bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix-Associated Chondrocyte Implantation Is Associated With Fewer Reoperations Than Microfracture: Results of a Population-Representative, Matched-Pair Claims Data Analysis for Cartilage Defects of the Knee
Authors: Niemeyer Philipp , Schubert Tino , Grebe Marco , Hoburg Arnd
Published: October 2019

Background:

Symptomatic cartilage defects of the knee are commonly surgically treated by microfracture (MFX) or matrix-associated chondrocyte implantation (M-ACI). Several randomized controlled trials have compared MFX and M-ACI, showing a tendency to lower reoperation rates for M-ACI, but results vary widely between studies.

Purpose:

To compare reoperation rates after MFX and M-ACI in cartilage defects of the knee outside clinical trials in a representative sample of the population.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

This study was based on anonymized, population-representative claims data of 4 million insured persons in Germany. Patients who underwent MFX or M-ACI for cartilage defects of the knee with a follow-up of 2 years were compared. The primary endpoint was the need for a reoperation, defined as a claim for a second surgical procedure from the same patient at the knee joint (27 procedure codes), meniscus and cartilage (35 procedure codes), or patella (102 procedure codes) or the need for knee replacement (11 procedure codes). Group comparisons were performed using log-rank tests, with a 2-sided P value of <.05 to indicate significance. For adjusted analysis, propensity score matching was applied. Age, sex, comedications, and comorbidities were used as matching parameters.

Results:

A total of 6425 patients fulfilled the inclusion criteria: 6273 treated with MFX and 152 treated with M-ACI (mean age, 53 and 36 years, respectively). In the 2 years after treatment, 1271 patients in the MFX group needed a reoperation compared with 19 in the M-ACI group (20.3% vs 12.5%, respectively; P = .0199). For adjusted analysis after propensity score matching, 127 patients per group were analyzed. Their mean age was 37 years. At the end of the second follow-up year, 28 and 16 patients needed reoperations in the MFX and M-ACI groups, respectively (22.0% vs 12.6%, respectively; P = .0498).

Conclusion:

This study used a representative sample of the population and a broad definition of a reoperation, thus expanding evidence from clinical trials. We found a significant advantage of M-ACI in reoperation rates 2 years after treatment. After adjusting for age, sex, comedications, and comorbidities, M-ACI still showed significantly lower reoperation rates after 2 years.
Emotions in Social Media: An Analysis of Tweet Responses to MH370 Search Suspension Announcement
Authors: Yeo Su Lin , Pang Augustine , Cheong Michelle , Yeo Jerome Quincy
Published: October 2019

Considered one of the deadliest incidents in the history of aviation crises and labelled a “continuing mystery,” the ongoing search for the missing Malaysia Airlines Flight 370 offers no closure. With endless media attention, and negative reactions of stakeholders to every decision made by the airline, this study investigates the types of emotions found in social media posted by publics to the MH370 search suspension announcement. It content analyzed 5,062 real-time tweet messages guided by the revised integrated crisis mapping model. Our findings indicated that, in addition to the four original emotions posited, there was a fifth emotion because of the long-drawn crisis and only two dominant emotions were similar to the model. A redrawn version to better encapsulate all the emotions is offered for one quadrant in the model. Implications for both crisis communication scholarship and the importance of social listening for organizations are discussed.
Multiple Myeloma Presenting as Recalcitrant Macular Edema
Authors: Wisely C. Ellis , Zhang Wenlan , Grewal Dilraj S.
Published: October 2019

Purpose:

This article presents an unusual case of ocular involvement of multiple myeloma masquerading as macular edema associated with diabetic retinopathy.

Methods:

A report of a single case.

Results:

The presence of concomitant type 2 diabetes and scattered retinal hemorrhages presented a diagnostic challenge. Large globular vitreous opacities and significant weight loss were suggestive of a neoplastic process. We demonstrate multimodal imaging findings that can be associated with plasma cell dyscrasias and also describe the purported mechanism by which plasma cell dyscrasias cause macular edema and exudative retinal detachments.

Conclusion:

Although multiple myeloma and related plasma cell dyscrasias are rare causes of ocular disease, they should be considered in the differential diagnosis of recalcitrant macular edema, and there should be a low threshold for systemic evaluation.
Progressing the Governance Standards: Role of HR
Authors: Mukherjee Rachna
Published: October 2019

To have a robust governance standard become a practice in an organisation requires both a lucid stating of the principles and code of conduct along with creating a culture where a respect for these principles is acknowledged and positively reinforced. The human resources team plays a critical role in this scenario by offering a cogent professional conduct template as well as fostering a sustained culture, reflective of this, given the interventions which HR can facilitate across business units and different sets of professional segments.
Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia
Authors: Gökbuget Nicola , Kantarjian Hagop M. , Brüggemann Monika , Stein Anthony S. , Bargou Ralf C. , Dombret Hervé , Fielding Adele K. , Heffner Leonard , Rigal-Huguet Françoise , Litzow Mark , O’Brien Susan , Zugmaier Gerhard , Gao Shan , Nagorsen Dirk , Forman Stephen J. , Topp Max S.
Published: October 2019

