bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell transcriptional profiling reveals the heterogenicity in colorectal cancer
Authors: Dai Weier , Zhou Fangbin , Tang Donge , Lin Liewen , Zou Chang , Tan Wenyong , Dai Yong
Published: August 2019

Background:

Colorectal Cancer (CRC) is a highly heterogeneous disease. RNA profiles of bulk tumors have enabled transcriptional classification of CRC. However, such ways of sequencing can only target a cell colony and obscure the signatures of distinct cell populations. Alternatively, single-cell RNA sequencing (scRNA-seq), which can provide unbiased analysis of all cell types, opens the possibility to map cellular heterogeneity of CRC unbiasedly.

Methods:

In this study, we utilized scRNA-seq to profile cells from cancer tissue of a CRC patient. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of genes within the clusters.

Results and Conclusion:

The 2824 cells were analyzed and categorized into 5 distinct clusters by scRNA-seq. For every cluster, specific cell markers can be applied, indicating each 1 of them different from another. We discovered that the tumor of CRC displayed a clear sign of heterogenicity, while genes within each cluster serve different functions. GO term analysis also stated that different cluster's relatedness towards the tumor of CRC differs. Three clusters participate in peripheral works in cells, including, energy transport, extracellular matrix generation, etc; Genes in other 2 clusters participate more in immunology processes. Lastly, trajectory plot analysis also supports the viewpoint, in that some clusters present in different states and pseudo-time, while others present in a single state or pseudo time. Our analysis provides more insight into the heterogeneity of CRC, which can provide assistance to further researches on this topic.
Influence of hypercholesterolemia and diabetes on long-term outcome in patients with stable coronary artery disease receiving percutaneous coronary intervention
Authors: Lin Mao-Jen , Chang Yu-Jun , Chen Chun-Yu , Huang Chia-Chen , Chuang Tzu-Yao , Wu Han-Ping
Published: August 2019

Coronary artery disease (CAD) is a life-threatening medical emergency which needs urgent medical attention. Percutaneous coronary intervention (PCI) is common and necessary for patients with CAD. The effect of hypercholesterolemia and diabetes on long-term outcomes in patients with stable CAD receiving PCI is unclear.

In this study, patients with stable CAD who underwent PCI were prospectively divided into 4 groups according to the presence or absence of diabetes or hypercholesterolemia. Clinical characteristics, risk factors, medications, angiographic findings, and outcome predictors were analyzed and long-term outcomes compared between groups.

Of the 1676 patients studied, those with hypercholesterolemia and diabetes had the highest all-cause mortality rate after PCI (P < .01); those with diabetes only had the highest cardiovascular (CV) mortality (P < .01). However, the 4 groups did not differ in rates of myocardial infarction (MI) or repeated PCI. In Kaplan–Meier survival analysis, patients with diabetes only had the highest rates of all-cause mortality and CV mortality (both P < .001). In the Cox proportional hazard model, patients with both hypercholesterolemia and diabetes had the highest risk of all-cause mortality (hazard ratio: 1.70), but groups did not differ in rates of MI, CV mortality, and repeated PCI.

With or without hypercholesterolemia, diabetes adversely impacts long-term outcomes in patients receiving PCI. Diabetes mellitus seemed to be a more hazardous outcome predictor than hypercholesterolemia. Hypercholesterolemia and diabetes seemed to have an additive effect on all-cause mortality in patients after receiving PCI.
Impaired heart rate recovery as a predictor for poor health-related quality in patients with transient ischemic attack
Authors: Li Xuanmin , Wang Yafang , Mi Xue , Qiao Zhaona , Liang Yongmei
Published: August 2019

We aimed to investigate heart rate recovery (HRR) in patients with transient ischemic attack (TIA) and the relationship between HRR and health-related quality of life (HRQOL).

All available patients were enrolled during the enrollment period. A total of 120 patients with TIA and 120 healthy controls were included in this study. A treadmill stress test was performed to calculate the HRR. The HRR were calculated as follows: HRR 1, 2, 3, and 5 minutes = heart rate at peak during exercise − heart rate at 1, 2, 3, and 5 minutes at rest. All patients enrolled were asked to fill in the Short Form 36 Health Survey to calculate HRQOL.

We found that the maximum heart rate of TIA patients was significantly higher than that of healthy controls (166 ± 11 vs. 162 ± 14 beats/min, P = .015). Similarly, maximum systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in TIA group compared with healthy control group (SBP: 172 ± 15 vs. 165 ± 14 mm Hg, P < .001; DBP: 102 ± 12 vs. 93 ± 16 mm Hg, P < .001). The HRR were significantly lower in TIA group compared with control group (TIA vs. controls, HRR1: 17 ± 7 vs. 30 ± 8 beats/min, HRR2: 32 ± 11 vs. 49 ± 9 beats/min, HRR3: 43 ± 13 vs. 63 ± 12 beats/min, HRR5: 54 ± 16 vs. 73 ± 15 beats/min, all P < .001). Multivariate analysis showed that older age (P = .03) and high BMI (P = .04) were risk factors associated with abnormal HRR in patients with TIA. With regard to HRQOL, we found that role limitations due to physical problems, general health, vitality, and role limitations due to emotional problems were significantly lower in patients with abnormal HRR compared with patients with normal HRR. Multivariate analysis showed that older age (P = .04) and abnormal HRR (P = .03) were predictors for poor HRQOL in TIA patients.

