bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of a DNA Barcoding Database for Legume and Grass Species Identification
Authors: Li Yongqing , La Zunongjiang A. Bu , Cao Lijun , Zhao Shengguo
Published: March 2022

Background: DNA barcoding, an emerging approach, is being widely used to accurately and quickly identify species using conserved DNA sequences. Methods: Herein we designed seven universal primers for matK (matK1, matK2, matK3 and matK4), rbcL, psbA-trnH and ITS based on their nucleotide sequences in GenBank to amplify 40 species of leguminosae and grass forages. Sequence alignment was performed using MEGA 5.0 and haplotype and mutation sites were analyzed with DnaSP 5.10. PCR amplification efficiency on using the primers designed for psbA-trnH and ITS was relatively low, making these sequences unsuitable for DNA barcoding. Further, we optimized target fragment amplification conditions for all 40 species analyzed in this study. On purifying, sequencing and analysing amplification products, we selected 5′ - and 3′ -end conserved fragments in four marked fragments. Result: Sequences of each maker loci showed that there were 12, 17 and 6 haplotypes of matK1, matK2 and matK3, respectively and 13 of rbcL. Based on these haplotypes of matK1, matK2, matK3 and rbcL, we established a DNA barcoding database for 20 forage species.
Genetic Variability among the Isolates of Alternaria brassicae in Mustard of Northern Madhya Pradesh
Authors: Singh Bhagyashree , Pandya R.K. , Singh P.K.
Published: March 2022

Background: Alternaria blight is most destructive fungal disease of oilseed which cause severe losses 47% in seed quality and quantity. The current research aimed to identify the specific pathogen species and its aggressiveness prevailing in M.P. area. Methods: Isolates of A. brassicae from five districts viz., Gwalior-A1, Morena-A2, Bhind-A3, Datia-A4 and Sheopur-A5 were cultured on potato dextrose agar medium to study their cultural characteristic and genetically variability in 7 days old culture. Genomic DNA from different fungal isolate culture having concentration of DNA to ~25 ng/µl was used for amplification of RAPD primers. Result: The distance matrix analysis was drawn phylogenetic tree by PCR data showed genetic distance among the fungal isolates. The phylogenetic tree was clearly showed isolated of A. brassicae illustrated in dendogram framing three major cluster, in which Isolate A1 was completely different from rest of the isolates and made separate cluster. All other samples were also significantly different from each other i.e. A4 (78%), A5 (37%) and A2 and A3 (94%).
Magnitude of Resistance and Metabolism of Acaricides in Two-spotted Spider Mite, Tetranychus urticae Koch on Vegetables in Southern Districts of Tamil Nadu
Authors: Naveena K. , Shanthi M. , Chinniah C. , Jayaraj J. , Ramasubramanian T. , Mini M.L. , Renuka R.
Published: March 2022

Background: Two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) is a destructive, polyphagous and cosmopolitan pest infesting a wide range of vegetables. Farmers frequently use acaricides in the vegetable ecosystem for mite management leading to increased probability for the development of resistance against acaricides in mite species. Literature about resistance in T. urticae to novel acaricides is scanty from this region. Hence, this study was aimed to evaluate the magnitude of acaricide resistance in T. urticae populations on vegetable crops from Southern districts of Tamil Nadu against seven acaricides. The role of detoxification enzymes in conferring bio-chemical resistance in the mite species was also studied. Methods: The laboratory experiments were conducted at completely randomized design (CRD) during 2019-2021 in central instrumentation laboratory, Department of Agricultural Entomology, Agricultural College and Research Institute, Tamil Nadu Agricultural University, Madurai. The level of resistance in T. urticae populations to fenazaquin, propargite, spiromesifen, buprofezin, fenpropathrin, diafenthiuron and chlorfenapyr was evaluated following the leaf dip bioassay technique. The activity of the detoxifying enzymes viz., Glutathione S Transferase (GST), Mixed Function Oxidase (MFO) and Carboxylesterase (CarE) were estimated. Result: Fenazaquin was highly toxic to T. urticae, which recorded a low level of resistance (2.00 to 8.62-fold). T. urticae exhibited a low to moderate level of resistance to fenpropathrin (1.86 to 37.28-fold), moderate to a high level of resistance to diafenthiuron (15.81 to 50.53-fold), high level of resistance to propargite (45.16 to 65.10-fold) and chlorfenapyr (54.67 to 100.14-fold) and extremely high level of resistance to spiromesifen (193.04 to 452.61-fold) and buprofezin (377.97 to 514.44-fold). Among all the test populations, the highly resistant DAmRg population exhibited the highest specific activity of the detoxifying enzymes, viz., GST (26.98 nmoles ml-1 min-1 mg of protein-1), MFO (5.07 nmoles ml-1 min-1 mg of protein-1) and CarE (827.90 nmoles ml-1 min-1 mg of protein-1). The CarE activity was found to be positively correlated with highly resistant acaricide, propargite (r = 0.995) and MFO activity with buprofezin having an extremely high level of resistance (r = 0.997). This preliminary knowledge would be instrumental in framing the acaricide resistant management (ARM) strategies.
The Problem of Moral Agency: Prospects of the Sociological Approach in the Context of the “Moral Dyad” Theory
Authors: Naryan Svetlana , Bykov Andrey
Published: March 2022

