bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet count as a biomarker for monitoring treatment response and disease recurrence in recurrent epithelial ovarian cancer
Authors: Hu Qinghong , Hada Abha , Han Liping
Published: July 2020

Objectives

We sought to determine the impact of pretreatment plasma platelet levels, dimerized plasmin fragment (D-dimer) and fibrinogen in recurrent epithelial ovarian cancer (EOC) and the impact of platelet levels on SKOV3 cell lines growth and responsiveness to chemotherapy.

Methods

Under approval of ethical committee, we identified 104 women with recurrent EOC who underwent treatment between January 2010 and February 2015. Reviewing clinical, laboratory, and pathologic records from this retrospective cohort, we analyzed the correlation between pretreatment plasma D-dimer, fibrinogen, platelet levels and clinicopathological parameters, progression free survival (PFS) and overall survival (OS). Inco-culture experiments human ovarian cancer SKOV3 cell lines were used to test the effect of platelet levels on tumor growth and responsiveness to docetaxel.

Results

Of the 104 recurrent EOC, thrombocytosis at diagnosis and the decrease of platelet count by less than 25% after primary therapy were associated with worse median progression free survival (P = 0.003;P = 0.021) and median overall survival (P = 0.009;P = 0.009). Mean platelet levels declined at the end of primary therapy(P < 0.001) and rose at recurrence(P = 0.007). In multivariate analysis, elevated platelet levels at primary therapy and the decrease of platelet count less than 25% after primary therapy were unfavorable prognostic factor for PFS(P = 0.022; P = 0.015) and OS(P = 0.013;P = 0.007) in recurrent EOC, but elevated plasma D-dimer and fibrinogen were not. In SKOV-3 ovarian cancer cell lines, suitable concentration platelet co-culture protected against apoptosis (P < 0.05).

Conclusions

Platelet count during treatment could be used as a biomarker used for monitoring the disease recurrence and predicting treatment response. And platelet with suitable concentration co-culture protected against apoptosis in SKOV3 cell line, which may explain clinical observations.
Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention—MACUSTAR
Authors: Terheyden Jan H. , Holz Frank G. , Schmitz-Valckenberg Steffen , Lüning Anna , Schmid Matthias , Rubin Gary S. , Dunbar Hannah , Tufail Adnan , Crabb David P. , Binns Alison , Sánchez Clara I. , Hoyng Carel , Margaron Philippe , Zakaria Nadia , Durbin Mary , Luhmann Ulrich , Zamiri Parisa , Cunha-Vaz José , Martinho Cecília , Leal Sergio , Finger Robert P. ,   on behalf of the MACUSTAR consortium, Basile P. , Behning C. , Berger M. , Binns A. , Böttger M. , Bouchet C. , Brazier J. E. , Butt T. , Carapezzi C. , Carlton J. , Charil A. , Coimbra R. , Nunes S. , Crabb D. , Cunha-Vaz J. , Dunbar H. , Durbin M. , Finger R. , Holz F. , Hoyng C. , Krätzschmar J. , Leal S. , Luhmann U. , Lüning A. , Margaron Ph. , Martinho C. , Melício B. , Mohand-Saïd S. , Rowen D. , Rubin G. S. , Sahel J. , Sánchez C. I. , Sanches Fernandes D. , Schmid M. , Schmitz-Valckenberg S. , Skelly A. , Stöhr L. , Taylor D. , Terheyden J. , Tufail A. , Vieweg L. , Wintergerst L. , Wojek C. , Zakaria N. , Zamiri P.
Published: July 2020

Background

There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials.

Methods

The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part’s primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part’s primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities.

Discussion

The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition.

Trial registration

ClinicalTrials.govNCT03349801. Registered on 22 November 2017
Conversion among photo-oxidative products of polypropylene in solid, liquid and gaseous states
Authors: Liu Xuan , Yang Rui
Published: July 2020

During aging of polymers, oxidized species on macromolecular chains in solid state, volatile degradation products in liquid state and gaseous degradation products in gaseous state are often investigated separately. The conversion among these products is not especially concerned and biased results may be obtained based on the products in a single state. In this paper, photo-oxidative products of commercial polypropylene (PP) and unstabilized PP in solid, liquid and gaseous states were investigated by using Fourier transform infrared spectroscopy (FTIR), pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS) and gas chromatography (GC). By comparing the formation profiles, conversion among the photo-oxidative products in three states was traced. During photo-oxidative aging, the main chains of PP were first oxidized to form carbonyl species in solid state, or fractured to form volatile alkenes as liquid. With the proceeding of aging, the oxidized main chains fractured to form small molecules, resulting in the conversion of oxidized species from solid state to liquid and gaseous states. When the aging degree was extremely high, the accumulation of liquid oxidized products was limited due to migration and condensation. Therefore, both the carbonyl index (CI) and the concentrations of volatile oxidized products were increased first and then decreased, while the concentrations of gaseous products kept increasing all along.
Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius rotula for toxicological studies on human cancer cells
Authors: Steinbrecht Susanne , Kiebist Jan , König Rosalie , Thiessen Markus , Schmidtke Kai-Uwe , Kammerer Sarah , Küpper Jan-Heiner , Scheibner Katrin
Published: July 2020

