bluuebunny/crossref_metadata_2025 huggingface dataset:
New management of surveillance in patients with baseline serrated polyps: a large single-center retrospective cohort study in China
Authors: Ye Xiangxi , Han Peiyi , Wu Zhijie , Cui Yun , Chen Yingxuan , Chen Zhaofei , Gao Qinyan
Published: December 2022

Background

Serrate d polyps (SP) is associated with an increased risk of colorectal cancer. Patients with SP history tend to have SP recurrence. However, the risk factors for metachronous polyps (MP) in those patients are not well established.

Methods

Data of colonoscopy were retrospectively reviewed from October 2012 to October 2021. The pathology database, electronic medical records and telephone follow-up data were also observed.

Results

A total of 906 patients were studied including 278 patients with MPs and 628 patients without. The multiplicity of polyps (OR, 13.63; 95% CI, 8.80–21.75), older age (OR, 5.71; 95% CI, 1.87–20.63), abdominal obesity (OR, 2.46; 95% CI, 0.98–6.42), current smoker (OR, 2.93; 95% CI, 1.15–7.83) and sedentary lifestyle (OR, 1.41; 95% CI, 1.22–1.65) are significantly associated with the risk of MPs. Patients with baseline SP < 10 mm were more likely to develop higher or same risk-grade polyps (HSRGP) (P = 0.0014). Patients with non-clinically significant SPs whether coexisted with adenoma or not were more likely to develop HSRGPs when compared to others (P < 0.001).

Conclusion

Total number of polyps, older age, sedentary behavior, abdominal obesity and smoking status contributed to the risk of MPs at surveillance colonoscopy. Patients with grade 1 SPs might require closer surveillance. SPs coexisting with conventional adenoma did not increase the risk of MPs but may increase the risk of developing HSRGPs.
Plasma Biomarkers and Fractional Exhaled Nitric Oxide in the Diagnosis of Eosinophilic Esophagitis
Authors: Josyabhatla Rohit , Abrenica Cristoniel , Mai Tu , Hashmi Syed Shahrukh , Liu Yuying , Mosquera Ricardo , Van Arsdall Melissa , Navarro Fernando , Tchakarov Amanda , Tatevian Nina , Wu Guoyao , Rhoads Jon Marc
Published: December 2022

Objectives:

Eosinophilic esophagitis (EoE) is a chronic disease which requires endoscopy with biopsies for diagnosis and monitoring. We aimed to identify a panel of non‐invasive markers that could help identify patients with active EoE.

Methods:

In this prospective cohort study, we enrolled 128 children aged 5–18 years old, scheduled for endoscopy for suspected esophageal or peptic disease. On the day of the endoscopy, fractionated exhaled nitric oxide (FeNO) was measured; and blood was collected for peripheral absolute eosinophil count (AEC), plasma amino acids, and plasma polyamine analysis. Patients were grouped into controls (n = 91), EoE in remission (n = 16), or active EoE (n = 21), based on esophageal eosinophilia and history of EoE.

Results:

AEC was not statistically significant different among the groups compared (P = 0.056). Plasma amino acids: citrulline (CIT), β‐alanine (β‐ALA), and cysteine (CYS) were higher in active EoE compared to controls (P < 0.05). The polyamine spermine was lower in active EoE versus controls (P < 0.05). Receiver operator characteristic (ROC) curve to assess the predictive capability of a combined score made of FeNO, β‐ALA, CYS, and spermine had an area under curve (AUC) of 0.90 (95% CI: 0.80–0.96) in differentiating active EoE from controls and 0.87 (95% CI: 0.74–1.00) when differentiating active EoE from EoE in remission.

Conclusion:

A panel comprising FeNO, 2 plasma amino acids (β‐ALA, CYS) and the polyamine spermine can be used as a non‐invasive tool to differentiate active EoE patients from controls.
Physician Burnout in Pediatric Gastroenterology
Authors: Chien Kimberley A. , Thomas Charlene , Cooley Victoria , Weinstein Toba , Murray Karen F. , Muir Linda , Hayes Christopher , Gold Benjamin D. , Gerber Linda M. , Sauer Cary G. , Tomer Gitit
Published: December 2022

Objectives:

Physicians are prone to burnout which can negatively affect the quality of patient care and lead to medical errors. Burnout can also affect physicians by impacting their personal relationships, their sense of career fulfillment, and job satisfaction. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a taskforce to investigate burnout among pediatric gastroenterologists.

Methods:

A 35‐item electronic survey was developed to collect demographic and practice information and characterize the well‐being of pediatric gastroenterologists. Burnout was assessed employing 2 single‐item measures adapted from the Maslach Burnout Inventory. The survey was distributed to NASPGHAN members 3 times from February 2020 to March 2020. Descriptive statistics, Chi‐square, and Fisher exact tests were used.

