bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the patchy legislative landscape of non-native tree species in Europe
Authors: Pötzelsberger Elisabeth , Lapin Katharina , Brundu Giuseppe , Adriaens Tim , Andonovski Vlatko , Andrašev Siniša , Bastien Jean-Charles , Brus Robert , Čurović Milić , Čurović Željka , Cvjetković Branislav , Đodan Martina , Domingo-Santos Juan M , Gazda Anna , Henin Jean-Marc , Hernea Cornelia , Karlsson Bo , Keča Ljiljana , Keren Srđan , Keserű Zsolt , Konstantara Thomai , Kroon Johan , La Porta Nicola , Lavnyy Vasyl , Lazdina Dagnija , Lukjanova Aljona , Maaten Tiit , Madsen Palle , Mandjukovski Dejan , Marín Pageo Francisco J , Marozas Vitas , Martinik Antonin , Mason William L , Mohren Frits , Monteverdi Maria Cristina , Neophytou Charalambos , Neville Pat , Nicolescu Valeriu-Norocel , Nygaard Per Holm , Orazio Christophe , Parpan Taras , Perić Sanja , Petkova Krasimira , Popov Emil Borissov , Power Mick , Rédei Károly , Rousi Matti , Silva Joaquim S , Sivacioğlu Ahmet , Socratous Michalis , Straigytė Lina , Urban Josef , Vandekerkhove Kris , Wąsik Radosław , Westergren Marjana , Wohlgemuth Thomas , Ylioja Tiina , Hasenauer Hubert
Published: March 2020

Europe has a history rich in examples of successful and problematic introductions of trees with a native origin outside of Europe (non-native trees, NNT). Many international legal frameworks such as treaties and conventions and also the European Union have responded to the global concern about potential negative impacts of NNT that may become invasive in natural ecosystems. It is, however, national and regional legislation in particular that affects current and future management decisions in the forest sector and shapes the landscapes of Europe. We identified all relevant legal instruments regulating NNT, the different legal approaches and the regulatory intensity in 40 European countries (no microstates). Information on hard and effective soft law instruments were collected by means of a targeted questionnaire and consultation of international and national legislation information systems and databases. In total, 335 relevant legal instruments were in place in June/July 2019 to regulate the use of NNT in the investigated 116 geopolitical legal units (countries as well as sub-national regions with their own legislation). Countries and regions were empirically categorized according to ad hoc-defined legislation indicators. These indicators pay respect to the general bans on the introduction of non-native species, the generally allowed and prohibited NNT, approval mechanisms and specific areas or cases where NNT are restricted or prohibited. Our study revealed a very diverse landscape of legal frameworks across Europe, with a large variety of approaches to regulating NNT being pursued and the intensity of restriction ranging from very few restrictions on species choice and plantation surface area to the complete banning of NNT from forests. The main conclusion is that there is a clear need for more co-ordinated, science-based policies both at the local and international levels to enhance the advantages of NNT and mitigate potential negative effects.
The Meaningful Participation of Refugees in Decision-Making Processes: Questions of Law and Policy
Authors: Harley Tristan , Hobbs Harry
Published: March 2020

There has been a significant push in recent years for greater and more meaningful participation of refugees in decision-making processes that affect them. This push is identifiable in a range of international instruments, including the 2016 New York Declaration for Refugees and Migrants and the 2018 Global Compact on Refugees, as well as numerous initiatives developed by refugees, civil society organizations, and international organizations at the local, national, and international level. This article considers the emergent drive for refugee participation from the perspective of both law and policy. It examines the evolution of the international legal framework, analysing the extent to which international refugee and human rights law mandate the inclusion of refugees in decisions that affect them. The article also explores the notion of participation in detail, teasing out several key challenges for consideration in the development of inclusive participatory processes. Drawing this material together, it explores two options that could further promote the moral, political, and ultimately legal authority for meaningfully including refugees in the design and implementation of policy. These options are indicators that establish baselines and track refugee participation in decision-making processes, and a new, non-binding United Nations declaration that clearly details the right of refugees to have some authority in decision-making processes that affect them.
National Public Health Burden Estimates of Endocarditis and Skin and Soft-Tissue Infections Related to Injection Drug Use: A Review
Authors: See Isaac , Gokhale Runa H , Geller Andrew , Lovegrove Maribeth , Schranz Asher , Fleischauer Aaron , McCarthy Natalie , Baggs James , Fiore Anthony
Published: March 2020

