bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Artificial Intelligence-Assisted Psychotherapy in Patients With Anxiety Disorders: A Prospective, National Multicenter Randomized Controlled Trial Protocol
Authors: Su Shanshan , Wang Yuan , Jiang Wenhui , Zhao Wenqing , Gao Rui , Wu Yanru , Tao Jing , Su Yousong , Zhang Jie , Li Kangzheng , Zhang Zhuojun , Zhao Min , Wang Zhen , Luo Yanli , Huang Xiao , Wang Lanlan , Wang Xiaoping , Li Yi , Jia Qiufang , Wang Lianzi , Li Huafang , Huang Jingjing , Qiu Jianyin , Xu Yifeng
Published: January 2022

Background

Anxiety disorders have the highest prevalence of all psychiatric disorders in China. Medication and psychotherapy are two main treatment approaches for this group of disorders, and when used in combinations are significantly more beneficial than medication alone. The resources are insufficient. The availability of psychotherapy is low due to the limited resources. Artificial intelligence (AI)-assisted psychotherapy offers an opportunity to develop an efficient and standardized psychotherapy model and improve the availability of psychotherapy, which is key to improve the clinical efficacy of anxiety disorder treatments.

Objectives

The present protocol aims to determine whether medication plus AI-assisted psychotherapy has greater efficacy than medication alone in the treatment of anxiety disorders.

Methods

We will recruit patients in eight hospitals in China. Seven hundred and eight patients with anxiety disorders will be randomly allocated on a 1:1 basis to either medication plus AI-assisted psychotherapy group, or medication alone group. We have built an AI psychotherapy robot named XIAO AN. In this study we will deliver psychotherapy to patients in the medication plus AI-assisted psychotherapy group. Patients will be assessed at baseline and at the end of week 2, 4, 8, and 12. Follow-up assessments will be conducted at 3 and 6 months posttreatment. The primary outcome is change of Hamilton Anxiety Rating Scale (HAMA) score from baseline the end of 12-week treatment. A secondary efficacy outcome will be improvement in treatment at an early stage (score reduction in HAMA ≥25% after 2 weeks of treatment). Other measurements include Hamilton Depression Scale, Clinical Global Impression, Treatment Emergent Symptom Scale, Social Disability Screening Schedule, Insomnia Severity Index and so on. Scales will be assessed by independent raters who are blind to treatment allocation and analyses will be conducted by a statistician who is also blind to treatment allocation.

Discussion

This will be the first multicentered randomized controlled single-blind trial in China to assess the efficacy of medication plus AI-assisted psychotherapy compared with medication alone for anxiety disorders. The study has the potential to address the limitations of the limited availability of psychotherapy, and to augment the efficacy of the treatment of anxiety disorders in China.
Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine
Authors: Beversdorf David Q. , Sohl Kristin , Levitskiy David , Tennant Priscilla , Goin-Kochel Robin P. , Shaffer Rebecca C. , Confair Alexandra , Middleton Frank A. , Hicks Steven D.
Published: January 2022

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.
Taking Pause: A COVID-19 Student Reflection on Global Health Research Opportunities, Training, and Institutional Reform
Authors: Chu Casey , Griffin Gianna , Williams Joseph L.
Published: January 2022

Restrictions to research due to COVID-19 have required global health researchers to factor public health measures into their work and discuss the most ethical means to pursue research under safety concerns and resource constraints. In parallel, global health research opportunities for students have also adapted to safety concerns and resource constraints. Some projects have been canceled or made remote, but inventively, domestic research opportunities have been created as alternatives for students to continue gaining global health learning competencies. Knowing the ethical challenges inherent in short-term student global health research and research in strained health systems, it is intriguing why these safer alternatives were not previously pervasive in global health education. This paper provides perspectives from students training at academic institutions in the US on how COVID-19 disrupted student research and what can be learned from the associated shifts in global health research. Additionally, the authors take this opportunity to advocate for academic institutions from high-income countries to reflect on long-standing global health research conventions that have been perpetuated and bolster training for students conducting global health research. The authors draw on their experiences, existing literature, and qualitative interviews with students who pursued global health research during COVID-19.
The Ecology-Economy-Transport Nexus: Evidence from Fujian Province, China
Authors: Wang Wulin , Gong Jiao , Yang Wenyue , Zeng Jingyu
Published: January 2022

