bluuebunny/crossref_metadata_2025 huggingface dataset:
LLAMA: a robust and scalable machine learning pipeline for analysis of large scale 4D microscopy data: analysis of cell ruffles and filopodia
Authors: Lefevre James G. , Koh Yvette W. H. , Wall Adam A. , Condon Nicholas D. , Stow Jennifer L. , Hamilton Nicholas A.
Published: August 2021

Background

With recent advances in microscopy, recordings of cell behaviour can result in terabyte-size datasets. The lattice light sheet microscope (LLSM) images cells at high speed and high 3D resolution, accumulating data at 100 frames/second over hours, presenting a major challenge for interrogating these datasets. The surfaces of vertebrate cells can rapidly deform to create projections that interact with the microenvironment. Such surface projections include spike-like filopodia and wave-like ruffles on the surface of macrophages as they engage in immune surveillance. LLSM imaging has provided new insights into the complex surface behaviours of immune cells, including revealing new types of ruffles. However, full use of these data requires systematic and quantitative analysis of thousands of projections over hundreds of time steps, and an effective system for analysis of individual structures at this scale requires efficient and robust methods with minimal user intervention.

Results

We present LLAMA, a platform to enable systematic analysis of terabyte-scale 4D microscopy datasets. We use a machine learning method for semantic segmentation, followed by a robust and configurable object separation and tracking algorithm, generating detailed object level statistics. Our system is designed to run on high-performance computing to achieve high throughput, with outputs suitable for visualisation and statistical analysis. Advanced visualisation is a key element of LLAMA: we provide a specialised tool which supports interactive quality control, optimisation, and output visualisation processes to complement the processing pipeline. LLAMA is demonstrated in an analysis of macrophage surface projections, in which it is used to i) discriminate ruffles induced by lipopolysaccharide (LPS) and macrophage colony stimulating factor (CSF-1) and ii) determine the autonomy of ruffle morphologies.

Conclusions

LLAMA provides an effective open source tool for running a cell microscopy analysis pipeline based on semantic segmentation, object analysis and tracking. Detailed numerical and visual outputs enable effective statistical analysis, identifying distinct patterns of increased activity under the two interventions considered in our example analysis. Our system provides the capacity to screen large datasets for specific structural configurations. LLAMA identified distinct features of LPS and CSF-1 induced ruffles and it identified a continuity of behaviour between tent pole ruffling, wave-like ruffling and filopodia deployment.
Correction to: Myocardial bridging of the left anterior descending coronary artery as a risk factor for atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy: a matched case–control study
Authors: Nie Changrong , Zhu Changsheng , Yang Qiulan , Xiao Minghu , Meng Yanhai , Wang Shuiyun
Published: August 2021

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Baseline-adjusted proportional odds models for the quantification of treatment effects in trials with ordinal sum score outcomes
Authors: Buri Muriel , Curt Armin , Steeves John , Hothorn Torsten
Published: August 2021

An amendment to this paper has been published and can be accessed via the original article.
A genome epidemiological study of mycobacterium tuberculosis in subpopulations with high and low incidence rate in Guangxi, South China
Authors: Lin Dingwen , Wang Junning , Cui Zhezhe , Ou Jing , Huang Liwen , Wang Ya
Published: August 2021

Background

Tuberculosis (TB) is caused by a bacterium calledMycobacterium tuberculosis(Mtb). China is the third in top 8 high TB burden countries and Guangxi is one of the high incidence areas in South China. Determine bacterial factors that affected TB incidence rate is a step toward Ending the TB epidemic.

Results

Genomes ofM. tuberculosiscultures from a relatively high and low incidence region in Guangxi have been sequenced. 347 of 358(96.9%) were identified asM. tuberculosis. All the strains belong to Lineage 2 and Lineage 4, except for one in Lineage 1. We found that the genetic structure of theM. tuberculosispopulation in each county varies enormously. Low incidence rate regions have a lower prevalence of Beijing genotypes than other regions. Four isolates which harboredmutT4-48 also hadmutT2-58 mutations. It is suggested that strains from the ancestors of modern Beijing lineage is circulating in Guangxi. Strains of modern Beijing lineage (OR=2.04) were more likely to acquire drug resistances than Lineage 4. Most of the lineage differentiation SNPs are related to cell wall biosynthetic pathways.

Conclusions

These results provided a higher resolution to better understand the history of transmission ofM. tuberculosisfrom/to South China. And the incidence rate of tuberculosis might be affected by bacterial population structure shaped by demographic history. Our findings also support the hypothesis that Modern Beijing lineage originated in South China.
Prevalence and associated characteristics of anti-SARS-CoV-2 antibodies in Mexico 5 months after pandemic arrival
Authors: Díaz-Salazar Cristina , Sánchez-García Adriana , Rodríguez-Gutiérrez René , Camacho-Ortiz Adrián , Saldívar-Rodríguez Donato , González-González José Gerardo
Published: August 2021

Background

Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence.

