bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical characteristics and molecular mechanism of an exo-type alginate lyase VxAly7D and its use for the preparation of unsaturated monosaccharides
Authors: Tang Luyao , Wang Ying , Gao Shan , Wu Hao , Wang Danni , Yu Wengong , Han Feng
Published: June 2020

Background

As the most abundant polysaccharide in brown algae, alginate has become a promising economical material for bioethanol production. Recently, exo-type alginate lyases have received extensive attention because the unsaturated monosaccharides produced by their degradation of alginate can be easily converted into 4-deoxy-l-erythro-5-hexoseulose uronate (DEH), a promising material for bioethanol production and biorefinery systems.

Results

In this study, we cloned and characterized an exo-type polysaccharide lyase family 7 (PL7) alginate lyase VxAly7D from the marine bacterium Vibrio xiamenensis QY104. Recombinant VxAly7D was most active at 30 °C and exhibited 21%, 46% and 90% of its highest activity at 0, 10 and 20 °C, respectively. Compared with other exo-type alginate lyases, recombinant VxAly7D was shown to be a bifunctional alginate lyase with higher specific activity towards sodium alginate, polyG and polyM (462.4 ± 0.64, 357.37 ± 0.53 and 441.94 ± 2.46 U/mg, respectively). A total of 13 μg recombinant VxAly7D could convert 3 mg sodium alginate to unsaturated monosaccharides in 1 min with a yield of 37.6%, and the yield reached 95% in 1 h. In addition, the three-dimensional structure of VxAly7D was modelled using the crystal structure of AlyA5 from Zobellia galactanivorans DsijT as the template. The action mode and the end products of the W295A mutant revealed that Trp295 is a key amino acid residue responsible for the exolytic action mode of VxAly7D.

Conclusion

Overall, our results show that VxAly7D is a PL7 exo-type alginate lyase with high activity and a high conversion rate at low/moderate temperatures, which provides a useful enzymatic tool for the development of biofuel production from brown algae and enriches the understanding of the structure and functional relationships of polysaccharide lyases.
Evaluation of a pan-Leishmania SL RNA qPCR assay for parasite detection in laboratory-reared and field-collected sand flies and reservoir hosts
Authors: Pareyn Myrthe , Hendrickx Rik , Girma Nigatu , Hendrickx Sarah , Van Bockstal Lieselotte , Van Houtte Natalie , Shibru Simon , Maes Louis , Leirs Herwig , Caljon Guy
Published: June 2020

Background

In eco-epidemiological studies,Leishmaniadetection in vectors and reservoirs is frequently accomplished by high-throughput and sensitive molecular methods that target minicircle kinetoplast DNA (kDNA). A pan-LeishmaniaSYBR green quantitative PCR (qPCR) assay which detects the conserved spliced-leader RNA (SL RNA) sequence was developed recently. This study assessed the SL RNA assay performance combined with a crude extraction method for the detection ofLeishmaniain field-collected and laboratory-reared sand flies and in tissue samples from hyraxes as reservoir hosts.

Methods

Field-collected and laboratory-infected sand fly and hyrax extracts were subjected to three different qPCR approaches to assess the suitability of the SL RNA target forLeishmaniadetection. Nucleic acids of experimentally infected sand flies were isolated with a crude extraction buffer with ethanol precipitation and a commercial kit and tested for downstream DNA and RNA detection. Promastigotes were isolated from culture and sand fly midguts to assess whether there was difference in SL RNA and kDNA copy numbers. Naive sand flies were spiked with a serial dilution of promastigotes to make a standard curve.

Results

The qPCR targeting SL RNA performed well on infected sand fly samples, despite preservation and extraction under presumed unfavorable conditions for downstream RNA detection. Nucleic acid extraction by a crude extraction buffer combined with a precipitation step was highly compatible with downstream SL RNA and kDNA detection. Copy numbers of kDNA were found to be identical in culture-derived parasites and promastigotes isolated from sand fly midguts. SL RNA levels were slightly lower in sand fly promastigotes (ΔCq 1.7). The theoretical limit of detection and quantification of the SL RNA qPCR respectively reached down to 10−3and 10 parasite equivalents. SL RNA detection in stored hyrax samples was less efficient with some false-negative assay results, most likely due to the long-term tissue storage in absence of RNA stabilizing reagents.

