bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Increases in Human Immunodeficiency Virus Neutralization Sensitivity Due to Alterations in the Membrane-Proximal External Region of the Envelope Glycoprotein Can Be Minimized by Distant State 1-Stabilizing Changes
Authors: Wang Qian , Esnault Florian , Zhao Meiqing , Chiu Ta-Jung , Smith Amos B. , Nguyen Hanh T. , Sodroski Joseph G.
Published: March 2022

The pretriggered shape of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) is a major target for antibodies that can neutralize many strains of the virus. An effective HIV-1 vaccine may need to raise these types of antibodies, but this goal has proven difficult.
Copper Induces Protein Aggregation, a Toxic Process Compensated by Molecular Chaperones
Authors: Zuily Lisa , Lahrach Nora , Fassler Rosi , Genest Olivier , Faller Peter , Sénèque Olivier , Denis Yann , Castanié-Cornet Marie-Pierre , Genevaux Pierre , Jakob Ursula , Reichmann Dana , Giudici-Orticoni Marie-Thérèse , Ilbert Marianne
Published: March 2022

With the increase of antibiotic drug resistance, alternative antibacterial treatment strategies are needed. Copper is a well-known antimicrobial and antiviral agent; however, the underlying molecular mechanisms by which copper causes cell death are not yet fully understood.
Complete Genome Sequence of Alcaligenes faecalis Phage Piluca
Authors: Wan Joshua , Yu Zihao , Clark James , Le Tram , Young Ryland , Liu Mei
Published: March 2022

Alcaligenes faecalis
is an opportunistic pathogen exhibiting drug resistance. Here, the 35,451-bp genome of
A. faecalis
phage Piluca is described. Piluca is not closely related to any isolated phages in the NCBI database. Piluca possesses genes encoding CI-like and Cro-like repressors and a tyrosine integrase, suggesting its temperate lifestyle.
The Rhizosphere Microbiomes of Five Species of Coffee Trees
Authors: de Sousa Leandro Pio , Guerreiro-Filho Oliveiro , Mondego Jorge Maurício Costa
Published: March 2022

The microbiome has been identified as a fundamental factor for the maintenance of plant health, helping plants to fight diseases and the deleterious effects of abiotic stresses. Despite this, in-depth studies of the microbiome have been limited to a few species, generally with a short life cycle, and perennial species have mostly been neglected.
Supplemental Material: Middle and late Miocene marine mammal assemblages from the Monterey Formation of Orange County, California
Authors: Parham James F. , al. et
Published: March 2022

Table S1: Diatom sampling localities; Table S2: Marine mammal occurrences; and Table S3: Previously published occurrences
Rectal duplication cyst in an adult with a history of imperforate anus: a diagnostic challenge
Authors: Cavadas Sofia , Gonçalves Eduarda , Costa-Pereira Carlos , Costa-Pereira Joaquim
Published: March 2022

Rectal duplications are rare congenital anomalies that represent 1%–6% of alimentary tract duplications. We report a case of a woman in her 50s who presented to our hospital with perianal pain and urinary retention. She had a history of imperforate anus repaired after birth and dynamic graciloplasty performed during her adulthood for faecal incontinence. Abdominal CT scan showed a fluid collection extending from the electrostimulator, placed in a subcutaneous pocket in the abdomen, to the rectouterine pouch. Infection related to the electrostimulator was assumed and, after a course of antibiotics without patient improvement, the electrostimulator was removed. The symptoms and the pelvic fluid collection persisted, and diagnostic laparoscopy was performed. Diagnosis of rectal duplication cyst was made intraoperatively, and the cyst was completely resected. Patient fully recovered after surgery. This is a rare case of a rectal duplication cyst presenting during adulthood and associated with imperforate anus.
Systemic capillary leak syndrome (SCLS) after receiving BNT162b2 mRNA COVID-19 (Pfizer-BioNTech) vaccine
Authors: Inoue Masatoshi , Yasue Yu , Kobayashi Yoichi , Sugiyama Yutaka
Published: March 2022

Systemic capillary leak syndrome (SCLS), also known as Clarkson’s disease, is a rare disorder of unknown aetiology. Since SCLS was first described in 1960, fewer than 500 cases have been reported. SCLS is diagnosed by the classic triad of hypotension, haemoconcentration and hypoalbuminaemia resulting from fluid extravasation. Some reports show that SCLS may sometimes occur as a side effect of adenoviral vector COVID-19 vaccines, although there is only one report (two cases) of SCLS after receiving a messenger RNA vaccine. Survival rates for SCLS are very poor without treatment, so it is crucial for clinicians to recognise this disorder. A middle-aged woman who presented with generalised malaise and anasarca after receiving the BNT162b2 COVID-19 vaccine was diagnosed with SCLS. Treatment with methylprednisolone and intravenous immunoglobulin was commenced and her symptoms resolved. We expect that this case report will add to the existing literature on this rare disorder and the side effects of vaccinations.
Could the perioperative use of opioids influence cancer outcomes after surgery? A scoping review protocol
Authors: Cascella Marco , Cuomo Arturo , Bifulco Francesca , Perri Francesco , Carbone Francesca , Aprea Marika , Forte Cira Antonietta , Fiore Marco
Published: March 2022

Background

During and after general anaesthesia, opioids are commonly used for pain treatment. Since preclinical studies underlined the potential immunosuppressive activity of these drugs, it was postulated that their perioperative administration could influence cancer outcomes after surgery. Nevertheless, clinical data have been extrapolated mainly from retrospective analyses. Consequently, the precise link between perioperative opioid use and cancer recurrence/metastasis or cancer-related mortality/morbidity is still an unsolved issue.