Methods

We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student’s t-test and the Mann–Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics.

Results

Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1–6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9–5.5).

Conclusions

There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.
A highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis: a multicenter prospective study in China
Authors: Sun Wenwen , Wu Zheyuan , Zhou Ying , Xia Fan , Tang Qin , Wang Jie , Yang Jinghui , Yu Fangyou , Yang Hua , Xiao Heping , Fan Lin
Published: August 2021

Background

To verify the efficacy and safety of an inexpensive standardized regimen for multidrug-resistant tuberculosis (MDR-TB) with low resistance to isoniazid (INH), a multicenter prospective study was conducted in eastern China.

Methods

Patients diagnosed as MDR-TB with low concentration INH resistance and rifampicin resistance, second-line/injectable agents sensitive were prospectively enrolled, given the regimen of Amikacin (Ak)–Fluoroquinolones (FQs)–Cycloserine (Cs)–Protionamide (Pto)–PasiniaZid (Pa)–Pyrazinamide (Z) for 6 months followed by 12 months of FQs–Cs–Pto–Pa–Z, and then followed up for treatment outcomes and adverse events (AEs).

Results

A total of 114 patients were enrolled into the study. The overall favorable treatment rate was 79.8% (91/114). Among 91 cases with favorable treatment, 75.4% (86/114) were cured and 4.4% (5/114) were completed treatment. Regarding to unfavorable outcomes, among 23 cases, 8.8% (10/114) had failures, 8.8% (10/114) losing follow up, 0.9% (1/114) had treatment terminated due to intolerance to drugs and 1.8% (2/114) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78,p0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients (26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42).

Conclusions

The regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen.

Clinical trials registrationChina Clinical Trial Registry ChiCTR-OPC-16009380
Cesarean delivery rates, hospital readiness and quality of clinical management in Ethiopia: national results from two cross-sectional emergency obstetric and newborn care assessments
Authors: Beyene Misrak Getnet , Zemedu Theodros Getachew , Gebregiorgis Azmach Hadush , Ruano Ana Lorena , Bailey Patricia E.
Published: August 2021

Background

Cesarean delivery (CD) rates have reached epidemic levels in many high and middle income countries while increasingly, low income countries are challenged both by high urban CD rates and high unmet need in rural areas. The managing authority of health care institutions often plays a role in these disparities. This paper shows changes between 2008 and 2016 in Ethiopian CD rates, readiness of hospitals to provide CD and quality of clinical care, while highlighting the role of hospital management authority.

Methods

This secondary data analysis draws from two national cross-sectional studies to assess emergency obstetric and newborn care. The sample includes 111 hospitals in 2008 and 316 hospitals in 2016, and 275 women whose CD chart was reviewed in 2008 and 568 in 2016. Descriptive statistics are used to describe our primary outcome measures: population- and institutional-based CD rates; hospital readiness to perform CD; quality of clinical management, including the relative size of Robson classification groups.

Results

The national population CD rate increased from 2008 to 2016 (< 1 to 2.7%) as did all regional rates. Rates in 2016 ranged from 24% in urban settings to less than 1% in several rural regions. The institutional rate was 54% in private for-profit hospitals in 2016, up from 46% in 2008. Hospital readiness to perform CDs increased in public and private for-profit hospitals. Only half of the women whose charts were reviewed received uterotonics after delivery of the baby, but use of prophylactic antibiotics was high. Partograph use increased from 9 to 42% in public hospitals, but was negligible or declined elsewhere. In 2016, 40% of chart reviews from public hospitals were among low-risk nulliparous women (Robson groups 1&2).

Conclusions

Between 2008 and 2016, government increased the availability of CD services, improved public hospital readiness and some aspects of clinical quality. Strategies tailored to further reduce the high unmet need for CD and what appears to be an increasing number of unnecessary cesareans are discussed. Adherence to best practices and universal coverage of water and electricity will improve the quality of hospital services while the use of the Robson classification system may serve as a useful quality improvement tool.
Regional differences in cervical cancer incidence and associated risk behaviors among Norwegian women: a population-based study
Authors: Hansen Bo T. , Campbell Suzanne , Nygård Mari
Published: August 2021

Background

Cervical cancer incidence is influenced by screening and risk factors in the population. The main risk factor for cervical cancer is sexually transmitted human papillomavirus (HPV), which is sexually transmitted and thus associated with sexual behavior. Smoking, parity and hormonal contraceptive use may also be associated with cervical cancer risk. We compared incidence, screening coverage and risk behaviors for cervical cancer between health regions in Norway.

Methods

We obtained data on incidence of cervical cancer among Norwegian women during 1992–2016 and data on screening coverage from the Cancer Registry of Norway. We obtained data on sexual behavior and smoking from a population-based survey of 16,575 Norwegian women who were 18–45 years old in 2005.

