bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal medicine residents identify gaps in medical education on outpatient referrals
Authors: Slavin Masha J. , Rajan Mangala , Kern Lisa M.
Published: July 2020

Background

Relevant clinical information is often missing when a patient sees a specialist after being referred by another physician in the ambulatory setting. This can result in missed or delayed diagnoses, delayed treatment, unnecessary testing, and drug interactions. Residents’ attitudes toward providing clinical information at the time of referral and their perspectives toward training on referral skills are not clear. We sought to assess internal medicine residents’ attitudes toward and experiences with outpatient referrals.

Methods

We conducted a cross-sectional survey in October–December 2018 of all internal medicine interns and residents affiliated with a large, urban internal medicine residency program in New York, NY. We used a novel survey instrument that included 13 questions about attitudes toward and experiences with outpatient referrals. We used descriptive statistics to characterize the results.

Results

Overall, 122 of 132 residents participated (92% response rate). Respondents were approximately equally distributed across post-graduate years 1–3. Although 83% of residents reported that it is “always” important to provide the clinical reason for a referral, only 11% stated that they “always” provide a sufficient amount of clinical information for the consulting provider when making a referral. Only 9% of residents “strongly agree” that residency provides sufficient training in knowing when to refer patients, and only 8% “strongly agree” that residency provides sufficient training in what information to provide the consulting physician.

Conclusions

These results suggest a substantial discrepancy between the amount of information residents believe they should provide at the time of a referral and the amount they actually provide. Many residents report not receiving adequate training during residency on when to refer patients and what clinical information to provide at the time of referral. Improvements to medical education regarding outpatient referrals are urgently needed.
Genetic background mutations drive neural circuit hyperconnectivity in a fragile X syndrome model
Authors: Kennedy Tyler , Rinker David , Broadie Kendal
Published: July 2020

Background

Neural circuits are initially assembled during development when neurons synapse with potential partners and later refined as appropriate connections stabilize into mature synapses while inappropriate contacts are eliminated. Disruptions to this synaptogenic process impair connectivity optimization and can cause neurodevelopmental disorders. Intellectual disability (ID) and autism spectrum disorder (ASD) are often characterized by synaptic overgrowth, with the maintenance of immature or inappropriate synapses. Such synaptogenic defects can occur through mutation of a single gene, such as fragile X mental retardation protein (FMRP) loss causing the neurodevelopmental disorder fragile X syndrome (FXS). FXS represents the leading heritable cause of ID and ASD, but many other genes that play roles in ID and ASD have yet to be identified.

Results

In a Drosophila FXS disease model, one dfmr150M null mutant stock exhibits previously unreported axonal overgrowths at developmental and mature stages in the giant fiber (GF) escape circuit. These excess axon projections contain both chemical and electrical synapse markers, indicating mixed synaptic connections. Extensive analyses show these supernumerary synapses connect known GF circuit neurons, rather than new, inappropriate partners, indicating hyperconnectivity within the circuit. Despite the striking similarities to well-characterized FXS synaptic defects, this new GF circuit hyperconnectivity phenotype is driven by genetic background mutations in this dfmr150M stock. Similar GF circuit synaptic overgrowth is not observed in independent dfmr1 null alleles. Bulked segregant analysis (BSA) was combined with whole genome sequencing (WGS) to identify the quantitative trait loci (QTL) linked to neural circuit hyperconnectivity. The results reveal 8 QTL associated with inappropriate synapse formation and maintenance in the dfmr150M mutant background.

Conclusions

Synaptogenesis is a complex, precisely orchestrated neurodevelopmental process with a large cohort of gene products coordinating the connectivity, synaptic strength, and excitatory/inhibitory balance between neuronal partners. This work identifies a number of genetic regions that contain mutations disrupting proper synaptogenesis within a particularly well-mapped neural circuit. These QTL regions contain potential new genes involved in synapse formation and refinement. Given the similarity of the synaptic overgrowth phenotype to known ID and ASD inherited conditions, identifying these genes should increase our understanding of these devastating neurodevelopmental disease states.
Impact of lockdown on COVID-19 epidemic in Île-de-France and possible exit strategies
Authors: Di Domenico Laura , Pullano Giulia , Sabbatini Chiara E. , Boëlle Pierre-Yves , Colizza Vittoria
Published: July 2020

Background

More than half of the global population is under strict forms of social distancing. Estimating the expected impact of lockdown and exit strategies is critical to inform decision makers on the management of the COVID-19 health crisis.