Methods and analysis

This scoping review is planned to follow the Joanna Briggs Institute recommendations. The authors will conduct a literature review through the PRISMA statement using PubMed and EMBASE databases; the Grey literature will be explored using Google Scholar and Conference Proceedings Citation Index (via Web of Science). The search strategy will be limited to articles published in the English language and to human studies. The database searches are planned from the inception to January 2022. Two reviewers will independently screen titles and abstracts, followed by a full-text screening of potentially relevant articles with standardised data extraction. Any disagreement for the inclusion between the two reviewers will be discussed with a third reviewer.

Ethics and dissemination

The review aims to map the available literature, focusing on a possible association between perioperative opioid use and cancer outcomes in patients undergoing surgery. The proposed approach will be useful to identify and analyse the knowledge gap in the field and serve as a prerequisite for future research.

Scoping review registration

Open Science Framework https://osf.io/vfhw6/ DOI 10.17605/OSF.IO/VFHW6
What can general practice learn from primary care nurses’ and healthcare assistants’ experiences of the COVID-19 pandemic? A qualitative study
Authors: Russell Alice , de Wildt Gilles , Grut Minka , Greenfield Sheila , Clarke Joanne
Published: March 2022

Objectives

UK general practice has radically altered in response to COVID-19. The general practice nursing team has been central to these changes. To help learn from COVID-19 and maintain a sustainable nursing workforce, general practice should reflect on their support needs and perceptions of organisational strategies. This study aimed to explore primary care nurses’ and healthcare assistants’ experiences and perceptions of general practice, and the changes made to it, during the pandemic.

Design

Exploratory qualitative study using semistructured interviews. Interview data were analysed using Braun and Clarke’s ‘codebook’ thematic analysis.

Setting

General practices in the Midlands, South East and South West England. Interviews were conducted in February and March 2021, as England began to unlock from its third national lockdown.

Participants

Practice nurses (n=12), healthcare assistants (n=7), advanced nurse practitioners (n=4) and nursing associates (n=1) recruited using convenience and snowball sampling.

Results

Three themes were identified. Difficult changes describes dramatic changes made to general practice at the onset of the pandemic, creating confusion and anxiety. Dealing with change characterises how negative emotions were intensified by fear of infection, problematic government guidance, personal protective equipment (PPE) shortages and friction with doctors; but could be mitigated through effective practice communication, peer support and individual coping strategies. An opportunity for improvement highlights certain changes (eg, the increased use of telehealth) that participants believed could be adopted long term to improve efficiency.

Conclusion

General practice should learn from the COVID-19 pandemic to nurture the clinical role and resilience of nurses and healthcare assistants in the postpandemic ‘new normal’. Robust PPE provision could enable them to undertake their patient-facing duties safely and confidently. Judicious implementation of telehealth could help preserve the practical and caring nature of nursing. Improving channels of communication and interprofessional collaboration could help realise their potential within the primary care team.
Determinants of immunisation dropout among children under the age of 2 in Zambézia province, Mozambique: a community-based participatory research study using Photovoice
Authors: Powelson Jocelyn , Magadzire Bvudzai Priscilla , Draiva Abel , Denno Donna , Ibraimo Abdul , Benate Bonifácia Beleza Lucas , Jahar Lídia Carlos , Marrune Zélia , Chilundo Baltazar , Chinai Jalilo Ernesto , Emerson Michelle , Beima-Sofie Kristin , Lawrence Emily
Published: March 2022

Objective

Immunisations are highly impactful, cost-effective public health interventions. However, substantial gaps in complete vaccination coverage persist. We aimed to describe caregivers’ immunisation experiences and identify determinants of vaccine dropout.

Design

We used a community-based participatory research approach employing Photovoice, SMS (short messaging service) exchanges and in-depth interviews. A team-based approach was used for thematic analysis. The Increasing Vaccination Model guided the analysis and identification of vaccination facilitators and barriers.

Setting

This study was conducted in Zambézia province, Mozambique, in Namarroi and Gilé districts, where roughly 19% of children under 2 start but do not complete the recommended vaccination schedule.

Participants

Participants were identified through health facility vaccination records and included caregivers of children aged 25–34 months who were fully vaccinated (n=10) and partially vaccinated (n=22). We also collected data from 12 health workers responsible for delivering immunisations at the selected health facilities.

