bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element analysis of archwire parameters and activation forces on the M/F ratio of vertical, L- and T-loops
Authors: Cai Yongqing
Published: March 2020

Background

The ability of a loop to generate a certain moment/force ratio (M/F ratio) can achieve the desired tooth movement in orthodontics. The present study aimed to investigate the effects of elastic modulus, cross-sectional dimensions, loop configuration geometry dimensions, and activation force on the generated M/F ratio of vertical, L- and T-loops.

Methods

A total of 120 three-dimensional loop models were constructed with the Solidworks 2017 software and used for simulating loop activation with the Abaqus 6.14 software. Six vertical loop variations, 9 L-loop variations, and 9 T-loop variations were evaluated. In each group, only one parameter was variable [loop height, ring radius, leg length, leg step distance, legs distance, upper length, different archwire materials (elastic modulus), cross-sectional dimension, and activation force].

Results

The simulation results of the displacement and von Mises stress of each loop were investigated. The maximum displacement in the height direction was recorded to calculate the M/F ratio. The quantitative change trends in the generated M/F ratio of the loops with respect to various variables were established.

Conclusions

Increasing the loop height can increase the M/F ratio of the loop. This increasing trend is, especially, much more significant in T-loops compared with vertical loops and L-loops. In vertical loops, increasing the ring radius is much more effective than increasing the loop height to increase the M/F ratio of the loop. Compared with SS, TMA archwire loops can generate a higher M/F ratio due to its lower elastic modulus. Loops with a small cross-sectional area and high activation force can generate a high M/F ratio. The introduction of a leg step to loops does not increase the M/F ratio of loops.
“They are talking from the Encyclopedia Britannica brain”: diabetes patients’ perceptions of barriers to communicating with physicians
Authors: Gordon Howard S. , Sharp Lisa K. , Schoenthaler Antoinette
Published: March 2020

Background

Understanding patients’ beliefs about their role communicating in medical visits is an important pre-requisite to encourage patients’ use of active participatory communication, and these beliefs may be particularly relevant for patients with diabetes.

Methods

Focus groups were conducted to examine patients with diabetes view of their role communicating in medical encounters. Patients had type 2 diabetes, A1C ≥ 8% (64 mmol/mol), and were from an inner-city VA hospital. Guiding questions for the focus groups were based on theoretical models of patient-physician communication. Focus group transcripts were analyzed with the constant comparative method.

Results

Four focus groups were conducted with a total of 20 male Veterans. Participants mean age was 61 years, 65% self-identified as black or African-American, 80% completed high school or higher education, and mean A1C was 10.3% (89 mmol/mol). Eight themes were identified as to why patients might have difficulty communicating with physicians. These themes were grouped into three overarching categories explaining reasons why patients might avoid participatory communication and included patients’ view about their condition; about physician’s communication behaviors; and about external influences on patient-physician communication. For example, patients described how use of the EHR may deter patients’ use of active participatory communication.

Conclusions

These results are important for understanding how patients’ use of active participatory communication is influenced by their beliefs and expectations, physicians’ behaviors, and structural factors. The results may be useful for educational efforts to increase patient, physician, and healthcare systems awareness of problems that patients perceive when communicating with physicians.
A rapid and simple method for routine determination of antibiotic sensitivity to biofilm populations of Pseudomonas aeruginosa
Authors: Wannigama Dhammika Leshan , Hurst Cameron , Hongsing Parichart , Pearson Lachlan , Saethang Thammakorn , Chantaravisoot Naphat , Singkham-in Uthaibhorn , Luk-in Sirirat , Storer Robin James , Chatsuwan Tanittha
Published: March 2020

Treatment of infections by Pseudomonas aeruginosa forming biofilms after antimicrobial testing on planktonic bacteria can result in substantial failure. Therefore, we offer a robust and simple experimental platform to test the impact of antimicrobials on biofilms. Antibiotic response patterns varied uniquely within biofilm formation capacity and minimal biofilm eradication concentrations (MBECs) has a significantly better discriminatory power than minimum inhibitory concentrations (MICs) to differentiate the overall efficiency of antibiotics to eradicate biofilm. Our resazurin-based 96-well-plate platform is able to emulate bacterial responses to antibiotics under biofilm conditions in a fast, simple, and cost-effective screening method adaptable to automation, and warrants trials in the clinic.
Epidemiology of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in Africa: a systematic review and meta-analysis
Authors: Ayano Getinet , Yohannes Kalkidan , Abraha Mebratu
Published: March 2020

Background

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorders in childhood and adolescence, affecting 2.2 to 17.8% of all school-aged children and adolescents. ADHD in children has been associated with a wide range of developmental deficits including limitations of learning or control of executive functions as well as global impairments of social skills. However, no review has been conducted to report the consolidated magnitude of ADHD in children and adolescents in Africa. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of ADHD in Africa.