Key Points

MRD response has value as a prognostic factor for blinatumomab treatment in R/R B-cell precursor ALL. MRD response was associated with better outcomes in terms of OS and RFS in blinatumomab-treated R/R ALL.
Pulmonary hypertension and chronic lung disease: where are we headed?
Authors: Elia Davide , Caminati Antonella , Zompatori Maurizio , Cassandro Roberto , Lonati Chiara , Luisi Francesca , Pelosi Giuseppe , Provencher Steeve , Harari Sergio
Published: October 2019

Pulmonary hypertension related to chronic lung disease, mainly represented by COPD and idiopathic pulmonary fibrosis, is associated with a worse outcome when compared with patients only affected by parenchymal lung disease. At present, no therapies are available to reverse or slow down the pathological process of this condition and most of the clinical trials conducted to date have had no clinically significant impact. Nevertheless, the importance of chronic lung diseases is always more widely recognised and, along with its increasing incidence, associated pulmonary hypertension is also expected to be growing in frequency and as a health burden worldwide. Therefore, it is desirable to develop useful and reliable tools to obtain an early diagnosis and to monitor and follow-up this condition, while new insights in the therapeutic approach are explored.
A feasibility, randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis (BREEZE-IPF): study protocol
Authors: Wright Caroline , Hart Simon P. , Allgar Victoria , English Anne , Swan Flavia , Dyson Judith , Richardson Gerry , Twiddy Maureen , Cohen Judith , Hussain Jamilla , Johnson Miriam , Hargreaves Ian , Crooks Michael G.
Published: October 2019

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that causes breathlessness and cough that worsen over time, limiting daily activities and negatively impacting quality of life. Although treatments are now available that slow the rate of lung function decline, trials of these treatments have failed to show improvement in symptoms or quality of life. There is an immediate unmet need for evidenced-based interventions that improve patients' symptom burden and make a difference to everyday living. This study aims to assess the feasibility of conducting a definitive randomised controlled trial of a holistic, complex breathlessness intervention in people with IPF.

Methods and analysis

The trial is a two-centre, randomised controlled feasibility trial of a complex breathlessness intervention compared with usual care in patients with IPF. 50 participants will be recruited from secondary care IPF clinics and randomised 1:1 to either start the intervention within 1 week of randomisation (fast-track group) or to receive usual care for 8 weeks before receiving the intervention (wait-list group). Participants will remain in the study for a total of 16 weeks. Outcome measures will be feasibility outcomes, including recruitment, retention, acceptability and fidelity of the intervention. Clinical outcomes will be measured to inform outcome selection and sample size calculation for a definitive trial.

Ethics and dissemination

Yorkshire and The Humber – Bradford Leeds Research Ethics Committee approved the study protocol (REC 18/YH/0147). Results of the main trial and all secondary end-points will be submitted for publication in a peer-reviewed journal.
Adapting the engine to the fuel: mutator populations can reduce the mutational load by reorganizing their genome structure
Authors: Rutten Jacob Pieter , Hogeweg Paulien , Beslon Guillaume
Published: October 2019

Background

Mutators are common in bacterial populations, both in natural isolates and in the lab. The fate of these lineages, which mutation rate is increased up to 100 ×, has long been studied using population genetics models, showing that they can spread in a population following an environmental change. However in stable conditions, they suffer from the increased mutational load, hence being overcome by non-mutators. However, these results don’t take into account the fact that an elevated mutation rate can impact the genetic structure, hence changing the sensitivity of the population to mutations. Here we used Aevol, an in silico experimental evolution platform in which genomic structures are free to evolve, in order to study the fate of mutator populations evolving for a long time in constant conditions.

Results

Starting from wild-types that were pre-evolved for 300,000 generations, we let 100 mutator populations (point mutation rate ×100) evolve for 100,000 further generations in constant conditions. As expected all populations initially undergo a fitness loss. However, after that the mutator populations started to recover. Most populations ultimately recovered their ancestors fitness, and a significant fraction became even fitter than the non-mutator control clones that evolved in parallel. By analyzing the genomes of the mutators, we show that the fitness recovery is due to two mechanisms: i. an increase in robustness through compaction of the coding part of the mutator genomes, ii. an increase of the selection coefficient that decreases the mean-fitness of the population. Strikingly the latter is due to the accumulation of non-coding sequences in the mutators genomes.

Conclusion

Our results show that the mutational burden that is classically thought to be associated with mutator phenotype is escapable. On the long run mutators adapted their genomes and reshaped the distribution of mutation effects. Therewith the lineage is able to recover fitness even though the population still suffers the elevated mutation rate. Overall these results change our view of mutator dynamics: by being able to reduce the deleterious effect of the elevated mutation rate, mutator populations may be able to last for a very long time; A situation commonly observed in nature.
Correction to: Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome
Authors: Lutschinger Leon L. , Rigopoulos Angelos G. , Schlattmann Peter , Matiakis Marios , Sedding Daniel , Schulze Paul Christian , Noutsias Michel
Published: October 2019