Cyclophosphamide (CPA) represents a widely used anti-cancer prodrug that is converted by liver cytochrome P450 (CYP) enzymes into the primary metabolite 4-hydroxycyclophosphamide (4-OH-CPA), followed by non-enzymatic generation of the bioactive metabolites phosphoramide mustard and acrolein. The use of human drug metabolites as authentic standards to evaluate their toxicity is essential for drug development. However, the chemical synthesis of 4-OH-CPA is complex and leads to only low yields and undesired side products. In past years, fungal unspecific peroxygenases (UPOs) have raised to powerful biocatalysts. They can exert the identical selective oxyfunctionalization of organic compounds and drugs as known for CYP enzymes with hydrogen peroxide being used as sole cosubstrate. Herein, we report the efficient enzymatic hydroxylation of CPA using the unspecific peroxygenase from Marasmius rotula (MroUPO) in a simple reaction design. Depending on the conditions used the primary liver metabolite 4-OH-CPA, its tautomer aldophosphamide (APA) and the overoxidized product 4-ketocyclophosphamide (4-keto-CPA) could be obtained. Using a kinetically controlled approach 4-OH-CPA was isolated with a yield of 32% (purity > 97.6%). Two human cancer cell lines (HepG2 and MCF-7) were treated with purified 4-OH-CPA produced by MroUPO (4-OH-CPAUPO). 4-OH-CPAUPO–induced cytotoxicity as measured by a luminescent cell viability assay and its genotoxicity as measured by γH2AX foci formation was not significantly different to the commercially available standard. The high yield of 4-OH-CPAUPO and its biological activity demonstrate that UPOs can be efficiently used to produce CYP-specific drug metabolites for pharmacological assessment.
Epigenetic regulation of matrix metalloproteinases in inflammatory diseases: a narrative review
Authors: He Jie , Qin Man , Chen Yingyi , Hu Ziqi , Xie Fei , Ye Ling , Hui Tianqian
Published: July 2020

With the acceleration of urbanization and aging and the change of lifestyle, inflammatory diseases have become one of the important threats to the health of the global population. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the metabolism of extracellular matrix (ECM). They play a key role in inflammation-related diseases. Factors such as inflammation, oxidative stress and growth factors stimulate the production of MMPs with subsequent ECM remodeling. Recently, the studies of epigenetic regulation, including the ability to predict disease progression, important pathophysiological deficiencies as well as treatment methods have been extensively discussed. This article reviews the current studies on epigenetic alterations in MMPs during inflammatory response. It is likely to provide new insights into development of efficient medications of epigenetic therapy for inflammatory diseases.
Two-level frame precoding with non-cooperative gateways
Authors: Ramírez Tomás , Mosquera Carlos , López-Valcarce Roberto
Published: July 2020

This paper considers the pre-processing design to mitigate the multibeam interference in the downlink of a high-throughput satellite, with a common precoder for several users sharing the same frame, and limited adaptation capabilities on-board the satellite. Beams are grouped in clusters managed by different non-cooperative gateways. A two-level approach is performed, with an on-board beamforming network complemented by on-ground precoders. The former, designed with the SLNR (signal-to-leakage and noise ratio) criterion, mitigates the inter-cluster interference, whereas the latter fight the intra-cluster multiuser co-channel interference. Judicious user scheduling is also addressed to limit the impact of the multicasting and limited adaptation capabilities. Several two-level precoding designs can be obtained by setting accordingly the degree of cooperation and the frame adaptation, with an overall satisfactory performance with respect to the single-gateway benchmark. In particular, a sector-based solution with non-cooperative gateways presents a good trade-off between gateway autonomy and performance.
A novel authentication scheme based on edge computing for blockchain-based distributed energy trading system
Authors: Ren Yan , Zhao Qiuxia , Guan Haipeng , Lin Zhiqiang
Published: July 2020

Distributed energy trading system is a new business model of energy industry. Applying blockchain technology, energy supply contracts can be communicated directly between producers and consumers. However, blockchain is without any identity authentication and legitimate user identities are possibly forged if there is not any user identity authentication procedure in a trading system. In this paper, we design an authentication scheme for blockchain-based energy trading systems by using edge computing, including journalizing processes, registration, and identity authentication. In our scheme, each node has computing power, which can ensure the meter data can be processed locally or on the edge. In addition, the correctness and security analysis of the scheme are also given in this paper. The analysis shows that our scheme is unforgeability and can protect users’ privacy.
Combining abbreviated literature searches with single-reviewer screening: three case studies of rapid reviews
Authors: Affengruber Lisa , Wagner Gernot , Waffenschmidt Siw , Lhachimi Stefan K. , Nussbaumer-Streit Barbara , Thaler Kylie , Griebler Ursula , Klerings Irma , Gartlehner Gerald
Published: July 2020

Background

Decision-makers increasingly request rapid answers to clinical or public health questions. To save time, personnel, and financial resources, rapid reviews streamline the methodological steps of the systematic review process. We aimed to explore the validity of a rapid review approach that combines a substantially abbreviated literature search with a single-reviewer screening of abstracts and full texts using three case studies.