Background

Despite concerns about the burden of the bacterial and fungal infection syndromes related to injection drug use (IDU), robust estimates of the public health burden of these conditions are lacking. The current article reviews and compares data sources and national burden estimates for infective endocarditis (IE) and skin and soft-tissue infections related to IDU in the United States.

Methods

A literature review was conducted for estimates of skin and soft-tissue infection and endocarditis disease burden with related IDU or substance use disorder terms since 2011. A range of the burden is presented, based on different methods of obtaining national projections from available data sources or published data.

Results

Estimates using available data suggest the number of hospital admissions for IE related to IDU ranged from 2900 admissions in 2013 to more than 20 000 in 2017. The only source of data available to estimate the annual number of hospitalizations and emergency department visits for skin and soft-tissue infections related to IDU yielded a crude estimate of 98 000 such visits. Including people who are not hospitalized, a crude calculation suggests that 155 000–540 000 skin infections related to IDU occur annually.

Discussion

These estimates carry significant limitations. However, regardless of the source or method, the burden of disease appears substantial, with estimates of thousands of episodes of IE among persons with IDU and at least 100 000 persons who inject drugs (PWID) with skin and soft-tissue infections annually in the United States. Given the importance of these types of infections, more robust and reliable estimates are needed to better quantitate the occurrence and understand the impact of interventions.
Deregulation of tumor suppressive ASXL1−PTEN/AKT axis in myeloid malignancies
Authors: Cao Lei , Xia Xianyou , Kong Yu , Jia Fengqin , Yuan Bo , Li Rui , Li Qian , Wang Yuxin , Cui Mingrui , Dai Zhongye , Zheng Huimin , Christensen Jesper , Zhou Yuan , Wu Xudong
Published: March 2020

Mutations of epigenetic regulators are pervasive in human tumors. ASXL1 is frequently mutated in myeloid malignancies. We previously found that ASXL1 forms together with BAP1 a complex that can deubiquitinylate mono-ubiquitinylated lysine 119 on histone H2A (H2AK119ub1), a Polycomb repressive mark. However, a complete mechanistic understanding of ASXL1 in transcriptional regulation and tumor suppression remains to be defined. Here, we find that depletion of Asxl1 confers murine 32D cells to IL3-independent growth at least partly due to sustained activation of PI3K/AKT signaling. Consistently, Asxl1 is critical for the transcriptional activation of Pten, a key negative regulator of AKT activity. Then we confirm that Asxl1 is specifically enriched and required for H2AK119 deubiquitylation at the Pten promoter. Interestingly, ASXL1 and PTEN expression levels are positively correlated in human blood cells and ASXL1 mutations are associated with lower expression levels of PTEN in human myeloid malignancies. Furthermore, malignant cells with ASXL1 downregulation or mutations exhibit higher sensitivity to the AKT inhibitor MK2206. Collectively, this study has linked the PTEN/AKT signaling axis to deregulated epigenetic changes in myeloid malignancies. It also provides a rationale for mechanism-based therapy for patients with ASXL1 mutations.
Progress in human liver organoids
Authors: Sun Lulu , Hui Lijian
Published: March 2020

Understanding the development, regeneration, and disorders of the liver is the major goal in liver biology. Current mechanistic knowledge of human livers has been largely derived from mouse models and cell lines, which fall short in recapitulating the features of human liver cells or the structures and functions of human livers. Organoids as an in vitro system hold the promise to generate organ-like tissues in a dish. Recent advances in human liver organoids also facilitate the understanding of the biology and diseases in this complex organ. Here we review the progress in human liver organoids, mainly focusing on the methods to generate liver organoids, their applications, and possible future directions.
High spatiotemporal-resolution imaging in the scanning transmission electron microscope
Authors: Ishikawa Ryo , Jimbo Yu , Terao Mitsuhisa , Nishikawa Masashi , Ueno Yujiro , Morishita Shigeyuki , Mukai Masaki , Shibata Naoya , Ikuhara Yuichi
Published: March 2020