Results

Four main patterns of barriers leading to dropout emerged: (1) social norms and limited family support place the immunisation burden on mothers; (2) perceived poor quality of health services reduces caregivers’ trust in vaccination services; (3) concern about side effects causes vaccine hesitancy; and (4) caregivers hesitate to seek and advocate for vaccination due to power imbalances with health workers. COVID-19 created additional barriers related to social distancing, mask requirements, supply chain challenges and disrupted outreach services. For most caregivers, dropout becomes increasingly likely with compounding barriers. Caregivers of fully-vaccinated children noted facilitators, including accompaniment to health facilities or assistance caring for other children, which enabled them to complete vaccination.

Conclusions

Overcoming immunisation barriers requires strengthening health systems, including improving logistics to avert vaccine stockouts and building health worker capacity, including empathic communication with caregivers. Consistent and reliable immunisation outreach services could address access challenges and improve immunisation uptake, particularly in distant communities.
Establishing an incentive-based multistakeholder approach to dual-use DNA screening
Authors: Isaac Christopher R.
Published: March 2022

Fast, accessible, and high-quality deoxyribonucleic acid (DNA) is fundamental to advancement in the life sciences that will drive forward fields such as agriculture, energy, and medicine. Despite their importance in accelerating global progress, bioscience research and biotechnologies can also be misused, endangering humans, animals, and the environment. The ability to accidentally or deliberately endow or enhance the pathogenicity of biological systems is of particular concern. Access to DNA sequences with a clear potential for dual use should be limited to responsible and identifiable groups with legitimate uses. Yet, none of the 195 countries party to the International Health Regulations have national laws that mandate this type of screening. Many DNA providers voluntarily screen orders and absorb increased costs, but this practice is not universally adopted for a variety of reasons. This article explores the incentives and regulatory structures that can bring the screening coverage of DNA orders toward 100%, which may include expedited orders for approved customers, better tools and technology for more efficient screening, funding requirements that grantees use screened DNA, and early education in biosecurity aimed at researchers and students. Ultimately, an incentive-based multistakeholder approach to DNA screening can benefit researchers, industry, and global health security.
Criteria-based critical review of artificial intelligence applications in water-leak management
Authors: Abdelmageed Sherif , Tariq Salman , Boadu Vincent , Zayed Tarek
Published: March 2022

Leakages in water distribution networks (WDNs) cause economic losses and environmental hazards. It is, therefore, unsurprising that water-leak management has been a focus of research over the last couple of decades, but leaks in WDNs still occur frequently. Thus, this domain is experiencing a transformation from traditional signal processing and statistical-based models to artificial intelligence (AI) based models for recognizing complex leak patterns, handling large datasets, and establishing accurate leak-management models, especially in leak detection and localization. However, a comprehensive review of the application of AI in water-leak management is largely missing from the literature. To bridge this gap, this review presents a criteria-based critical review to systematically investigate the existing literature on the application of AI in four sub-domains of leak management including leak detection, localization, prediction, and sizing. The first criterion (research attributes) established the (1) research trends, (2) links between influential countries and sources, and (3) popular keywords using scientometric analysis. The systematic analysis of the second criterion (research technicality) and the third criterion (research focus) revealed the (1) AI-techniques adopted, (2) equipment used for collecting data, (3) data features used in the models, (4) objectives of different models adopted, (5) type of experiments conducted to collect the data, and (6) types of pipes for which models were developed. The study highlighted research gaps, future research directions, and proposed a leak management framework for upcoming AI studies in this domain. This review is intended to serve early researchers by enhancing their understanding of existing research in AI-based leak management as well as seasoned researchers by providing a platform for future research.
Temporal Action Detection Methods Based on Deep Learning
Authors: Shen Junyi , Li Ma , Zhang Jikai
Published: March 2022

Temporal action detection is one of the most important and challenging tasks in video analysis. Due to its wide application prospects, it has received extensive attention in recent years. With the development of deep learning, great progress has been made in temporal behavior detection, but there are still many difficulties to be solved, such as accurate proposal generation and high computational cost. In this paper, deep learning-based temporal action detection methods are classified according to full supervision and weak supervision, and then the representative models of the two methods are summarized in detail, and the ideas, advantages and disadvantages of different models and the evolution between different models are analyzed. At the same time, the performance of different models on mainstream datasets is compared. The mainstream dataset and evaluation index used in temporal action detection are introduced in detail, and the calculation method of evaluation index is also elaborated. Finally, through in-depth analysis, the possible future research directions of temporal action detection and the whole review are summarized.
Powered-Coast-Powered Guidance Reconfiguration Method of Launch Vehicle with Thrust Drop Fault
Authors: Wang Cong , Song Zhengyu
Published: March 2022