Results

Cervical cancer incidence was higher in the northern and southeastern region than in the middle and western region (range in incidence per 100,000 person-years during 1992–2016; north: 10.5 to 14.6; southeast: 9.3 to 12.9; mid: 6.8 to 9.5; west: 8.4 to 10.0). The incidence decreased modestly in the north (average annual percentage change (95% confidence interval) − 1.0 (− 1.2 to − 0.7)) and southeast (− 0.7 (− 1.0 to − 0.3)), but did not change significantly in the mid (− 0.3 (− 1.0 to 0.4)) and west (− 0.3 (− 0.6 to 0.0)). Compared to the national average, women in the north had earlier sexual debut, more partners and higher prevalence of ever having had a sexually transmitted infection (STI), while the opposite was observed among women in the west. Women in the middle and southeastern regions tended to be similar to the national average for sexual behaviors. Although less pronounced, the prevalence of smoking showed regional patterns similar to that observed for sexual behaviors, while ever-use of hormonal contraceptives and cervical screening coverage was similar between regions.

Conclusions

There were regional differences in cervical cancer incidence during the era of nationally organized cervical screening in Norway. To some extent, these differences corresponded to regional differences in risk behavior for cervical cancer in the Norwegian female population.
Spatiotemporal distribution and determinants of delayed first antenatal care visit among reproductive age women in Ethiopia: a spatial and multilevel analysis
Authors: Belay Daniel Gashaneh , Aragaw Fantu Mamo , Anley Denekew Tenaw , Tegegne Yibeltal Shitu , Gelaye Kassahun Alemu , Tessema Zemenu Tadesse
Published: August 2021

Background

Antenatal care (ANC) is one of the four pillars of the initiative for safe motherhood. ANC helps to improve the health of pregnant women and reduce the risk of adverse pregnancy outcome. First ANC is used to know the health status of the mothers and the fetus, to estimate the gestational age and expected date of delivery. Our research aims to investigate the Spatio-temporal distribution of delayed first ANC visit and its predictors using multilevel binary logistic regression analysis.

Method

A total of 10,184 women (2061 in 2005, 3366 in 2011, and 4757 in 2016) were included for this study. The data were cleaned and weighted using STATA version 14. A multilevel binary logistic regression model was fitted to identify significant predictors of delayed first ANC visit. ArcGIS software was used to explore the spatial distribution of delayed first ANC visits and a Bernoulli model was fitted using SaTScan software to identify significant clusters of delayed first ANC visits.

Results

Overall, 77.69, 73.95, and 67.61% of women had delayed their first ANC visit in 2005, 2011, and 2016 EDHSs respectively. Women education [AOR = 0.71; 95%CI; 0.60, 0.84], unwanted pregnancy [AOR = 1.41;95%CI; 1.04, 1.89], and rural residence [AOR = 1.68;95%CI; 1.19, 2.38] have significantly associated with delayed first ANC visit. The spatial analysis revealed that delayed first ANC visit varies in each EDHS period. The SaTScan analysis result of EDHS 2005 data identified 122 primary clusters located between the border of Oromia and Eastern SNNPR regions (RR = 1.30, LLR = 32.31, P-value< 0.001), whereas in 2011 EDHS, 145 primary clusters were identified in entire Tigray, B/Gumuz, Amhara western part of Afar and northwest Oromia regions (RR = 1.30, LLR = 40.79, P-value< 0.001). Besides in 2016 EDHS,198 primary clusters were located in the entire SNNPR, Gambella, Northen B/Gumuz, and western Oromia regions. (RR = 1.35, LLR = 83.21, P-value< 0.001).

Conclusion

In Ethiopia delayed first ANC visit was significantly varied across the country over time Women’s education, wanted the last child, and residence were significantly associated with delayed first ANC booking. The effect of each predictor was found to be different across regions of Ethiopia. Therefore, a targeted intervention program is required in highly affected areas of Ethiopia.
Occupational class differences in outcomes after ischemic stroke: a prospective observational study
Authors: Zhu Yinwei , Lu Yaling , Zhou Mo , Huang Ping , Zhang Peipei , Guo Yumei , Lv Liying , Zhang Yonghong , Zhong Chongke , Xu Tan
Published: August 2021

Background

Occupational class is an integral part of socioeconomic status. The studies focused on the occupational difference in ischemic stroke outcome in a Chinese population are limited. We aimed to investigate the associations between occupational class and the prognosis of patients with ischemic stroke in China.

Methods

We included 1484 ischemic stroke participants (mean age: 63.42 ± 11.26 years) from the prospective cohort study: Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke (IIPAIS). Occupational class was categorized into white-collar workers, blue-collar workers and farmers in our study. Study outcomes were cardiovascular events and all-cause mortality within 12 months after ischemic stroke onset. We applied Cox proportional hazard model to evaluate the associations between the occupational class and study outcomes after ischemic stroke.

