bluuebunny/crossref_metadata_2025 huggingface dataset:
c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease
Authors: Smith Abigail O. , Jonassen Julie A. , Preval Kenley M. , Davis Roger J. , Pazour Gregory J.
Published: December 2021

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects ofPkdmutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused byPkd2loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal ofJnk1andJnk2suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. WhileJnk1andJnk2are thought to have largely overlapping functions, we find thatJnk1loss is nearly as effective as the double loss ofJnk1andJnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD.
Prevalence and spatial distribution characteristics of human echinococcosis in China
Authors: Wang Li-Ying , Qin Min , Liu Ze-Hang , Wu Wei-Ping , Xiao Ning , Zhou Xiao-Nong , Manguin Sylvie , Gavotte Laurent , Frutos Roger
Published: December 2021

Background

Echinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people’s health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement.

Methods

Report data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering.

Results

A total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces.

Conclusion

This study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau.
Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin
Authors: Gnimavo Ronald , Besnard Alban , Degnonvi Horace , Pipoli Da Fonseca Juliana , Kempf Marie , Johnson Christian Roch , Boccarossa Alexandra , Brou Yao Télesphore , Marsollier Laurent , Marion Estelle
Published: December 2021

Background

Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection.

Methodology/Principal findings

We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated.

Conclusions/Significance

Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.
Genetic diversity of Leptospira isolates in Lao PDR and genome analysis of an outbreak strain
Authors: Grillová Linda , Robinson Matthew T. , Chanthongthip Anisone , Vincent Antony T. , Nieves Cecilia , Oppelt Jan , Mariet Jean-François , Lorioux Céline , Vongsouvath Manivanh , Mayxay Mayfong , Phonemeexay Ooyanong , Rattanavong Sayaphet , Phommasone Koukeo , Douangnouvong Anousone , Šmajs David , Veyrier Frédéric J. , Newton Paul N. , Picardeau Mathieu
Published: December 2021

Background

Although Southeast Asia is one of the most leptospirosis afflicted regions, little is known about the diversity and molecular epidemiology of the causative agents of this widespread and emerging zoonotic disease.

Methodology/Principal findings

We used whole genome sequencing to examine genetic variation in 75 Leptospira strains isolated from patients in the Lao PDR (Laos) between 2006 and 2017.

Eleven serogroups from 4 Leptospira species and 43 cgMLST-defined clonal groups (CGs) were identified. The most prevalent CG was CG272 (n = 18, 26.8%), composed of L. interrogans serogroup Autumnalis isolates. This genotype was recovered throughout the 12-year period and was associated with deaths, and with a large outbreak in neighbouring Thailand. Genome analysis reveals that the CG272 strains form a highly clonal group of strains that have, for yet unknown reasons, recently spread in Laos and Thailand. Additionally, accessory genes clearly discriminate CG272 strains from the other Leptospira strains.

Conclusions/Significance

The present study reveals a high diversity of Leptospira genotypes in Laos, thus extending our current knowledge of the pan- and core-genomes of these life-threatening pathogens. Our results demonstrate that the CG272 strains belong to a unique clonal group, which probably evolved through clonal expansion following niche adaptation. Additional epidemiological studies are required to better evaluate the spread of this genotype in Southeast Asia. To further investigate the key factors driving the virulence and spread of these pathogens, more intense genomic surveillance is needed, combining detailed clinical and epidemiological data.
Genetic diversity, viability and conservation value of the global captive population of the Moroccan Royal lions
Authors: Lehocká Kristina , Black Simon A. , Harland Adrian , Kadlečík Ondrej , Kasarda Radovan , Moravčíková Nina
Published: December 2021