In the context of developing a new sociology of morality, the article examines such phenomena as moral agency and moral patiency, understood as an actor’s attributed ability to be seen as a subject or object of morally relevant actions. The authors analyze the concept of the “moral dyad” as the most popular general approach that addresses various aspects of attributing moral agency and patiency through mind ascription. We also examine the four key principles of the moral dyad concept: causing harm as a prerequisite for the moral relevance of the action, the inseparable link between mind ascription and moral agency/patiency, the phenomenon of moral typecasting, and the principle of the moral scheme’s completion being a necessity. Based on the criticisms of these basic principles, we consider the prospects for further research in the field of studying these moral qualities of actors of various types. For this purpose, we identify and discuss three key problems of the concept of the “moral dyad”, which, as we argue, should be addressed from a sociological perspective: explaining the moral status of actors in the case of pro-social actions, as well as the moral status of collective (groups, corporations, states, institutions) and non-human (robots, computer algorithms) actors. In conclusion we suggest that focusing on these problems in the context of actual social interactions can become one of the key research areas within the framework of the new sociology of morality.
Pseudo-static Simplified Analysis Method of the Pile-liquefiable Soil Interaction Considering Rate-dependent Characteristics
Authors: Zhang Xinlei , Ji Zhanpeng , Gao Hongmei , Wang Zhihua , Li Wenwen
Published: March 2022

The lateral pressure generated by liquefied soil on pile is a critical parameter in the analysis of soil-pile interaction in liquefaction-susceptible sites. Previous studies have shown that liquefied sand behaves like a non-Newton fluid, and its effect on piles has rate-dependent properties. In this study, a simplified pseudo-static method for liquefiable soil-pile interaction analysis is proposed by treating the liquefied soil as a thixotropic fluid, which considers the rate-dependent behavior. The viscous shear force generated by the relative movement between the viscous fluid (whose viscosity coefficient varies with excess pore pressure and shear strain rate) and the pile was assumed to be the lateral load on the pile. The results from the simplified analysis show that the distribution of bending moment is in good agreement with experiments data. Besides, the effects of various parameters, including relative density, thickness ratio of non-liquefiable layer to liquefiable layer, and frequency of input ground motion, on the pile-soil rate-dependent interaction were discussed in detail.
Understanding Racial Inequities in the Implementation of Harm Reduction Initiatives
Authors: Lopez Andrea M. , Thomann Matthew , Dhatt Zena , Ferrera Julieta , Al-Nassir Marwa , Ambrose Maggie , Sullivan Shane
Published: March 2022

Objectives. To elucidate a structurally oriented theoretical framework that considers legacies of racism, trauma, and social exclusion and to interrogate the “unmet obligations” of the institutionalization of the harm reduction infrastructure to provide equitable protections to Black and Latinx people who use drugs (PWUD) in Maryland.

Methods. In 2019, we conducted a rapid ethnographic assessment of and qualitative interviews with PWUD (n = 72) and stakeholders (n = 85) in 5 Maryland counties. We assessed PWUD’s experiences, service gaps in as well as barriers and facilitators to accessing services, and the potential to expand harm reduction programs.

Results. The unmet obligations we found included enforcement and punitive governance of syringes, naloxone, and other drug use equipment; racism and racialization, social exclusion, and legacies of trauma; and differential implications of harm reduction for populations experiencing racialized criminalization.

Conclusions. The implementation of harm reduction policies are a first step, but assessment of structural dynamics are needed for diverse communities with unique histories. This research illuminates a key paradox: progressive policy is implemented, yet the overdose crisis escalates in communities where various forms of racialized exclusions are firmly entrenched. (Am J Public Health. 2022;112(S2):S173–S181. https://doi.org/10.2105/AJPH.2022.306767 )
Mothers Who Use Drugs: Closing the Gaps in Harm Reduction Response Amidst the Dual Epidemics of Overdose and Violence in a Canadian Urban Setting
Authors: Boyd Jade , Maher Lisa , Austin Tamar , Lavalley Jennifer , Kerr Thomas , McNeil Ryan
Published: March 2022

Objectives. To identify key gaps in overdose prevention interventions for mothers who use drugs and the paradoxical impact of institutional practices that can increase overdose risk in the context of punitive drug policies and a toxic drug supply.

Methods. Semistructured interviews were conducted with 40 women accessing 2 women-only, low-barrier supervised consumption sites in Greater Vancouver, British Columbia, Canada, between 2017 and 2019. Our analysis drew on intersectional understandings of structural, everyday, and symbolic violence.

Results. Participants’ substance use and overdose risk (e.g., injecting alone) was shaped by fear of institutional and partner scrutiny and loss (or feared loss) of child custody or reunification. Findings indicate that punitive policies and institutional practices that frame women who use drugs as unfit parents continue to negatively shape the lives of women, most significantly among Indigenous participants.