Conclusions

This study shows that a crude extraction method in combination with the SL RNA qPCR assay is suitable for the detection and quantification ofLeishmaniain sand flies. The assay is inexpensive, sensitive and pan-Leishmaniaspecific, and accordingly an excellent assay for high-throughput screening in entomological research.
Assessment of knowledge, attitude and practices and the analysis of risk factors regarding schistosomiasis among fishermen and boatmen in the Dongting Lake Basin, the People’s Republic of China
Authors: Guan Zhou , Dai Si-Min , Zhou Jie , Ren Xiao-Bing , Qin Zhi-Qiang , Li Yin-Long , Lv Shan , Li Shi-Zhu , Zhou Xiao-Nong , Xu Jing
Published: June 2020

Background

Fishermen and boatmen are a population at-risk for contracting schistosomiasis due to their high frequency of water contact in endemic areas of schistosomiasis in the People’s Republic of China (P. R. China). To develop specific interventions towards this population, the present study was designed to assess the knowledge, attitudes and practices (KAPs) towards schistosomiasis of fishermen and boatmen, and to identify the risk factors associated with schistosome infection using a molecular technique in a selected area of Hunan Province in P. R. China.

Methods

A cross sectional survey was conducted in the Dongting Lake Basin of Yueyang County, Hunan Province. A total of 601 fishermen and boatmen were interviewed between October and November 2017. Information regarding sociodemographic details and KAPs towards schistosomiasis were collected using a standardized questionnaire. Fecal samples of participants were collected and tested by polymerase chain reaction (PCR). Logistic regression analysis was conducted to explore the risk factors related to the positive results of PCR.

Results

Of the 601 respondents, over 90% knew schistosomiasis and how the disease was contracted, the intermediate host of schistosomes and preventive methods. The majority of respondents had a positive attitude towards schistosomiasis prevention. However, only 6.66% (40/601) of respondents had installed a latrine on their boats, while 32.61% (196/601) of respondents defecated in the public toilets on shore. In addition, only 4.99% (30/601) respondents protected themselves while exposed to freshwater. The prevalence of schistosomiasis, as determined by PCR, among fishermen and boatmen in Yueyang County was 13.81% (83/601). Age, years of performing the current job, number of times receiving treatment, and whether they were treated in past three years were the main influencing factors of PCR results among this population.

Conclusions

Fishermen and boatmen are still at high risk of infection in P. R. China and gaps exist in KAPs towards schistosomiasis in this population group. Chemotherapy, and health education encouraging behavior change in combination with other integrated approaches to decrease the transmission risk in environments should be improved.
Care transition from hospital to home: cancer patients’ perspective
Authors: Lorenzini Elisiane , Boell Julia Estela Willrich , Oelke Nelly D. , Rodrigues Caroline Donini , Trindade Letícia Flores , Winter Vanessa Dalsasso Batista , Malkiewiez Michelle Mariah , Flôres Gabriela Ceretta , Pluta Pâmella , Kolankiewicz Adriane Cristina Bernat
Published: June 2020

Objectives

The present database contains information on sociodemographic and clinical data as well as data from the Care Transition Measure (CTM 15-Brazil) of cancer patients undergoing clinical or surgical treatment. Data collection was carried out 7 to 30 days after patients’ hospital discharge from June to August 2019. Understanding these data can contribute to improving quality of care transitions and avoiding hospital readmissions.

Data description

This data set encompasses 213 cancer patients characterized by the follow variables: gender, age range, place of residence, race, marital status, schooling, paid work activity, type of treatment, cancer staging, metastasis, comorbidities, main complaint, main complaint grouped as, continuing medication, diagnosis, diagnosis grouped as, cancer type, year of diagnosis, oncology treatment, first hospitalization, readmission in the last 30 days, number of hospitalizations in the last 30 days, readmission in the last 6 months, number of hospitalizations in the last 6 months, readmission in the last year, number of hospitalizations in the last year and the questions 1–15 from CTM 15-Brazil.
The Efficiency of self-employed general practitioners and factors affecting it: a study in Iran
Authors: Hajibagheri Razie , Lotfi Farhad , Bayati Mohsen
Published: June 2020

Objective

Physicians as an economic firm make use of available resources such as time, human forces and space to provide healthcare services. The current study aimed at estimating the technical efficiency of Iranian self-employed general practitioners (GPs) and its effective factors using data envelopment analysis and regression analysis.

