PFT evolution analysis in different lung lobes indicated consistent findings as well.

Conclusion

Steroid therapy showed a positive effect on the COVID-19 recovery, and its effect was related to the disease severity.
Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review
Authors: Lombardi Yannis , François Hélène
Published: July 2022

The current gold standard to prevent allograft rejection for maintenance immunosuppression in kidney transplantation currently consists in glucocorticoids, an antiproliferative agent and a calcineurin inhibitor (CNI), with better outcome for tacrolimus than cyclosporin. Although, CNI drastically improved early graft survival, so far, CNI have failed to significantly improve long-term survival mainly because of nephrotoxicity. In addition, CNI carry several other side effects such as an increased risk for cardiovascular events and for diabetes mellitus. Therefore, seeking alternatives to CNI remains of paramount importance in kidney transplantation. Belatacept is a fusion protein composed of the human IgG1 Fc fragment linked to the modified extracellular domain of cytotoxic T lymphocyte–associated antigen 4. In kidney transplant recipients, pivotal phase III randomized studies suggested clinical benefits of belatacept as an initial maintenance regimen, as compared with cyclosporine, mainly on kidney function. Recently, a randomized study also suggested a clinical benefit on renal function of a conversion from a CNI-based to a belatacept-based maintenance regimen in patients. However, conversion from CNIs to belatacept is probably associated with an increased risk of biopsy-proven acute rejection and should prompt close clinical surveillance. On the other hand, other studies suggest a decrease in de novo humoral transplant immunization. Belatacept is probably associated with an increase in both risk and severity of some infectious diseases, including EBV-linked post-transplantation lymphoproliferative disorders, and with a decreased response to vaccines. Most studies on belatacept are observational, retrospective, and non-comparative. Consequently, high-quality data about the safety and efficacy profile of belatacept, as compared with the current gold standard for maintenance regimens (tacrolimus-based), is uncertain. Our review will therefore focus on the most recent published data aiming at evaluating the evidence-based or the “true” benefits and risks of belatacept-based regimens in kidney transplantation.
Diversity and Selection of Surface Marine Microbiomes in the Atlantic-Influenced Arctic
Authors: Aalto Nerea J. , Schweitzer Hannah D. , Krsmanovic Stina , Campbell Karley , Bernstein Hans C.
Published: July 2022

Arctic marine environments are experiencing rapid changes due to the polar amplification of global warming. These changes impact the habitat of the cold-adapted microbial communities, which underpin biogeochemical cycles and marine food webs. We comparatively investigated the differences in prokaryotic and microeukaryotic taxa between summer surface water microbiomes sampled along a latitudinal transect from the ice-free southern Barents Sea and into the sea-ice-covered Nansen Basin to disentangle the dominating community (ecological) selection processes driving phylogenetic diversity. The community structure and richness of each site-specific microbiome were assessed in relation to the physical and biogeochemical conditions of the environment. A strong homogeneous deterministic selection process was inferred across the entire sampling transect via a phylogenetic null modeling approach. The microbial species richness and diversity were not negatively influenced by northward decreasing temperature and salinity. The results also suggest that regional phytoplankton blooms are a major prevalent factor in governing the bacterial community structure. This study supports the consideration that strong homogeneous selection is imposed across these cold-water marine environments uniformly, regardless of geographic assignments within either the Nansen Basin or the Barents Sea.
The Role of Chicken Prolactin, Growth Hormone and Their Receptors in the Immune System
Authors: Mo Guodong , Hu Bowen , Wei Ping , Luo Qingbin , Zhang Xiquan
Published: July 2022

Prolactin (PRL) and growth hormone (GH) exhibit important roles in the immune system maintenance. In poultry, PRL mainly plays its roles in nesting, hatching, and reproduction, while GH is primarily responding to body weight, fat formation and feed conversion. In this review, we attempt to provide a critical overview of the relationship between PRL and GH, PRLR and GHR, and the immune response of poultry. We also propose a hypothesis that PRL, GH and their receptors might be used by viruses as viral receptors. This may provide new insights into the pathogenesis of viral infection and host immune response.
The Unique Seed Protein Composition of Quality Protein Popcorn Promotes Growth of Beneficial Bacteria From the Human Gut Microbiome
Authors: Korth Nate , Parsons Leandra , Van Haute Mallory J. , Yang Qinnan , Hurst Preston , Schnable James C. , Holding David R. , Benson Andrew K.
Published: July 2022

