bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Incidence, Progression, and Risk Factors of Age-Related Macular Degeneration and Projection of Disease Statistics in 30 Years: A Modeling Study
Authors: Wang Yuye , Zhong Yifan , Zhang Liang , Wu Qijun , Tham Yihchung , Rim Tyler Hyungtaek , Kithinji David Mutugi , Wu Jingyang , Cheng Chingyu , Liang Huiying , Yu Honghua , Yang Xiaohong , Liu Lei
Published: September 2021

Objective: Age-related macular degeneration(AMD) has become a major cause of visual impairment worldwide, especially in the elderly. Estimates of incidence, progression rates, and risk factors of AMD vary among studies, complicating the understanding of its epidemiology. Methods: For this systematic review and meta-analysis, literature published up to March 1, 2021, was searched in both English and Chinese databases. Hierarchical Bayesian approaches were used to estimate pooled incidence, progression, and 95% credible intervals (CrIs). Results: Thirty studies were included. The pooled annual early and late AMD incidence rates were 1.59 (95% CrI: 1.18–2.11) and 0.23 (95% CrI: 0.14–0.34) per 100 person-years, respectively. The annual progression rate of AMD was 5.5 (95% CrI: 2.3–8.8) per 100 person-years. Smoking was an independent risk factor for both early and late AMD, whereas age, high-density lipoprotein cholesterol, and alcohol consumption were risk factors for early AMD incidence only. The projected number of new cases of early and late AMD in 2050 would be 39.05 million (95% CrI: 23.12–63.57) and 6.41 million (95% CrI: 3.37–13.22), respectively. Conclusion: The prediction the number of new cases of AMD is not equal across the globe. Our findings indicate the need for more rigorous control and prevention measures in AMD focus on its risk factors for early intervention. The epidemiological estimates reported in this study could inform to identify effective strategies for preventing AMD worldwide.
Ichthyosis Prematurity Syndrome: A Rare Form but Easily Recognizable Ichthyosis
Authors: Al-Khenaizan Sultan , AlSwailem Asma , AlBalwi Mohammed Ali
Published: September 2021

Ichthyosis prematurity syndrome is a rare autosomal recessive genodermatosis that is associated with mutations in the SLC27A4 gene. Its onset occurs in early childhood and presents with the clinical triad of premature birth, thick caseous desquamating epidermis, and neonatal asphyxia. Here, we describe a prematurely born baby patient (33 weeks of gestation) with a homozygous variant at the initiation codon site (c.1 A> G, p.Met1Val) in the SLC27A4 gene to raise awareness of this rare syndrome despite its distinctive features as we believe it is still underdiagnosed.
Snapping Scapula Syndrome in the Setting of Elastofibroma Dorsi: A Case Report
Authors: Nadeem Ibrahim M. , Shah Muffaqam , Parasu Naveen , Khan Moin , Munir Sohaib
Published: September 2021

A 54-year-old woman presented with a 15-year history of progressively worsening left snapping scapula syndrome (SSS) in the setting of ipsilateral elastofibroma dorsi. Her pain was refractory to multiple conservative measures. She was successfully treated with focal ultrasound-guided corticosteroid injection to the superomedial border of the scapula. There was demonstrable improvement in findings between pre- and post-procedural MRI examinations. Despite the underlying cause of SSS, trials of nonoperative treatment techniques are warranted before considering surgical options. Focal ultrasound-guided corticosteroid injection, in conjunction with physiotherapy, is one such example.
Value of HSP90α in Lung Cancer Diagnosis and Recurrence Prediction: A Cohort Study
Authors: Wang Yaqian , Seyed Barghi Seyedeh Maryam , Yang Yanhong , Akhavan-Sigari Reza
Published: September 2021

Purpose: In the current study, we tried to analyze the diagnostic value of HSP90α expression during the course of disease in patients treated with and without surgery. Methods: Three hundred and twelve patients with lung cancer who referred to Qinhuangdao First Hospital from June 2016 to March 2021 were selected as the experimental group and 160 healthy individuals subjected as the control group in this cohort study. The ELISA method was used to detect the expression level of plasma HSP90α. Results: We observed significant differences in the level of HSP90α in pathologic type, differentiation degree, stage, and presence of lung, liver, and bone metastasis; HSP90α was significantly higher in non-small cell lung carcinoma in comparison with small cell lung carcinoma, especially in lung adenocarcinoma. Our results demonstrated that HSP90α at 71.45 ng/mL had a sensitivity of 66.3% and a specificity of 95.0% for diagnosing lung cancer. Also, we observed that the HSP90α expression was significantly increased prior to lung cancer relapse in patients treated with chemoradiotherapy and surgery. Conclusion: Serum level of plasma HSP90α could be a reliable biomarker in diagnosing lung cancer and its subtypes and might be a valid biomarker for predicting lung cancer relapse in patients treated with chemoradiotherapy and surgery.
Desenhos de uma casa
Authors: Bucci Angelo
Published: September 2021