Results:

One thousand seven hundred ninety‐one e‐mails were successfully sent and 408 participants (22.7%) returned surveys. A total of 28.8% reported high risk for emotional exhaustion, 17.5% reported high risk for depersonalization, and 33% reported overall burnout. Participants 44 years of age or younger reported significantly more burnout than those 45 years and older (P = 0.018). Contributors to high burnout identified included increased patient load/demands, insufficient nursing support, electronic health record (EHR) use, insufficient administrative staff, excessive on‐call coverage, and more complex patients. Forty‐four percent reported not having enough time for their personal life including family. A total of 16.2% of participants reported that they would not choose to be a pediatric gastroenterologist again.

Conclusions:

Pediatric gastroenterologists are at risk for emotional exhaustion, depersonalization, and overall burnout. Strategies to prevent physician burnout should be implemented as soon as feasibly possible to improve individual mental health and patient care.
Diazepam induces retrograde facilitation of object recognition and object location memory in male mice
Authors: Iwashita Hikaru , Sano Masahiro , Chiba Atsuhiko
Published: December 2022

Benzodiazepines are widely prescribed for patients suffering from anxiety and insomnia. Although amnesic effects of benzodiazepines are commonly known as side effects, it has also been reported that these drugs improve memory for information learned before drug intake, a phenomenon called retrograde facilitation. However, the retrograde effects of benzodiazepines on cognitive performances in rodents remain controversial. It should be considered that studies on diazepam-induced retrograde facilitation in humans have been conducted using a recall paradigm focused on short-term memory, whereas these studies in rodents have been conducted using memory tasks that mainly target long-term memory and/or require negative or positive reinforcers. In the current study, we investigated whether diazepam, a benzodiazepine, induces retrograde facilitation for object recognition memory and spatial memory in mice, using a novel object recognition test and an object location test, respectively. These tests are available for short-term memory and do not require any reinforcer. The mice treated with diazepam retained object recognition memory for at least 180 min and spatial memory for at least 150 min. In contrast, vehicle-treated control mice retained object recognition memory for 120 min but not 150 min or longer, and spatial memory for 90 min but not 120 min or longer. These data clearly demonstrated diazepam-induced retrograde facilitation for both object recognition and spatial memories in mice. The present study is expected to contribute to the elucidation of the neural basis of retrograde facilitation.
Building Large-Scale Registries from Unstructured Clinical Notes using a Low-Resource Natural Language Processing Pipeline
Authors: Tavabi Nazgol , Pruneski James , Golchin Shahriar , Singh Mallika , Sanborn Ryan , Heyworth Benton , Kimia Amir , Kiapour Ata
Published: December 2022

Building clinical registries is an important step in improving the quality and safety of patient care. With the growing size of medical records, manual abstraction becomes more and more infeasible and impractical. On the other hand, Natural Language Processing Techniques have shown promising results in extracting valuable information from unstructured clinical notes. However, the structure and nature of clinical notes are very different from regular text that state-of-the-art NLP models are trained and tested on and they have their own set of challenges. In this study, we propose SE-K, an efficient and interpretable classification approach for extracting information from clinical notes, and show that it outperforms current state-of-the-art models in text classification. We use this approach to generate a 20-year comprehensive registry of anterior cruciate ligament reconstruction operations, one of the most common orthopedics operations among children and young adults. This registry can help us better understand the outcomes of this surgery and identify potential areas for improvement which can ultimately lead to better treatment outcomes.
Epitopes- Based Vaccine Design Against Foot and Mouth DiseaseSAT2Serotype from Sudanese Isolate by Using Immunoinformatic Approaches
Authors: Habiballa Inas. I. , Raouf Y. A , Alhaj M , Mohamed Sana. I. , Elhassan Reham M. , Salim Oubi. O. , Mustafa Essra , Mohamed A. , Ahmed K , Mona M , Sirdar Mohamed. M. , Hassan Mohammed A.
Published: December 2022

Foot and mouth disease (FMD) has been endemic in Sudan for decades and causes continuous outbreaks that have a direct negative impact on the animal population and prevent the exportation of animals from the country. The high diversity of FMD serotypes, especially SAT2 and A serotypes, hinders the development of effective vaccines since the most important component of vaccination is the degree of cross-protection provided by the vaccine against currently circulating field viruses. An immunoinformatic approach was utilized to predict a multi-epitope peptide vaccine design against theSAT2serotype from a Sudanese isolate targeting virus capsid regionP1. The virus capsid regionP1comprises the major immunogenic epitopes that confer protection against the FMD virus. Two predicted T-cell epitopes were identified that showed high binding affinity with MHC1 alleles (VQRSRQSTLandYHAEWDTGL) and high conservation with SAT2 African serotypes and were located within the VP1 and VP3 proteins, respectively. Only one epitope was predicted for B cells (LPATPEDAAH), which scored above the threshold in Bepipred linear epitope, Emini surface accessibility, and Kolaskar and Tongaonkar antigenicity and is located in VP3 protein. Molecular docking of the peptides (VQRSRQSTLandYHAEWDTGL) with the MHC1 allele showed satisfactory interaction with the binding sites of BoLA-HD6 using UCSF chimera 1.13.1 software. The peptideVQRSRQSTLshowed remarkable hydrophobic interaction with the BoLA-HD6 allele, which was superior to the other peptides. This study is the first to propose a peptide vaccine againstFMD SAT2serotypes from a Sudanese isolate.
Molecular evolution of protein sequences and codon usage in monkeypox viruses
Authors: Shan Ke-jia , Wu Changcheng , Tang Xiaolu , Lu Roujian , Tan Wenjie , Lu Jian
Published: December 2022