This paper describes the study of a powered-coast-powered guidance reconfiguration (PCPGR) method used to solve the autonomous rescue problem for the mission profile of a launch vehicle with a coasting phase when the thrust drop fault occurs in the first powered phase (FPP) of the final stage. We first described the constraints of the final stage and the construction of the PCP guidance problem. Then we evaluated the adaptability of the guidance reconfiguration (GR) offline with numerical optimization by adjusting the constraints of the FPP, the coast phase, and the second powered phase. To determine the fault state set where the rocket can enter the prescribed target orbit through the GR initiate, we proposed a Newton method-based rapid replanning method of the transfer orbit that transforms the complex multi-flight phase trajectory planning problem into a feasible transfer orbit search problem to produce a fast solution onboard. Combined with the adaptive adjustment of the coasting time and the iterative guidance mode, we realized the autonomous online rescue of the payload. The simulation results showed that the proposed method achieved a reliable and rapid solution and improved a launch vehicle’s adaptability to a thrust drop fault.
Mining World Indicators for Analyzing and Modeling the Development of Countries
Authors: Huang Hong , Chi Mingyuan , Song Yu , Jin Hai
Published: March 2022

The world indicators released by the World Bank or other organizations usually give the basic public knowledge about the world. However, separate and static index lacks the complex interplay among different indicators and thus cannot help us have an overall understanding of the world. To this end, we study the world indicators from a different angle. Firstly, we discover that there exist correlations between indicators either from a static view or from a dynamic view. Moreover, taking the trade and diplomatic relationships into consideration, we construct a multi-relational network to depict the interactions between different countries, and propose a Multiple Relations to Vector (MR2vec) model to study world indicators from a network perspective. The experimental results show the changes of world indicators are predictable with the proposed model, and our proposed MR2vec has wide adaptability in predicting multi-relation networks.
Time Dependent Biased Random Walks
Authors: Haslegrave John , Sauerwald Thomas , Sylvester John
Published: March 2022

We study the biased random walk where at each step of a random walk a “controller” can, with a certain small probability, move the walk to an arbitrary neighbour. This model was introduced by Azar et al. [STOC’1992]; we extend their work to the time dependent setting and consider cover times of this walk. We obtain new bounds on the cover and hitting times. Azar et al. conjectured that the controller can increase the stationary probability of a vertex from
p
to
p
1-ε
; while this conjecture is not true in full generality, we propose a best-possible amended version of this conjecture and confirm it for a broad class of graphs. We also consider the problem of computing an optimal strategy for the controller to minimise the cover time and show that for directed graphs determining the cover time is
PSPACE
-complete.
Clean Vibes: Hand Washing Monitoring Using Structural Vibration Sensing
Authors: Fagert Jonathon , Bonde Amelie , Srinidhi Sruti , Hamilton Sarah , Zhang Pei , Noh Hae Young
Published: March 2022

We present a passive and non-intrusive sensing system for monitoring hand washing activity using structural vibration sensing. Proper hand washing is one of the most effective ways to limit the spread and transmission of disease, and has been especially critical during the COVID-19 pandemic. Prior approaches include direct observation and sensing-based approaches, but are limited in non-clinical settings due to operational restrictions and privacy concerns in sensitive areas such as restrooms. Our work introduces a new sensing modality for hand washing monitoring, which measures hand washing activity-induced vibration responses of sink structures, and uses those responses to monitor the presence and duration of hand washing. Primary research challenges are that vibration responses are similar for different activities, occur on different surfaces/structures, and tend to overlap/coincide. We overcome these challenges by extracting information about signal periodicity for similar activities through cepstrum-based features, leveraging hierarchical learning to differentiate activities on different surfaces, and denoting “primary/secondary” activities based on their relative frequency and importance. We evaluate our approach using real-world hand washing data across four different sink structures/locations, and achieve an average F1-score for hand washing activities of 0.95, which represents an 8.8X and 10.2X reduction in error over two different baseline approaches.
Flexibility Versus Routineness in Multimodal Health Indicators: A Sensor-based Longitudinal in Situ Study of Information Workers
Authors: Amon Mary Jean , Mattingly Stephen , Necaise Aaron , Mark Gloria , Chawla Nitesh , Dey Anind , D'mello Sidney
Published: March 2022

Although some research highlights the benefits of behavioral routines for individual functioning, other research indicates that routines can reflect an individual's inflexibility and lower well-being. Given conflicting accounts on the benefits of routine, research is needed to examine how routineness versus flexibility in health-related behaviors correspond to personality traits, health, and occupational outcomes. We adopt a nonlinear dynamical systems approach to understanding routine using automatically sensed health-related behaviors collected from 483 information workers over a roughly two-month period. We utilized multidimensional recurrence quantification analysis to derive a measure of health regularity (routineness) from measures of daily step count, sleep duration, and heart rate variability (which relates to stress). Participants also completed measures of personality, health, and job performance at the start of the study and for two months via Ecological Momentary Assessments. Greater regularity was associated with higher neuroticism, lower agreeableness, and greater interpersonal and organizational deviance. Importantly, these results were independent of overall levels of each health indicator in addition to demographics. It is often believed that routine is desirable, but the results suggest that associations with routineness are more nuanced, and wearable sensors can provide insights into beneficial health behaviors.
Online Reviews Sentiment Analysis and Product Feature Improvement with Deep Learning
Authors: Cao Jihua , Li Jie , Yin Miao , Wang Yunfeng
Published: March 2022