This study evaluates the diversity of the so-called ‘Moroccan Royal lions’ using genealogical information. Lions are no longer extant in North Africa, but the previous wild population was an important element of the now-recognised northern subspecies (Panthera leo leo) that ranged across West Africa, North Africa and the Middle East into India. The remaining captive population of ‘Moroccan Royal lions’ seems to be significantly endangered by the loss of diversity due to the effective population size decrease. The pedigree file of this captive lion population consisted of 454 individuals, while the reference population included 98 animals (47 males and 51 females). The completeness of the pedigree data significantly decreased with an increasing number of generations. The highest percentage of pedigree completeness (over 70%) was achieved in the first generation of the reference population. Pedigree-based parameters derived from the common ancestor and gene origin were used to estimate the state of diversity. In the reference population, the average inbreeding coefficient was 2.14%, while the individual increase in inbreeding over generations was 2.31%. Overall, the reference population showed lower average inbreeding and average relatedness compared with the pedigree file. The number of founders (47), the effective number of founders (24) and the effective number of ancestors (22) were estimated in the reference population. The effective population size of 14.02 individuals confirms the critically endangered status of the population and rapid loss of diversity in the future. Thus, continuous monitoring of the genetic diversity of the ‘Moroccan Royal lion’ group is required, especially for long-term conservation management purposes, as it would be an important captive group should further DNA studies establish an affinity to P. leo leo.
Do patients with high versus low treatment and illness burden have different needs? A mixed-methods study of patients living on dialysis
Authors: Boehmer Kasey R. , Pine Kathleen H. , Whitman Samantha , Organick Paige , Thota Anjali , Espinoza Suarez Nataly R. , LaVecchia Christina M. , Lee Alexander , Behnken Emma , Thorsteinsdottir Bjorg , Pawar Aditya S. , Beck Annika , Lorenz Elizabeth C. , Albright Robert C.
Published: December 2021

Background

Approximately 750,000 people in the U.S. live with end-stage kidney disease (ESKD); the majority receive dialysis. Despite the importance of adherence to dialysis, it remains suboptimal, and one contributor may be patients’ insufficient capacity to cope with their treatment and illness burden. However, it is unclear what, if any, differences exist between patients reporting high versus low treatment and illness burden.

Methods

We sought to understand these differences using a mixed methods, explanatory sequential design. We enrolled adult patients receiving dialysis, including in-center hemodialysis, home hemodialysis, and peritoneal dialysis. Descriptive patient characteristics were collected. Participants’ treatment and illness burden was measured using the Illness Intrusiveness Scale (IIS). Participants scoring in the highest quartile were defined as having high burden, and participants scoring in the lowest quartile as having low burden. Participants in both quartiles were invited to participate in interviews and observations.

Results

Quantitatively, participants in the high burden group were significantly younger (mean = 48.4 years vs. 68.6 years respectively, p = <0.001). No other quantitative differences were observed. Qualitatively, we found differences in patient self-management practices, such as the high burden group having difficulty establishing a new rhythm of life to cope with dialysis, greater disruption in social roles and self-perception, fewer appraisal focused coping strategies, more difficulty maintaining social networks, and more negatively portrayed experiences early in their dialysis journey.

Conclusions and relevance

Patients on dialysis reporting the greatest illness and treatment burden have difficulties that their low-burden counterparts do not report, which may be amenable to intervention.
A study to investigate the implementation process and fidelity of a hospital to community pharmacy transfer of care intervention
Authors: Khayyat Sarah M. , Nazar Zachariah , Nazar Hamde
Published: December 2021

Background

Hospital to community pharmacy transfer of care medicines-related interventions for inpatients discharged home aim to improve continuity of care and patient outcomes. One such intervention has been provided for seven years within a region in England. This study reports upon the implementation process and fidelity of this intervention.

Methods

The process evaluation guidance issued by the Medical Research Council has informed this study. A logic model to describe the intervention and causal assumptions was developed from preliminary semi-structured interviews with project team members. Further semi-structured interviews were undertaken with intervention providers from hospital and community pharmacy, and with patient and public representatives. These aimed to investigate intervention implementation process and fidelity. The Consolidated Framework for Implementation Research and the Consolidated Framework for Intervention Fidelity informed interview topic guides and underpinned the thematic framework analysis using a combined inductive and deductive approach.

Results

Themes provided information about intervention fidelity and implementation that were mapped across the sub processes of implementation: planning, execution, reflection and evaluation, and engagement. Interviewees described factors such as lack of training, awareness, clarity on the service specification, governance and monitoring and information and feedback which caused significant issues with the process of intervention implementation and suboptimal intervention fidelity.