Methods

We used a convenience sample of three ongoing Cochrane reviews as reference standards. Two reviews addressed oncological topics and one addressed a public health topic. For each of the three topics, three reviewers screened the literature independently. Our primary outcome was the change in conclusions between the rapid reviews and the respective Cochrane reviews. In case the rapid approach missed studies, we recalculated the meta-analyses for the main outcomes and asked Cochrane review authors if the new body of evidence would change their original conclusion compared with the reference standards. Additionally, we assessed the sensitivity of the rapid review approach compared with the results of the original Cochrane reviews.

Results

For the two oncological topics (case studies 1 and 2), the three rapid reviews each yielded the same conclusions as the Cochrane reviews. However, the authors would have had less certainty about their conclusion in case study 2. For case study 3, the public health topic, only one of the three rapid reviews led to the same conclusion as the Cochrane review. The other two rapid reviews provided insufficient information for the authors to draw conclusions. Using the rapid review approach, the sensitivity was 100% (3 of 3) for case study 1. For case study 2, the three rapid reviews identified 40% (4 of 10), 50% (5 of 10), and 60% (6 of 10) of the included studies, respectively; for case study 3, the respective numbers were 38% (8 of 21), 43% (9 of 21), and 48% (10 of 21).

Conclusions

Within the limitations of these case studies, a rapid review approach that combines abbreviated literature searches with single-reviewer screening may be feasible for focused clinical questions. For complex public health topics, sensitivity seems to be insufficient.
Standardising care in the ICU: a protocol for a scoping review of tools used to improve care delivery
Authors: Allum Laura , Apps Chloe , Hart Nicholas , Pattison Natalie , Connolly Bronwen , Rose Louise
Published: July 2020

Background

Increasing numbers of critically ill patients experience a prolonged intensive care unit stay contributing to greater physical and psychological morbidity, strain on families and cost to health systems. Quality improvement tools such as checklists concisely articulate best practices with the aim of improving quality and safety; however, these tools have not been designed for the specific needs of patients with prolonged ICU stay.

The primary objective of this review will be to determine the characteristics including format and content of multicomponent tools designed to standardise or improve ICU care. Secondary objectives are to describe the outcomes reported in these tools, the type of patients and settings studied, and to understand how these tools were developed and implemented in clinical practice.

Methods

We will search the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, PsycINFO, Web of Science, OpenGrey, NHS evidence and Trial Registries from January 2000 onwards. We will include primary research studies (e.g. experimental, quasi-experimental, observational and qualitative studies) recruiting more than 10 adult participants admitted to ICUs, high dependency units and weaning centres regardless of length of stay, describing quality improvement tools such as structured care plans or checklists designed to standardize more than one aspect of care delivery. We will extract data on study and patient characteristics, tool design and implementation strategies and measured outcomes. Two reviewers will independently screen citations for eligible studies and perform data extraction. Data will be synthesised with descriptive statistics; we will use a narrative synthesis to describe review findings.

Discussion

The findings will be used to guide development of tools for use with prolonged ICU stay patients. Our group will use experience-based co-design methods to identify the most important actionable processes of care to include in quality improvement tools these patients. Such tools are needed to standardise practice and thereby improve quality of care. Illustrating the development and implementation methods used for such tools will help to guide translation of similar tools into ICU clinical practice and future research.

Systematic review registration

This protocol is registered on the Open Science Framework, https://osf.io/, DOI 10.17605/OSF.IO/Z8MRE
Maternal and perinatal outcomes and pharmacological management of Covid-19 infection in pregnancy: a systematic review protocol
Authors: Thomas Binny , Pallivalapila Abdulrouf , El Kassem Wessam , Tarannum Asma , Al Hail Fatema , Rijims Mohammed , Parappil Hussain , Bayo Arabo Ibrahim , Ahmad Shamsa , Nazar Zachariah , Stewart Derek , Al Hail Moza
Published: July 2020

Background

Over 4.2 million confirmed cases and more than 285,000 deaths, COVID-19 pandemic continues to harm significant number of people worldwide. Several studies have reported the impact of COVID-19 in general population; however, there is scarcity of information related to pharmacological management and maternal and perinatal outcomes during the pandemic. Altered physiological, anatomical, and immunological response during pregnancy makes it more susceptible to infections. Furthermore, during pregnancy, a woman undergoes multiple interactions with the health care system that increases her chance of getting infected; therefore, managing pregnant population presents a unique challenge.

Research questions

This systematic review seeks to answer the following questions in relation to COVID-19:

What are the different clinical characteristics presented in maternal and perinatal population?

What are the different maternal and perinatal outcome measures reported?

What are the distinct therapeutic interventions reported to treat COVID-19?

Is it safe to use “medications” used in the treatment of COVID-19 during antenatal, perinatal, postnatal, and breastfeeding?

