bluuebunny/crossref_metadata_2025 huggingface dataset:
An H/V geostatistical approach for building pseudo-3D Vs models to account for spatial variability in ground response analyses Part II: Application to 1D analyses at two downhole array sites
Authors: Hallal Mohamad M , Cox Brady R
Published: January 2021

Common procedures used to account for spatial variability of shear wave velocity (Vs) in one-dimensional (1D) ground response analyses (GRAs), such as stochastic randomization of Vs or increasing small-strain damping, have been shown to improve seismic site response predictions relative to 1D GRAs where no attempts are made to account for spatial variability. However, even after attempting to account for spatial variability using common procedures, 1D GRAs often still yield results that are different than ground motions recorded at many downhole array sites. When 1D predictions differ from observations, the site is typically considered to be too spatially variable to effectively use 1D GRAs. While there is no doubt that some sites are indeed too variable for 1D GRAs, it is also possible that simple 1D analyses could still be effectively used at many sites if spatial variability is accounted for through a more rational, site-specific approach. In this study, an H/V geostatistical approach for building pseudo-3D Vs models is implemented to account for spatial variability in 1D GRAs. The geostatistical approach is used to generate a uniform grid of Vs profiles that have been scaled to match fundamental site frequency estimates from horizontal-to-vertical spectral ratio (H/V) noise measurements. In this article, 1D GRAs are performed for each grid point and the results are statistically combined to reflect the average site response and its variability. This 1D application is demonstrated at the Treasure Island and Delaney Park Downhole Array sites, where it is shown to produce superior fits to the small-strain recorded site response relative to existing approaches used to account for spatial variability in 1D GRAs. Using the proposed approach, we also investigate the lateral area that is likely influencing site response at each site and show that it could extend to significant distances (as much as 1 km) from the boreholes.
Governing Collaborative Project Delivery as a Common-Pool Resource Scenario
Authors: Hall Daniel M. , Bonanomi Marcella M.
Published: January 2021

When collaborative project delivery models such as integrated project delivery (IPD) combine project resources, share decision-making rights, and distribute risk-and-reward among participants, the project can be conceptualized as a common-pool resource scenario. Multiple project appropriators have contractual rights to withdraw units from the shared resource system (i.e., the project budget). This theorization suggests project managers avoid the tragedy of the project by crafting effective self-governance structures in the face of pluralism. Using IPD as an example, this article suggests these project governance structures reflect Ostrom’s design principles for the successful governance of long-enduring common-pool resource scenarios.
Model Parameter Transfer for Gear Fault Diagnosis under Varying Working Conditions
Authors: Chen Chao , Shen Fei , Xu Jiawen , Yan Ruqiang
Published: January 2021

Gear fault diagnosis technologies have received rapid development and been effectively implemented in many engineering applications. However, the various working conditions would degrade the diagnostic performance and make gear fault diagnosis (GFD) more and more challenging. In this paper, a novel model parameter transfer (NMPT) is proposed to boost the performance of GFD under varying working conditions. Based on the previous transfer strategy that controls empirical risk of source domain, this method further integrates the superiorities of multi-task learning with the idea of transfer learning (TL) to acquire transferable knowledge by minimizing the discrepancies of separating hyperplanes between one specific working condition (target domain) and another (source domain), and then transferring both commonality and specialty parameters over tasks to make use of source domain samples to assist target GFD task when sufficient labeled samples from target domain are unavailable. For NMPT implementation, insufficient target domain features and abundant source domain features with supervised information are fed into NMPT model to train a robust classifier for target GFD task. Related experiments prove that NMPT is expected to be a valuable technology to boost practical GFD performance under various working conditions. The proposed methods provides a transfer learning-based framework to handle the problem of insufficient training samples in target task caused by variable operation conditions.
Pathways involved in pony body size development
Authors: Fang Jun , Zhang Dong , Cao Jun Wei , Zhang Li , Liu Chun Xia , Xing Yan Ping , Wang Feng , Xu Hong Yang , Wang Shi Chao , Ling Yu , Wang Wei , Zhang Yan Ru , Zhou Huan Min
Published: January 2021

Background

The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages.