Conclusions

This provides in-depth insight into the implementation process and fidelity of a ToC intervention, and the extant barriers and facilitators. The findings offer learning to inform the design and implementation of similar interventions, contribute to the evidence base about barriers and facilitators to such interventions and provides in-depth description of the implementation and mechanisms of impact which have the potential to influence clinical and economic outcome evaluation.
The circuits of healthcare: Understanding healthcare seeking behaviour—A qualitative study with tuberculosis patients in Lisbon, Portugal
Authors: Ribeiro Rafaela M. , Havik Philip J. , Craveiro Isabel
Published: December 2021

Background

Understanding health delivery service from a patient´s perspective, including factors influencing healthcare seeking behaviour, is crucial when treating diseases, particularly infectious ones, like tuberculosis. This study aims to trace and contextualise the trajectories patients pursued towards diagnosis and treatment, while discussing key factors associated with treatment delays. Tuberculosis patients’ pathways may serve as indicator of the difficulties the more vulnerable sections of society experience in obtaining adequate care.

Methods

We conducted 27 semi-structured interviews with tuberculosis patients attending a treatment centre in a suburban area of Lisbon. We invited nationals and migrant patients in active treatment to participate by sharing their illness experiences since the onset of symptoms until the present. The Health Belief Model was used as a reference framework to consolidate the qualitative findings.

Results

By inductive analysis of all interviews, we categorised participants’ healthcare seeking behaviour into 4 main types, related to the time participants took to actively search for healthcare (patient delay) and time the health system spent to diagnose and initiate treatment (health system delay). Each type of healthcare seeking behaviour identified (inhibited, timely, prolonged, and absent) expressed a mindset influencing the way participants sought healthcare. The emergency room was the main entry point where diagnostic care cascade was initiated. Primary Health Care was underused by participants.

Conclusions

The findings support that healthcare seeking behaviour is not homogeneous and influences diagnostic delays. If diagnostic delays are to be reduced, the identification of behavioural patterns should be considered when designing measures to improve health services’ delivery. Healthcare professionals should be sensitised and perform continuous capacity development training to deal with patients´ needs. Inhibited and prolonged healthcare seeking behaviour contributes significantly to diagnostic delays. These behaviours should be detected and reverted. Timely responses, from patients and the healthcare system, should be promoted.
Epidemiological evidence relating risk factors to chronic obstructive pulmonary disease in China: A systematic review and meta-analysis
Authors: Chen Hong , Liu Xiang , Gao Xiang , Lv Yipeng , Zhou Liang , Shi Jianwei , Wei Wei , Huang Jiaoling , Deng Lijia , Wang Zhaoxin , Jin Ying , Yu Wenya
Published: December 2021

Background

Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China. The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD.

Methods

A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched. Based on the inclusion and exclusion criteria, 20 articles were selected. Stata 11.0 was used for meta-analysis. After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD. Heterogeneity between studies was assessed using I2 and Cochran’s Q tests. Begg’s test was used to assess publication bias.

Results

Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population.

Conclusion

Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases.
Real-world treatment patterns and clinical outcomes for inpatients with COVID-19 in the US from September 2020 to February 2021
Authors: Ayodele Olulade , Ren Kaili , Zhao Jing , Signorovitch James , Jonsson Funk Michele , Zhu Julia , Bao Ying , Gondek Kathleen , Keenan Hillary ,   for the R&D COVID Alliance
Published: December 2021