Results

About 2% of the GPs were fully efficient and the remaining (98%) were inefficient. Almost, 2.09% of the physicians had constant returns to scale, and 31.41% and 66.49% of them had increasing and decreasing returns to scale, respectively. According to the regression estimates, gender (female) (β = 3.776, P = 0.072), age (β = 0.475, P = 0.013), practice experience (β = − 0.477, P = 0.015), contract with the insurer (β = − 6.475, P = 0.005) and economic expectations (β = 1.939, P = 0.014) showed significant effect on GPs inefficiency. Most of the GPs surveyed did not optimally allocate their time and physical and human resources to provide their services. Female GPs, older ones, those with fewer practice experience, those with higher economic expectations, and the GPs with no insurance contract were more inefficient. Increasing the insurance coverage of self-employed GPs and providing them with training in office economic management can reduce their inefficiency.
Estrogen-related mechanisms in sex differences of hypertension and target organ damage
Authors: Sabbatini Andrea Rodrigues , Kararigas Georgios
Published: June 2020

Hypertension (HTN) is a primary risk factor for cardiovascular (CV) events, target organ damage (TOD), premature death and disability worldwide. The pathophysiology of HTN is complex and influenced by many factors including biological sex. Studies show that the prevalence of HTN is higher among adults aged 60 and over, highlighting the increase of HTN after menopause in women. Estrogen (E2) plays an important role in the development of systemic HTN and TOD, exerting several modulatory effects. The influence of E2 leads to alterations in mechanisms regulating the sympathetic nervous system, renin-angiotensin-aldosterone system, body mass, oxidative stress, endothelial function and salt sensitivity; all associated with a crucial inflammatory state and influenced by genetic factors, ultimately resulting in cardiac, vascular and renal damage in HTN. In the present article, we discuss the role of E2 in mechanisms accounting for the development of HTN and TOD in a sex-specific manner. The identification of targets with therapeutic potential would contribute to the development of more efficient treatments according to individual needs.
A dynamic model of viruses with the effect of removable media on a computer network with heterogeneous immunity
Authors: Al-Tuwairqi Salma M. , Bahashwan Walaa
Published: June 2020

In this paper, we build a mathematical model to study the impact of external removable devices on a network with weakly- and strongly-protected computers. The model describes the dynamics between weak, strong, infected computers and susceptible, infected removable media. Analytical investigations of the model produce two equilibrium points: virus-free and endemic. Moreover, we investigate the local and global stability of both equilibria. The existence and stability conditions of the equilibrium points depend primarily on the basic reproduction number ($R_{0}$R0) of the model. Furthermore, we perform numerical simulations to substantiate the analytical results. Also, a sensitivity analysis is carried out to examine the critical parameters that lead to strategies to control the dissipation of viruses.
Identifying the space source term problem for a generalization of the fractional diffusion equation with hyper-Bessel operator
Authors: Luc Nguyen Hoang , Huynh Le Nhat , Baleanu Dumitru , Can Nguyen Huu
Published: June 2020

In this paper, we consider an inverse problem of identifying the source term for a generalization of the time-fractional diffusion equation, where regularized hyper-Bessel operator is used instead of the time derivative. First, we investigate the existence of our source term; the conditional stability for the inverse source problem is also investigated. Then, we show that the backward problem is ill-posed; the fractional Landweber method and the fractional Tikhonov method are used to deal with this inverse problem, and the regularized solution is also obtained. We present convergence rates for the regularized solution to the exact solution by using an a priori regularization parameter choice rule and an a posteriori parameter choice rule. Finally, we present a numerical example to illustrate the proposed method.
Social media use disorder and loneliness: any association between the two? Results of a cross-sectional study among Lebanese adults
Authors: Youssef Lara , Hallit Rabih , Kheir Nelly , Obeid Sahar , Hallit Souheil
Published: June 2020

Background

In Lebanon, it is already established that mental disorders are prevalent among the population. Lebanese people are active users of social media platforms. To date, no study has previously explored the relationship between mental health and social media use disorder in Lebanon. The present study aims to learn more about the link between social media use disorder and loneliness among Lebanese people.

Methods

This cross-sectional study was carried out between January and December 2018. It enrolled 456 residents of the community randomly selected from Lebanon’s governorates in a proportionate rate.