O presente artigo se permite uma leve transgressão: falar de desenhos sem exibi-los. Propõe-se mostrar-lhes uma única obra, “Casa de fim de semana em São Paulo”1, pois através dela pode-se lhes fazer inferir os desenhos que permitiram pensá-la em projeto. É uma espécie de filtro, de prova do valor efetivo do desenho aplicado ao projeto nas suas diversas formas e nas sucessivas fases, isto é, se nessa “visita” à obra e suas razões os desenhos não afloram, é porque eles não eram necessários ao processo. Enfim, os desenhos, aqueles que realmente contam para o processo de projeto e obra, permanecem impressos na própria obra.
Entrevista com Paulo Mendes da Rocha
Authors: Fernandes Francisco Barata , Silva Vitor Manuel Oliveira da , Medeiros Givaldo Luiz , Lancha Joubert José , Castral Paulo Cesar , Vizioli Simone Helena Tanoue
Published: September 2021

Entrevista realizada em 2 de julho de 2012 no escritório do arquiteto. Entrevistadores: Francisco Barata Fernandes é arquiteto e professor doutores da Faculdade de Arquitectura da Universidade do Porto; Vitor Manuel Oliveira da Silva é artista plástico e professor doutor da Faculdade de Arquitectura da Universidade do Porto; Givaldo Luiz Medeiros, Joubert José Lancha, Paulo Cesar Castral e Simone Helena Tanoue Vizioli são arquitetos e professores doutores do Instituto de Arquitetura e Urbanismo da Universidade de São Paulo.
Task Learnability Modulates Surprise but Not Valence Processing for Reinforcement Learning in Probabilistic Choice Tasks
Authors: Wurm Franz , Walentowska Wioleta , Ernst Benjamin , Severo Mario Carlo , Pourtois Gilles , Steinhauser Marco
Published: September 2021

The goal of temporal difference (TD) reinforcement learning is to maximize outcomes and improve future decision-making. It does so by utilizing a prediction error (PE), which quantifies the difference between the expected and the obtained outcome. In gambling tasks, however, decision-making cannot be improved because of the lack of learnability. On the basis of the idea that TD utilizes two independent bits of information from the PE (valence and surprise), we asked which of these aspects is affected when a task is not learnable. We contrasted behavioral data and ERPs in a learning variant and a gambling variant of a simple two-armed bandit task, in which outcome sequences were matched across tasks. Participants were explicitly informed that feedback could be used to improve performance in the learning task but not in the gambling task, and we predicted a corresponding modulation of the aspects of the PE. We used a model-based analysis of ERP data to extract the neural footprints of the valence and surprise information in the two tasks. Our results revealed that task learnability modulates reinforcement learning via the suppression of surprise processing but leaves the processing of valence unaffected. On the basis of our model and the data, we propose that task learnability can selectively suppress TD learning as well as alter behavioral adaptation based on a flexible cost–benefit arbitration.
Trichoderma dumbbelliforme sp. nov. an undescribed fungus of order Hypocreales from India
Authors: T PRAMEELADEVI , KAMIL DEEBA , TOPPO R. SUDEEP , CHOUDHARY SHIV PRATAP
Published: September 2021

Trichoderma is an important genus of family Hypocreaceae, which contain nearly 375 known species. In current study, a new species Trichoderma dumbbelliforme collected from virgin forest soil of Nagaland and confirmed based on morphological and phylogenetic analyses. Morphologically, T. dumbbelliforme sp. nov. distinguished from other species of Trichoderma by producing nodules on sterile part of the conidiophores and pyriform to dumbbell shaped conidia with the size of 4.0–6.0×2.5–3.0µm and having two big guttulae at each end. Furthermore, the fungus was confirmed by molecular characterization using Translation elongation factor 1-α (tef-1) gene sequencing.  The phylogenetic relationship was established for generated sequence and many related ex-type sequences downloaded from NCBI GenBank by maximum-parsimony analysis. Tef-1 sequence data clarified the phylogenetic affinity to clade-1 of Trichoderma as per new authoritative guide line on molecular identification of Trichoderma. Phylogenetically, this new species of Trichoderma closely related to T. crassum, T. spirale, T. sulawesense, T. longisporum, T. virens, T. gelatinosum and T. gliocladium species. Therefore, the morphological comparisons were done with closely related species viz., T. crassum and T. spirale which lead to the conclusion that the collected taxon is new to science.
Luteolin-Loading Her-2 Nanospheres Enhances Targeting and Therapeutic Effects of Breast Cancer
Authors: Xiao Chuanguang , Wang Xiaohong , Shen Jiacheng , Xia Yanjie , Qiu Shusheng , Liang Xiaodong , Gu Wenyue
Published: September 2021