HRR was impaired in patients with TIA. In addition, TIA patients with abnormal HRR suffered from a significantly poorer HRQOL. Hence, given the prognostic value of HRR, patients with TIA should be monitored to prevent cardiovascular events and to improve HRQOL.
Laparoscopic spleen-preserving distal versus central pancreatectomy for tumors in the pancreatic neck and proximal body
Authors: Zhang Hao , Xu Qiaoyu , Tan Chunlu , Wang Xing , Peng Bing , Liu Xubao , Li Kezhou
Published: August 2019

For benign and borderline tumors in the pancreatic neck and proximal body, laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and laparoscopic central pancreatectomy (LCP) are alternative surgical procedures. Choosing between LSPDP and LCP is difficult. This retrospective cohort study was looking forward to provide evidence for clinical decision.

A total of 59 patients undergoing LSPDP (Kimura procedure) and LCP between June 2013 and March 2017 were selected. The clinical outcomes of patients were compared by χ
2 test or Fisher exact test and Student t test.

This study included 36 patients in LSPDP group, and 23 patients in LCP group. The overall complications incidence in LCP group was significantly higher than LSPDP group (35 vs 6%, P = .004), and the postoperative pancreatic fistula (POPF) (grade B and C) rate and abdominal infection rate in LCP group were still significantly higher than LSPDP group (POPF 22 vs 3%, P = .019; abdominal infection 35 vs 3%, P = .001, respectively). The length of resected pancreas was significantly longer in LSPDP group (9.8 ± 2.0 vs 5.3 ± 1.1 cm, P = .007). The median follow-up was 39 months (range 12–57 months). No patient was confronted by tumor recurrence. The proportion of postoperative pancreatin and insulin treatment in LCP group were similar to LSPDP group (9 vs 17%, P = .383; 0 vs 3%, P = 1.000, respectively).

For patients with poor general condition, the safety of LCP needs to be taken seriously; in some ways, LSPDP may be more secure, physiological, and easier operation for tumor located in pancreatic neck and proximal body.
Zusanli (ST36) acupoint injection for acute diarrhea in children under 5 years old
Authors: Tian Yuan , Hu Hengchang , Zhang Yuan , Zhou Linyue , Wang Lizhen , Xie Chunguang
Published: August 2019

Background:

Acute diarrhea is the 2nd highest prevalence disease among children under 5 years of age. It can cause malnutrition and even death in children, especially in developing country. Traditional Chinese medicine therapy has been applied and already in the guidelines for clinical practice of acute infectious diarrhea in children in China, but there is no specific methods or recommendations due to lacking of evidence. Zusanli acupoint injection as a form of acupuncture therapy, which is proved to be effective in randomised controlled trials (RCTs) and very suitable for children, has been used in acute diarrhea in children for a long time; therefore, a systematic review is necessary to provide available evidence for further study.

Methods:

Different studies from various databases will be involved in this study. Only RCTs of children under 5 years of age diagnosed with acute diarrhea using any recognized diagnostic criteria will be included. We will search manually the literature in the databases from China Conference Paper Database. Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet, WanFang, Chongqing VIP, and China Biomedical Literature CDROM Database. Primary outcomes: clinical cure rate (clinical cure is defined as the frequency, timing and character of stool back to normal status, as well as disappearance of diarrhea symptoms), diarrhea duration (from admission to the cessation of diarrhea). Secondary outcomes: stool frequency within 24 hours, rate of adverse effect. Data will be extracted by 2 researchers independently; risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0.

Results:

This study will synthesize and provide evidence based on the data of the currently published zusanli (ST36) acupoint injection for acute diarrhea in children under 5 years old, especially in terms of clinical efficacy and safety.

Conclusion:

This systematic review aims to evaluate the benefits and harms of zusanli acupoint injection for acute diarrhea in children under 5 years old reported in RCTs, and provide evidence reference in TCM field for Chinese guidelines on the treatment of acute diarrhea in children.

Ethics and dissemination:

This study is a systematic review; the outcomes are based on the published evidence, and hence examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.

PROSPERO registration number:

PROSPERO 2019 CRD42019135275.
The impact of teaching status on trauma center clinical outcomes in the United States
Authors: Elkbuli Adel , Dowd Brianna , Flores Rudy , Boneva Dessy , McKenney Mark
Published: August 2019

Teaching status/academic ranking may play a role in the variations in trauma center (TC) outcomes. Our study aimed to determine the relationship between TC teaching status and injury-adjusted, all-cause mortality in a national sampling.

Retrospective review of the National Sample Program (NSP) from the National Trauma Data bank (NTDB). TCs were categorized based on teaching status. Adjusted mortality was determined by observed/expected (O/E) mortality ratios, derived using TRauma Injury Severity Score methodology from the Injury Severity Score and Revised Trauma Score. Chi-square and t test analyses were utilized with a statistical significance defined as P <.05.