Results

The results showed that 107 (23.7%) participants were classified as having social media use disorder. The results of a stepwise linear regression, taking the loneliness score as the dependent variable, showed that female gender compared to males (Beta = 0.42), having a secondary level of education compared to illiteracy (Beta = 0.65), higher social media use disorder (Beta = 0.03) and higher insomnia (Beta = 0.02) and alexithymia (Beta = 0.02) were significantly associated with higher loneliness.

Conclusion

The present study was able to contribute to the literature and showed the association between social media use disorder and loneliness. These findings can benefit psychologists and public health practitioners in their future prevention and intervention plans.
What influences antibiotic sales in rural Bangladesh? A drug dispensers’ perspective
Authors: Matin Mohammad Abdul , Khan Wasif Ali , Karim Mohammad Mahbubul , Ahmed Sabeena , John-Langba Johannes , Sankoh Osman A. , Gyapong Margaret , Kinsman John , Wertheim Heiman
Published: June 2020

Background

Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance.

Objective

This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers.

Methods

We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis.

Results

A total of 301 antibiotic dispensers were identified, of whom 92% (n = 278) were private and 8% (n = 23) public. 52% (n = 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician’s prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies’ information.

Conclusion

Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.
Impact of truncal vagotomy on complicated peptic ulcer after distal gastrectomy with reconstruction by jejunal pouch interposition
Authors: Yamashita Reika , Takahashi Naoto , Tsuboi Kazuto , Mitsumori Norio , Kashiwagi Hideyuki , Yanaga Katsuhiko
Published: June 2020

Background

We encountered a case of marginal ulcer in the jejunum after distal gastrectomy with jejunal pouch interposition. However, it has not been reported and not confirmed the treatment. We chose truncal vagotomy, considering reduced morbidity and postoperative complications.

Case presentation

A case was a 69-year-old woman who was admitted to our hospital with melena. She had received curative distal gastrectomy with a 15-cm jejunal pouch reconstruction for early gastric cancer. Marginal ulcer in the jejunal pouch was detected by upper gastrointestinal endoscopy. She was given medication; however, she repeated hospitalization for melena and abdominal pain. Therefore, we decided to perform surgery, and truncal vagotomy was performed. The patient’s postoperative course was uneventful and was discharged on the 22nd postoperative day. Symptoms such as abdominal pain and melena were improved after truncal vagotomy.

Conclusion

We presented a case with a complicated peptic ulcer after distal gastrectomy with reconstruction by jejunal pouch interposition, which was successfully treated by truncal vagotomy, a surgical acid-reducing procedure which does not require resection of remnant stomach.
Total proctocolectomy with end ileostomy for acute onset of ulcerative colitis during chemoradiotherapy for lung adenocarcinoma (successfully treated by surgery): a case report
Authors: Mohri Koichi , Hiramatsu Kazuhiro , Shibata Yoshihisa , Aoba Taro , Fujii Masahiro , Arimoto Atsuki , Ito Akira , Kato Takehito
Published: June 2020

Background

Ulcerative colitis (UC) developing during chemotherapy is very rare. Here, we describe a case of acute onset during chemoradiotherapy for lung adenocarcinoma, requiring a total proctocolectomy.

Case presentation

A 52-year-old man was admitted to the hospital for chemoradiotherapy of lung cancer. He had no obvious history of gastrointestinal diseases, and concurrent chemoradiotherapy was initiated. Thirteen days after 2 cycles of cisplatin and vinorelbine, he experienced persistent hematochezia. Findings of the colonoscopy revealed edematous thickening from the rectum to the transverse colon, suggesting UC, drug-induced colitis, or infectious colitis. Results from bacterial culture were negative for Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA). Immunohistological staining for cytomegalovirus was also negative. Although he was clinically diagnosed with UC and treated with intravenous glucocorticoid, his symptoms gradually worsened and an abdominal X-ray revealed megacolon. Thirty-five days after conservative therapy, a total proctocolectomy with end permanent ileostomy was performed. Based on pathological findings and clinical course, he was diagnosed with UC.

Conclusion

Although the pathogenesis of UC during chemotherapy has been unknown, chemotherapy could be one of the causes of UC in this case. UC should be included in the differential diagnosis in patients with progressive colitis during chemotherapy.
Biochemical and electrophoretic study for diagnosis of the disease stage in patients with asthmatic bronchitis
Authors: Aboulthana Wael M. , Darwish Marwa K. , Halim Mohab H. , El-Baz Hatim A. , Ahmed Osama S.
Published: June 2020

Background

Asthmatic bronchitis is a chronic allergic airway disease diagnosed after development of chronic obstructive pulmonary disease symptoms. This study was designed to reveal relation of the different electrophoretic patterns to impairment of the lung functions in patients with asthmatic bronchitis.