The effects of fiber, complex carbohydrates, lipids, and small molecules from food matrices on the human gut microbiome have been increasingly studied. Much less is known about how dietary protein can influence the composition and function of the gut microbial community. Here, we used near-isogenic maize lines of conventional popcorn and quality-protein popcorn (QPP) to study the effects of the opaque-2 mutation and associated quality-protein modifiers on the human gut microbiome. Opaque-2 blocks the synthesis of major maize seed proteins (α-zeins), resulting in a compensatory synthesis of new seed proteins that are nutritionally beneficial with substantially higher levels of the essential amino acids lysine and tryptophan. We show that QPP lines stimulate greater amounts of butyrate production by human gut microbiomes in in vitro fermentation of popped and digested corn from parental and QPP hybrids. In human gut microbiomes derived from diverse individuals, bacterial taxa belonging to the butyrate-producing family Lachnospiraceae, including the genera Coprococcus and Roseburia were consistently increased when fermenting QPP vs. parental popcorn lines. We conducted molecular complementation to further demonstrate that lysine-enriched seed protein can stimulate growth and butyrate production by microbes through distinct pathways. Our data show that organisms such as Coprococcus can utilize lysine and that other gut microbes, such as Roseburia spp., instead, utilize fructoselysine produced during thermal processing (popping) of popcorn. Thus, the combination of seed composition in QPP and interaction of protein adducts with carbohydrates during thermal processing can stimulate the growth of health-promoting, butyrate-producing organisms in the human gut microbiome through multiple pathways.
Improving the Diagnosis of Bacterial Infections: Evaluation of 16S rRNA Nanopore Metagenomics in Culture-Negative Samples
Authors: Bouchiat Coralie , Ginevra Christophe , Benito Yvonne , Gaillard Tiphaine , Salord Hélène , Dauwalder Olivier , Laurent Frédéric , Vandenesch François
Published: July 2022

While 16S rRNA PCR-Sanger sequencing has paved the way for the diagnosis of culture-negative bacterial infections, it does not provide the composition of polymicrobial infections. We aimed to evaluate the performance of the Nanopore-based 16S rRNA metagenomic approach, using both partial and full-length amplification of the gene, and to explore its feasibility and suitability as a routine diagnostic tool for bacterial infections in a clinical laboratory. Thirty-one culture-negative clinical samples from mono- and polymicrobial infections based on Sanger-sequencing results were sequenced on MinION using both the in-house partial amplification and the Nanopore dedicated kit for the full-length amplification of the 16S rRNA gene. Contamination, background noise definition, bacterial identification, and time-effectiveness issues were addressed. Cost optimization was also investigated with the miniaturized version of the flow cell (Flongle). The partial 16S approach had a greater sensitivity compared to the full-length kit that detected bacterial DNA in only 24/31 (77.4%) samples. Setting a threshold of 1% of total reads overcame the background noise issue and eased the interpretation of clinical samples. Results were obtained within 1 day, discriminated polymicrobial samples, and gave accurate bacterial identifications compared to Sanger-based results. We also found that multiplexing and using Flongle flow cells was a cost-effective option. The results confirm that Nanopore technology is user-friendly as well as cost- and time-effective. They also indicate that 16S rRNA targeted metagenomics is a suitable approach to be implemented for the routine diagnosis of culture-negative samples in clinical laboratories.
APOE Is Associated With Serum Tau Following Uncomplicated Mild Traumatic Brain Injury
Authors: Lippa Sara M. , Lange Rael T. , Dalgard Clifton L. , Soltis Anthony R. , Guedes Vivian A. , Brickell Tracey A. , French Louis M. , Gill Jessica
Published: July 2022

Background and Objectives

APOE e4 has been linked to poor outcome following traumatic brain injury (TBI); however, the mechanisms behind this relationship are unclear. Few studies have investigated the relationship between the APOE genotype and established brain related protein biomarkers following TBI. The purpose of this study was to examine this relationship in service members and veterans (SMVs) following TBI.

Methods

Participants were 209 SMVs [124 uncomplicated mild TBI (mTBI); 85 complicated mild, moderate, severe, or penetrating TBI (mod-sev TBI)] prospectively enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI Study. APOE genotyping was undertaken using non-fasting blood serum samples. Participants were divided into three groups: APOE e2+, APOE e3/e3, and APOE e4+.

Results

In participants with mTBI, those with the APOE e2 allele had significantly lower levels of tau than those with APOE e4 (p = 0.005, r = 0.43, medium-large effect size). Those with APOE e3/e3 trended toward having higher tau than those APOE e2+ (p = 0.076, r = 0.20, small-medium effect size) and lower tau than those with APOE e4+ (p = 0.062, r = 0.21, small-medium effect size). There were no significant differences in biomarkers based on APOE in the mod-sev TBI group.