Of the 94 TCs in the NSP, 46 were university, 38 were community teaching, and 10 were community nonteaching. For the University TCs, 62.8% were American College of Surgeons (ACS) level 1 and 81.2% state level 1. Of the community teaching TCs, 39.0% was ACS level 1 and 35.1% was state level 1. Of the community nonteaching TCs, 0% was ACS level 1 and 11.1% was state level 1. University TCs had a significantly higher O/E mortality rate than community teaching (0.75 vs 0.71; P = .04). There were no differences in O/E between community teaching and nonteaching TCs (0.71 vs 0.70; P = .70).

Community teaching and nonteaching TCs have lower injury-adjusted, all-cause mortality rates than University Centers. Future studies should further investigate key differences between University TCs and community teaching TC to evaluate possible quality and performance improvement measures.
Clinical trial to evaluate the efficacy of botulinum toxin type A injection for reducing scars in patients with forehead laceration
Authors: Kim Seong Hwan , Lee Seong Joo , Lee Jun Won , Jeong Hii Sun , Suh In Suck
Published: August 2019

Background:

Botulinum toxin type A (BoNTA) is known to prevent fibroblast proliferation and expression of transforming growth factor beta 1 (TGF-β1). It also induces temporary muscle paralysis and decreases tension vectors. Fibroblasts induce scar contracture and hypertrophy by producing collagen fibers in wound healing processes. The aim of this study is to identify the effect of BoNTA on the scar formation.

Methods:

Forty-five patients with forehead laceration were enrolled in this study and randomized into 2 groups with or without injection of BoNTA. When the patients presented to the clinic to remove the stitches, BoNTA was injected to the BoNTA group with 24 patients and saline was injected to the control group with 21 patients. The BoNTA was injected on dermal layer with 5 IU/cm. After that, follow-up was done in 1, 3, and 6 months. The scars were analyzed with the patient and observer scar assessment scale, Stony Brook scar evaluation scales (SBSESs), and visual analog scale (VAS) and analyzed with independent T-test, along with clinical photographs, cutometer, and biopsies.

Results:

In all scar scales, the scores changed into favorable direction in both groups and the changes were larger in BoNTA group compared with the control group. On SBSES and VAS, better improvements on BoNTA group showed statistical significance. Skin biopsy showed less collagen deposition on dermal layer in BoNTA group.

Conclusion:

Improvement of aesthetic, functional, and emotional aspect of the scar formation in the groups treated with BoNTA was illustrated. The application of BoNTA may be expanded to prevent hypertrophic scar after trauma, burns, or operations.
Efficacy of Juglandis semen complex extract for knee osteoarthritis
Authors: Kong Hae Jin , Kang Jae Hui
Published: August 2019

Background:

Knee osteoarthritis (KOA) is a common disease in elderly individuals. Many medications for KOA have the potential to cause side effects. We used Juglandis semen complex extract (JCE) consisting of 4 herbs derived from Cheong-A-Won, which has been commonly used for KOA treatment. In this study, we will evaluate whether JCE improves symptoms in patients with KOA and will identify the changes in the inflammation factor.

Methods:

This study will be a single-center, randomized, double-blind, and placebo-controlled trial. Three groups, JCE 1000 mg, 2000 mg, and placebo, will be randomly allocated. Total duration of the clinical trial will be 12 to 14 weeks. Study participants will be followed up every 6 weeks and the effect and safety will be assessed at the 2nd, 3rd, and 4th visit. All participants were asked to maintain a dosage schedule for this protocol. The primary outcomes will be measured using Korean Western Ontario and McMaster Universities Questionnaire and the secondary outcomes will include pain Visual analog scale score, EuroQol Five Dimensions questionnaire, Patient Global Impression of Change, and the changes in the laboratory test parameters of inflammation. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set.

Discussion:

This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to assess the efficacy and safety of JCE in patients with KOA. This study provides insights into the mechanisms that explain the therapeutic effects of JCE in KOA and will lay the groundwork for further studies.
Efficacy and safety of Chinese medicines for asthma
Authors: Shi Qi , Si Dongxu , Bao Haipeng , Yan Yue , Kong Yanhua , Li Chunlei , He Wenfeng , Damchaaperenlei Dashzeveg , Yu Mingxia , Li Youlin
Published: August 2019

Background:

Asthma is a complex disease associated with many factors such as immunologic, environmental, genetic, and other factors. Common medicines used to treat asthma include β-agonist and glucocorticoid. However, in the long-term treatment, the effect of the above-mentioned drugs is not satisfactory, so many patients choose oral Chinese medicines instead of western medicines. The introduction of Chinese medicines therapies, a rapid proliferation of the literature on management of asthma in general, call for novel ways of evidence synthesis in this area. This systematic review is to systematically summarize and evaluate a large number of evidences for Chinese herbal interventions for asthma. Evaluate the efficacy and safety of Chinese medicines in the treatment of asthma and inform a decision aid for the clinical encounter between patients and clinicians. In addition, it helps to establish a future research agenda.