Conclusions. Nonpunitive policies, including access to safe, nontoxic drug supplies, are critical first steps to decreasing women’s overdose risk alongside gender-specific and culturally informed harm-reduction responses, including community-based, peer-led initiatives to maintain parent–child relationships. (Am J Public Health. 2022;112(S2):S191–S198. https://doi.org/10.2105/AJPH.2022.306776 )
Protocolo de intervención en flexibilidad psicológica y regulación emocional con terapia contextual en familias: una serie de casos
Authors: Flujas-Contreras Juan M.
Published: March 2022

Las habilidades de regulación emocional y de flexibilidad psicológica pueden tener influencia en la forma en la que los padres interaccionan, manejan o afrontan las dificultades de sus hijos. El presente estudio tiene como objetivo valorar los efectos de un programa de intervención para familias en la promoción de habilidades de regulación emocional y flexibilidad psicológica parental mediante un protocolo clínico de parentalidad basado en estrategias de tercera generación. Participaron 9 padres con hijos, con edades entre 1 y 7 años (M = 3.8; DT = 2.03), diagnosticados de Trastorno del Espectro Autista, con una media de edad de 36.11 años (DT = 4.88). El 77% fueron madres. Se siguió un diseño pre-experimental con medidas prepost y seguimiento a los tres meses, sin grupo control. La intervención para el fomento de la flexibilidad psicológica parental y la regulación emocional de los padres tuvo una duración de 8 sesiones de una hora. Los resultados mostraron efectos positivos en la flexibilidad psicológica general y parental, concretamente en un estilo de respuesta abierto y centrado en el presente. Mejoró las puntuaciones de estrés parental y habilidades de regulación emocional en el post y se mantuvieron en el seguimiento. En los hijos se observó una reducción de los problemas de conducta y una mejor conducta prosocial. Los resultados del estudio muestran evidencias de la eficacia preliminar de la intervención familiar mediante terapias contextuales. Palabras clave: parentalidad; flexibilidad psicológica; regulación emocional; familias, serie de casos.
Integrating Community-Based HIV and Non-Communicable Disease Care with Microfinance Groups: A Formative Study in Western Kenya
Authors: Kafu Catherine , Wachira Juddy , Omodi Victor , Said Jamil , Pastakia Sonak D , Tran Dan , Onyango Jael Adongo , Aburi Dan , Wilson-Barthes Marta , Galárraga Omar , Genberg Becky Lynn
Published: March 2022

Background: The Harambee Study is a cluster randomized trial in western Kenya that tests the effect, mechanisms, and cost-effectiveness of integrating community-based HIV and non-communicable disease (NCD) care with group microfinance (MF) on HIV treatment outcomes. This paper documents the formative work to: (1) identify, enumerate, and characterize existing community-based microfinance groups to refine the study’s eligibility criteria, and (2) elicit support from multi-sectoral stakeholders in preparation for trial start. Methods: This mixed methods formative research took place between November 2019 and February 2020 in western Kenya. Surveys were administered to 115 group leaders of community-based MF groups. Field notes and GPS coordinates of group meeting locations and HIV healthcare facilities were also taken. A further 28 in-person meetings and two workshops involving stakeholders from multiple sectors of the health system took place throughout the formative phase. Quantitative survey data was analyzed using STATA IC/13. Longitude and latitude coordinates were mapped to County boundaries using Esri ArcMap. Qualitative data obtained from the meetings and field notes were analyzed thematically.Results: A total of 105 community-based microfinance groups were reached and 77 were eligible for the study. Of the eligible groups, we found differences in terms of definition of active membership, microfinance models, meeting location, and meeting frequency. Despite these differences, all the groups had an annual cycle period. Predominant themes emerging from the minutes and field notes revealed enthusiasm and support for the intervention among key stakeholders. Key stakeholders expressed a desire to have interventions integrated into the AMPATH care model for sustainability after the study period. Continuous engagement of various stakeholders, collaboration on various aspects of the study, identification of areas that could potentially lead to conflict, and overall increased transparency were identified as crucial to this integration.Conclusions: For randomized controlled trials (RCTs) conducted in rural communities, formative research is essential for pre-determining eligibility, mapping implementation sites and eliciting buy-in from community leaders. Adaptations identified from formative work should be addressed prior to study start.Trial registration: NCT04417127. Registered 4 June 2020 - Retrospectively registered, https:// www.clinicaltrials.gov/ct2/show/NCT04417127
Labelling of subpleural deposited pulmonary foci of blue dye and contrast agent substances under CT-guided control and their subsequent video thoracoscopic wedge resection: The BLUEPAT prospective randomized study
Authors: Červeňák Vladimír , Chovanec Zdeněk , Čundrle Ivan , Šitina Michal , Berková Alena , Hanslík Tomáš , Penka Igor , Vaníček Jiří , Součková Lenka
Published: March 2022