Results

Within 12 months after ischemic stroke, there were 106 (7.5%) cardiovascular events and 69 (4.9%) all-cause deaths. The Kaplan–Meier plots showed that white-collar workers had highest risk of cardiovascular events after 12-month follow-up (Log-rankP = 0.02). Multivariate adjusted hazard ratio and 95% confidence intervals (CIs) of farmers versus white-collar workers was 0.43(0.20–0.91) for cardiovascular events. No significant difference showed in blue-collar workers versus white-collar workers, with fully adjusted hazard ratio 0.62(95% CIs, 0.23–1.67).

Conclusions

Compared with white-collar workers, farmers are associated with less risk of cardiovascular events at 12 months after ischemic stroke, while there are no significant differences in blue-collar workers.
External control of fluoridation in the public water supplies of Brazilian cities as a strategy against caries: a systematic review and meta-analysis
Authors: Rosário Bárbara Souza Martins , Rosário Henrique Damian , de Andrade Vieira Walbert , Cericato Graziela Oro , Nóbrega Diego Figueiredo , Blumenberg Cauane , Hugo Fernando Neves , Costa Márcio Magno , Paranhos Luiz Renato
Published: August 2021

Background

Among the methods currently available to provide fluoride in population levels, fluoridated water is the most successful for presenting high efficacy, safety and good cost–benefit. However, recent studies on external control have shown great variability of fluoride concentrations in the water from treatment stations in Brazilian cities, which must present concentration between 0.6 and 0.8 mg/L to be considered acceptable in most cities. Thus, this study aimed to perform a systematic review of the literature to assess the adequacy of fluoride concentration in the water in Brazilian cities using external control.

Methods

The protocol was registered in PROSPERO. Six databases were used as primary search sources and three databases were used to partially capture the "gray literature". Only observational studies that assessed the fluoride concentration of artificially fluoridated water from the public supply network were included. The JBI Critical Appraisal Tools for Systematic Reviews was used to assess the risk of bias of the studies. A proportion meta-analyses using random-effect models were performed. The heterogeneity between studies was determined by I2statistic. Meta-regressions were conducted to identify relevant moderators to be used in stratified meta-analyses. Publication bias was investigated by Egger’s tests.

Results

The search provided 2038 results, from which 14 met the eligibility criteria and were included in the data extraction of the review. Overall, the water samples were collected from 449 different sources in three Brazilian regions. Thirteen studies presented a low risk of bias. The mean concentration of fluoride ranged from 0.17 to 0.89 ppmF. The meta-analyis demonstrated that more than half of the water samples analyzed had fluoride concentration levels outside the acceptable range (56.6%; 95% CI 45.5; 67.3), with high heterogeneity.

Conclusion

More than half of the public water supply analyzed in the studies selected had fluoride concentration levels outside the acceptable range, which may affect the risk of developing oral diseases in the Brazilian population, having an important impact on public health.
A case of adenomyosis with leiomyoma that was effectively treated with relugolix and kamishoyosan add-on therapy
Authors: Sasamori Yukifumi , Takehara Kohei , Terashima Tsuyoshi , Onodera Takako , Yatsuki Keita , Nakagawa Ippei , Takahashi Yuko , Nishida Haruka , Ichinose Takayuki , Hiraike Haruko , Nagasaka Kazunori
Published: August 2021

Background

Recently, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, has been considered an effective therapy for leiomyoma based on a phase 3 study in Japanese women. Leiomyoma combined with severe adenomyosis occasionally occurs in perimenopausal women; however, little information on the effectiveness of relugolix against severe adenomyosis exists.

Case presentation

A 49-year-old woman was referred to our hospital with acute lower abdominal pain and abnormal uterine bleeding. Magnetic resonance imaging revealed multiple leiomyomas with diffuse adenomyosis. Left hydrosalpinx was also observed. The patient refused surgical treatment and preferred oral relugolix. Since she experienced a hot flush and headache induced by relugolix, a traditional Japanese Kampo, kamishoyosan, was added to improve the side effects of relugolix. The patient was asymptomatic at the time of this report and experienced a significant shrinkage in uterine volume. Ultimately, she avoided hysterectomy as desired.

Conclusions

To our knowledge, this is the first report of co-occurring adenomyosis and leiomyoma, which was effectively treated with relugolix. Although the management of adverse side effects, including hot flush and headache by relugolix, has recently attracted attention and controversy, relugolix add-on therapy with kamishoyosan may help treat menopausal symptoms.
Impact of the COVID-19 pandemic on teaching and learning in health professional education: a mixed methods study protocol
Authors: Kumar Arunaz , Sarkar Mahbub , Davis Elizabeth , Morphet Julia , Maloney Stephen , Ilic Dragan , Palermo Claire
Published: August 2021

Background

Due to the complex nature of healthcare professionals’ roles and responsibilities, the education of this workforce is multifaceted and challenging. It relies on various sources of learning from teachers, peers, patients and may focus on Work Integrated Learning (WIL). The COVID-19 pandemic has impacted many of these learning opportunities especially those in large groups or involving in person interaction with peers and patients. Much of the curriculum has been adapted to an online format, the long-term consequence of which is yet to be recognized. The changed format is likely to impact learning pedagogy effecting both students and teachers. This requires a systematic approach to evaluation of online teaching and learning adaptation, in comparison to the previous format, where, in person education may have been the focus.