After publication of the original article [1], we were notified that an author’s name is not complete.
Giant cell tumor of tendon sheath in the hand: analysis of risk factors for recurrence in 50 cases
Authors: Ozben Hakan , Coskun Tamer
Published: October 2019

Background

Giant cell tumor of the tendon sheath is the most common form of giant cell tumors and is the second most common soft tissue tumor of the hand region after ganglion cyst. Magnetic resonance imaging is the diagnostic tool of choice for both diagnosis and treatment planning. The current standard treatment of choice is simple excision. The main concern about the treatment is related to the high recurrence rates. Besides incomplete excision, there is no consensus concerning the effect of other risk factors on recurrence. The literature lacks detailed reports on surgical excision of these tumors with a standardized surgical treatment and an appropriate patient follow up. The aim of this study was to investigate the recurrence rate and the associated recurrence risk factors for giant cell tumor of tendon sheath of the hand following a standardized treatment.

Methods

The records of patients treated for giant cell tumor of tendon sheath of the hand treated by the same hand surgeon were evaluated retrospectively. The features obtained from preoperative magnetic resonance imaging, final physical examination, patients’ age and sex, anatomical site of the tumor, relationship of the tumor with bone, joint or neurovascular structures, bone invasion, recurrence after surgery and complications like skin necrosis, digital neuropathy or limitation in range of motion were documented. Chi-square test was used to compare categorical variables.

Results

Fifty patient were included in the study. The average follow-up time was 84 months. Three recurrences (6%) were recorded. The only significant risk factor for the recurrence was tumor adjacency to the interphalangeal joints of the fingers other than thumb. No major or minor complications were encountered in the postoperative period.

Conclusion

With adequate surgical exposure and meticulous dissection provided by the magnification loupes, we were able demonstrate one of the lowest recurrence rates in the literature. Well-designed studies combining the recurrence rates of several hand surgery centers implementing a standardized treatment are needed to better demonstrate the associated risk factors for recurrence.
Neurobrucellosis in a common bottlenose dolphin (Tursiops truncatus) stranded in the Canary Islands
Authors: Sierra Eva , Fernández Antonio , Felipe-Jiménez Idaira , Zucca Daniele , Di Francesco Gabriella , Díaz-Delgado Josué , Sacchini Simona , Rivero Miguel A. , Arbelo Manuel
Published: October 2019

Background

Brucella spp. isolation is increasingly reported in cetaceans, although associated pathologies, including lesions of the musculoskeletal and nervous systems, are less frequently described. Concerning the nervous system, Brucella sp. infection causing meningitis, meningoencephalitis or meningoencephalomyelitis have been extensively reported in striped dolphins (Stenella coeruleoalba), and less frequently in other cetacean species.

Case presentation

A juvenile female common bottlenose dolphin (Tursiops truncatus) was found stranded alive in Lanzarote (Canary Islands, Spain) in 2005, but died shortly after. On physical examination, the dolphin showed a moderate body condition and was classified as code 2 (fresh dead) at the time of necropsy. The main gross findings were severe multiorgan parasitism, thickened and congested leptomeninges, and (sero)fibrino-suppurative and proliferative arthritis of the shoulder joint. Histopathological examination revealed the distinct features of a sub-acute systemic disease associated with Cetacean Morbillivirus (CeMV) infection. However, brain lesions diverged from those reported in systemic CeMV infection. This led to suspect that there was a coinfecting pathogen, based on the characteristics of the inflammatory response and the lesion distribution pattern in the central nervous system. Brucella sp. was detected in the brain tissue by PCR and Brucella antigen was demonstrated by immunohistochemistry in the brain and shoulder joint lesions.

Conclusions

The zoonotic potential of marine mammal strains of Brucella has been demonstrated both in natural and laboratory conditions. In this study, PCR detected Brucella sp. in the brain of a common bottlenose dolphin stranded in the Canary Islands; the dolphin was also co-infected with CeMV. This is the first detection of Brucella sp. infection in a stranded cetacean in this archipelago. Therefore, we stress the importance of taking adequate measures during the handling of these species to prevent the transmissions of the infection to humans.
Association of lipid accumulation product trajectories with 5-year incidence of type 2 diabetes in Chinese adults: a cohort study
Authors: Yan Guangyu , Li Fei , Elia Christelle , Zhao Yating , Wang Jiangguang , Chen Zhiheng , Yuan Hong , Lu Yao
Published: October 2019

Background

Lipid accumulation product (LAP) is an index describing the overaccumulation of lipid. Baseline LAP was used for type 2 diabetes (T2D) prediction in previous studies. But the longitudinal trajectories of LAP, which reflect the efficacy of patients’ lipid-lowering treatment and lifestyle improvement, have rarely been studied. The aim of this study is to explore the association of lipid accumulation product trajectories with 5-year incidence of type 2 diabetes.

Methods

This cohort study included 4508 non-diabetic participants with a median age of 42 years. Using the group-based trajectory modeling (GBTM), LAP from 2011 to 2016 were determined and identified as three trajectories: low (n = 3639), moderate (n = 800), and high (n = 69). Baseline LAP was divided into groups by percentiles and tertiles respectively for the comparison of LAP trajectories. The associations between 5-year T2D incidence and LAP trajectories and baseline LAP were both assessed by generalized linear models.