Methods

We use a stochastic age-structured transmission model integrating data on age profile and social contacts in Île-de-France to (i) assess the epidemic in the region, (ii) evaluate the impact of lockdown, and (iii) propose possible exit strategies and estimate their effectiveness. The model is calibrated to hospital admission data before lockdown. Interventions are modeled by reconstructing the associated changes in the contact matrices and informed by mobility reductions during lockdown evaluated from mobile phone data. Different types and durations of social distancing are simulated, including progressive and targeted strategies, with large-scale testing.

Results

We estimate the reproductive number at 3.18 [3.09, 3.24] (95% confidence interval) prior to lockdown and at 0.68 [0.66, 0.69] during lockdown, thanks to an 81% reduction of the average number of contacts. Model predictions capture the disease dynamics during lockdown, showing the epidemic curve reaching ICU system capacity, largely strengthened during the emergency, and slowly decreasing. Results suggest that physical contacts outside households were largely avoided during lockdown. Lifting the lockdown with no exit strategy would lead to a second wave overwhelming the healthcare system, if conditions return to normal. Extensive case finding and isolation are required for social distancing strategies to gradually relax lockdown constraints.

Conclusions

As France experiences the first wave of COVID-19 pandemic in lockdown, intensive forms of social distancing are required in the upcoming months due to the currently low population immunity. Extensive case finding and isolation would allow the partial release of the socio-economic pressure caused by extreme measures, while avoiding healthcare demand exceeding capacity. Response planning needs to urgently prioritize the logistics and capacity for these interventions.
Identifying and combating the impacts of COVID-19 on malaria
Authors: Rogerson Stephen J. , Beeson James G. , Laman Moses , Poespoprodjo Jeanne Rini , William Timothy , Simpson Julie A. , Price Ric N. ,   the ACREME Investigators, Anstey Nicholas , Fowkes Freya , McCarthy James , McCaw James , Mueller Ivo , Gething Peter
Published: July 2020

Background

The COVID-19 pandemic has resulted in millions of infections, hundreds of thousands of deaths and major societal disruption due to lockdowns and other restrictions introduced to limit disease spread. Relatively little attention has been paid to understanding how the pandemic has affected treatment, prevention and control of malaria, which is a major cause of death and disease and predominantly affects people in less well-resourced settings.

Main body

Recent successes in malaria control and elimination have reduced the global malaria burden, but these gains are fragile and progress has stalled in the past 5 years. Withdrawing successful interventions often results in rapid malaria resurgence, primarily threatening vulnerable young children and pregnant women. Malaria programmes are being affected in many ways by COVID-19. For prevention of malaria, insecticide-treated nets need regular renewal, but distribution campaigns have been delayed or cancelled. For detection and treatment of malaria, individuals may stop attending health facilities, out of fear of exposure to COVID-19, or because they cannot afford transport, and health care workers require additional resources to protect themselves from COVID-19. Supplies of diagnostics and drugs are being interrupted, which is compounded by production of substandard and falsified medicines and diagnostics. These disruptions are predicted to double the number of young African children dying of malaria in the coming year and may impact efforts to control the spread of drug resistance. Using examples from successful malaria control and elimination campaigns, we propose strategies to re-establish malaria control activities and maintain elimination efforts in the context of the COVID-19 pandemic, which is likely to be a long-term challenge. All sectors of society, including governments, donors, private sector and civil society organisations, have crucial roles to play to prevent malaria resurgence. Sparse resources must be allocated efficiently to ensure integrated health care systems that can sustain control activities against COVID-19 as well as malaria and other priority infectious diseases.

Conclusion

As we deal with the COVID-19 pandemic, it is crucial that other major killers such as malaria are not ignored. History tells us that if we do, the consequences will be dire, particularly in vulnerable populations.
Abnormal expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma based on data mining
Authors: Liang Taotao , Sang Siyao , Shao Qi , Chen Chen , Deng Zhichao , Wang Ting , Kang Qiaozhen
Published: July 2020

Background

EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remain to be investigated.

Methods

In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC was analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. The function of EPB41L1 in cell adhesion and migration was confirmed by wound healing assay using 786-O cells in vitro. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them was visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.

Results

The results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 were associated with cell adhesion and confirmed in vitro. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion.

Conclusions

In summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.
Changes in bowel sounds of inpatients undergoing general anesthesia
Authors: Wang Guojing , Wang Mingjun , Liu Hongyun , Zhao Suping , Liu Lu , Wang Weidong
Published: July 2020

Background

General anesthesia can affect intestinal function, but there is no objective, practical and effective indicator to evaluate the inhibition and recovery of intestinal function. The main objectives of this study were to assess whether bowel sounds (BSs) changed before, immediately after and 3 h after general anesthesia, and whether these changes in BSs are an effective indicator of intestinal function and an accurate guide for postoperative feeding.