Results

We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components (P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses.

Conclusion

Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.
Characterization of histological changes at the tillering stage (Z21) in resistant and susceptible wheat plants infected by Tilletia controversa Kühn
Authors: Xu Tongshuo , Qin Dandan , Muhae Ud Din Ghulam , Liu Taiguo , Chen Wanquan , Gao Li
Published: January 2021

Background

Dwarf bunt, which is caused by Tilletia controversa Kühn, is a soilborne and seedborne disease that occurs worldwide and can lead to 70% or even total losses of wheat crops. However, very little information is available about the histological changes that occur in dwarf bunt-resistant and dwarf bunt-susceptible wheat plants at the tillering stage (Z21). In this study, we used scanning electron microscopy and transmission electron microscopy to characterize the histological changes at this stage in resistant and susceptible wheat cultivars infected by T. controversa.

Results

Using scanning electron microscopy, the root, stem, and leaf structures of resistant and susceptible cultivars were examined after T. controversa infection. The root epidermal and vascular bundles were more severely damaged in the susceptible T. controversa-infected plants than in the resistant plants. The stem cell and longitudinal sections were much more extensively affected in susceptible plants than in resistant plants after pathogen infection. However, slightly deformed mesophyll cells were observed in the leaves of susceptible plants. With transmission electron microscopy, we found that the cortical bundle cells and the cell contents and nuclei in the roots were more severely affected in the susceptible plants than in the resistant plants; in the stems and leaves, the nuclei, chloroplasts, and mesophyll cells changed significantly in the susceptible plants after fungal infection. Moreover, we found that infected susceptible and resistant plants were affected much more severely at the tillering stage (Z21) than at the seedling growth stage (Z13).

Conclusion

Histological changes in the wheat roots, stems and leaves were much more severe in T. controversa-infected susceptible plants than in infected resistant plants at the tillering stage (Z21).
A novel electromagnetic guidance ultrasound system on radial artery cannulation: a prospective randomized controlled trial
Authors: Kim Namo , Kim Hyun Il , Kim Do-Hyeong , Park Dahee , Song Sei Han , Byon Hyo-Jin
Published: January 2021

Background

Radial artery cannulation can cause complications such as haematoma formation or thrombosis due to its small diameter. Recently, a novel ultrasound device equipped with an electromagnetic guidance system was introduced, showing the path and alignment of the needle during the procedure. The aim of this study was to investigate the effects of this novel system on both success and complication rates during radial artery cannulation under ultrasound guidance.

Methods

In this randomized controlled trial, 76 adults scheduled for neurosurgery requiring radial artery cannulation were recruited. In group E (n = 38), radial artery cannulation was performed using the electromagnetic guidance ultrasound system, whereas in group C (n = 38), the procedure was performed using conventional ultrasound guidance. The success rates of cannulation on the first attempt, cannulation times, number of attempts, and incidence of complications were compared between the two groups.

Results

There was a significant difference in the success rates on the first attempt between the two groups (group C = 78.9% vs. group E = 94.7%, P = 0.042). Incidences of posterior wall puncture and haematoma formation (group C = 8 vs. group E = 1; P = 0.028) were significantly lower in group E than in group C. The median cannulation time for successful attempts was comparable between groups.

Conclusions

Use of the novel electromagnetic guidance system resulted in a better success rate on the first attempt and a lower incidence of complications during radial artery cannulation.