The text mining of online reviews is currently a popular research direction of e-commerce and is considered the next blue ocean. Online reviews can dig out consumer preferences and provide theoretical guidance for the improvement of product features. However, current research mostly focuses on sentiment analysis methods and rarely involves feature extraction and large-scale data recognition. This article uses word segmentation technology to create a new feature extraction method. With the long short-term memory neural network and latent Dirichlet allocation topic model, we propose a product feature improvement model—CESC (Consumer online reviews–Extract short text–Sentiment analysis–Cluster feature). The model can derive the product features and attitudes that consumers prefer based on consumer online reviews and use it to improve product features. According to the experimental results of three electronic products sold on the e-commerce platform, the model can effectively dig out consumer preferences for online reviews. Enterprises can improve the quality of products and services, better meet the needs of consumers, promote consumers’ consumption, and achieve the enterprises’ goals and values.
A Survey of Practical Formal Methods for Security
Authors: Kulik Tomas , Dongol Brijesh , Larsen Peter Gorm , Macedo Hugo Daniel , Schneider Steve , Tran-Jørgensen Peter W. V. , Woodcock James
Published: March 2022

In today’s world, critical infrastructure is often controlled by computing systems. This introduces new risks for cyber attacks, which can compromise the security and disrupt the functionality of these systems. It is therefore necessary to build such systems with strong guarantees of resiliency against cyber attacks. One way to achieve this level of assurance is using formal verification, which provides proofs of system compliance with desired cyber security properties. The use of Formal Methods (FM) in aspects of cyber security and safety-critical systems are reviewed in this article. We split FM into the three main classes: theorem proving, model checking, and lightweight FM. To allow the different uses of FM to be compared, we define a common set of terms. We further develop categories based on the type of computing system FM are applied in. Solutions in each class and category are presented, discussed, compared, and summarised. We describe historical highlights and developments and present a state-of-the-art review in the area of FM in cyber security. This review is presented from the point of view of FM practitioners and researchers, commenting on the trends in each of the classes and categories. This is achieved by considering all types of FM, several types of security and safety-critical systems, and by structuring the taxonomy accordingly. The article hence provides a comprehensive overview of FM and techniques available to system designers of security-critical systems, simplifying the process of choosing the right tool for the task. The article concludes by summarising the discussion of the review, focusing on best practices, challenges, general future trends, and directions of research within this field.
AIP: A Named Entity Recognition Method Combining Glyphs and Sounds
Authors: Liu Bo , Su Zhuo , Qu Guangzhi
Published: March 2022

In recent years, a large number of Chinese electronic texts have been produced in the process of information construction in various fields. Identifying specific entities in these electronic texts has become a major research focus. Most existing research methods use radicals to extract the glyph features of Chinese characters but have seen its limitation. This paper extracts the features of Chinese characters from three aspects: glyph features, phonetic features, and character features, and improves conventional feature extraction methods for each kind of feature. A new named entity recognition method (AIP) is proposed by transforming Chinese characters into corresponding images for glyph feature extraction, dividing pinyin into initials, vowels, and tones for phonetic feature extraction, and fine-tuning the A Lite Bert model for character feature extraction to improve the performance of the model. This paper compares the performance of the AIP model and mainstream neural network models on Chinese named entity recognition tasks on commonly used data sets and the data sets in specific domains. The results showed that AIP achieved better results than the related work. The F1 values on the two data sets are 94.4% and 80.5%, respectively, which validates the model's versatility.
Persistence Programming
Authors: Cobbs Archie L.
Published: March 2022

A few years ago, my team was working on a commercial Java development project for Enhanced 911 (E911) emergency call centers. We were frustrated by trying to meet the data-storage requirements of this project using the traditional model of Java over an SQL database. After some reflection about the particular requirements (and nonrequirements) of the project, we took a deep breath and decided to create our own custom persistence layer from scratch.
Middleware 101
Authors: Gazis Alexandros , Katsiri Eleftheria
Published: March 2022

Whether segregating a sophisticated software component into smaller services, transferring data between computers, or creating a general gateway for seamless communication, you can rely on middleware to achieve communication between different devices, applications, and software layers. Following the increasing agile movement, the tech industry has adopted the use of fast waterfall models to create stacks of layers for each structural need, including integration, communication, data, and security. Given this scope, emphasis must now be on endpoint connection and agile development. This means that middleware should not serve solely as an object-oriented solution to execute simple request-response commands. Middleware can incorporate pull-push events and streams via multiple gateways by combining microservices architectures to develop a holistic decentralized ecosystem.
Role of the TOM Complex in Protein Import into Mitochondria: Structural Views
Authors: Araiso Yuhei , Imai Kenichiro , Endo Toshiya
Published: March 2022