The monkeypox virus (mpox virus, MPXV) epidemic in 2022 poses a significant public health risk. However, the evolutionary principles of MPXV are largely unknown. Here, we examined the evolutionary patterns of protein sequences and codon usage in MPXV. We first showed the signal of positive selection inOPG027specifically in Clade I. We then discovered accelerated protein sequence evolution over time in 2022 outbreak-causing variants. We also found strong epistasis between amino acid substitutions located in different genes. Codon adaptation index (CAI) analysis revealed that MPXV tended to use more unpreferred codons than human genes and that the CAI decreased with time and diverged between clades, with Clade I > IIa and IIb-A > IIb-B. Although the decrease in fatality rate in the three groups matched the CAI pattern, it is unclear whether this is a coincidence or if the deoptimization of codon usage in MPXV induced a decrease in fatality. This study sheds new light on the processes influencing the evolution of MPXV in human populations.
Superinfection plays an important role in the acquisition of complexPlasmodium falciparuminfections among femaleAnophelesmosquitoes
Authors: Bérubé Sophie , Freedman Betsy , Menya Diana , Kipkoech Joseph , Abel Lucy , Lapp Zena , Taylor Steve M. , O’Meara Wendy Prudhomme , Obala Andrew A. , Wesolowski Amy
Published: December 2022

Studies of human malaria infections with multiple, genetically distinct parasites have illuminated mechanisms of malaria transmission. However, few studies have used the genetic diversity in mosquito infections to understand how transmission is sustained. We identified likely human sources of mosquito infections from a longitudinal cohort in Western Kenya based on genetic similarity between parasites and the timing of infections. We found that several human infections were required to reconstitute each mosquito infection and that multiple parasite clones were likely transmitted from infected humans to mosquitoes in each bite, suggesting that superinfection and co-transmission occur simultaneously and are important mechanisms of transmission. We further investigated this using an individual human and mosquito simulation model and found that co-transmission alone was unlikely to reproduce the high complexity of mosquito infections. We concluded that the superinfection of mosquitoes likely plays an important, but under studied, role in sustaining moderate to high malaria transmission.
Amplification and extraction free quantitative detection of viral nucleic acids and single-base mismatches using magnetic signal amplification circuit
Authors: Rösch Enja Laureen , Sack Rebecca , Chowdhury Mohammad Suman , Wolgast Florian , Schilling Meinhard , Viereck Thilo , Lak Aidin
Published: December 2022

Established nucleic acid detection assays require extraction and purification before sequence amplification and/or enzymatic reactions, hampering their widespread applications in point-of-care (POC) formats. Magnetic immunoassays based on magnetic particle spectroscopy and magnetic nanoparticles (MNPs) are isothermal, extraction- and purification-free, and can be quantitative and benchtop, making them suitable for POC settings. Here, we demonstrate a Magnetic signal Amplification Circuit (MAC) that combines specificity of toehold-mediated DNA strand displacement with magnetic response of MNPs to a clustering/declustering process. Our MAC assays require neither amplification nor extraction of target nucleic acids, and reveal four times better sensitivity than that of a magnetic circuit without signal amplification. Using MAC, we detect a highly specific 43 nucleotides sequence of SARS-CoV-2 virus. The MAC enables sensing both DNA and RNA targets with varying lengths and resolving single-base mismatches. Our MAC can be a powerful tool for translating research of nucleic acids detection to the clinic.
Structural insights into human ABCC4 mediated transport of platelet agonist and inhibitor
Authors: Chen Yu , Wang Liang , Hou Wen-Tao , Zha Zhi-Hui , Xu Kang , Zhou Cong-Zhao , Li Qiong , Chen Yuxing
Published: December 2022

The activation and accumulation of human platelets contributes to hemostasis and thrombosis, the imbalance of which would cause cardiovascular diseases, an increasing threat to the global health. Human ABC transporter ABCC4 that pumps out the platelet agonist and anti-platelet drug such as aspirin, might become a promising target for preventing cardiovascular diseases. Here we solve the structures of human ABCC4 in the apo and two complexed forms, all of which adopt a typical architecture of type-IV ABC transporters in an inward-facing conformation. Structure of ABCC4 complexed with U46619, an analog of the unstable TXA2, provides the first structural evidence that the platelet agonist TXA2is also exported via ABCC4. The dipyridamole-complexed structure reveals the inhibitory mechanism of dipyridamole against ABCC4. Structural comparisons enabled us to identify a transmembrane pocket in ABCC4 that provides a defined space for the rational design of specific anti-platelet drugs.
Genetic diversity, virulence, antimicrobial resistance genes, and antimicrobial susceptibility of group BStreptococcus(GBS) linked to mass mortalities of cultured Nile tilapia in Brazil
Authors: Assane Inácio Mateus , de Oliveira Neto Rubens Ricardo , de Abreu Reis Ferreira Daniel , do Vale Oliveira André , Hashimoto Diogo Teruo , Pilarski Fabiana
Published: December 2022