The coordinated relationship between ecology, economy and transportation is essential for regional sustainable development. Does the high-quality ecological environment mean the lagging development of economy and transportation, or does the rapid growth of the economy and transportation lead to the deterioration of the ecological environment? To shed new light on the complicated relationship between ecology, economy and transportation, our study aims to construct three comprehensive indicators, including an ecological index (EI), economic development level (EC) and transport superiority degree (TR), to reflect the systems mentioned above, and to measure the coordination of the three indicators’ development and evolution using a model of the coordination degree (CD). Specifically, and by applying methods for the indicators’ normalization, including superposition analysis and principal component analysis, the three indicators’ values are reasonably evaluated for measuring their coordination relationship. The above three indicators use data from 58 counties in Fujian province from 2000 to 2018 in our study. All three indicators show differences in the west and east of Fujian province; the EI is relatively low in the eastern coastal areas and relatively high in the western mountainous areas, the EC shows a relatively discrete and irregular distribution and the distribution pattern of the TR is almost the opposite of the EI. The CD shows a relationship among the three indicators, with the EI and EC coordinated in most counties and the EI and TR coordinated in most counties, while the highly coordinated counties are mainly distributed in the northwest and east coastal regions of Fujian province in 2000, and the northwest, south and northeast of Fujian province in 2018. More than 50% of the county EC and TR values are kept in a coordinated state, and are mainly distributed in the eastern coast and central part of Fujian province. Over 50% of counties’ CD between EI and EC, EI and TR and EC and TR are in a coordinated state. The CD of the EI and EC and TR, in most counties, are in a coordinated state, mainly distributed in the eastern coast and central areas of Fujian province. In other words, the findings show that the coordinated state of ecology, economy and transportation can be achieved at the county level of Fujian province. These conclusions have significant reference value for understanding regional sustainable development.
Piezomagnetic Anomalies Associated with the 2021 MW 7.3 Maduo (China) Earthquake
Authors: Song Chengke , Zhang Pengtao , Wang Can , Chu Fei
Published: January 2022

Stress changes due to earthquake rupture can disturb geomagnetic fields significantly. In order to investigate the impact of the 2021 MW 7.3 Maduo earthquake on geomagnetic fields, a piezomagnetic model is constructed based on the coseismic slip to calculate the static coseismic piezomagnetic anomalies (PMs). The PMs are considerable in near-field. However, the PMs are negligible in regions tens of kilometers from the fault rupture. The PMs of our model are consistent with those of other strike-slip earthquakes, indicating that our piezomagnetic model is reasonable. The east component of observed coseismic geomagnetic changes and calculated PMs on a geomagnetic repeat station located about 6 km from fault trace are +4.8 ± 2.2 nanotesla and +4.3 nanotesla, respectively. It seems that the piezomagnetic model can explain the observed data. The PMs are up to 10 nanotesla in the near-field with the initial magnetization of 3 A/m and stress sensitivity of 2 × 10−3 MPa−1. Consequently, considerable coseismic geomagnetic changes that are above error could be observed along the fault, especially at locations with geometrical complexities.
Nanoindentation of Historic and Artists’ Paints
Authors: Łukomski Michał , Bridarolli Alexandra , Fujisawa Naoki
Published: January 2022

The micromechanical analysis of composite materials has become indispensable in the field of material science and for industrial applications, where small sample sizes predominate. In recent years, nanoindentation has been more readily utilized within the cultural heritage field, producing invaluable insight in the properties of artists’ materials. To take full advantage of the technique, however, issues related to the scale of the analysis need to be addressed. These include understanding the influence of sample preparation and material heterogeneity on the obtained results as well as establishing correlations between micro/nano-scale and macro-scale mechanical parameters. Moreover, the nanoindentation tests of time-dependent paints and adhesives can be difficult to interpret and thus require the development of unique measuring protocols. This review discusses nanoindentation studies of artists’ paints carried out over the last two decades. Analysis of presented experimental and theoretical works focuses on comprehending limitations of the technique and developing strategies to overcome them. We demonstrate how consistent and reliable measurements can be performed when experimental protocols consider the effects of geometry, roughness, and time-dependent properties of paint, as well as the compliance of the measuring system. Development of measurement protocols accounting for specific properties of historic and artists’ paints opens up the prospect of more routine application of nanoindentation in the field of cultural heritage.
Effect of Short-Term Deep-Pressure Portable Seat on Behavioral and Biological Stress in Children with Autism Spectrum Disorders: A Pilot Study
Authors: Afif Ilham Yustar , Farkhan Muhammad , Kurdi Ojo , Maula Mohamad Izzur , Ammarullah Muhammad Imam , Setiyana Budi , Jamari J. , Winarni Tri Indah
Published: January 2022

Children with autism spectrum disorder (ASD) have challenging behaviors, which are associated with difficulties in parenting. Deep pressure is a therapeutic modality in occupational therapy, and it was reported to produce a calming effect. This study aimed to determine whether the short-term use of an autism hug machine portable seat (AHMPS) improves behavioral and neurobiological stress in children with ASD, and to determine whether AHMPS with an inflatable wrap or manual pull is more effective. This study enrolled children with ASD who were administered with the inflatable wrap (group I) and manual pull (group II) for 20 min twice a week for 3 weeks. Conners’ Parent Rating Scale-48 (CPRS-48) was used to rate behavioral improvements, and galvanic skin response (GSR) was used to measure sympathetic stress response. A total of 20 children with ASD (14 boys and 6 girls; aged 7–13 years) were included. CPRS-48 presented conduct problems: behavior was significantly decreased in the inflatable group (p = 0.007) compared to the manual pull group. The GSR captured a significant reduction in sympathetic response (p = 0.01) only in group I. Neurobiological stress was reduced in children who were wearing the AHMPS inflatable wrap; therefore, AHMPS inflatable wrap is an effective method to reduce emotional arousal.
Expression of the Adenosine A2A-A3 Receptor Heteromer in Different Brain Regions and Marked Upregulation in the Microglia of the Transgenic APPSw,Ind Alzheimer’s Disease Model
Authors: Lillo Alejandro , Raïch Iu , Lillo Jaume , Pérez-Olives Catalina , Navarro Gemma , Franco Rafael
Published: January 2022

