bluuebunny/crossref_metadata_2025 huggingface dataset:
Single nucleotide polymorphisms in the non-coding region of STIM1 gene are associated with Parkinson disease risk in Chinese Han population
Authors: Lou Danning , Wang Jun , Wang Xiaohang
Published: March 2020

The stromal interaction molecule 1 (STIM1) gene contributes essentially to Ca2+ transport, thus it is functionally related to neurodegenerative disorders. The objective of this study was to investigate the correlation between single nucleotide polymorphisms (SNP) in the non-coding region of STIM1 gene and the risk for Parkinson disease (PD) in a Chinese Han population.

In a cohort composed of 300 PD patients and 300 healthy individuals from a Chinese Han population, we analyzed genotypes for five novel SNPs, rs7934581, rs3794050, rs1561876, rs3750994 and rs3750996 in the non-coding region of STIM1 gene. The levels of STIM1 protein in plasma of these subjects were also assessed by enzyme-linked immunosorbent assay (ELISA).

We found that the SNPs of STIM1 gene rs7934581, rs3794050, rs1561876, and rs3750996 were associated with increased PD risk, while rs3750994 SNP was not. An increased risk of PD was observed in subjects with the TAAG and TGAG haplotypes of rs7934581, rs3794050, rs1561876, rs3750996. Moreover, PD risk was significantly elevated only in subjects with age ≥60 years or females who carry the STIM1 rs3794050 minor allele. There was a significant difference in plasma STIM1 protein levels between subjects with different genotypes of STIM1 rs7934581, rs3794050, rs1561876, and rs3750996.

STIM1 gene rs7934581, rs3794050, rs1561876, rs3750996 SNPs are associated with increased PD risk, and its mechanism may be related to abnormal STIM1 gene expression.
Trunk fat mass correlates with balance and physical performance in a community-dwelling elderly population
Authors: Kim Jae Hoon , Chon Jinmann , Soh Yunsoo , Han Young Rok , Won Chang Won , Lee Seung Ah
Published: March 2020

This study aimed to investigate whether trunk fat mass measured using dual-energy X-ray absorptiometry (DEXA) correlates with balance and physical performance.

This study utilized 2-year baseline data pertaining to 3014 participants from the database of the Korean frailty and aging cohort study. The trunk lean mass and fat mass were measured by DEXA. Trunk fat mass index (tFMI) was established using the following standard equation: Trunk fat mass (Kg)/height2 (m2). The clinical balance tests were performed using the timed up and go test (TUG), total balance score in short physical performance battery (SPPB). We performed SPPB and evaluated independence of daily living using activities of daily living, instrumental activities of daily living (IADL), sarcopenia screening tool (SARC-F) and both hand grip power. In our study, we tried to check the correlation of tFMI with balance and physical performance and to determine the factors associated with tFMI.

The tFMI was positively correlated with mean values of 4 m gait speed, repeat chair stand time in SPPB, TUG, and SARC-F and negatively correlated with hand grip, IADL, total balance test score in SPPB, total SPPB score, and age. The results of the multiple generalized linear model analysis that assessed the factors associated with balance and physical performance indicated that tFMI had a significant correlation with repeat chair stand time in SPPB (seconds) (Beta estimate [B]: 0.252), TUG (seconds) (B: 0.25), 4 m gait speed (seconds) (B: 0.055), and total balance score in SPPB (B: −0.035).

Higher tFMI using DEXA was correlated with low physical performance and balance, indicating that trunk fat mass was associated with balance and physical performance in community-dwelling older people.
Role of autoimmune hemolytic anemia as an initial indicator for chronic myeloid leukemia
Authors: Li Xiang , Cai Sisi , Zhong Zhaodong , Wang Hongxiang , Wang Li , You Yong , Zhang Min
Published: March 2020

Introduction:

We report here the case of a patient with chronic myeloid leukemia (CML) in the chronic phase who was diagnosed 1 year after receiving a diagnosis of autoimmune hemolytic anemia (AIHA). The objective was to assess if the CML patient progressed from AIHA and explore the underlying factors of the poor outcome after the achievement of molecular complete remission (MCR).

Patient concerns:

A patient with AIHA underwent splenectomy because of poor response to immune inhibitors. The spleen biopsy showed reactive hyperplasia.

Diagnosis:

The patient was diagnosed with CML because of over-expression of the BCR-ABL (P210) gene in the bone marrow (BM), 1 year after receiving the diagnosis of AIHA.

Interventions:

The splenectomy was performed as the patient was unresponsive to the standard treatments consisting of immunoglobulin and dexamethasone. The removed spleen was sent for pathological examination. After she was diagnosed with CML, she received imatinib treatment.

Outcomes:

The spleen biopsy confirmed the translocation of 22q11/9q34. No BCR-ABL kinase domain mutation was detected and there was no expression of the WT1 or EVI1 genes. After splenectomy, the number of peripheral white blood cells was consistently higher than normal during the total therapy time for CML even though she showed MCR. Two years after CML was diagnosed, the patient died from severe infection. The BM gene array analysis displayed 3 types of chromosomal abnormalities: gain (14q32.33), uniparental disomy (UPD) Xp11.22-p11.1), and UPD Xp11.1-q13.1.