Methods

Following the PRISMA guideline, we systematically reviewed and meta-analyzed studies that investigated the prevalence of ADHD in Africa from three electronic databases (PubMed, Embase, and Scopus). We also looked at the reference lists of included studies to include other relevant studies. Subgroup and sensitivity analysis was carried out based on the study setting, tools used to measure ADHD, sex of participants, and the subtype of ADHD. Heterogeneity across the studies was evaluated using Cochran's Q- and the I2-test. We assessed potential publication bias using Egger's test and visual inspection of the symmetry in funnel plots.

Results

In the present meta-analysis, 7452 articles were initially identified and evaluated. Of these, 12 studies that met the inclusion criteria were included in the final analysis. The pooled prevalence of ADHD in children and adolescents in Africa was 7.47% (95% CI 60–9.26). The prevalence of ADHD was apparently greater in boys (10.60%) than in girls (5.28%) with a male:female ratio of 2.01:1. In our subgroup analysis, the predominantly inattentive type (ADHD-I) was found to be the most common subtype of ADHD, followed by hyperactive–impulsive type (ADHD-HI) and the combined type (ADHD-C) with the prevalence of 2.95%, 2.77%, and 2.44% respectively. The predominantly inattentive type (ADHD-I) was the most common type of ADHD in both boys (4.05%) and girls (2.21%). The funnel plot and Egger's regression tests provided no evidence of substantial publication bias in the prevalence of ADHD.

Conclusion

Our systematic review suggested a higher prevalence of ADHD (7.47%) in children and adolescents in Africa, indicating that ADHD is a serious public health problem in children and adolescents in Africa. The prevalence of ADHD was considerably greater in males than in females. The predominantly inattentive type (ADHD-I) was the most common type of ADHD in both males and females. Greater attention needs to be paid to the prevention and treatment of ADHD.
Primary small intestine mesenteric low-grade fibromyxoid sarcoma with foci of atypical epithelioid whorls and diffuse DOG1 expression: a case report
Authors: Huang Jialing , Cohen Steven , Jour Gerorge
Published: March 2020

Background

Low-grade fibromyxoid sarcoma (LGFMS) is a rare fibroblastic tumor often involving deep tissue of trunk and lower extremities in young to middle-aged patients. Rarely, LGFMS can occur in other sites including head and neck, chest, abdomen and female reproductive system. Three cases of LGFMS in mesentery of small intestine have been reported and all have conventional histologic features. Herein we reported a unique case of LGFMS in mesentery of small intestine.

Case presentation

A 43 year-old male with chief complaint of lower back pain for 4 years presented to our hospital. Physical exam reveal a firm, non-tender, non-distended, mobile large abdominal mass, which was shown on abdominal CT as a 10 cm retroperitoneal tumor. Biopsy revealed a spindle cell neoplasm in a myxoid background with a delicate vascular network. Tumor resection was performed. Gross examination of the resected specimen showed a 10.8 cm, tan-white, smooth, firm, lobulated mesenteric mass with bulging and gelatinous cut surface and confined within small bowel serosa. Microscopic examination demonstrated foci epithelioid cords and whorls with prominent atypia, in additional of regular, bland-appearing spindle cells in a fibrous and myxoid stroma and osseous metaplasia. The tumor cells stained diffusely positive for DOG1 with moderate staining density, and diffusely and strongly positive for MUC4. Rearrangement involving FUS (16p11.2) gene was identified with break-apart probe and confirmed by Anchored Multiplex PCR. A final diagnosis of low-grade fibromyxoid sarcoma was rendered.

Conclusion

Our case highlights the importance of including LGFMS in the differential diagnosis of mesenteric tumors and the DOG1 positivity which could represent a potential diagnostic pitfall.
PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease
Authors: Ge Preston , Dawson Valina L. , Dawson Ted M.
Published: March 2020

That certain cell types in the central nervous system are more likely to undergo neurodegeneration in Parkinson’s disease is a widely appreciated but poorly understood phenomenon. Many vulnerable subpopulations, including dopamine neurons in the substantia nigra pars compacta, have a shared phenotype of large, widely distributed axonal networks, dense synaptic connections, and high basal levels of neural activity. These features come at substantial bioenergetic cost, suggesting that these neurons experience a high degree of mitochondrial stress. In such a context, mechanisms of mitochondrial quality control play an especially important role in maintaining neuronal survival. In this review, we focus on understanding the unique challenges faced by the mitochondria in neurons vulnerable to neurodegeneration in Parkinson’s and summarize evidence that mitochondrial dysfunction contributes to disease pathogenesis and to cell death in these subpopulations. We then review mechanisms of mitochondrial quality control mediated by activation of PINK1 and Parkin, two genes that carry mutations associated with autosomal recessive Parkinson’s disease. We conclude by pinpointing critical gaps in our knowledge of PINK1 and Parkin function, and propose that understanding the connection between the mechanisms of sporadic Parkinson’s and defects in mitochondrial quality control will lead us to greater insights into the question of selective vulnerability.
Management of first metatarsophalangeal joint osteoarthritis by physical therapists and podiatrists in Australia and the United Kingdom: a cross‐sectional survey of current clinical practice
Authors: Paterson Kade L. , Hinman Rana S. , Menz Hylton B. , Bennell Kim L.
Published: March 2020

Background

First metatarsophalangeal (MTP) joint osteoarthritis (OA) is a common and painful problem that causes significant disability. There is limited research on assessment and treatment options, and the efficacy of current management strategies is unknown. The aim of this study was to determine how podiatrists and physical therapists in Australia and the United Kingdom (UK) manage people with first MTP joint OA.