Trial registration

This study was registered at http://cris.nih.go.kr (registration number: KCT0002476).
The prevalence of cardiovascular disease in Ethiopia: a systematic review and meta-analysis of institutional and community-based studies
Authors: Angaw Dessie Abebaw , Ali Rahma , Tadele Afework , Shumet Shegaye
Published: January 2021

Background

Worldwide cardiovascular disease is the major cause of disability and premature death. This is due to the ascending trend of consuming an unhealthy diet and obesity which increases the risk of hypertension and type 2 diabetes mellitus. Thus this study aimed to determine the pooled prevalence of the cardiovascular disease in Ethiopia.

Methods

Medline, Scopus, and Google Scholar search engines were accessed using medical subject heading (MeSH) terms for studies based in Ethiopia, from 2000 to 2018. However, studies done among a specific group of the population were excluded from the study. Data were extracted by one reviewer and then checked independently by a second reviewer. Studies were qualitatively synthesis in terms of design, quality, study population, outcomes, and result. Sub-group analysis and sensitivity tests were conducted to identify potential influences on the prevalence estimates. Quantitative results were pooled in a statistical meta-analysis using STATA version 14 software.

Result

Nine eligible cross-sectional studies were included in the analysis. The prevalence ranges from 1 to 20%. The pooled prevalence of cardiovascular disease (CVD) was 5% (95% CI: 3–8%). The prevalence was higher in the population who visits hospitals, 8% (95% CI: 4–12%) compared to the general population, 2% (95% CI: 1–5%). There was no significant difference in the overall prevalence of CVD between males and females.

Conclusion

The prevalence of cardiovascular disease was high. A higher prevalence of CVD was found among patients who visited health institutions than the general population and no observed significant sex difference in the prevalence
Higher comorbidities and early death in hospitalized African-American patients with Covid-19
Authors: Gupta Raavi , Agrawal Raag , Bukhari Zaheer , Jabbar Absia , Wang Donghai , Diks John , Alshal Mohamed , Emechebe Dokpe Yvonne , Brunicardi F. Charles , Lazar Jason M. , Chamberlain Robert , Burza Aaliya , Haseeb M. A.
Published: January 2021

Background

African-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions.

Methods

We performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a 52-day period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black population.

Results

Of the 1103 consecutive patients who tested positive for COVID-19, 529 required hospitalization and were included in the study. 88% of patients were Black; and a majority (52%) were 61–80 years old with a mean body mass index in the “obese” range. 98% had one or more comorbidities. Hypertension was the most common (79%) pre-existing condition followed by diabetes mellitus (56%) and chronic kidney disease (17%). Patients with chronic kidney disease who received hemodialysis were found to have lower mortality, than those who did not receive it, suggesting benefit from hemodialysis Age > 60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox proportional hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil:lymphocyte ratio (8.3:10.0) were predictive of mortality on admission and at 48–96 h. Of the 529 inpatients 48% died, and one third of them died within the first 3 days of admission. 159/529patients received invasive mechanical ventilation, of which 86% died and of the remaining 370 patients, 30% died.

Conclusions

COVID-19 patients in our predominantly Black neighborhood had higher in-hospital mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.
Predictive value of the neutrophil to lymphocyte ratio for disease deterioration and serious adverse outcomes in patients with COVID-19: a prospective cohort study
Authors: Zeng Zhi-Yong , Feng Shao-Dan , Chen Gong-Ping , Wu Jiang-Nan
Published: January 2021

Background

Early identification of patients who are at high risk of poor clinical outcomes is of great importance in saving the lives of patients with novel coronavirus disease 2019 (COVID-19) in the context of limited medical resources.

Objective

To evaluate the value of the neutrophil to lymphocyte ratio (NLR), calculated at hospital admission and in isolation, for the prediction of the subsequent presence of disease progression and serious clinical outcomes (e.g., shock, death).

Methods

We designed a prospective cohort study of 352 hospitalized patients with COVID-19 between January 9 and February 26, 2020, in Yichang City, Hubei Province. Patients with an NLR equal to or higher than the cutoff value derived from the receiver operating characteristic curve method were classified as the exposed group. The primary outcome was disease deterioration, defined as an increase of the clinical disease severity classification during hospitalization (e.g., moderate to severe/critical; severe to critical). The secondary outcomes were shock and death during the treatment.

