bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of mean platelet volume/lymphocyte ratio with inflammation in non-dialysis patients with chronic kidney disease stages 1–4: A retrospective study
Authors: Xu Bei , Zhang Yamei , Chen Gang , Feng Jiafu , Gan Lingling
Published: November 2022

Objective

The mean platelet volume/ratio (MPVLR) is recognized as a novel marker of inflammation. We evaluated whether the MPVLR is associated with inflammation in non-dialysis patients with chronic kidney disease (CKD) stages 1–4.

Methods

A total of 402 non-dialysis patients with CKD stages 1–4 were included. The indicators of hematological, renal function (urea, serum creatinine [Scr], estimated glomerular filtration rate [eGFR], and urine albumin to creatinine ratio [ACR]) and the markers of inflammation (high-sensitivity C-reactive protein [hsCRP] and fibrinogen [FIB]) were recorded. The MPVLR values at different CKD stages were analyzed. Next, based on the absence (hsCRP level < 5 mg/L) and presence (hsCRP level > 5 mg/L) of inflammation, the patients were categorized, and the differences in indices between the two groups were observed. The patients were divided into two groups based on the median MPVLR value (6.39) at admission. The laboratory indices of patients with CKD were compared. Simultaneously, a correlation analysis was performed to identify the association between the MPVLR and each parameter. A binary logistic regression analysis was performed to test whether the MPVLR was associated independently with the presence of inflammation in non-dialysis patients with CKD. The receiver operating characteristic (ROC) curve was used to analyzed diagnostic performance of the MPVLR in evaluating the inflammation of non-dialysis patients with CKD stages 1-4.

Results

The MPVLR was higher in patients with CKD stages 3–4 than in those with CKD stages 1 and 2. Significant differences in urea, Scr, eGFR, ACR, lymphocyte (LYM), red blood cell (RBC), hemoglobin (HGB), RBC distribution width (RDW-CV), MPVLR, and FIB values were observed between the groups with and without inflammation. The patients with a higher MPVLR had higher urea, Scr, ACR, WBC, neutrophils (NEU), RDW-CV, platelet distribution width (PDW), mean platelet volume (MPV), and hsCRP values and lower eGFR, LYM, RBC, HGB, and platelet (PLT) values. The MPVLR showed a positive correlation with age, urea, Scr, WBC, NEU, RDW-CV, PDW, MPV, and hsCRP values and a negative correlation with the eGFR, LYM, RBC, HGB, and PLT values. A logistic analysis revealed that the MPVLR was associated independently with the presence of inflammation in non-dialysis patients with CKD, after adjustment for the confounding factors (odds ratio = 1.020; P = 0.024). Furthermore, MPVLR exhibited a modest diagnostic performance for the assessment of inflammation in non-dialysis patients with CKD stages 1-4, with an area under the curve (AUC) of 0.706, and the sensitivity, specificity being 46.2% and 83.2%, respectively.

Conclusions

The MPVLR was associated independently with the presence of inflammation in non-dialysis patients with CKD and may be useful for monitoring inflammation.
The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model
Authors: Graham Peter T. , Nowak Anna K. , Cornwall Scott M. J. , Larma Irma , Nelson Delia J.
Published: November 2022

We assessed the murine Stimulator of Interferon Genes (STING) agonist, DMXAA, for anti-mesothelioma potential using the AE17-sOVA model that expresses ovalbumin (OVA) as a neo tumor antigen. Dose response experiments alongside testing different routes of administration identified a safe effective treatment regimen that induced 100% cures in mice with small or large tumors. Three doses of 25mg/kg DMXAA given intra-tumorally every 9 days induced tumor regression and long-term survival (>5 months). Re-challenge experiments showed that tumor-free mice developed protective memory. MTT and propidium-iodide assays showed that DMXAA exerted direct cytotoxic effects at doses >1mg/ml on the murine AE17 and AB1 mesothelioma cell lines. In-vivo studies using a CFSE-based in-vivo proliferation assay showed that DMXAA improved tumor-antigen presentation in tumor-draining lymph nodes, evidenced by OVA-specific OT-1 T cells undergoing more divisions. An in-vivo cytotoxic T lymphocyte (CTL) assay showed that DMXAA blunted the lytic quality of CTLs recognizing the dominant (SIINFEKL) and a subdominant (KVVRFDKL) OVA epitopes. DMXAA reduced tumor vessel size in-vivo and although the proportion of T cells infiltrating tumors reduced, the proportion of tumor-specific T cells increased. These data show careful dosing and treatment protocols reduce mesothelioma cell viability and modulate tumor vessels such that tumor-antigen specific CTLs access the tumor site. However, attempts to enhance DMXAA-induced anti-tumor responses by combination with an agonist anti-CD40 antibody or IL-2 reduced efficacy. These proof-of-concept data suggest that mesothelioma patients could benefit from treatment with a STING agonist, but combination with immunotherapy should be cautiously undertaken.
China’s regulatory respond to plastic pollution: Trends and trajectories
Authors: Fürst Kathinka , Feng Yidi
Published: November 2022