Materials and methods

Patients were categorized into patients at mild stage (n= 10) and those at severe stage (n= 12) in comparison to healthy group (n= 21). The major blood components, arterial blood gases and electrolytes were immediately assayed in addition to assessment of liver enzymes and kidney functions. The pulmonary indices including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC and maximal expiratory pressure (MEP) were assayed. Furthermore, protein, lipid and calcium moieties of native protein patterns in addition to isoenzemes were electrophoretically detected.

Results

It was found that liver and kidney functions were significantly (P< 0.05) elevated in asthmatic bronchitis patients. Ca2+is the only electrolyte that decreased significantly (P< 0.05) at the severe stage. Electrophoretic patterns showed that asthmatic bronchitis disease at mild and severe stages were physiologically similar to control by 54.5 and 75.6% (protein), 73.1 and 41.6% (lipid moiety), 66.4 and 30.6% (calcium moiety), respectively. As regards to electrophoretic isoenzymes, the disease at mild and severe stages were similar to control by 95.2 and 35.4% (catalase (CAT)), 40.1 and 50.5% (peroxidase (POX)), 67.9 and 69.6% (α-esterase (α-EST)), 83.1 and 73.1% (β-esterase (β-EST)), respectively.

Conclusion

The native electrophoretic patterns used as diagnostic tool for determining the stage at which the patients with asthmatic bronchitis exist.
Least-squares reverse time migration in TTI media using a pure qP-wave equation
Authors: Mu Xinru , Huang Jianping , Yang Jidong , Guo Xu , Guo Yundong
Published: June 2020

Anisotropy is a common phenomenon in subsurface strata and should be considered in seismic imaging and inversion. Seismic imaging in a vertical transversely isotropic (VTI) medium does not take into account the effects of the tilt angles, which can lead to degraded migrated images in areas with strong anisotropy. To correct such waveform distortion, reduce related image artifacts, and improve migration resolution, a tilted transversely isotropic (TTI) least-squares reverse time migration (LSRTM) method is presented. In the LSRTM, a pure qP-wave equation is used and solved with the finite-difference method. We have analyzed the stability condition for the pure qP-wave equation using the matrix method, which is used to ensure the stability of wave propagation in the TTI medium. Based on this wave equation, we derive a corresponding demigration (Born modeling) and adjoint migration operators to implement TTI LSRTM. Numerical tests on the synthetic data show the advantages of TTI LSRTM over VTI RTM and VTI LSRTM when the recorded data contain strong effects caused by large tilt angles. Our numerical experiments illustrate that the sensitivity of the adopted TTI LSRTM to the migration velocity errors is much higher than that to the anisotropic parameters (including epsilon, delta, and tilted angle parameters), and its sensitivity to the epsilon model and tilt angle is higher than that to the delta model.
Analysis of the internal architectural elements of tidal-influenced meandering fluvial deposits using well logging and seismic data: The study of the Athabasca Oil Sands, Alberta, Canada
Authors: Cheng Lifang , Yin Yanshu , Wang Hui , Feng Wenjie , Wang Lixin , Liu Zhenkun , Wang Pangen , Liu Jiong
Published: June 2020

A reservoir was dominated by inclined heterolithic stratification (IHS) formed in large point bars of the McMurray Formation. We have used high-resolution seismic data and logging data to identify the internal architectural elements of the reservoir. From the core data, we defined four lithofacies and recognized the architectural element boundary. Then, we used stratum dip data across wells, combined with seismic reflectivity, isopach, and amplitude attributes, to understand the lateral continuity of the boundaries. Later, we established the sedimentary model and found the differences between tidal-influenced meandering fluvial channels and conventional meandering fluvial channels. Research showed that tidal bedding was especially well-developed, and breccia deposition and muddy IHS were also frequent. The development of the lateral accretion packages was more frequent than that in the conventional meandering fluvial channels. The characteristics of the interbedded layers in sandy IHS were very thin, mainly approximately 20 to 40 cm. The dip of the lateral accretion packages was smaller and distributed from 4° to 8°. The studies were expected to have a major impact on the understanding of reservoir formation, distribution, and heterogeneity for improved hydrocarbon recovery purpose in the area.
Security needs among patients referred for high secure care in Broadmoor Hospital England
Authors: Williams Hannah Kate , Senanayke Madhri , Ross Callum C. , Bates Rob , Davoren Mary
Published: June 2020

Background

Security needs among patients referred to forensic mental health services have rarely been systematically studied.