Methods

The proposed study is a broad based evaluation of health professional education in a major Australian University. The protocol describes a mixed methods convergent design to evaluate the impact of online education on students and teachers in health professional courses including Medicine, Nursing, Allied Health and Biomedical Science. A framework, developed at the university, using Contribution Analysis (CA), will guide the evaluation. Quantitative data relating to student performance, student evaluation of units, quantity of teaching activities and resource utilization will be collected and subjected to relevant statistical analysis. Data will be collected through surveys (500 students and 100 teachers), focus groups (10 groups of students) and interviews of students and teachers (50 students beyond graduation and 25 teachers, for long term follow up to 12 months). Application of CA will be used to answer the key research questions on the short term and long-term impact of online education on teaching and learning approaches.

Discussion

The protocol describes the study, which will be widely implemented over the various courses in Health Professional Education and Biomedical Science. It will evaluate how students and teachers engage with the online delivery of the curriculum, student performance, and resources used to implement these changes. It also aims to evaluate longitudinal outcome of student learning attributes and impact on graduate outcomes, which is poorly reported in educational literature.
Living life in limbo: experiences of healthcare professionals during the HCPC fitness to practice investigation process in the UK
Authors: Maben Jill , Hoinville Linda , Querstret Dawn , Taylor Cath , Zasada Magdalena , Abrams Ruth
Published: August 2021

Background

It is the responsibility of healthcare regulators to ensure healthcare professionals remain fit for practice in healthcare settings. If there are concerns about an individual healthcare professional they may undergo a fitness to practice investigation. This process is known to be hugely stressful for doctors and social workers, but little is known about the impact of this experience on other professions. This study explores the experiences of registrants going through the process of being reported to the UK’s Health and Care Professions Council (HCPC) and attending fitness to practice (FTP) hearings. We discuss the implications of this process on registrants’ wellbeing and, from our findings, present recommendations based on registrants experiences. In doing so we articulate the structural processes of the HCPC FTP process and the impact this has on individuals.

Methods

This study uses semi-structured interviews and framework analysis to explore the experiences of 15 registrants who had completed the FTP process. Participants were sampled for maximum variation and were selected to reflect the range of possible processes and outcomes through the FTP process.

Results

The psychological impact of undergoing a FTP process was significant for the majority of participants. Their stories described influences on their wellbeing at both a macro (institutional/organisational) and micro (individual) level. A lack of information, long length of time for the process and poor support avenues were macro factors impacting on the ability of registrants to cope with their experiences (theme 1). These macro factors led to feelings of powerlessness, vulnerability and threat of ruin for many registrants (theme 2). Suggested improvements (theme 3) included better psychological support (e.g. signposting or provision); proportional processes to the incident (e.g. mediation instead of hearings); and taking context into account.

Conclusions

Findings suggest that improvements to both the structure and conduct of the FTP process are warranted. Implementation of better signposting for support both during and after a FTP process may improve psychological wellbeing. There may also be value in considering alternative ways of organising the FTP process to enable greater consideration of and flexibility for registrants’ context and how they are investigated.
Invasive snails, parasite spillback, and potential parasite spillover drive parasitic diseases of Hippopotamus amphibius in artificial lakes of Zimbabwe
Authors: Schols Ruben , Carolus Hans , Hammoud Cyril , Muzarabani Kudzai C. , Barson Maxwell , Huyse Tine
Published: August 2021

Background

Humans impose a significant pressure on large herbivore populations, such as hippopotami, through hunting, poaching, and habitat destruction. Anthropogenic pressures can also occur indirectly, such as artificial lake creation and the subsequent introduction of invasive species that alter the ecosystem. These events can lead to drastic changes in parasite diversity and transmission, but generally receive little scientific attention.

Results

In order to document and identify trematode parasites of the common hippopotamus (Hippopotamus amphibius) in artificial water systems of Zimbabwe, we applied an integrative taxonomic approach, combining molecular diagnostics and morphometrics on archived and new samples. In doing so, we provide DNA reference sequences of the hippopotamus liver fluke Fasciola nyanzae, enabling us to construct the first complete Fasciola phylogeny. We describe parasite spillback of F. nyanzae by the invasive freshwater snail Pseudosuccinea columella, as a consequence of a cascade of biological invasions in Lake Kariba, one of the biggest artificial lakes in the world. Additionally, we report an unknown stomach fluke of the hippopotamus transmitted by the non-endemic snail Radix aff. plicatula, an Asian snail species that has not been found in Africa before, and the stomach fluke Carmyerius cruciformis transmitted by the native snail Bulinus truncatus. Finally, Biomphalaria pfeifferi and two Bulinus species were found as new snail hosts for the poorly documented hippopotamus blood fluke Schistosoma edwardiense.