Despite China having an international reputation as one of the largest contributors to plastic pollution in the world’s oceans, research analyzing China’s regulatory approach to governing plastic has been limited and fragmented, and as such, little is known about trends and trajectories dominating China’s plastic policy landscape. In this paper, we seek to address this gap in the literature through the construction and analysis of a complete inventory of China plastic-related policies from 1 January 2000 to 30 June 2021. Utilizing NVIVO (a qualitative analysis software), our analysis of 231 Chinese plastic policy documents shows that China’s serious and concentrated effort to governing plastics really took off in the year 2016. From 2016, China saw a rapid increase in the attention paid to plastic pollution in the regulatory realm. In 2000, there were only four plastic-pertinent policies, but by the first half of 2021, this number has grown to 41, representing an increase of 925%. In this period, China has also significantly transformed its approach to governing plastics; not only has the goal and purpose of regulating plastic increased in complexity, but the type of plastics targeted and the different aspects of the plastic value chain included in various policies have become increasingly comprehensive over time. Concurrently, the deployment of different types of regulatory instruments utilized for the purpose of governing plastics in China has become much more diversified, with a major focus on prohibitive bans and information campaigns currently dominating Chinese plastic policy instruments. Economic policy instruments, on the other hand, especially economic incentives, have only recently been gaining popularity. Finally, today, most government agencies have published policies that are relevant to the regulation of plastic pollution control and prevention in China. Despite the massive increase in plastic pertinent policies in China, the predominant focus is still on back-end policy, with little regulatory attention on the upstream part of the plastic lifecycle (i.e., prodigious production of plastics). China’s fairly recent plastic policy awakening should be understood in light of China’s focus on the circular economy, the county’s ramping up of regulatory focus, and fiscal investment in solid waste management and pertinent infrastructure. Towards the end of the paper, we point to some possible trajectories for the China plastic policy landscape, highlighting the synergies between reducing plastic production, consumption, and waste treatment and China’s carbon neutrality ambition, as well as predicting a stronger policy focus and emphasis on plastic cleanup efforts.
Atomistic simulations of dislocation plasticity in concentrated VCoNi medium entropy alloys: Effects of lattice distortion and short range order
Authors: Esfandiarpour Amin , Alvarez-Donado Rene , Papanikolaou Stefanos , Alava Mikko
Published: November 2022

Face-centered cubic (fcc) high and medium entropy alloys (H/MEAs) have been shown to display superior mechanical properties at low temperatures, but significant improvement of their strength at high temperatures is required for industrial applications at extreme conditions. Recently, it has been shown that the breakthrough of the MEAs from equiatomic/near-equiatomic to non-equiatomic ratios leads to strong MEAs with good ductility. To design new H/MEAs, we consider two important factors that may influence strength: the chemical composition and chemical short range order (CSRO). In this study, we investigate the depinning stress (σc) as a criterion of strength of several compositions of VCoNi concentrated solid solution alloys (CSSAs) including V0.33Co0.33Ni0.33, V0.35Co0.2Ni0.45, V0.33Co0.17Ni0.5, and V0.17Co0.33Ni0.5 at 5 K and 300 K, using atomistic simulations. The chosen interatomic potential is shown to be reliable by comparing experimental/ab initio values and calculated parameters such as lattice constant, shear modulus, depinning stress, and temperature variation of stacking fault width for equimolar VCoNi. We find a good agreement between experimental friction stress and the depinning stress extracted from our results for equimolar VCoNi. Also, we find that Vclusters are the main pinning points of dislocations, and With a random distribution of atoms, we find that the alloy composition V0.33Co0.17Ni0.5 displays the largest depinning stress at both 5 and 300 K. Furthermore, to investigate how CSRO affects the strength of these alloys, we design CSRO into the microstructure using two different methods: In the first method, hybrid Molecular-dynamics/Monte-Carlo simulations were employed to simulate annealing at various temperatures. We observe that such simulations create CSRO so that it increases with decreasing annealing temperature. Recently, the CSRO motif and its concentration in an equimolar VCoNi have been determined by experiment. By modeling this experiment, we also implemented the CSRO into microstructure as the second method. By using both methods, the effect of CSRO on the magnitude of the depinning stress is discussed. It was shown that in both methods, CSRO significantly influences the strength of non-equimolar VCoNi alloys.
Path planning and intelligent control of a soft robot arm based on gas-structure coupling actuators
Authors: Xu Yan , Li Hongwei , Li Hua , Fang Guanhui , Jia He
Published: November 2022