Lessons:

AIHA may be a clinical phase of CML progression in this patient. Both splenectomy and prolonged oral tyrosine kinase inhibitors may have contributed to the high risk of infection and her subsequent death. In addition, the gain of chromosome 14q32.33 may be related to her poor outcome.
Preoperative imatinib treatment in patients with locally advanced and metastatic/recurrent gastrointestinal stromal tumors
Authors: Wang Jian , Yin Yuan , Shen Chaoyong , Yin Xiaonan , Cai Zhaolun , Pu Lin , Fu Wei , Wang Yaxuan , Zhang Bo
Published: March 2020

The advent of imatinib mesylate (IM) has dramatically revolutionized the prognosis of advanced and metastatic/recurrent gastrointestinal stromal tumors (GISTs). The objective of this retrospective study is to investigate the safety and efficacy of combination of surgery following IM treatment in the management of advanced and metastatic/recurrent GISTs. We further explore the long-term clinical outcomes in these who underwent therapy of preoperative IM.

Eligible patients with GISTs before the onset of the IM therapy and were periodically followed up in the outpatient clinic were included in this study. Detailed clinical and pathologic characteristics were obtained from the medical records of our institution. Univariate and multivariate regression analyses were performed to use for the evaluation of potential prognostic factors.

A total of 51 patients were included in the study, of these patients, 36 patients underwent surgery and median duration of preoperative IM is 8.2months (range 3.5–85 months). Significant median tumor shrinkage rate was 29.27% (95% confidence interval 21.00%–34.00%) observed in these patients who responded to IM, and partial response and stable disease were achieved in 24 patients (47.06%) and 23 patients (45.10%), respectively, in light of the RECIST guideline (version 1.1). After the median follow-up of 43.70 months (range 14.2–131.1 months), 1- and 3-year overall survival (OS) were estimated to be 96.1% and 94.0%, respectively, and there was a significant improvement in OS for patients who received surgical intervention versus those who did not.

Our study consolidates that patients were received preoperative IM therapy could shrink the size of tumors and facilitate organ-function preservation. The long-term analysis on this study supports that surgical intervention following IM therapy benefits for patients with primary advanced and recurrent or metastatic GISTs on long-term prognosis.
The short-term and long-term outcomes of transcatheter or surgical aortic valve replacement in elderly patients
Authors: Lei Xiang , Wei Zhili , Liu Shidong , Liang Fuxiang , Song Bing
Published: March 2020

Background:

Transcatheter aortic valve replacement (TAVR) has become an essential alternate option for people suffering from aortic stenosis. However, the efficacy and safety of TAVR for elderly population (aged over 80 years) is still unclear.

Methods:

We plan to perform a systematic review and meta-analysis of clinical controlled trials and propensity-match cohort studies to evaluate the short- and long-term outcomes in elderly aortic stenosis patients who undergo a transcatheter or surgical aortic valve replacement. We will search PubMed, EMBASE, and Cochrane Library using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information, and assess the risk of bias independently. STATA software will be used to conduct data synthesis. There is no requirement of ethical approval and informed consent.

Results:

This study will be submitted to a peer-reviewed journal for publication.

Conclusion:

This is the first systematic assessment of TAVR for elderly patients with aortic stenosis. We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials.

Ethics and dissemination:

Ethics approval and patient consent are not required as this study is a systematic review and meta-analysis.

PROSPERO registration number:

CRD42019140857.

Study protocol registry:

The protocol has been registered in PROSPERO, which is an International Prospective Register of Systematic Reviews. The registration number is CRD42019140857
Application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of non-small-cell lung cancer
Authors: Zhang Longguo , Wu Fanqi , Zhu Rui , Wu Di , Ding Yao , Zhang Zhongmei , Gao Ya , Wan Yixin
Published: March 2020

Background:

Ruling out distant metastases, non-small cell lung cancer (NSCLC)treatment depends on the results of mediastinal node staging (N staging). Several diagnostic methods play central roles in mediastinal N staging. This study is intended to evaluate the existing diagnostic methods and report quality, and to search for the best method for staging mediastinal lymph nodes.

Methods:

We searched PubMed, Embase, and the Cochrane Library to identify relevant studies, including randomized controlled trials and retrospective studies. These studies report the application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of NSCLC. The quality of the literature was assessed using the Quality Assessment of Diagnostic Accuracy Study 2. The true positive, false positive, true negative, and false negative of each study was extracted. The corresponding sensitivity, specificity, and other indicators were calculated and the Summary Receiver Operating curve was established. Then, head-to-head and indirect comparison meta-analyses will be conducted.

Results:

The results of this study will be published in a peer-reviewed journal.

Conclusion:

This study will provide basis for mediastinal lymph node staging of non-small cell lung cancer.

