bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic body size variation of a tropical anuran: effects of water deficit and precipitation seasonality on Asian common toad from southern Asia
Authors: Guo Cheng , Gao Shuai , Krzton Ali , Zhang Long
Published: November 2019

Background

Two previous studies on interspecific body size variation of anurans found that the key drivers of variation are the species’ lifestyles and the environments that they live in. To examine whether those findings apply at the intraspecific level, we conducted a study of the Asian common toad (Duttaphrynus melanostictus), a terrestrial anuran distributed in tropical regions. The body size of toads from 15 locations, covering the majority of their geographic range, and local environmental data were summarized from published literature. We used a model selection process based on an information-theoretic approach to examine the relationship between toad body size and those environmental parameters.

Results

We found a positive correlation between the body size of the Asian common toad and the water deficit gradient, but no linkage between body size and temperature-related parameters. Furthermore, there was a positive correlation between the seasonality of precipitation and body size of females from different sampled populations.

Conclusions

As a terrestrial anuran, the Asian common toad should experience greater pressure from environmental fluctuations than aquatic species. It is mainly distributed in tropical regions where temperatures are generally warm and stable, but water availability fluctuates. Therefore, while thermal gradients are not strong enough to generate selection pressure on body size, the moisture gradient is strong enough to select for larger size in both males and females in dryer regions. Larger body size supports more efficient water conservation, a pattern in accordance with the prediction that lifestyles of different species and their local habitats determine the relationship between body size and environment. In addition, larger females occur in regions with greater seasonality in precipitation, which may happen because larger females can afford greater reproductive output in a limited reproductive season.
Genome-wide prediction and prioritization of human aging genes by data fusion: a machine learning approach
Authors: Arabfard Masoud , Ohadi Mina , Rezaei Tabar Vahid , Delbari Ahmad , Kavousi Kaveh
Published: November 2019

Background

Machine learning can effectively nominate novel genes for various research purposes in the laboratory. On a genome-wide scale, we implemented multiple databases and algorithms to predict and prioritize the human aging genes (PPHAGE).

Results

We fused data from 11 databases, and used Naïve Bayes classifier and positive unlabeled learning (PUL) methods, NB, Spy, and Rocchio-SVM, to rank human genes in respect with their implication in aging. The PUL methods enabled us to identify a list of negative (non-aging) genes to use alongside the seed (known age-related) genes in the ranking process. Comparison of the PUL algorithms revealed that none of the methods for identifying a negative sample were advantageous over other methods, and their simultaneous use in a form of fusion was critical for obtaining optimal results (PPHAGE is publicly available at https://cbb.ut.ac.ir/pphage).

Conclusion

We predict and prioritize over 3,000 candidate age-related genes in human, based on significant ranking scores. The identified candidate genes are associated with pathways, ontologies, and diseases that are linked to aging, such as cancer and diabetes. Our data offer a platform for future experimental research on the genetic and biological aspects of aging. Additionally, we demonstrate that fusion of PUL methods and data sources can be successfully used for aging and disease candidate gene prioritization.
Molecular and transcriptional characterization of phosphatidyl ethanolamine-binding proteins in wild peanuts Arachis duranensis and Arachis ipaensis
Authors: Jin Hanqi , Tang Xuemin , Xing Mengge , Zhu Hong , Sui Jiongming , Cai Chunmei , Li Shuai
Published: November 2019

Background

Phosphatidyl ethanolamine-binding proteins (PEBPs) are involved in the regulation of plant architecture and flowering time. The functions ofPEBPgenes have been studied in many plant species. However, little is known about the characteristics and expression profiles ofPEBPgenes in wild peanut species,Arachis duranensisandArachis ipaensis,the diploid ancestors of cultivated peanuts.

Results

In this study, genome-wide identification methods were used to identify and characterize a total of 32 peanutPEBPgenes, 16 from each of the two wild peanut species,A. duranensisandA. ipaensis. ThesePEBPgenes were classified into 3 groups (TERMINAL FLOWER1-like,FLOWERING LOCUS T-like, andMOTHER OF FT AND TFL1-like) based on their phylogenetic relationships. The gene structures, motifs, and chromosomal locations for each of thesePEBPswere analyzed. In addition, 4 interchromosomal duplications and 1 tandem duplication were identified inA. duranensis, and 2 interchromosomal paralogs and 1 tandem paralog were identified inA. ipaensis. Ninety-five differentcis-acting elements were identified in thePEBPgene promoter regions and most genes had different numbers and types ofcis-elements. As a result, the transcription patterns of thesePEBPgenes varied in different tissues and under long day and short day conditions during different growth phases, indicating the functional diversities ofPEBPsin different tissues and their potential functions in plant photoperiod dependent developmental pathways. Moreover, our analysis revealed thatAraduF950M/AraduWY2NXinA. duranensis, andAraip344D4/Araip4V81GinA. ipaensisare good candidates for regulating plant architecture, and thatAradu80YRY, AraduYY72S,andAraduEHZ9YinA. duranensisandAraipVEP8TinA. ipaensismay be key factors regulating flowering time.