Results

From 2011 to 2016, 169 participants developed T2D (the 5-year incidence of 3.8%). For participants with low, moderate, and high trajectories, the incidence of T2D was 2.1, 10.0, and 15.9%, respectively. A significant trend was observed in the relative risks (RRs) of 5-year incident T2D in participants with moderate (RR, 1.95; 95% CI: 1.41–2.70) and high LAP trajectory (RR, 2.20; 95% CI: 1.12–4.30) in the fully adjusted model (p for trend< 0.001). However, there were no statically significant trends in RRs in different tertiles of baseline LAP found after full adjustments.

Conclusion

The trajectories of LAP has an independent effect on 5-year T2D incidence beyond LAP measured at baseline.
Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana
Authors: Bhatia Rohini K. , Narasimhamurthy Mohan , Martei Yehoda M. , Prabhakar Pooja , Hutson Jeré , Chiyapo Sebathu , Makozhombwe Ignetious , Feldman Michael , Kayembe Mukendi K. A. , Cooper Kum , Grover Surbhi
Published: October 2019

Background

To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status.

Methods

This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records.

Results

A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44–66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%,p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER−/PR−/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER−/PR−/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals.

Conclusions

Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.
Resveratrol induces immunogenic cell death of human and murine ovarian carcinoma cells
Authors: Zhang Yanke , Yang Sufen , Yang Yang , Liu Teng
Published: October 2019

Purpose

This study aimed to clarify whether immunogenic cell death (ICD) contributed to the anti-tumor action of resveratrol against ovarian carcinoma.

Methods

Resveratrol suppressed cell proliferation and induced apoptosis in ovarian carcinoma cells. In addition, resveratrol treatment stimulated cell surface exposure of calreticulin, HMGB1 secretion and ATP release.

Results

Vaccination with resveratrol-pretreated ID8 cells significantly inhibited growth of subsequent inoculated xenograft tumor. Direct administration with resveratrol suppressed tumor progression accompanied with compromised cell proliferation and enhanced cell apoptosis. We further characterized increases of both mature dendritic cells and cytotoxic T cells in xenograft tumor in response to resveratrol treatment, which also inhibited TGF-β production and stimulated both IL12p7 and IFN-γ secretion. Most importantly, we demonstrated that combination with PD-1 antibody greatly inhibited tumor growth, while depletion of CD8+ T cells by neutralizing antibody restored xenograft progression.

Conclusion

Our data suggested resveratrol exerted anti-tumor action against ovarian cancer via both apoptosis and ICD pathways.
Cacna1b alternative splicing impacts excitatory neurotransmission and is linked to behavioral responses to aversive stimuli
Authors: Bunda Alexandra , LaCarubba Brianna , Bertolino Melanie , Akiki Marie , Bath Kevin , Lopez-Soto Javier , Lipscombe Diane , Andrade Arturo
Published: October 2019

Presynaptic CaV2.2 channels control calcium entry that triggers neurotransmitter release at both central and peripheral synapses. The Cacna1b gene encodes the α1-pore forming subunit of CaV2.2 channels. Distinct subsets of splice variants of CaV2.2 derived from cell-specific alternative splicing of the Cacna1b pre-mRNA are expressed in specific subpopulations of neurons. Four cell-specific sites of alternative splicing in Cacna1b that alter CaV2.2 channel function have been described in detail: three cassette exons (e18a, e24a, and e31a) and a pair of mutually exclusive exons (e37a/e37b). Cacna1b mRNAs containing e37a are highly enriched in a subpopulation of nociceptors where they influence nociception and morphine analgesia. E37a-Cacna1b mRNAs are also expressed in brain, but their cell-specific expression in this part of the nervous system, their functional consequences in central synapses and their role on complex behavior have not been studied. In this report, we show that e37a-Cacna1b mRNAs are expressed in excitatory projection neurons where CaV2.2 channels are known to influence transmitter release at excitatory inputs from entorhinal cortex (EC) to dentate gyrus (DG). By comparing behaviors of WT mice to those that only express e37b-CaV2.2 channels, we found evidence that e37a-CaV2.2 enhances behavioral responses to aversive stimuli. Our results suggest that alternative splicing of Cacna1b e37a influences excitatory transmitter release and couples to complex behaviors.
Activity of MCPIP1 RNase in tumor associated processes
Authors: Miekus Katarzyna , Kotlinowski Jerzy , Lichawska-Cieslar Agata , Rys Janusz , Jura Jolanta
Published: October 2019

The monocyte chemoattractant protein-induced protein (MCPIP) family consists of 4 members (MCPIP1–4) encoded by theZC3h12A-Dgenes, which are located at different loci. The common features of MCPIP proteins are the zinc finger domain, consisting of three cysteines and one histidine (CCCH), and the N-terminal domain of the PilT protein (PilT-N-terminal domain (PIN domain)). All family members act as endonucleases controlling the half-life of mRNA and microRNA (miRNA). The best-studied member of this family is MCPIP1 (also known as Regnase-1).