A fully 3D-printed soft pneumatic robotic arm based on two types of gas-structure coupling actuators is designed for on-orbit servicing. The path planning algorithm and trajectory tracking control strategy of the arm are developed. A model-free closed-loop control system with a PID controller and an iterative learning controller is built to improve the performance speed for repeated tasks. An experiential knowledge database for an iterative learning controller is described. The effectiveness of the iterative learning controller is verified by comparative experiments. The obstacle avoidance path planning algorithm based on the A* algorithm is presented. The validity of the path planning algorithm and trajectory tracking control strategy are verified by obstacle avoidance path planning experiments. The experimental results show that intelligent motion control and obstacle avoidance of the fully 3D-printed soft robotic arms are realized within an acceptable error.
AlphaBet: Combination of Radium-223 and [177Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol)
Authors: Kostos Louise , Buteau James P. , Yeung Theresa , Iulio Juliana Di , Xie Jing , Cardin Anthony , Chin Kwang Y. , Emmerson Brittany , Owen Katie L. , Parker Belinda S. , Fettke Heidi , Furic Luc , Azad Arun A. , Hofman Michael S.
Published: November 2022

Background

[177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 μm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses.

Methods

This is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&T, concurrently with 223Ra in escalating doses (28 kBq/kg – 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&T and the 50% PSA response rate.

Conclusion

The AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months.

Study registration

NCT05383079.
Advances and challenges in automated malaria diagnosis using digital microscopy imaging with artificial intelligence tools: A review
Authors: Maturana Carles Rubio , de Oliveira Allisson Dantas , Nadal Sergi , Bilalli Besim , Serrat Francesc Zarzuela , Soley Mateu Espasa , Igual Elena Sulleiro , Bosch Mercedes , Lluch Anna Veiga , Abelló Alberto , López-Codina Daniel , Suñé Tomàs Pumarola , Clols Elisa Sayrol , Joseph-Munné Joan
Published: November 2022

Malaria is an infectious disease caused by parasites of the genus Plasmodium spp. It is transmitted to humans by the bite of an infected female Anopheles mosquito. It is the most common disease in resource-poor settings, with 241 million malaria cases reported in 2020 according to the World Health Organization. Optical microscopy examination of blood smears is the gold standard technique for malaria diagnosis; however, it is a time-consuming method and a well-trained microscopist is needed to perform the microbiological diagnosis. New techniques based on digital imaging analysis by deep learning and artificial intelligence methods are a challenging alternative tool for the diagnosis of infectious diseases. In particular, systems based on Convolutional Neural Networks for image detection of the malaria parasites emulate the microscopy visualization of an expert. Microscope automation provides a fast and low-cost diagnosis, requiring less supervision. Smartphones are a suitable option for microscopic diagnosis, allowing image capture and software identification of parasites. In addition, image analysis techniques could be a fast and optimal solution for the diagnosis of malaria, tuberculosis, or Neglected Tropical Diseases in endemic areas with low resources. The implementation of automated diagnosis by using smartphone applications and new digital imaging technologies in low-income areas is a challenge to achieve. Moreover, automating the movement of the microscope slide and image autofocusing of the samples by hardware implementation would systemize the procedure. These new diagnostic tools would join the global effort to fight against pandemic malaria and other infectious and poverty-related diseases.
Antarctic Sphingomonas sp. So64.6b showed evolutive divergence within its genus, including new biosynthetic gene clusters
Authors: Núñez-Montero Kattia , Rojas-Villalta Dorian , Barrientos Leticia
Published: November 2022

Introduction

The antibiotic crisis is a major human health problem. Bioprospecting screenings suggest that proteobacteria and other extremophile microorganisms have biosynthetic potential for the production novel antimicrobial compounds. An Antarctic Sphingomonas strain (So64.6b) previously showed interesting antibiotic activity and elicitation response, then a relationship between environmental adaptations and its biosynthetic potential was hypothesized. We aimed to determine the genomic characteristics in So64.6b strain related to evolutive traits for the adaptation to the Antarctic environment that could lead to its diversity of potentially novel antibiotic metabolites.

Methods

The complete genome sequence of the Antarctic strain was obtained and mined for Biosynthetic Gene Clusters (BGCs) and other unique genes related to adaptation to extreme environments. Comparative genome analysis based on multi-locus phylogenomics, BGC phylogeny, and pangenomics were conducted within the closest genus, aiming to determine the taxonomic affiliation and differential characteristics of the Antarctic strain.