Methods

A survey of podiatrists and physiotherapists was conducted. Potential respondents were recruited through professional representative organisations in Australia and the UK. Participants completed a bespoke online survey regarding the assessment and treatment approaches they most commonly use for patients with first MTP joint OA. Descriptive statistics were calculated and differences between professions compared using chi‐square.

Results

Two hundred respondents (n = 113 (57%) podiatrists and n = 140 (70%) from Australia) completed the survey. Assessment tests were similar between professions and included x‐ray (n = 151/164; 92%), range of motion (n = 127/141; 90%), and a pain scale (n = 78/99; 79%). Podiatrists were more likely than physical therapists to discuss over‐the‐counter medication (42% vs 17%; p < 0.001), prescribe orthoses (97% vs 66%; p < 0.001), particularly custom orthoses (78% vs 42%; p < 0.001), and provide advice on footwear (92% vs 78%; p < 0.01) when treating first MTP joint OA. In contrast, physical therapists used more exercise‐based approaches to treatment, including exercise therapy (91% vs 34%; p < 0.001), increasing general activity (70% vs 49%; p < 0.01), and advice to pace activities (83% vs 48%; p < 0.001).

Conclusion

Podiatrists and physical therapists use an array of assessment and treatment approaches for people with first MTP joint OA, albeit there is limited evidence to support their clinical utility. Treatment strategies differ between professions, particularly with respect to medication, orthoses and exercise. It is unclear whether these commonly‐used strategies improve symptoms associated with first MTP joint OA.
Gene targets for engineering osmotolerance in Caldicellulosiruptor bescii
Authors: Sander Kyle B. , Chung Daehwan , Klingeman Dawn M. , Giannone Richard J. , Rodriguez Miguel , Whitham Jason , Hettich Robert L. , Davison Brian H. , Westpheling Janet , Brown Steven D.
Published: March 2020

Background

Caldicellulosiruptor bescii, a promising biocatalyst being developed for use in consolidated bioprocessing of lignocellulosic materials to ethanol, grows poorly and has reduced conversion at elevated medium osmolarities. Increasing tolerance to elevated fermentation osmolarities is desired to enable performance necessary of a consolidated bioprocessing (CBP) biocatalyst.

Results

Two strains of C. bescii showing growth phenotypes in elevated osmolarity conditions were identified. The first strain, ORCB001, carried a deletion of the FapR fatty acid biosynthesis and malonyl-CoA metabolism repressor and had a severe growth defect when grown in high-osmolarity conditions—introduced as the addition of either ethanol, NaCl, glycerol, or glucose to growth media. The second strain, ORCB002, displayed a growth rate over three times higher than its genetic parent when grown in high-osmolarity medium. Unexpectedly, a genetic complement ORCB002 exhibited improved growth, failing to revert the observed phenotype, and suggesting that mutations other than the deleted transcription factor (the fruR/cra gene) are responsible for the growth phenotype observed in ORCB002. Genome resequencing identified several other genomic alterations (three deleted regions, three substitution mutations, one silent mutation, and one frameshift mutation), which may be responsible for the observed increase in osmolarity tolerance in the fruR/cra-deficient strain, including a substitution mutation in dnaK, a gene previously implicated in osmoresistance in bacteria. Differential expression analysis and transcription factor binding site inference indicates that FapR negatively regulates malonyl-CoA and fatty acid biosynthesis, as it does in many other bacteria. FruR/Cra regulates neighboring fructose metabolism genes, as well as other genes in global manner.

Conclusions

Two systems able to effect tolerance to elevated osmolarities in C. bescii are identified. The first is fatty acid biosynthesis. The other is likely the result of one or more unintended, secondary mutations present in another transcription factor deletion strain. Though the locus/loci and mechanism(s) responsible remain unknown, candidate mutations are identified, including a mutation in the dnaK chaperone coding sequence. These results illustrate both the promise of targeted regulatory manipulation for osmotolerance (in the case of fapR) and the challenges (in the case of fruR/cra).
Mechanical ventilation weaning issues can be counted on the fingers of just one hand: part 2
Authors: Vetrugno Luigi , Brussa Alessandro , Guadagnin Giovanni Maria , Orso Daniele , De Lorenzo Francesco , Cammarota Gianmaria , Santangelo Erminio , Bove Tiziana
Published: March 2020