Adenosine (Ado) receptors have been instrumental in the detection of heteromers and other higher-order receptor structures, mainly via interactions with other cell surface G-protein-coupled receptors. Apart from the first report of the A1 Ado receptor interacting with the A2A Ado receptor, there has been more recent data on the possibility that every Ado receptor type, A1, A2A, A2B, and A3, may interact with each other. The aim of this paper was to look for the expression and function of the A2A/A3 receptor heteromer (A2AA3Het) in neurons and microglia. In situ proximity ligation assays (PLA), performed in primary cells, showed that A2AA3Het expression was markedly higher in striatal than in cortical and hippocampal neurons, whereas it was similar in resting and activated microglia. Signaling assays demonstrated that the effect of the A2AR agonist, PSB 777, was reduced in the presence of the A3R agonist, 2-Cl-IB-MECA, whereas the effect of the A3R agonist was potentiated by the A2AR antagonist, SCH 58261. Interestingly, the expression of the heteromer was markedly enhanced in microglia from the APPSw,Ind model of Alzheimer’s disease. The functionality of the heteromer in primary microglia from APPSw,Ind mice was more similar to that found in resting microglia from control mice.
Magnesium as a Methanation Suppressor for Iron- and Cobalt-Based Oxide Catalysts during the Preferential Oxidation of Carbon Monoxide
Authors: Fadlalla Mohamed I. , Nyathi Thulani M. , Claeys Michael
Published: January 2022

The preferential oxidation of CO (CO-PrOx) to CO2 is an effective catalytic process for purifying the H2 utilized in proton-exchange membrane fuel cells for power generation. Our current work reports on the synthesis, characterization and CO-PrOx performance evaluation of unsubstituted and magnesium-substituted iron- and cobalt-based oxide catalysts (i.e., Fe3O4, Co3O4, MgFe2O4 and MgCo2O4). More specifically, the ability of Mg to stabilize the MgFe2O4 and MgCo2O4 structures, as well as suppress CH4 formation during CO-PrOx was of great importance in this study. The cobalt-based oxide catalysts achieved higher CO2 yields than the iron-based oxide catalysts below 225 °C. The highest CO2 yield (100%) was achieved over Co3O4 between 150 and 175 °C, however, undesired CH4 formation was only observed over this catalyst due to the formation of bulk fcc and hcp Co0 between 200 and 250 °C. The presence of Mg in MgCo2O4 suppressed CH4 formation, with the catalyst only reducing to a CoO-type phase (possibly containing Mg). The iron-based oxide catalysts did not undergo bulk reduction and did not produce CH4 under reaction conditions. In conclusion, our study has demonstrated the beneficial effect of Mg in stabilizing the active iron- and cobalt-based oxide structures, and in suppressing CH4 formation during CO-PrOx.
Phenylketonuria Patients’ and Their Caregivers’ Perception of the Pandemic Lockdown: The Results of a National Online Survey
Authors: Walkowiak Dariusz , Mikołuć Bożena , Mozrzymas Renata , Kałużny Łukasz , Didycz Bożena , Korycińska-Chaaban Dorota , Patalan Michał , Jagłowska Joanna , Chrobot Agnieszka , Staszewski Rafał , Walkowiak Jarosław
Published: January 2022

The first pandemic lockdown dramatically impacted many aspects of everyday life, including healthcare systems. The purpose of this study was to identify problems of patients with phenylketonuria (PKU) and their parents/caregivers during that time. We aimed to analyse potential differences in the self-reported compliance and characteristics of contacts with a doctor/dietitian before and during the pandemic lockdown and the perception of access to special food and opinions on remote contacts between a particular group of respondents. All participants (n = 614) were asked to complete an online questionnaire that consisted of 31 questions on pandemic-related events and circumstances which may have directly or indirectly impacted health and treatment. The people who completed the survey were divided into three groups: parents of PKU children (n = 403), parents of PKU adults (n = 58) and PKU patients older than 16 years (n = 153). The differences among the three analysed groups were found in the number of contacts, the way of contacting a doctor/dietitian during the pandemic and satisfaction with remote contact. Caregivers of children with PKU reported better therapy compliance, more frequent contacts with specialists and more satisfaction with remote visits than adult patients. We also observed a relationship between satisfaction from remote contact and self-reported frequency of contacts with a doctor/dietitian, as well as a relationship between satisfaction from remote contact and recommended blood Phe levels reported by both patients and caregivers. Travel time exceeding three hours from the respondents’ location to their doctor was associated with higher odds of their recognition of remote contact as a method of PKU treatment only in the group of caregivers. In the caregiver groups, the reported worse access to low-Phe products during the lockdown was linked to the perceived difficulty of maintaining the diet. However, such a relationship was not found among patients. In conclusion, significant differences in the perception of the pandemic lockdown and its impact on health and treatment-related issues were found.
Two-Year Follow-Up of Trypanosoma brucei gambiense Serology after Successful Treatment of Human African Trypanosomiasis: Results of Four Different Sero-Diagnostic Tests
Authors: Inocencio da Luz Raquel , Tablado Alonso Sara , Büscher Philippe , Verlé Paul , De Weggheleire Anja , Mumba Ngoyi Dieudonné , Pyana Pati Patient , Hasker Epco
Published: January 2022