Results and discussion

The Antarctic strain So64.6b showed a closest identity with Sphingomonas alpina, however containing a significant genomic difference of ortholog cluster related to degradation multiple pollutants. Strain So64.6b had a total of six BGC, which were predicted with low to no similarity with other reported clusters; three were associated with potential novel antibiotic compounds using ARTS tool. Phylogenetic and synteny analysis of a common BGC showed great diversity between Sphingomonas genus but grouping in clades according to similar isolation environments, suggesting an evolution of BGCs that could be linked to the specific ecosystems. Comparative genomic analysis also showed that Sphingomonas species isolated from extreme environments had the greatest number of predicted BGCs and a higher percentage of genetic content devoted to BGCs than the isolates from mesophilic environments. In addition, some extreme-exclusive clusters were found related to oxidative and thermal stress adaptations, while pangenome analysis showed unique resistance genes on the Antarctic strain included in genetic islands. Altogether, our results showed the unique genetic content on Antarctic strain Sphingomonas sp. So64.6, −a probable new species of this genetically divergent genus–, which could have potentially novel antibiotic compounds acquired to cope with Antarctic poly-extreme conditions.
Isolation of novel cold-tolerance genes from rhizosphere microorganisms of Antarctic plants by functional metagenomics
Authors: de Francisco Martínez Patricia , Morgante Verónica , González-Pastor José Eduardo
Published: November 2022

The microorganisms that thrive in Antarctica, one of the coldest environments on the planet, have developed diverse adaptation mechanisms to survive in these extreme conditions. Through functional metagenomics, in this work, 29 new genes related to cold tolerance have been isolated and characterized from metagenomic libraries of microorganisms from the rhizosphere of two Antarctic plants. Both libraries were hosted in two cold-sensitive strains ofEscherichia coli:DH10B ΔcsdAand DH10B ΔcsdA Δrnr. ThecsdAgene encodes a DEAD-box RNA helicase andrnrgene encodes an exoribonuclease, both essential for cold-adaptation. Cold-tolerance tests have been carried out in solid and liquid media at 15°C. Among the cold-tolerance genes identified, 12 encode hypothetical and unknown proteins, and 17 encode a wide variety of different proteins previously related to other well-characterized ones involved in metabolism reactions, transport and membrane processes, or genetic information processes. Most of them have been connected to cold-tolerance mechanisms. Interestingly, 13 genes had no homologs inE. coli, thus potentially providing entirely new adaptation strategies for this bacterium. Moreover, ten genes also conferred resistance to UV-B radiation, another extreme condition in Antarctica.
The advances in the regulation of immune microenvironment by Candida albicans and macrophage cross-talk
Authors: Zhao Shuo , Shang Anquan , Guo Mengchen , Shen Liangliang , Han Yu , Huang Xin
Published: November 2022

Candida albicans (C. albicans) is the most common causative agent of invasive fungal infections in hospitals. The body defends against and eliminates C. albicans infection by various mechanisms of immune response, and the latter mechanism of immune evasion is a major challenge in the clinical management of C. albicans infection. The role of macrophages in combating C. albicans infection has only recently been recognized, but the mechanisms remain to be elucidated. This review focuses on the interaction between C. albicans and macrophages (macrophages), which causes the body to generate an immune response or C. albicans immune escape, and then regulates the body’s immune microenvironment, to explore the effect of C. albicans virulence resistance vs. macrophage killing and clarify the role and mechanism of C. albicans pathogenesis. In general, a thorough understanding of the molecular principles driving antifungal drug resistance is essential for the development of innovative treatments that can counteract both existing and emerging fungal threats.
Revisiting the role of cyanobacteria-derived metabolites as antimicrobial agent: A 21st century perspective
Authors: Kar Joyeeta , Ramrao Devde Pandurang , Zomuansangi Ruth , Lalbiaktluangi C. , Singh Shiv Mohan , Joshi Naveen Chandra , Kumar Ajay , Kaushalendra  , Mehta Suryakant , Yadav Mukesh Kumar , Singh Prashant Kumar
Published: November 2022