Streptococcus agalactiae, group BStreptococcus(GBS), is the main bacterial pathogen of cultured Nile tilapia in many countries and causes extensive deaths in all stages of the farming cycle throughout the year. This study investigated the genetic diversity, virulence, presence of antibiotic resistance genes and antimicrobial susceptibility of 72 GBS linked to mass mortalities of cultured Nile tilapia in Brazil. Isolate identity was confirmed by morphological, biochemical and molecular analyses. Capsular serotype, multi-locus sequence typing (MLST) allelic profiles and putative pathogenic factors were identified by polymerase chain reaction (PCR), gel electrophoresis, sequencing and molecular analyses of different genes. The presence of antimicrobial resistance genes and antimicrobial susceptibility to florfenicol (FFC), oxytetracycline (OTC), thiamphenicol (TAP) and their combination were evaluated by PCR, followed by gel electrophoresis, and broth microdilution antimicrobial susceptibility testing, respectively. All clinical isolates studied were confirmed to be GBS, one from serotype III (IA2022) and 71 from serotype Ib, suggesting that serotype Ib was the most prevalent strain between 2011 and 2016 in the south and southern and southeastern regions of Brazil. Eight different allelic profiles were identified for the first time, beingadhP-52,pheS-2,atr-31,glnA-4,sdhA-2,tkt-19 the most predominant. Between one (glcK) and three (adhPandglnA) alleles were present at each locus. All strains, except IA2022, showed a partial gene deletion event on theglcKgene. The surface proteinRiband hypervirulent GBS adhesinBibAwere detected in all strains, except for 18P, which was negative forrib. On the other hand, α and β antigens of the C protein were only detected in IA2022. All antimicrobials showed high minimum inhibitory concentration (MIC ≥ 16 µg/mL) values against several strains with negative results for resistance genes. Despite indifference and antagonism being the most predominant activities in all combinations evaluated, the record of synergism, including in a strain with a resistance gene and phenotypic resistance, suggests that combination therapy can have therapeutic efficacy when well planned. The combination involving OTC and TAP or FFC is a likely candidate for improving the treatment of streptococcosis using combination therapy, even for strains showing phenotypic and genotypic resistance to OTC. This study provides pertinent data on pathogenic GBS genetic diversity, virulence, the presence of antibiotic resistance genes and antimicrobial susceptibility, which may be useful in the development of effective vaccines and therapeutic strategies for the prevention and control of streptococcosis in aquaculture farms.
Morphology of the Ovaries, Uterine Tubes and Uterus ofPteronotus gymnonotus(Chiroptera: Mormoopidae)
Authors: Costa Erich Fernando Espinelo , de Morais Danielle Barbosa
Published: December 2022

The present study aimed to characterize the ovarian, tubal and uterine morphology in the insectivorous batPteronotus gymnonotus, in specimens collected in the state of Rio Grande do Norte, Brazil. After euthanasia, these organs were histologically processed for inclusion in historesin for morphological and morphometric analysis under light microscopy. The morphological characterization of the ovaries was based on the development of the oocyte and follicle growth, while the uterine tubes were characterized in terms of their anatomy and division of their parts into: infundibulum, ampulla and isthmus, where the height of the tubal epithelium and muscle layer thickness. The analysis of the uterus was based on the formation and thickness of its three layers: endometrium, myometrium and perimetrium. Morphometric analyzes were performed by capturing images of histological slides at different magnifications. The variables were submitted to descriptive analysis, with data expressed as mean and standard deviation. It was observed that the ovaries are bilateral and oval, presenting a squamous to simple cubic epithelium, forming the germinal epithelium, certain stratification regarding the location of the ovarian follicles, where most of the primordial follicles are arranged in the peripheral region of the ovary, however being it is possible to identify many follicles in various stages of maturation in the central region; the uterus is bicornuate and the layers of the uterus and uterine tubes observed follow the same pattern of other eutherian mammals. This information is important to allow comparisons between species, aiming at knowledge about reproductive morphology in mammals, especially those belonging to the order Chiroptera. Therefore, this research is essential to subsidize conservation measures that protect their natural populations, in an effort to maintain the ecological balance.
Integrating spatial transcriptomics data across different conditions, technologies, and developmental stages
Authors: Zhou Xiang , Dong Kangning , Zhang Shihua
Published: December 2022

With the rapid generation of spatial transcriptomics (ST) data, integrative analysis of multiple ST datasets from different conditions, technologies, and developmental stages is becoming increasingly important. However, identifying shared and specific spatial domains across ST datasets of multiple slices remains challenging. To this end, we develop a graph attention neural network STAligner for integrating and aligning ST datasets, enabling spatially-aware data integration, simultaneous spatial domain identification, and downstream comparative analysis. We apply STAligner to the integrative analysis of ST datasets of the human cortex slices from different samples, the mouse olfactory bulb slices generated by two profiling technologies, the mouse hippocampus tissue slices under normal and Alzheimer’s disease conditions, and the spatiotemporal atlases of mouse organogenesis. STAligner efficiently captures the shared tissue structures across different slices, the disease-related substructures, and the dynamical changes during mouse embryonic development. Additionally, the shared spatial domain and nearest neighbor pairs identified by STAligner can be further considered as corresponding pairs to guide the three-dimensional reconstruction of consecutive slices, achieving more accurate local structure-guided registration results than the existing method.
Visualization of mitochondrial cristae and mtDNA evolvement and interactions with super-resolution microscopy
Authors: Ren Wei , Ge Xichuan , Li Meiqi , Li Shiyi , Shan Chunyan , Gao Baoxiang , Xi Peng
Published: December 2022