Results

During the follow-up period, 51 (14.5%) patients’ conditions deteriorated, 15 patients (4.3%) had complicated septic shock, and 15 patients (4.3%) died. The NLR was higher in patients with deterioration than in those without deterioration (median: 5.33 vs. 2.14, P < 0.001), and higher in patients with serious clinical outcomes than in those without serious clinical outcomes (shock vs. no shock: 6.19 vs. 2.25, P < 0.001; death vs. survival: 7.19 vs. 2.25, P < 0.001). The NLR measured at hospital admission had high value in predicting subsequent disease deterioration, shock and death (all the areas under the curve > 0.80). The sensitivity of an NLR ≥ 2.6937 for predicting subsequent disease deterioration, shock and death was 82.0% (95% confidence interval, 69.0 to 91.0), 93.3% (68.0 to 100), and 92.9% (66.0 to 100), and the corresponding negative predictive values were 95.7% (93.0 to 99.2), 99.5% (98.6 to 100) and 99.5% (98.6 to 100), respectively.

Conclusions

The NLR measured at admission and in isolation can be used to effectively predict the subsequent presence of disease deterioration and serious clinical outcomes in patients with COVID-19.
Two cases of carfilzomib‐induced thrombotic microangiopathy successfully treated with Eculizumab in multiple myeloma
Authors: Rassner Michael , Baur Rebecca , Wäsch Ralph , Schiffer Mario , Schneider Johanna , Mackensen Andreas , Engelhardt Monika
Published: January 2021

Background

Treatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking.

Case Presentation

The first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved.

Conclusion

In this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.
Integrated knowledge translation to strengthen public policy research: a case study from experimental research on income assistance receipt among people who use drugs
Authors: Mendell Joanna , Richardson Lindsey
Published: January 2021

Background

Solutions to complex public health issues should be informed by scientific evidence, yet there are important differences between policy and research processes that make this relationship challenging. Integrated knowledge translation (IKT) is a strategy of sustained stakeholder engagement that intends to address barriers to evidence use. We highlight an example of an IKT project alongside a randomized controlled trial of a public policy intervention that tested different disbursement patterns of income assistance among people who use drugs in Vancouver, British Columbia.

Methods

A case study design was used where an IKT strategy led by a knowledge broker embedded within the research team acts as the case. This case study evaluates the process and effectiveness of the integrated knowledge translation project by measuring intermediate outcomes within a Theory of Change created to map pathways to impact. Content analysis was performed using an evaluation template through document review, post-event evaluations, and detailed tracking of media, knowledge translation activities and requests for information.

Results

A host of knowledge translation products synthesized existing research about the harms of synchronized income assistance disbursement and supported stakeholder engagement, facilitating conversation, relationship building and trust with stakeholders. Engagement improved knowledge of the contextual feasibility for system change, and contributed experiential knowledge to study findings. A combination of access to information and stakeholder and media engagement led to increased acknowledgement of the issue by policy makers directly involved in the income assistance system.

Conclusions

This project shows how a multipronged approach to IKT addressed barriers to evidence-informed public policy and successfully contributed to increased public discourse around income assistance policy reform. Additionally, sustained engagement with diverse stakeholders led to improved contextual knowledge and understanding of potential community level impacts that, along with scientific results, improved the evidence available to inform system change. This case study provides insight into the role IKT can play alongside research aimed at public policy improvements.