Methods:

Five English databases (PubMed, Web of science, EBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wanfang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to the present. The literature screening, data extraction, and quality assessment will be conducted by 2 researchers independently. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. Asthma control test symptom score will be assessed as the primary outcome. The curative effect of single symptom and sign; Withdrawal and reduction of western medicines in a course of treatment, including: time, type, and quantity; Maintenance of western medicines after the course of treatment, including: type, quantity; Asthma Quality of Life Questionnaire; laboratory efficacy indexes as the secondary outcome. General physical examination; routine examination of blood, urine, and stool; electrocardiogram; liver and kidney function examination; possible adverse reactions and related detection indicators as the security indexes. Meta-analysis will be performed using RevMan5.3.5 software provided by the Cochrane Collaboration.

Results:

This study will provide high-quality synthesis based on current evidence of Chinese medicines treatment for asthma in several aspects, including asthma control score, side effects and laboratory examination such as lung-function test, serum total immunoglobulin, and so on.

Conclusion:

The results of this study will provide updated evidence for whether Chinese medicines is an effective and safe intervention for asthma.

PROSPERO registration number:

PROSPERO CRD42019136074.
Effect of auriculotherapy and intervention types on weight control
Authors: Yao Junpeng , Chen Liping , Zhang Leixiao , Zhou Siyuan , Zheng Qianhua , Feng Xiumei , You Xi , Zhang Lin , Li Ying
Published: August 2019

Background:

Overweight and obesity characterized by abnormal or excessive fat accumulation, can cause many complications. Auriculotherapy, as the traditional Chinese technique, is widely applied in clinical trials for the management of body weight. The program aims to evaluate the effect and safety of auriculotherapy therapy and intervention types on weight control.

Methods:

All randomized controlled trials related to auriculotherapy targeting overweight and obesity will be searched in online databases, such as Medline, EMbase, Cochrane Central Register of Controlled Trials, AMED, CBM, Wanfang Data, and other databases from their inception to July 2019. The primary outcome is the difference in BMI from baseline to the end of studies. Secondary outcomes include the change of weight, percentage of body fat, waist circumference, serum lipid before and after treatment. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 reviewers. Comprehensive Meta-Analysis software (Version 3; Biostat Inc.) will be used for data synthesis.

Results:

This study will provide a comprehensive review of the available evidence for the treatment of obesity with auriculotherapy.

Conclusion:

The conclusion of this study will provide evidence to judge whether auriculotherapy is an effective therapeutic intervention for obesity.

PROSPERO registration number:

CRD42019136827.
The clinical effects of antibiotic prophylaxis for hysteroscopic procedures
Authors: Guo Tao , Zeng Ni , Yang Jian , Wu Ping , Liu Pengpeng , Liu Zhisu , Cao Jun
Published: August 2019

Background:

Hysteroscopic procedures were widely applied but the clinical effects of antibiotic prophylaxis for these operations were not specifically addressed. In current study, we aimed to investigate the role of prophylactic antibiotics in hysteroscopic procedures by meta-analysis.

Methods:

We conducted literature retrieval in electronic databases, including MEDLINE, EMBASE, and Cochrane Central, to identify relevant randomized controlled trials (RCTs) investigating the clinical effects of antibiotic prophylaxis for hysteroscopic procedures. The postoperative infection rate was selected for pooled estimation. The I
2 index statistic was used to assess heterogeneity. Publication bias was evaluated using funnel plots and Egger test. Sensitivity analysis based on different subcategories was conducted to examine the stability of the main results.

Results:

Four RCTs including 2221 patients were identified for the final quantitative analysis. Pooled estimation indicated no significant difference in infection rate between the antibiotic prophylaxis group and control group (test for OR: Z = 0.50, P = .616; 95% CI: 0.987–1.008). Sensitivity analysis based on surgical procedure, antibiotic application, follow-up time and administration time revealed similar results.

Conclusion:

Based on current objective evidence, we conclude that antibiotic prophylaxis exhibits no clinical benefit for hysteroscopic procedures. Therefore, it is not recommended. Meanwhile, more high-quality RCTs are needed to support our conclusion.
Prognosis of synchronous colorectal carcinoma compared to solitary colorectal carcinoma: a matched pair analysis
Authors: He Wanbin , Zheng Chengjun , Wang Yonghong , Dan Jie , Zhu Mingjie , Wei Mingtian , Wang Jian , Wang Ziqiang
Published: August 2019

Background

Synchronous colorectal carcinoma (CRC) is a specific and rare type of colorectal malignancy. The data on the impact of synchronous CRC are controversial. This study aimed to compare the characteristics and prognosis between synchronous CRC and solitary CRC.

Patients and methods

252 patients who underwent surgery between October 2009 and June 2013 with synchronous CRC (n = 126) or solitary CRC (n = 126) were included. The patients were matched according to age, sex, American Society of Anesthesiologists score, BMI, cancer grade, tumor location, and tumor stage. The short-term outcomes included the length of hospital stay, complications, and 30-day mortality. Long-term endpoints were overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS).

Results

The median follow-up duration for all patients were 42.5 months. The incidence of synchronous CRC was high than in older and male patients as well as in mucinous adenocarcinoma containing signet-ring cell carcinoma, tumor deposit, and polypus. The length of hospital stay after surgery was longer for synchronous CRC than solitary CRC (median: 10 vs. 4 days, P = 0.033). In multivariate analysis, synchronous CRC was an independent prognostic factor associated with poor OS (hazard ratio: 2.355, 95% confidence interval: 1.322–4.195, P = 0.004), DFS (hazard ratio: 2.079, 95% confidence interval: 1.261–3.429, P = 0.004), and CSS (hazard ratio: 2.429, 95% confidence interval: 1.313–4.493, P = 0.005).

