bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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

IntroductionIdiopathic 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 analysisThe 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 disseminationYorkshire 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

AbstractBackgroundMutators 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.ResultsStarting 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.ConclusionOur 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.
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

Abstract

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

Abstract

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

Abstract

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

AbstractBackgroundTo 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.MethodsThis 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.ResultsA 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.ConclusionsMajority 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

Abstract

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

Abstract
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

AbstractThe 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

Abstract
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

Abstract

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

Abstract

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.