In this review, we discuss the current knowledge on the role of MCPIP1 in cancer-related processes. Because the characteristics of MCPIP1 as a fundamental negative regulator of immune processes have been comprehensively described in numerous studies, we focus on the function of MCPIP1 in modulating apoptosis, angiogenesis and metastasis.
The Jun N-terminal kinases signaling pathway plays a “seesaw” role in ovarian carcinoma: a molecular aspect
Authors: Dou Yingyu , Jiang Xiaoyan , Xie Hui , He Junyu , Xiao Songshu
Published: October 2019

Ovarian cancer is the most common gynecological malignancy that causes cancer-related deaths in women today; this being the case, developing an understanding of ovarian cancer has become one of the major driving forces behind cancer research overall. Moreover, such research over the last 20 years has shown that the Jun N-terminal kinase (JNK) signaling pathway plays an important role in regulating cell death, survival, growth and proliferation in the mitogen-activated protein kinases (MAPK) signaling pathway, an important pathway in the formation of cancer. Furthermore, the JNK signaling pathway is often regulated by an abnormal activation in human tumors and is frequently reported in the literature for its effect on the progression of ovarian cancer. Although the FDA has approved some JNK inhibitors for melanoma, the agency has not approved JNK inhibitors for ovarian cancer. However, there are some experimental data on inhibitors and activators of the JNK signaling pathway in ovarian cancer, but related clinical trials need to be further improved. Although the Jun N-terminal kinase (JNK) signaling pathway is implicated in the formation of cancer in general, research has also indicated that it has a role in suppressing cancer as well. Here, we summarize this seemingly contradictory role of the JNK signaling pathway in ovarian cancer, that ‘seesaws’ between promoting and suppressing cancer, as well as summarizing the application of several JNK pathway inhibitors in cancer in general, and ovarian cancer in particular.
Cardiovascular diseases risk factors among recently arrived Eritrean refugees in Switzerland
Authors: Chernet Afona , Probst-Hensch Nicole , Sydow Véronique , Paris Daniel H. , Neumayr Andreas , Labhardt Niklaus D.
Published: October 2019

Objective

For the past 10 years, refugees from Eritrea represented the majority of asylum seekers in Switzerland. However, data on their health status remains limited. In this cross-sectional survey followed by a 1-year cohort study, we screened newly arrived Eritrean refugees for cardiovascular risk factors at arrival and 1-year post registration.

Results

Among 107 participants (88.8% male; median age 25, 9 (9%) had a body mass index ≥ 25 kg/m2, one (1%) had elevated blood pressure, one (1%) had diabetes, 19% smoked and two (2%) had a low density lipoprotein (LDL) cholesterol ≥ 4.1 mmol/l. Among the 48 participants (5 females, 43 males) followed, there were no significant changes in cardiovascular risk profile 1 year post-arrival.
Identifying incident cancer cases in routinely collected hospital data: a retrospective validation study
Authors: Goldsbury David E. , Weber Marianne F. , Canfell Karen , O’Connell Dianne L.
Published: October 2019

Objective

Population-level cancer incidence data are critical for epidemiological cancer research, however provision of cancer registry data can be delayed. We previously reported that in a large population-based Australian cohort, registry-based incidence data were well matched by routinely collected hospital diagnosis data (sensitivities and positive predictive values (PPVs) > 80%) for six of the 12 most common cancer types: breast, colorectum, kidney, lung, pancreas and uterus. The available hospital data covered more recent time periods. We have since obtained more recent cancer registry data, allowing us to further test the validity of hospital diagnosis records in identifying incident cases.

Results

The more recent hospital diagnosis data were valid for identifying incident cases for the six cancer types, with sensitivities 81–94% and PPVs 86–96%. However, 2–10% of cases were identified > 3 months after the registry’s diagnosis date and detailed clinical cancer information was unavailable. The level of identification was generally higher for cases aged < 80 years, those with known disease stage and cases living in higher socioeconomic areas. The inclusion of death records increased sensitivity for some cancer types, but requires caution due to potential false-positive cases. This study validates the use of hospital diagnosis records for identifying incident cancer cases.
DNA methylation of individual repetitive elements in hepatitis C virus infection-induced hepatocellular carcinoma
Authors: Zheng Yinan , Hlady Ryan A. , Joyce Brian T. , Robertson Keith D. , He Chunyan , Nannini Drew R. , Kibbe Warren A. , Achenbach Chad J. , Murphy Robert L. , Roberts Lewis R. , Hou Lifang
Published: October 2019

Background

The two most common repetitive elements (REs) in humans, long interspersed nuclear element-1 (LINE-1) and Alu element (Alu), have been linked to various cancers. Hepatitis C virus (HCV) may cause hepatocellular carcinoma (HCC) by suppressing host defenses, through DNA methylation that controls the mobilization of REs. We aimed to investigate the role of RE methylation in HCV-induced HCC (HCV-HCC).