The temporal resolution in scanning transmission electron microscopy (STEM) is limited by the scanning system of an electron probe, leading to only a few frames per second (fps) at most in the current microscopes. To push the boundary of atomic-resolution STEM imaging into dynamic observations, an unprecedentedly faster scanning system combined with fast electron detection systems should be a prerequisite. Here we develop a new scanning probe system with the acquisition time of 83 nanoseconds per pixel and the fly-back time of 35 microseconds, leading to 25 fps STEM imaging with the image size of 512 × 512 pixels that is faster than a human perception speed. Using such high-speed probe scanning system, we have demonstrated the observations of shape-transformation of Pt nanoparticles and Pt single atomic motions on TiO2 (110) surface at atomic-resolution with the temporal resolution of 40 milliseconds. The present probe scanning system opens the door to use atomic-resolution STEM imaging for in situ observations of material dynamics under the temperatures of cooling or heating, the atmosphere of liquid or gas, electric-basing or mechanical test.
Music Therapist Experiences of a Randomized Controlled Trial as Clinician Researchers
Authors: Henley Amanda K , Collier Elizabeth , Robertson Kim , Biard Marial A , Bruno Kathryn , Bush Hannah , Frees Erinn , Krater Caitlin , Woolever Sarah , Burns Debra S , Robb Sheri L
Published: March 2020

Music therapy clinicians bring an important perspective to the design and conduct of clinically meaningful studies. Unfortunately, there continue to be roadblocks that hinder clinician involvement in research and the development of successful partnerships between academic researchers and practicing clinicians. To help grow clinician involvement, it is important that research teams share their experiences. As such, the purpose of this qualitative study was to share music therapists’ perspectives about their experience of working as a research clinician on a large multisite randomized controlled trial. 10 board-certified music therapists provided written responses to 6 data-generating questions about: (a) reasons for participating, (b) perceived challenges and benefits, (c) experiences of quality assurance monitoring, (d) professional growth, (e) value of research, and (f) advice for clinicians considering research involvement. Using thematic content analysis, we identified primary themes and subthemes for each question (20 themes; 30 subthemes). Qualitative analysis revealed not only common challenges, such as reconciling clinical and research responsibilities, but also benefits, including continued professional growth, greater understanding of research processes, and research participation as a way to advocate and advance the profession. Finally, for clinicians interested in becoming involved in research, therapists noted the importance of having workplace support from a mentor, supervisor, and/or administrator; seeking out available resources; and knowing roles and responsibilities before initiating research involvement. Findings offer important insight and recommendations to support the involvement of clinicians in research and support further exploration of clinician involvement in dissemination efforts to improve translation and uptake of research into practice.
Experience of Music Used With Psychedelic Therapy: A Rapid Review and Implications
Authors: O’Callaghan Clare , Hubik Daniel J , Dwyer Justin , Williams Martin , Ross Margaret
Published: March 2020

Bonny Method of Guided Imagery and Music emerged following discontinuation of psychedelic therapy research in the early 1970s, but psychedelic therapy research has since revived. Music remains a vital component. This study examined participants’ experiences of music in psychedelic therapy research. A rapid review of qualitative and quantitative journal articles in four major databases was conducted in February to April, 2019, using the terms hallucinogens, psychedelic, “lysergic acid diethylamide,” psilocybin, ayahuasca, music, and/or “music therapy.” Of 406 articles retrieved, 10 were included (n = 180; 18–69 years old). Participants had varied backgrounds. Music was widely considered integral for meaningful emotional and imagery experiences and self-exploration during psychedelic therapy. Music transformed through its elicitation of anthropomorphic, transportive, synesthetic, and material sensations. Music could convey love, carry listeners to other realms, be something to “hold,” inspire, and elicit a deep sense of embodied transformation. Therapeutic influence was especially evident in music’s dichotomous elicitations: Music could simultaneously anchor and propel. Participant openness to music and provision of participant-centered music were associated with optimal immediate and longer-term outcomes. Many studies reported scarce details about the music used and incidental findings of music experienced. Further understanding of participants’ idiosyncratic and shared responses to music during drug therapy phases will inform optimal development of flexible music protocols which enhance psychedelic therapy. Music therapists could be involved in the psychedelic therapy research renaissance through assisting with research to optimize music-based protocols used. If psychedelics become approved medicines, music therapists may be involved in offering psychedelic therapy as part of therapeutic teams.
The Semantics of Evidentials in Questions
Authors: Bhadra Diti
Published: March 2020