Method

The search will follow a comprehensive, sequential three step search strategy. Several databases relevant to COVID-19 and its impact on pregnancy including Medline, CINAHL, and LitCovid will be searched from the inception of the disease until the completion of data collection. The quality of this search strategy will be assessed using Peer Review of Electronic Search Strategies Evidence-Based Checklist (PRESS EBC). An eligibility form will be developed for a transparent screening and inclusion/exclusion of studies. All studies will be sent to RefWorks, and abstraction will be independently performed by two researchers. Risk of bias will be assessed using Cochrane Risk of Bias tool for randomized controlled trials, Newcastle–Ottawa Quality Assessment Scale for non-randomized studies, and for case reports, Murad et al. tool will be used. Decision to conduct meta-analysis will be based on several factors including homogeneity and outcome measures reported; otherwise, a narrative synthesis will be deemed appropriate.

Discussion

This systematic review will summarize the existing data on effect of COVID-19 on maternal and perinatal population. Furthermore, to the best of our knowledge, this is the first systematic review addressing therapeutic management and safety of medicines to treat COVID-19 during pregnancy and breastfeeding.

Systematic review registration

This systematic review has been registered and published with Prospero (CRD42020172773).
The T-pod is as stable as supraacetabular fixation using 1 or 2 Schanz screws in partially unstable pelvic fractures: a biomechanical study
Authors: Zeckey Christian , Cavalcanti Kußmaul Adrian , Suero Eduardo M. , Kammerlander Christian , Greiner Axel , Woiczinski Matthias , Braun Christian , Flatz Wilhelm , Boecker Wolfgang , Becker Christopher A.
Published: July 2020

Introduction

Unstable fractures of the pelvis remain the predominant cause of severe hemorrhage, shock and early death in severely injured patients. The use of pelvic binders has become increasingly popular, particularly in the preclinical setting. There is currently insufficient evidence available about the stability of the pelvic binder versus supraacetabular fixation using 1 or 2 Schanz screws. We aimed to analyze the stability of the pelvic binder and supraacetabular fixateurs using either 1 or 2 Schanz screws in a cadaver model of an induced pelvic B-type fracture.

Materials and methods

The study was undertaken in 7 human fresh-frozen cadaveric pelvises with induced AO-type B fractures. Three stabilization techniques were compared: T-POD (pelvic bandage), supraacetabular external fixator with 1 pin on each side and external fixator with 2 pins on each side. Stability and stiffness were analyzed in a biomechanical testing machine using a 5-step protocol with static and dynamic loading, dislocation data were retrieved by ultrasound sensors at the fracture sites.

Results

No significant differences in fracture fragment displacement were detected when using either the T-POD, a 1-pin external fixator or a 2-pin external fixator (P > 0.05). The average difference in displacement between the three methods was < 1 mm.

Conclusions

Pelvic binders are suitable for reduction of pelvic B-type fractures. They provide stability comparable to that of supraacetabular fixators, independently of whether 1 or 2 Schanz screws per side are used. Pelvic binders provide sufficient biomechanical stability for transferring patients without the need to first replace them with surgically applied external fixators. However, soft tissue irritation has to be taken into consideration and prolonged wear should be avoided.

Level of evidence

Level III
Fine-tuning the metabolic rewiring and adaptation of translational machinery during an epithelial-mesenchymal transition in breast cancer cells
Authors: Fernández-Calero Tamara , Davyt Marcos , Perelmuter Karen , Chalar Cora , Bampi Giovana , Persson Helena , Tosar Juan Pablo , Hafstað Völundur , Naya Hugo , Rovira Carlos , Bollati-Fogolín Mariela , Ehrlich Ricardo , Flouriot Gilles , Ignatova Zoya , Marín Mónica
Published: July 2020

Background

During breast cancer progression, the epithelial to mesenchymal transition has been associated with metastasis and endocrine therapy resistance; however, the underlying mechanisms remain elusive. To gain insight into this process, we studied the transition undergone by MCF7-derived cells, which is driven by the constitutive nuclear expression of a MKL1 variant devoid of the actin-binding domain (MKL1 ΔN200). We characterized the adaptive changes that occur during the MKL1-induced cellular model and focused on regulation of translation machinery and metabolic adaptation.

Methods

We performed a genome-wide analysis at the transcriptional and translational level using ribosome profiling complemented with RNA-Seq and analyzed the expression of components of the translation machinery and enzymes involved in energy metabolism. NGS data were correlated with metabolomic measurements and quantification of specific mRNAs extracted from polysomes and western blots.

Results

Our results reveal the expression profiles of a luminal to basal-like state in accordance with an epithelial to mesenchymal transition. During the transition, the synthesis of ribosomal proteins and that of many translational factors was upregulated. This overexpression of the translational machinery appears to be regulated at the translational level. Our results indicate an increase of ribosome biogenesis and translation activity. We detected an extensive metabolic rewiring occurring in an already “Warburg-like” context, in which enzyme isoform switches and metabolic shunts indicate a crucial role of HIF-1α along with other master regulatory factors. Furthermore, we detected a decrease in the expression of enzymes involved in ribonucleotide synthesis from the pentose phosphate pathway. During this transition, cells increase in size, downregulate genes associated with proliferation, and strongly upregulate expression of cytoskeletal and extracellular matrix genes.