Trial registration

This IKT project was embedded within the study titled: The impact of Alternative Social Assistance Disbursement on Drug-Related Harm (TASA), known as Cheque Day Study, registered on ClinicalTrials.gov (NCT02457949) May 29, 2015.
COVID-19 outbreak in Brazil: adherence to national preventive measures and impact on people’s lives, an online survey
Authors: Faria de Moura Villela Edlaine , López Rossana Verónica Mendoza , Sato Ana Paula Sayuri , de Oliveira Fábio Morato , Waldman Eliseu Alves , Van den Bergh Rafael , Siewe Fodjo Joseph Nelson , Colebunders Robert
Published: January 2021

Background

The first case of COVID-19 infection was diagnosed in Brazil 26th February 2020. By March 16th, physical distancing and confinement measures were implemented by the Brazilian government. Little is known about how these measures were followed up by the Brazilian people and their impact on daily routine.

Methods

In early April 2020, using an online platform, we organized an online survey among adults living in Brazil about their COVID-19 preventive behavior and impact on their daily routine.

Results

Data from 23,896 respondents were analyzed (mean age: 47.4 years). Due to COVID-19 restrictions, half (51.1%) of the professionals reported working from home. Regular handwashing was practiced by 98.7% of participants; 92.6% reported adhering to the 1.5-2 m physical distancing rule, but only 45.5% wore a face mask when going outside. While 29.3% of respondents found it relatively easy to stay at home, indoor confinement was extremely difficult for 7.9% of participants. Moreover, 11% of participants were extremely worried about their health during the COVID-19 epidemic. Younger people, male, persons living in a rural area/village or popular neighbourhoods, students and workers reported less preventive behaviour.

Conclusion

Restrictive measures markedly affected the daily and professional routines of Brazilians. Participants showed a satisfactory level of adherence to national COVID-19 prevention guidelines. Qualitative and follow-up studies are needed to monitor the impact of COVID-19 in the Brazilian society.
Antipsychotic medication adherence and preventive diabetes screening in Medicaid enrollees with serious mental illness: an analysis of real-world administrative data
Authors: Stockbridge Erica L. , Webb Nathaniel J. , Dhakal Eleena , Garg Manasa , Loethen Abiah D. , Miller Thaddeus L. , Nandy Karabi
Published: January 2021

Background

There is excess amenable mortality risk and evidence of healthcare quality deficits for persons with serious mental illness (SMI). We sought to identify sociodemographic and clinical characteristics associated with variations in two 2015 Healthcare Effectiveness Data and Information Set (HEDIS) measures, antipsychotic medication adherence and preventive diabetes screening, among Medicaid enrollees with serious mental illness (SMI).

Methods

We retrospectively analyzed claims data from September 2014 to December 2015 from enrollees in a Medicaid specialty health plan in Florida. All plan enrollees had SMI; analyses included continuously enrolled adults with antipsychotic medication prescriptions and schizophrenia or bipolar disorder. Associations were identified using mixed effects logistic regression models.

Results

Data for 5502 enrollees were analyzed. Substance use disorders, depression, and having both schizophrenia and bipolar disorder diagnoses were associated with both HEDIS measures but the direction of the associations differed; each was significantly associated with antipsychotic medication non-adherence (a marker of suboptimal care quality) but an increased likelihood of diabetes screening (a marker of quality care). Compared to whites, blacks and Hispanics had a significantly greater risk of medication non-adherence. Increasing age was significantly associated with increasing medication adherence, but the association between age and diabetes screening varied by sex. Other characteristics significantly associated with quality variations according to one or both measures were education (associated with antipsychotic medication adherence), urbanization (relative to urban locales, residing in suburban areas was associated with both adherence and diabetes screening), obesity (associated with both adherence and diabetes screening), language (non-English speakers had a greater likelihood of diabetes screening), and anxiety, asthma, and hypertension (each positively associated with diabetes screening).