This paper presents a novel cross-linguistic exploration of the phenomenon of Interrogative Flip at the semantics-pragmatics interfaces. Most previous studies describe an obligatory shift in the anchor of an evidential from the speaker to the addressee in interrogatives, across a diverse set of languages. In this work, we discuss a lesser-studied set of facts, which show that in many languages this shift does not take place. Modeling the contribution of evidentials with ‘judge’-sensitivity in the semantics and with newly refined notions of commitment and sourcehood in an extended dynamic pragmatics framework, the presence or absence of Interrogative Flip is shown to lie in an evidential’s ability to license a commitment update operator $\uparrow $. All attested evidential systems are shown to fall in either the class of $\uparrow $ licensors or not, with apparent exceptions explained across a heterogeneous array of data. A dynamic polar question operator is formulated and its interaction with $\uparrow $ explored. Finally, a novel link between evidentiality and bias is established, by arguing that the lack of the Flip results in biased questions.
Towards A Comprehensive Model For Interpreting Word Order In Classical Biblical Hebrew
Authors: Khan Geoffrey , Van Der Merwe Christo H.J.
Published: March 2020

In this paper we examine the function of fronting constructions in verbal clauses in Classical Biblical Hebrew, i.e. constructions that involve the placement of a clause constituent before the verb. We present a model that accommodates the vast majority of cases of fronting in a sample corpus of 1 Samuel. A key feature of our model is the recognition that fronting constructions include both categorical sentences, which make a predication about a base of predication, and also thetic sentences, which present a unitary situation. We classify fronting constructions into three types: (i) narrow constituent focus constructions, (ii) selecting topic constructions, (iii) thetic constructions. An innovative idea that is developed in the paper is that constructions (i) and (iii), although exhibiting different configurations of information structure, nevertheless share various functional properties on the level of discourse organization. On account of these shared properties, we argue that thetic constructions (iii) can be regarded as functional extensions of narrow focus constructions (i). Recognition of these various types of fronting and their interrelationship contributes to a better understanding of the phenomenon.
Genetically encoded X-ray cellular imaging for nanoscale protein localization
Authors: Kong Huating , Zhang Jichao , Li Jiang , Wang Jian , Shin Hyun-Joon , Tai Renzhong , Yan Qinglong , Xia Kai , Hu Jun , Wang Lihua , Zhu Ying , Fan Chunhai
Published: March 2020

Spatial resolution defines the physical limit of microscopes for probing biomolecular localization and interactions in cells. Whereas synchrotron-based X-ray microscopy (XRM) represents a unique approach for imaging a whole cell with nanoscale resolution due to its intrinsic nanoscale resolution and great penetration ability, existing approaches to label biomolecules rely on the use of exogenous tags that are multi-step and error-prone. Here, we repurpose engineered peroxidases as genetically encoded X-ray-sensitive tags (GXET) for site-specific labeling of protein-of-interest in mammalian cells. We find that 3,3′-diaminobenzidine (DAB) polymers that are in-situ catalytically formed by fusion-expressed peroxidases are visible under XRM. Using this new tag, we imaged the protein location associated with the alteration of a DNA-methylation pathway with an ultra-high resolution of 30 nanometers. Importantly, the excellent energy resolution of XRM enables multicolor imaging using different peroxidase tags. The development of GXET enlightens the way to nanoscopic imaging for biological studies.
Contact Transmission of Vaccinia to an Infant Diagnosed by Viral Culture and Metagenomic Sequencing
Authors: Martin Rebekah M , Burke Kristina , Verma Dinesh , Xie Heng , Langer Janine , Schlaberg Robert , Swaminathan Sankar , Hanson Kimberly E
Published: March 2020