Conclusion

SixteenPEBPgenes were identified and characterized from each of the two diploid wild peanut genomes,A. duranensisandA. ipaensis. Genetic characterization and spatio-temporal expression analysis support their importance in plant growth and development. These findings further our understanding ofPEBPgene functions in plant species.
Predictors of one-year outcomes in chronic heart failure: the portrait of a middle income country
Authors: Gioli-Pereira Luciana , Marcondes-Braga Fabiana G. , Bernardez-Pereira Sabrina , Bacal Fernando , Fernandes Fábio , Mansur Alfredo J. , Pereira Alexandre C. , Krieger José E.
Published: November 2019

Background

Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge.

We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort.

Methods

We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use.

Results

We screened 2314 consecutive patients for eligibility and enrolled 700 participants.

The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008–1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347–2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969–0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies.

Conclusions

High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample.

Trial registration

Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.
Cascade screening for familial hypercholesterolemia-identification of the C308Y mutation in multiple family members and relatives for the first time in mainland China
Authors: Jin Weirong , Zhang Qiuwang , Wang Bei , Pan Lili , Qin Hongyou , Yang Daying , Zhou Xiangqun , Du Yongcai , Lin Ling , Kutryk Michael J.
Published: November 2019

Background

Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is underdiagnosed and undertreated. The majority of FH cases are caused by low density lipoprotein receptor (LDL-R) gene mutations. The C308Y mutation in LDL-R results in approximately 70% loss of LDL-R activity, leading to the elevation of low density lipoprotein-cholesterol (LDL-C) and an increased risk of premature coronary heart disease (CHD). The aim of this study was to identify FH cases by cascade screening in family members and relatives of a 37-year old male with premature CHD and hypercholesterolemia.

Methods

Clinical exam, blood lipid profiling and genomic DNA sequencing of all exons of LDL-R were performed for the proband and his 14 family members and relatives. FH diagnosis was carried out using the Dutch Lipid Clinic Network (DLCN) criteria.

Results

Lipid profiling showed that 9 individuals, including the proband, had hypercholesterolemia. All these 9 subjects had a G > A substitution at nucleotide 986 in exon 7 resulting in the C308Y mutation as determined by DNA sequencing, and all those carrying the mutation were diagnosed as having definite FH under the DLCN criteria. However, most (7/9) did not have suggestive clinical manifestations of CHD.

Conclusions

The C308Y mutation was discovered in multiple family members and relatives for the first time in mainland China. Cascade screening is key for the confirmatory diagnosis of FH. Our hypothesis that the C308Y is a common variant in the population of Southern China origin warrants further validation by screening for the C308Y mutation in a large population.
Gothenburg Very Early Supported Discharge study (GOTVED): a randomised controlled trial investigating anxiety and overall disability in the first year after stroke
Authors: Rafsten Lena , Danielsson Anna , Nordin Asa , Björkdahl Ann , Lundgren-Nilsson Asa , Larsson Maria E. H. , Sunnerhagen Katharina S.
Published: November 2019

Background and purpose

Early supported discharge (ESD) has been shown to be efficient and safe as part of the stroke care pathway. The best results have been seen with a multidisciplinary team and after mild to moderate stroke. However, how very early supported discharge (VESD) works has not been studied.

The aim of this study was to investigate whether VESD for stroke patients in need of ongoing individualized rehabilitation affects the level of anxiety and overall disability for the patient compared with ordinary discharge routine.

Methods

A randomized controlled trial was performed with intention to treat analyses comparing VESD and ordinary discharge from hospital. All patients admitted at the stroke care unit at Sahlgrenska University Hospital of Gothenburg between August 2011 and April 2016 were screened. Inclusion occurred on day 4 using a block randomization of 20 and with a blinded assessor. Assessments were made 5 days post-stroke and 3 and 12 months post-stroke. Patients in the VESD group underwent continued rehabilitation in their homes with a multidisciplinary team from the stroke care unit for a maximum of 1 month. The patients in the control group had support as usual after discharge when needed such as home care service and outpatient rehabilitation.