Results

We studied methylation of over 30,000 locus-specific REs across the genome in HCC, cirrhotic, and healthy liver tissues obtained by surgical resection. Relative to normal liver tissue, we observed the largest number of differentially methylated REs in HCV-HCC followed by alcohol-induced HCC (EtOH-HCC). After excluding EtOH-HCC-associated RE methylation (FDR < 0.001) and those unable to be validated in The Cancer Genome Atlas (TCGA), we identified 13 hypomethylated REs (11 LINE-1 and 2 Alu) and 2 hypermethylated REs (1 LINE-1 and 1 Alu) in HCV-HCC (FDR < 0.001). A majority of these REs were located in non-coding regions, preferentially enriched with chromatin repressive marks H3K27me3, and positively associated with gene expression (median correlation r = 0.32 across REs). We further constructed an HCV-HCC RE methylation score that distinguished HCV-HCC (lowest score), HCV-cirrhosis, and normal liver (highest score) in a dose-responsive manner (p for trend < 0.001). HCV-cirrhosis had a lower score than EtOH-cirrhosis (p = 0.038) and HCV-HCC had a lower score than EtOH-HCC in TCGA (p = 0.024).

Conclusions

Our findings indicate that HCV infection is associated with loss of DNA methylation in specific REs, which could implicate molecular mechanisms in liver cancer development. If our findings are validated in larger sample sizes, methylation of these REs may be useful as an early detection biomarker for HCV-HCC and/or a target for prevention of HCC in HCV-positive individuals.
Dynamic derangement in amino acid profile during and after a stroke-like episode in adult-onset mitochondrial disease: a case report
Authors: Fukuda Mai , Nagao Yoshiro
Published: October 2019

Background

Maternally inherited diabetes and deafness, and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are examples of mitochondrial diseases that are relatively common in the adult population. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are assumed to be associated with decreases in arginine and citrulline. Biomarkers, such as growth differentiation factor-15, were developed to assist in the diagnosis of mitochondrial diseases.

Case presentation

A 55-year-old Japanese man, an insulin user, presented after a loss of consciousness. A laboratory test showed diabetic ketoacidosis. He and his mother had severe hearing difficulty. Bilateral lesions on magnetic resonance imaging, the presence of seizure, and an elevated ratio of lactate to pyruvate, altogether suggested a diagnosis of mitochondrial disease. Mitochondrial DNA in our patient’s peripheral blood was positive with a 3243A>G mutation, which is the most frequent cause of maternally inherited diabetes and deafness, and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. As a result, maternally inherited diabetes and deafness/mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes was diagnosed. We measured growth differentiation factor-15 and multiple amino acids in his blood, longitudinally during and after the stroke-like episode. Growth differentiation factor-15 was increased to an immeasurably high level on the day of the stroke-like episode. Although his diabetes improved with an increased dose of insulin, the growth differentiation factor-15 level gradually increased, suggesting that his mitochondrial insufficiency did not improve. Multiple amino acid species, including arginine, citrulline, and taurine, showed a decreased level on the day of the episode and a sharp increase the next day. In contrast, the level of aspartic acid increased to an extremely high level on the day of the episode, and decreased gradually thereafter.

Conclusions

Growth differentiation factor-15 can be used not only for the diagnosis of mitochondrial disease, but as an indicator of its acute exacerbation. A stroke-like episode of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes reflects a drastic derangement of multiple amino acids. The involvement of aspartic acid in the episodes should be explored in future studies.
Multi-compositional MRI evaluation of repair cartilage in knee osteoarthritis with treatment of allogeneic human adipose-derived mesenchymal progenitor cells
Authors: Zhao Xinxin , Ruan Jingjing , Tang Hui , Li Jia , Shi Yingxuan , Li Meng , Li Suke , Xu Cuili , Lu Qing , Dai Chengxiang
Published: October 2019

Background

We used multimodal compositional magnetic resonance imaging (MRI) techniques, combined with clinical outcomes, to differentiate the alternations of composition in repair cartilage with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) in knee osteoarthritis (KOA) patients.

Methods

Eighteen patients participated a phase I/IIa clinical trial. All patients were divided randomly into three groups with intra-articular injections of haMPCs: the low-dose (1.0 × 107 cells), mid-dose (2.0 × 107), and high-dose (5.0 × 107) groups with six patients each. Compositional MRI examinations and clinical evaluations were performed at different time points.

Results

Significant differences were observed in quantitative T1rho, T2, T2star, R2star, and ADC measurements in patients of three dose groups, suggesting a possible compositional changes of cartilage with the treatment of allogeneic haMPCs. Also significant reduction in WOMAC and SF-36 scores showed the symptoms might be alleviated to some extent with this new treatment. As regards sensibilities of multi-parametric mappings to detect compositional or structural changes of cartilage, T1rho mapping was most sensitive to differentiate difference between three dose groups.

Conclusions

These results showed that multi-compositional MRI sequences might be an effective tool to evaluate the promotion of the repair of cartilage with allogeneic haMPCs by providing information of compositional alterations of cartilage.