Cyanobacterial species are ancient photodiazotrophs prevalent in freshwater bodies and a natural reservoir of many metabolites (low to high molecular weight) such as non-ribosomal peptides, polyketides, ribosomal peptides, alkaloids, cyanotoxins, and isoprenoids with a well-established bioactivity potential. These metabolites enable cyanobacterial survival in extreme environments such as high salinity, heavy metals, cold, UV-B, etc. Recently, these metabolites are gaining the attention of researchers across the globe because of their tremendous applications as antimicrobial agents. Many reports claim the antimicrobial nature of these metabolites; unfortunately, the mode of action of such metabolites is not well understood and/or known limited. Henceforth, this review focuses on the properties and potential application, also critically highlighting the possible mechanism of action of these metabolites to offer further translational research. The review also aims to provide a comprehensive insight into current gaps in research on cyanobacterial biology as antimicrobials and hopes to shed light on the importance of continuing research on cyanobacteria metabolites in the search for novel antimicrobials.
The protective immunity induced by intranasally inoculated serotype 63 chimpanzee adenovirus vector expressing human respiratory syncytial virus prefusion fusion glycoprotein in BALB/c mice
Authors: Huang Lei , Liu Mei-Qing , Wan Chang-Qing , Cheng Ning-Ning , Su Yan-Bin , Zheng Yan-Peng , Peng Xiang-Lei , Yu Jie-Mei , Fu Yuan-Hui , He Jin-Sheng
Published: November 2022

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the full-length and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development.
Microalgae production in human urine: Fundamentals, opportunities, and perspectives
Authors: Tao Yewen , Liu Zhipeng , Zheng Junjian , Zhou Jieqin , He Di , Ma Jinxing
Published: November 2022

The biological treatment of source-separated human urine to produce biofuel, nutraceutical, and high-value chemicals is getting increasing attention. Especially, photoautotrophic microalgae can use human urine as media to achieve environmentally and economically viable large-scale cultivation. This review presents a comprehensive overview of the up-to-date advancements in microalgae cultivation employing urine in photobioreactors (PBRs). The standard matrices describing algal growth and nutrient removal/recovery have been summarized to provide a platform for fair comparison among different studies. Specific consideration has been given to the critical operating factors to understand how the PBRs should be maintained to achieve high efficiencies. Finally, we discuss the perspectives that emphasize the impacts of co-existing bacteria, contamination by human metabolites, and genetic engineering on the practical microalgal biomass production in urine.
Internet of medical things-enabled CRISPR diagnostics for rapid detection of SARS-CoV-2 variants of concern
Authors: Lin Huihuang , Zheng Weibo , Li Shenwei , Wang Yu , Wei Dong , Xie Leiying , Lu Wei , Tian Zhengan , Wang Shaowei , Qu Jieming , Liu Jia
Published: November 2022

Previous studies have highlighted CRISPR-based nucleic acid detection as rapid and sensitive diagnostic methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported an optimized CRISPR-Cas12a diagnostic platform for the safe and rapid detection of SARS-CoV-2 variants of concern (VOCs). This platform, which was referred to as CALIBURN-v2, could complete the diagnosis on extracted RNA samples within 25 min in a closed-lid reaction mode and had 100-fold increase in detection sensitivity in comparison with previous platforms. Most importantly, by integrating a portable device and smartphone user interface, CALIBURN-v2 allowed for cloud server-based data collection and management, thus transforming the point-of-care testing (POCT) platform to internet of medical things (IoMT) applications. It was found that IoMT-enabled CALIBURN-v2 could achieve 95.56% (172 out of 180) sensitivity for SARS-CoV-2 wild type and 94.38% (84 out of 89) overall sensitivity for SARS-CoV-2 variants including Delta and Omicron strains. Therefore, our study provides a feasible approach for IoMT-enabled CRISPR diagnostics for the detection of SARS-CoV-2 VOCs.
Deep learning approaches for noncoding variant prioritization in neurodegenerative diseases
Authors: Lan Alexander Y. , Corces M. Ryan
Published: November 2022

Determining how noncoding genetic variants contribute to neurodegenerative dementias is fundamental to understanding disease pathogenesis, improving patient prognostication, and developing new clinical treatments. Next generation sequencing technologies have produced vast amounts of genomic data on cell type-specific transcription factor binding, gene expression, and three-dimensional chromatin interactions, with the promise of providing key insights into the biological mechanisms underlying disease. However, this data is highly complex, making it challenging for researchers to interpret, assimilate, and dissect. To this end, deep learning has emerged as a powerful tool for genome analysis that can capture the intricate patterns and dependencies within these large datasets. In this review, we organize and discuss the many unique model architectures, development philosophies, and interpretation methods that have emerged in the last few years with a focus on using deep learning to predict the impact of genetic variants on disease pathogenesis. We highlight both broadly-applicable genomic deep learning methods that can be fine-tuned to disease-specific contexts as well as existing neurodegenerative disease research, with an emphasis on Alzheimer’s-specific literature. We conclude with an overview of the future of the field at the intersection of neurodegeneration, genomics, and deep learning.
Gait variability predicts cognitive impairment in older adults with subclinical cerebral small vessel disease
Authors: Mukli Peter , Detwiler Sam , Owens Cameron D. , Csipo Tamas , Lipecz Agnes , Pinto Camila Bonin , Tarantini Stefano , Nyul-Toth Adam , Balasubramanian Priya , Hoffmeister Jordan R. , Csiszar Anna , Ungvari Zoltan , Kirkpatrick Angelia C. , Prodan Calin I. , Yabluchanskiy Andriy
Published: November 2022

Introduction

Advanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD.