Despite the broad anticancer activity, whereas the clinical application of luteolin is hindered by unsatisfactory water solubility and non-targeting. Herein, targeted inhibitory effects of luteolin-loading HER2 nanospheres (Her-2-NPs) were successfully prepared by thin film ultrasonic
method. In comparison with the non-targeted nanospheres, Her-2 nanospheres could significantly boost the intake of luteolin in SK-BR-3 cells. The proliferation and apoptosis of breast cancer cells were detected by MTT testing and flow cytometry examination, respectively. Consequently, the
expressions of FOXO1 mRNA level was detected using qPCR assay and protein level was detected using Westernblot. We discovered that Luteolin-loading Her-2 nanospheres could significantly hinder the proliferation of breast cancer cells, down-regulation their migration, and up-regulation FOXO1
expression at mRNA and protein levels, reveal a mechanism whereby luteolin interferes with breast cancer. Collectively, these results suggest Her-2-modified nanospheres increases the efficiency of luteolin uptake and thus improves the treatment benefit of breast cancer.
NAO Influence on the MJO and its Prediction Skill in the Subseasonal-to-Seasonal Prediction Models
Authors: Lin Hai , Huang Zhiyong , Hendon Harry , Brunet Gilbert
Published: September 2021

Based on the database of the Subseasonal to Seasonal (S2S) Prediction project of the World Weather Research Programme (WWRP) / World Climate Research Programme (WCRP), the influence of the North Atlantic Oscillation (NAO) on the Madden- Julian Oscillation (MJO) and its forecast skill is investigated. It is found that most models can capture the MJO phase changes following positive and negative NAO events. About 20 days after initialized with a positive (negative) NAO, the forecast MJO appears more frequently in phase 7 (3), which corresponds to reduced (enhanced) convection in the tropical Indian Ocean and enhanced (suppressed) convection in the western Pacific. In most S2S models the MJO prediction skill is dependent on the NAO amplitude and phase in the initial condition. A strong NAO leads to a better MJO forecast skill than a weak NAO. The MJO skill tends to be higher when the forecast starts from a negative NAO than a positive NAO. These results indicates that there is a strong Northern extratropical influence on the MJO and its forecast skill. It is important for numerical models to better represent the NAO influence to improve the simulation and prediction of the MJO.
Soil moisture continues declining in North China over the regional warming slowdown of the past 20 years
Authors: Li Xin , Ren Guoyu , You Qinglong , Wang Suyan , Zhang Wen
Published: September 2021

Soil moisture is an important variable of the climate system and is used to measure dry–wet change in hydro-climate. The warming trend has slowed in China over the past 20 years since 1998, and how the soil moisture changes in this period deserves our attention. With North China as a research region, this study uses the Global Land Data Assimilation System and ground observations to investigate the causes of changes in soil moisture during 1998–2017 versus 1961–1997. The results show that: (1) annual mean soil moisture experienced an almost continued decrease from to 1960s to 2010s, and no pause in the decrease of soil moisture over the regional warming slowdown of the past 20 years could be detected; (2) with the stabilization or even increase in solar radiation and wind speed as well as the continuous increase land surface air temperature, the impact of potential evapotranspiration on soil moisture gradually became prominent, and the impact of precipitation decreased, since 1998; (3) the percent contribution of annual potential evapotranspiration to soil moisture variation increased by 26% during 1998–2017 relative to that in 1961–1997, and the percent contribution of summer potential evapotranspiration even increased by 45%. Our results will provide insight into the land surface water budget and mechanism involved in drought development in North China.
Pressure Fields in the Airflow over Wind-Generated Surface Waves
Authors: Funke Christoph S. , Buckley Marc P. , Schultze Larissa K. P. , Veron Fabrice , Timmermans Mary-Louise E. , Carpenter Jeffrey R.
Published: September 2021