Methods

We randomly selected 26 inpatients and collected three sets of 5-min continuous BS data before the operation (Pre-op), immediately after the operation (Pro-op) and 3 h after the operation (3 h-Pro-op) for each patient. Then, the linear and nonlinear characteristic values (CVs) of each effective bowel sound were extracted and paired t tests and rank-sum tests were used to evaluate the changes in the BSs.

Results

The differences in CVs, between Pre-op and Pro-op, as well as between Pro-op and 3 h-Pro-op, were statistically significant (p < 0.05). However, there are no statistically significant differences between all the CVs between Pre-op and 3 h-Pro-op (p > 0.05).

Conclusion

BSs change before and after general anesthesia. Furthermore, the BSs are weakened due to general anesthesia and recover to the pre-op state 3 h later. Therefore, the BSs can be an indicator of intestinal function under general anesthesia, so as to provide guidance for postoperative feeding, which is of considerable clinical significance.
Barriers to access and organization of primary health care services for rural riverside populations in the Amazon
Authors: Garnelo Luiza , Parente Rosana Cristina Pereira , Puchiarelli Maria Laura Rezende , Correia Priscilla Cabral , Torres Matheus Vasconcelos , Herkrath Fernando José
Published: July 2020

Background

The ways of life in the Amazon are diverse and not widely known. In addition, social inequities, large geographic distances and inadequate health care network noticeably limit access to health services in rural areas. Over the last decades, Brazilian health authorities have implemented fluvial mobile units (FMU) as an alternative to increase access and healthcare coverage. The aim of the study was to identify the strategies of access and utilization of primary health care (PHC) services by assessing the strengths and limitations of the healthcare model offered by the FMU to reduce barriers to services and ensure the right to healthcare.

Methods

Qualitative and ethnographic research involving participant observation and semi-structured interviews. Data collection consisted of interviews with users and health professionals and the observation of service organization and healthcare delivered by the FMU, in addition to the therapeutic itineraries that determine demand, access and interaction of users with healthcare services.

Results

Primary care is offered by the monthly locomotion of the FMU that serves approximately 20 rural riverside communities. The effectiveness of the actions of the FMU proved to be adequate for conditions such as antenatal care for low-risk pregnancy, which require periodic consultations. However, conditions that require continued attention are not adequately met through the organization of care established in the FMU. The underutilization of the workforce of community health workers and disarrangement between their tasks and those of the rest of the multi-professional team are some of the reasons pointed out, making the healthcare continuity unfeasible within the intervals between the trips of the FMU. From the users’ perspective, although the presence of the FMU provides healthcare coverage, the financial burden generated by the pursuit for services persists, since the dispersed housing pattern requires the locomotion of users to reach the mobile unit services as well as for specialized care in the urban centers.

Conclusions

The implementation of the FMU represents an advance in terms of accessibility to PHC. However, the organization of their activity uncritically replicates the routines adopted in the daily routine of health services located in urban spaces, proving to be inadequate for providing healthcare strategies capable of mitigating social and health inequalities faced by the users.
Maternal height associated with cesarean section. A cross-sectional study using the 2014–2015 national maternal-child health survey in Guatemala
Authors: Roldán Evelyn , Grajeda Laura M , Pérez Wilton
Published: July 2020

Background

Socioeconomic status is associated with cesarean section (CS). Maternal height, however, may be another related factor to CS. In Guatemala, a quarter of women between 15 and 49 years of age are shorter than 145 cm. Therefore, this study aims to examine the association of maternal height with cesarean section in Guatemala.

Methods

We carried out a secondary analysis study using data from the 2014–15 Guatemalan national maternal and child health survey—9542 mothers aged 15–49 and 12,426 live births were analyzed. We obtained the prevalence ratio of the association between maternal height and CS based on three Poisson regression models. One model included all live births, another the first live birth, and a third model the last live birth. For each model, we accounted for covariates and sampling design.

Results

The national prevalence of CS was 26.3% (95%CI: 25.0, 27.7). The adjusted prevalence ratio of CS, including all live births, was 1.63 (95%CI: 1.37, 1.94) more likely in mothers shorter than 145 cm compared with those equal or greater than 170 cm. This figure was 1.45 (95%CI: 1.19, 1.76) in the model with the first live birth. In the model with the last birth, maternal height was not associated with CS after accounting for previous CS as one of the covariates.