The primary outcome was anxiety as assessed by the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). The secondary outcome was the patients’ degree of overall disability, measured by the modified Rankin Scale (mRS).

Results

No significant differences were found between the groups regarding anxiety at three or 12 months post-stroke (p = 0.811). The overall disability was significantly lower in the VESD group 3 months post-stroke (p = 0.004), compared to the control group. However, there was no significant difference between the groups 1 year post-stroke.

Conclusions

The VESD does not affects the level of anxiety compared to ordinary rehabilitation. The VESD leads to a faster improvement of overall disability compared to ordinary rehabilitation. We suggest considering coordinated VESD for patients with mild to moderate stroke in addition to ordinary rehabilitation as part of the service from a stroke unit.

Trial registration

Clinical Trials.gov: NCT01622205. Registered 19 June 2012 (retrospectively registered).
RETRACTED ARTICLE: Bronchial blocker versus double-lumen endobronchial tube in minimally invasive cardiac surgery
Authors: Zhang Chuncheng , Yue Jing , Li Mingyue , Jiang Wei , Pan Yu , Song Zhimin , Shi Cailian , Fan Weixuan , Pan Zhenxiang
Published: November 2019

Background

To compare the therapeutic value of a bronchial blocker (BB) with a double-lumen tube (DLT) in minimally invasive cardiac surgery (MICS).

Methods

Sixty patients who underwent MICS were randomized to use either a DLT (Group D, n = 30) or a BB (Group B, n = 29; one failed was omitted). The following data were collected: time of intubation and tube localization; incidence of tube displacement; postoperative sore throat and hoarseness; time of cardiopulmonary bypass; maintenance time for SpO2 < 90% (PaCO2 < 60 mmHg); mean arterial pressure and heart rate; SpO2, PaO2, PaCO2, EtCO2, mean airway pressure, and airway peak pressure; surgeons’ satisfaction with anesthesia; and short-term complications.

Results

The times of intubation and tube localization were significantly longer in Group B than in Group D (P < 0.05). Patients in Group B exhibited significantly lower incidence of tube displacement, postoperative sore throat, and hoarseness when compared with patients in Group D (P < 0.05). Mean arterial pressure and heart rate were significantly lower in Group B than in Group D after tracheal intubation (P < 0.05). The mean airway pressure and airway peak pressure were significantly lower in Group B than in Group D after one-lung ventilation (P < 0.05). SpO2 and PaO2 in Group B were significantly higher than in group D after cardiopulmonary bypass (P < 0.05). No short-term postoperative complications were observed in patients of Groups B and D during 3 month follow-up.

Conclusion

BB can be a potential alternative to the conventional DLT for lung isolation in MICS. Trial registration: ChiCTR1900024250, July 2, 2019.
What do patients with unmet medical needs want? A qualitative study of patients’ views and experiences with expanded access to unapproved, investigational treatments in the Netherlands
Authors: Bunnik Eline M. , Aarts Nikkie
Published: November 2019

Background

Patients with unmet medical needs sometimes resort to non-standard treatment options, including the use of unapproved, investigational drugs in the context of clinical trials, compassionate use or named-patient programs. The views and experiences of patients with unmet medical needs regarding unapproved, investigational drugs have not yet been examined empirically.

Methods

In this qualitative study, exploratory interviews and focus groups were held with patients with chronic or life-threatening diseases (n = 39), about topics related to non-standard treatment options, such as the search for non-standard treatment options, patients’ views of the moral obligations of doctors, and the conditions under which they would or would not wish to use non-standard treatment options, including expanded access to unapproved, investigational drugs.

Results

Respondents had very little knowledge about and/or experience with existing opportunities for expanded access to investigational drugs, although some respondents were actively looking for non-standard treatment options. They had high expectations of their treating physicians, assuming them to be aware of non-standard treatment options, including clinical trials elsewhere and expanded access programs, and assuming that they would inform their patients about such options. Respondents carefully weighed the risks and potential benefits of pursuing expanded access, citing concerns related to the scientific evidence of the safety and efficacy of the drug, side effects, drug-drug interactions, and the maintaining of good quality of life. Respondents stressed the importance of education and assertiveness to obtain access to good-quality health care, and were willing to pay out of pocket for investigational drugs. Patients expressed concerns about equal access to new and/or non-standard treatment options.