PROSPERO registration number:

CRD42019145667
Macroscopic hematuria as a risk factor for hypertension in ageing people with hemophilia and a family history of hypertension
Authors: Qvigstad Christian , Sørensen Lars Q. , Tait R. Campbell , de Moerloose Philippe , Holme Pål Andre
Published: March 2020

Ageing people with hemophilia (PWH) have a higher prevalence of hypertension than the general population. This study aimed to determine whether macroscopic hematuria was associated with hypertension in PWH in a post hoc analysis using data from a cross-sectional study conducted by the ADVANCE Working Group (the H3 study), which included PWH ≥ 40 years of age. Data from 16 contributing centers, located in 13 European countries and Israel, were analyzed using logistic regression models. Of 532 recruited PWH in the H3 study, 117 had hypertension and a positive family history of hypertension (hypertension FH+), 75 had hypertension and a negative family history of hypertension (hypertension FH−), 290 had no diagnosis of hypertension, and the remaining 50 had missing hypertension data. Logistic regressions showed that macroscopic hematuria was associated with hypertension FH+, both in the univariate (OR = 1.84 [1.17–2.90], P = .01) and in the multivariate model (OR = 1.80 [1.03–3.16], P = .04). Macroscopic hematuria was not associated with hypertension FH−. Moreover, in a multivariate logistic regression the odds of hypertension FH+ were increased with the number of macroscopic hematuria episodes. The association between macroscopic hematuria and hypertension was significant for PWH with a family history of hypertension.
Streptococcus pneumoniae colonization in pneumococcal vaccine-naïve human immunodeficiency virus-exposed infected and -uninfected South African children
Authors: Nunes Marta Coelho , Kim Soyeon , Zeldow Bret , Violari Avy , Dittmer Sylvia , Cassim Haseena , Thomas Teena , van Niekerk Nadia , Cotton Mark Fredric , Mitchell Charles , Adrian Peter , Madhi Shabir Ahmed
Published: March 2020

Pneumococcal nasopharyngeal colonization is a pre-requisite for pneumococcal disease; the risk for pneumococcal disease is high in children born to women living with human immunodeficiency virus (HIV). We investigated pneumococcal colonization, serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by perinatal HIV-infected and HIV-exposed-uninfected (HEU) children.

Serial nasopharyngeal swabs were collected from 331 HIV-infected and 491 HEU children, at up to 6 scheduled timepoints, between median ages of 25 to 181 weeks. Pneumococcus was identified by culture; serotyping and antibiotic susceptibility testing were done by conventional methods. No pneumococcal vaccine was given.

HIV-infected children were less likely to be colonized with 7-valent pneumococcal conjugate vaccine 7 serotypes than HEU at a median of 25 weeks of age (23% vs 36%; P < .001); however, no differences in colonization between the 2 groups were observed at subsequent study-visits. Over the 36-months study-period pneumococcal colonization increased in both HIV-infected (from 45% to 77%) and HEU (from 57% to 61%) children. Over the study-period, pneumococcal isolates non-susceptible to cotrimoxazole decreased from 92% to 57% and had a similar trend to penicillin (from 65% to 42%) in HIV-infected children. Similarly, pneumococcal nonsusceptible to cotrimoxazole decreased from 93% to 57% and to penicillin from 69% to 37% in HEU children.

Vaccine serotype colonization was common in this population and similar rates were observed in HIV-infected and HEU children. The prevalence of pneumococcal isolates non-susceptible to cotrimoxazole and penicillin decreased with age.
Extreme delta brush patterns guide the complex motor phenomenon of anti-NMDA receptor encephalitis
Authors: Chen Yu-Ming , Kuo Pei-Hsin
Published: March 2020

Rationale:

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease that is associated with cell-surface NMDAR-targeting autoantibodies. Typical anti-NMDAR encephalitis symptoms include psychosis, seizure and extrapyramidal side effects. However, early diagnosis of anti-NMDAR encephalitis remains challenging due to the complexity of the motor phenomenon.

Patient concerns:

Here, we report a new diagnosis of anti-NMDAR encephalitis in a young woman with a history of epilepsy.

Diagnoses:

Electroencephalography revealed a typical “extreme delta brush” pattern, which indicated anti-NMDAR encephalitis.

Interventions:

The clinical status of the patient markedly improved after immediate and aggressive immunosuppression therapies.

Outcomes:

The patient was discharged with mild cognitive impairment. However, this was completely resolved 1 month postdischarge.

Lessons:

We conclude that subacute onset focal seizure with psychosis as well as compatible electroencephalography findings (i.e., extreme delta brush patterns) should be considered notable early indicators of anti-NMDAR encephalitis. This would ensure early and effective clinical interventions, which are essential for favorable outcomes.
Extreme intrusive force affects the expression of c-Fos and matrix metallopeptidase 9 in human dental pulp tissues
Authors: Han Guanghong , Liu Weiwei , Jiang Huan , Yu Dongsheng , Hu Min
Published: March 2020

This study aimed to investigate the expression of c-Fos and matrix metallopeptidase 9 (MMP-9) in dental pulp of patients receiving orthodontic treatment via wire appliance.

Fifteen patients (30 teeth in total) were randomly assigned to five groups: t = 0, t = 1, t = 4, t = 8 and t = 12 (n = 6). The first maxillary premolars of patients in the t = 0 group were extracted without any orthodontic treatment. An intrusive force of 300 g was applied on first maxillary premolars in the other four groups via wire appliances. This force was maintained for 1 week for t = 1 group, 4 weeks for t = 4 group, 8 weeks for t = 8 group, or 12 weeks for t = 12 group, before the teeth were extracted.