Conclusions

Prevalence of CS in this setting was high and above international recommendations. Further, very short mothers were more likely to experience CS compared to taller mothers after accounting for covariates, except when a previous CS was present. Maternal height should be included in clinical assessments during prenatal care.
Measuring socioeconomic and health financing inequality in maternal mortality in Colombia: a mixed methods approach
Authors: Rivillas Juan Carlos , Devia-Rodriguez Raúl , Ingabire Marie-Gloriose
Published: July 2020

Background

Understanding health financing reforms and means is key to evaluate how maternal health has improved. Problems related to health financing policies are contributing to inadequate quality of care and inequitable use of healthcare by pregnant women, resulting in poor maternal health outcomes. The purpose of the study was to measure socioeconomic and health financing related inequality in maternal mortality in Colombia as well as identifying potential epicenters of this inequality.

Methods

The data used was obtained from National Information of Social Protection (Sispro), the Department of Planning and National Statistics Department. Maternal mortality ratios were calculated by health insurance scheme and disaggregated by health spending per capita quintiles to allow for closer examination of inequality. The Slope Index of Inequality and Concentration Index were estimated to express absolute and relative inequality. We conducted interviews with key informants involved in the implementation of health financing and maternal health policies.

Results

The main finding shows inequality in maternal mortality across regions and in particular in the subsidized health insurance. The contributory health insurance scheme is closing gaps over time, but inequality in the subsidized scheme is significantly widening, which impacts the severity of overall measurements of inequality. 20% of territories with the lowest health spending per capita have reached 35% of maternal mortality, and it such rates are worsening. This means that there is a marginal exclusion in which most of maternal deaths still occur in the regions with lowest resources.

Conclusions

Beyond the key issues in health financing, issues of quality of care must be addressed. The country must define its own approach to financing for maternal health coverage given its unique situation and starting point. Potential policy implications that emerged are: i) afro-Colombian, indigenous, poorer and migrant women must be put at the center of the maternal health care services; ii) better skills, Reproductive, Maternal, Newborn and Child Health RMNCH training and health worker retention strategies and training in rural, insular and remote geographical areas; ii) a better understanding of provider payment mechanisms and the incentives that influence provider behaviors; and iv) inequality prompt calls for a targeted approach, whereby care is directed toward the most disadvantaged regions.
Geographic Targeting and Normative Frames: Revisiting the Equity of Conditional Cash Transfer Program Distribution in Bolivia, Colombia, Ecuador, and Peru
Authors: Poirier Mathieu J. P.
Published: July 2020

Background

Four Andean countries of Bolivia, Colombia, Ecuador, and Peru introduced national health-focused conditional cash transfer (CCT) programs in the 2000s. This study probes whether policymakers in these countries targeted CCT programs to subregions with the highest prevalence of ill-health or those with the lowest socioeconomic status (SES) to evaluate the equity of geographic targeting and means-testing, as well as the potential role of normative frames, bounded rationality, and clientelism as explanatory mechanisms for inequities in social spending.

Methods

The distribution of vaccination coverage, underweight, stunting, and child deaths is established both within and between subnational regions and SES quintiles from 1998 to 2012 using every available nationally representative household survey. The equity of CCT program targeting and strength of association with subregional SES and health outcomes are measured using generalized entropy index decomposition and meta-regression. Finally, simple predictive models for CCT targeting are created using lagged subregional SES, health outcomes, and concentration indices.

Results

Bolivia and Peru both effectively targeted at-risk subregions, but subregions in Peru with no CCT program coverage result in higher mistargeting rates for the country as a whole. Only Bolivia failed to attain CCT coverage concentration indices that are at least as large as the health inequalities they are targeting. Despite this insufficient progressivity, Bolivia has the most efficient subregional targeting, while the lowest rates of mistargeting for child deaths are found in Colombia and Ecuador. Finally, the simple predictive model performs as well or better than observed CCT coverage distribution for every country, year, and outcome.

Conclusions

Both Peru and Ecuador have targeted programs to their poorest populations effectively, demonstrating that this is possible with both universal and geographic targeting. No clear evidence of clientelism was found, while the dominant normative frame underlying CCT program targeting decisions appears to be the relative SES of subregions, rather than absolute SES, prevalence of health outcomes, or health inequalities. To reduce the inequitable impacts of bounded rationality, policymakers can use simple predictive models to target CCT coverage effectively and without leaving behind the most vulnerable populations that happen to live in more affluent subregions.
Complications of peritonsillar abscess
Authors: Klug Tejs Ehlers , Greve Thomas , Hentze Malene
Published: July 2020

Background

The vast majority of patients with peritonsillar abscess (PTA) recover uneventfully on abscess drainage and antibiotic therapy. However, occasionally patient´s condition deteriorates as the infection spread in the upper airway mucosa, through cervical tissues, or hematogenously. The bacterial etiology of PTA is unclarified and the preferred antimicrobial regimen remains controversial. The current narrative review was carried out with an aim to (1) describe the spectrum of complications previously recognized in patients with peritonsillar abscess (PTA), (2) describe the bacterial findings in PTA-associated complications, and (3) describe the time relation between PTA and complications.