The quantification of pressure fields in the airflow over water waves is fundamental for understanding the coupling of the atmosphere and the ocean. The relationship between the pressure field and the water surface slope and velocity are crucial in setting the fluxes of momentum and energy. However, quantifying these fluxes is hampered by difficulties in measuring pressure fields at the wavy air–water interface. Here we utilize results from laboratory experiments of wind-driven surface waves. The data consist of particle image velocimetry of the airflow combined with laser-induced fluorescence of the water surface. These data were then used to develop a pressure field reconstruction technique based on solving a pressure Poisson equation in the airflow above water waves. The results allow for independent quantification of both the viscous stress and pressure-induced form drag components of the momentum flux. Comparison of these with an independent bulk estimate of the total momentum flux (based on law-of-the-wall theory) shows that the momentum budget is closed to within approximately 5%. In the partitioning of the momentum flux between viscous and pressure drag components, we find a greater influence of form drag at high wind speeds and wave slopes. An analysis of the various approximations and assumptions made in the pressure reconstruction, along with the corresponding sources of error, is also presented.
Improvement of interface anchoring by ultrasonic vibration for adhesively bonded CFRP/Al joints
Authors: Wang Hui , Tong Xuetong , Ji Wei , Chen Yizhe , Hua Lin , Wu Min
Published: September 2021

Adhesively bonded carbon fiber reinforced polymer (CFRP)/Al joints have been widely used in engineering field. However, the bonding strength still needs to be improved. In this study, ultrasonic vibration was applied during the adhesive bonding to promote the micromechanical anchoring at the interface of CFRP/Al joints. Ultrasonic vibration was exerted on the CFRP laminate to transmit the vibration to the adhesive bonding area once the joint was assembled. The strength and the strength consistency of the joints were increased by 45% and 50%, respectively. Scanning electron microscope (SEM) and energy dispersive spectrometer (EDS) results showed that the ultrasonic vibration promoted the filling of the adhesive into the microstructures of the adherends and achieved a more compact bonding. Viscosity and contact angle of the adhesive were measured, and both of them were decreased greatly under the ultrasonic vibration, indicating that the ultrasonic vibration can increase the fluidity of the adhesive and force the wetting between the materials. Ultrasonic capillary experiment was then conducted. The adhesive in the capillary tube was prompted to rise obviously, and the meniscus was inverted with ultrasonic vibration, showing that the ultrasonic vibration produced a driving effect on filling of the adhesive in the microstructures. Therefore, the joints exhibited improved bonding strength owing to the enhanced micromechanical anchoring and physical adsorption at the bonding interface. This study is of great significance for understanding and optimization of the ultrasonic vibration strengthened adhesive bonding.
Role of ribosomal RNA released from red cells in blood coagulation in zebrafish and humans
Authors: Alharbi Abdulmajeed , Iyer Neha , Al Qaryoute Ayah , Raman Revathi , Burks David J. , Azad Rajeev K. , Jagadeeswaran Pudur
Published: September 2021

Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. It has previously been shown that the RNA released from damaged blood cells activates clotting. However, the nature of the RNA released from hemolysis is still elusive. We found that after hemolysis, red blood cells from both zebrafish and humans released RNA that contained mostly 5.8S ribosomal RNA (5.8S rRNA), This RNA activated coagulation in zebrafish and human plasmas. By using both natural and synthetic 5.8S rRNA and its truncated fragments, we found that the 3'-end 26-nucleotide-long RNA (3'-26 RNA) and its stem-loop secondary structure were necessary and sufficient for clotting activity. Corn trypsin inhibitor (CTI), a coagulation factor XII (FXII) inhibitor, blocked 3'-26 RNA–mediated coagulation activation in the plasma of both zebrafish and humans. CTI also inhibited zebrafish coagulation in vivo. 5.8S rRNA monoclonal antibody inhibited both 5.8S rRNA– and 3'-26 RNA–mediated zebrafish coagulation activity. Both 5.8S rRNA and 3'-26 RNA activated normal human plasma but did not activate FXII-deficient human plasma. Taken together, these results suggested that the activation of zebrafish plasma is via an FXII-like protein. Because zebrafish have no FXII and because hepatocyte growth factor activator (Hgfac) has sequence similarities to FXII, we knocked down the hgfac in adult zebrafish. We found that plasma from this knockdown fish does not respond to 3'-26 RNA. To summarize, we identified that an rRNA released in hemolysis activates clotting in human and zebrafish plasma. Furthermore, we showed that fish Hgfac plays a role in rRNA-mediated activation of coagulation.
Constructing xenobiotic maps of metabolism to predict enzymes catalyzing metabolites capable of binding to DNA
Authors: Conan Mael , Théret Nathalie , Langouet Sophie , Siegel Anne
Published: September 2021

Background

The liver plays a major role in the metabolic activation of xenobiotics (drugs, chemicals such as pollutants, pesticides, food additives...). Among environmental contaminants of concern, heterocyclic aromatic amines (HAA) are xenobiotics classified by IARC as possible or probable carcinogens (2A or 2B). There exist little information about the effect of these HAA in humans. While HAA is a family of more than thirty identified chemicals, the metabolic activation and possible DNA adduct formation have been fully characterized in human liver for only a few of them (MeIQx, PhIP, A$$\alpha$$αC).