The expression of c-Fos and MMP-9 in the pulps of each group was analyzed by immunohistochemical staining and real-time PCR. The relationship in the protein expression between c-Fos and MMP-9 in the dental pulp was analyzed by Pearson correlation analysis.

Intrusive force of 300 g increased the expression of both c-Fos and MMP-9 in the dental pulp. The protein expression of MMP-9 in the dental pulp was significantly correlated with the expression of c-Fos (P < .001).

Extreme intrusive force upregulates c-Fos and MMP-9 expression in the dental pulp. Moreover, protein expression of c-Fos and MMP-9 is significantly correlated under intrusive force.
Anti-HBc impacts on the risk of hepatitis B reactivation but not on survival of solid-organ transplant recipients
Authors: Álvarez-López Patricia , Riveiro-Barciela Mar , Oleas-Vega Diana , Flores-Cortes Claudia , Román Antonio , Perelló Manel , Berastegui Cristina , Castells Lluis , Esteban Rafael , Buti María
Published: March 2020

Immunosuppression can lead to hepatitis B virus (HBV) reactivation in hepatitis B core antigen antibodies (anti-HBc) positive patients, especially those undergoing chemotherapy, although there is limited data on solid organ recipients, especially lung transplantation. Our aim was to analyze the risk of HBV reactivation and the potential impact of anti-HBc-positive status (both donors and recipients) on prognosis in a lung, kidney, and liver transplantation cohort.

Retrospective analysis including data from all transplants in adults (2011–2012) in a tertiary hospital, with prospective HBV serology study to assess the risk of reactivation and its possible impact on survival.

In total, 392 transplant recipients were included (196 kidney, 113 lung, 83 liver). Pre-transplantation anti-HBc screening was more frequent in liver recipients (P < .001) and donors (P < .001) than in kidney or lung. Fifty-five (14%) recipients were anti-HBc-positive and were not undergoing antiviral prophylaxis. Three (5.4%) cases of HBV reactivation occurred: 2 in pre-transplant anti-HBc-positive recipients and 1 with prior unknown anti-HBc status. All were HBeAg+ with HBV deoxyribonucleic acid (DNA) >10E8 IU/mL and only mild fibrosis. Baseline recipient anti-HBc positive status was the only factor associated with HBV reactivation. No reactivation cases occurred in lung or kidney recipients of anti-HBc positive grafts. Survival was lower in lung transplants, especially in human immunodeficiency virus-infected patients and those with prior immunosuppression.

Anti-HBc positive status is a risk factor for HBV reactivation in solid organ recipients. Anti-HBc testing is highly recommended in solid-organ transplant recipients in order to identify those anti-HBc positive and therefore candidates for periodical hepatitis B surface antigen (HBsAg) and HBV DNA screening after transplant.
Body mass index and serum uric acid level
Authors: Zhang Lin , Li Jin-Long , Zhang Li-Li , Guo Lei-Lei , Li Hong , Li Dan
Published: March 2020

Few studies on the individual and combined analysis between serum uric acid (SUA) and body mass index (BMI) and blood pressure (BP) were conducted in individuals aged ≥45 years. We aimed to assess the extent to which BMI and SUA and their interaction affect BP in Chinese middle-aged and older adults.

Data were selected from the China Health and Retirement Longitudinal Study (CHARLS). A total of 5888 individuals aged 45 to 96 was included. Differences between BMI, or between categories of blood pressure were evaluated by t test or chi-square test. The trend of related variables according to four BMI categories was also tested using contrast analysis. The adjusted associations between various characteristics and BP status were first compared using linear regression models, as appropriate. Then, general linear models adjusting for related potential confounders were used to examine the synergistic effect of SUA and BMI level on BP for middle-aged and elderly individuals in China.

Age-adjusted partial Pearson correlation coefficient showed that BMI was significantly and positively correlated with BP both in male and female, SUA positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in males with BMI <24.0 kg/m2 and females with BMI <24.0 kg/m2. However, SUA level significantly and positively correlated with DBP, but not with SBP, in females with BMI ≥24.0 kg/m2. Multiple linear regression analysis showed that BMI was independently associated with BP both in male and female, SUA significantly and positively associated with SBP in both males and females with BMI <24.0 kg/m2, However, SUA level positively correlated with DBP in females with BMI <24.0 kg/m2, but not with males with BMI <24.0 kg/m2, independent of other confounding factors. A general linear model analysis adjusted for confounding factors did not reveal interaction between BMI, SUA levels and SBP (β=-1.404, P = .686 in males; β=-2.583, P = .575 in females) and DBP (β=-2.544, P = .263 in males; β=-2.619, P = .622 in females).

No interaction between BMI, SUA levels, and BP was observed in either males or females; However, BMI was independently associated with BP both in male and female, SUA independently associated with SBP both in males and females with BMI <24.0 kg/m2, and SUA independently associated with DBP in females with BMI ≥24.0 kg/m2.
Endoscopic resection of early squamous neoplasia of the oesophagus: long-term follow-up in a UK population from a tertiary hospital
Authors: Kuan Jen Yee , Baskind Sameul , Kim Yeson , McGrath Stephen , Chaparala Ramakrishna , Assadsangabi Arash , Prasad Neeraj , Regi George , Ang Yeng
Published: March 2020

Aim

To review the efficacy and outcomes of endoscopic resection in the diagnosis and treatment of oesophageal squamous dysplasia and early neoplasia.