The objective of this retrospective cohort study was to describe pre-treatment characteristics, treatment patterns, health resource use, and clinical outcomes among adults hospitalized with COVID-19 in the United States (US) who initiated common treatments for COVID-19. The Optum® COVID-19 electronic health records database was used to identify patients >18 years, diagnosed with COVID-19, who were admitted to an inpatient setting and received treatments of interest for COVID-19 between September 2020 and January 2021. Patients were stratified into cohorts based on index treatment use. Patient demographics, medical history, care setting, medical procedures, subsequent treatment use, patient disposition, clinical improvement, and outcomes were summarized descriptively. Among a total of 26,192 patients identified, the most prevalent treatments initiated were dexamethasone (35.4%) and dexamethasone + remdesivir (14.9%), and dexamethasone was the most common subsequent treatment. At day 14 post-index, <10% of patients received any treatments of interest. Mean (standard deviation [SD]) patient age was 65.6 (15.6) years, and the most prevalent comorbidities included hypertension (44.8%), obesity (35.4%), and diabetes (25.7%). At the end of follow-up, patients had a mean (SD) 8.1 (6.6) inpatient days and 1.4 (4.1) days with ICU care. Oxygen supplementation, non-invasive, or invasive ventilation was required by 4.5%, 3.0%, and 3.1% of patients, respectively. At the end of follow-up, 84.2% of patients had evidence of clinical improvement, 3.1% remained hospitalized, 83.8% were discharged, 4% died in hospital, and 9.1% died after discharge. Although the majority of patients were discharged alive, no treatments appeared to alleviate the inpatient morbidity and mortality associated with COVID-19. This highlights an unmet need for effective treatment options for patients hospitalized with COVID-19.
Sustainable development and health assessment model of higher education in India: A mathematical modeling approach
Authors: Deng Chenchen , Yang Song , Liu Qingyang , Feng Songjie , Chen Chuangbin
Published: December 2021

The Coronavirus Disease 2019 has resulted in a transition from physical education to online learning, leading to a collapse of the established educational order and a wisdom test for the education governance system. As a country seriously affected by the pandemic, the health of the Indian higher education system urgently requires assessment to achieve sustainable development and maximize educational externalities. This research systematically proposes a health assessment model from four perspectives, including educational volume, efficiency, equality, and sustainability, by employing the Technique for Order Preference by Similarity to an Ideal Solution Model, Principal Component Analysis, DEA-Tobit Model, and Augmented Solow Model. Empirical results demonstrate that India has high efficiency and an absolute health score in the higher education system through multiple comparisons between India and the other selected countries while having certain deficiencies in equality and sustainability. Additionally, single-target and multiple-target path are simultaneously proposed to enhance the Indian current education system. The multiple-target approach of the India-China-Japan-Europe-USA process is more feasible to achieve sustainable development, which would improve the overall health score from .351 to .716. This finding also reveals that the changes are relatively complex and would take 91.5 years considering the relationship between economic growth rates and crucial indicators. Four targeted policies are suggested for each catching-up period, including expanding and increasing the social funding sources, striving for government expenditure support to improve infrastructures, imposing gender equality in education, and accelerating the construction of high-quality teachers.
Amount and type of physical activity and sports from one year forward after hip or knee arthroplasty—A systematic review
Authors: Mooiweer Yvet , van den Akker-Scheek Inge , Stevens Martin ,   On behalf of the PAIR study group
Published: December 2021

Introduction

After rehabilitation following total hip or knee arthroplasty (THA/TKA), patients are advised to participate in physical activity (PA) and sports. However, profound insight into whether people adopt a physically active lifestyle is lacking. Aim is to gain insight into the performed amount and type of PA (including sports) and time spent sedentarily by persons after THA/TKA.

Methods

A systematic review (PROSPERO: CRD42020178556). Pubmed, Cinahl, EMBASE and PsycInfo were systematically searched for articles reporting on amount of PA, and on the kind of activities performed between January 1995-January 2021. Quality of the articles was assessed with the adapted tool from Borghouts et al.

Results

The search retrieved 5029 articles, leading to inclusion of 125 articles reporting data of 123 groups; 53 articles reported on subjects post-THA, 16 on post-hip-resurfacing arthroplasty, 40 on post-TKA, 15 on post-unicompartimental knee arthroplasty and 12 on a mix of arthroplasty types. With respect to quality assessment, 14 articles (11%) met three or fewer criteria, 29 (24%) met four, 32 (26%) met five, 42 (34%) met six, and 6 (5%) met seven out of the eight criteria. PA levels were comparable for THA and TKA, showing a low to moderately active population. Time spent was mostly of low intensity. Roughly 50% of -subjects met health-enhancing PA guidelines. They spent the largest part of their day sedentarily. Sports participation was relatively high (rates above 70%). Most participation was in low-impact sports at a recreational level. Roughly speaking, participants were engaged in sports 3 hours/week, consisting of about three 1-hour sessions.