Gambiense human African trypanosomiasis (gHAT), also known as gambiense sleeping sickness, is a parasitic infection caused by Trypanosoma brucei gambiense. During the last decades, gHAT incidence has been brought to an all-time low. Newly developed serological tools and drugs for its diagnosis and treatment put the WHO goal of interruption of transmission by 2030 within reach. However, further research is needed to efficiently adapt these new advances to new control strategies. We assessed the serological evolution of cured gHAT patients over a two-year period using four different tests: the rapid diagnostic test (RDT) HAT Sero K-SeT, ELISA/T.b. gambiense, Trypanosoma brucei gambiense inhibition ELISA (iELISA), and the immune trypanolysis test. High seropositive rates were observed in all the tests, although sero-reversion rates were different in each test: ELISA/T.b. gambiense was the test most likely to become negative two years after treatment, whereas RDT HAT Sero-K-SeT was the least likely. iELISA and trypanolysis showed intermediate and comparable probabilities to become negative. Stage 1 patients were also noted to be more likely to become negative than Stage 2 patients in all four serological tests. Our results confirm previous findings that trypanosome-specific antibody concentrations in blood may persist for up to two years, implying that HAT control programs should continue to take the history of past HAT episodes into consideration.
An Efficient Multi-Level Convolutional Neural Network Approach for White Blood Cells Classification
Authors: Cheuque César , Querales Marvin , León Roberto , Salas Rodrigo , Torres Romina
Published: January 2022

The evaluation of white blood cells is essential to assess the quality of the human immune system; however, the assessment of the blood smear depends on the pathologist’s expertise. Most machine learning tools make a one-level classification for white blood cell classification. This work presents a two-stage hybrid multi-level scheme that efficiently classifies four cell groups: lymphocytes and monocytes (mononuclear) and segmented neutrophils and eosinophils (polymorphonuclear). At the first level, a Faster R-CNN network is applied for the identification of the region of interest of white blood cells, together with the separation of mononuclear cells from polymorphonuclear cells. Once separated, two parallel convolutional neural networks with the MobileNet structure are used to recognize the subclasses in the second level. The results obtained using Monte Carlo cross-validation show that the proposed model has a performance metric of around 98.4% (accuracy, recall, precision, and F1-score). The proposed model represents a good alternative for computer-aided diagnosis (CAD) tools for supporting the pathologist in the clinical laboratory in assessing white blood cells from blood smear images.
Peculiarities of Pore Water Ionic Composition in the Bottom Sediments and Subsea Permafrost: A Case Study in the Buor-Khaya Bay
Authors: Ulyantsev Alexander , Polyakova Natalya , Trukhin Ivan , Parotkina Yulia , Dudarev Oleg , Semiletov Igor
Published: January 2022

This paper emphasises an ionic composition of the pore water of bottom sediments and subsea permafrost as an indicator of salinization of the thawed strata. Based on measurements of concentration of sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) cations, chlorides (Cl–) and sulphates (SO42–) in water extracts from bottom sediments and subsea permafrost deposits from three boreholes, a spatial difference in salinization of thawed strata within the Buor-Khaya Bay was shown. The vertical pattern of the macroions in the unfrozen segment was formed under subsea thawing of permafrost. The frozen strata contain fresh pore water and have been evolving under downward penetration of salt and subsequent thawing of subsea permafrost. Based on the analyses of thawed deposits, it was shown that the maximum pore water salinity was observed in the horizons enriched with sand and plant detritus. Over the boundary of subsea permafrost in the Ivashkina Lagoon, the pronounced total ion concentration (up to 50 g/L of Cl–) of pore water was observed. This segment consists of moss debris, which is characterised by high porosity. The moss layer promotes the accumulation of dissolved pore water compounds and subsequent thawing of the frozen sediments.
Estimation of Vegetative Growth in Strawberry Plants Using Mobile LiDAR Laser Scanner
Authors: Saha Kowshik Kumar , Tsoulias Nikos , Weltzien Cornelia , Zude-Sasse Manuela
Published: January 2022