Conclusion

The clinical and pathological features exhibit differences between synchronous CRC and solitary CRC and the prognosis of patients with synchronous CRC was poorer than those with solitary CRC.
Nanofat Cell Aggregates: A Nearly Constitutive Stromal Cell Inoculum for Regenerative Site-Specific Therapies
Authors: Sesé Borja , Sanmartín Javier M. , Ortega Bernat , Matas-Palau Aina , Llull Ramon
Published: August 2019

Background:

Recent technology developed by Tulip Medical Products allows clinicians to mechanically disaggregate fat tissue into small fat particles known as nanofat. The present study aimed to evaluate the cell yield obtained from nanofat generation in comparison to traditional methods involving enzymatic dissociation (stromal vascular fraction).

Methods:

Nanofat preparations were characterized by cell content and viability, based on DNA quantification and image cytometry, respectively. DNA analysis was also used to determine the cell content in unprocessed dry lipoaspirate and native adipose tissue (excised adipose tissue). To evaluate cell yield, the authors compared the number of cells recovered from 1 g of lipoaspirate between stromal vascular fraction and nanofat preparations, and subsequently determined the final cell inoculum obtained following their respective protocols.

Results:

The data showed that nanofat samples presented a cell burden of 7.3 million cells/g, close to 80 percent of unprocessed dry lipoaspirate, and 70 percent of native excised adipose tissue. Moreover, cell viability was not altered by mechanical disaggregation in nanofat samples compared to unprocessed dry lipoaspirate. Nanofat samples exhibited a cell yield of 6.63 million cells/g lipoaspirate, whereas stromal vascular fraction preparations resulted in only 0.68 million cells/g lipoaspirate. The final cell inoculum obtained from stromal vascular fraction isolation was 120 million cells and it required 200 to 250 cc of raw lipoaspirate as starting material, whereas nanofat preparation resulted in 125 million cells with only 20 cc of raw lipoaspirate.

Conclusion:

Mechanical disaggregation offers a better cell inoculum than conventional enzymatic dissociation methods by using 10 times less fat tissue as starting material and delivering a higher cell yield.
Lean-Oriented Layout Design of a Health Care Facility
Authors: Fogliatto Flavio S. , Tortorella Guilherme L. , Anzanello Michel J. , Tonetto Leandro M.
Published: August 2019

Background:

In this article, we propose a method that integrates systematic layout planning techniques to lean health care practices aided by multicriteria decision analysis that could be applied to reformulate the layout of health care facilities.

Methods:

We analyze a high-variety sterilization unit of a large public hospital located in Brazil. The unit is currently implementing lean practices, and layout changes are required to provide more efficient materials and information flows.

Results:

Traditional design of health care facilities is not aligned with lean implementation and its underlying practices and principles. We propose the integration of such approaches to enhance their benefits. To rank and select the best layout alternative, a multicriteria decision analysis method (analytic hierarchy process) is adopted.

Conclusions:

There are 3 contributions here: the integration of lean principles into traditional health care facility design practices, the use of multicriteria decision analysis to refine the determination of the best layout solution, and the application of our propositions in a real case study.
A Rapid Cycle Improvement Approach to Increase Patient Readiness at Their Scheduled Appointment Time
Authors: Cowdell Jed Colt , Smoot Teresa B. , Murray Loren P. , Stancampiano Fernando F. , Hedges Mary S.
Published: August 2019

Background:

Patient unpunctuality negatively affects quality care. We found that 39% of patients at an academic primary care center were not ready to be evaluated at their scheduled appointment time. Our aim was to reduce this to 20% in 3 months' time.

Intervention:

A multidisciplinary quality improvement team utilized quality improvement tools and methodology to determine that patient punctuality was a major modifiable factor contributing to the care gap. Reforming the scheduling process to include a built in 15-minute early arrival was implemented for acute visits for a 2-week trial period. Based on the successful results, this was then disseminated to all appointment types for a 3-month trial.

Results:

Of the 182 patients seen during the 2-week trial period, 34 (19%) were not ready to be seen at the time of their appointment, a 20% improvement (P value < .001) from baseline. A total of 2832 patients were followed up for all visits during the next 3 months and 590 (21%) were not ready on time (P value < .001). Physician and patient satisfaction results improved after the intervention.

Conclusions:

Utilizing quality improvement tools we were able to find a simple and inexpensive intervention to improve patient punctuality as well as patient and provider satisfaction.
Patient Involvement in Evaluation of Safety in Oral Antineoplastic Treatment: A Failure Mode and Effects Analysis in Patients and Health Care Professionals
Authors: Mattsson Thea Otto , Lipczak Henriette , Pottegård Anton
Published: August 2019

Objectives:

To identify risks associated with delivery of treatment with oral antineoplastic agents in an outpatient setting and to evaluate additional value and feasibility of engaging patients in a proactive risk analysis.