Conclusions

Our findings indicate that artificial lakes are breeding grounds for endemic and non-endemic snails that transmit trematode parasites of the common hippopotamus. This has important implications, as existing research links trematode parasite infections combined with other stressors to declining wild herbivore populations. Therefore, we argue that monitoring the anthropogenic impact on parasite transmission should become an integral part of wildlife conservation efforts.

Graphical abstract
Real-time fluorometric and end-point colorimetric isothermal assays for detection of equine pathogens C. psittaci and equine herpes virus 1: validation, comparison and application at the point of care
Authors: Jelocnik Martina , Nyari Sharon , Anstey Susan , Playford Nicole , Fraser Tamieka A. , Mitchell Keith , Blishen Anna , Pollak Nina M. , Carrick Joan , Chicken Catherine , Jenkins Cheryl
Published: August 2021

Background

C. psittaci has recently emerged as an equine abortigenic pathogen causing significant losses to the Australian Thoroughbred industry, while Equine herpesvirus-1 (EHV-1) is a well-recognized abortigenic agent. Diagnosis of these agents is based on molecular assays in diagnostic laboratories.

In this study, we validated C. psittaci and newly developed EHV-1 Loop Mediated Isothermal Amplification (LAMP) assays performed in a real-time fluorometer (rtLAMP) against the reference diagnostic assays. We also evaluated isothermal amplification using commercially available colorimetric mix (cLAMP), and SYBR Green DNA binding dye (sgLAMP) for “naked eye” end-point detection when testing ‘real-world’ clinical samples. Finally, we applied the C. psittaci LAMP assays in two pilot Point-of-Care (POC) studies in an equine hospital.

Results

The analytical sensitivity of C. psittaci and EHV-1 rt-, and colorimetric LAMPs was determined as one and 10 genome equivalents per reaction, respectively. Compared to reference diagnostic qPCR assays, the C. psittaci rtLAMP showed sensitivity of 100%, specificity of 97.5, and 98.86% agreement, while EHV-1 rtLAMP showed 86.96% sensitivity, 100% specificity, and 91.43% agreement.

When testing rapidly processed clinical samples, all three C. psittaci rt-, c-, sg-LAMP assays were highly congruent with each other, with Kappa values of 0. 906 for sgLAMP and 0. 821 for cLAMP when compared to rtLAMP. EHV-1 testing also revealed high congruence between the assays, with Kappa values of 0.784 for cLAMP and 0.638 for sgLAMP when compared to rtLAMP. The congruence between LAMP assays and the C. psittaci or EHV-1 qPCR assays was high, with agreements ranging from 94.12 to 100% for C. psittaci, and 88.24 to 94.12% for EHV-1, respectively.

At the POC, the C. psittaci rt- and c-LAMP assays using rapidly processed swabs were performed by technicians with no prior molecular experience, and the overall congruence between the POC C. psittaci LAMPs and the qPCR assays ranged between 90.91–100%.

Conclusions

This study describes reliable POC options for the detection of the equine pathogens: C. psittaci and EHV-1. Testing ‘real-world’ samples in equine clinical setting, represents a proof-of-concept that POC isothermal diagnostics can be applied to rapid disease screening in the equine industry.
The regulatory roles of microRNAs toward pathogenesis and treatments in Huntington's disease
Authors: Tung Chih-Wei , Huang Pin-Yu , Chan Siew Chin , Cheng Pei-Hsun , Yang Shang-Hsun
Published: August 2021

Huntington’s disease (HD) is one of neurodegenerative diseases, and is defined as a monogenetic disease due to the mutation ofHuntingtingene. This disease affects several cellular functions in neurons, and further influences motor and cognitive ability, leading to the suffering of devastating symptoms in HD patients. MicroRNA (miRNA) is a non-coding RNA, and is responsible for gene regulation at post-transcriptional levels in cells. Since one miRNA targets to several downstream genes, it may regulate different pathways simultaneously. As a result, it raises a potential therapy for different diseases using miRNAs, especially for inherited diseases. In this review, we will not only introduce the update information of HD and miRNA, but also discuss the development of potential miRNA-based therapy in HD. With the understanding toward the progression of miRNA studies in HD, we anticipate it may provide an insight to treat this devastating disease, even applying to other genetic diseases.
Contribution of nuclear BCL10 expression to tumor progression and poor prognosis of advanced and/or metastatic pancreatic ductal adenocarcinoma by activating NF-κB-related signaling
Authors: Kuo Sung-Hsin , Yang Shih-Hung , Wei Ming-Feng , Lee Hsiao-Wei , Tien Yu-Wen , Cheng Ann-Lii , Yeh Kun-Huei
Published: August 2021

Background

We previously demonstrated that nuclear BCL10 translocation participates in the instigation of NF-κB in breast cancer and lymphoma cell lines. In this study, we assessed whether nuclear BCL10 translocation is clinically significant in advanced and metastatic pancreatic ductal adenocarcinoma (PDAC).