Assessing heart and diaphragm function constitutes only one of the steps to consider along the weaning path. In this second part of the review, we will deal with the more systematic evaluation of the pulmonary parenchyma—often implicated in the genesis of respiratory failure. We will also consider the other possible causes of weaning failure that lie beyond the cardio-pulmonary-diaphragmatic system. Finally, we will take a moment to consider the remaining unsolved problems arising from mechanical ventilation and describe the so-called protective approach to parenchyma and diaphragm ventilation.
Influence of storage conditions of small volumes of blood on immune transcriptomic profiles
Authors: Mathew Rebecca , Toufiq Mohammed , Mattei Valentina , Al Hashmi Muna , Shobha Manjunath Harshitha , Syed Ahamed Kabeer Basirudeen , Calzone Rita , Cugno Chiara , Chaussabel Damien , Deola Sara , Tomei Sara
Published: March 2020

Objective

Transcriptome analysis of human whole blood is used to discover biomarkers of diseases and to assess phenotypic traits. Here we have collected small volumes of blood in Tempus solution and tested whether different storage conditions have an impact on transcriptomic profiling. Fifty µl of blood were collected in 100µl of Tempus solutions, freezed at − 20 °C for 1 day and eventually thawed, stored and processed under five different conditions: (i) − 20 °C for 1 week; (ii) +4 °C for 1 week; (iii) room temperature for 1 week; (iv) room temperature for 1 day, − 20 °C for 1 day, room temperature until testing at day 7, (v) − 20 °C for 1 week, RNA was isolated and stored in GenTegra solution. We used 272 immune transcript specific assays to test the expression profiling using qPCR based Fluidigm BioMark HD dynamic array.

Results

RNA yield ranged between 0.17 and 1.39µg. Except for one sample, RIN values were > 7. Using Principal Component Analysis, we saw that the storage conditions did not drive sample distribution. The condition that showed larger variability was the RT-FR-RT (room temperature–freezing–room temperature), suggesting that freezing–thawing cycles may have a worse effect on data reproducibility than keeping the samples at room temperature.
Electronic cleansing of tagged residue in CT colonography: what radiologists need to know
Authors: Mang Thomas , Bräuer Christian , Gryspeerdt Stefaan , Scharitzer Martina , Ringl Helmut , Lefere Philippe
Published: March 2020

CT colonography (CTC) is the radiological examination of choice for the diagnosis of colorectal neoplasia. Faecal tagging is considered a mandatory part of bowel preparation. However, the colonic mucosa, obscured by tagged residue, is not accessible to endoluminal 3D views and requires time-consuming 2D evaluation. Electronic cleansing (EC) software algorithms can overcome this limitation by digitally subtracting tagged residue from the colonic lumen. Ideally, this enables a seamless 3D endoluminal evaluation. Despite this benefit, EC is a potential source of a wide range of artefacts. Accurate EC requires proper CTC examination technique and faecal tagging. The digital subtraction process has been shown to affect the relevant morphological features of both colonic anatomy and colonic lesions, if submerged under faecal residue. This article summarises the potential effects of EC on CTC imaging, the consequences for reporting and patient management, and strategies to avoid pitfalls. Furthermore, potentially negative effects on clinical reporting and patient management are shown, and problem-solving techniques, as well as recommendations for the appropriate use of EC techniques, are presented. Radiologists using EC should be familiar with EC-related effects on polyp size and also with correct measurement techniques.
Design of a reservoir for cloud-enabled echo state network with high clustering coefficient
Authors: Akrami Abbas , Rostami Habib , Khosravi Mohammad R.
Published: March 2020

Reservoir computing (RC) is considered as a suitable alternative for descending gradient methods in recursive neural networks (RNNs) training. The echo state network (ESN) is a platform for RC and nonlinear system simulation in the cloud environment with many external users. In the past researches, the highest eigenvalue of reservoir connection weight (spectral radius) was used to predict reservoir dynamics. Some researchers have illustrated; the characteristics of scale-free and small-world can improve the approximation capability in echo state networks; however, recent studies have shown importance of the infrastructures such as clusters and the stability criteria of these reservoirs as altered. In this research, we suggest a high clustered ESN called HCESN that its internal neurons are interconnected in form of clusters. Each of the clusters contains one backbone and a number of local nodes. We implemented a classical clustering algorithm, called K-means, and three optimization algorithms including genetic algorithm (GA), differential evolution (DE), and particle swarm optimization (PSO) to improve the clustering efficiency of the new reservoir and compared them with each other. For investigating the spectral radius and predictive power of the resulting reservoirs, we also applied them to the laser time series and the Mackey-Glass dynamical system. It is demonstrated that new clustered reservoirs have some specifications of biologic neural systems and complex networks like average short path length, high clustering coefficient, and power-law distribution. The empirical results illustrated that the ESN based on PSO could strikingly enhance echo state property (ESP) and obtains less chaotic time series prediction error compared with other works and the original version of ESN. Therefore, it can approximate nonlinear dynamical systems and predict the chaotic time series.
Integrating science and engineering practices: outcomes from a collaborative professional development
Authors: Brand Brenda R.
Published: March 2020

Background

The Next Generation Science Standards accentuate engineering design along with scientific inquiry, emphasizing the relationship between scientific investigations and engineering design in solving problems and devising new ideas and technologies. The goal is for students to realize the importance of science and engineering in innovation and in solving many of today’s challenges. The Next Generation Science Standards contends that a working knowledge and practicality of engineering design prepares students for embracing the challenges of the future. To support students in developing these capabilities, teachers are tasked with the responsibility of facilitating science instruction that integrates science and engineering practices. This is a challenge since a majority of them have little to no understanding of engineering applications.