Methods:

We conducted 2 separate but parallel failure mode and effects analyses (FMEAs) among patients and health care professionals (HCPs) at a clinical oncology department in Denmark. Comparative analyses were performed using the FMEA process maps and risk priority numbers (RPNs) as main outcome measures. The FMEAs were augmented by semistructured interviews with HCPs and patients on acceptability and feasibility of FMEAs analyzed using systematic text condensation.

Results:

Patients and HCPs found failures in information regarding treatment (cause, aim, and plan) to be of high risk. Also, HCPs found failures in checking for potential interactions to be of high risk. HCPs focused on the in-hospitals procedures, whereas patients identified risks related to both the hospital and the home setting. Both HCPs and patients found participation in the FMEA process meaningful but found the use of RPNs difficult.

Conclusions:

Patient engagement in proactive risk analysis using FMEA is acceptable, meaningful, and feasible, with patients providing a different perspective on the risks associated with oral antineoplastic treatment compared with HCPs.
Alternative Complement Pathway Activation Provokes a Hypercoagulable State with Diminished Fibrinolysis
Authors: Samuels Jason M. , Coleman Julia R. , Moore Ernest E. , Bartley Matt , Vigneshwar Navin , Cohen Mitchell , Silliman Christopher C. , Sauaia Angela , Banerjee Anirban
Published: August 2019

Introduction:

Several disease processes trigger prolonged activation of the alternative complement pathway. Crosslinks between complement activation and physiologic changes in platelets and neutrophils have been identified, but how this interplay alters the hemostatic potential in humans remains undefined. We hypothesize that activation of the alternative pathway triggers a hypercoagulable state.

Methods:

C3/C5 convertase Cobra Venom Factor (CVF, 10 Units/mL) was employed to activate the alternative complement pathway in whole blood. Complement inhibition was completed with inhibitors for C3/C3b (Compstatin, 25 and 50 μM), C3a receptor (SB290157, 300 nM, C3aR), and C5a receptor (W54011, 6 nM, C5aR). Coagulation was assessed using native thrombelastography which produces the following: reaction time (R time); angle; maximum amplitude (MA); percent fibrinolysis at 30-min post-MA (LY30).

Results:

Inhibition with C3aR and C5aR inhibitors did not alter clot formation (R time, 11.2 vs 11.6 min, P = 0.36), clot strength (MA, 52.0 vs 52.3 mm, P = 0.43), or fibrinolysis (LY30, 1.6 vs 4.0%, P = 0.19). Compstatin did not influence clot formation or clot strength but did induce a dose-dependent increase in fibrinolysis (control LY30 3.0 vs 7.8% and 12.4% for 25 and 50 μM respectively, P = 0.0002). CVF increased MA (58.0 vs 62.8 mm, P < 0.0001), decreased LY30 (2.3 vs 1.4%, P = 0.004), and increased R time (8.4 vs 9.9 min, P = 0.008). Compstatin reversed the effects of CVF, while C5a reversed only the change in LY30.

Conclusions:

C3 contributes to fibrinolysis, as inhibition with Compstatin enhanced fibrinolysis, and CVF cleavage of C3 decreased fibrinolysis. CVF also induced a hypercoagulable state with increased clot strength.
Complete metamorphosis of insects
Authors: Rolff Jens , Johnston Paul R. , Reynolds Stuart
Published: August 2019

The majority of described hexapod species are holometabolous insects, undergoing an extreme form of metamorphosis with an intercalated pupal stage between the larva and adult, in which organs and tissues are extensively remodelled and in some cases completely rebuilt. Here, we review how and why this developmental strategy has evolved. While there are many theories explaining the evolution of metamorphosis, many of which fit under the hypothesis of decoupling of life stages, there are few clear adaptive hypotheses on why complete metamorphosis evolved. We propose that the main adaptive benefit of complete metamorphosis is decoupling between growth and differentiation. This facilitates the exploitation of ephemeral resources and enhances the probability of the metamorphic transition escaping developmental size thresholds. The evolution of complete metamorphosis comes at the cost of exposure to predators, parasites and pathogens during pupal life and requires specific adaptations of the immune system at this time. Moreover, metamorphosis poses a challenge for the maintenance of symbionts and the gut microbiota, although it may also offer the benefit of allowing an extensive change in microbiota between the larval and adult stages. The regulation of metamorphosis by two main players, ecdysone and juvenile hormone, and the related signalling cascades are now relatively well understood. The mechanics of metamorphosis have recently been studied in detail because of the advent of micro-CT and research into the role of cell death in remodelling tissues and organs. We support the argument that the adult stage must necessarily have preceded the larval form of the insect. We do not resolve the still contentious question of whether the larva of insects in general originated through the modification of existing preadult forms or through heterochrony as a modified embryonic stage (pronymph), nor whether the holometabolous pupa arose as a modified hemimetabolous final stage larva.