Conclusion

Activity levels seem to be low; less than half of them seemed to perform the advised amount of PA following health-enhancing guidelines Sports participation levels were high. However, many articles were unclear about the definition of sports participation, which could have led to overestimation.
International professional practices in mental health, organization of psychiatric care, and COVID-19: A survey protocol
Authors: Fond-Harmant Laurence , Kane Hélène , Gourret Baumgart Jade , Rusch Emmanuel , Breton Hervé , el-Hage Wissam , Deloyer Jocelyn , Lebas Marie-Clotide , Marazziti Donatella , Thome Johannes , Denis Frédéric
Published: December 2021

Objective

Our project aims to provide:

an overview of the impact of the COVID-19 pandemic on the field of mental health professionals in 23 countries;

a model of recommendations for good practice and proposals for methods and digital tools to improve the well-being at work of mental health professionals and the quality of services offered during crisis and post-crisis periods;

an in-depth ethics review of the assessment of the use of numerical tools for psychiatry professionals and patient support, including teleconsulting.

Methods

This is a large international survey conducted among 2,000 mental health professionals in 23 countries over a 12-month period. This survey will be based on 30 individual interviews and 20 focus group sessions, and a digital questionnaire will be sent online to 2,000 professionals based on the criteria of gender, age, professional experience, psychiatric specialty, context of work in psychiatry, and geographical location. Regarding the development of telepsychiatry during the COVID-19 pandemic, a pilot study on the use of digital tools will be carried out on 100 clients of psychiatry professionals in France and Belgium.

Discussion-conclusion

This study will contribute to the co-construction of an international organization and monitoring system that takes into account psychiatric health professionals as major resources to fight against the COVID-19 pandemic and to develop efficient processes for preparing and anticipating crises by reducing psychosocial risks as much as possible. This project also aims to design tools for remote medicine and to develop the use of numerical tools for monitoring and supporting professionals and helping professionals to build the conditions for satisfactory operational work during crises and post-crisis situations, using adapted organizational methods. Our ongoing research should support professionals in the search for existing concrete solutions to cope with emergency work situations while maintaining an optimal quality of life.
Analysis of the spatial differentiation and scale effects of the three-dimensional architectural landscape in Xi’an, China
Authors: Ren Wenjing , Zhao Jingyuan , Ma Xina , Wang Xiao
Published: December 2021

Three-dimensional landscape patterns are an effective means to study the relationship between landscape pattern evolution and eco-environmental effects. This paper selects six districts in Xi’an as the study area to examine the spatial distribution characteristics of the three-dimensional architectural landscape in the city’s main urban area using three-dimensional information on the buildings in 2020 with the support of GIS. In this study, two new architectural landscape indices—landscape height variable coefficient and building rugosity index—were employed in landscape pattern analysis, whilst a system of rigorous and comprehensive three-dimensional architectural landscape metrics was established using principal component analysis. A mathematical model of weighted change of landscape metrics based on the objective weighting method was applied to carry out scale analysis of the landscape patterns. Spatial statistical analysis and spatial autocorrelation analysis were conducted to comprehensively study the differentiation of three-dimensional architectural landscape spatial patterns. The results show that the characteristic scale of the three-dimensional landscape pattern in Xi’an’s main urban area is around 8 km. Moreover, the three-dimensional landscape of the buildings in this area is spatially positively correlated, exhibiting a high degree of spatial autocorrelation whilst only showing small spatial differences. The layout of the architectural landscape pattern is disorderly and chaotic within the second ring, whilst the clustering of patch types occurs near the third ring. Moreover, the building density in the Beilin, Lianhu, and Xincheng districts is large, the building height types are rich, and the roughness of the underlying surface is high, such that these are key areas to be improved through urban renewal. The height, volume, density, morphological heterogeneity, and vertical roughness of the architectural landscape vary amongst functional areas within the study area. This paper is the first to apply the study of spatial heterogeneity of three-dimensional landscape patterns to Xi’an. It does so in order to provide a quantitative basis for urban landscape ecological design for urban renewal and the rational planning of built-up areas, which will promote the sustainable development of the city’s urban environment.
Developmental gene regulatory network connections predicted by machine learning from gene expression data alone
Authors: Zhang Jingyi , Ibrahim Farhan , Najmulski Emily , Katholos George , Altarawy Doaa , Heath Lenwood S. , Tulin Sarah L.
Published: December 2021