Methods

To test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions.

Results

Patients with CSVD exhibited lower performance in a visual learning test (p = 0.030) and in a sustained attention test (p = 0.007). CSVD also affected step time variability (p = 0.009) and step length variability (p = 0.017). Step lengths of CSVD participants were more asymmetric (p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups.

Discussion

Our findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD.
Effects of exercise types on white matter microstructure in late midlife adults: Preliminary results from a diffusion tensor imaging study
Authors: Chen Feng-Tzu , Soya Hideaki , Yassa Michael A. , Li Ruei-Hong , Chu Chien-Heng , Chen Ai-Guo , Hung Chiao-Ling , Chang Yu-Kai
Published: November 2022

Higher aerobic fitness during late midlife is associated with higher white matter (WM) microstructure. Compared with individuals engaged in irregular exercise, those who engage in regular aerobic exercise show higher fractional anisotropy (FA), a diffusion tenor imaging (DTI) measure that provides an index of WM microstructural integrity. However, whether other types of exercise, such as Tai Chi, can also facilitate WM changes in adults during late midlife remains unknown. The present study compares two types of exercise, Tai Chi and walking, with a sedentary control group, in order to examine the effects of exercise on WM microstructure and determine the regional specificity of WM differences. Thirty-six healthy adults between the ages of 55 and 65 years participated in the study. Based on the participants’ exercise habits, they were allocated into three groups: Tai Chi, walking, or sedentary control. All participants were required to complete physical fitness measurements and completed magnetic reasoning imaging (MRI) scans. Our results revealed that the Tai Chi group exhibited a higher FA value in the left cerebral peduncle, compared to the sedentary control group. We also observed that both the Tai Chi and walking groups exhibited higher FA values in the right uncinate fasciculus and the left external capsule, in comparison to the sedentary control group. Increased FA values in these regions was positively correlated with higher levels of physical fitness measurements (i.e., peak oxygen uptake [VO2peak], muscular endurance/number of push-up, agility, power). These findings collectively suggest that regular exercise is associated with improved WM microstructural integrity, regardless of the exercise type, which could guide the development and application of future prevention and intervention strategies designed to address age-related cognitive impairments during late midlife.
Prospects of TiO2-based photocatalytic degradation of microplastic leachates related disposable facemask, a major COVID-19 waste
Authors: Rex M Camil , Mukherjee Amitava
Published: November 2022

COVID-19 is one of the serious catastrophes that have a substantial influence on human health and the environment. Diverse preventive actions were implemented globally to limit its spread and transmission. Personnel protective equipment (PPE) was an important part of these control approaches. But unfortunately, these types of PPE mainly comprise plastics, which sparked challenges in the management of plastic waste. Disposable face masks (DFM) are one of the efficient strategies used across the world to ward off disease transmission. DFMs can contribute to micro and nano plastic pollution as the plastic present in the mask may degrade when exposed to certain environmental conditions. Microplastics (MPs) can enter the food chain and devastate human health. Recognizing the possible environmental risks associated with the inappropriate disposal of masks, it is crucial to avert it from becoming the next plastic crisis. To address this environmental threat, titanium dioxide (TiO2)-based photocatalytic degradation (PCD) of MPs is one of the promising approaches. TiO2-based photocatalysts exhibit excellent plastic degradation potential due to their outstanding photocatalytic ability, cost efficiency, chemical, and thermal stability. In this review, we have discussed the reports on COVID-19 waste generation, the limitation of current waste management techniques, and the environmental impact of MPs leachates from DFMs. Mainly, the prominence of TiO2 in the PCD and the applications of TiO2-based photocatalysts in MPs degradation are the prime highlights of this review. Additionally, various synthesis methods to enhance the photocatalytic performance of TiO2 and the mechanism of PCD are also discussed. Furthermore, current challenges and the future research perspective on the improvement of this approach have been proposed.
A robust zeroing neural network and its applications to dynamic complex matrix equation solving and robotic manipulator trajectory tracking
Authors: Jin Jie , Zhao Lv , Chen Lei , Chen Weijie
Published: November 2022