Mitochondrial cristae host the respiratory chain complexes composed of mitochondrial DNA (mtDNA)-encoded and nuclear-encoded proteins and are responsible for ATP production. Movement of mtDNA located in the matrix is limited due to blockade by the cristae; yet, the dynamic interaction between the inner membrane and mtDNA remains unknown due to the insufficient spatiotemporal resolution of conventional microscopy and the lack of appropriatein vivoprobes targeted to the mitochondrial inner membrane. Here, we developed a novel fluorescence probe to visualize the inner membrane using low-power stimulated emission depletion (STED) microscopy. Dual-color imaging of the inner membrane and mtDNA demonstrated that mtDNA is more likely to spread at mitochondrial tips or branch points under an overall even distribution. Interestingly, exploration of forming this distribution propensity uncovered that the mitochondrial dynamics are closely related to the location of mtDNA, and further insight found that fusion always occurs near mtDNA in order to minimize the pressure for cristae remodeling. In healthy cells, mitochondrial dynamics based on cristae remodeling promotes the even distribution of mtDNA, on the contrary, when cristae structure fails in apoptosis and ferroptosis, leading to mtDNA distribution disorder. Observation of active changes during apoptosis further captured the dynamic process of inner membrane herniation and mtDNA leakage along with cristae remodeling. Under ferroptosis, the mitochondria shrank into ellipsoids and mtDNA converged at the center of mitochondria. The rich dynamics between the cristae and mtDNA, revealed at unprecedented spatiotemporal resolution, show the motive and outgrowth of mtDNA distribution.
Structural basis for the ligand promiscuity of the neofunctionalized, carotenoid-binding fasciclin domain protein AstaP
Authors: Kornilov Fedor D. , Slonimskiy Yury B. , Lunegova Daria A. , Egorkin Nikita A. , Savitskaya Anna G. , Kleymenov Sergey Yu. , Maksimov Eugene G. , Goncharuk Sergey A. , Mineev Konstantin S. , Sluchanko Nikolai N.
Published: December 2022

Fasciclins (FAS1) are ancient adhesion protein domains found across different phyla from bacteria to humans, with no common small ligand binding function reported. A unique FAS1-containing astaxanthin-binding protein (AstaP) from green algae can efficiently bind an unusually broad repertoire of carotenoids (astaxanthin, zeaxanthin, canthaxanthin, β-carotene), but the underlying mechanism is largely unknown. Here we dissect the structural basis for the ligand binding promiscuity of AstaP-orange1 (AstaPo1) by determining its solution NMR structure in complex with its natural ligand, astaxanthin (AXT), and validate this structure by SAXS, calorimetry, optical spectroscopy and mutagenesis data. While the unstructured tails of AstaPo1 are not essential for carotenoid binding, they enhance protein solubility. The a1-a2 helices of the AstaPo1 FAS1 domain embrace the carotenoid polyene like a jaw, organizing a conserved hydrophobic tunnel, too short to prevent the AXT β-ionone rings from protruding on both sides of the tunnel, thereby not imposing specificity restrictions. The only specific protein-AXT interactions involve H-bonds between the oxygenated groups on AXT and a peripheral Gln56 residue. Remarkably, mapping of this and other AXT-contacting AstaPo1 residues revealed their different conservation in AstaP orthologs with the tentative carotenoid-binding function and in FAS1 proteins in general, supporting neofunctionalization of AstaPs within green algae. Correspondingly, a cyanobacterial homolog with a similar domain structure cannot bind carotenoids due to subtle differences in residues decorating the tunnel. These structure-activity relationships inform the sequence-based prediction of the carotenoid-binding FAS1 members.

SIGNIFICANCE

A water-soluble astaxanthin-binding protein (AstaP) is a photoprotective protein in green algae helping them to tolerate stress conditions. While belonging to a ubiquitous protein family sharing an ancient structural domain, fasciclin, involved in cell adhesion, AstaP possesses an outstanding ability to bind carotenoid pigments of a different type, which are potent antioxidants. To understand the molecular basis for such carotenoid-binding promiscuity of AstaP, here we determined its spatial structure – the first structure of a carotenoid-protein complex solved by nuclear magnetic resonance spectroscopy. Together with biochemical and sequence conservation analyses, our data illustrate a remarkable case of neofunctionalization of the ancient protein domain and pave the way for its bioengineering and practical use as antioxidant transporter for biomedical applications.
ESCRT recruitment to mRNA-encoded SARS-CoV-2 spike induces virus-like particles and enhanced antibody responses
Authors: Hoffmann Magnus A. G. , Yang Zhi , Huey-Tubman Kathryn E. , Cohen Alexander A. , Gnanapragasam Priyanthi N. P. , Nakatomi Leesa M. , Storm Kaya N. , Moon Woohyun J. , Lin Paulo J.C. , Bjorkman Pamela J.
Published: December 2022

Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain antibody levels. We present a natural infection-mimicking technology that combines features of mRNA- and protein nanoparticle-based vaccines through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- and ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins to induce eVLP budding from cells. Purified spike-EABR eVLPs presented densely-arrayed spikes and elicited potent antibody responses in mice. Two immunizations with mRNA-LNP encoding spike-EABR elicited potent CD8+ T-cell responses and superior neutralizing antibody responses against original and variant SARS-CoV-2 compared to conventional spike-encoding mRNA-LNP and purified spike-EABR eVLPs, improving neutralizing titers >10-fold against Omicron-based variants for three months post-boost. Thus, EABR technology enhances potency and breadth of vaccine-induced responses through antigen presentation on cell surfaces and eVLPs, enabling longer-lasting protection against SARS-CoV-2 and other viruses.
Sodium channel slow inactivation normalizes firing in axons with uneven conductance distributions
Authors: Zang Yunliang , Marder Eve , Marom Shimon
Published: December 2022

The Na+channels that are important for action potentials show rapid inactivation, a state in which they do not conduct, although the membrane potential remains depolarized1,2. Rapid inactivation is a determinant of millisecond scale phenomena, such as spike shape and refractory period. Na+channels also inactivate orders of magnitude more slowly, and therefore have impacts on excitability over much longer time scales than those of a single spike or a single inter-spike interval3-9. Here, we focus on the contribution of slow inactivation to the resilience of axonal excitability10,11when ion channels are unevenly distributed across the axonal membrane. We study models in which the voltage-gated Na+and K+channels are unevenly distributed along axons with different variances, capturing the heterogeneity that biological axons display12. In the absence of slow inactivation many conductance distributions result in spontaneous tonic activity. Faithful axonal propagation is achieved with the introduction of Na+channel slow inactivation. This “normalization” effect depends on relations between the kinetics of slow inactivation and the firing frequency. Consequently, neurons with characteristically different firing frequencies will need to implement different sets of channel properties to achieve resilience. The results of this study demonstrate the importance of the intrinsic biophysical properties of ion channels in normalizing axonal function.

Highlights

Variation in ion channel density in axons may compromise axonal spike propagation.

Slow inactivation of Na+channels modulates their availability.

Na+channel slow inactivation increases the reliability of spike propagation.

Normalization by slow inactivation can compensate for uneven channel distributions.
Tissue protective role of Ganetespib in SARS-CoV-2-infected Syrian golden hamsters
Authors: Teixeira Alves Luiz Gustavo , Baumgardt Morris , Hoppe Judith , Firsching Theresa C. , Adler Julia M. , Mastrobuoni Guido , Grobe Jenny , Hönzke Katja , Kempa Stefan , Gruber Achim D. , Hocke Andreas C. , Trimpert Jakob , Wyler Emanuel , Landthaler Markus
Published: December 2022

The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are therefore urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyper-inflammatory state generated upon infection, at reducing lung tissue pathology and endothelial damages, along with viral replication. Previous research has pointed a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. In this study, we analyzed the effects of the potent HSP90 inhibitor Ganetespibin vitroon alveolar epithelial cells and alveolar macrophages to characterize its effects on cell activation and viral replication. Additionally, to evaluate its efficacy in controlling systemic inflammation and the viral burden after infectionin vivo, a Syrian hamster model was used.In vitro, Ganetespib reduced viral replication on AECs in a dose-dependent manner and lowered significantly the expression of pro-inflammatory genes, in both AECs and alveolar macrophages.In vivo, administration of Ganetespib led to an overall improvement of the clinical condition of infected animals, with decreased systemic inflammation, reduced edema formation and lung tissue pathology. Altogether, we show that Ganetespib could be a potential medicine to treat moderate and severe cases of COVID-19.
Creating “Artificial Suns”: the Sino-Western race to master limitless clean energy through nuclear fusion
Authors: Wong Wilson Kia Onn
Published: December 2022

Purpose

This paper aims to examine the intensifying efforts by China and the West to harness the clean, limitless energy of nuclear fusion. However, it argues that this “holy grail” of a fusion future is only achievable through an optimal combination of mission-oriented public–private cooperation and genuine intergovernmental cooperation.

Design/methodology/approach

This study deploys a case-study approach, augmented by relevant literature, to analyse the advances in fusion technology.

Findings

Despite purported recent advances in fusion technology, these advances remain largely “proof of concept” experiments rather than commercially viable technologies that enable us to truly harness the infinite power of these “artificial suns”. To achieve the moonshot goal of delivering practicable “net energy gain” from fusion power, this study advocates shedding hubristic political “one-upmanship” amongst rival governments. Further, it urges focussing the ingenuity, along with the financial and scientific resources of all stakeholders (both public and private) across the globe to bring about this “fusion dawn”. Moreover, efforts to deliver fusion power face significant competition from other clean energy sources (wind, solar power and nuclear fission reactors) that are not only technically far less challenging but also economically more viable with their declining cost structures.