Results

We have developed a modeling approach in order to predict all the possible metabolites of a xenobiotic and enzymatic profiles that are linked to the production of metabolites able to bind DNA. Our prediction of metabolites approach relies on the construction of an enriched and annotated map of metabolites from an input metabolite.The pipeline assembles reaction prediction tools (SyGMa), sites of metabolism prediction tools (Way2Drug, SOMP and Fame 3), a tool to estimate the ability of a xenobotics to form DNA adducts (XenoSite Reactivity V1), and a filtering procedure based on Bayesian framework. This prediction pipeline was evaluated using caffeine and then applied to HAA. The method was applied to determine enzymes profiles associated with the maximization of metabolites derived from each HAA which are able to bind to DNA. The classification of HAA according to enzymatic profiles was consistent with their chemical structures.

Conclusions

Overall, a predictive toxicological model based on anin silicosystems biology approach opens perspectives to estimate the genotoxicity of various chemical classes of environmental contaminants. Moreover, our approach based on enzymes profile determination opens the possibility of predicting various xenobiotics metabolites susceptible to bind to DNA in both normal and physiopathological situations.
Genome-wide identification and characterization of the BES/BZR gene family in wheat and foxtail millet
Authors: Liu Dan , Cui Yanjiao , Zhao Zilong , Li Suying , Liang Dan , Wang Conglei , Feng Gang , Wang Jianhe , Liu Zhengli
Published: September 2021

Background

BES/BZR family genes have vital roles in plant growth, development, and adaptation to environmental stimuli. However, they have not yet been characterized and systematically analyzed in wheat and foxtail millet.

Results

In the current study, five common and two uniqueBES/BZRgenes were identified by genome-wide analysis in wheat and foxtail millet, respectively. These genes were unevenly distributed on 14 and five chromosomes of wheat and foxtail millet, respectively, and clustered in two subgroups in a phylogenetic analysis. The BES/BZR gene family members in each subgroup contained similar conserved motifs. Investigation ofcis-acting elements and expression profile analysis revealed that theBES/BZRgenes were predominantly expressed in leaf tissues of wheat and foxtail millet seedlings and responded to brassinosteroid, abscisic acid, and NaCl treatments.

Conclusions

Our results provide a basis for future studies on the function and molecular mechanisms of the BES/BZR gene family in wheat, foxtail millet, and other plants.
Facility-based surveillance for influenza and respiratory syncytial virus in rural Zambia
Authors: Loevinsohn Gideon , Hamahuwa Mutinta , Sinywimaanzi Pamela , Fenstermacher Katherine Z. J. , Shaw-Saliba Kathryn , Pekosz Andrew , Monze Mwaka , Rothman Richard E. , Simulundu Edgar , Thuma Philip E. , Sutcliffe Catherine G.
Published: September 2021

Background

While southern Africa experiences among the highest mortality rates from respiratory infections, the burden of influenza and respiratory syncytial virus (RSV) in rural areas is poorly understood.

Methods

We implemented facility-based surveillance in Macha, Zambia. Outpatients and inpatients presenting with influenza-like illness (ILI) underwent testing for influenza A, influenza B, and RSV and were prospectively followed for 3 to 5 weeks to assess clinical course. Log-binomial models assessed correlates of infection and clinical severity.

Results

Between December 2018 and December 2019, 17% of all outpatients presented with ILI and 16% of inpatients were admitted with an acute respiratory complaint. Influenza viruses and RSV were detected in 17% and 11% of outpatient participants with ILI, and 23% and 16% of inpatient participants with ILI, respectively. Influenza (July–September) and RSV (January-April) prevalence peaks were temporally distinct. RSV (relative risk [RR]: 1.78; 95% confidence interval [CI] 1.51–2.11), but not influenza, infection was associated with severe disease among patients with ILI. Underweight patients with ILI were more likely to be infected with influenza A (prevalence ratio [PR]: 1.72; 95% CI 1.04–2.87) and to have severe influenza A infections (RR: 2.49; 95% CI 1.57–3.93).