Conclusions

Our study reveals multiple regulatory events associated with metabolic and translational machinery adaptation during an epithelial mesenchymal-like transition process. During this major cellular transition, cells achieve a new homeostatic state ensuring their survival. This work shows that ribosome profiling complemented with RNA-Seq is a powerful approach to unveil in-depth global adaptive cellular responses and the interconnection among regulatory circuits, which will be helpful for identification of new therapeutic targets.
Treatment quality and outcome for multidrug-resistant tuberculosis patients in four regions of China: a cohort study
Authors: Zheng Xu-Bin , Diwan Vinod K. , Zhao Qi , Hu Yi , Bruchfeld Judith , Jiang Wei-Li , Hoffner Sven , Xu Biao
Published: July 2020

Background

China incurs an extremely low treatment coverage of multidrug-resistant tuberculosis (MDR-TB). This study aimed to understand the experience of MDR-TB patients on quality of health care, and the clinical impact through an up to six-year follow-up.

Methods

Cohorts of MDR-TB patients were built in TB/MDR-TB designated hospitals in four regions of China from 2014 to 2015. Patients were followed up during treatment course, and yearly confirmation afterward until 2019. Delay in MDR-TB diagnosis and treatment was calculated upon bacteriological confirmation and treatment initiation. Risk factors for unfavourable outcomes were identified by multivariate logistic regression.

Results

Among 1168 bacteriological-positive TB patients identified from a 12-million population, 58 (5.0%) MDR-TB cases were detected. The median delay for MDR-TB diagnosis was 90.0 days, with 13.8% having a delay above 180.0 days. MDR-TB treatment was only recommended to 19 (32.8%) participants, while the rest continued with regimen for drug-susceptible TB. In MDR-TB treatment group, 36.8% achieved treatment success, while the others had incomplete treatment (21.1%), loss to follow-up (36.8%) and TB relapse (5.3%). For non-MDR-TB treatment group, 33.3% succeeded, 25.6% relapsed, 2.6% failed, 23.1% died, and 15.4% were lost to follow-up. Overall, only 35.7% (20/56) of detected MDR-TB patients had favourable outcomes and higher education level was positively associated with it (adjusted odds ratio [aOR]: 3.60, 95% confidence interval [CI]: 1.04–12.5).

Conclusions

A large proportion of patients did not receive MDR-TB treatment and had unfavourable outcomes. Delayed MDR-TB diagnosis resulted in poor quality of MDR-TB care. Rapid diagnosis, regulated patient management and high-quality MDR-TB treatment should be enhanced in China.
Designing and validating a potential assessment inventory for assessing ELTs’ assessment literacy
Authors: Nikmard Fateme , Mohamadi Zenouzagh Zohre
Published: July 2020

English teachers' assessment literacy has always been considered as an important factor in their performance. However, no instrument has ever been developed to assess this construct among Iranian EFL teachers. To fill this gap, in the first phase of the present study a theoretical framework for the main four components of teacher assessment literacy, named validity, reliability, interpretability of the results, and efficiency, was developed through extensive review of the related literature and conducting interviews with PhD candidates of TEFL. In the second phase, a questionnaire was developed and piloted with 150 participants who took part in the study through the rules of convenience sampling. More specifically, the 30 items of the newly-developed “ELTs’ Assessment Literacy” questionnaire were subjected to factor analysis which revealed the presence of all the four components consisting of different number of items. These phases led to the development of a questionnaire with four components and 25 items on the basis of a five point Likert scale that measured: (1) “Validity” including six items, (2) “Reliability” including ten items, (3) “Interpretability of the Results” including eight item, and (4) “Efficiency” including five items. The findings of this study may shed lights on this subject and help researchers and teaching practitioners assess EFL teachers’ assessment literacy and make principled decisions as far as assessment is concerned.
CT features associated with EGFR mutations and ALK positivity in patients with multiple primary lung adenocarcinomas
Authors: Han Xiaoyu , Fan Jun , Gu Jin , Li Yumin , Yang Ming , Liu Tong , Li Nan , Zeng Wenjuan , Shi Heshui
Published: July 2020

Background

In multiple primary lung adenocarcinomas (MPLAs), the relationship between imaging and gene mutations remains unclear. This retrospective study aimed to identify the correlation of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) status with CT characteristics in MPLA patients.

Methods

Sixty-seven patients (135 lesions) with MPLAs confirmed by pathology were selected from our institution. All subjects were tested for EGFR mutations and ALK status and underwent chest CT prior to any treatment. The criteria for MPLA definitions closely adhered to the comprehensive histologic assessment (CHA).