Methods

Systematic searches in the Medline and EMBASE databases were conducted and data on cases with PTA and one or more complications were elicited.

Results

Seventeen different complications of PTA were reported. The most frequently described complications were descending mediastinitis (n = 113), para- and retropharyngeal abscess (n = 96), necrotizing fasciitis (n = 38), and Lemierre´s syndrome (n = 35). Males constituted 70% of cases and 49% of patients were > 40 years of age. The overall mortality rate was 10%. The most prevalent bacteria were viridans group streptococci (n = 41, 25%), beta-hemolytic streptococci (n = 32, 20%),F. necrophorum(n = 21, 13%),S. aureus(n = 18, 11%),Prevotella species(n = 17, 10%), andBacteroides species(n = 14, 9%). Simultaneous diagnosis of PTA and complication was more common (59%) than development of complication after PTA treatment (36%) or recognition of complication prior to PTA (6%).

Conclusion

Clinicians involved in the management of PTA patients should be aware of the wide range of complications, which may arise in association with PTA development. Especially males and patients  > 40 years of age seem to be at an increased risk of complicated disease. In addition to Group A streptococci andF. necrophorum, the current findings suggest that viridans group streptococci,S. aureus,Prevotella, andBacteroidesmay also play occasional roles in the development of PTA as well as spread of infection. Complications occasionally develop in PTA patients, who are treated with antibiotics and surgical drainage.
Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis
Authors: Tang Jia , Hui Jiangjin , Ma Jing , Mingquan Chen
Published: July 2020

Aim

To assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are Staphylococcus aureus carriers undergoing different types of surgeries and diverse measures of decolonization.

Methods

Relevant randomized controlled trials (RCTs) were identified through systematic searches of the PubMed, Embase, Web of science, and the Cochrane Library databases. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and the effects model was chosen according to the heterogeneity. Subgroup analyses were performed according to different types of surgeries and measures of decolonization that Staphylococcus aureus carriers were applied.

Results

Twenty RCTs published between 1996 and 2019 involving 10,526 patients were included. Pooled results showed that the overall SSIs and pulmonary surgery SSIs presented with a statistical difference in measures of nasal decontamination (RR = 0.59 and 0.47, respectively, both p < 0.01). However, the associations between nasal decolonization and increased risks of SSIs in orthopedics surgery or cardiovascular surgery remained insignificant in studies. As for the diverse measures of nasal decontamination, 50% used mupirocin, 15% used chlorhexidine, 30% used different types of antimicrobial drugs, and 5% use others. The SSIs rate were decreased after chlorhexidine (RR = 0.474, 95% CI 0.259–0.864), while no significant difference was shown in the use of mupirocin (RR = 0.871, 95% CI 0.544–1.394).

Conclusion

It seems that nasal decolonization of Staphylococcus aureus may be associated with a reduction of SSIs in these patients, especially in patients who have been administered by pulmonary surgeries or treated with chlorhexidine.
Clinicopathological and prognostic significance of platelet-lymphocyte ratio (PLR) in gastric cancer: an updated meta-analysis
Authors: Zhang Xunlei , Zhao Wenjing , Yu Yang , Qi Xue , Song Li , Zhang Chenfei , Li Guoxing , Yang Lei
Published: July 2020

Background

Pre-treatment PLR (platelet-lymphocyte ratio) was reported to be associated with the prognosis in gastric cancer (GC), but the results remain inconclusive. This meta-analysis aimed to investigate the prognostic potential of the pre-treatment PLR in gastric cancer.

Methods

We performed a systematic literature search in PubMed, Embase, and the Cochrane Library to identify eligible publications. The hazard ratio (HR)/odds ratio (OR) and its 95% confidence (CI) of survival outcomes and clinicopathological parameters were calculated.

Results

A total of 49 studies (51 cohorts), collecting data from 28,929 GC patients, were included in the final analysis. The pooled results demonstrated that the elevated pre-treatment PLR was significantly associated with poor overall survival (OS) (HR 1.37, 95% CI 1.26–1.49, p < 0.001; I2 = 79.90%, Ph < 0.001) and disease-free survival (DFS) (HR 1.52, 95% CI 1.22–1.90, p < 0.001, I2 = 88.6%, Ph < 0.001). Furthermore, the patients with the elevated PLR had a higher risk of lymph node metastasis (OR = 1.17, 95% CI 1.02–1.33, p = 0.023), serosal invasion (T3+T4) (OR = 1.34, 95% CI 1.10–1.64, p = 0.003), and increased advanced stage (III+IV) (OR = 1.20, 95% CI 1.06–1.37, p = 0.004).