Conclusions

Populations in rural Zambia bear a sizeable burden of viral respiratory infections and severe disease. The epidemiology of infections in this rural area differs from that reported from urban areas in Zambia.
Processing speed is affected by early impairment in kidney function in the general elder population
Authors: Månsson Tomas , Elmståhl Sölve
Published: September 2021

Background

Chronic kidney disease, cardiovascular disease, and cognitive dysfunction are common in the elder population. There is evidence of a connection between these conditions, possibly by a shared vascular pathogenesis. Processing speed is commonly impaired in cerebrovascular disease.

Methods

The data was obtained from the population based study “Good aging in Skåne” (GÅS), and included 905 individuals (mean age = 68 years). We investigated the impact of impaired kidney function at baseline on the development of dementia, MCI, and impairment in specific cognitive domains at follow up 6 years later, using logistic regression models. Impaired kidney function was defined as GFR < 60 ml/min/1,73 m2. GFR was estimated from creatinine and cystatin C, using the CKD-EPI formula. Function in the cognitive domains learning and memory, language, complex attention, executive function, perceptual-motor, as well as meta-memory, and global cognitive function, was assessed using a neuropsychological test battery consisting of 12 tests. We compared the test results from follow up, with the results obtained at baseline, using linear regression models in order to assess changes in performance in cognitive domains.

Results

At follow up, 14 and 158 participants had developed dementia and MCI, respectively. We did not find evidence that moderately impaired eGFR at baseline increased the odds of dementia or MCI. A decline in processing speed was associated with impaired kidney function.

Conclusions

The effect on processing speed could represent early vascular implications on cognition. Even at moderately impaired kidney function, overview of cardiovascular risk factors could potentially prevent further cognitive impairment.
ER expression associates with poor prognosis in male lung squamous carcinoma after radical resection
Authors: Yang Xue , Jin Xiangfeng , Xu Rongjian , Yu Zhuang , An Ning
Published: September 2021

Background

Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient.

Methods

We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay.

Results

Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037).

Conclusion

ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.
Geographical variability and factors associated with caesarean section delivery in India: a comparative assessment of Bihar and Tamil Nadu
Authors: Roy Avijit , Paul Pintu , Chouhan Pradip , Rahaman Margubur , Kapasia Nanigopal
Published: September 2021

Background

Caesarean section delivery is a major life-saving obstetric surgical intervention for mothers and babies from pregnancy and childbirth related complications. This paper attempts to investigate the geographical variations and correlating factors of caesarean section delivery in India, particularly focusing on the states of Bihar and Tamil Nadu, accounting for one of the lowest and highest prevalence states of caesarean section delivery respectively.

Methods

This study is based on secondary data, collected from the fourth round of the National Family Health Survey (NFHS-4), 2015–16. We utilized 190,898 women aged 15–49 years who had a living child during the past 5 years preceding the survey. In this study, caesarean section delivery was the outcome variable. A variety of demographic, socio-economic, and pregnancy- and delivery-related variables were considered as explanatory variables. Descriptive statistics, bivariate percentage distribution, Pearson’s Chi-square test, and multivariate binary logistic regression models were employed to draw the inferences from data.

Results

Of participants, about 19% of women had undergone caesarean section delivery in the country. The state-wise distribution shows that Telangana (60%) followed by Andhra Pradesh (42%) and Tamil Nadu (36%) represented the topmost states in caesarean delivery, while Bihar (7%), Madhya Pradesh (10%), and Jharkhand (11%) placed at the bottom end. Multivariate logistic models show that the likelihood of caesarean delivery was higher among older women (35–49 years), women with higher levels of education, Muslims, women belonging to the upper quintiles of the household wealth, and those who received antenatal care (ANC), experienced pregnancy loss and delivery complications. Moreover, the odds of caesarean section delivery were remarkably greater for the private health sector than the public health sector in both focused states: Bihar (odds ratio [OR] = 12.84; 95% confidence interval [CI]: 10.90, 15.13) and Tamil Nadu (OR = 2.90; 95% CI: 2.54, 3.31).

Conclusion

Findings of this study suggest that improvement in female education, providing economic incentives, and spreading awareness through mass media could raise the caesarean section delivery among women whose vaginal delivery could be unsafe for them as well as for their babies. Moreover, providing adequate ANC and well-equipped public healthcare services would facilitate caesarean delivery among needy women.
Ang-(1–7) protects skeletal muscle function in aged mice
Authors: Li Ying , Song Jiao , Jiang Yangyang , Yang Xue , Cao Li , Xiao Chun , Li Suli , Dong Birong , Huang Xiaoli
Published: September 2021

Background

The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang-(1–7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms.

Methods

We measured the expression levels of Ang-(1–7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1–7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1–7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4).