Gene regulatory network (GRN) inference can now take advantage of powerful machine learning algorithms to complement traditional experimental methods in building gene networks. However, the dynamical nature of embryonic development–representing the time-dependent interactions between thousands of transcription factors, signaling molecules, and effector genes–is one of the most challenging arenas for GRN prediction. In this work, we show that successful GRN predictions for a developmental network from gene expression data alone can be obtained with the Priors Enriched Absent Knowledge (PEAK) network inference algorithm. PEAK is a noise-robust method that models gene expression dynamics via ordinary differential equations and selects the best network based on information-theoretic criteria coupled with the machine learning algorithm Elastic Net. We test our GRN prediction methodology using two gene expression datasets for the purple sea urchin, Stronglyocentrotus purpuratus, and cross-check our results against existing GRN models that have been constructed and validated by over 30 years of experimental results. Our results find a remarkably high degree of sensitivity in identifying known gene interactions in the network (maximum 81.58%). We also generate novel predictions for interactions that have not yet been described, which provide a resource for researchers to use to further complete the sea urchin GRN. Published ChIPseq data and spatial co-expression analysis further support a subset of the top novel predictions. We conclude that GRN predictions that match known gene interactions can be produced using gene expression data alone from developmental time series experiments.
A novel class of Candida glabrata cell wall proteins with β-helix fold mediates adhesion in clinical isolates
Authors: Reithofer Viktoria , Fernández-Pereira Jordan , Alvarado María , de Groot Piet , Essen Lars-Oliver
Published: December 2021

Candida glabrata is an opportunistic pathogenic yeast frequently causing infections in humans. Though it lacks typical virulence factors such as hyphal development, C. glabrata contains a remarkably large and diverse set of putative wall adhesins that is crucial for its success as pathogen. Here, we present an analysis of putative adhesins from the homology clusters V and VI. First, sequence similarity network analysis revealed relationships between cluster V and VI adhesins and S. cerevisiae haze protective factors (Hpf). Crystal structures of A-regions from cluster VI adhesins Awp1 and Awp3b reveal a parallel right-handed β-helix domain that is linked to a C-terminal β-sandwich. Structure solution of the A-region of Awp3b via single wavelength anomalous diffraction phasing revealed the largest known lanthanide cluster with 21 Gd3+ ions. Awp1-A and Awp3b-A show structural similarity to pectate lyases but binding to neither carbohydrates nor Ca2+ was observed. Phenotypic analysis of awp1Δ, awp3Δ, and awp1,3Δ double mutants did also not confirm their role as adhesins. In contrast, deletion mutants of the cluster V adhesin Awp2 in the hyperadhesive clinical isolate PEU382 demonstrated its importance for adhesion to polystyrene or glass, biofilm formation, cell aggregation and other cell surface-related phenotypes. Together with cluster III and VII adhesins our study shows that C. glabrata CBS138 can rely on a set of 42 Awp1-related adhesins with β-helix/α-crystallin domain architecture for modifying the surface characteristics of its cell wall.
Intragenic proviral elements support transcription of defective HIV-1 proviruses
Authors: Kuniholm Jeffrey , Armstrong Elise , Bernabe Brandy , Coote Carolyn , Berenson Anna , Patalano Samantha D. , Olson Alex , He Xianbao , Lin Nina H. , Fuxman Bass Juan I. , Henderson Andrew J.
Published: December 2021

HIV-1 establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription droplet digital PCR identified env and nef transcripts which lacked 5’ untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5’UTR-deficient env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5’ rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH.
An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity
Authors: Monticelli Stephanie R. , Bryk Peter , Brewer Matthew G. , Aguilar Hector C. , Norbury Christopher C. , Ward Brian M.
Published: December 2021