Trial registration

Clinicaltrials, NCT02641860. Registered 3 December 2015.
The dynamic properties of solutions for a nonlinear shallow water equation
Authors: Su Yeqin , Lai Shaoyong , Ming Sen
Published: October 2019

The local well-posedness for the Cauchy problem of a nonlinear shallow water equation is established. The wave-breaking mechanisms, global existence, and infinite propagation speed of solutions to the equation are derived under certain assumptions. In addition, the effects of coefficients λ, β, a, b, and index k in the equation are illustrated.
Infection control management and surveillance of carbapenem-resistant Gram-negative bacteria in hematopoietic stem cell recipients
Authors: Baier Claas , Beck Maleen , Panagiota Viktoria , Lueck Catherina , Kharazipour Daniel , Hintze Sophie Charlotte , Bollin Robin , Ebadi Ella , Ziesing Stefan , Eder Matthias , Bange Franz-Christoph , Beutel Gernot
Published: October 2019

Hematopoietic stem cell transplantation (HSCT) is a curative treatment option for selected diseases of the hematopoietic system. In the context of HSCT, bloodstream infections caused by Gram-negative bacteria (GNB) significantly contribute to morbidity and mortality. Antibiotic treatment of bloodstream infections with carbapenem-resistant (CR) GNB presents a particular challenge. As a part of our infection control management, the admission of a patient who was known to be colonized with a CR Acinetobacter baumannii triggered an active weekly screening of all patients to determine the prevalence and potential transmission of CR GNB and CR Acinetobacter baumannii in particular. Over a 3 month period a total of 71 patients were regularly screened for colonization with CR GNB. Including the index patient, a total of three patients showed CR GNB colonization representing a prevalence of 4.2%. Nosocomial transmission of CR Acinetobacter baumannii or other CR GNB was not observed. However, the index patient developed a subsequent bloodstream infection with the CR Acinetobacter baumannii, therefore empiric antibiotic therapy based on the known resistance profile was initiated. A weekly prevalence screening for CR GNB might be an effective monitoring tool for potential transmission, may enhance existing infection control management concepts and may support the decision making for empiric antibiotic therapy.
Linezolid use in German acute care hospitals: results from two consecutive national point prevalence surveys
Authors: Kramer Tobias Siegfried , Schwab Frank , Behnke Michael , Hansen Sonja , Gastmeier Petra , Aghdassi Seven Johannes Sam
Published: October 2019

Background

Linezolid belongs to a reserve group of antibiotics. In recent years, reports on linezolid resistance in gram-positive cocci have become more frequent. Overuse of linezolid is a relevant factor for resistance development. The objective of this study was to describe current prescription practices of linezolid in German hospitals and identify targets for antimicrobial stewardship interventions.

Methods

We analyzed all linezolid prescriptions from the datasets of the consecutive national point prevalence surveys performed in German hospitals in 2011 and 2016. In both surveys, data on healthcare-associated infections and antimicrobial use were collected following the methodology of the European Centre for Disease Prevention and Control.

Results

Overall, the percentage of linezolid among all documented antimicrobials increased significantly from 2011 to 2016 (p < 0.01). In 2011, 0.3% (119 of 41,539) patients received linezolid, in 2016 this proportion was significantly higher (0.4%; 255 of 64,412 patients; p < 0.01). In 2016, intensive care units (ICUs) were the wards most frequently prescribing linezolid. The largest proportion of patients receiving linezolid were non-ICU patients. Roughly 38% of linezolid prescriptions were for treatment of skin/soft tissue and respiratory tract infections. In 2016, linezolid was administered parenterally in 70% (n = 179) of cases. Multivariable analysis showed that the ward specialty ICU posed an independent risk factor, while Northern and Southwestern regions in Germany were independent protective factors for a high rate of linezolid prescriptions.

Conclusions

In conclusion, we detected potentials for improving linezolid prescription practices in German hospitals. Given the emergence of linezolid resistance, optimization of linezolid use must be a target of future antimicrobial stewardship activities.
Patterns of self-medication with antibiotics in Maputo City: a qualitative study
Authors: Torres Neusa F. , Solomon Vernon P. , Middleton Lyn E.
Published: October 2019

Background

Mozambique classifies but does not yet enforce antibiotics as prescription-only-medicine (POM) allowing the public access to a variety of antibiotics that otherwise are provided on prescription. This contributes to the growing practice of self-medication with antibiotics (SMA) which systematically exposes individuals to the risk of developing antibiotic resistance, antibiotic side effects and increases the health service costs and morbidity. This study aimed at describing the patterns of SMA among Maputo city pharmacy customers.

Methods

A qualitative study conducted between October 2018 and March 2019 was developed with thirty-two pharmacy customers and seventeen pharmacists. Using convenience sampling, customers were recruited after buying antibiotics without prescription from nine private pharmacies. Of the thirty-two participants, twenty participated in in-depth interviews and twelve in two focus groups discussions (FGD) with six participants each. Purposive sampling and a snowball technique were used to recruit pharmacists. The transcripts were coded and analyzed using latent content analysis. Nvivo 11 was used to store and retrieve the data. The COREQ (Tong, 2007) checklist for interviews and FGD was performed.

Results

Customers admitted practices of SMA, pharmacists admitted dispensing a variety of antibiotics without prescription. Non-prescribed antibiotics (NPA) were obtained through five different patterns including; using the generic name, describing the physical appearance and using empty package, describing symptoms or health problem to pharmacists, using old prescriptions and sharing antibiotics with family, friends, and neighbors.