Methods

This was a retrospective study between May 2012–2018. Twenty-one patients were treated with or considered for treatment with endoscopic resection at a tertiary hospital in the UK. The primary outcome was curative resection, defined as histologically proven complete resection of the lesion with deep/vertical margin ≥1 mm from neoplasia. Secondary outcomes were changes in staging from endoscopic resection histology, whether there was a complete reversal of dysplasia at 12-months or the latest endoscopic follow-up and 5-year overall survival rate.

Results

Seventeen patients (mean age = 66.5 years) with 20 lesions (35% en-bloc; 65% piecemeal resections) had endoscopic resection performed. Complete resection was achieved in 90% of lesions by endoscopic criteria, but this was confirmed in fewer lesions histologically. Curative resection was achieved histologically in 60% of lesions (11 patients) and noncurative resection in 40% of lesions (6 patients). Changes in staging from endoscopic resection histology were found in 79.2% of lesions (41.7% upstaged; 37.5% downstaged). No patients were found to have recurrence at their 12-month endoscopic follow-up. Eight of the 11 patients (72.7%) with curative resection remained clear of dysplasia/neoplasia throughout their follow-up (mean, 24.3 months; median, 19 months). The five-year overall survival rate was 64%.

Conclusion

In UK, endoscopic resection is useful in the management of early squamous neoplasia both for staging and (by piecemeal endoscopic resection in elderly unfit) for medium- to long-term disease clearance.
A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia
Authors: Paunescu Horia , Dima Lorena , Ghita Isabel , Coman Laurenţiu , Ifteni Petru Iulian , Fulga Ion , Coman Oana Andreia
Published: March 2020

Background:

The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD).

The Study Question:

Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD?

Study Design:

PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression.

Measures and Outcomes:

The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009.

Results:

The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation).

Conclusions:

No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.
Prognostic and Predictive Role of Excision Repair Cross-complementation Group 1 and Thymidylate Synthase in Colorectal Carcinoma Patients Received FOLFOX Chemotherapy: An Immunohistochemical Study
Authors: Badary Dalia M. , Elkabsh Mai M. , Mady Hussam H. , Gabr Adel , Kroosh Sana S.
Published: March 2020

Background and Study Aims:

We aim to determine the frequency of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC-1) immunohistochemical (IHC) expression and its relationship with clinicopathologic variables in colorectal carcinoma (CRC) patients. In addition, we aim to assess the correlation between TS and ERCC-1 expression and the response of these cases to oxaliplatin and 5-fluorouracil chemotherapy (FOLFOX).

Patients and Methods:

Fifty-one CRC patients were prepared for IHC analysis of ERCC-1 and TS protein expression. All patients received oxaliplatin and 5-fluorouracil combined chemotherapy (FOLFOX) and were followed up for 24 months.

Results:

The data analysis showed that high ERCC-1 and TS expression was significantly associated with early treatment failure (P=0.020 and 0.000). In contrast, TS immunoexpression affects the disease-free survival rate (P=0.010). The presence of deep tumor invasion, distant metastasis, lymph node metastasis, and high Dukes’ classification were significantly statistically associated with early treatment failure (P=0.001, 0.000, 0.041, and 0.015, respectively).

Conclusions:

Our results showed that both ERCC-1 and TS are predictive factors for early treatment failure in CRC patients. TS protein is a prognostic factor for disease-free survival rates. This supports the theory that both ERCC-1 and TS can be used to improve chemotherapeutic outcomes in CRC patients. High expression of TS and ERCC-1 helps in the identification of cases that will get fewer benefits from FOLFOX chemotherapy. As an innovative strategy, in these cases, we can use alternative chemotherapeutic regimens or add an extra agent. In addition, Dukes’ classification and lymph node metastasis are predictive factors for early treatment failure. Thus, all those values can be used to predict CRC patients with bad prognosis and those who will get fewer benefits from FOLFOX.
A Front-end Redesign With Implementation of a Novel “Intake” System to Improve Patient Flow in a Pediatric Emergency Department
Authors: Carney Kevin P. , Crespin Ann , Woerly Gray , Brethouwer Nicholas , Baucum Jeff , DiStefano Michael C.
Published: March 2020

Introduction:

Children’s Hospital Colorado is an academic, tertiary-care Level 1 Trauma Center with an emergency department (ED) that treats >70,000 patients/year. Patient volumes continue to increase, leading to worsening wait times and left-without-being-seen (LWBS) rates. In 2015, the ED’s median door-to-provider time was 49 minutes [interquartile range (IQR) = 26–90], with a 3.2% LWBS rate. ED leadership, staff, and providers aimed to improve patient flow with specific goals to (1) decrease door-to-provider times to a median of <30 minutes and (2) decrease annual LWBS rate to <1%.