Results

Among MPLA patients, EGFR mutations were more common in females (p = 0.002), in those who had never smoked (p = 0.010), and in those with less lymph node metastasis (p < 0.001), and the tumours typically presented with ground-glass opacity (GGO) (p = 0.003), especially mixed GGO (p < 0.001), and with air bronchograms (p = 0.012). Logistics regression analysis showed that GGO (OR = 6.550, p = 0.010) was correlated with EGFR mutation, while air bronchograms were not correlated with EGFR mutation (OR = 3.527, p = 0.060). A receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.647 and 0.712 for clinical-only or combined CT features, respectively, for prediction of EGFR mutations, and a significant difference was found between them (p = 0.0344). ALK-positive status was found most frequently in MPLA patients who were younger (p = 0.002) and had never smoked (p = 0.010). ALK positivity was associated with solid nodules or masses in MPLAs (p < 0.004) on CT scans. Logistics regression analysis showed that solid nodules (OR = 6.550, p = 0.010) were an independent factor predicting ALK positivity in MPLAs. For prediction of ALK positivity, the ROC curve yielded AUC values of 0.767 and 0.804 for clinical-only or combined CT features, respectively, but no significant difference was found between them (p = 0.2267).

Conclusion

Among MPLA patients, nonsmoking women with less lymph node metastasis and patients with lesions presenting GGO or mixed GGO and air bronchograms on CT were more likely to exhibit EGFR mutations. In nonsmoking patients, young patients with solid lesions on CT are recommended to undergo an ALK status test.
Cerebellum and micturition: what do we know? A systematic review
Authors: Bastide Laure , Herbaut Anne-Geneviève
Published: July 2020

Aims

Micturition depends on a complex voluntary and involuntarily neuronal network located at various levels of the nervous system. The mechanism is highly dependent on the hierarchical organization of central nervous system pathways. If the role of the cortex and brainstem centres is well established, the role of other subcortical areas structures, such as the cerebellum is poorly understood. We are interested in discussing the current knowledge on the role of cerebellum in micturition.

Methods

A systematic search is performed in the medical literature, using the PubMed database with the keyword « cerebellum ». The latter is combined with «urination » OR « micturition » OR « urinary bladder ».

Results

Thirty-one articles were selected, focussing on micturition and describing the role of the cerebellum. They were grouped in 6 animal experimental studies, 20 functional brain imaging in micturition and 5 clinical studies.

Conclusions

Although very heterogeneous, experimental and clinical data clearly indicate the cerebellum role in the micturition control. Cerebellum modulates the micturition reflex and participates to the bladder sensory-motor information processing. The cerebellum is involved in the reflex micturition modulation through direct or indirect pathways to major brainstem or forebrain centres.
Goblet cell carcinoid of the rectum: a case report
Authors: Inoue Yoshiyuki , Horie Hisanaga , Homma Yuko , Sadatomo Ai , Tahara Makiko , Koinuma Koji , Yamaguchi Hironori , Mimura Toshiki , Kihara Atsushi , Lefor Alan Kawarai , Sata Naohiro
Published: July 2020

Background

Goblet cell carcinoid (GCC) is a neuroendocrine tumor usually found in the appendix. GCCs exhibit characteristic findings with mixed endocrine-exocrine features such as staining positive for neuroendocrine markers and producing mucin. The primary GCC of the rectum is exceedingly rare.

Case presentation

A 77-year-old Japanese male presented with hematochezia. Anal tenderness and a hard mass in the anal canal were found on the digital rectal examination, and colonoscopy was performed. Colonoscopy showed an irregularly shaped mass in the anal canal. Biopsy showed mixed features including adenocarcinoma in situ, well-differentiated adenocarcinoma, and mucinous carcinoma with invasive proliferation. No metastatic lesions were found on the computed tomography scan. Pelvic magnetic resonance imaging scan showed extramural growth of a tumor on the ventral side of the rectum without invasion to the prostate. Laparoscopic abdominoperineal resection was performed. The final diagnosis was well-differentiated adenocarcinoma in the mucosa and goblet cell carcinoid from the submucosa to the adventitia of the rectum. The patient was discharged from the hospital on postoperative day 16. Six months after resection, a computed tomography scan revealed multiple metastatic lesions in the liver. Several chemotherapy regimens were given, and the patient has stable disease 27 months after surgery.

Conclusion

We present a patient with rectal GCC with metachronous liver metastases. Since GCC grows intramurally and is biologically aggressive compared to typical carcinoid lesions, the disease is usually diagnosed at an advanced stage. The development of optimal adjuvant chemotherapy is needed for those patients.
Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review
Authors: Sasaki Ken , Noda Masahiro , Tsuruda Yusuke , Uchikado Yasuto , Omoto Itaru , Kita Yoshiaki , Arigami Takaaki , Mori Shinichiro , Kurahara Hiroshi , Nakajo Akihiro , Higashi Michiyo , Ohtsuka Takao
Published: July 2020

Background

Synovial sarcoma (SS) of the esophagus is extremely rare. Because of the microscopic features of SS, the monophasic type can easily be misdiagnosed as other spindle cell tumors. Here, we present the first case of a primary SS of the esophagus in the presence of SS18-SSX2 fusion transcripts.