Mitochondria are central to energy production, metabolism and signaling, and apoptosis. To make new mitochondria from preexisting mitochondria, the cell needs to import mitochondrial proteins from the cytosol into the mitochondria with the aid of translocators in the mitochondrial membranes. The translocase of the outer membrane (TOM) complex, an outer membrane translocator, functions as an entry gate for most mitochondrial proteins. Although high-resolution structures of the receptor subunits of the TOM complex were deposited in the early 2000s, those of entire TOM complexes became available only in 2019. The structural details of these TOM complexes, consisting of the dimer of the β-barrel import channel Tom40 and four α-helical membrane proteins, revealed the presence of several distinct paths and exits for the translocation of over 1,000 different mitochondrial precursor proteins. High-resolution structures of TOM complexes now open up a new era of studies on the structures, functions, and dynamics of the mitochondrial import system.
High-Resolution Single-Molecule Magnetic Tweezers
Authors: Choi Hyun-Kyu , Kim Hyun Gyu , Shon Min Ju , Yoon Tae-Young
Published: March 2022

Single-molecule magnetic tweezers deliver magnetic force and torque to single target molecules, permitting the study of dynamic changes in biomolecular structures and their interactions. Because the magnetic tweezer setups can generate magnetic fields that vary slowly over tens of millimeters—far larger than the nanometer scale of the single molecule events being observed—this technique can maintain essentially constant force levels during biochemical experiments while generating a biologically meaningful force on the order of 1–100 pN. When using bead–tether constructs to pull on single molecules, smaller magnetic beads and shorter submicrometer tethers improve dynamic response times and measurement precision. In addition, employing high-speed cameras, stronger light sources, and a graphics programming unit permits true high-resolution single-molecule magnetic tweezers that can track nanometer changes in target molecules on a millisecond or even submillisecond time scale. The unique force-clamping capacity of the magnetic tweezer technique provides a way to conduct measurements under near-equilibrium conditions and directly map the energy landscapes underlying various molecular phenomena. High-resolution single-molecule magnetic tweezerscan thus be used to monitor crucial conformational changes in single-protein molecules, including those involved in mechanotransduction and protein folding.
Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS–cGAMP–STING Pathway
Authors: Ritchie Christopher , Carozza Jacqueline A. , Li Lingyin
Published: March 2022

In the decade since the discovery of the innate immune cyclic GMP–AMP synthase (cGAS)–2′3′-cyclic GMP–AMP (cGAMP)–stimulator of interferon genes (STING) pathway, its proper activation and dysregulation have been rapidly implicated in many aspects of human disease. Understanding the biochemical, cellular, and regulatory mechanisms of this pathway is critical to developing therapeutic strategies that either harness it to boost defense or inhibit it to prevent unwanted inflammation. In this review, we first discuss how the second messenger cGAMP is synthesized by cGAS in response to double-stranded DNA and cGAMP's subsequent activation of cell-type-dependent STING signaling cascades with differential physiological consequences. We then review how cGAMP as an immunotransmitter mediates tightly controlled cell–cell communication by being exported from producing cells and imported into responding cells via cell-type-specific transporters. Finally, we review mechanisms by which thecGAS–cGAMP–STING pathway responds to different sources of mislocalized double-stranded DNA in pathogen defense, cancer, and autoimmune diseases.
Constellation diagram techniques for NGS
Authors: Gradov Oleg
Published: March 2022

Due to the increasing amount of NGS data and the increasing complexity of quick analytics, the semi-quantitative interpretation of sequencing data, approaches of the so-called “signal-processing-based bioinformatics” [1-7] become very popular, providing extraction of the valuable information not post factum from data mining, but in real time during analysis of the signal from a physical device (sequencer). In the framework of signal-processing-based bioinformatics principle, two main trends can be distinguished: DSP-B (based on digital signal processing - DSP) and ASP-B (based on analog signal processing - ASP), the difference between which is evident not only in the speed and quantization / discretization or their absence, but also in the types of modulation / manipulation of the signal, which is rarely emphasized, limited to a simple set of basic settings. We propose to use the method of visualization of constellation diagrams, “signal constellations” displaying various types of modulation / manipulation, convenient for visualization in specific cases of NGS, including ASP-NGS. To analyze the frequency of occurrence, it is possible to visualize the ASP signal in the PFM (Pulse-Frequency Modulation) mode. To analyze the complementarity using two nucleotides, we suggest using binary phase shift keying (BPSK), and for visualization using four bases (without minor bases) it is rational to use quadrature phase shift keying (QPSK). For a number of tasks, the analyst can also use PPM (pulse-porosity modulation).
Efficacy and Safety of Chuan Huang Fang Combining Reduced Glutathione in Treating Acute Kidney Injury (Grades 1–2) on Chronic Kidney Disease (Stages 2–4): Study Protocol for a Multicenter Randomized Controlled Clinical Trial
Authors: Chen Ling , Gong Xuezhong
Published: March 2022