Conclusion

When the end of a standard treatment trajectory comes into view, patients may prefer that treating physicians discuss non-standard treatment options with them, including opportunities for expanded access to unapproved, investigational drugs. Although our respondents had varying levels of understanding of expanded access programs, they seemed capable of making well-considered choices with regard to non-standard treatment options and had realistic expectations with regard to the safety and efficacy of such options. Dutch patients might be less likely to fall prey to false hope than often presumed.
Antiparasitic effect of synthetic aromathecins on Leishmania infantum
Authors: Reguera Rosa M. , Álvarez-Velilla Raquel , Domínguez-Asenjo Bárbara , Gutiérrez-Corbo Camino , Balaña-Fouce Rafael , Cushman Mark , Pérez-Pertejo Yolanda
Published: November 2019

Background

Canine leishmaniasis is a zoonotic disease caused by Leishmania infantum, being the dogs one of the major reservoirs of human visceral leishmaniasis. DNA topology is a consolidated target for drug discovery. In this regard, topoisomerase IB – one of the enzymes controlling DNA topology – has been poisoned by hundreds of compounds that increase DNA fragility and cell death. Aromathecins are novel molecules with a multiheterocyclic ring scaffold that have higher stability than camptothecins.

Results

Aromathecins showed strong activity against both forms of L. infantum parasites, free-living promastigotes and intra-macrophagic amastigotes harbored in ex vivo splenic explant cultures obtained from infected BALB/c mice. However, they prevented the relaxation activity of leishmanial topoisomerase IB weakly, which suggests that the inhibition of topoisomerase IB partially explains the antileishmanial effect of these compounds. The effect of aromathecins was also studied against a strain resistant to camptothecin, and results suggested that the trafficking of these compounds is not through the ABCG6 transporter.

Conclusions

Aromathecins are promising novel compounds against canine leishmaniasis that can circumvent potential resistances based on drug efflux pumps.
Determinants of malaria treatment delay in northwestern zone of Tigray region, Northern Ethiopia, 2018
Authors: Tesfahunegn Afewerki , Zenebe Dawit , Addisu Alefech
Published: November 2019

Background

Globally malaria affects 212 million people and causes 438,000 deaths each year. Ensuring early and timely treatment of malaria is important for preventing and controlling of life-threatening complications and further transmission. Even though malaria treatment is widely available in Ethiopia, 47–84% of patients present after 24 h of onset of first symptoms. This study assessed the determinants of delay for malaria treatment in Tigray, Ethiopia.

Methods

A health facility-based case–control study design in northwestern zone of Tigray was conducted from September 2018 to January 2019. All the study participants enrolled were confirmed malaria patients (by microscopy or rapid diagnostic test) and who sought treatment. Cases were defined as malaria patients who sought treatment after 24 h of the onset of the first symptom and control were those who sought treatment within 24 h onset of symptom. A structured questionnaire was used to collect data on the determinants of malaria treatment delay. Data were entered into EpiInfo 7.0 and exported to SPSS 20.0 for analysis. Binary logistic regression was computed to identify predictors of delay for malaria treatment.

Results

In total 161 cases and 161 controls were identified. Being residents of Tahtay Adyabo district (AOR = 2.84, 95% CI 1.29–6.27), having no formal education (AOR = 2.39, 95% CI 1.09–5.22), the decisions to seek health care being taken by the patient (AOR = 2.38 95% CI 1.09–5.2), the decisions to seek health care being taken by their fathers (AOR = 2.52, 95% CI 1.13–5.62), and having good knowledge about malaria symptoms (AOR = 2.02, 95% CI 1.21–3.39) were found determinants of delay for malaria treatment.

Conclusion

In this study, delays in obtaining treatment for malaria were associated with having no formal education, knowing about the signs and symptoms of malaria, living in Tahtay Adyabo district, and decision-making on seeking malaria treatment. The results suggests having treatment commenced at sites closer to the community and strengthened awareness-raising activity about the importance of early seeking for all with malaria-like symptoms, especially for household heads would contribute to improved treatment and reduced complications from malaria.
Comparing the cost of essential nutrients from different food sources in the American diet using NHANES 2011–2014
Authors: Hess Julie M. , Cifelli Christopher J. , Agarwal Sanjiv , Fulgoni Victor L.
Published: November 2019

Background

One reason that some Americans do not meet nutrient needs from healthy eating patterns is cost. Food cost affects how people eat, and healthy diets tend to be more expensive. Cost is also important for diet sustainability. Sustainable eating patterns must be both nutritionally adequate and affordable. The objective of this study was to compare the cost of obtaining shortfall nutrients from different food groups to help identify cost-effective ways Americans can move towards healthy and sustainable eating patterns.