Targeted molecular diagnostic tests and accurate immunoassays have transformed the landscape of clinical virology, calling into question the usefulness of traditional viral culture. Here we present a case where viral culture, followed by metagenomic sequencing, was central to the diagnosis of an unexpected viral infection, with significant clinical and public health implications.
Remarkable response of a patient with secondary glioblastoma to a histone deacetylase inhibitor
Authors: Gurbani Saumya S , Weinberg Brent D , Salgado Eric , Voloschin Alfredo , Velazquez Vega Jose Enrique , Olson Jeffrey J , Shu Hui-Kuo G , Shim Hyunsuk
Published: March 2020

Secondary glioblastoma is a rare brain tumor characterized by a mutation in isocitrate dehydrogenase, which is reported to lead to epigenetic modification. Patients with secondary glioblastoma experience poor survival and quality-of-life outcomes due to the disease’s aggressiveness and a lack of targeted therapies. In this report, a patient with a secondary glioblastoma was treated with a histone deacetylase inhibitor, an epigenetic drug with potent anti-inflammatory properties, in addition to the standard regimen. The patient showed very favorable survival and quality-of-life measures, and a restoration of several neuro-metabolites as measured by spectroscopic magnetic resonance imaging.
Prevalence of high blood pressure among Canadian Children: 2017 American Academy of Pediatrics guidelines with the Canadian Health Measures Survey
Authors: Robinson Suzanne K , Rodd Celia J , Metzger Daniel L , Sharma Atul K
Published: March 2020

Background

We assess the impact of the 2017 American Academy of Pediatrics (AAP) guidelines on the prevalence of high blood pressure (BP) in generally healthy Canadian children and identify risk factors associated with high BP (elevated, stage 1, or stage 2 at a single visit).

Methods

A cohort of 7,387 children aged 6 to 18 years in the Canadian Health Measures Survey (CHMS, 2007 to 2015) had BPTru oscillometry with centiles and stages assigned using both the 2017 AAP guidelines and the 2004 Fourth Report from the National Institute of Health/National Heart Lung and Blood Institute (NIH/NHLBI).

Results

Although both shifted upwards significantly, mean population systolic BP and diastolic BP percentiles are now 24.2 (95% confidence interval: 23.3 to 25.2) and 46.4 (45.3 to 47.6). As a result, the population prevalence of high BP increased from 4.5% (3.9 to 5.2, NIH/NHLBI) to 5.8% (5.0 to 6.6, AAP), less than in US children measured by auscultation (14.2%, 13.4 to 15.0). Children with high BP were more likely to be overweight/obese, to be exposed to prenatal/household smoking, and to have hypertriglyceridemia, without differences in dietary salt, infant breastfeeding, neonatal hospitalizations, or exercise frequency.

Conclusion

The 2017 AAP guidelines increase the prevalence of high BP in Canadian children; Canadian prevalence appears lower than in the USA. This may reflect differences in measurement methods or in the prevalence of childhood overweight/obesity between countries, that is, 31.1% (28.9 to 33.3) versus 40.6% (39.5 to 42.0), respectively. Those with high BP were more likely to have other cardiac risk factors, including overweight/obesity, prenatal/household smoking exposure, and hypertriglyceridemia.
Association of Physical Activity and Cognitive Activity With Disability: A 2-Year Prospective Cohort Study
Authors: Kurita Satoshi , Doi Takehiko , Tsutsumimoto Kota , Nakakubo Sho , Kim Minji , Ishii Hideaki , Shimada Hiroyuki
Published: March 2020

Objective

Engaging in physical activity (PA) and/or cognitive activity (CA) retains function in older adults, but whether the combination of these activities is associated with disability onset is still unknown. This study aimed to examine the prospective association of PA and/or CA with disability onset in older adults.