Background. Acute kidney injury (AKI) is a global public health challenge resulting in considerable morbidity and mortality. AKI on chronic kidney disease (CKD) (AKI on CKD, A on C) accounts for about a third of total AKI. For severe AKI grade 3, renal replacement therapy (RRT) should be implemented in time. However, the lack of recognized drug treatment method for AKI grades 1–2 is a crucial problem in clinic. Chuan Huang Fang (CHF) is a Chinese herbal formulation developed for the treatment of A on C from the Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies suggested that CHF might effectively protect renal functions of A on C patients. As a widely used antioxidant in clinic, reduced glutathione (RG) is reported to improve the clinical efficacy of high-flux hemodialysis (HFHD) in severe AKI patients recently. To address the crucial problem mentioned above, thus we design a new clinical protocol of CHF combining RG and try to evaluate the efficacy and safety of this protocol in treating patients diagnosed with CKD stages 2–4 complicated with AKI grades 1–2. Methods. This is a multicenter randomized controlled clinical trial. We intend to enroll 162 participants, and these participants will be divided into the RG group, the CHF group, and the RG + CHF group randomly assigning 1 : 1 : 1 principle. The RG group will be general treatments combining RG, the CHF group will be general treatments combining CHF, and the RG + CHF group will be general treatments combining RG and CHF. The duration of treatment will last two weeks. The primary evaluation outcome will be the change in the slope of serum creatinine (Scr) over 2 weeks. Secondary evaluation outcomes include changes in blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), gamma-glutamyl transpeptidase (γ-GT), etc.), traditional Chinese medicine (TCM) symptoms, inflammatory indicators, and oxidative stress indicators. Meanwhile, the vital sign indicators and adverse events (AEs) will be closely observed. These dates will be meticulously recorded and properly handled by investigators throughout the study. Discussion. This study will provide convictive research-derived data to evaluate clinical efficacy and safety of CHF combing RG for CKD stages 2–4 complicated with AKI grades 1–2 and provide an evidence-based recommendation for clinicians. The timely completion of this trial will provide a novel drug treatment method for A on C. This trial is registered with ChiCTR2100043311 and registered on February 9, 2021.
Depleted Long Noncoding RNA GAS5 Relieves Intervertebral Disc Degeneration via microRNA-17-3p/Ang-2
Authors: Yu Xiaojun , Liu Qikun , Wang Yinguang , Bao Yuan , Jiang Yongqiao , Li Mengwei , Li Zhiwei , Wang Baodong , Yu Lei , Wang Shanxi , Shao Ming , Kang Hao
Published: March 2022

Intervertebral disc degeneration (IVDD) remains a clinical challenge and requires more effective therapeutic targets. Long noncoding RNAs (lncRNAs) have emerged as critical modulators of multiple biological processes, such as cell proliferation and extracellular matrix (ECM) remodeling. Accordingly, the current study sets out to explore the influence of the lncRNA growth arrest-specific 5 (GAS5) on IVDD and investigate the possible involvement of microRNA-17-3p (miR-17-3p)/Angiopoietin-2 (Ang-2) axis. Firstly, the expression patterns of GAS5, miR-17-3p, and Ang-2 were characterized by RNA quantification from the isolated human degenerative nucleus pulposus (NP) tissues. miR-17-3p was found to express at an abnormal low level while GAS5 and Ang-2 expressed at aberrant high level in the human degenerative NP tissues. Utilizing dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays, GAS5 was found to competitively bound to miR-17-3p and further upregulate the expression of Ang-2, a target gene of miR-17-3p. Employing gain- and loss-of-function approaches, their expressions were altered in human degenerative nucleus pulposus cells (NPCs), followed by IL-1β treatment, in order to identify their roles in NP cell proliferation, apoptosis, and ECM metabolism. Silencing of GAS5 expression restrained the levels of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, MMP3, MMP13, ADAMTS4, and ADAMTS5 and increased collagen II and aggrecan levels. In vitro experiments also revealed that GAS5 depletion inhibited apoptosis and ECM degradation in HDNPCs, while elevating the proliferation through downregulation of Ang-2 by increasing miR-17-3p. Furthermore, in vivo data further validated that either GAS5 silencing or miR-17-3p reexpression alleviated IVDD degree with the help of IVDD mouse models. Altogether, our findings substantiated that downregulation of GAS5 reduced NPC apoptosis and promoted ECM remodeling, ultimately ameliorating the IVDD via miR-17-3p-dependent inhibition of Ang-2. We hope our discoveries offer a fresh molecular insight that can aid the development of novel therapies against IVDD.
Exosomes from Bone Marrow Mesenchymal Stem Cells with Overexpressed Nrf2 Inhibit Cardiac Fibrosis in Rats with Atrial Fibrillation
Authors: Xu Lijuan , Fan Yingchao , Wu Liting , Zhang Cui , Chu Min , Wang Yuan , Zhuang Wenfang
Published: March 2022