Monitoring of plant vegetative growth can provide the basis for precise crop management. In this study, a 2D light detection and ranging (LiDAR) laser scanner, mounted on a linear conveyor, was used to acquire multi-temporal three-dimensional (3D) data from strawberry plants (‘Honeoye’ and ‘Malling Centenary’) 14–77 days after planting (DAP). Canopy geometrical variables, i.e., points per plant, height, ground projected area, and canopy volume profile, were extracted from 3D point cloud. The manually measured leaf area exhibited a linear relationship with LiDAR-derived parameters (R2 = 0.98, 0.90, 0.93, and 0.96 with number of points per plant, volume, height, and projected canopy area, respectively). However, the measuring uncertainty was high in the dense canopies. Particularly, the canopy volume estimation was adapted to the plant habitus to remove gaps and empty spaces in the canopy point cloud. The parametric values for maximum point to point distance (Dmax) = 0.15 cm and slice height (S) = 0.10 cm resulted in R² = 0.80 and RMSPE = 26.93% for strawberry plant volume estimation considering actual volume measured by water displacement. The vertical volume profiling provided growth data for cultivars ‘Honeoye’ and ‘Malling Centenary’ being 51.36 cm³ at 77 DAP and 42.18 cm3 at 70 DAP, respectively. The results contribute an approach for estimating plant geometrical features and particularly strawberry canopy volume profile based on LiDAR point cloud for tracking plant growth.
Protein Disulfide Isomerase A3 Regulates Influenza Neuraminidase Activity and Influenza Burden in the Lung
Authors: Chamberlain Nicolas , Ruban Mona , Mark Zoe F. , Bruno Sierra R. , Kumar Amit , Chandrasekaran Ravishankar , Souza De Lima Dhemerson , Antos Danielle , Nakada Emily M. , Alcorn John F. , Anathy Vikas
Published: January 2022

Influenza (IAV) neuraminidase (NA) is a glycoprotein required for the viral exit from the cell. NA requires disulfide bonds for proper function. We have recently demonstrated that protein disulfide isomerase (PDI)A3 is required for oxidative folding of IAV hemagglutinin (HA), and viral propagation. However, it not known whether PDIs are required for NA maturation or if these interactions represent a putative target for the treatment of influenza infection. We sought to determine whether PDIA3 is required for disulfide bonds of NA, its activity, and propagation of the virus. Requirement of disulfides for NA oligomerization and activity were determined using biotin switch and redox assays in WT and PDIA3−/− in A549 cells. A PDI specific inhibitor (LOC14) was utilized to determine the requirement of PDIs in NA activity, IAV burden, and inflammatory response in A549 and primary mouse tracheal epithelial cells. Mice were treated with the inhibitor LOC14 and subsequently examined for IAV burden, NA activity, cytokine, and immune response. IAV-NA interacts with PDIA3 and this interaction is required for NA activity. PDIA3 ablation or inhibition decreased NA activity, viral burden, and inflammatory response in lung epithelial cells. LOC14 treatment significantly attenuated the influenza-induced inflammatory response in mice including the overall viral burden. These results provide evidence for PDIA3 inhibition suppressing NA activity, potentially providing a novel platform for host-targeted antiviral therapies.
CRISPR Editing Enables Consequential Tag-Activated MicroRNA-Mediated Endogene Deactivation
Authors: Papasavva Panayiota L. , Patsali Petros , Loucari Constantinos C. , Kurita Ryo , Nakamura Yukio , Kleanthous Marina , Lederer Carsten W.
Published: January 2022

Molecular therapies and functional studies greatly benefit from spatial and temporal precision of genetic intervention. We therefore conceived and explored tag-activated microRNA (miRNA)-mediated endogene deactivation (TAMED) as a research tool and potential lineage-specific therapy. For proof of principle, we aimed to deactivate γ-globin repressor BCL11A in erythroid cells by tagging the 3′ untranslated region (UTR) of BCL11A with miRNA recognition sites (MRSs) for the abundant erythromiR miR-451a. To this end, we employed nucleofection of CRISPR/Cas9 ribonucleoprotein (RNP) particles alongside double- or single-stranded oligodeoxynucleotides for, respectively, non-homologous-end-joining (NHEJ)- or homology-directed-repair (HDR)-mediated MRS insertion. NHEJ-based tagging was imprecise and inefficient (≤6%) and uniformly produced knock-in- and indel-containing MRS tags, whereas HDR-based tagging was more efficient (≤18%), but toxic for longer donors encoding concatenated and thus potentially more efficient MRS tags. Isolation of clones for robust HEK293T cells tagged with a homozygous quadruple MRS resulted in 25% spontaneous reduction in BCL11A and up to 36% reduction after transfection with an miR-451a mimic. Isolation of clones for human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells tagged with single or double MRS allowed detection of albeit weak γ-globin induction. Our study demonstrates suitability of TAMED for physiologically relevant modulation of gene expression and its unsuitability for therapeutic application in its current form.
Mechanisms of Abscisic Acid-Mediated Drought Stress Responses in Plants
Authors: Muhammad Aslam Mehtab , Waseem Muhammad , Jakada Bello Hassan , Okal Eyalira Jacob , Lei Zuliang , Saqib Hafiz Sohaib Ahmad , Yuan Wei , Xu Weifeng , Zhang Qian
Published: January 2022