Method and materials

We analyzed the expression of BCL10-, cell cycle-, and NF-κB- related signaling molecules, and the DNA-binding activity of NF-κB in three PDAC cell lines (mutant KRAS lines: PANC-1 and AsPC-1; wild-type KRAS line: BxPC-3) using BCL10 short hairpin RNA (shBCL10). To assess the anti-tumor effect of BCL10 knockdown in PDAC xenograft model, PANC-1 cells treated with or without shBCL10 transfection were inoculated into the flanks of mice. We assessed the expression patterns of BCL10 and NF-κB in tumor cells in 136 patients with recurrent, advanced, and metastatic PDAC using immunohistochemical staining.

Results

We revealed that shBCL10 transfection caused cytoplasmic translocation of BCL10 from the nuclei, inhibited cell viability, and enhanced the cytotoxicities of gemcitabine and oxaliplatin in three PDAC cell lines. Inhibition of BCL10 differentially blocked cell cycle progression in PDAC cell lines. Arrest at G1 phase was noted in wild-type KRAS cell lines; and arrest at G2/M phase was noted in mutant KRAS cell lines. Furthermore, shBCL10 transfection downregulated the expression of phospho-CDC2, phospho-CDC25C, Cyclin B1 (PANC-1), Cyclins A, D1, and E, CDK2, and CDK4 (BxPC-3), p-IκBα, nuclear expression of BCL10, BCL3, and NF-κB (p65), and attenuated the NF-κB pathway activation and its downstream molecule, c-Myc, while inhibition of BCL10 upregulated expression of p21, and p27 in both PANC-1 and BxPC-3 cells. In a PANC-1-xenograft mouse model, inhibition of BCL10 expression also attenuated the tumor growth of PDAC. In clinical samples, nuclear BCL10 expression was closely associated with nuclear NF-κB expression (p < 0.001), and patients with nuclear BCL10 expression had the worse median overall survival than those without nuclear BCL10 expression (6.90 months versus 9.53 months, p = 0.019).

Conclusion

Nuclear BCL10 translocation activates NF-κB signaling and contributes to tumor progression and poor prognosis of advanced/metastatic PDAC.
Environmental epidemiology in a crossfire
Authors: Etzel Ruth A. , Grandjean Philippe , Ozonoff David M.
Published: August 2021

Two tendencies have emerged in environmental epidemiology that hamper the translation of research findings into prevention of environmental hazards. One is the increased focus on highlighting weaknesses of epidemiology research that is clearly meant to explain away the research conclusions and weaken their possible implications for interventions to control environmental hazards. Another is the voluminous amount of information sharing that involves a substantial amount of misinformation, as part of the ongoing infodemic. In this light, the appearance of the catalogue of doubt-raising strategies, indeed the worst practices of scientific inference, is good news. Collected under the auspices of the International Network for Epidemiology in Policy, it serves to illustrate the range of possible (and impossible) forms of critique that may be raised on behalf of vested interests or other groups who for some reason disagree with the epidemiological conclusions. We believe that this systematic list will be useful in our field and help to identify critiques of policy options that are hidden and sometimes suppressed in weighing the epidemiological evidence.
A modified Delphi study to enhance and gain international consensus on the Physical Activity Messaging Framework (PAMF) and Checklist (PAMC)
Authors: Williamson Chloë , Kelly Paul , Tomasone Jennifer R. , Bauman Adrian , Mutrie Nanette , Niven Ailsa , Richards Justin , Baker Graham
Published: August 2021

Introduction

Physical activity messaging is an important step in the pathway towards improving population physical activity levels, but best practice is not yet understood. A gap in the literature exists for a physical activity messaging framework to help guide creation and evaluation of messages. This study aimed to further develop and improve, and gain international expert consensus on, a standardised Physical Activity Messaging Framework and Checklist.

Methods

A modified Delphi study consisting of three online survey rounds was conducted. Each survey gathered feedback from an international expert panel using quantitative and qualitative methods. The framework and checklist were amended between each round based on survey results until consensus (defined a priori as 80% agreement) was reached.

Results

The final expert panel (n = 40, 55% female) came from nine countries and comprised academics (55%), healthcare and other professionals (22.5%) and government officials or policymakers (22.5%). Consensus was reached in survey 3 with 85 and 87.5% agreement on the framework and checklist, respectively.

Conclusion

This study presents an expert- and evidence-informed framework and checklist for physical activity messaging. If used consistently, the Physical Activity Messaging Framework and Checklist may improve practice by encouraging evidence-based and target audience-focused messages, as well as enhance the research base on physical activity messaging by harmonising key terminologies and improving quality of reporting. Key next steps include further refining the Physical Activity Messaging Framework and Checklist based on their use in real-world settings.
High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase
Authors: Liu Yanwei , Li Yanong , Wang Peng , Chen Li , Feng Jin , Qiu Xiaoguang
Published: August 2021

Background

Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethylation (MGMT-non-pM) have a particularly short survival and are great resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.

Methods

268 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005–2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariate analysis were performed using the Cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose–response on MGMT status defined subtypes was analyzed.