Background: Colour marking of indicated deposits is an innovative, accurate and gentle method that allows subsequent wedge resection of the marked tissue using a mini-invasive, video-assisted thoracoscopic (VATS) method with all its benefits. One of the expected benefits of this clinical trial is the introduction and optimization of the evaluated method into routine management in the diagnosis and treatment of focal lung diseases. The BLUEPAT clinical trial aims to evaluate the method of colour marking of subpleural deposited small lung deposits with the subsequent performance of VATS wedge resection in surgical practice.Methods: The BLUEPAT clinical trial is a prospective, monocentric, open-label, randomized study that will include 72 subjects with subpleural deposited lesions with the need for additional histological diagnostics to optimize subsequent treatment. These patients will be randomized into 2 groups in a 1:1 ratio. The first group will undergo VATS wedge resection of lung deposits marked with patent blue and contrast agent iohexol under CT-guided control. The second group will undergo VATS resection without prior colour coding of the lung deposits. The feasibility and safety of both methods will be assessed based on the evaluation of the parameters of the primary and secondary objectives of the study. The safety of the methods will be monitored by recording all related adverse events. The patients will participate in the clinical trial for 30 days.Discussion: The BLUEPAT clinical trial provides a unique evaluation of this innovative approach in the diagnosis and treatment of focal lung diseases. Clinical trials support the patent blue dyeing diagnostic procedures for the detection of breast cancer.Trial registration: EudraCT Number 2021-001122-22, Registered on 20.04.2021, https://www.sukl.eu/modules/evaluation/detail.php?id=51957&lang=2
ISSI 2021: Terahertz Spectroscopic Characterization and Thickness Evaluation of Internal Delamination Defects in GFRP Composites
Authors: Nsengiyumva Walter , ZHONG Shuncong , Luo Manting , Wang Bing
Published: March 2022

In recent years, terahertz time-domain spectroscopy (THz-TDS) has attracted significant attention due to its superior time and spatial resolution as well as its capabilities of localizing and characterizing internal defects in glass-fiber-reinforced polymer-matrix (GFRP) composite materials. In this study, the THz-TDS system is used to detect and evaluate hidden multi-delamination in plastic multilayered GFRP composite laminates. To remove the noise from the time-of-flight (TOF) signals, a wavelet shrinkage de-noising algorithm was used, leading to enhanced THz signals and further enabling an easy localization and evaluation of overlapping multi-delamination defects in GFRP composite laminates. In particular, both the thicknesses and locations of these delamination defects in the z-direction (i.e., through-the-thickness direction) were analyzed and measured considering the interaction between pulsed THz waves and the GFRP composite laminate. THz wave power and absorbance levels at every interface with different refractive indices in the GFRP composite samples were discussed based on analytical and experimental results. The present study shows the capabilities of the THz-TDS for the spectroscopic characterization of composite materials and helps users to know how they can theoretically estimate the thickness of the composite material that can be nondestructively evaluated by the THz-TDS.
The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis
Authors: Almulla Abbas F. , Supasitthumrong Thitiporn , Tunvirachaisakul Chavit , Algon Ali Abbas Abo , Al-Hakeim Hussein K. , Maes Michael
Published: March 2022

Background: Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both may induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of the current study was to systematically review and meta-analyze the TRYCAT pathway status including levels of TRP and kynurenine (KYN) and IDO activity, as assessed using the KYN/TRP ratio. Methods: This systematic review was performed in December 2021 and searched data in PubMed, Google Scholar, and Web of sciences. In our meta-analysis we included 14 articles which examine TRP and TRYCATs in COVID-19 patients versus non-COVID-19 controls, and severe/critical versus mild/moderate COVID-19. Overall, the analysis was performed on 1269 individuals, namely 794 COVID-19 patients and 475 controls. Results: The results show a significant (p <0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD=1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD= 1.123, 95% CI: 0.730;1.516) and significantly lower TRP ((SMD= -1.002, 95%CI: -1.738; -0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD= 0.945, 95%CI: 0.629; 1.262) and KYN (SMD= 0.806, 95%CI: 0.462; 1.149) were also significantly (p <0.001) higher and TRP lower (SMD= -0.909, 95% CI: -1.569; -0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in the kynurenic acid (KA)/KYN ratio and KA between COVID-19 patients and controls. Conclusions: Our results indicate increased activity of the IDO enzyme in COVID-19 and in severe/critical patients. The TRYCAT pathway is probably implicated in the pathophysiology and progression of COVID-19 and may signal a worse outcome of the disease.
Quantitative electroencephalographic biomarker of pharmacological treatment response in anxiety disorder: A retrospective study
Authors: Byeon Jun , Moon Jung Yeon , Je Se Ryoung , Kim Jun Won
Published: March 2022

Objectives: This study investigated the effectiveness of a quantitative electroencephalography(qEEG) biomarker in predicting the response to pharmacological treatment in patients with anxiety disorder.Methods: A total of 86 patients were diagnosed with anxiety disorder by using the Diagnostic and Statistical Manual of Mental Disorders 5th edition and treated with antidepressants. After 8-12weeks, the participants were divided into treatment-resistant(TRS) and treatment-response(TRP) groups on the basis of the Clinical Global Impressions-Severity(CGI-S) score. We obtained the absolute-EEG measurements for 19-channels and analyzed qEEG findings according to the Hz range: delta, theta, alpha, and beta. The beta-wave was subdivided into low-beta, beta, and high-beta. The theta-beta ratio(TBR) was calculated, and an analysis of covariance was performed.Results: Among the 86 patients with anxiety disorder, 65% were classified in the TRS group. The TRS and TRP groups did not differ regarding age, sex, and medication-dosage. However, the baseline CGI-S was higher in the TRP. After calibration by covariates, the TRP showed a higher beta-wave and high-beta-waves in T3 and T4. The TRP showed a lower TBR, especially in T3 and T4. Conclusion: These results indicate that patients with a lower TBR and higher beta and high-beta waves in T3 and T4 are more likely to respond to medication.
Equate groups: An innovative method to link multi-item instruments across studies
Authors: Eekhout Iris , Weber Ann M. , Buuren Stef
Published: March 2022