Drought is one of the major constraints to rain-fed agricultural production, especially under climate change conditions. Plants evolved an array of adaptive strategies that perceive stress stimuli and respond to these stress signals through specific mechanisms. Abscisic acid (ABA) is a premier signal for plants to respond to drought and plays a critical role in plant growth and development. ABA triggers a variety of physiological processes such as stomatal closure, root system modulation, organizing soil microbial communities, activation of transcriptional and post-transcriptional gene expression, and metabolic alterations. Thus, understanding the mechanisms of ABA-mediated drought responses in plants is critical for ensuring crop yield and global food security. In this review, we highlighted how plants adjust ABA perception, transcriptional levels of ABA- and drought-related genes, and regulation of metabolic pathways to alter drought stress responses at both cellular and the whole plant level. Understanding the synergetic role of drought and ABA will strengthen our knowledge to develop stress-resilient crops through integrated advanced biotechnology approaches. This review will elaborate on ABA-mediated drought responses at genetic, biochemical, and molecular levels in plants, which is critical for advancement in stress biology research.
Sexual Habits and Sexual Dysfunctions in a Sample of Patients with Psychotic Disorders Compared to a Group of Healthy Adults
Authors: Barchielli Benedetta , Accinni Tommaso , Ferracuti Stefano , Carlone Luca , Petrini Federica , Biondi Massimo , Pasquini Massimo
Published: January 2022

Background: There is a growing body of literature on the association between psychosis and sexual dysfunction. However, most studies have focused on sexual dysfunction and have not investigated the sexual lives of patients with psychosis across a broader range. Material and Methods: Consecutive patients with a diagnosis of acute psychosis or schizophrenia were recruited to the study after obtaining informed consent (n = 46). In addition, healthy control subjects were recruited (n = 52). Sociodemographic and clinical data, psychopathology, and sexual functioning were assessed. Independent sample t-test to determine group differences was obtained. Results: In both the male and female groups, there are significant differences between psychotic individuals and healthy controls in several areas of their sexual functioning: the control group seemed to better perceive Couple sexuality, Self-eroticism, and overall appeared to have a higher Quality of sexual life; on the other hand, the group of patients with psychosis displayed higher scores in Sexual dysfunction. Conclusions: A poor sexual quality of life may be found in patients with psychotic disorders. Assessment of sexual function in these patients is necessary to identify and manage issues and provide support and help to patients in this important area of life.
On Global Offensive Alliance in Zero-Divisor Graphs
Authors: Juárez Morales Raúl , Reyna Hernández Gerardo , Rosario Cayetano Omar , Romero Valencia Jesús
Published: January 2022

Let Γ(V,E) be a simple connected graph with more than one vertex, without loops or multiple edges. A nonempty subset S⊆V is a global offensive alliance if every vertex v∈V−S satisfies that δS(v)≥δS¯(v)+1. The global offensive alliance numberγo(Γ) is defined as the minimum cardinality among all global offensive alliances. Let R be a finite commutative ring with identity. In this paper, we study the global offensive alliance number of the zero-divisor graph Γ(R).
Lightweight Secure Integer Comparison
Authors: Veugen Thijs
Published: January 2022

We solve the millionaires problem in the semi-trusted model with homomorphic encryption without using intermediate decryptions. This leads to the computationally least expensive solution with homomorphic encryption so far, with a low bandwidth and very low storage complexity. The number of modular multiplications needed is less than the number of modular multiplications needed for one Pallier encryption. The output of the protocol can be either publicly known, encrypted, or secret-shared. The private input of the first player is computationally secure towards the second player, and the private input of the second player is even unconditionally secure towards the first player. We also introduce an efficient client-server solution for the millionaires problem with similar security properties.
On the Highly Accurate Evaluation of the Voigt/Complex Error Function with Small Imaginary Argument
Authors: Wang Yihong , Zhou Bin , Wang Bubin , Zhao Rong , Liu Qi , Dai Minglu
Published: January 2022

A rapidly convergent series, based on Taylor expansion of the imaginary part of the complex error function, is presented for highly accurate approximation of the Voigt/complex error function with small imaginary argument y ≤ 0.1. Error analysis and run-time tests in double-precision arithmetic reveals that in the real and imaginary parts, the proposed algorithm provides an average accuracy exceeding 10−15 and 10−16, respectively, and the calculation speed is as fast as that reported in recent publications. An optimized MATLAB code providing rapid computation with high accuracy is presented.
Preparation of Edible Films with Lactobacillus plantarum and Lactobionic Acid Produced by Sweet Whey Fermentation
Authors: Sáez-Orviz Sara , Marcet Ismael , Rendueles Manuel , Díaz Mario
Published: January 2022