Discussion

This study is the first to demonstrate APOE genotype is related to serum tau levels following a mTBI, extending prior findings to human serum following mTBI. In addition to higher serum tau levels in APOE e4 carriers, lower tau levels were observed in APOE e2 carriers, suggesting a possible protective effect.
Ischemic Stroke at a Tertiary Academic Hospital in Tanzania: A Prospective Cohort Study With a Focus on Presumed Large Vessel Occlusion
Authors: Matuja Sarah Shali , Ahmed Rashid Ali , Munseri Patricia , Khanbhai Khuzeima , Tessua Kezia , Lyimo Frederick , Rodriguez Gustavo J. , Gupta Vikas , Maud Alberto , Chaudhury Mohammad Rauf , Manji Mohamed , Sheriff Faheem
Published: July 2022

Background

Large vessel ischemic strokes account for more than one-third of all strokes associated with substantial morbidity and mortality without early intervention. The incidence of large vessel occlusion (LVO) is not known in sub-Saharan Africa (SSA). Definitive vessel imaging is not routinely available in resource-limited settings.

Aims

We aimed to investigate the burden and outcomes of presumed LVO among patients with ischemic stroke admitted to a large tertiary academic hospital in Tanzania.

Methods

This cohort study recruited all consenting first-ever ischemic stroke participants admitted at a tertiary hospital in Tanzania. Demographic data were recorded, and participants were followed up to 1 year using the modified Rankin Scale (mRS). A diagnosis of presumed LVO was made by a diagnostic neuroradiologist and interventional neurologist based on contiguous ischemic changes in a pattern consistent with proximal LVO on a non-contrast computed tomography head. We examined factors associated with presumed LVO using logistic regression analysis. Inter-observer Kappa was calculated.

Results

We enrolled 158 first-ever ischemic strokes over 8 months with a mean age of 59.7 years. Presumed LVO accounted for 39.2% [95% confidence interval (CI) 31.6–47.3%] and an overall meantime from the onset of stroke symptoms to hospital arrival was 1.74 days. Participants with presumed LVO were more likely to involve the middle cerebral artery (MCA) territory (70.9%), p < 0.0001. Independent factors on multivariate analysis associated with presumed LVO were hypertension [adjusted odds ratio (aOR) 5.74 (95% CI: 1.74–18.9)] and increased waist-hip ratio [aOR 7.20 (95% CI: 1.83–28.2)]. One-year mortality in presumed LVO was 80% when compared with 73.1% in participants without presumed LVO. The Cohen's Kappa inter-observer reliability between the diagnostic neuroradiologist and interventional neurologist was 0.847.

Conclusion

There is a high burden of presumed LVO associated with high rates of 1-year morbidity and mortality at a tertiary academic hospital in Tanzania. Efforts are needed to confirm these findings with definitive vessel imaging, promoting cost-effective preventive strategies to reduce the burden of non-communicable diseases (NCDs), and a call for adopting endovascular therapies to reduce morbidity and mortality.
Absence of Susceptibility Vessel Sign in Patients With Malignancy-Related Acute Ischemic Stroke Treated With Mechanical Thrombectomy
Authors: Beyeler Morin , Belachew Nebiyat F. , Kielkopf Moritz , Aleman Enrique B. , León Betancourt Alejandro Xavier , Genceviciute Kotryna , Kurmann Christoph , Grunder Lorenz , Birner Barbara , Meinel Thomas R. , Scutelnic Adrian , Bücke Philipp , Seiffge David J. , Dobrocky Tomas , Piechowiak Eike I. , Pilgram-Pastor Sara , Mattle Heinrich P. , Mordasini Pasquale , Arnold Marcel , Fischer Urs , Pabst Thomas , Gralla Jan , Berger Martin D. , Jung Simon , Kaesmacher Johannes
Published: July 2022

Background and Purpose

Clots rich in platelets and fibrin retrieved from patients with acute ischemic stroke (AIS) have been shown to be independently associated with the absence of the susceptibility vessel sign (SVS) on MRI and active malignancy. This study analyzed the association of SVS and the presence of active malignancy in patients with AIS who underwent mechanical thrombectomy (MT).

Methods

This single-center, retrospective, and cross-sectional study included consecutive patients with AIS with admission MRI treated with MT between January 2010 and December 2018. SVS status was evaluated on susceptibility-weighted imaging. Adjusted odds ratios (aORs) were calculated to determine the association between absent SVS and the presence of active or occult malignancy. The performance of predictive models incorporating and excluding SVS status was compared using areas under the receiver operating characteristics curve (auROC).