Methods

This analysis used dietary intake data from the National Health and Nutrition Examination Survey from 2011 to 2012 and 2013–2014 (n = 5876 children 2–18 years and n = 9953 adults 19–99 years). Americans’ nutrient intake from food categories in “What We Eat in America” and the 2015–2020 Dietary Guidelines for Americans was determined using the Food and Nutrient Database for Dietary Studies. Food cost and the cost of nutrients were obtained from Center for Nutrition Promotion and Policy food cost database 2001–2002 and 2003–2004 (adjusted for inflation).

Results

The daily mean cost of food was $4.74 ± 0.06 for children and $6.43 ± 0.06 for adults. “Protein foods” and “mixed dishes” were the two most expensive food categories (43–45% of daily food costs), while “grains,” “fruits,” and “vegetables” combined accounted for ~ 18% of the daily cost, and “milk and dairy” accounted for 6–12% of total daily food costs in both adults and children. “Milk and dairy” were the least expensive dietary sources of calcium and vitamin D in the American diet, while “grains” were the least expensive sources of iron and magnesium, and “protein foods” were the least expensive sources of choline. “Fruits” and “vegetables” were the least expensive sources of potassium and vitamin C, respectively, and “snacks and sweets” were the least expensive sources of vitamin E.

Conclusion

“Milk and dairy” were inexpensive sources of three of the four nutrients of public health concern (calcium, vitamin D, and potassium), while “grains” were the least expensive source of fiber. The results of this work reinforce the importance of consuming a variety of nutrient-rich foods for cost-effective, sustainable eating patterns.
A new combination rule for Spatial Decision Support Systems for epidemiology
Authors: de Lima Luciana Moura Mendes , de Sá Laísa Ribeiro , dos Santos Macambira Ana Flávia Uzeda , de Almeida Nogueira Jordana , de Toledo Vianna Rodrigo Pinheiro , de Moraes Ronei Marcos
Published: November 2019

Background

Decision making in the health area usually involves several factors, options and data. In addition, it should take into account technological, social and spatial aspects, among others. Decision making methodologies need to address this set of information , and there is a small group of them with focus on epidemiological purposes, in particular Spatial Decision Support Systems (SDSS).

Methods

Makes uses a Multiple Criteria Decision Making (MCDM) method as a combining rule of results from a set of SDSS, where each one of them analyzes specific aspects of a complex problem. Specifically, each geo-object of the geographic region is processed, according to its own spatial information, by an SDSS using spatial and non-spatial data, inferential statistics and spatial and spatio-temporal analysis, which are then grouped together by a fuzzy rule-based system that will produce a georeferenced map. This means that, each SDSS provides an initial evaluation for each variable of the problem. The results are combined by the weighted linear combination (WLC) as a criterion in a MCDM problem, producing a final decision map about the priority levels for fight against a disease. In fact, the WLC works as a combining rule for those initial evaluations in a weighted manner, more than a MCDM, i.e., it combines those initial evaluations in order to build the final decision map.

Results

An example of using this new approach with real epidemiological data of tuberculosis in a Brazilian municipality is provided. As a result, the new approach provides a final map with four priority levels: “non-priority”, “non-priority tendency”, “priority tendency” and “priority”, for the fight against diseases.

Conclusion

The new approach may help public managers in the planning and direction of health actions, in the reorganization of public services, especially with regard to their levels of priorities.
Monostotic fibrous dysplasia at C7 treated with vertebroplasty: a case report and review of the literature
Authors: Xin Xin , Feng Jianhong , Yue Chen , Jin Tao , Liu Xinxin
Published: November 2019

Background

Monostotic fibrous dysplasia (MFD) involving the spine is rare, and the treatment options are controversial. Surgery is needed when patients suffer from persistent pain, spinal cord compression/injury, and vertebral collapse/instability. Treatment methods include biopsy/observation, corpectomy with instrumented fusion, posterior fusion, vertebroplasty (VP), curettage and bone graft, and complete removal of the vertebra with a combined anterior and posterior fusion procedure.

Case presentation

The patient was a 56-year-old woman with a 2-year history of neck pain. No obvious abnormalities were detected on neurological or physical examination, and laboratory findings were all within normal limits. An imaging examination suggested a C7 vertebral bone tumor. The patient refused to continue conservative observation treatment and requested surgery. Open VP of the C7 vertebral body was carried out, and her postoperative neck pain was completely relieved. The postoperative pathological results supported the diagnosis of fibrous dysplasia, and the patient was ultimately diagnosed with MFD. At the 12-month follow-up visit, the patient reported no clinical symptoms, and no signs of tumor recurrence were detected.