Results

An interdisciplinary team, consisting of science education and mechanical engineering faculty and doctoral students from each discipline, and science, mathematics, and career and technical curriculum supervisors, collaborated with middle school science, mathematics, and career and technical education teachers to develop a framework for integrating engineering practices into their curricula. The exploratory nature of the project, and instructional outcomes with their students, supported teachers in developing an understanding and value for science and engineering practices. As a result, they were motivated to critique and revise their practices, aiming to develop and implement instruction that they perceived as beneficial to their students.

Conclusion

With the surge in emphasis on preparing K-12 students for the STEM workforce, initiatives devoted to exposing teachers and students to STEM applications have also increased. The findings from this study could be useful for informing these initiatives, since they reveal the learning experiences of the teachers while processing instructional strategies for integrating science and engineering practices into their curriculum. The findings highlight factors that motivated these teachers to reform their instructional practices, as well as their deliberations while endeavoring to assimilate the strategies into their curricular activities.
Pragmatic randomised evaluation of stable thoracolumbar fracture treatment outcomes (PRESTO): study protocol for a randomised controlled feasibility trial combined with a qualitative study and survey
Authors: Cook Elizabeth , Booth Alison , Coleman Elizabeth , Scantlebury Arabella , McDaid Catriona , Hewitt Catherine , Corbacho Belen , Rangan Amar , Adamson Joy , Ranganathan Arun , Khan Almas , Ahuja Sashin , Turner Emma , May Peter , Hilton Catherine , Torgerson David J.
Published: March 2020

Background

A thoracolumbar fracture is the most common fracture of the spinal column. Where the fracture is not obviously stable or unstable, the optimal management is uncertain. There are variations between surgeons, treating centres and within the evidence base as to whether surgical or non-surgical approaches should be used. In addition, the boundaries of this zone of uncertainty for stability are unclear.

This study has been designed in response to an NIHR HTA commissioning brief to assess the feasibility of undertaking a large-scale trial to evaluate the effectiveness of surgical and non-surgical treatments for thoracolumbar fractures without neurological deficit.

Methods

Assessment of feasibility will be addressed through three elements: a randomised external feasibility study, a national survey of surgeons and a qualitative study.

The external feasibility study is a pragmatic, parallel-group, randomised controlled trial comparing surgical fixation (intervention) versus non-surgical management (control). Recruitment will take place in three secondary care centres in the UK.

The primary outcome is recruitment rate, defined as the proportion of eligible participants who are randomised. Further outcomes related to recruitment, randomisation, drop-out, cross-over, loss to follow-up, completeness of outcome data, study processes and details of the interventions delivered will be collected.

The survey of surgeons and qualitative study of clinicians, recruiting staff and patients will enhance the feasibility study, enabling a broad overview of current practice in the field in addition to perceived facilitators and barriers to running a full-scale trial.

Discussion

PRESTO is a feasibility study which aims to inform methodology for a definitive trial comparing surgical fixation with non-surgical management for patients with stable thoracolumbar fractures.

Trial registration

The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN12094890). Date of registration was 22/02/2018 (http://www.isrctn.com/ISRCTN12094890).
Applying intervention mapping approach to a program for early intervention in first-episode mental crisis of a psychotic type
Authors: Machado Daniela Martins , Murta Sheila Giardini , da Costa Ileno Izídio
Published: March 2020

The holotropic mind perspective, an integral part of the framework of transpersonal psychology, has been considered a revolutionary approach to a certain spectrum of experiences in Non-ordinary states of consciousness (NOSC) which conventional approaches tend to treat indiscriminately as pathological processes, because PHM recognizes in these experiences their healing and evolutionary potential. This article describes the needs assessment, implementation, and evaluation of an experiential and educational program on the holotropic mind perspective and its praxis, Holotropic Breathwork® (HB), with students and professionals from the Group for Early Intervention in First-Episode Mental Crisis of a Psychotic Type of the University of Brasilia. The intervention aimed to establish change goals and objectives that would promote the adoption of the holotropic mind perspective’s elements, such as a framework to broaden and strengthen mental health programs that assist people experiencing NOSC. The stages developed, inspired by the Intervention Mapping protocol, included a needs assessment; elaboration of change objective matrices; selection and description of methods based on theory and their applications; conception, planning, and implementation of the intervention; and results evaluation. Participants reported that the intervention allowed the expansion of their theoretical-conceptual and technical frameworks, giving them a less pathologizing understanding of and approach to NOSC and allowing them to perceive and manage such states, not as indiscriminately pathological expressions, but as phenomena inherent to the human condition that can be accepted and cared for without the exclusionary and exhaustive bias of mental disorders. Limitations and practical implications are discussed.
Ground-penetrating radar monitoring of fast subsurface processes
Authors: Allroggen Niklas , Beiter Daniel , Tronicke Jens
Published: March 2020