Conclusions

The characteristics associated with variations in the quality of care provided to Medicaid enrollees with SMI as gauged by two HEDIS measures often differed, and at times associations were directionally opposite. The variations in the quality of healthcare received by persons with SMI that were identified in this study can guide quality improvement and delivery system reform efforts; however, given the sociodemographic and clinical characteristics’ differing associations with different measures of care quality, multidimensional approaches are warranted.
Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines
Authors: Levi Michela , Salaroli Roberta , Parenti Federico , De Maria Raffaella , Zannoni Augusta , Bernardini Chiara , Gola Cecilia , Brocco Antonio , Marangio Asia , Benazzi Cinzia , Muscatello Luisa Vera , Brunetti Barbara , Forni Monica , Sarli Giuseppe
Published: January 2021

Background

Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC).

Results

Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis.

Conclusions

DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.
Evaluation of hematological alteration of vector‐borne pathogens in cats from Bangkok, Thailand
Authors: Do Thom , Kamyingkird Ketsarin , Chimnoi Wissanuwat , Inpankaew Tawin
Published: January 2021

Background

Cats can be carriers of infected arthropods and be infected with several vector-borne pathogens (VBPs) but there is limited knowledge about their pathogenic role in cats. This study aimed to assess the prevalence of some feline vector-borne agents by molecular technique and to characterize the hematological findings associated with these infections in a cat population from Bangkok Thailand.

Results

PCR was positive with at least one pathogen in 237 out of 372 subjects (63.7%), with prevalence of 39.5% (147/372) for Babesia spp., 36.9% (137/372) for hemoplasmas and 3.2% (12/372) for Hepatozoon spp. The cats older than 1 year were at significantly greater risk for VBPs infection (P = 0.001; OR = 1.43; 95% CI: 1.12 – 1.81) and hemoplasmas infection (χ2 = 10.8, df = 1; P < 0.0001; OR = 2.45; 95% CI: 1.49 – 4.01). A significant association between hematological findings and hemoplasma infection were identified in the present study. Besides, VBPs infection revealed more frequent in male cats (χ2= 6.38, df = 1, P = 0.01). Macrocytic hypochromic type of anemia was observed in cats infested with blood-sucking arthropods compared to the non-infested cats presented.

Conclusions

The current study confirmed that Babesia, Hepatozoon and hemoplasmas had infected semi-domesticated cats in Bangkok, Thailand, with Babesia and hemoplasmas being dominant in prevalence. Some hematological findings were significantly associated with cats infected with vector-borne pathogens in this study including leukocyte count and platelets count that may help support veterinary technicians in diagnosis and appropriate treatment. Campaigns of VBPs monitoring in Bangkok emphasizing on the investigation of vectors and possible routes of the infection in animals should be conducted to prevent the transmission of the pathogens.
MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges
Authors: Rabaan Ali A. , Al-Ahmed Shamsah H. , Sah Ranjit , Alqumber Mohammed A. , Haque Shafiul , Patel Shailesh Kumar , Pathak Mamta , Tiwari Ruchi , Yatoo Mohd. Iqbal , Haq Abrar Ul , Bilal Muhammad , Dhama Kuldeep , Rodriguez-Morales Alfonso J.
Published: January 2021

The Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.
Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer
Authors: Wu Shaocong , Luo Min , To Kenneth K. W. , Zhang Jianye , Su Chaoyue , Zhang Hong , An Sainan , Wang Fang , Chen Da , Fu Liwu
Published: January 2021

Background

Epidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored.

Methods

Exosomes isolation was performed by differential centrifugation. Co-culture assays were conducted to explore the alteration of drug sensitivity by cell viability and apoptosis assays. Immunofluorescence and flow cytometry were performed to visualize the formation or absorption of exosomes. Exosomes secretion was measured by Nanoparticle Tracking Analysis or ELISA. The xenograft tumor model in mice was established to evaluate the effect of exosomes on osimertinib sensitivity in vivo.