Background. Even though nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling has been associated with the pathogenesis of multiple heart conditions, data on roles of Nrf2 within atrial fibrillation (AF) still remain scant. The present investigation had the aim of analyzing Nrf2-overexpressing role/s upon bone mesenchymal stem cell- (BMSC-) derived exosomes in rats with AF. Methods. Exosomes were collected from control or Nrf2 lentivirus-transduced BMSCs and then injected into rats with AF through the tail vein. AF duration was observed using electrocardiography. Immunohistochemical staining was then employed for assessing Nrf2, HO-1, α-SMA, collagen I, or TGF-β1 expression profiles within atrial myocardium tissues. Conversely, Masson staining was utilized to evaluate atrial fibrosis whereas apoptosis within myocardia was evaluated through TUNEL assays. In addition, TNF-α, IL-1β, IL-4, or IL-10 serum expression was assessed through ELISA. Results. Results of the current study showed significant downregulation of Nrf2/HO-1 within AF rat myocardia. It was found that injection of the control or Lv-Nrf2 exosomes significantly alleviated and lowered AF timespans together with reducing cardiomyocyte apoptosis. Moreover, injection of Lv-Nrf2 exosomes essentially lowered AF-driven atrial fibrosis and also inhibited inflammatory responses in the rats with AF. Conclusion. Delivery of BMSC-derived exosomes using overexpressed Nrf2 inhibited AF-induced arrhythmias, myocardial fibrosis, apoptosis, and inflammation via Nrf2/HO-1 pathway triggering.
A Note on Lacunary Sequence Spaces of Fractional Difference Operator of Orderα,β
Authors: Cai Qing-Bo , Sharma Sunil K. , Ayman Mursaleen Mohammad
Published: March 2022

In the present paper, we defined lacunary sequence spaces of fractional difference operator of orderα,βovern-normed spaces via Musielak-Orlicz functionM=Ik. Our aim in this paper is to study some topological properties and inclusion relation between the spacesI−NαβA,M,u,θ,Δγ,·,⋯,·0,I−NαβA,M,u,θ,Δγ,·,⋯,·, andI−NαβA,M,u,θ,Δγ,·,⋯,·∞.
Multiple Micronutrient Supplementation: As a Supportive Therapy in the Treatment of COVID‐19
Authors: Diyya A Salomy Monica , Thomas Noel Vinay
Published: March 2022

During the infection and treatment of the SARS‐CoV‐2 viral infection, age and comorbidities play a major role in the successful management of COVID‐19. The nutritional status changes which occur in the body vary with the age and underlying conditions and has a vital role in the functioning of the immune system and cellular membrane integrity, thus minimizing the vulnerability to the infection. Considering the data already published by eminent researchers, a few micronutrients have shown outstanding results as supportive therapies in the treatment of viral infections. Micronutrient like zinc improves the membrane barrier integrity, has anti‐inflammatory activity, and is involved in antibody production. Vitamin A supports the phagocytic activity of macrophages, while vitamin C reduces the worsening of respiratory tract infections by restoring the dysfunctional epithelial barrier of the lungs. Vitamin D, vitamin E, selenium, and omega‐3 fatty acid metabolites play a major role in immunomodulation and in the inhibition of proinflammatory cytokine production. Magnesium is involved in the synthesis of antibodies, while copper, vitamin B12, and folate have significant effects on immune cells. A few researchers suggest that iron supplementation has reduced the risk of acquiring respiratory tract infections in children. As the age of the patient increases, the need for micronutrients increases, thus leading to an imbalanced nutritional status which in turn increases the risk and fatality of the infections. The use of micronutrients in modulating the inflammatory, immune responses, and the epithelial barrier integrity is explored during the treatment of viral infections for faster recovery.
Hierarchical Network Emotional Assistance Mechanism for Emotion Cause Extraction
Authors: Wang Yu , Wei Bingjie , Ruan Shuhua , Chen Xingshu , Wang Haizhou
Published: March 2022

The fine-grained task of emotion analysis, emotion cause extraction, is a current research hotspot. It aims to discover the underlying reasons behind the emotional expression in texts. Most of the existing work regards the task as an independent text clause classification problem, ignoring the relationship between the clauses and failing to use the indicative relationship between emotional sentences and emotional cause sentences. The existence of these problems greatly affects the accuracy of the task. In this work, an emotion cause extraction method based on a hierarchical network emotional assistance mechanism is proposed. This method uses a hierarchical network composed of bidirectional gated recurrent units, attention mechanism, and graph convolutional networks to capture clause context information, deep semantic information, and structural information between clause neighborhoods. At the same time, by enhancing the emotional information representation of the graph convolutional network nodes, the clause features of the text emotional keywords are introduced into the discovery of candidate cause sentences. Thus, a model of the deep neural network combined with the emotional assistance mechanism is established. Compared with the existing methods, the model established in this paper has better classification performance on the Chinese emotion cause dataset.