Earth and environmental sciences rely on detailed information about subsurface processes. Whereas geophysical techniques typically provide highly resolved spatial images, monitoring subsurface processes is often associated with enormous effort and, therefore, is usually limited to point information in time or space. Thus, the development of spatial and temporal continuous field monitoring methods is a major challenge for the understanding of subsurface processes. We have developed a novel method for ground-penetrating-radar (GPR) reflection monitoring of subsurface flow processes under unsaturated conditions and applied it to a hydrological infiltration experiment performed across a periglacial slope deposit in northwest Luxembourg. Our approach relies on a spatial and temporal quasicontinuous data recording and processing, followed by an attribute analysis based on analyzing differences between individual time steps. The results demonstrate the ability of time-lapse GPR monitoring to visualize the spatial and temporal dynamics of preferential flow processes with a spatial resolution in the order of a few decimeters and temporal resolution in the order of a few minutes. We observe excellent agreement with water table information originating from different boreholes. This demonstrates the potential of surface-based GPR reflection monitoring to observe the spatiotemporal dynamics of water movements in the subsurface. It provides valuable, and so far not accessible, information for example in the field of hydrology and pedology that allows studying the actual subsurface processes rather than deducing them from point information.
Targets and Antibody Formats for Immunotherapy of Neuroblastoma
Authors: Park Jeong A. , Cheung Nai-Kong V.
Published: March 2020

Neuroblastoma (NB) is a malignant embryonal tumor of the sympathetic nervous system that is most commonly diagnosed in the abdomen, often presenting with signs and symptoms of metastatic spread. Three decades ago, high-risk NB metastatic to bone and bone marrow in children was not curable. Today, with multimodality treatment, 50% of these patients will survive, but most suffer from debilitating treatment-related complications. Novel targeted therapies to improve cure rates while minimizing toxicities are urgently needed. Recent molecular discoveries in oncology have spawned the development of an impressive array of targeted therapies for adult cancers, yet the paucity of recurrent somatic mutations or activated oncogenes in pediatric cancers poses a major challenge to the evolving paradigm of personalized medicine. Although low tumor mutational burden is a major hurdle for immune checkpoint inhibitors, an immature or impaired immune system and inhibitory tumor microenvironment can further complicate the prospects for successful immunotherapy. In this regard, despite the poor immunogenic properties of NB, the success of antibody-based immunotherapy and radioimmunotherapy directed at single targets (eg, GD2 and B7-H3) is both encouraging and surprising, given that most solid tumor antibodies that use Fc-dependent mechanisms or radioimmunotargeting have largely failed. Here, we summarize the current information on the immunologic properties of this tumor, its potential immunotherapeutic targets, and novel antibody-based strategies on the horizon.
Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma
Authors: Catenacci Daniel V.T. , Rasco Drew , Lee Jeeyun , Rha Sun Young , Lee Keun-Wook , Bang Yung Jue , Bendell Johanna , Enzinger Peter , Marina Neyssa , Xiang Hong , Deng Wei , Powers Janine , Wainberg Zev A.
Published: March 2020

PURPOSE

To evaluate the safety, pharmacokinetics, and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma (GEA).

PATIENTS AND METHODS

FPA144-001 was a phase I, open-label, multicenter trial consisting of the following 3 parts: part 1a involved dose escalation in patients with recurrent solid tumors at doses ranging from 0.3 to 15 mg/kg; part 1b involved dose escalation in patients with advanced-stage GEA; and part 2 involved dose expansion in patients with advanced-stage GEA that overexpressed FGFR2b at various levels (4 cohorts; high, medium, low, and no FGFR2b overexpression) and 1 cohort of patients with FGFR2b-overexpressing advanced-stage bladder cancer.

RESULTS

Seventy-nine patients were enrolled; 19 were enrolled in part 1a, 8 in part 1b, and 52 in part 2. No dose-limiting toxicities were reported, and the recommended dose was identified as 15 mg/kg every 2 weeks based on safety, tolerability, pharmacokinetic parameters, and clinical activity. The most frequent treatment-related adverse events (TRAEs) were fatigue (17.7%), nausea (11.4%), and dry eye (10.1%). Grade 3 TRAEs included nausea (2 patients) and anemia, neutropenia, increased AST, increased alkaline phosphatase, vomiting, and an infusion reaction (1 patient each). Three (10.7%) of 28 patients assigned to a cohort receiving a dose of ≥ 10 mg/kg every 2 weeks for ≥ 70 days reported reversible grade 2 corneal TRAEs. No TRAEs of grade ≥ 4 were reported. Five (17.9%; 95% CI, 6.1% to 36.9%) of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response.