Conclusions

An elevated pre-treatment PLR was a prognostic factor for poor OS and DFS and associated with poor clinicopathological parameters in GC patients.
COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis
Authors: Zhang Yong-Chen , Zhao Hui , Chen Chen , Ali Mohammad Amzad
Published: July 2020

Background

Several studies have reported the Cyclooxygenase 2 (COX-2) rs689466 polymorphism as a susceptibility locus of colorectal cancer (CRC), but their findings are inconsistent. Thus, this meta-analysis was performed to more accurately identify the effects of this polymorphism on CRC risk.

Methods

Potential case-control studies on EMBASE, Google Scholar, Web of Science, Cochrane Library, and PubMed were searched. The strength of association was quantified by pooled odds ratio and 95% confidence interval. Totally 16 articles involving 8998 cases and 11,917 controls were included.

Results

None of the five tested genetic models revealed an association between rs689466 polymorphism and CRC risk. Stratified analysis by ethnicity uncovered a positive association between this polymorphism and higher CRC risk in Caucasians, but not in Asians. In addition, we found that high expression of COX-2 was associated with better overall survival for all CRC patients.

Conclusion

To sum up, the COX-2 rs689466 polymorphism may be related with susceptibility to CRC in Caucasians. This finding should be verified by larger-size studies with different ethnic groups.
Diagnostic value of miR-186-5p for carotid artery stenosis and its predictive significance for future cerebral ischemic event
Authors: Lv Weibo , Zhang Tao , Zhao Hongwei , He Shuang , Li Bingwei , Gao Yang , Pan Wenying
Published: July 2020

Background

MicroRNAs (miRNAs) serve as novel promising biomarkers for the diagnosis and prognosis of many human diseases. This study investigated the diagnostic value of miR-186-5p for asymptomatic carotid artery stenosis (CAS), and its predictive value for future cerebral ischemic events (CIEs).

Methods

Sixty-seven cases with asymptomatic CAS and 60 healthy individuals were recruited. Serum levels of miR-186-5p were tested by using qRT-PCR. Receiving–operator characteristic (ROC) curve was drawn based on sensitivity and specificity analyses. All asymptomatic CAS cases were followed up for 5 years. Kaplan-Meier method was applied for the evaluation of the predictive value of miR-186-5p for the occurrence of CIE.

Results

The serum level of miR-186-5p was increased significantly in asymptomatic CAS patients. MiR-186-5p was the most significant factor associated with the high degree of carotid stenosis in asymptomatic CAS patients. In the ROC curve analysis, the AUC was 0.919, with the sensitivity of 89.6% and specificity of 81.7% at the cutoff value of 1.221. Kaplan-Meier method results revealed that high miR-186-5p level was associated with the occurrence of CIEs. High miR-186-5p level and high degree of carotid stenosis were independent factors for the occurrence of CIEs.

Conclusion

MiR-186-5p serves as a potential diagnostic biomarker for patients with asymptomatic CAS, and predicts the occurrence of future CIEs.
Potential mechanism prediction of Cold-Damp Plague Formula against COVID-19 via network pharmacology analysis and molecular docking
Authors: Han Lin , Wei Xiu-Xiu , Zheng Yu-Jiao , Zhang Li-Li , Wang Xin-Miao , Yang Hao-Yu , Ma Xu , Zhao Lin-Hua , Tong Xiao-Lin
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold‒Damp Plague Formula (CDPF) against COVID-19, which was used to treat “cold‒dampness stagnation in the lung” in Trial Versions 6 and 7 of the “Diagnosis and Treatment Protocol for COVID-19”, have been demonstrated, but the effective components and their mechanism of action remain unclear.

Methods

In this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein‒protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment.

Results

The active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs—ingredients—targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through “multi components‒multi targets‒multi pathways” at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a “CDPF—herbs—ingredients—targets—pathways—COVID-19” network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities.

Conclusions

This study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19.
Artificial neural networks improve early outcome prediction and risk classification in out-of-hospital cardiac arrest patients admitted to intensive care
Authors: Johnsson Jesper , Björnsson Ola , Andersson Peder , Jakobsson Andreas , Cronberg Tobias , Lilja Gisela , Friberg Hans , Hassager Christian , Kjaergard Jesper , Wise Matt , Nielsen Niklas , Frigyesi Attila
Published: July 2020

Background

Pre-hospital circumstances, cardiac arrest characteristics, comorbidities and clinical status on admission are strongly associated with outcome after out-of-hospital cardiac arrest (OHCA). Early prediction of outcome may inform prognosis, tailor therapy and help in interpreting the intervention effect in heterogenous clinical trials. This study aimed to create a model for early prediction of outcome by artificial neural networks (ANN) and use this model to investigate intervention effects on classes of illness severity in cardiac arrest patients treated with targeted temperature management (TTM).