Case presentation

A 47-year-old Japanese woman was initially diagnosed with thyroid papillary carcinoma in the left lobe and leiomyoma of the cervical esophagus and subsequently underwent left thyroid lobectomy and enucleation of the esophageal tumor. Four years after the first surgery, the esophageal tumor recurred. Endoscopic biopsy of the tumor revealed atypical cell proliferation with spindle cell features and mitoses. Immunohistochemistry showed focal positivity for bcl-2 and HHF35. Furthermore, the presence of SS18-SSX2 fusion transcripts was confirmed by reverse transcription-polymerase chain reaction analysis, using a paraffin-embedded tumor specimen. Therefore, the tumor was diagnosed as monophasic SS of the cervical esophagus. We re-evaluated the surgical specimen enucleated 3 years previously, which was initially diagnosed as leiomyoma, and the diagnosis of SS was confirmed. The patient underwent cervical esophagectomy with isolated jejunal interposition reconstruction. Three years after the second surgery, SS recurred in the distal anastomotic site between the jejunum and the esophagus, and the patient underwent thoracoscopic esophagectomy with gastric conduit reconstruction. The pathological grade of the lesion worsened with every recurrence.

Conclusions

Monophasic SS can be difficult to discriminate from other spindle cell tumors based on microscopy alone, and molecular analysis could be useful for confirming the precise diagnosis of monophasic SS.
Validation of a German version of the Caregiver Quality of Life Index-Cancer (CQOLC) in a sample of significant others of breast and gynaecologic cancer patients
Authors: Ehmann Anna Tamara , Mahler Cornelia , Klafke Nadja
Published: July 2020

There is no disease-specific instrument to measure the quality of life of significant others of cancer patients in Germany. In this study, we evaluated the reliability and construct validity of a German version of the Caregiver Quality of Life Index-Cancer (CQOLC) in a sample of 212 caregivers of breast and gynaecologic cancer patients. The CQOLC was administered along with the World Health Organization Quality of Life short version (WHOQOL-BREF) to caregivers of patients taking part in a randomized-controlled intervention study. Data of 212 caregivers were gained at the baseline of the study. Internal consistency was determined by Cronbach’s α. Construct validity was examined by conducting a confirmatory factor analysis (CFA) and hypothesis testing. Correlations between change scores with patients’ global health-related quality of life (HRQoL) were calculated for three time points to evaluate the responsiveness. The three subscales “burden”, “disruptiveness”, and “financial concerns” indicate to a good reliability of the instrument (Cronbach’s α ranged between 0.754 and 0.832), while the subscale “positive adaptation” demonstrated low reliability (α = 0.579). A CFA based on data from the whole set of CQOLC items resulted in CFI levels < .90, and a CFA without problematic items resulted in CFI levels also < .90.

The construct validity of the CQOLC could be approved by a moderate to high convergence with close variables as the global HRQoL. Mean differences between caregivers of curatively or palliatively treated patients were nonsignificant (p = 0.959) at T1. Correlations for responsiveness were low with correlation coefficients ranging from 0.030 to 0.326. These data indicate that additional research is needed to further verify the validity of the instrument. The German scale of the CQOLC might be appropriate for clinical and research use, if the wording of some items is refined and if content validity is also assessed by caregivers themselves. The assessment of cancer patients’ caregiver’s quality of life can contribute to a better understanding of the effects of patient-oriented interventions including also closely involved next of kin’s around the cancer patients.
Inversion of surface vegetation water content based on GNSS-IR and MODIS data fusion
Authors: Pan Yalong , Ren Chao , Liang Yueji , Zhang Zhigang , Shi Yajie
Published: July 2020

Obtaining high-precision, long-term sequences of vegetation water content (VWC) is of great significance for assessing surface vegetation growth, soil moisture, and fire risk. In recent years, the global navigation satellite system-interferometric reflection (GNSS-IR) has become a new type of remote sensing technology with low cost, all-weather capability, and a high temporal resolution. It has been widely used in the fields of snow depth, sea level, soil moisture content, and vegetation water content. The normalized microwave reflectance index (NMRI) based on GNSS-IR technology has been proven to be effective in monitoring changes in VWC. This paper considers the advantages and disadvantages of remote sensing technology and GNSS-IR technology in estimating VWC. A point-surface fusion method of GNSS-IR and MODIS data based on the GA–BP neural network is proposed to improve the accuracy of VWC estimation. The vegetation index products (NDVI, GPP, LAI) and the NMRI that unified the temporal and spatial resolution were used as the input and output data of the training model, and the GA–BP neural network was used for training and modeling. Finally, a spatially continuous NMRI product was generated. Taking a particular area of the United States as a research object, experiments show that (1) a neural network can realize the effective fusion of GNSS-IR and MODIS products. By comparing the GA–BP neural network, BP neural network, and multiple linear regression (MLR), the three models fusion effect. The results show that the GA–BP neural network has the best modeling effect, and the r and RMSE between the model estimation result and the reference value are 0.778 and 0.0332, respectively; this network is followed by the BP neural network, in which the r and RMSE are 0.746 and 0.0465, respectively. MLR has the poorest effect, with r and RMSE values of 0.500 and 0.0516, respectively. (2) The spatiotemporal variation in the 16 days/500 m resolution NMRI product obtained by GA–BP neural network fusion is consistent with that in the experimental area. Through the testing of GNSS stations that did not participate in the modeling, the r between the estimated value of the NMRI and the reference value is greater than 0.87, and the RMSE is less than 0.049. Therefore, the method proposed in this paper is optional and effective. The spatially continuous NMRI products obtained by fusion can reflect the changes in VWC in the experimental area more intuitively.
Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy
Authors: Ferrara Roberto , Mezquita Laura , Texier Matthieu , Lahmar Jihene , Audigier-Valette Clarisse , Tessonnier Laurent , Mazieres Julien , Zalcman Gerard , Brosseau Solenn , Le Moulec Sylvestre , Leroy Laura , Duchemann Boris , Lefebvre Corentin , Veillon Remi , Westeel Virginie , Koscielny Serge , Champiat Stephane , Ferté Charles , Planchard David , Remon Jordi , Boucher Marie Eve , Gazzah Anas , Adam Julien , Lo Russo Giuseppe , Signorelli Diego , Garassino Marina Chiara , Soria Jean Charles , Caramella Caroline , Besse Benjamin
Published: July 2020