Aims

To ascertain security needs among patients referred to a high secure hospital, Broadmoor High Secure Hospital, England. We also aimed to compare the security needs for those referred to mental illness services with those referred to personality disorder services in the hospital.

Method

A retrospective complete cohort study of all referrals to Broadmoor Hospital over a 2-year period was conducted. All referred patients (n = 204) were assessed for need for high secure care by two Broadmoor clinicians. The final decision on need for admission was taken by a multidisciplinary admission panel. Independent of the panel, researchers rated need for security using the DUNDRUM-1 triage security scale.

Results

Those admitted to Broadmoor Hospital had higher triage security scores than those declined (F = 4.209, d.f. = 1, P = 0.042). Referrals to the personality disorder pathway had higher security needs than those referred to the mental illness pathway high secure service (F = 6.9835, d.f. = 1, P = 0.0089). Overall security needs among referrals to Broadmoor were extremely high, both by comparison with previous needs identified in UK medium secure services and international medium and high secure services.

Conclusions

High secure patient cohorts represent a uniquely vulnerable group within mental health services, with extremely high security needs identified in this study. This has significant implications for services given the high levels of resources needed to provide therapeutically safe and secure care and treatment to this group.
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial
Authors: Palma David A. , Olson Robert , Harrow Stephen , Gaede Stewart , Louie Alexander V. , Haasbeek Cornelis , Mulroy Liam , Lock Michael , Rodrigues George B. , Yaremko Brian P. , Schellenberg Devin , Ahmad Belal , Senthi Sashendra , Swaminath Anand , Kopek Neil , Liu Mitchell , Moore Karen , Currie Suzanne , Schlijper Roel , Bauman Glenn S. , Laba Joanna , Qu X. Melody , Warner Andrew , Senan Suresh
Published: June 2020

PURPOSE

The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking.

METHODS

We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of .20 (wherein P < .20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial.

RESULTS

Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P = .001). There were no new grade 2-5 adverse events and no differences in QOL between arms.

CONCLUSION

With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.
Years of Potential Life Lost Because of Breast and Cervical Cancers in Guatemala
Authors: Kihn-Alarcón Alba J. , Alvarado-Muñoz Juan F. , Orozco-Fuentes Loida I. , Calgua-Guerra Erwin , Fuentes-de Falla Vicky , Velarde Angel
Published: June 2020

PURPOSE

Worldwide cervical and breast cancers are among the most commonly diagnosed cancers and are leading cause of cancer deaths among females in low- and middle-income countries. In Guatemala, breast and cervical cancers are the main cause of cancer-related deaths among women. Therefore, the aim of this study was to determine the years of potential life lost (YPLL) as an indicator of premature deaths as a result of breast and cervical cancers.

METHODS

Data on the number of deaths as a result of breast and cervical cancers (International Classification of Diseases [10th revision] codes C50 and C53) between 2012 and 2016 and age composition by quinquennials were retrieved from the Health Information System of the Guatemalan Health Ministry. On the basis of each individual’s age at death, YPLL was estimated for females between 20 and 70 years of age.

RESULTS

A total of 1,476 deaths related to breast and cervical cancers was reported over the study period. The trend in breast cancer mortality rate and YPLL did not change from 2012 to 2016. The cervical cancer mortality rate has decreased to 10 deaths per 1 million habitants ( P = .046). There has been a reduction in YPLL because of cervical cancer, from 50.18 YPLL in 2012 to 29.19 YPLL by 2016, mainly in women between 30 and 34 years of age, in whom YPLL decreased from 600 to 112.50 ( P = .046).

CONCLUSION

Cervical cancer screening has significantly reduced the mortality rate of this malignancy, and screening of breast cancer must include creating awareness of the disease and providing access to women at risk.
Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test
Authors: Elder Charlotte J , Vilela Ruben , Johnson Trevor N , Taylor Rosie N , Kemp E Helen , Keevil Brian G , Cross Alexandra S , Ross Richard J , Wright Neil P
Published: June 2020

Context

The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive.

Objective

To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response.

Design

We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study.