Conclusion

VP can relieve pain while stabilizing the spine. Thus, the surgical treatment of MFD vertebral lesions by VP is a valuable option.
Successful use of the left portal vein as graft for middle hepatic vein reconstruction in left hemihepatectomy: preliminary experience on six cases
Authors: Lv Tao , Kong Ling Xiang , Yang Jiayin , Wu Hong , Wen Tianfu , Jiang Li , Yang Jian
Published: November 2019

Background

The purpose of this research was to assess the feasibility of reconstructing the middle hepatic vein (MHV) with resected left portal vein during left hemihepatectomy.

Methods

From January 2014 to January 2018, six patients received left hemihepatectomy combined with MHV reconstruction using the resected left portal vein in West China Hospital. We reviewed the clinical data including patient details, surgical technique, graft patency, and operative results.

Results

All six patients underwent left hemihepatectomy for liver tumors located at left hepatocaval confluence. In these patients, MHV was resected due to tumor invading and reconstructed using the resected left portal vein as graft. The mean operating time was 316 min. Two patients developed complications: one experienced bile leakage and one experienced pleural effusion. No patient developed vascular graft complications. All the grafts remained unobstructed, and no local tumor recurrence occurred during the observation period of 13–41 months.

Conclusions

Our results indicated that the left portal vein was a safe graft for hepatic vein reconstruction. In addition, left hemihepatectomy combined with middle hepatic vein resection and reconstruction using the left portal vein can be performed safely to treat liver tumors located at hepatocaval confluence.
Higher glycolytic capacities in muscle of carnivorous rainbow trout juveniles after high dietary carbohydrate stimulus at first feeding
Authors: Song Yan , Alami-Durante Hélène , Skiba-Cassy Sandrine , Marandel Lucie , Panserat Stephane
Published: November 2019

Background

Rainbow trout is a “glucose-intolerant” carnivorous species. Using the metabolic programming strategy, we used early nutritional stimuli in order to modify carbohydrate utilization in trout juveniles.

Method

Fish were fed two diets during the first feeding, namely HP (no carbohydrate / high protein) diet and LP (high carbohydrate / low protein) diet. HP diet was used as the control diet and LP diet as an early stimulus diet. We also used another early stimulus with fish fed HP diet every other day during the first feeding (HP restriction feeding - HPR). After the first-feeding stage (4 weeks), all fish were subsequently subjected to a growth trial with a commercial diet followed by a challenge test with the LP diet (11 weeks). At the end of the first feeding stimulus and of the challenge test, we investigated growth performance, glucose metabolism-related parameters and global DNA CmCGG methylation in trout.

Results

LP and HPR dietary stimuli have been a success as shown by the direct modifications of growth performance and mRNA levels for glucose metabolism-related genes at the end of first feeding compared to alevins fed the HP diet. At the end of the challenge trial, no variation in growth performance and hepatic metabolism of LP-history and HPR-history in trout juveniles were observed. However, in muscle of trout juvenile subjected to LP diet at the first feeding, we found an up-regulation of mRNA levels of some glucose metabolism (glucose transport and glycolysis)-related genes and an increase of activities of important glycolysis-related enzymes (hexokinase, phosphofructokinase and pyruvate kinase). These observations are associated with a decrease in the content of glycogen compared to fish fed the HP diet. Moreover, global CmCGG DNA methylation in the muscle of fish with LP history was significantly lower than those fed the HP diet.

Conclusion

Dietary LP stimulus at first feeding could permanently modify glucose metabolism and global CmCGG DNA methylation level in muscle of trout juveniles, showing that the first feeding stage is efficient for programming the glucose metabolism in fish.
The prognosis benefits of adjuvant versus salvage radiotherapy for patients after radical prostatectomy with adverse pathological features: a systematic review and meta-analysis
Authors: Tao Ronggui , Dai Jindong , Bai Yunjin , Yang Jiyu , Sun Guangxi , Zhang Xingming , Zhao Jinge , Zeng Hao , Shen Pengfei
Published: November 2019

Background

The appropriate timing of radiotherapy (RT) for patients after radical prostatectomy (RP) with adverse pathological features (APFs) remains controversial. This systematic review was conducted to compare the efficacy of adjuvant radiotherapy (ART) and salvage radiotherapy (SRT).