Originality/value

This study is possibly one of the few social science papers that examines the prospect of clean, limitless fusion power along with the challenges it faces and its societal implications.
The accident-adjusted dynamic efficiency of public bus operators in metropolitan cities of India
Authors: Gulati Rachita
Published: December 2022

Purpose

The study evaluates the accident-adjusted dynamic efficiency of public bus operators providing bus transportation services in eight major metropolitan cities of India.

Design/methodology/approach

The slack-based measure (SBM)–undesirable window analysis approach is used to gauge the dynamic efficiency levels and identify the sources of inefficiency in bus transportation services. This innovative approach integrates the SBM model developed by Tone (2001, 2004) and the window analysis approach of Charnes et al. (1985). The main advantage of this approach is that one can explicitly incorporate the number of accidents in the production technology specification as an undesirable (bad) output and potently handle the issue of the “curse of dimensionality” in a small sample like ours.

Findings

The key empirical findings suggest wide variations in average efficiency levels across sample bus operators in metropolitan cities. The Chennai Transport Corporation is observed as the most efficient and consistent bus operator due to its most stable efficiency performance. The results additionally unveil that the role of managerial inefficiency was diminutive, and the scale-related issues were the real cause of sub-optimal or supra-optimal behaviour of sample bus operators in the resource-utilisation process.

Practical implications

There is an urgent requirement for effective policy intercessions to mitigate the sizeable observed inefficiency in the production process and resolve scale-related issues of public bus operators offering transit services in major metropolitan cities of India.

Originality/value

This paper is maybe the first to assess the dynamic efficiency of public bus transit systems in India's major metropolitan cities after treating accidents.
Sensorless DTC-SVM applied to an induction motor controlled by a three-level inverter using SMSFO
Authors: Jnayah Salma , Khedher Adel
Published: December 2022

Purpose

The direct torque control (DTC) of induction motor (IM) drive is featured by high ripples in the electromagnetic torque and stator flux profiles because they are controlled by two hysteresis regulators. Furthermore, the machine flux is not directly measurable. Hence, it is better to reconstitute it from the instantaneous electrical equations of the machine. Once the stator flux is estimated, we can guarantee a reliable sensorless DTC control. Thus, the purpose of this research work is to ensure fast response and full reference tracking of the IM under sensorless DTC strategy with desired dynamic behavior and low ripple levels.

Design/methodology/approach

In this work, an improved DTC strategy, which is DTC_SVM_3L, is suggested. The first step of the designed approach is to substitute the conventional inverter feeding the motor with a three-level inverter because it guarantees reduced switching losses, improved quality of voltage waveform and low-current total harmonic distortion rate. The second aim of this paper is to make the IM operate at a constant switching frequency by using the nearest three vectors-based space vector modulation (SVM) technique rather than hysteresis controllers. The third objective of this study is to conceive a sliding-mode stator flux observer, which can improve the control performances by using a sensorless algorithm to get an accurate estimation, and consequently, increase the reliability of the system and decrease the cost of using sensors. The stability of the proposed observer is demonstrated based on the Lyapunov theory. To overcome the load change disturbance in the proposed DTC control strategy, this paper exhibits a comparative assessment of four speed regulation methods: classical proportional and integral (PI) regulator, fuzzy logic PI controller, particle swarm optimization PI controller and backstepping regulator. The entire control algorithm was tested under different disturbances such as stator resistance and load torque variations.

Findings

It was ascertained that the IM, controlled with three-level inverter, exhibits good performances under the proposed DTC-SVM strategy based on a sliding-mode observer. The robustness of the suggested approach against parameter variations is also proved.

Originality/value

The theoretical development of the proposed control strategy is thoroughly described. Then, simulations using Matlab/Simulink software are launched to investigate the merits of the sensorless DTC-SVM command of three-level inverter-fed IM drive with different speed regulators.
The impact of library and information science knowledge from the perspective of external citations
Authors: Si Li , Guo Caiqiang
Published: December 2022

Purpose

This paper aims to explore the characteristics of knowledge diffusion in library and information science (LIS) to reveal the impact of knowledge in LIS on other disciplines and the disciplinary status of LIS.

Design/methodology/approach

Taking the 573 highly cited papers (HCP) of LIS during the years 2000–2019 in Web of Science and 85,638 papers citing them from non-LIS disciplines as the analysis object, this paper analysed the disciplines to which the citing papers belonged regarding the Biglan model, and the topics and their characteristics of the citing disciplines using latent Dirichlet allocation topic clustering.

Findings

The results showed that the knowledge in LIS was exported to multiple disciplines and topics. (1) Citations from other disciplines were overall increasing, and the main citing disciplines, mainly from applied science disciplines, were medicine, computer science, management, economics, education, sociology, psychology, journalism and communication, earth science, engineering, biology, political science, chemistry and agronomy. However, those disciplines had fewer citations to LIS during for the years from 2000 to 2004, with rapid growth in the next three time periods. (2) The citing papers had various topics and showed an increasing trend in quantity. Moreover, topics of different disciplines from 2000 to 2019 had various characteristics.