Background: Combining existing data sets for meta-analyses enables analyses across multiple contexts and conditions. However, the use of different measurement instruments in different studies hampers comparability. This paper proposes a novel method to link tools administered across multiple studies. Methods: The proposed methodology starts by forming equate groups, i.e., sets of items from different instruments with similar meanings. We fit the Rasch model to all data, with the additional restriction that items within the same equate group obtain identical difficulty estimates. The main modelling task is to divide equate groups into active (where the restriction holds) and passive (without the restriction) groups. We studied the method's performance in a simulation study and illustrated its practical application to early childhood development. Results: If we treat all equate groups as passive, the difficulty estimates of the identical items are unduly affected by differences in abilities between the study samples. On the other hand, when abilities are similar across samples, it is safer to set all equate groups to passive because any mis-specified equate groups can lead the restricted model to underperform. Our method deals with the common case between these two extremes where 1) we suspect a priori ability differences between samples, and 2) at least some of the items are equivalent across instruments. Conclusions: Our equating method presents a flexible alternative to the classic common-item nonequivalent-group design for existing data. We conclude that equate groups are an economical and exciting concept that enables insightful statistical analysis from seemingly disparate data sources.
Evaluation of the Gut Microbiome and Sex Hormones in Postmenopausal Women with Newly Diagnosed Hormone Receptor-Positive Breast Cancer Versus Healthy Women: A Prospective Case-Control Study
Authors: Kwa Maryann , Ruggles Kelly V , Novik Yelena , Franke Adrian A , Volkova Angelina , Flores Karina , Blaser Martin J , Speyer James , Oratz Ruth , Meyers Marleen , Jhaveri Komal , Fadel Ezeddin , Zamora Shelby , Heguy Adriana , Schluter Jonas , Adams Sylvia
Published: March 2022

Purpose
The functional composition and diversity of the gut microbiome (estrobolome) may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investigated the relationship between the gut bacterial microbiome and endogenous estrogens and related sex hormones in women with hormone receptor-positive breast cancer compared to healthy control women.
Methods
In this prospective case-control study, postmenopausal women (n = 46) with newly diagnosed stage I-III estrogen and/or progesterone receptor-positive breast cancer were compared with healthy postmenopausal female controls (n = 22). Bacterial composition of the gut microbiome was analyzed by 16S rRNA gene sequencing from fecal specimens. Plasma and urine sex hormones were quantified using high-performance liquid chromatography/mass spectrometry.
Results
We found evidence that some β-glucuronidase positive bacteria were enriched in the breast cancer patients compared to healthy controls, whereas abundances of some β-glucuronidase negative bacteria were reduced. There was also a wide distribution of prevalence of β-glucuronidase positive taxa in both the breast cancer subjects and healthy controls, as well as higher probability of breast cancer subjects having higher average β-glucuronidase levels. Significant differences were found in endogenous progesterone levels between the breast cancer patients and healthy controls.
Conclusion
This pilot study showed differences in the gut microbiome and endogenous progesterone levels among postmenopausal women with hormone receptor-positive breast cancer compared with healthy controls. These interesting findings may have implications for breast cancer risk and prevention and warrant further exploration.
Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX
Authors: Trabelsi Khaled , Zakour Meriem Ben , Jordan Ingo , Sandig Volker , rourou Samia , Kallel Hela
Published: March 2022

Background: Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines.Results: The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging.CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4x108 FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine 2-fold, and increased the number of doses 9.6 fold.Conclusion: This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.
Clinicopathologic Features, Chronic Renal Damage and Short-Term Outcomes of Glomerular Diseases in a Middle East Tertiary Care Center
Authors: Abdulaziz Hoda M. M. , Sayed-Ahmed Nagy , Atwa Dina Abdallah Ibrahim , Nassar Mohammed K.
Published: March 2022