This article is part of the theme issue ‘The evolution of complete metamorphosis’.
The evolution of insect metamorphosis: a developmental and endocrine view
Authors: Truman James W. , Riddiford Lynn M.
Published: August 2019

Developmental, genetic and endocrine data from diverse taxa provide insight into the evolution of insect metamorphosis. We equate the larva–pupa–adult of the Holometabola to the pronymph–nymph–adult of hemimetabolous insects. The hemimetabolous pronymph is a cryptic embryonic stage with unique endocrinology and behavioural modifications that probably served as preadaptations for the larva. It develops in the absence of juvenile hormone (JH) as embryonic primordia undergo patterning and morphogenesis, the processes that were arrested for the evolution of the larva. Embryonic JH then drives tissue differentiation and nymph formation. Experimental treatment of pronymphs with JH terminates patterning and induces differentiation, mimicking the processes that occurred during the evolution of the larva. Unpatterned portions of primordia persist in the larva, becoming imaginal discs that form pupal and adult structures. Key transcription factors are associated with the holometabolous life stages:Krüppel-homolog 1(Kr-h1) in the larva,broadin the pupa andE93in the adult. Kr-h1 mediates JH action and is found whenever JH acts, while the other two genes direct the formation of their corresponding stages. In hemimetabolous forms, the pronymph has low Broad expression, followed by Broad expression through the nymphal moults, then a switch to E93 to form the adult.

This article is part of the theme issue ‘The evolution of complete metamorphosis’.
Visualization of insect metamorphosis
Authors: Hall Martin J. R. , Martín-Vega Daniel
Published: August 2019

Metamorphosis and, in particular, holometaboly, the development of organisms through a series of discrete stages (egg, larva, pupa, adult) that hardly resemble one another but are finely adapted to specific roles in the life cycle of the organism, has fascinated and mystified humans throughout history. However, it can be difficult to visualize the dramatic changes that occur during holometaboly without destructive sampling, traditionally through histology. However, advances in imaging technologies developed mainly for medical sciences have been applied to studies of insect metamorphosis over the past couple of decades. These include micro-computed tomography, magnetic resonance imaging and optical coherence tomography. A major advantage of these techniques is that they are rapid and non-destructive, enabling virtual dissection of an organism in any plane by anyone who has access to the image files and the necessary software. They can also be applied in some cases to visualize metamorphosis
in vivo
, including the periods of most rapid and dramatic morphological change. This review focusses on visualizing the intra-puparial holometabolous metamorphosis of cyclorraphous flies (Diptera), including the primary model organism for all genetic investigations,
Drosophila melanogaster
, and the blow flies of medical, veterinary and forensic importance, but also discusses similar studies on other insect orders.

This article is part of the theme issue ‘The evolution of complete metamorphosis’.
Evaluating responses to temperature during pre-metamorphosis and carry-over effects at post-metamorphosis in the wood tiger moth (Arctia plantaginis)
Authors: Galarza Juan A. , Dhaygude Kishor , Ghaedi Behnaz , Suisto Kaisa , Valkonen Janne , Mappes Johanna
Published: August 2019

Insect metamorphosis is one of the most recognized processes delimiting transitions between phenotypes. It has been traditionally postulated as an adaptive process decoupling traits between life stages, allowing evolutionary independence of pre- and post-metamorphic phenotypes. However, the degree of autonomy between these life stages varies depending on the species and has not been studied in detail over multiple traits simultaneously. Here, we reared full-sib larvae of the warningly coloured wood tiger moth (Arctia plantaginis) in different temperatures and examined their responses for phenotypic (melanization change, number of moults), gene expression (RNA-seq and qPCR of candidate genes for melanization and flight performance) and life-histories traits (pupal weight, and larval and pupal ages). In the emerging adults, we examined their phenotypes (melanization and size) and compared them at three condition proxies: heat absorption (ability to engage flight), flight metabolism (ability to sustain flight) and overall flight performance. We found that some larval responses, as evidenced by gene expression and change in melanization, did not have an effect on the adult (i.e. size and wing melanization), whereas other adult traits such as heat absorption, body melanization and flight performance were found to be impacted by rearing temperature. Adults reared at high temperature showed higher resting metabolic rate, lower body melanization, faster heating rate, lower body temperature at take-off and inferior flight performance than cold-reared adults. Thus, our results did not unambiguously support the environment-matching hypothesis. Our results illustrate the importance of assessing multiple traits across life stages as these may only be partly decoupled by metamorphosis.

This article is part of the theme issue ‘The evolution of complete metamorphosis'.
A flexible quantitative phase imaging microscope for label-free imaging of thick biological specimens using aperture masks
Authors: Seniya Chandrabhan , Towers Catherine E , Towers David P
Published: August 2019