Originality/value

From the perspective of discipline and topic, this study analyses papers citing the HCP of LIS from non-LIS disciplines, revealing the impact of knowledge in LIS on other disciplines.
CEO gender and readability of annual reports: do female CEOs’ demographic attributes matter?
Authors: E-Vahdati Sahar , Oradi Javad , Nazari Jamal A.
Published: December 2022

Purpose

This study examines the association between chief executive officer (CEO) gender and the readability of annual reports by considering some demographic attributes of female CEOs.

Design/methodology/approach

Ordinary least squares (OLS) regression is used to test the research hypotheses on a sample of S&P 500 firms between 2004 and 2016.

Findings

The results show that female CEOs are significantly positively associated with the readability of 10-K reports – in line with ethical-sensitivity theory. Further results show that this association is variable depending on the demographic attributes of female CEOs – in line with upper echelon theory. Specifically, older female CEOs and those with financial expertise are significantly associated with more readable 10-K reports. In contrast, female CEOs hired from within the firm are negatively associated with the readability of 10-K.

Research limitations/implications

This study provides evidence on the effect of female CEOs and their demographic attributes on annual report readability, which was not addressed in prior research.

Practical implications

The findings show that the appointment of female CEOs seems like a helpful avenue to reduce concerns among the regulators about the textual complexity of annual reports. However, the most important policy implication of the study is that the decision to appoint female CEOs should be based more on their demographic attributes than on gender equality recommendations and full trust in women's behavioral consequences.

Originality/value

This study contributes to the academic literature on readability and gender. Prior research has not clarified which attributes and skills of female CEOs drive their abilities to improve shareholder value and make more ethical decisions. This study suggests that female CEOs are not better “per se” to improve corporate governance practices, and the impacts of female CEOs are not the same and differ according to their demographic attributes.
An enhanced solution approach for multi-period discrete manufacturing product assembly inventory routing problem with supply failure risks and customer demand uncertainty
Authors: Prakash Satya , Mukherjee Indrajit
Published: December 2022

Purpose

This study primarily aims to develop and solve an enhanced optimisation model for an assembly product multi-period inbound inventory routing problem (IRP). The many-to-one (inbound) model considers the bill of materials (BOM), supply failure risks (SFR) and customer demand uncertainty. The secondary objective is to study the influence of potential time-dependent model variables on the overall supply network costs based on a full factorial design of experiments (DOE).

Design/methodology/approach

A five-step solution approach is proposed to derive the optimal inventory levels, best sourcing strategy and vehicle route plans for a multi-period discrete manufacturing product assembly IRP. The proposed approach considers an optimal risk mitigation strategy by considering less risk-prone suppliers to deliver the required components in a specific period. A mixed-integer linear programming formulation was solved to derive the optimal supply network costs.

Findings

The simulation results indicate that lower demand variation, lower component price and higher supply capacity can provide superior cost performance for an inbound supply network. The results also demonstrate that increasing supply capacity does not necessarily decrease product shortages. However, when demand variation is high, product shortages are reduced at the expense of the supply network cost.

Research limitations/implications

A two-echelon supply network for a single assembled discrete product with homogeneous vehicle fleet availability was considered in this study.

Originality/value

The proposed multi-period inbound IRP model considers realistic SFR, customer demand uncertainties and product assembly requirements based on a specific BOM. The mathematical model includes various practical aspects, such as supply capacity constraints, supplier management costs and target service-level requirements. A sensitivity analysis based on a full factorial DOE provides new insights that can aid practitioners in real-life decision-making.
A service evaluation of the assessment process in a Step4 Psychological Therapies Service
Authors: Robinson Amie , De Boos Danielle , Moghaddam Nima
Published: December 2022

Purpose

This study aims to improve the efficiency of the assessment process within a Step4 Psychological Therapies Service by identifying factors related to assessment non-attendance and service suitability for referred clients.

Design/methodology/approach

Referral and assessment information was accessed between October 2019 and March 2020 from Step4 routine service data, electronic client records where necessary and Step4 staff self-report questionnaires.

Findings

All clients offered an assessment during this time attended. Findings indicated several factors could influence service suitability in meeting client need. These included individual differences such as readiness to change, which was not necessarily identified at referral or prior to assessment, and potential systemic factors, such as the opt-in procedure, which possibly impeded access. Though the necessity for assessment in clarifying client needs and treatment was indicated, an assessment (from referral to assessment appointment) that led to discharge could take an excess of one working day of service time, associated with considerable opportunity cost to other clients awaiting assessment. Recommendations are made for improving assessment efficiency.

Originality/value

With a high prevalence of poor mental health in the UK, efforts must be made to identify and reduce additional demand upon service time and resources within mental health services to effectively meet people’s needs. Recommendations to improve assessment process efficiency include the use of a standardised referral form, offer of follow-up support procedures, increased client involvement, a streamlined opt-in battery and ongoing monitoring to ensure shared practice between clinicians. These are transferable to other mental health services, with implications for subsequent quality and timeliness of care.