Background
Glomerular diseases (GDs) place a significant burden on patients and health-care systems, and they are a leading cause of end-stage renal disease (ESRD) globally. There is no national register for GDs in Egypt, and the outcomes of GDs are not extensively examined. As a result, studying GDs patterns and outcomes, as well as the association between chronic renal injury at presentation and GDs outcome, was of great interest.
Methods
Patients with biopsy-proven GDs, presenting to an Egyptian tertiary care center were enrolled and prospectively followed-up for 6 months, death or reaching ESRD. Chronic renal damage was assessed at diagnosis by the total renal chronicity.
Results
Sixty-six individuals with biopsy-confirmed GDs were enrolled in the study. The most common reasons for a renal biopsy were unexplained kidney function decrease (62%), followed by subnephrotic (23%) and nephrotic presentation (15%). The most common histological patterns were diffuse proliferative glomerulonephritis (GN), membranoproliferative GN (MPGN), and sclerosing GN. Primary and secondary GDs made up 30.3% and 69.7% of the cases, respectively. At the end of the 6-month follow-up, 28 patients had recovered their renal function, 19 had advanced to ESRD, and 7 had died. The most significant predictors of renal recovery were hemoglobin level and the total renal chronicity score.
Conclusion
In this tertiary care center Egyptian cohort, secondary GDs appear to be more frequent than primary GDs, diffuse proliferative GN was the most common histopathological pattern, and rapid renal recovery was not the rule in this short period. The renal chronicity score could accurately predict the renal outcome.
Trial Registration:
Approval for this study was granted by the Mansoura Faculty of Medicine Institutional Research Board (IRB) (approval no. MD/17.05.13).
Constitutive Chitosanase from Bacillus Thuringiensis B-387 and its Potential for Preparation of Antimicrobial Chitooligomers
Authors: Aktuganov Gleb , Safina Violetta , Galimzianova Nailya , Gilvanova Elena , Kuzmina Lyudmila , Melentiev Alexander , Baymiev Andrei , Lopatin Sergey
Published: March 2022

Ability of the insecticide strain B. thuringiensis var. dendrolimus B-387 to high constitutive production (3-12.5 U/mL) of extracellular chitosanase was found for first time. The enzyme was purified in 94-fold by ultrafiltration, affinity sorption and cation-exchanged chromatography and characterized biochemically. Molecular mass of the chitosanase determined using SDS-PAGE is 40 kDa. Temperature and pH-optima of the enzyme are 55◦C and pH 6.5, respectively; the chitosanase was stable under 50–60◦C and pH 4-10.5. Purified chitosanase most rapidly (Vmax~43 µM/mL×min, KM~0.22 mg/mL, kcat ~ 4.79×104 s− 1) hydrolyzed soluble chitosan of deacetylation degree (DD) 85% by endo-mode, and no degraded colloidal chitin, CM-cellulose and some other glucans. Main reaction products of the chitosan enzymolysis included chitobiose, chitotriose and chitotetraose. In addition to small chitooligosaccharides (CHOs), studied chitosanase generated also low-molecular weight chitosan (LMWC) with average Mw in range 14–46 kDa and recovery 14–35%, depending of enzyme / substrate ratio and incubation temperature. Chitosan (DD 85 and 50%) oligomers prepared using crude chitosanase from B. thuringiensis B-387 indicated higher antifungal and antibacterial activities in vitro in comparison with initial polysaccharides. The findings evidence the chitosanase B-387 promising for bioactive CHOs preparation.
AI-powered pan-species computational pathology: bridging clinic and wildlife care
Authors: AbdulJabbar Khalid , Castillo Simon , Hughes Katherine , Davidson Hannah , Boddy Amy , Abegglen Lisa , Murchison Elizabeth , Graham Trevor , Spiro Simon , Palmieri Chiara , Yuan Yinyin
Published: March 2022

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for advancing human healthcare, animal welfare, and wildlife conservation. We built the pan-species cancer digital pathology atlas (PANCAD) and conducted the first pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). Furthermore, in 18 other vertebrate species (mammalia=11, reptilia=4, aves=2, and amphibia=1), accuracy (0.57-0.94) was influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. A new metric, named morphospace overlap, was developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on a new understanding of morphological conservation, which could vastly accelerate new developments in veterinary medicine and comparative oncology.
Landscape-scale repercussions of global action for climate and biodiversity protection
Authors: von Jeetze Patrick , Weindl Isabelle , Johnson Justin , Borrelli Pasquale , Panagos Panos , Bacca Edna Molina , Karstens Kristine , Humpenöder Florian , Dietrich Jan , Minoli Sara , Müller Christoph , Lotze-Campen Hermann , Popp Alexander
Published: March 2022

Habitat loss and biotic homogenisation are undermining the stable supply of nature’s contributions to people (NCP) that underpin the long-term productivity and resilience in farmed landscapes. Growing demand for land-based products, and global ambitions for climate and area-based protection are likely to increase land competition, which could further drive intensification and landscape simplification. Yet, little is known about the repercussions of such global land-use transitions for key regulating NCP in farmed landscapes. By using an integrated, globally consistent modelling approach, we analyse how global land-use dynamics could drive fine-scale changes in landscape structure, pollination, and soil erosion across different land-use futures. Here we show that, if not addressed, increased land competition and concurrent landscape-scale changes could reinforce global negative trends for key regulating NCP. However, we also find that global efforts towards land carbon uptake and biodiversity conservation could be augmented to produce co-benefits in agricultural settings. Our results indicate that integrating at least 20 % (semi-)natural habitat into farmed landscapes would not cause trade-offs of carbon emissions or natural land conversion, despite shifts in spatial land-use patterns. Our findings underline the importance of considering landscape-scale repercussions while assessing changes in multiple material and regulating NCP across different land-use futures.
The clinical relevance of unfolded protein response signaling in breast cancer
Authors: Oshi Masanori , Roy Arya Mariam , Gandhi Shipra , Tokumaru Yoshihisa , Yan Li , Yamada Akimitsu , Endo Itaru , Takabe Kazuaki
Published: March 2022