Results

Of 577 patients with AIS with assessable SVS status, 40 (6.9%) had a documented active malignancy and 72 (12.5%) showed no SVS. The absence of SVS was associated with active malignancy (aOR 4.85, 95% CI 1.94–12.11) or occult malignancy (aOR 11.42, 95% CI 2.36–55.20). The auROC of predictive models, including demographics and common malignancy biomarkers, was higher but not significant (0.85 vs. 0.81, p = 0.07) when SVS status was included.

Conclusion

Absence of SVS on admission MRI of patients with AIS undergoing MT is associated with malignancy, regardless of whether known or occult. Therefore, the SVS might be helpful in detecting paraneoplastic coagulation disorders and occult malignancy in patients with AIS.
Montreal Brain Injury Vision Screening Test for General Practitioners
Authors: Abbas Farishta Reza , Farivar Reza
Published: July 2022

Visual disturbances are amongst the most commonly reported symptoms after a traumatic brain injury (TBI) despite vision testing being uncommon at initial clinical evaluation. TBI patients consistently present a wide range of visual complaints, including photophobia, double vision, blurred vision, and loss of vision which can detrimentally affect reading abilities, postural balance, and mobility. In most cases, especially in rural areas, visual disturbances of TBI would have to be diagnosed and assessed by primary care physicians, who lack the specialized training of optometry. Given that TBI patients have a restricted set of visual concerns, an opportunity exists to develop a screening protocol for specialized evaluation by optometrists—one that a primary care physician could comfortably carry out and do so in a short time. Here, we designed a quick screening protocol that assesses the presence of core visual symptoms present post-TBI. The MOBIVIS (Montreal Brain Injury Vision Screening) protocol takes on average 5 min to perform and is composed of only “high-yield” tests that could be performed in the context of a primary care practice and questions most likely to reveal symptoms needing further vision care management. The composition of our proposed protocol and questionnaire are explained and discussed in light of existing protocols. Its potential impact and ability to shape a better collaboration and an integrative approach in the management of mild TBI (mTBI) patients is also discussed.
Evaluation of a New Lightweight EEG Technology for Translational Applications of Passive Brain-Computer Interfaces
Authors: Sciaraffa Nicolina , Di Flumeri Gianluca , Germano Daniele , Giorgi Andrea , Di Florio Antonio , Borghini Gianluca , Vozzi Alessia , Ronca Vincenzo , Babiloni Fabio , Aricò Pietro
Published: July 2022

Technologies like passive brain-computer interfaces (BCI) can enhance human-machine interaction. Anyhow, there are still shortcomings in terms of easiness of use, reliability, and generalizability that prevent passive-BCI from entering real-life situations. The current work aimed to technologically and methodologically design a new gel-free passive-BCI system for out-of-the-lab employment. The choice of the water-based electrodes and the design of a new lightweight headset met the need for easy-to-wear, comfortable, and highly acceptable technology. The proposed system showed high reliability in both laboratory and realistic settings, performing not significantly different from the gold standard based on gel electrodes. In both cases, the proposed system allowed effective discrimination (AUC > 0.9) between low and high levels of workload, vigilance, and stress even for high temporal resolution (<10 s). Finally, the generalizability of the proposed system has been tested through a cross-task calibration. The system calibrated with the data recorded during the laboratory tasks was able to discriminate the targeted human factors during the realistic task reaching AUC values higher than 0.8 at 40 s of temporal resolution in case of vigilance and workload, and 20 s of temporal resolution for the stress monitoring. These results pave the way for ecologic use of the system, where calibration data of the realistic task are difficult to obtain.
Automatic Schizophrenia Detection Using Multimodality Media via a Text Reading Task
Authors: Zhang Jing , Yang Hui , Li Wen , Li Yuanyuan , Qin Jing , He Ling
Published: July 2022