Methods

Using the cohort of the TTM trial, we performed a post hoc analysis of 932 unconscious patients from 36 centres with OHCA of a presumed cardiac cause. The patient outcome was the functional outcome, including survival at 180 days follow-up using a dichotomised Cerebral Performance Category (CPC) scale with good functional outcome defined as CPC 1–2 and poor functional outcome defined as CPC 3–5. Outcome prediction and severity class assignment were performed using a supervised machine learning model based on ANN.

Results

The outcome was predicted with an area under the receiver operating characteristic curve (AUC) of 0.891 using 54 clinical variables available on admission to hospital, categorised as background, pre-hospital and admission data. Corresponding models using background, pre-hospital or admission variables separately had inferior prediction performance. When comparing the ANN model with a logistic regression-based model on the same cohort, the ANN model performed significantly better (p = 0.029). A simplified ANN model showed promising performance with an AUC above 0.852 when using three variables only: age, time to ROSC and first monitored rhythm. The ANN-stratified analyses showed similar intervention effect of TTM to 33 °C or 36 °C in predefined classes with different risk of a poor outcome.

Conclusion

A supervised machine learning model using ANN predicted neurological recovery, including survival excellently, and outperformed a conventional model based on logistic regression. Among the data available at the time of hospitalisation, factors related to the pre-hospital setting carried most information. ANN may be used to stratify a heterogenous trial population in risk classes and help determine intervention effects across subgroups.
Population variation in miRNAs and isomiRs and their impact on human immunity to infection
Authors: Rotival Maxime , Siddle Katherine J. , Silvert Martin , Pothlichet Julien , Quach Hélène , Quintana-Murci Lluis
Published: July 2020

Background

MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized.

Results

We generate 977 miRNA-sequencing profiles from primary monocytes from individuals of African and European ancestry following activation of three TLR pathways (TLR4, TLR1/2, and TLR7/8) or infection with influenza A virus. We find that immune activation leads to important modifications in the miRNA and isomiR repertoire, particularly in response to viral challenges. These changes are much weaker than those observed for protein-coding genes, suggesting stronger selective constraints on the miRNA response to stimulation. This is supported by the limited genetic control of miRNA expression variability (miR-QTLs) and the lower occurrence of gene-environment interactions, in stark contrast with eQTLs that are largely context-dependent. We also detect marked differences in miRNA expression between populations, which are mostly driven by non-genetic factors. On average, miR-QTLs explain approximately 60% of population differences in expression of their cognate miRNAs and, in some cases, evolve adaptively, as shown in Europeans for a miRNA-rich cluster on chromosome 14. Finally, integrating miRNA and mRNA data from the same individuals, we provide evidence that the canonical model of miRNA-driven transcript degradation has a minor impact on miRNA-mRNA correlations, which are, in our setting, mainly driven by co-transcription.

Conclusion

Together, our results shed new light onto the factors driving miRNA and isomiR diversity at the population level and constitute a useful resource for evaluating their role in host differences of immunity to infection.
18F-FDG PET and DCE kinetic modeling and their correlations in primary NSCLC: first voxel-wise correlative analysis of human simultaneous [18F]FDG PET-MRI data
Authors: Besson Florent L. , Fernandez Brice , Faure Sylvain , Mercier Olaf , Seferian Andrei , Mignard Xavier , Mussot Sacha , le Pechoux Cecile , Caramella Caroline , Botticella Angela , Levy Antonin , Parent Florence , Bulifon Sophie , Montani David , Mitilian Delphine , Fadel Elie , Planchard David , Besse Benjamin , Ghigna-Bellinzoni Maria-Rosa , Comtat Claude , Lebon Vincent , Durand Emmanuel
Published: July 2020

Objectives

To decipher the correlations between PET and DCE kinetic parameters in non-small-cell lung cancer (NSCLC), by using voxel-wise analysis of dynamic simultaneous [18F]FDG PET-MRI.