Methods

PubMed, EMBASE, Web of Science and the Cochrane Library electronic databases were searched to retrieve the required. The hazard ratio (HR) and corresponding 95% confidence interval (CI) of overall survival (OS), biochemical recurrence-free survival (BRFS) and distant metastases-free survival (DMFS) were extracted. The survival benefits of ART with SRT (including early salvage radiotherapy (ESRT)) were analyzed. The process of the meta-analysis was performed with RevMan version 5.3.

Results

A total of fifteen retrospective studies were finally included in the final analysis including 5586 patients. The pooled analysis indicated that ART could achieve better control of prostate cancer and improve OS (p = 0.0006), BRFS (p < 0.0001) and DMFS (p < 0.0001), when compared to SRT. The subgroup analysis of the 5-year OS rate demonstrated that the ART group still had survival advantages compared to the SRT group (p = 0.0006). However, ART and SRT were comparable in 10-year OS rate (p = 0.07). ART had advantages over SRT in both 5-year (p = 0.0003) and 10-year BRFS (p = 0.0003). The subgroup analysis with different follow-up starting points from RP or RT was essentially consistent with the above results. The pooled analysis also showed that ART was superior to ESRT on OS (p = 0.008) and DMFS (p = 0.03), and comparable to ESRT on BRFS (p = 0.1).

Conclusions

According to this meta-analysis, ART could be served as a preferential treatment for patients with APFs after RP to improve prognosis. Certainly, high-quality, multicenter randomized controlled trials (RCTs) are expecting to confirm the outcomes of our meta-analysis in the future.
A two-stage retrospective analysis to determine the effect of entry point on higher exit of proximal pins in lateral pinning of supracondylar humerus fracture in children
Authors: Ji Xianglu , Kamara Allieu , Wang Enbo , Liu Tianjing , Shi Liwei , Li Lianyong
Published: November 2019

Background

Kirschner wire fixation remains to be the mainstream treatment modality in unstable or displaced supracondylar humerus fracture in children, with divergent lateral pins being the most preferred due to their sufficient stability and decreased risk of ulnar nerve injury. However, the entry point at which the proximal lateral pin can be inserted to achieve a more proximal exit and maximum divergence has not been reported. This study retrospectively analyzed the characteristics and factors influencing the entry and exit points of the proximal lateral pins.

Methods

The study was divided into two stages. In stage one, the entry and exit points of the proximal pins of lateral pinning configuration were analyzed from intra-operative radiographs of children treated for extension-type supracondylar humerus fractures. The coronal and sagittal pin angles formed by the proximal pins were also measured. Using the findings of stage one, we intentionally tried to achieve a more proximal exit with the proximal pins in stage two. Comparisons between groups of patients treated by random and intentional pinnings were done statistically.

Results

In the first stage, 47 (29.2%) of the 161 proximal pins exited above the metaphyseal-diaphyseal junction (MDJ) region. Of these, 85.1% entered from lateral and posterior to the ossific nucleus of the capitellum (ONC). The pin angles averaged 58.4° and 90.5° in the coronal and sagittal planes respectively. In the second stage, 47 (65.3%) proximal pins in the intended group exited above the MDJ region, while only 32 (36%) in the random group exited above the MDJ region.

Conclusion

While aiming at the upper border of the distal MDJ during pinning, lateral pins can easily achieve a higher, proximal exit above the MDJ if inserted from lateral and posterior to the ONC and parallel to the humeral shaft in the sagittal plane. Higher exit can also be easily achieved in younger patients and patients fixated with smaller diameter pins.
Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway
Authors: Wang Yiwei , Zhao Minghui , He Sijia , Luo Yuntao , Zhao Yucui , Cheng Jin , Gong Yanping , Xie Jianzhu , Wang Yulan , Hu Binjie , Tian Ling , Liu Xinjian , Li Chuanyuan , Huang Qian
Published: November 2019

Background

Tumor cell repopulation after radiotherapy is a major cause for the tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of tumor repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process.

Methods

Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo tumor repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal tumor specimens to verify the relationship with clinical outcome.

Results

Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated tumor cells on living tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced tumor repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients.

Conclusions

Necroptosis associated tumor repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of tumor radioresistance and repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking tumor repopulation to enhance the efficacy of colorectal cancer radiotherapy.
Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016–2017 epidemic season: a systematic review of seven Italian reports
Authors: Cutrera Renato , Wolfler Andrea , Picone Simonetta , Rossi Giovanni A. , Gualberti Giuliana , Merolla Rocco , Del Vecchio Antonio , Villani Alberto , Midulla Fabio , Dotta Andrea
Published: November 2019

Background

The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016–2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis.