Methods:

An inter-professional team utilized quality improvement and Lean methodology to study, redesign, and implement significant changes to ED front-end processes. Key process elements included (1) new Flow Nurse/EMT roles, (2) elimination of traditional registration and triage processes, (3) immediate “quick registration” and nurse assessment upon walk-in, (4) direct-bedding of patients, and (5) a novel “Intake” system staffed by a pediatric emergency medicine physician.

Results:

In the 12 months following full implementation of the new front-end system, the median door-to-provider time decreased 49% to 25 minutes (IQR = 13–50), and the LWBS rate decreased from 3.2% to 1.4% (a 56% relative decrease). Additionally, the percentage of patients seen within 30 minutes of arrival increased, overall ED length-of-stay decreased, patient satisfaction improved, and no worsening of the unexpected 72-hour return rate occurred.

Conclusions:

Using quality improvement and Lean methodology, an inter-professional team decreased door-to-provider times and LWBS rates in a large pediatric ED by redesigning its front-end processes and implementing a novel pediatric emergency medicine-led Intake system.
Viscoelastic testing in combat resuscitation: Is it time for a new standard?
Authors: Lammers Daniel T. , Marenco Christopher W. , Morte Kaitlin R. , Bingham Jason R. , Martin Matthew J. , Eckert Matthew J.
Published: March 2020

BACKGROUND

Traumatic hemorrhage and coagulopathy represent major sources of morbidity and mortality on the modern battlefield. Viscoelastic testing (VET) offers a potentially more personalized approach to resuscitation. We sought to evaluate outcomes of combat trauma patients who received VET-guided resuscitation compared with standard balanced blood product resuscitation.

METHODS

Retrospective analysis of the Department of Defense Trauma Registry, 2008 to 2016 was performed. Multivariate logistic regression analyses of all adult patients initially presenting to NATO Role III facilities who required blood products were performed to identify factors associated with VET-guided resuscitation and mortality. A propensity score matched comparison of outcomes in patient cohorts treated at VET versus non-VET Role III facilities was performed.

RESULTS

There are 3,320 patients, predominately male (98%), median age ranges from 25 years to 29 years, Injury Severity Score of 18.8, with a penetrating injury (84%) were studied. Overall mortality was 9.7%. Five hundred ninety-four patients had VET during their initial resuscitation. After adjusting for confounders, VET during initial resuscitation was independently associated with decreased mortality (odds ratio, 0.63; p = 0.04). Propensity analysis confirmed this survival advantage with a 57% reduction in overall mortality (7.3% vs. 13.1%; p = 0.001) for all patients requiring blood products.

CONCLUSION

Viscoelastic testing offers the possibility of a product-specific resuscitation for critically injured patients requiring transfusion in combat settings. Routine VET may be superior to non–VET-guided resuscitation for combat trauma victims.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
Comparison of American Association for the Surgery of Trauma grading scale with modified Hinchey classification in acute colonic diverticulitis: A pilot study
Authors: Ebersole Joseph , Medvecz Andrew J. , Connolly Cara , Sborov Katherine , Matevish Lauren , Wile Geoffrey , Gondek Stephen , Gunter Oliver , Guillamondegui Oscar , Dennis Bradley
Published: March 2020

BACKGROUND

The American Association for the Surgery of Trauma (AAST) developed a severity scale for surgical conditions, including diverticulitis. The Hinchey classification requires operative intervention yet remains the established scoring system for acute diverticulitis. This is a pilot study to compare the AAST grading scale for acute colonic diverticulitis with the traditional Hinchey classification. We hypothesize that the AAST classification scale is equivalent to the Hinchey in predicting outcomes.

METHODS

This is a retrospective cohort study at an academic medical center. A consecutive sample of patients with acute diverticulitis and computed tomography imaging was reviewed. Chart review identified demographic and physiologic data with interventional and clinical outcomes. Each computed tomography scan was assigned AAST and modified Hinchey classification scores by a radiologist. Multivariate regression and receiver operating characteristic curve analysis compared six outcomes: need for procedure, complication, intensive care unit (ICU) admission, length of stay, 30-day readmission, and mortality.

RESULTS

One hundred twenty-nine patients were included. Of the total patients, 42.6% required procedural intervention, 21.7% required ICU admission, 18.6% were readmitted, and 6.2% died. Both AAST and Hinchey predicted the need for operation (AAST odds ratios, 1.55, 12.7, 18.09, and 77.24 for stages 2–5; Hinchey odds ratios, 8.85, 11.49, and 22.9 for stages 1b–3, stage 4 predicted perfectly). The need for operation c-statistics (area under the curve) for AAST and Hinchey was 0.80 and 0.83 for Hinchey and AAST, respectively (p = 0.35). The complication c-statistics curve for AAST and Hinchey was 0.83 and 0.80, respectively (p = 0.33). The AAST and Hinchey scores were less predictive for ICU admission, readmission, and mortality with c-statistics of less than 0.80.

CONCLUSION

The AAST grading of acute diverticulitis is equivalent to the modified Hinchey classification in predicting procedural intervention and complications. The AAST system may be preferable to Hinchey because it can be applied preoperatively. Although this pilot study demonstrated that the AAST score predicts surgical need, a larger study is required to evaluate the AAST score for other outcomes.