Dynamic complex matrix equation (DCME) is frequently encountered in the fields of mathematics and industry, and numerous recurrent neural network (RNN) models have been reported to effectively find the solution of DCME in no noise environment. However, noises are unavoidable in reality, and dynamic systems must be affected by noises. Thus, the invention of anti-noise neural network models becomes increasingly important to address this issue. By introducing a new activation function (NAF), a robust zeroing neural network (RZNN) model for solving DCME in noisy-polluted environment is proposed and investigated in this paper. The robustness and convergence of the proposed RZNN model are proved by strict mathematical proof and verified by comparative numerical simulation results. Furthermore, the proposed RZNN model is applied to manipulator trajectory tracking control, and it completes the trajectory tracking task successfully, which further validates its practical applied prospects.
The MeshCODE to scale—visualising synaptic binary information
Authors: Barnett Samuel F. H. , Goult Benjamin T.
Published: November 2022

The Mercator projection map of the world provides a useful, but distorted, view of the relative scale of countries. Current cellular models suffer from a similar distortion. Here, we undertook an in-depth structural analysis of the molecular dimensions in the cell’s computational machinery, the MeshCODE, that is assembled from a meshwork of binary switches in the scaffolding proteins talin and vinculin. Talin contains a series of force-dependent binary switches and each domain switching state introduces quantised step-changes in talin length on a micrometre scale. The average dendritic spine is 1 μm in diameter so this analysis identifies a plausible Gearbox-like mechanism for dynamic regulation of synaptic function, whereby the positioning of enzymes and substrates relative to each other, mechanically-encoded by the MeshCODE switch patterns, might control synaptic transmission. Based on biophysical rules and experimentally derived distances, this analysis yields a novel perspective on biological digital information.
Effectiveness of COVID-19 vaccines in a large European hemodialysis cohort
Authors: Bernardo Ana Paula , Carioni Paola , Stuard Stefano , Kotanko Peter , Usvyat Len A. , Kovarova Vratislava , Arkossy Otto , Bellocchio Francesco , Tupputi Antonio , Gervasoni Federica , Winter Anke , Zhang Yan , Zhang Hanjie , Ponce Pedro , Neri Luca
Published: November 2022

Background

Hemodialysis patients have high-risk of severe SARS-CoV-2 infection but were unrepresented in randomized controlled trials evaluating the safety and efficacy of COVID-19 vaccines. We estimated the real-world effectiveness of COVID-19 vaccines in a large international cohort of hemodialysis patients.

Methods

In this historical, 1:1 matched cohort study, we included adult hemodialysis patients receiving treatment from December 1, 2020, to May 31, 2021. For each vaccinated patient, an unvaccinated control was selected among patients registered in the same country and attending a dialysis session around the first vaccination date. Matching was based on demographics, clinical characteristics, past COVID-19 infections and a risk score representing the local background risk of infection at vaccination dates. We estimated the effectiveness of mRNA and viral-carrier COVID-19 vaccines in preventing infection and mortality rates from a time-dependent Cox regression stratified by country.

Results

In the effectiveness analysis concerning mRNA vaccines, we observed 850 SARS-CoV-2 infections and 201 COVID-19 related deaths among the 28110 patients during a mean follow up of 44 ± 40 days. In the effectiveness analysis concerning viral-carrier vaccines, we observed 297 SARS-CoV-2 infections and 64 COVID-19 related deaths among 12888 patients during a mean follow up of 48 ± 32 days. We observed 18.5/100-patient-year and 8.5/100-patient-year fewer infections and 5.4/100-patient-year and 5.2/100-patient-year fewer COVID-19 related deaths among patients vaccinated with mRNA and viral-carrier vaccines respectively, compared to matched unvaccinated controls. Estimated vaccine effectiveness at days 15, 30, 60 and 90 after the first dose of a mRNA vaccine was: for infection, 41.3%, 54.5%, 72.6% and 83.5% and, for death, 33.1%, 55.4%, 80.1% and 91.2%. Estimated vaccine effectiveness after the first dose of a viral-carrier vaccine was: for infection, 38.3% without increasing over time and, for death, 56.6%, 75.3%, 92.0% and 97.4%.

Conclusion

In this large, real-world cohort of hemodialyzed patients, mRNA and viral-carrier COVID-19 vaccines were associated with reduced COVID-19 related mortality. Additionally, we observed a strong reduction of SARS-CoV-2 infection in hemodialysis patients receiving mRNA vaccines.
A comparative analysis of body composition assessment by BIA and DXA in children with type II and III spinal muscular atrophy
Authors: Wang Wenqiao , Feng Yijie , Long Qi , Chen Fei , Chen Yuzhi , Ma Ming , Mao Shanshan
Published: November 2022

Background

Body composition analysis is a valuable tool for assessing and monitoring the nutritional status of children with spinal muscular atrophy (SMA). This study was designed to compare the consistency of bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), as the gold standard method for assessing body composition in clinical practice when treating children with type II and III SMA.