Schizophrenia is a crippling chronic mental disease that affects people worldwide. In this work, an automatic schizophrenia detection algorithm is proposed based on the reading deficit of schizophrenic patients. From speech and video modalities, the automatic schizophrenia detection algorithm illustrates abnormal speech, head movement, and reading fluency during the reading task. In the speech modality, an acoustic model of speech emotional flatness in schizophrenia is established to reflect the emotional expression flatness of schizophrenic speech from the perspective of speech production and perception. In the video modality, the head-movement-related features are proposed to illustrate the spontaneous head movement caused by repeated reading and unconscious movement, and the reading-fluency-related features are proposed to convey the damaged degree of schizophrenic patients' reading fluency. The experimental data of this work are 160 segments of speech and video data recorded by 40 participants (20 schizophrenic patients and 20 normal controls). Combined with support vector machines and random forest, the accuracy of the proposed acoustic model, the head-movement-related features, and the reading-fluency-related features range from 94.38 to 96.50%, 73.38 to 83.38%, and 79.50 to 83.63%, respectively. The average accuracy of the proposed automatic schizophrenia detection algorithm reaches 97.50%. The experimental results indicate the effectiveness of the proposed automatic detection algorithm as an auxiliary diagnostic method for schizophrenia.
Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice
Authors: Li Yufeng , Yu Huiqian , Zhou Xuehua , Jin Lin , Li Wen , Li Geng-Lin , Shen Xia
Published: July 2022

Objectives

This study aims to investigate the effects of multiple sevoflurane exposures in neonatal mice on hearing function in the later life and explores the underlying mechanisms and protective strategies.

Materials and Methods

Neonatal Kunming mice were exposed to sevoflurane for 3 days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests, immunofluorescence, patch-clamp recording, and quantitative real-time PCR were performed to observe hearing function, hair cells, ribbon synapses, nerve fibers, spiral ganglion neurons, and oxidative stress.

Results

Compared to control group, multiple sevoflurane exposures during the neonatal time significantly elevated ABR thresholds at 8 kHz (35.42 ± 1.57 vs. 41.76 ± 1.97 dB, P = 0.0256), 16 kHz (23.33 ± 1.28 vs. 33.53 ± 2.523 dB, P = 0.0012), 24 kHz (30.00 ± 2.04 vs. 46.76 ± 3.93 dB, P = 0.0024), and 32 kHz (41.25 ± 2.31 vs. 54.41 ± 2.94 dB, P = 0.0028) on P30, caused ribbon synapse loss on P15 (13.10 ± 0.43 vs. 10.78 ± 0.52, P = 0.0039) and P30 (11.24 ± 0.56 vs. 8.50 ± 0.84, P = 0.0141), and degenerated spiral ganglion neuron (SGN) nerve fibers on P30 (110.40 ± 16.23 vs. 55.04 ± 8.13, P = 0.0073). In addition, the Vhalf of calcium current become more negative (−21.99 ± 0.70 vs. −27.17 ± 0.60 mV, P < 0.0001), exocytosis was reduced (105.40 ± 19.97 vs. 59.79 ± 10.60 fF, P < 0.0001), and Lpo was upregulated (P = 0.0219) in sevoflurane group than those in control group. N-acetylcysteine (NAC) reversed hearing impairment induced by sevoflurane.

Conclusion

The findings suggest that multiple sevoflurane exposures during neonatal time may cause hearing impairment in adult mice. The study also demonstrated that elevated oxidative stress led to ribbon synapses impairment and SGN nerve fibers degeneration, and the interventions of antioxidants alleviated the sevoflurane-induced hearing impairment.
Awareness and consciousness in humans and animals – neural and behavioral correlates in an evolutionary perspective
Authors: Ehret Günter , Romand Raymond
Published: July 2022

Awareness or consciousness in the context of stimulus perception can directly be assessed in well controlled test situations with humans via the persons’ reports about their subjective experiences with the stimuli. Since we have no direct access to subjective experiences in animals, their possible awareness or consciousness in stimulus perception tasks has often been inferred from behavior and cognitive abilities previously observed in aware and conscious humans. Here, we analyze published human data primarily on event-related potentials and brain-wave generation during perception and responding to sensory stimuli and extract neural markers (mainly latencies of evoked-potential peaks and of gamma-wave occurrence) indicating that a person became aware or conscious of the perceived stimulus. These neural correlates of consciousness were then applied to sets of corresponding data from various animals including several species of mammals, and one species each of birds, fish, cephalopods, and insects. We found that the neural markers from studies in humans could also successfully be applied to the mammal and bird data suggesting that species in these animal groups can become subjectively aware of and conscious about perceived stimuli. Fish, cephalopod and insect data remained inconclusive. In an evolutionary perspective we have to consider that both awareness of and consciousness about perceived stimuli appear as evolved, attention-dependent options added to the ongoing neural activities of stimulus processing and action generation. Since gamma-wave generation for functional coupling of brain areas in aware/conscious states is energetically highly cost-intensive, it remains to be shown which animal species under which conditions of lifestyle and ecological niche may achieve significant advantages in reproductive fitness by drawing upon these options. Hence, we started our discussion about awareness and consciousness in animals with the question in how far these expressions of brain activity are necessary attributes for perceiving stimuli and responding in an adaptive way.