A flexible quantitative phase imaging microscope is reported that offers new capabilities in terms of phase measurement from both thin and thick biological specimens. The method utilises Zernike’s phase contrast approach for label-free imaging with a Twymann-Green based phase shifting module in the back focal plane. The interfering wave fronts are manipulated by laser cut apertures to form the scattered and non-scattered fields. The design is flexible and low-cost. It is shown that the bandwidth of the optical source can be optimised to enable larger optical path differences to be measured whilst giving essentially speckle free imaging. Phase maps of the cell membrane, nucleus and nucleolus of transparent epidermis cells of Allium cepa have been examined as proof of concept. Measurements from a range of glass beads confirm the optical path difference capability. The implementation of the phase shifting module is < 10% of the cost of that using a spatial light modulator whilst delivering equivalent phase resolution.
Multiple Myeloma DREAM Challenge Reveals Epigenetic RegulatorPHF19As Marker of Aggressive Disease
Authors: Mason Mike J , Schinke Carolina , Eng Christine L P , Towfic Fadi , Gruber Fred , Dervan Andrew , White Brian S , Pratapa Aditya , Guan Yuanfang , Chen Hongjie , Cui Yi , Li Bailiang , Yu Thomas , Neto Elias Chaibub , Mavrommatis Konstantinos , Ortiz Maria , Lyzogubov Valeriy , Bisht Kamlesh , Dai Hongyue Y , Schmitz Frank , Flynt Erin , Rozelle Dan , Danziger Samuel A , Ratushny Alexander ,   Multiple Myeloma DREAM Consortium, Dalton William S , Goldschmidt Hartmut , Avet-Loiseau Herve , Samur Mehmet , Hayete Boris , Sonneveld Pieter , Shain Kenneth H , Munshi Nikhil , Auclair Daniel , Hose Dirk , Morgan Gareth , Trotter Matthew , Bassett Douglas , Goke Jonathan , Walker Brian A , Thakurta Anjan , Guinney Justin
Published: August 2019

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients do not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involve assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post challenge analysis identified a novel expression-based risk marker and histone modifier,PHF19, which featured prominently in several independent models. Lastly, we show that a simple four feature predictor composed of age, International Staging System stage (ISS), and expression ofPHF19andMMSETperforms similarly to more complex models with many more gene expression features included.

Key points

Most comprehensive and unbiased assessment of prognostic biomarkers in MM resulting in a robust and parsimonious model.

Identification ofPHF19as the expression based biomarker most strongly associated with rapid progression in MM patients.
Structural-stability studies on recombinant human transferrin
Authors: Kulakova A. , Indrakumar S. , Sønderby P. , Gentiluomo L. , Streicher W. , Roessner D. , Frieß W. , Peters G. H.J. , Harris P.
Published: August 2019

Transferrin is an attractive candidate for drug delivery due to its ability to cross the blood brain barrier. However, in order to be able to use it for therapeutic purposes, it is important to investigate how its stability depends on different formulation conditions. Combining high-throughput thermal and chemical denaturation studies with small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, it was possible to connect the stability of transferrin with its conformational changes. The release of iron induces opening of transferrin, which results in a negative effect on its stability. Presence of NaCl, arginine, and histidine leads to opening of the transferrin N-lobe and has a negative impact on the overall protein stability.

Statement of significance

Protein-based therapeutics have become an essential part of medical treatment. They are highly specific, have high affinity and fewer off-target effects. However, stabilization of proteins is critical, time-consuming, and expensive, and it is not yet possible to predict the behavior of proteins under different conditions. The current work is focused on a molecular understanding of the stability ofhumanserum transferrin; a protein which is abundant in blood serum, may pass the blood brain barrier and therefore with high potential in drug delivery. Combination of high throughput unfolding techniques and structural studies, using small angle X-ray scattering and molecular dynamic simulation, allows us to understand the behavior of transferrin on a molecular level.
Population genomics of Vibrionaceae isolated from an endangered oasis reveals local adaptation after an environmental perturbation
Authors: Vazquez-Rosas-Landa Mirna , Ponce-Soto Gabriel Yaxal , Aguirre-Liguori Jonás A. , Thakur Shalabh , Scheinvar Enrique , Barrera-Redondo Josué , Ibarra-Laclette Enrique , Guttman David S. , Eguiarte Luis E. , Souza Valeria
Published: August 2019

Background

In bacteria, pan-genomes are the result of the evolutionary “tug of war” between selection and horizontal gene transfer (HGT). High rates of HGT increase the genetic pool and the effective population size, resulting in open pan-genomes. In contrast, selective pressures can lead to local adaptation by purging the variation introduced by HGT, resulting in closed pan-genomes and clonal lineages. In this study, we explored both hypotheses elucidating the pan-genome of Vibrionaceae isolates after a perturbation event in the endangered oasis of Cuatro Ciénegas Basin (CCB), Mexico, and looking for signals of adaptation to the environments in their genomes.

Results

We obtained 42 genomes of Vibrionaceae distributed in six lineages, two of them did not showed any close reference strain in databases. Five of the lineages showed closed pan-genomes and were associated to either water or sediment environment; their high effective population size (Ne) estimates suggest that these lineages are not from a recent origin. The only clade with an open pan-genome was found in both environments and was formed by ten genetic groups with lowNe, suggesting a recent origin. The recombination and mutation estimators (r/m) ranged from 0.0052 to 2.7249, which are similar to oceanic Vibrionaceae estimations; however, we identified 367 gene families with signals of positive selection, most of them found in the core genome; suggesting that despite recombination, natural selection moves the Vibrionaceae CCB lineages to local adaptation purging the genomes and keeping closed pan-genome patterns. Moreover, we identify 598 SNPs associated with an unstructured environment; some of the genes under this SNPs were related to sodium transport.

Conclusions

Different lines of evidence suggest that the sampled Vibrionaceae, are part of the rare biosphere usually living under famine conditions. Two of these lineages were reported by the first time. Most Vibrionaceae lineages of CCB are adapted to their microhabitats rather than to the sampled environments. This pattern of adaptation agrees with the association of closed pan-genomes and local adaptation.