Cheese whey, one of the most abundant by-products of the dairy industry, causes economic losses and pollution problems. In this study, deproteinised sweet whey was fermented by Pseudomonas taetrolens LMG 2336 to produce a prebiotic compound (lactobionic acid, LBA). Endotoxins produced by these microorganisms were successfully removed using microfiltration techniques, allowing the fermented whey permeate to be used in the food industry. The fermented whey permeate was used to develop prebiotic edible films by adding two different concentrations of gelatine (0.45 and 0.9 g gelatine g−1 LBA; LBA45 and LBA90). Furthermore, Lactobacillus plantarum CECT 9567 was added as a probiotic microorganism (LP45 and LP90), creating films containing both a prebiotic and a probiotic. The mechanical properties, water solubility, light transmittance, colour, and microstructure of the films were fully characterised. Additionally, the LBA and probiotic concentration in LP45 and LP90 were monitored under storage conditions. The strength and water solubility of the films were affected by the presence of LBA, and though all these films were homogeneous, they were slightly opaque. In LP45 and LP90, the presence of LBA as a prebiotic improved the viability of L. plantarum during cold storage, compared to the control. Therefore, these films could be used in the food industry to coat different foodstuffs to obtain functional products.
Separating Silver from Tin Silver Alloy Residue: Effect of Agitation Rate
Authors: Kabatesi Juliette Confiance , Wang Jei-Pil
Published: January 2022

In this paper, research on the effects of agitation rate for desilvering tin silver alloy residue by using pyrometallurgy was carried out. SnAg alloy residue with 92 wt.% tin and 3.56 wt.% silver was used in this study, and 99.999 wt.% zinc was added as metal solvent. Residues were melted to a temperature of 400 °C for enriching tin silver alloy. The obtained tin silver alloy was melted in a temperature range of 450 °C to 500 °C by adding zinc to evaluate zinc dissolution. The obtained tin silver zinc was agitated at different agitation rates for 20 min at a temperature of 480 °C, then cooled down while stirring to an eutectic point of tin zinc alloy (198.9 °C) to remove silver zinc dross. X-ray Fluorescent-1800 (XRF-1800) and Field Emission Scanning Electron Microscopy Energy Dispersive Spectroscopy (FE-SEM-EDS) analyses were performed in this research. Different factors including holding time, zinc dissolution, agitation time and agitation rate were evaluated. The results revealed that an agitation rate of 600 RPM, 25% Zn and 60 min at a temperature of 198.9 °C were efficient. Zinc silver was removed as dross every 20 min to get 92% silver separation efficiency, and the use of supergravity centrifuge is highly recommended to get best separation efficiency.
Tensile Fracture Behavior of 2A14 Aluminum Alloy Produced by Extrusion Process
Authors: Meng Yunpeng , Zhang Hua , Li Xia , Zhou Xin , Mo Huajun , Wang Lifei , Fan Jianfeng
Published: January 2022

In this study, the tensile mechanical properties of a 2A14 aluminum alloy produced by extrusion were tested at room temperature to investigate the tensile fracture behavior. The results showed that the tensile fracture of the alloy was mixed intergranular and transgranular ductile fracture, as numerous coarse second-phase particles were distributed in a band along the loading direction, making it prone to microcracking. This was determined to be the main cause of fracture failure of the alloy. In addition, we observed large α-AlFeMnSi(Cu), Al(Fe,Mn)Cu, AlCuMgSi, and Al2Cu phases in the microstructure of the 2A14 aluminum alloy, and both Al2Cu second phase and precipitation-free phase zone (PFZ) at the grain boundaries were observed, which made the alloy susceptible to fracture failure and reduced the mechanical properties of the alloy.
Infection Biomarkers Based on Metabolomics
Authors: Araújo Rúben , Bento Luís F. N. , Fonseca Tiago A. H. , Von Rekowski Cristiana P. , da Cunha Bernardo Ribeiro , Calado Cecília R. C.
Published: January 2022

Current infection biomarkers are highly limited since they have low capability to predict infection in the presence of confounding processes such as in non-infectious inflammatory processes, low capability to predict disease outcomes and have limited applications to guide and evaluate therapeutic regimes. Therefore, it is critical to discover and develop new and effective clinical infection biomarkers, especially applicable in patients at risk of developing severe illness and critically ill patients. Ideal biomarkers would effectively help physicians with better patient management, leading to a decrease of severe outcomes, personalize therapies, minimize antibiotics overuse and hospitalization time, and significantly improve patient survival. Metabolomics, by providing a direct insight into the functional metabolic outcome of an organism, presents a highly appealing strategy to discover these biomarkers. The present work reviews the desired main characteristics of infection biomarkers, the main metabolomics strategies to discover these biomarkers and the next steps for developing the area towards effective clinical biomarkers.
Echinacea as a Potential Force against Coronavirus Infections? A Mini-Review of Randomized Controlled Trials in Adults and Children
Authors: Nicolussi Simon , Ardjomand-Woelkart Karin , Stange Rainer , Gancitano Giuseppe , Klein Peter , Ogal Mercedes
Published: January 2022