LEVEL OF EVIDENCE

Prognostic and epidemiological study, level III.
A Case of Biopharmaceutical-Induced Catatonia and the Implication of a Novel Mechanism
Authors: Durns Tyler , Rich Bianca , Benson Carlie , Mickey Brian , Weischedel Kamile
Published: March 2020

Catatonia can be described structurally as a motor dysregulation syndrome with a concomitant behavioral component. However, despite its initial recognition nearly 150 years ago, the exact pathophysiological causes underlying this syndrome are still somewhat unknown and are potentially variable. This report reviews a case of a patient with multiple catatonic episodes precipitated by the use of an immunomodulator medication, and in doing so suggests a possible mechanism speaking to the immune system's role in the etiology of some cases of catatonia.
Gallium nitride micro-light-emitting diode structured light sources for multi-modal optical wireless communications systems
Authors: Griffiths A. D. , Herrnsdorf J. , McKendry J. J. D. , Strain M. J. , Dawson M. D.
Published: March 2020

Gallium nitride-based light-emitting diodes (LEDs) have revolutionized the lighting industry with their efficient generation of blue and green light. While broad-area (square millimetre) devices have become the dominant LED lighting technology, fabricating LEDs into micro-scale pixels (micro-LEDs) yields further advantages for optical wireless communications (OWC), and for the development of smart-lighting applications such as tracking and imaging. The smaller active areas of micro-LEDs result in high current density operation, providing high modulation bandwidths and increased optical power density. Fabricating micro-LEDs in array formats allows device layouts to be tailored for target applications and provides additional degrees of freedom for OWC systems. Temporal and spatial control is crucial to use the full potential of these micro-scale sources, and is achieved by bonding arrays to pitch-matched complementary metal-oxide-semiconductor control electronics. These compact, integrated chips operate as digital-to-light converters, providing optical signals from digital inputs. Applying the devices as projection systems allows structured light patterns to be used for tracking and self-location, while simultaneously providing space-division multiple access communication links. The high-speed nature of micro-LED array devices, combined with spatial and temporal control, allows many modes of operation for OWC providing complex functionality with chip-scale devices.

This article is part of the theme issue ‘Optical wireless communication’.
Identification of Acinetobacter baumannii loci for capsular polysaccharide (KL) and lipooligosaccharide outer core (OCL) synthesis in genome assemblies using curated reference databases compatible with Kaptive
Authors: Wyres Kelly L. , Cahill Sarah M. , Holt Kathryn E. , Hall Ruth M. , Kenyon Johanna J.
Published: March 2020

Multiply antibiotic-resistant

Acinetobacter baumannii

infections are a global public health concern and accurate tracking of the spread of specific lineages is needed. Variation in the composition and structure of capsular polysaccharide (CPS), a critical determinant of virulence and phage susceptibility, makes it an attractive epidemiological marker. The outer core (OC) of lipooligosaccharide also exhibits variation. To take better advantage of the untapped information available in whole genome sequences, we have created a curated reference database of 92 publicly available gene clusters at the locus encoding proteins responsible for biosynthesis and export of CPS (K locus), and a second database for 12 gene clusters at the locus for outer core biosynthesis (OC locus). Each entry has been assigned a unique KL or OCL number, and is fully annotated using a simple, transparent and standardized nomenclature. These databases are compatible with Kaptive, a tool for in silico typing of bacterial surface polysaccharide loci, and their utility was validated using (a) >630 assembled

A. baumannii

draft genomes for which the KL and OCL regions had been previously typed manually, and (b) 3386

A. baumannii

genome assemblies downloaded from NCBI. Among the previously typed genomes, Kaptive was able to confidently assign KL and OCL types with 100 % accuracy. Among the genomes retrieved from NCBI, Kaptive detected known KL and OCL in 87 and 90 % of genomes, respectively, indicating that the majority of common KL and OCL types are captured within the databases; 13 of the 92 KL in the database were not detected in any publicly available whole genome assembly. The failure to assign a KL or OCL type may indicate incomplete or poor-quality genomes. However, further novel variants may remain to be documented. Combining outputs with multilocus sequence typing (Institut Pasteur scheme) revealed multiple KL and OCL types in collections of a single sequence type (ST) representing each of the two predominant globally distributed clones, ST1 of GC1 and ST2 of GC2, and in collections of other clones comprising >20 isolates each (ST10, ST25, and ST140), indicating extensive within-clone replacement of these loci. The databases are available at https://github.com/katholt/Kaptive and will be updated as further locus types become available.
Applying Tensile and Compressive Force to Xenopus Animal Cap Tissue
Authors: Goddard Georgina K. , Tarannum Nawseen , Woolner Sarah
Published: March 2020

Over many years, the Xenopus laevis embryo has provided a powerful model system to investigate how mechanical forces regulate cellular function. Here, we describe a system to apply reproducible tensile and compressive force to X. laevis animal cap tissue explants and to simultaneously assess cellular behavior using live confocal imaging.
Structural and biochemical characterization of mitochondrial citrate synthase 4 from Arabidopsis thaliana
Authors: Nishio Kazuya , Mizushima Tsunehiro
Published: March 2020