Methods

Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29–36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016–2017, versus 2 seasons before (2014–2015 and 2015–2016) and one season after (2017–2018) the AIFA limitation.

Results

During the 2016–2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016–2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk.

Conclusions

The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29–36 wGA) infants aged < 6 months at the beginning of the RSV season.
Effects of a swallowing and oral care intervention for patients following endotracheal extubation: a pre- and post-intervention study
Authors: Wu Chung-Pei , Xu Yu-Juan , Wang Tyng-Guey , Ku Shih-Chi , Chan Ding-Cheng , Lee Jang-Jaer , Wei Yu-Chung , Hsiao Tzu-Yu , Chen Cheryl Chia-Hui
Published: November 2019

Background

For patients who survive a critical illness and have their oral endotracheal tube removed, dysphagia is highly prevalent, and without intervention, it may persist far beyond hospital discharge. This pre- and post-intervention study with historical controls tested the effects of a swallowing and oral care (SOC) intervention on patients’ time to resume oral intake and salivary flow following endotracheal extubation.

Methods

The sample comprised intensive care unit patients (≥ 50 years) successfully extubated after ≥ 48 h endotracheal intubation. Participants who received usual care (controls, n = 117) were recruited before 2015, and those who received usual care plus the intervention (n = 54) were enrolled after 2015. After extubation, all participants were assessed by a blinded nurse for daily intake status (21 days) and whole-mouth unstimulated salivary flow (2, 7, 14 days). The intervention group received the nurse-administered SOC intervention, comprising toothbrushing/salivary gland massage, oral motor exercise, and safe-swallowing education daily for 14 days or until hospital discharge.

Results

The intervention group received 8.3 ± 4.2 days of SOC intervention, taking 15.4 min daily with no reported adverse event (coughing, wet voice, or decreased oxygen saturation) during and immediately after intervention. Participants who received the intervention were significantly more likely than controls to resume total oral intake after extubation (aHR 1.77, 95% CI 1.08–2.91). Stratified by age group, older participants (≥ 65 years) in the SOC group were 2.47-fold more likely than their younger counterparts to resume total oral intake (aHR 2.47, 95% CI 1.31–4.67). The SOC group also had significantly higher salivary flows 14 days following extubation (β = 0.67, 95% CI 0.29–1.06).

Conclusions

The nurse-administered SOC is safe and effective, with greater odds of patients’ resuming total oral intake and increased salivary flows 14 days following endotracheal extubation. Age matters with SOC; it more effectively helped participants ≥ 65 years old resume total oral intake postextubation.

Trial registration

NCT02334774, registered on January 08, 2015
Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas
Authors: Yorita Kenji , Ohno Akinobu , Nishida Takahiro , Kondo Kazuhiro , Ohtomo Toshihiko , Kataoka Hiroaki
Published: November 2019

Objective

We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC to improve our understanding of aggressive HCC phenotypes. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses.

Results

The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.
Two-step genomic sequence comparison strategy to design Trichoderma strain-specific primers for quantitative PCR
Authors: Zhang Yang , Wang Xiang , Pang Guan , Cai Feng , Zhang Jian , Shen Zongzhuan , Li Rong , Shen Qirong
Published: November 2019

Survival of inoculated fungal strains in a new environment plays a critical role in functional performance, but few studies have focused on strain-specific quantitative PCR (qPCR) methods for monitoring beneficial fungi. In this study, theTrichoderma guizhouensestrain NJAU 4742 (transformed with thegfpgene and namedgfp-NJAU 4742), which exhibits a growth-promoting effect by means of phytohormone production and pathogen antagonism, was selected as a model to design strain-specific primer pairs using two steps of genomic sequence comparison to detect its abundance in soil. After a second comparison with the closely related speciesT. harzianumCBS 226-95 to further differentiate the strain-specific fragments that had shown no homology to any sequence deposited in the databases used in the first comparison, ten primer pairs were designed from the whole genome. Meanwhile, 3 primer pairs, P11, P12 and P13, were also designed from the inserted fragment containing thegfpgene. After verification testing with three types of field soils, primer pairs P6, P7 and P8 were further selected by comparison with P11, P12 and P13. A practical test using a pot experiment showed that stable colonization ofgfp-NJAU 4742 in pepper rhizosphere soil could be detected using primer pairs P6 and P7, showing no significant difference from the results of primers P11 and P12. Hence, the strategy described here for designing fungal-strain-specific primers may theoretically be used for any other fungi for which the whole genome sequence is available in a database, and the qPCR methodology developed can also be used to further monitor the population dynamics of different strains based on the designed primers.