Methods

From 2019 to 2021, we performed a retrospective analysis of body composition by DXA and BIA measurement methods in patients with type II and III SMA treated at a Chinese tertiary children's hospital. Fat mass (FM), muscle mass (MM), bone mineral content (BMC), and visceral fat area (VFA) were compared using paired sample t-tests. We calculated Lin's concordance correlation coefficient (CCC) and Spearman correlation coefficient to verify the correlation between DXA and BIA measurements. Bland–Altman analysis was used to assess the consistency of the two methods.

Results

Fifty-seven children with type II and III SMA were recruited. Compared with body composition measured by DXA, the average FM measured by BIA is significantly lower (P <0.001), whereas the average MM, BMC, and VFA measured by BIA are significantly higher (P < 0.001) in children with SMA. Overall, the difference between MM (Delta [BIA-DAX] = 1.6 kg) and FM (Delta [BIA-DAX] = −1.6 kg) measured by DXA and BIA was minor, whereas the difference of VFA (Delta [BIA-DAX] = −43.5 cm) was significantly large. Correlation analysis indicated a substantial correlation of MM (CCC = 0.96 [95% confidence interval (CI) = 0.93–0.98], r = 0.967 [P < 0.0001]) and FM (CCC = 0.95 [95% CI = 0.92–0.97], r = 0.953 [P < 0.0001]), and poor correlation of BMC (CCC = 0.61 [95% CI = 0.42–0.75], r = 0.612 [P < 0.0001]) and VFA (CCC = 0.54 [95% CI = 0.33–0.70], r = 0.689 [P < 0.0001]) measurements between the two methods. The Bland–Altman analysis suggests that the majority of participants were within LOA. In addition, differences in MM and VFA measurements between BIA and DAX increased according to patients' increasing height, whereas differences in FM and BMC did not differ with height.

Conclusion

BIA overestimates MM and underestimates the FM, BMC, and VFA in children with SMA compared with DXA measurements. Overall, the non-invasive, easy-to-use, and repeatable BIA measurements were found to be in good agreement with DXA measurements, especially for FM and MM, which are essential parameters for the nutritional evaluation of children with SMA.
Affective Theory of Mind as a residual ability to preserve mentalizing in amnestic Mild Cognitive Impairment: A 12-months longitudinal study
Authors: Rossetto Federica , Isernia Sara , Cabinio Monia , Pirastru Alice , Blasi Valeria , Baglio Francesca
Published: November 2022

Introduction

Theory of Mind (ToM) decline has been outlined in people with amnestic Mild Cognitive Impairment (aMCI), but evidence from longitudinal studies is lacking. This longitudinal study aims to investigate changes in cognitive and affective ToM performance in an aMCI sample (n = 28; 14 females, mean age = 76.54 ± 4.35).

Method

Participants underwent two steps of neurocognitive evaluation, at the baseline (T1) and 12-month follow-up (T2), to obtain their global cognitive level and both affective (Reading the Mind in the Eyes test, ET) and cognitive (Strange Stories, SS) ToM profile. Then, participants were categorized into two groups based on ToM changes: people who worsened (ETΔ < 0; SSΔ < 0) and people who did not (ETΔ≥0; SSΔ≥0) at follow-up. Differences between groups in cognitive functions and ToM profiles at baseline have been investigated.

Results

Our results showed that 46% of subjects worsened in affective (ET) and 28% in cognitive (SS) ToM at follow-up. People who worsened in ET reported a statistically significantly higher performance in ET at baseline (p = 0.002) but not at follow-up than people who did not worsen. In contrast, subjects who worsened in SS showed a lower Immediate Free Recall (IFR, p = 0.026) and Delayed Free Recall (DFR, p = 0.028) score of the Free and Cued Selective Reminding test at baseline and at follow-up, a lower ET (p = 0.020) baseline score, a lower SS and MMSE level at follow-up than people who not worsened. About 71% of MCI subjects showed the same trend of evolution of the Mini-Mental State Examination and SS. Variables that significantly differed between groups have been inserted in a stepwise logistic regression to pilot explore predictors of affective and cognitive ToM evolution. Logistic regression showed ET at baseline (p = 0.015) as the only significant predictor of affective ToM evolution (R2 = 0.450), while both ET (p = 0.044) and memory performance (p = 0.045) at baseline significantly predicted cognitive ToM evolution (R2 = 0.746).

Discussion

In conclusion, our results support the role of affective ToM as a residual mentalizing ability in preserving the mentalizing level in people with aMCI.