Setting

Adult and children’s clinical research facilities.

Participants

A total of 36 healthy adult males and 24 healthy children.

Intervention

We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 µg or 1 µg SST.

Main Outcome Measures

We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone.

Results

The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (P = 0.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg IV Synacthen (P = 0.17). The repeatability coefficient at 60 minutes was 105 nmol/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults.

Conclusions

Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-µg IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.
Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study
Authors: Basciani Sabrina , Camajani Elisabetta , Contini Savina , Persichetti Agnese , Risi Renata , Bertoldi Loris , Strigari Lidia , Prossomariti Giancarlo , Watanabe Mikiko , Mariani Stefania , Lubrano Carla , Genco Alfredo , Spera Giovanni , Gnessi Lucio
Published: June 2020

Context

We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions.

Subjects and Methods

Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded.

Results

Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein.

Conclusions

VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.
Environmental estrogen exposure disrupts sensory processing and nociceptive plasticity in the cephalopod, Euprymna scolopes
Authors: Bazarini Stephanie N. , Crook Robyn J.
Published: June 2020

Endogenous estrogens affect multiple sensory systems, including those involved in processing noxious and painful stimuli. Extensive evidence demonstrates that estrogenic environmental pollutants have profound, negative effects on growth and reproductive physiology, but there is limited information about how estrogenic pollutants might affect sensory systems known to be modulated by endogenous estrogens. Here, we show that ethinyl estradiol, the most common artificial estrogen found in coastal marine environments, disrupts normal behavioral and neural responses to tissue injury in the sepiolid, Euprymna scolopes (Hawaiian bobtail squid), which inhabits shallow tropical waters close to dense human habitation. Behavioral hypersensitivity and neural plasticity that occur normally after tissue injury were impaired both under chronic estrogen exposure beginning during embryogenesis, or after a single, high dose co-incident with injury. This suggests that these naturally selected responses to injury, which function to protect animals from predation and infection risk, may be impaired by anthropogenic pollution.
Carbonic anhydrases are influenced by the size and symbiont identity of the aggregating sea anemone Anthopleura elegantissima
Authors: Koch Jack Cushman , Verde E. Alan , Weis Virginia M.
Published: June 2020

Carbonic anhydrases (CA; EC 4.2.1.1.) play a vital role in dissolved inorganic carbon (DIC) transport to photosynthetic microalgae residing in symbiotic cnidarians. The temperate sea anemone Anthopleura elegantissima can occur in three symbiotic states: hosting Breviolum muscatinei (brown), Elliptochloris marina (green) or without algal symbionts (aposymbiotic). This provides a basis for A. elegantissima to be a model for detailed studies of the role of CA in DIC transport. This study investigated the effects of symbiosis, body size, and light on CA activity and expression, and suggests that A. elegantissima has a heterotrophy-dominated trophic strategy. We identified putative A. elegantissima CA genes and performed phylogenetic analyses to infer subcellular localization in anemones. We performed experiments on field-collected anemones to compare (1) CA activity and expression from anemones in different symbiotic states, (2) CA activity in brown anemones as a function of size, and (3) CA activity in anemones of different symbiotic states that were exposed to different light intensities. Carbonic anhydrase activity in brown anemones was highest, whereas activity in green and aposymbiotic anemones was low. Several CAs had expression patterns that mirrored activity while another had expression that was inversely correlated to activity suggesting that symbionts may induce different DIC transport pathways. Finally, CA activity was inversely correlated with anemone size. Our results suggest that the observed CA activity and expression patterns are not only affected by symbiosis but also by other factors in the host physiology including trophic strategy as it relates to body size and cellular pH homeostasis.
The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation
Authors: Myers Jonathan N. , Fonda Holly
Published: June 2020

In recent years, a growing body of research has demonstrated that an individual’s fitness level is a strong and independent marker of risk for cardiovascular and all-cause mortality. In addition, modest improvements in fitness through exercise intervention have been associated with considerable health outcome benefits. These studies have generally assessed fitness as a baseline marker in traditional epidemiological cohorts. However, there has been a recent recognition that fitness powerfully predicts outcomes associated with a wide range of surgical interventions. The concept of "prehabilitation" is based on the principle that patients with higher functional capability will better tolerate a surgical intervention, and studies have shown that patients with higher fitness have reduced postoperative complications and demonstrate better functional, psychosocial, and surgery-related outcomes. This review focuses on the impact of fitness on surgical outcomes and provides a rationale in support of routine application of prehabilitation in the management of patients undergoing surgery.
From a Vital Sign to Vitality: Selling Exercise So Patients Want to Buy It
Authors: Segar Michelle L. , Guérin Eva , Phillips Edward , Fortier Michelle
Published: June 2020