Results

On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas(p = 0.002 and p = 0.005), high-dose RT (> 54 Gy) (p = 0.021 and p = 0.029) and 1p/19q codeletion (p < 0.001 and p = 0.001). On multivariate analysis, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.47; 95%CI, 0.22–0.98; p = 0.045; and HR, 0.44; 95%CI, 0.21–0.96; p = 0.038, respectively) and PFS (HR, 0.48; 95%CI, 0.26–0.90; p = 0.022; and HR, 0.51; 95%CI, 0.26–0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.56; 95%CI, 0.32–0.96; p = 0.036) and PFS (HR, 0.58; 95%CI, 0.35–0.96; p = 0.033) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.

Conclusions

High-dose RT (> 54 Gy) is an independently protective factor for LGGs and is associated with improved survival in patients with MGMT-non-pM.
Dosimetric comparison and biological evaluation of fixed-jaw intensity-modulated radiation therapy for T-shaped esophageal cancer
Authors: Chen Hua , Huang Ying , Wang Hao , Shao Yan , Yue Ning J. , Gu Hengle , Duan Yanhua , Feng Aihui , Xu Zhiyong
Published: August 2021

Background

To evaluate the dosimetric and biological benefits of the fixed-jaw (FJ) intensity-modulated radiation therapy (IMRT) technique for patients with T-shaped esophageal cancer.

Methods

FJ IMRT plans were generated for thirty-five patients and compared with jaw tracking (JT) IMRT, static jaw (SJ) IMRT and JT volumetric modulated arc therapy (VMAT). Dosimetric parameters, tumor control probability (TCP) and normal tissue complication probability (NTCP), monitor units (MUs), delivery time and gamma passing rate, as a measure of dosimetric verification, were compared. The correlation between the length of PTV-C below the upper boundary of lung tissue (PTV-Cinferior) and dosimetric parameters and NTCP of the lung tissue were analyzed.

Results

The homogeneity and conformity of the target in the four plans were basically equivalent. When compared to the JT IMRT and SJ IMRT plans, FJ IMRT plan led to a statistically significant improvement in the NTCP and low-middle dosimetric parameters of the lung, and the improvement had a moderately positive correlation with the length of PTV-Cinferior, with a correlation coefficient ranging from 0.523 to 0.797; the FJ IMRT plan exhibited better lung sparing in low-dose volumes than the JT VMAT plan. The FJ IMRT plan had similar MUs (888 ± 99) and delivery times (516.1 ± 54.7 s) as the JT IMRT plan (937 ± 194, 522 ± 5.6 s) but higher than SJ IMRT (713 ± 137, 488.8 ± 45.2 s) and JT VMAT plan (517 ± 59, 263.7 ± 43.3 s).

Conclusions

The FJ IMRT technique is superior in reducing the low-dose volumes of lung tissues for patients with T-shaped esophageal cancer.
Clinical features of gastric duplications: evidence from primary case reports and published data
Authors: Li Yang , Li Chen , Wu Hao , Wang Quan , Gao Zhi-Dong , Yang Xiao-Dong , Jiang Ke-Wei , Ye Ying-Jiang
Published: August 2021

Background

Alimentary tract duplications are rare congenital lesions, and only 2–8% of them are located in the stomach. Gastric duplications (GD) can lead to severe adverse events. Thus, surgical resection is required once the disease is diagnosed. The main purpose of this study is to describe the clinical features of gastric duplications and to provide evidence for the diagnosis and treatment.

Methods

A retrospective review of eight gastric duplications at two medical centers Peking University People’s Hospital (PKUPH) and Shandong Provincial Hospital from 2010 to 2020 was conducted. Furthermore, the literature search was also conducted by retrieving data from PubMed, EMBASE and Cochrane Library databases from the date of the database inception to January 15, 2021.

Results

Eight patients who were diagnosed as gastric duplications and 311 published records were included in this study. In all, 319 patients were identified: Vomiting and abdominal pain were the most frequent clinical presentations among juveniles and adults respectively. There was no difference in gender distribution (F: 53.16% vs M: 46.84%), and the cystic gastric duplications were the most common type of the gastric duplications (87.04%). More than half (53.30%) of included cases were located in the greater curvature of stomach.

Conclusions

Gastric duplications could present with a wide spectrum of symptomatology, which might be misdiagnosed easily as other diseases. For cystic gastric duplications, the optimal treatment was a complete surgical removal. But conservative treatment might be an alternative strategy for tubular gastric duplications.
Outbreak of Pseudomonas aeruginosa producing VIM carbapenemase in an intensive care unit and its termination by implementation of waterless patient care
Authors: Catho Gaud , Martischang R. , Boroli F. , Chraïti M. N. , Martin Y. , Koyluk Tomsuk Z. , Renzi G. , Schrenzel J. , Pugin J. , Nordmann P. , Blanc D. S. , Harbarth S.
Published: August 2021

Background

Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa.

Methods

We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir.

Results

Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention.

Discussion

Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.