Results

Aged mice showed reduced skeletal muscle function and levels of Ang-(1–7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1–7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1–7) was shown to promote along with the upregulated expression of Glut4.

Conclusions

The ACE2/ Ang-(1–7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1–7) can delay the age-related decline in the function of skeletal muscle.
Comparing the locking screw direction of three locking plates for lateral clavicle fractures: a simulation study
Authors: Abe Shingo , Koizumi Kota , Murase Tsuyoshi , Kuriyama Kohji
Published: September 2021

Background

The locking plate is a useful treatment for lateral clavicle fractures, however, there are limits to the fragment size that can be fixed. The current study aimed to measure the screw angles of three locking plates for lateral clavicle fractures. In addition, to assess the number of screws that can be inserted in different fragment sizes, to elucidate the size limits for locking plate fixation.

Methods

The following three locking plates were analyzed: the distal clavicle plate [Acumed, LLC, Oregon, the USA], the LCP clavicle plate lateral extension [Depuy Synthes, LLC, PA, the USA], and the HAI clavicle plate [HOMS Engineering, Inc., Nagano, Japan]. We measured the angles between the most medial and lateral locking screws in the coronal plane and between the most anterior and posterior locking screws in the sagittal plane. A computer simulation was used to position the plates as laterally as possible in ten normal three-dimensional clavicle models. Lateral fragment sizes of 10, 15, 20, 25, and 30 mm were simulated in the acromioclavicular joint, and the number of screws that could be inserted in the lateral fragment was assessed. Subsequently, the area covered by the locking screws on the inferior surface of the clavicle was measured.

Results

The distal clavicle plate had relatively large screw angles (20° in the coronal plane and 32° in the sagittal plane). The LCP clavicle lateral extension had a large angle (38°) in the sagittal plane. However, the maximum angle of the HAI clavicle plate was 13° in either plane. The distal clavicle plate allowed most screws to be inserted in each size of bone fragment. For all locking plates, all screws could be inserted in 25 mm fragments. The screws of distal clavicle plate covered the largest area on the inferior surface of the clavicle.

Conclusions

Screw angles and the numbers of screws that could be inserted in the lateral fragment differed among products. Other augmented fixation procedures should be considered for fractures with fragment sizes < 25 mm that cannot be fixed with a sufficient number of screws.
Reframing cancer: challenging the discourse on cancer and cancer drugs—a Norwegian perspective
Authors: Stenmarck Mille Sofie , Engen Caroline , Strand Roger
Published: September 2021

Background

As the range of therapeutic options in the field of oncology increases, so too does the strain on health care budgets. The imbalance between what is medically possible and financially feasible is frequently rendered as an issue of tragic choices, giving rise to public controversies around health care rationing.

Main body

We analyse the Norwegian media discourse on expensive cancer drugs and identify four underlying premises: (1) Cancer drugs are de facto expensive, and one does not and should not question why. (2) Cancer drugs have an indubitable efficacy. (3) Any lifetime gained for a cancer patient is an absolute good, and (4) cancer patients and doctors own the truth about cancer. Applying a principle-based approach, we argue that these premises should be challenged on moral grounds. Within the Norwegian public discourse, however, the premises largely remain unchallenged due to what we find to be unjustified claims of moral superiority. We therefore explore alternative framings of the issue of expensive cancer drugs and discuss their potential to escape the predicament of tragic choices.

Conclusions

In a media discourse that has seemingly stagnated, awareness of the framings within it is necessary in order to challenge the current tragic choices predicament the discourse finds itself in. In order to allow for a discourse not solely concerned with the issue of tragic choices, the premises that underlie it must be subjected to critical examination. As the field of oncology advances rapidly, we depend on a discussion of its opportunities and challenges that is meaningful, and that soberly addresses the future of cancer care—both its potential and its limits.
Criteria for assessing the quality of clinical practice guidelines in paediatrics and neonatology: a mixed-method study
Authors: Dagard Joanna , Mazille-Orfanos Nadia , Georgi Nawras , Dechicha Intissar , Carrault Guy , Pladys Patrick , Beuchée Alain
Published: September 2021

Background

Evidenced-based practice is a key component of quality care. This study aims to explore users’ expectations concerning paediatric local clinical practice guidelines.

Methods

A mixed method approach was applied, including material from quantitative questionnaire and semi-structured interviews. Data were analysed using descriptive statistics and qualitative content analysis. Data were analysed with constant comparative method. Qualitative data were parsed and categorized to identify themes related to decision-making.