Exercise is Medicine® (EIM) and physical activity as a vital sign are based on health-focused research and reflect ideal frames and messages for clinicians. However, they are nonoptimal for patients because they do not address what drives patients’ decision-making and motivation. With the growing national emphasis on patient-centered and value-based care, it is the perfect time for EIM to evolve and advance a second-level consumer-oriented exercise prescription and communication strategy. Through research on decision-making, motivation, consumer behavior, and meaningful goal pursuit, this article features six evidence-based issues to help clinicians make physical activity more relevant and compelling for patients to sustain in ways that concurrently support patient-centered care. Physical activity prescriptions and counseling can evolve to reflect affective and behavioral science and sell exercise so patients want to buy it.
Radical Markets by Eric Posner and E. Glen Weyl: A Review Essay
Authors: Levine David K.
Published: June 2020

At a time when standards of living have improved more than any time in history, this book makes a proposal for radical change. It is based—loosely—on market design principles. The plan for attacking overlapping ownership is reasonably well thought out. Most of the book, however, proposes to use mechanisms designed for a narrow purpose; to attack real or imagined problems that they are ill—suited to solve. I conclude that while market design has a lot to offer when properly applied, the proposals here are not sufficiently well thought out to constitute a serious plan of action.(JEL D44, D47, D72, D82, P14)
Sins of Omission and the Practice of Economics
Authors: Akerlof George A.
Published: June 2020

This paper advances the proposition that economics, as a discipline, gives rewards that favor the “hard” and disfavor the “soft.” Such bias leads economic research to ignore important topics and problems that are difficult to approach in a “hard” way—thereby resulting in “sins of omission.” This paper argues for reexamination of current institutions for publication and promotion in economics—as it also argues for greatly increased tolerance in norms for publication and promotion as one way of alleviating narrow methodological biases. (JEL A11, B40)
Case Report: Primary melanoma of the gastroesophageal junction
Authors: Hussein Agha Yasmine , Parker Nathaniel A. , Alderson Joel
Published: June 2020

Primary malignant melanoma represents the fifth most common cancer in the United States. It is subdivided into two forms: cutaneous (90%), visceral (8%, including ocular and mucosal) and of unknown primary (2%). The vast majority of gastrointestinal melanomas are secondary lesions until proven otherwise. Primary esophageal melanoma in particular is exceedingly rare, less than 200 cases have been documented in the literature to date. It is highly prevalent in Japan and occurs twice as much in men than women around the 6th decade of life. It has a predilection for the middle and lower esophagus, with only 6 cases occurring at the gastroesophageal junction worldwide. Its etiology and pathogenesis are poorly understood, and no curative treatment has been established given the paucity of cases. We present a case of primary melanoma of the gastroesophageal junction which represents the 2nd incident case in the united states and 7th worldwide.
Development of a cell-free split-luciferase biochemical assay as a tool for screening for inhibitors of challenging protein-protein interaction targets
Authors: Cooley Rachel , Kara Neesha , Hui Ning Sze , Tart Jonathan , Roustan Chloë , George Roger , Hancock David C. , Binkowski Brock F. , Wood Keith V. , Ismail Mohamed , Downward Julian
Published: June 2020

Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc ® Binary Technology (NanoBiT ®) was originally developed to detect protein-protein interactions in live mammalian cells. Here we report the successful translation of the NanoBit cellular assay into a biochemical, cell-free format using mammalian cell lysates. We show that the assay is suitable for the detection of both strong and weak protein interactions such as those involving the binding of RAS oncoproteins to either RAF or phosphoinositide 3-kinase (PI3K) effectors respectively, and that it is also effective for the study of poorly soluble protein domains such as the RAS binding domain of PI3K. Furthermore, the RAS interaction assay is sensitive and responds to both strong and weak RAS inhibitors. Our data show that the assay is robust, reproducible, cost-effective, and can be adapted for small and large-scale screening approaches. The NanoBit Biochemical Assay offers an attractive tool for drug screening against challenging protein-protein interaction targets, including the interaction of RAS with PI3K.