Results

Intercellular transfer of exosomal wild type EGFR protein confers osimertinib resistance to EGFR-mutated sensitive cancer cells in vitro and in vivo. Co-culture of EGFR-mutated sensitive cells and EGFR-nonmutated resistant cells promoted osimertinib resistance phenotype in EGFR-mutated cancer cells, while depletion of exosomes from conditioned medium or blockade of exosomal EGFR by neutralizing antibody alleviated this phenotype. Mechanistically, osimertinib promoted the release of exosomes by upregulated a Rab GTPase (RAB17). Knockdown of RAB17 resulted in the decrease of exosomes secretion. Moreover, exosomes could be internalized by EGFR-mutated cancer cells via Clathrin-dependent endocytosis and then the encapsulated exosomal wild type EGFR protein activated downstream PI3K/AKT and MAPK signaling pathways and triggered osimertinib resistance.

Conclusions

Intercellular transfer of exosomal wild type EGFR promotes osimertinib resistance in NSCLC, which may represent a novel resistant mechanism of osimertinib and provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance.
STED lithography in microfluidics for 3D thrombocyte aggregation testing
Authors: Buchegger Bianca , Tanzer Alexander , Posch Sandra , Gabriel Christian , Klar Thomas A. , Jacak Jaroslaw
Published: January 2021

Three-dimensional photopolymerization techniques such as multiphoton polymerization lithography (MPL) and stimulated emission depletion (STED) lithography are powerful tools for fabricating structures in the sub-µm range. Combining these techniques with microfluidics enables us to broaden the range of their applications. In this study, we show a microfluidic device enhanced with MPL structures carrying STED-lithographically written nanoanchors that promote binding of the von Willebrand factor (vWF). The density of vWF is adjusted by varying the number of the nanoanchors on the 3D structures. This allows us to study the impact of the density of vWF on the activation of thrombocytes. The activation of the thrombocytes seems to decrease with the density of vWF on the 3D scaffolds inside the microfluidic channels.
Prioritizing knowledge translation in low- and middle-income countries to support pandemic response and preparedness
Authors: Mahendradhata Yodi , Kalbarczyk Anna
Published: January 2021

The COVID-19 pandemic has created urgent demand around the world for knowledge generation about a novel coronavirus, its transmission, and control, putting academic institutions at the frontline of politics. While many academic institutions are well poised to conduct research, there are well-documented barriers for these institutions, particularly in low- and middle-income countries (LMICs), to further conduct strategic synthesis and dissemination to promote knowledge utilization among policy-makers. These systemic barriers to knowledge translation (KT) pose significant challenges for academic institutions seeking to take advantage of unprecedented policy windows to inform evidence-based decision-making. Global health funding organizations should prioritize the support of academic institutions’ activities along the KT pathway, including both knowledge generation and strategic dissemination, to improve knowledge uptake for decision-making to improve health. Institutional capacity-building initiatives for KT have the potential to profoundly impact responses to this and future pandemics.
Mixed method evaluation of the CEBHA+ integrated knowledge translation approach: a protocol
Authors: Pfadenhauer Lisa M. , Grath Tanja , Delobelle Peter , Jessani Nasreen , Meerpohl Joerg J. , Rohwer Anke , Schmidt Bey-Marrié , Toews Ingrid , Akiteng Ann R. , Chapotera Gertrude , Kredo Tamara , Levitt Naomi , Ntawuyirushintege Seleman , Sell Kerstin , Rehfuess Eva A.
Published: January 2021

Background

The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA+) is a research consortium concerned with the prevention, diagnosis and treatment of non-communicable diseases. CEBHA+ seeks to engage policymakers and practitioners throughout the research process in order to build lasting relationships, enhance evidence uptake, and create long-term capacity among partner institutions in Ethiopia, Malawi, Rwanda, South Africa and Uganda in collaboration with two German universities. This integrated knowledge translation (IKT) approach includes the formal development, implementation and evaluation of country specific IKT strategies.