CONCLUSION

Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage GEA. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage GEA.
Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer
Authors: Makker Vicky , Taylor Matthew H. , Aghajanian Carol , Oaknin Ana , Mier James , Cohn Allen L. , Romeo Margarita , Bratos Raquel , Brose Marcia S. , DiSimone Christopher , Messing Mark , Stepan Daniel E. , Dutcus Corina E. , Wu Jane , Schmidt Emmett V. , Orlowski Robert , Sachdev Pallavi , Shumaker Robert , Casado Herraez Antonio
Published: March 2020

PURPOSE

Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

METHODS

Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST.

RESULTS

At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)–high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients.

CONCLUSION

Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile.
Rising Incidence and Incidence-Based Mortality of Thyroid Cancer in California, 2000-2017
Authors: Yan Kimberly L , Li Shanpeng , Tseng Chi-Hong , Kim Jiyoon , Nguyen Dalena T , Dawood Nardeen B , Livhits Masha J , Yeh Michael W , Leung Angela M
Published: March 2020

Context

The increased incidence of thyroid cancer globally over the past several decades is principally attributed to small, indolent papillary thyroid cancers. A possible concomitant increase in thyroid cancer-specific mortality remains debated.

Objective

The changes in thyroid cancer incidence and incidence-based mortality were assessed using a large population-based cohort over an 18-year period.

Design & Patients

A retrospective analysis of all thyroid cancers reported in the California Cancer Registry was performed (2000–2017). Age-adjusted incidence and incidence-based mortality rates were analyzed using a log-linear model to estimate annual percent change.

Results

We identified 69 684 individuals (76% female, median age 50 years) diagnosed with thyroid cancer. The incidence of thyroid cancer increased across all histological subtypes (papillary, follicular, medullary, and anaplastic) and all tumor sizes. The incidence increased from 6.43 to 11.13 per 100 000 person-years (average increase 4% per year; P < 0.001) over the study period. Thyroid cancer-specific mortality rates increased on average by 1.7% per year (P < 0.001). The increased mortality rates were greater in men (2.7% per year, P < 0.001) and patients with larger tumors (2-4 cm) (3.4% per year, P < 0.05).

Conclusions

Data from this statewide registry demonstrate that the incidence of thyroid cancer is increasing, and that this phenomenon is not restricted to small papillary thyroid cancers. Rising incidence in thyroid cancers of all sizes with concurrent increase of incidence-based mortality in men and those with larger tumors suggest a true increase in clinically significant disease.
Association Between Maternal Normal Range HbA1c Values and Adverse Birth Outcomes
Authors: Bi Jianing , Ji Cunwei , Wu Yuntao , Wu Mingyang , Liu Yunyun , Song Lulu , Khatiwada Shikha Upadhyaya , Yang Senbei , Li Bing , Wang Youjie , Wu Li
Published: March 2020

Context

Higher blood glucose level during gestational periods has been consistently associated with increased risk of adverse birth outcomes. Evidence regarding the association between higher glycated hemoglobin A1c (HbA1c) within the normal range and adverse birth outcomes is limited.

Objective

We aimed to examine the association between HbA1c within the normal range and the risk of adverse birth outcomes.

Design and Setting

The data were abstracted from the Information System of Guangdong Women and Children Hospital, China, from September 2014 to March 2018.

Patients

A total of 5658 pregnant women with normal gestational HbA1c were included in this analysis.

Main Outcome Measures

The adverse birth outcomes include preterm birth, macrosomia, and large for gestational age (LGA).

Results

Among 5658 subjects, the rates of preterm birth, macrosomia, and LGA were 4.6% (261/5658), 3.5% (200/5658), and 5.7% (325/5658), respectively. The results of multivariate logistic regression model showed that each 1% increase in maternal HbA1c was positively associated with increased risks of preterm birth (OR 1.58; 95% CI, 1.08-2.31), macrosomia (OR 1.70; 95% CI, 1.10-2.64), and LGA (OR 1.38; 95% CI, 0.98-1.96). The association between gestational HbA1c and preterm birth was more evident among women with prepregnancy body mass index (BMI) ≤ 24 kg/m2.

Conclusions

Gestational higher HbA1c level within the normal range is an independent risk factor for preterm birth, macrosomia, and LGA. Intervention for reducing HbAc1 may help to prevent adverse birth outcomes.
Intraoperative Cardiac Arrest During Adult Liver Transplantation: Incidence and Risk Factor Analysis From 7 Academic Centers in the United States
Authors: Smith Natalie K , Zerillo Jeron , Kim Sang Jo , Efune Guy E. , Wang Cynthia , Pai Sher-Lu , Chadha Ryan , Kor Todd M. , Wetzel David R. , Hall Michael A. , Burton Kristen K. , Fukazawa Kyota , Hill Bryan , Spad Mia-Ashley , Wax David B. , Lin Hung-Mo , Liu Xiaoyu , Odeh Jaffer , Torsher Laurence , Kindscher James D. , Mandell M. Susan , Sakai Tetsuro , DeMaria Samuel
Published: March 2020

Background:

Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks.