The extracellular virion (EV) form of Orthopoxviruses is required for cell-to-cell spread and pathogenesis, and is the target of neutralizing antibodies in the protective immune response. EV have a double envelope that contains several unique proteins that are involved in its intracellular envelopment and/or subsequent infectivity. One of these, F13, is involved in both EV formation and infectivity. Here, we report that replacement of vaccinia virus F13L with the molluscum contagiosum virus homolog, MC021L, results in the production of EV particles with significantly increased levels of EV glycoproteins, which correlate with a small plaque phenotype. Using a novel fluorescence-activated virion sorting assay to isolate EV populations based on glycoprotein content we determine that EV containing either higher or lower levels of glycoproteins are less infectious, suggesting that there is an optimal concentration of glycoproteins in the outer envelope that is required for maximal infectivity of EV. This optimal glycoprotein concentration was required for lethality and induction of pathology in a cutaneous model of animal infection, but was not required for induction of a protective immune response. Therefore, our results demonstrate that there is a sensitive balance between glycoprotein incorporation, infectivity, and pathogenesis, and that manipulation of EV glycoprotein levels can produce vaccine vectors in which pathologic side effects are attenuated without a marked diminution in induction of protective immunity.
Un curso de cálculo diferencial e integral en la academia de artillería de Segovia: el cuaderno escrito por el cadete Martín García Loygorri al dictado del profesor Isidoro Gómez (1775-1776)
Authors: Velamazán Gimeno M.ª Ángeles
Published: December 2021

En la segunda mitad del siglo XVIII los Borbones emprendieron la modernización de la artillería española renovando su oficialidad con jóvenes de la nobleza y creando un centro de formación de alto nivel, tanto en el ámbito científico como militar. Así, en 1764 se abrió el Real Colegio de Artillería de Segovia con un plan de estudios cuyo aspecto más renovador en el ámbito de las matemáticas fue la incorporación del cálculo diferencial e integral. Hasta el momento, el tercer tomo del Curso Matemático del profesor Pedro Giannini (1795) era la principal prueba documental del desarrollo y extensión de los distintos temas que comprendía la asignatura. Este artículo analiza el alcance y contenido de un manuscrito inédito, hasta ahora inexplorado, veinte años anterior: el curso de Cálculo Integral y Diferencial dictado por el profesor Isidoro Gómez entre el 5 diciembre de 1775 y el 12 de abril de 1776, escrito por el cadete Martín García Loygorri.
Effects of xylazine and adrenaline combinations: Preliminary clinical application for non-surgical protocols of nephrosplenic entrapment in horses
Authors: Cherdchutham Worakij , Sukhong Patskit , Sae-oueng Kanchanog , Supanwinijkul Nithisphat , Wiangnak Kittanai , Srimuang Jirayut , Apichaimongkonkun Tawanhathai , Limratchapong Sarocha , Petchdee Soontaree
Published: December 2021

Background and Aim: The medical treatment of horses with nephrosplenic entrapment (NSE) of the large colon through administrating phenylephrine and rolling during general anesthesia was effective and less expensive than surgical treatment. However, the selection of drugs for non-surgical treatment of NSE is not a usual method for clinical practice. This study aimed to identify the effects of combined drugs on the cardiac and splenic response in horses and provide information on the NSE of the large colon for clinical application.

Materials and Methods: Six healthy Thai native crossbred horses were enrolled in this study. Horses received two protocols with a withdrawal period of 14 days: Group 1 received xylazine (0.5 mg/kg IV) and adrenaline (1 mcg/kg IV), and Group 2 received xylazine (0.5 mg/kg IV) and adrenaline (3 mcg/kg IV). Heart rate (HR), HR variability (HRV), heart dimensions, and the splenic response of six horses were measured before the sedation, 30 and 60 min later, and 65, 70, 75, 80, 90, and 100 min after adrenaline administration. Doppler was used to obtain systolic blood pressure.

Results: The HRV low-frequency and high-frequency power ratios decreased after using xylazine. Hypertension was observed after adrenaline administration. In this study, there were only minimal differences in the HR and respiratory rate between groups. However, overall cardiac and splenic parameters were statistically higher in Group 2.