Results

A total of 83 physicians answered the survey (response rate 83%). 98% of the participants wanted protocols based on international guidelines, 80% expected a therapeutic content. 24 semi-structured interviews were conducted to understand implementation processes, barriers and facilitators. Qualitative analysis revealed 5 emerging themes: improvement of local clinical practice guidelines, patterns of usage, reasons for non-implementation, alternative sources and perspectives.

Conclusion

Some criteria should be considered for the redaction of local clinical practice guidelines: focus on therapeutic, ease of access, establish local clinical practice guidelines based on international guidelines adapted to the local setting, document references and include trainees such as residents in the redaction.
Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model
Authors: Ono Hanako , Arai Yasuhito , Furukawa Eisaku , Narushima Daichi , Matsuura Tetsuya , Nakamura Hiromi , Shiokawa Daisuke , Nagai Momoko , Imai Toshio , Mimori Koshi , Okamoto Koji , Hippo Yoshitaka , Shibata Tatsuhiro , Kato Mamoru
Published: September 2021

Background

Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling.

Results

We performed single-cell exome and transcriptome sequencing of 200 cells to investigate how ITH is generated in a mouse colorectal cancer model. In the model, a single normal intestinal cell is grown into organoids that mimic the intestinal crypt structure. Upon RNAi-mediated downregulation of a tumor suppressor gene APC, the transduced organoids were serially transplanted into mice to allow exposure to in vivo microenvironments, which play relevant roles in cancer development. The ITH of the transcriptome increased after the transplantation, while that of the exome decreased. Mutations generated during organoid culture did not greatly change at the bulk-cell level upon the transplantation. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes after the transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages.

Conclusions

This study revealed an evolutionary dynamics of single-cell RNA and DNA heterogeneity in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.
The effect of Helicobacter pylori eradication on prognosis of postoperative early gastric cancer: a multicenter study
Authors: Wang Liang , Wang Jinfeng , Li Sha , Bai Fei , Xie Hailong , Shan Hanguo , Liu Zhuo , Ma Tiexiang , Tang Xiayu , Tang Haibing , Qin Ang , Lei Sanlin , Zuo Chaohui
Published: September 2021

Objective

To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC).

Methods

This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group.

Result

Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84–5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51–4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08–2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient’s age ≥60 years old (HR, 3.32; 95% CI, 2.00–5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25–6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79–5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11–3.02; P = 0.018) were statistically significantly independent risk factors of overall survival.

Conclusion

H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC.
Diversity Interventions in the Classroom: From Resistance to Action
Authors: Thoman Dustin B. , Yap Melo-Jean , Herrera Felisha A. , Smith Jessi L.
Published: September 2021

The diversity intervention-resistance to action model is presented along with interviews of biology faculty undertaken to understand how resistance to implementing diversity-enhancing classroom interventions manifests at four specific input points within a rational decision-making process that too often results in inaction.
Successful Problem Solving in Genetics Varies Based on Question Content
Authors: Avena Jennifer S. , McIntosh Betsy B. , Whitney Oscar N. , Wiens Ashton , Knight Jennifer K.
Published: September 2021

Student and expert problem solving in genetics was characterized by analyzing written step-by-step processes in four different content areas. A few processes that were associated with correct answers differed depending on content area, but reasoning was consistently predictive of successful problem solving across all content areas.
Depression in pregnant women with and without COVID-19
Authors: Papadopoulos Alissa , Nichols Emily S. , Mohsenzadeh Yalda , Giroux Isabelle , Mottola Michelle F. , Van Lieshout Ryan J. , Duerden Emma G.
Published: September 2021

Evidence suggests that pregnant women who test positive for COVID-19 may develop more severe illness than non-pregnant women and may be at greater risk for psychological distress. The relationship between COVID-19 status (positive, negative, never tested) and symptoms of depression was examined in a survey study (May to September 2020) of pregnant women (n = 869). Pregnant women who reported testing positive for COVID-19 were significantly more likely to report depressive symptoms compared with women who tested negative (P = 0.027) and women who were never tested (P = 0.005). Findings indicate that pregnant women who test positive for COVID-19 should be screened and monitored for depressive symptoms.
Healthcare resource use and costs for people with type 2 diabetes mellitus with and without severe mental illness in England: longitudinal matched-cohort study using the Clinical Practice Research Datalink
Authors: Wang Han-I. , Han Lu , Jacobs Rowena , Doran Tim , Holt Richard I. G. , Prady Stephanie L. , Gilbody Simon , Shiers David , Alderson Sarah , Hewitt Catherine , Taylor Jo , Kitchen Charlotte E. W. , Bellass Sue , Siddiqi Najma
Published: September 2021

Background

Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions.

Aims

To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions.

Method

This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively.

Results

There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year.

Conclusions

Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.