Citrate synthase (CS) catalyzes the conversion of oxaloacetate and acetyl coenzyme A into citrate and coenzyme A in the mitochondrial tricarboxylic acid (TCA) cycle. In plants, mitochondrial metabolism, including the TCA cycle, occurs in interaction with photosynthetic metabolism. The controlled regulation of several enzymes in the TCA cycle, such as CS, is important in plants. Here, the first crystal structure of a plant mitochondrial CS, CSY4 from Arabidopsis thaliana (AtCSY4), has been determined. Structural comparison of AtCSY4 with mitochondrial CSs revealed a high level of similarity. Inhibition analysis showed a similar manner of inhibition as in mitochondrial CSs. The effect of oxidation on one of a pair of cysteine residues in AtCSY4 was speculated upon based on the folded structure.
Optimizing the refinement of merohedrally twinned P61 HIV-1 protease–inhibitor cocrystal structures
Authors: Lockbaum Gordon J. , Leidner Florian , Royer William E. , Kurt Yilmaz Nese , Schiffer Celia A.
Published: March 2020

Twinning is a crystal-growth anomaly in which protein monomers exist in different orientations but are related in a specific way, causing diffraction reflections to overlap. Twinning imposes additional symmetry on the data, often leading to the assignment of a higher symmetry space group. Specifically, in merohedral twinning, reflections from each monomer overlap and require a twin law to model unique structural data from overlapping reflections. Neglecting twinning in the crystallographic analysis of quasi-rotationally symmetric homo-oligomeric protein structures can mask the degree of structural non-identity between monomers. In particular, any deviations from perfect symmetry will be lost if higher than appropriate symmetry is applied during crystallographic analysis. Such cases warrant choosing between the highest symmetry space group possible or determining whether the monomers have distinguishable structural asymmetries and thus require a lower symmetry space group and a twin law. Using hexagonal cocrystals of HIV-1 protease, a C
2-symmetric homodimer whose symmetry is broken by bound ligand, it is shown that both assigning a lower symmetry space group and applying a twin law during refinement are critical to achieving a structural model that more accurately fits the electron density. By re-analyzing three recently published HIV-1 protease structures, improvements in nearly every crystallographic metric are demonstrated. Most importantly, a procedure is demonstrated where the inhibitor can be reliably modeled in a single orientation. This protocol may be applicable to many other homo-oligomers in the PDB.
Understanding the liminality of individual giving to the arts
Authors: Pitts Stephanie E. , Herrero Marta , Price Sarah M.
Published: March 2020

Purpose

The purpose of this paper is to explore the experiences of donors to a UK-based contemporary music organisation fundraising scheme through the theoretical lens of liminality.

Design/methodology/approach

In-depth interviews with 16 members of the Sound Investment scheme investigated the motivations and experiences of individual donors to the commissioning of new music. Thematic analysis suggested parallels with the framework of “liminality,” which shed new light on the ways in which membership changed donors' relationships with the organisation and audience.

Findings

Motivations for supporting contemporary music commissioning included personal interest, cultural responsibility and alignment to the values of the organisation. Tangible benefits, particularly access to rehearsals, brought donors into closer connection with the creative and managerial working of the organisation.

Research limitations/implications

The sample did not include any lapsed donors, or people who had chosen not to participate. Future research could test the liminal framework in different artforms and through different tangible benefits.

Practical implications

Understanding donors as liminals could help arts organisations to develop membership schemes that more effectively sustain individual giving. Key elements of involvement and access are identified that could engage audiences more widely.

Originality/value

This case study foregrounds lived experience of arts donors where previous literature has primarily focussed on motivations for donating. It highlights the liminal elements of becoming an individual donor, namely, the integration and socialisation processes, the space-and time-bound interactions with the organisation and the alignment of values with the organisation. This framework offers a new way for arts organisations to understand and enhance individual giving in a time of austerity.
Crowdfunding in digital humanities: some evidence from Indonesian social enterprises
Authors: Pratono Aluisius Hery , Prima Delta Ardy , Sinaga Nur Flora Nita Taruli , Permatasari Anggraeni , Ariani Mintarti , Han Ling
Published: March 2020

Purpose

This article aims to understand how social enterprises adopt crowdfunding in digital humanities by investigating the mission drifting, risk sharing and human resource practices.

Design/methodology/approach

This exploratory study uses a qualitative method by observing five different social ventures in Indonesia. The case study involves observation of social enterprises that concern digital humanities projects and interviews with those who manage the crowdfunding for financing the projects as the key respondents. The analysis uses an interpretative approach by involving the respondents to explain the phenomena.

Findings

(1) Adopting the crowdfunding platform encourages social enterprises to reshape social missions with more responsive action for digital humanities. (2) Crowdfunding allows social enterprises to share the risk with stakeholders who focus on fostering the social impact of digital humanities. (3) Crowdfunding stimulates social enterprises to hire professional workers with flexible work arrangements to attract specific donors and investors.

Originality/value

The result extends the principles of social enterprises by introducing some concepts of crowdfunding in digital humanities. This study also explains the boundary conditions of digital humanities projects and how crowdfunding can support the projects by adopting the principles of the social enterprise that works on digital humanities projects.