Conclusion: This study suggested that xylazine and three micrograms of adrenaline preserved the cardiac autonomic activity balance and were safe to use non-surgical applicability in horses.
EVALUATE HEALTH-RELATED QUALITY OF LIFE AMONG URBAN ELDERS IN DIFFERENT LIVING ENVIRONMENTS
Authors: Xing H. , Yu W. , Chen S. , Sun Y. , He X.
Published: December 2021

Background: This study aimed to assess and compare the health-related quality of life (HRQOL) in older people who lived with different living mode, including staying at home with spouse or child, staying at home alone and staying in nursing home. Methods: Data were collected by cross-sectional survey in 2013. The sample included 95 elderly people who were staying at home with spouse or child, 43 elderly people at home alone and 93 elderly people in nursing home. Results: The three groups were similar according to gender, education and existence of chronic disease. The univariate analysis showed that physical component summary (PCS) and mental component summary (MCS) scores of HRQOL were lower in those living in nursing home than those living in their own homes. The scores of PCS and MCS for the old elderly people (over 75 years old) were lower compared to the young elderly people (60-74 years old). The scores of PCS and MCS for elderly people who had part or incapacity of self-care ability were lower compared to complete self-care ability. There was a positive correlation between the number of weekly physical exercise and PCS and MCS. The main influential factors for PCS were physical exercise, age and self-care ability, physical exercise also affected MCS based on multiple linear regression analysis. Conclusion: These data suggest that PCS and MCS are not lower in elderly assisted living in nursing home compared to staying at home by multiple statistical analyses. HRQOL may be affected by physical exercise.
ADVANCING RESEARCH BY CLEARLY LABELING MEASURES OF PHYSICAL FUNCTION: EXTRACTING AMBULATION AND STAIR-CLIMBING FROM “MOBILITY DISABILITY”
Authors: Siordia C. , Lewis A.N.
Published: December 2021

The term “mobility disability” is used in different academic disciplines to discuss conceptualizations of physical movement. Inadequate attention has been paid to how this umbrella term refers to various forms of measurements on both hypothetical and enacted function. Refining what is meant by mobility disability may impact clinical practice by providing more specific information to clinicians. Less ambiguous labeling may have the potential to advance research by lowering measurement imprecision. We complement discussion by presenting empirical analysis on 5,995 participants (aged > 65) from National Health and Aging Trends Study (NHATS-2011). Ambiguous labeling of mobility may unintentionally obscure what is known about perceived capacity for ambulation and stair-climbing. Because creating low-cost and readily-available measures of health in the population has the potential to advance public health knowledge, efforts should continue to standardize and clarify measures of mobility.
INVESTIGATION INTO WATER CONSUMPTION AND ITS INFLUENCE ON DEPRESSION, MEMORY PROBLEMS AND CONSTIPATION IN OLDER PERSONS
Authors: Tsindos P.S. , Itsiopoulos C. , Kouris-Blazos A.
Published: December 2021

Objective: This study examines a possible relationship between plain water consumption, mild cognitive impairment, depression and constipation in a cohort of Greek-born Australians aged 65 and over. Design: A cross-sectional study using a semi-quantitative food frequency and lifestyle questionnaire. Participants: We recruited 150 elderly Greek migrant volunteers who were born on Greek Mediterranean islands and collected detailed diet and lifestyle data using an established protocol used in the Mediterranean Islands Study (MEDIS) in Greece. Measurements: Water intake from plain water, beverages and foods was assessed using a validated food frequency questionnaire. Depression and memory were assessed using the validated Geriatric Depression Scale – Short version. Results: Mean water intake from all sources for all participants was 2871 mL (p = 0.010), water derived from foods was 1048mL (p = 0.014), beverage intake other than plain water was 876mL (p < 0.001) and plain water consumption was low with a mean of 947mL (p = 0.001) per day. Those who reported as not depressed (GDS < 6) consumed 100 mL less total water from food and beverages than those who scored 6 or above and those who self-reported no constipation consumed nearly 300mL more water in foods than those who self-reported being constipated. Conclusion: Results suggest that habitual low consumption of plain water (< 1000mL/day) was not associated with constipation or self-reported mental-emotional disorders in this group. Water consumption from food was significantly higher in those with no constipation suggesting that consumption of water in food may be a significant factor in ensuring adequate water needs. Clinicians should consider water intake in food when assessing patient water intake.