Purpose
Protein homeostasis regulated by the Endoplasmic Reticulum (ER) is a recognized process involved in cancer progression. ER stress activates the Unfolded Protein Response (UPR) and has been implicated in a variety of cancers. Given the role of the UPR activation in carcinogenesis, we hypothesized that UPR activation could be associated with pathological progression, higher clinical stage, and worse survival in breast cancer.
Methods
A total of 4,416 breast cancer patients from multiple independent cohorts were analyzed. We defined the UPR pathway score by the degree of enrichment by Gene Set Variant Analysis and median was used to divide high vs low score groups in each cohort.
Results
High UPR breast cancer significantly enriched not only cell proliferation-related but also other pro-cancerous gene sets consistently in both METABIC and GSE96058 cohort. Majority of UPR pathway score high cells in the bulk tumor were tumor cells compared to other cells, including stromal, T-, B-, and myeloid-cells (p < 0.001). UPR score was significantly associated with advanced stage, high grade, and triple negative breast cancer (TNBC) (all p < 0.001). High UPR breast cancer was associated with worse patient survival in both cohorts (all p < 0.001). Among breast cancer subtype, ER-positive/HER2-negative breast cancer with high UPR was significantly associated with worse survival, but neither HER-positive nor TNBC. High UPR ER-positive/HER2-negative breast cancer was infiltrated with high level of Th1 and Th2 cells, M1 macrophage, and plasma cells. On the other hand, they were significantly infiltrated with high level of several types of stromal cells in tumor microenvironment (all p < 0.001). Finally, high UPR metastatic breast cancer was also associated with worse patient survival (p = 0.041).
Conclusion
UPR signaling is associated with cancer aggressiveness, and worse survival, especially ER-positive/HER2-negative breast cancer subtype.
Microbacterium caeni sp. nov., a novel species isolated from sludge in Yeosu, Korea
Authors: Jung You-Jung , Lee Sang-Hoon , Kim Na-Kyung , Yoon Hyeokjun , Jeong Garam , Lee Byoung-Hee , Park Hee-Deung , Hur Moonsuk
Published: March 2022

A gram-positive, white-pigmented, aerobic, rod-shaped bacterium, designated strain NIBRBAC000506063T, was isolated from a sludge sample from Yeosu, Korea. Optimal growth of strain NIBRBAC000506063T was observed at 25 °C and pH 8.0, in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain NIBRBAC000506063T belongs to the genus Microbacterium and is closely related to Microbacterium invictum DC-200T (98.3 % sequence similarity). Next-generation sequencing (NGS) analysis indicated that the strain NIBRBAC000506063T genome was comprised of one circular chromosome (2,576,190 bp, G+C content: 69.14 mol%) and one plasmid (465,341 bp, G+C content: 68.45 mol%) with 4,046 coding sequences, 47 tRNAs, and 4 rRNAs. The major respiratory isoprenoid quinone was MK12, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, aminophospholipids, and glycolipids. The major fatty acids of strain NIBRBAC000506063T were C16:0 iso and C15:0 anteiso, and the G+C content of the genomic DNA was 69.5 mol%. Based on the polyphasic taxonomic data obtained in this study, it is proposed that strain NIBRBAC000506063T represents a novel species of the genus Microbacterium. The type strain is NIBRBAC000506063T (=KCTC49453T =DSM111108T).
Screening of probable carcinogenic agonists of Aryl Hydrocarbon Receptor (AhR) from various pesticides using computational molecular biology approach
Authors: Singh Arshwinder , Singh Rhythumwinder , Kaur Prabhjot , Upadhyay Atul Kumar
Published: March 2022

Aryl hydrocarbon receptor (AhR) is a ligand-activated cytosolic transcription factor. Once activated AhR stimulates the pathways that are directly or indirectly linked to inflammation and breast cancer. Exogenous agonists of AhR including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzopyrene are found to be carcinogenic in nature. Breast cancer being the most prevalent cancer, makes it an important aspect to look for new exogenous agonists of AhR with carcinogenic properties. In this study, an effort has been made to screen new agonist from pesticides, which may have role in breast cancer development. Primarily, the structure of AhR PAS domain was determined by using SWISS-MODEL server. Thereafter, probable carcinogenic molecules from pesticides were screened and molecular docking studies were performed to identify potential binders with good energetics. Detailed structural analysis have resulted in four molecules namely, Isopyrazam, Noviflumuron, Oxyfluorfen and Resmethrin, that showed higher negative binding energy, when compared to TCDD. Molecular Dynamics Simulation studies of AhR- Isopyrazam were further carried out to prove the stability of the complex which suggests that presence of these agonist in different pesticides may have major role to play to cause breast cancer. Avoiding or minimizing the use of these compounds in the pesticides may be a strategy to combat breast cancer in future.
Study Protocol. Evaluating the life-course health impact of a city-wide system approach to improve air quality in Bradford, UK: A quasi-experimental study with implementation and process evaluation
Authors: McEachan Rosemary R C , Rashid Rukhsana , Santorelli Gillian , Tate James , Thorpe Jamie , McQuaid James B , Wright John , Pickett Kate E , Pringle Kirsty , Bojke Laura , Jones Sally , Islam Shahid , Walker Simon , Yang Tiffany C , Bryant Maria
Published: March 2022