Echinacea purpurea has been shown to broadly inhibit coronaviruses and SARS-CoV-2 in vitro. This review discusses the available clinical evidence from randomized, blinded and controlled human studies. Two RCTs capturing incidence of viral respiratory tract infections during Echinacea preventative treatment were identified including coronavirus infections. Incidence and/or viral loads were measured by RT-PCR and symptom severity was recorded. In a first study, Jawad et al. collected nasopharyngeal swabs from adults (N = 755) over 4 months of continuous prevention. Overall, 24 and 47 enveloped virus infections occurred, including 21 and 33 coronavirus detections (229E; HKU1; OC43) with Echinaforce® extract (2400 mg daily) and placebo, respectively (p = 0.0114). In a separate study, Ogal et al. administered the same extract (1200 mg) or control for 4 months to children (4–12 years) (N = 203). Echinacea reduced the incidence of enveloped virus infections from 47 to 29 (p = 0.0038) whereas 11 and 13 coronavirus detections (229E, OC43, NL63) were counted (p > 0.05). Respiratory symptoms during coronavirus infections were significantly lower with area-under-curve AUC = 75.8 (+/−50.24) versus 27.1 (+/−21.27) score points (p = 0.0036). Importantly, viral loads in nasal secretions were significantly reduced by 98.5% in the Echinacea group, with Ct-values 31.1 [95% CI 26.3; 35.9] versus 25.0 [95% CI 20.5; 29.5] in the control group (p = 0.0479). Results from clinical studies confirm the antiviral activity found for Echinacea in vitro, embracing enveloped respiratory pathogens and therefore coronaviruses as well. Substantiating results from a new, completed study seem to extrapolate these effects to the prevention of SARS-CoV-2 infections. As hypothesized, the established broad antiviral activity of Echinacea extract appears to be inclusive for SARS-CoV-2.
Lithospheric Structure of the East European Craton at the Transition from Sarmatia to Fennoscandia Interpreted from the TTZ-South Seismic Profile (SE Poland to Ukraine)
Authors: Janik Tomasz , Starostenko Vitaly , Aleksandrowski Paweł , Yegorova Tamara , Czuba Wojciech , Środa Piotr , Murovskaya Anna , Zayats Khrystyna , Mechie James , Kolomiyets Katerina , Lysynchuk Dmytro , Wójcik Dariusz , Omelchenko Victor , Legostaieva Olga , Głuszyński Andrzej , Tolkunov Anatoly , Amashukeli Tatiana , Gryn’ Dmytro , Chulkov Serhii
Published: January 2022

The TTZ-South seismic profile follows the Teisseyre-Tornquist zone (TTZ) at the SW margin of the East European craton (EEC). Investigation results reveal the upper lithospheric structure as representing the NW-vergent, NE-SW striking overthrust-type, Paleoproterozoic (~1.84–1.8 Ga) Fennoscandia-Sarmatia suture. The Sarmatian segment of the EEC comprises two crustal-scale tectonic thrust slices: the Moldavo-Podolian and Lublino-Volhynian basement units, overriding the northerly located Lysogoro-Radomian unit of Fennoscandian affinity. The combined results of the TTZ-South and other nearby deep seismic profiles are consistent with a continuation of the EEC cratonic basement across the TTZ to the SW and its plunging into the deep substratum of the adjacent Paleozoic platform. Extensional deformation responsible for the formation of the mid to late Proterozoic (~1.4–0.6 Ga), SW-NE trending Orsha-Volhynia rift basin is probably also recorded. The thick Ediacaran succession deposited in the rift was later tectonically thickened due to Variscan deformation. The Moho depth varies between 37 and 49 km, resulting in the thinnest crust in the SE, sharp depth changes across the TTZ, and slow shallowing from 49 to 43 km to the NW. The abrupt Moho depth increase from 43 to 49 km is considered to reflect the overlying lower crust tectonic duplication within the suture zone.
Boosted Cross-Linking and Characterization of High-Performing Self-Assembling Peptides
Authors: Ciulla Maria Gessica , Pugliese Raffaele , Gelain Fabrizio
Published: January 2022

Tissue engineering (TE) strategies require the design and characterization of novel biomaterials capable of mimicking the physiological microenvironments of the tissues to be regenerated. As such, implantable materials should be biomimetic, nanostructured and with mechanical properties approximating those of the target organ/tissue. Self-assembling peptides (SAPs) are biomimetic nanomaterials that can be readily synthesized and customized to match the requirements of some TE applications, but the weak interactions involved in the self-assembling phenomenon make them soft hydrogels unsuited for the regeneration of medium-to-hard tissues. In this work, we moved significant steps forward in the field of chemical cross-linked SAPs towards the goal of stiff peptidic materials suited for the regeneration of several tissues. Novel SAPs were designed and characterized to boost the 4-(N-Maleimidomethyl) cyclohexane-1-carboxylic acid 3-sulpho-N-hydroxysuccinimide ester (Sulfo-SMCC) mediated cross-linking reaction, where they reached G′ values of ~500 kPa. An additional orthogonal cross-linking was also effective and allowed to top remarkable G′ values of 840 kPa. We demonstrated that cross-linking fastened the pre-existing self-aggregated nanostructures, and at the same time, a strong presence of ß-structures is necessary for an effective cross-linking of (LKLK)3-based SAPs. Combining strong SAP design and orthogonal cross-linking reactions, we brought SAP stiffness closer to the MPa threshold, and as such, we opened the door of the regeneration of skin, muscle and lung to biomimetic SAP technology.