METHODS:

Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18–80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes.

RESULTS:

ICA occurred in 196 cases (3.7% 95% confidence interval [CI], 3.2–4.2) and mortality occurred in 62 patients (1.2%). The intraoperative mortality rate was 31.6% in patients who experienced ICA. In a multivariable generalized linear mixed model, ICA was associated with body mass index (BMI) <20 (odds ratio [OR]: 2.04, 95% CI, 1.05–3.98; P = .0386), BMI ≥40 (2.16 [1.12–4.19]; P = .022), Model for End-Stage Liver Disease (MELD) score: (MELD 30–39: 1.75 [1.09–2.79], P = .02; MELD ≥40: 2.73 [1.53–4.85], P = .001), postreperfusion syndrome (PRS) (3.83 [2.75–5.34], P < .001), living donors (2.13 [1.16–3.89], P = .014), and reoperation (1.87 [1.13–3.11], P = .015). Overall 30-day and 1-year mortality were 4.18% and 11.0%, respectively. After ICA, 30-day and 1-year mortality were 43.9% and 52%, respectively, compared to 2.6% and 9.3% without ICA.

CONCLUSIONS:

We established a 3.7% incidence of ICA and a 1.2% incidence of intraoperative mortality in liver transplantation and confirmed previously identified risk factors for ICA including BMI, MELD score, PRS, and reoperation and identified new risk factors including living donor and length of surgery in this multicenter retrospective cohort. ICA, while rare, is associated with high intraoperative mortality, and future research must focus on therapy to reduce the incidence of ICA.
Increased Anandamide and Decreased Pain and Depression after Exercise in Fibromyalgia
Authors: STENSSON NICLAS , GERDLE BJÖRN , ERNBERG MALIN , MANNERKORPI KAISA , KOSEK EVA , GHAFOURI BIJAR
Published: March 2020

Purpose

Physical exercise is increasingly being promoted by health care for chronic pain conditions with beneficial outcomes, such as pain and fatigue reduction, and increased quality of life. Nevertheless, knowledge about biochemical consequences of physical exercise in chronic pain is still relatively poor. The endocannabinoid system has been suggested to play a role for acute exercise-induced reward and pain inhibition. The aim of this study is to investigate the chronic outcomes of resistance exercise on levels of endocannabinoids and related lipids in fibromyalgia (FM).

Methods

This study examine the outcomes of a 15-wk person-centered resistance exercise program on plasma levels of the lipid mediators; anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide (SEA) sampled from 37 women with FM and 33 healthy controls. The associations between clinical scorings of pain, depression, anxiety, fatigue, and muscle strength with levels of these lipid mediators before and after the exercise program are also analyzed.

Results

After the 15-wk exercise program, anandamide levels were significantly increased, and SEA levels significantly decreased in FM. Pain intensity and depression scorings decreased and muscle strength increased, and in a multivariate context, muscle strength was positively associated with 2-AG levels after the resistance exercise program in FM.

Conclusions

The increased anandamide and decreased SEA in women with FM after the 15-wk program might point to a chronic effect of resistance exercise. Pain and depression scorings decreased in the FM group after the program, but no associations between pain, depression, and lipid level changes were assured.
A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs
Authors: Dors Arkadiusz , Czyżewska-Dors Ewelina , Woźniakowski Grzegorz
Published: March 2020

Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production includeBrachyspira hyodysenteriaeandBrachyspira pilosicoli. The aim of this study was to assess the current occurrence ofB. hyodysenteriaeandB. pilosicoliin Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence ofB. hyodysenteriaeandB. pilosicoliin pigs were investigated.

Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence ofB. hyodysenteriae,B. pilosicoliandLawsonia intracellularisby real-time PCR.

Results:B. pilosicoliwas detected in 4.5% (95% CI, 2.5–7.0%) (18/401) of pig fecal samples. At the herd level 13.7% (95% CI, 7.5–22.3%) (13/95) of herds were positive forB. pilosicoli.B. hyodysenteriaewas detected in 7.0% (95% CI, 4.7–9.9%) (28/401) of pig fecal samples and 18.9% (95% CI, 11.6–28.3%) (18/95) of pig herds were positive. Out of 18B. pilosicolipositive samples, this pathogen was detected alone in 5 samples; simultaneously withL. intracellularisin 9 samples; simultaneously withB. hyodysenteriaein 1 sample and in 3 samples was detected simultaneously with both of these bacteria. The presence ofB. hyodysenteriaein fecal samples was associated with the presence of diarrhea in pigs.

Conclusions: This study confirmed thatB. pilosicoliinfections occur in Polish pig herds, but the prevalence is at a low level and the presence ofB. pilosicoliis not associated with the development of diarrhea in pigs.B. hyodysenteriaeis still a common cause of diarrhea among pigs from Polish herds.