Background
Air quality is a major public health threat linked to poor birth outcomes, respiratory and cardiovascular disease, and premature mortality. Deprived groups and children are disproportionately affected. Bradford will implement a Clean Air Zone (CAZ) as part of the Bradford Clean Air Plan (B-CAP) in 2022 to reduce pollution, providing a natural experiment. The aim of the current study is to evaluate the impact of the B-CAP on health outcomes and air quality, inequalities and explore value for money. An embedded process and implementation evaluation will also explore barriers and facilitators to implementation, impact on attitudes and behaviours, and any adverse consequences.
Methods
The study is split into 4 work packages (WP). WP1A: 20 interviews with decision makers, 20 interviews with key stakeholders; 10 public focus groups and documentary analysis of key reports will assess implementation barriers, acceptability and adverse or unanticipated consequences at 1 year post-implementation (defined as point at which charging CAZ goes ‘live’). WP1B: A population survey (n = 2000) will assess travel behaviour and attitudes at baseline and change at 1 year post-implementation). WP2: Routine air quality measurements will be supplemented with data from mobile pollution sensors in 12 schools collected by N = 240 pupil citizen scientists (4 within, 4 bordering and 4 distal to CAZ boundary). Pupils will carry sensors over four monitoring periods over a 12 month period (two pre, and two post-implementation). We will explore whether reductions in pollution vary by CAZ proximity. WP3A: We will conduct a quasi-experimental interrupted time series analysis using a longitudinal routine health dataset of > 530,000 Bradford residents comparing trends (3 years prior vs 3 years post) in respiratory health (assessed via emergency/GP attendances. WP3B: We will use the richly-characterised Born in Bradford cohort (13,500 children) to explore health inequalities in respiratory health using detailed socio-economic data. WP4: will entail a multi-sectoral health economic evaluation to determine value for money of the B-CAP.
Discussion
This will be first comprehensive quasi-experimental evaluation of a city-wide policy intervention to improve air quality. The findings will be of value for other areas implementing this type of approach.
Registration:
ISRCTN67530835 https://doi.org/10.1186/ISRCTN67530835
Clinical Study of α 2-MG, PCX, AFU, RBP-4 and CysC in type 2 Diabetes Mellitus and Diabetic Nephropathy
Authors: Li JingJing , Yan ZhaoLi
Published: March 2022

BackgroundDiabetic nephropathy (DN) is one of the most common chronic complications of diabetes mellitus (DM). The changes of α2-macroglobulin (α2-MG), podocalysin (PCX), α-L-fucosidase (AFU), retinol binding protein-4 (RBP-4), cystatin C(CysC) and clinical indicators in patients with or without DN.To explore their role and significance in type 2 diabetes (T2DM) and DN.MethodsA total of 203 T2DM patients admitted to hospital from December 2018 to December 2020 were collected and divided into DN group (115 cases) and NDN group (88 cases). Urine α2-MG, PCX and AFU levels, serum RBP-4 and CysC levels were determined, and other clinical indicators were collected.Results1.Comparison of general data between groups: the levels of CysC, RBP-4, α2-MG/UCr,PCX/UCr and AFU/UCr in DN group were higher than those in NDN group (P<0.05). 2. Comparison of ACR stage and renal function stage of CKD: ①ACR stage: CysC, RBP-4, α2-MG/UCr,PCX/UCr,AFU/UCr increased with the increase of ACR stage(P<0.05). ② Renal function stage of CKD: CysC, RBP-4,α2-MG/UCr, PCX/UCr, AFU/UCr increased with the increase of renal function stage of CKD(P<0.05). 3. Partial correlation analysis after adjusting gender and age: CysC, RBP-4,α2-MG/UCr,PCX/UCr, AFU/UCr were positively correlated with UACR, Scr, Urea, UTP/24h, NLR, but negatively correlated with eGFR(P<0.05). 2.ROC curve: (1) Analysis of single index on DN diagnosis: AUCROC of UACR, eGFR, CysC,RBP-4, α2-MG/UCr,PCX/UCr and AFU/UCr were 0.97, 0.77, 0.80, 0.76, 0.83, 0.86, 0.79, respectively. (2) Analysis of combined indicators for DN diagnosis:AUCROC of α2-MG/UCr+PCX/UCr,α2-MG/UCr+AFU/UCr,α2-MG/UCr+PCX/UCr+AFU/UCr,α2-MG/UCr+PCX/UCr+AFU/UCr were 0.88, 0.88, 0.86, 0.89.Conclusion: ﻿1.α2-MG, PCX and AFU are related to the occurrence and development of DN. 2. RBP-4, CysC, PCX, AFU and α2-MG have better diagnostic value,but UACR has the best diagnostic value. 3.PCX can reflect early renal damage.