Conclusion

Different patterns of SMA are contributing to the indiscriminate use of antibiotics among customers. The NPA utilization is perceived as an expression of self-care where participants experience self-perceived symptoms and indulge in self-treatment as a method of caring for themselves. Moreover, antibiotics are mostly used to treat diseases that do not necessarily need antibiotics. Strong and effective public health education and promotion initiatives should be implemented to discourage inappropriate utilization of antibiotics and SMA practices.
Selection and dissemination of antimicrobial resistance in Agri-food production
Authors: Cheng Guyue , Ning Jianan , Ahmed Saeed , Huang Junhong , Ullah Rizwan , An Boyu , Hao Haihong , Dai Menghong , Huang Lingli , Wang Xu , Yuan Zonghui
Published: October 2019

Public unrest about the use of antimicrobial agents in farming practice is the leading cause of increasing and the emergences of Multi-drug Resistant Bacteria that have placed pressure on the agri-food industry to act. The usage of antimicrobials in food and agriculture have direct or indirect effects on the development of Antimicrobial resistance (AMR) by bacteria associated with animals and plants which may enter the food chain through consumption of meat, fish, vegetables or some other food sources. In addition to antimicrobials, recent reports have shown that AMR is associated with tolerance to heavy metals existing naturally or used in agri-food production. Besides, biocides including disinfectants, antiseptics and preservatives which are widely used in farms and slaughter houses may also contribute in the development of AMR. Though the direct transmission of AMR from food-animals and related environment to human is still vague and debatable, the risk should not be neglected. Therefore, combined global efforts are necessary for the proper use of antimicrobials, heavy metals and biocides in agri-food production to control the development of AMR. These collective measures will preserve the effectiveness of existing antimicrobials for future generations.
From fiction to science: clinical potentials and regulatory considerations of gene editing
Authors: Schacker Maria , Seimetz Diane
Published: October 2019

Gene editing technologies such as CRISPR/Cas9 have emerged as an attractive tool not only for scientific research but also for the development of medicinal products. Their ability to induce precise double strand breaks into DNA enables targeted modifications of the genome including selective knockout of genes, correction of mutations or precise insertion of new genetic material into specific loci. Gene editing‐based therapies hold a great potential for the treatment of numerous diseases and the first products are already being tested in clinical trials. The treatment indications include oncological malignancies, HIV, diseases of the hematopoietic system and metabolic disorders. This article reviews ongoing preclinical and clinical studies and discusses how gene editing technologies are altering the gene therapy landscape. In addition, it focusses on the regulatory challenges associated with such therapies and how they can be tackled during the drug development process.
Validation of the Recent Life Changes Questionnaire (RLCQ) for stress measurement among adults residing in urban communities in Pakistan
Authors: Artani Azmina , Kamal Ayeesha K. , Azam Syed Iqbal , Artani Moiz , Bhamani Shireen Shehzad , Saif Mehreen , Khan Fariha Afzal , Alam Nazir
Published: October 2019

Background

Recent Life Changes Questionnaire (RLCQ) developed by Richard Rahe has enabled quantification of stress by analyzing life events. The overall aim of the study was to create a reliable version of the Rahe’s RLCQ for measuring stress in individuals living in developing countries and assess its validity. This paper discusses criterion validation of the adapted RLCQ in urban communities in Pakistan.

Methods

This is a criterion validation study. Four urban communities of Karachi, Pakistan were selected for the study in which households were randomly chosen. Two data collectors were assigned to administer the adapted RLCQ to eligible participants after obtaining written informed consent. Following this interaction, two psychologists interviewed the same participants with a diagnostic gold standard of Mini International Neuropsychiatric Interview (MINI) which is utilized in usual practice within Pakistan to confirm the presence of stress related mental disorders such as Depression, Anxiety, Dysthymia, Suicide, Phobia, OCD, Panic Disorder, PTSD, Drug abuse and dependence, Alcohol abuse and dependence, Eating Disorders and Antisocial Personality Disorder to validate the accuracy of the adapted RLCQ. We generated the ROC curves for the adapted RLCQ with suggested cut-offs, and analyzed the sensitivity and specificity of the adapted RLCQ.

Results

The area under the receiver operating characteristic curve (ROC) of common mental disorders such as depression and anxiety was 0.64, where sensitivity was 66%, specificity was 56% and the corresponding cut off from the adapted RLCQ was 750. Individuals scoring ≥750 were classified as high stress and vice versa. In contrast, the area under the ROC curve for serious mental disorder and adverse outcomes such as suicide, bipolar and dysthymia was 0.75, where sensitivity was 72% and specificity was 60% at the cut off of 800 on the adapted RLCQ. Individuals scoring ≥800 were classified as high stress and vice versa. The rate of agreement between the two psychologists was 94.32% (Kappa = 0.84).

Conclusion

The adapted and validated RLCQ characterizes common mental disorders such as depression and anxiety with moderate accuracy and severe mental disorders such as suicide, bipolar and dysthymia with high accuracy.

Trial registration

Clinicaltrials.gov NCT02356263. Registered January 28, 2015. (Observational Study Only).