Methods

We have conceptualised the CEBHA+ IKT approach as a complex intervention in a complex system. We will employ a comparative case study (CCS) design and mixed methods to facilitate an in-depth evaluation. We will use quantitative surveys, qualitative interviews, quarterly updates, and a policy document analysis to capture the process and outcomes of IKT across the African CEBHA+ partner sites. We will conduct an early stage (early 2020) and a late-stage evaluation (early 2022), triangulate the data collected with various methods at each site and subsequently compare our findings across the five sites.

Discussion

Evaluating a complex intervention such as the CEBHA+ IKT approach is complicated, even more so when undertaken across five diverse countries. Despite conceptual, methodological and practical challenges, our comparative case study addresses important evidence gaps: While involving decision-makers in the research process is gaining traction worldwide, we still know very little regarding (i) whether this approach really makes a difference to evidence uptake, (ii) the mechanisms that make IKT successful, and (iii) relevant differences across socio-cultural contexts. The evaluation described here is intended to provide relevant insights on all of these aspects, notably in countries in Sub-Saharan Africa, and is expected to contribute to the science of IKT overall.
Review of Australian initiatives to reduce stigma towards people with complex mental illness: what exists and what works?
Authors: Morgan Amy J. , Wright Judith , Reavley Nicola J.
Published: January 2021

Background

Australian national mental health policy outlines the need for a nationally coordinated strategy to address stigma and discrimination, particularly towards people with complex mental illness that is poorly understood in the community. To inform implementation of this policy, this review aimed to identify and examine the effectiveness of existing Australian programs or initiatives that aim to reduce stigma and discrimination.

Method

Programs were identified via a search of academic databases and grey literature, and an online survey of key stakeholder organisations. Eligible programs aimed to reduce stigma towards people with complex mental illness, defined as schizophrenia, psychosis, personality disorder, or bipolar disorder; or they focused on nonspecific ‘mental illness’ but were conducted in settings relevant to individuals with the above diagnoses, or they included the above diagnoses in program content. Key relevant data from programs identified from the literature search and survey were extracted and synthesized descriptively.

Results

We identified 61 programs or initiatives currently available in Australia. These included face-to-face programs (n = 29), online resources (n = 19), awareness campaigns (n = 8), and advocacy work (n = 5). The primary target audiences for these initiatives were professionals (health or emergency), people with mental illness, family or carers of people with mental illness, and members of the general population. Most commonly, programs tended to focus on stigma towards people with non-specific mental illness rather than on particular diagnostic labels. Evidence for effectiveness was generally lacking. Face-to-face programs were the most well-evaluated, but only two used a randomised controlled trial design.

Conclusions

This study identified areas of strength and weakness in current Australian practice for the reduction of stigma towards people with complex mental illness. Most programs have significant input from people with lived experience, and programs involving education and contact with a person with mental illness are a particular strength. Nevertheless, best-practice programs are not widely implemented, and we identified few programs targeting stigma for people with mental illness and their families, or for culturally and linguistically diverse communities, Aboriginal and Torres Strait Islander communities and LGBTIQ people. These can inform stakeholder consultations on effective options for a national stigma and discrimination reduction strategy.
Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150glued
Authors: Suh Bo Kyoung , Lee Seol-Ae , Park Cana , Suh Yeongjun , Kim Soo Jeong , Woo Youngsik , Nhung Truong Thi My , Lee Su Been , Mun Dong Jin , Goo Bon Seong , Choi Hyun Sun , Kim So Jung , Park Sang Ki
Published: January 2021

Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150glued. Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150gluedthat regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.
Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort
Authors: Liu Yun , Wang Honglian , Wang Xin , Liu Jiaqi , Li Junjian , Wang Xiang , Zhang Yun , Bai Zhigang , Zhou Qinghua , Wu Ying , Shen Yi , Weng Xiaoling , Liu Fatao , Guo Jiancheng , Di Lijun , Gires Olivier , Zhang Zhongtao , Chen Yiding , Wang Hongxia
Published: January 2021

Accurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls.
Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers.
Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2–5 and 15–23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.