Material and methods

Fourteen treatment-naïve patients with biopsy-proven NSCLC prospectively underwent a 1-h dynamic [18F]FDG thoracic PET-MRI scan including DCE. The PET and DCE data were normalized to their corresponding T1-weighted MR morphological space, and tumors were masked semi-automatically. Voxel-wise parametric maps of PET and DCE kinetic parameters were computed by fitting the dynamic PET and DCE tumor data to the Sokoloff and Extended Tofts models respectively, by using in-house developed procedures. Curve-fitting errors were assessed by computing the relative root mean square error (rRMSE) of the estimated PET and DCE signals at the voxel level. For each tumor, Spearman correlation coefficients (rs) between all the pairs of PET and DCE kinetic parameters were estimated on a voxel-wise basis, along with their respective bootstrapped 95% confidence intervals (n = 1000 iterations).

Results

Curve-fitting metrics provided fit errors under 20% for almost 90% of the PET voxels (median rRMSE = 10.3, interquartile ranges IQR = 8.1; 14.3), whereas 73.3% of the DCE voxels showed fit errors under 45% (median rRMSE = 31.8%, IQR = 22.4; 46.6). The PET-PET, DCE-DCE, and PET-DCE voxel-wise correlations varied according to individual tumor behaviors. Beyond this wide variability, the PET-PET and DCE-DCE correlations were mainly high (absolute rs values > 0.7), whereas the PET-DCE correlations were mainly low to moderate (absolute rs values < 0.7). Half the tumors showed a hypometabolism with low perfused/vascularized profile, a hallmark of hypoxia, and tumor aggressiveness.

Conclusion

A dynamic “one-stop shop” procedure applied to NSCLC is technically feasible in clinical practice. PET and DCE kinetic parameters assessed simultaneously are not highly correlated in NSCLC, and these correlations showed a wide variability among tumors and patients. These results tend to suggest that PET and DCE kinetic parameters might provide complementary information. In the future, this might make PET-MRI a unique tool to characterize the individual tumor biological behavior in NSCLC.
A case report of Kaposiform haemangioendothelioma; response with propranolol and steroids
Authors: Verma Saurav , Dhamija Ekta , Barwad Adarsh , Kumar Venkatesan S. , Rastogi Sameer
Published: July 2020

Background

Kaposiform haemangioendothelioma is a rare vascular tumor and may involve skin, deep soft tissue or bone. It is a locally aggressive tumor usually seen in infants. Here we report a case of kaposiform hemagioendothelioma in a child who responded to propranolol and steroids.

Case presentation

A 3-year-old male child presented with a swelling below his right knee with characteristic violet skin lesion. There was no evidence of Kasabach–Merritt phenomenon. After no improvement with several attempts at debridement and anti-tubercular treatment; a diagnosis of Kaposiform Haemangioendothelioma was reached on the basis of overall clinical picture and histology. The child was treated with propranolol and steroids and had an excellent clinical response and a near complete resolution on imaging at 5 months.

Conclusions

These cases are often misdiagnosed and despite a delay in diagnosis have good outcomes with appropriate multimodality management. This case highlights the unique and typical characteristics of kaposiform haemangioendothelioma.
exCTF simulator: Simulation tool for phase contrast transfer function for aberration-corrected transmission electron microscopy
Authors: Lee Sang-Chul , Jeung Jong-Man , Lee Sang-Gil , Kim Jin-Gyu
Published: July 2020

Background

The contrast transfer function (CTF) is an important principle in the field of transmission electron microscopy (TEM) imaging. It provides information on how the electron wave that interacted with a sample (in frequency domain) in an objective lens is transferred to the imaging system (in real space domain) depending on the effects of lens aberrations. Based on the CTF calculation, various useful results, such as the TEM instrumental information limit and optimal imaging condition, can be estimated. Recently, aberration-corrected TEM (AC-TEM) has been widely applied in various research fields for imaging at the nanoscale or atomic scale. To use AC-TEM effectively, a deep understanding of the complicated CTF with an electron wave controlled via an aberration corrector is required. Unfortunately, this complicated CTF is difficult to understand for most microscopists without the use of computational tools. In this study, we develop the extended CTF (exCTF) simulator to perform the full as well as simple CTF calculation.

Findings

We successfully developed the exCTF simulator, which can obtain more information than previously reported software. The exCTF simulator not only calculates the CTF for basic optical information that can be obtained in conventional TEM, but also can calculate the extended CTF with various aberrations (up to fifth order) for more detailed information obtained in advanced high-performance AC-TEM in one-dimensional and two-dimensional formats. The user interface of the simulator includes CTF calculation, saving, and edit functions for five graphs for different conditions, allowing for detailed comparative analysis.

Conclusion

We confirmed that the exCTF simulator produced reliable calculation data for various applications. The exCTF simulator made it easy to obtain instrumental performance information and demonstrated the influence of optical aberrations on the actual resolution of AC-TEM. Consequently, the proposed exCTF simulator is expected to be useful to microscopists as a simulation tool for electron microscopy and as a training tool for electron optics.