PURPOSE

Hyperprogressive disease (HPD), fast progression (FP), and early death (ED) have been described in 13.8%, 4.7%, and 5.6% and in 5.1%, 2.8%, and 6.8%, respectively, of patients with non–small-cell lung cancer (NSCLC) treated with single-agent programmed cell death ligand 1 inhibitors (ICI) or chemotherapy, respectively. Whether FP/ED and HPD represent overlapping patterns is unknown.

PATIENTS AND METHODS

FP, ED, and HPD were retrospectively assessed in patients with NSCLC treated with single-agent ICI or chemotherapy. Eligibility required 2 computed tomography (CT) scans before and 1 CT scan during treatment. (1) HPD, (2) FP, (3) ED were defined as (1) RECIST version 1.1 progression at first CT scan and tumor growth rate variation per month > 50%, (2) ≥ 50% increase in the sum of the longest diameters of target lesions within 6 weeks from baseline, and (3) death as a result of radiologic progression within 12 weeks from baseline CT scan, respectively.

RESULTS

Of 406 ICI-treated NSCLC, 56 patients (13.8%), 9 patients (2.2%), and 36 patients (8.8%) were HPD, FP, and ED, respectively. Eight (14.2%) and 20 (35.7%) of 56 patients with HPD were also FP and ED. ED significantly correlated with baseline Eastern Cooperative Oncology Group performance status ≥ 2 compared with HPD (33% v 13%, P = .02). Overall survival was significantly longer for HPD (3.4 months [95% CI, 2.7 to 4.0 months]) compared with FP (0.7 months [95% CI, 0.6 to 0.8 months]); HR, 0.18 [95% CI, 0.08 to 0.42]; P < .0001) and ED (1.4 months [95% CI, 1.3 to 1.6 months]); HR, 0.19 [95% CI, 0.11 to 0.34]); P < .0001), whereas it did not differ between FP and ED (HR, 1.3 [95% CI, 0.56 to 3.0]; P = .55). Of 59 patients with NSCLC treated with single-agent chemotherapy, the HPD, FP, and ED rates were 5.1%, 1.7%, and 6.7%, respectively.

CONCLUSION

FP, ED, and HPD represent distinct progression patterns with limited overlap and different survival outcomes.
Sex-Specific Metabolite Biomarkers of NAFLD in Youth: A Prospective Study in the EPOCH Cohort
Authors: Perng Wei , Francis Ellen C , Smith Harry A , Carey John , Wang Dongqing , Kechris Katerina M , Dabelea Dana
Published: July 2020

Context

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth.

Objective

Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth.

Design/Setting

This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 (“T1 visit”) and followed for 5 years (“T2 visit”). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC).

Results

Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant.

Conclusions

The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.
Riedel Thyroiditis
Authors: Zala Aakansha , Berhane Thomas , Juhlin C Christofer , Calissendorff Jan , Falhammar Henrik
Published: July 2020

Context

Riedel thyroiditis (RT) is a rare inflammatory autoimmune disease that is often a clinically diagnostic dilemma because of its insidious presentation and nonspecific symptoms.

Objective

The aim of the present systematic review and meta-analysis is to clarify the presentation, management, and outcomes of RT.

Study Selection

A systematic search of PubMed/MEDLINE and Web of Science was conducted to identify relevant reports published up to September 2019.

Data Extraction

First author, country, patient sex, ethnicity, presentation, biochemical status, duration of symptoms, histology, treatment, follow-up duration, and short- and long-term outcomes.

Data Synthesis

Data from 212 RT patients were retrieved. The mean age was 47 years with a predominantly female population (81%). Neck swelling (89%), dyspnea (50%), and neck pain (41%) were the most common presenting symptoms. Inflammatory markers were elevated in 70% to 97% and thyroid antibody positivity was present in less than 50%. Up to 82% underwent surgical intervention, with the most common being total thyroidectomy in 34% of individuals. Glucocorticoids were used in 70% of individuals with median duration 3 months. Prognosis was reasonable with 90% having resolution or improvement of symptoms.

Conclusions

This analysis is the largest and most comprehensive to date of RT and provides clinicians with vital information on the common presentation features that may alert to the diagnosis and highlight management options.