Methods

This was an ongoing prospective community-based cohort study. Data collection was conducted through a health check. An analyzable sample of 2668 participants (mean age = 75.5 years; 51.6% female) were categorized into 4 groups based on quartile 1 (low) and 2 to 4 (high) values of accelerometer-measured moderate-to-vigorous PA and CA scale scores based on the frequency of 6 activities including reading, writing for pleasure, doing crossword puzzles, and playing board games or cards. Disability onset was monitored through long-term care insurance certification for at least 2 years.

Results

A log-rank test showed significantly lower incidence of disability in the high PA and low CA group and the high PA and high CA group compared with the low PA and low CA group. Cox-proportional hazards models (referring to the low PA and low CA group) showed that only the high PA and high CA group was significantly associated with a lowered hazard ratio for disability onset (0.51; 95% CI = 0.29–0.90) after adjusting for covariates.

Conclusions

Engaging in both PA and CA is effective for reducing risk of disability onset, but engaging in either PA or CA is not effective.

Impact

Physical therapists can be guided by this research to design intervention strategies for people at risk of disability.
The Efficacy of Surgical Excision Plus Adjuvant Multimodal Therapies in the Treatment of Keloids: A Systematic Review and Meta-Analysis
Authors: Ellis Morgan M. , Jones Lamont R. , Siddiqui Farzan , Sunkara Pranit R. , Ozog David M.
Published: March 2020

BACKGROUND

Research evaluating the efficacy of multimodal therapy for the treatment of keloids has reported combination regimens are most effective.

OBJECTIVE

To compare recurrence rates for keloids treated with surgery plus one adjuvant intervention (dual therapy) versus surgery plus 2 or more adjuvant interventions (triple therapy).

MATERIALS AND METHODS

Systematic literature review and meta-analysis of combination treatment for keloids.

RESULTS

After full-text review, we included 60 articles representing 5,547 keloids: 5,243 received dual therapy, 259 received triple therapy, and 45 received quadruple therapy (the latter 2 groups were combined for analysis). The difference in recurrence rates between dual (19%) and triple therapy (11.2%) was not significant (p = .343). However, the difference in recurrence rates between dual therapy using surgery and radiation (18.7%) and triple therapy using surgery, radiation, and a third intervention (7.7%) was significant (p = .002). The differences for surgery and intralesional triamcinolone (TAC) showed trends toward significance, because keloids treated with dual therapy (21.7%) had a higher recurrence rate than those treated with triple therapy comprised of surgery, TAC, and another intervention (13.7%; p = .099).

CONCLUSION

Triple therapy using surgery plus radiation and/or TAC as one of the adjuvant treatment modalities may achieve the lowest recurrence rates for keloids.
Surgery in the Obese Pregnant Patient
Authors: KARIMYAR TAHMINA , PEREIRA LEONARDO
Published: March 2020

This chapter reviews issues which complicate surgery in obese pregnant patients. Maternal obesity is prevalent in the United States and is associated with numerous adverse health outcomes. When surgery is indicated during pregnancy, the presence of maternal obesity increases surgical risks for both the fetus and mother. Specific risks are identified and strategies to avoid them are evaluated. The prognosis and management of pregnant women who have undergone bariatric surgery is also discussed, and practical guidelines for obstetric management of these patients are presented.
Fluctuations in Vestibular Afferent Excitability in Menière's Disease
Authors: Rubinstein Jay T. , Phillips Christopher , Ling Leo , Nie Kaibao , Phillips James O.
Published: March 2020

Objective:

To determine if Menière's disease is associated with fluctuations in afferent excitability in four human subjects previously implanted with vestibular stimulators.

Study design: Longitudinal repeated measures.

Setting: Tertiary referral center, human vestibular research laboratory.

Patients: Four human subjects with previously uncontrolled Menière's disease unilaterally implanted in each semicircular canal with a vestibular stimulator. One subject had only two canals implanted.

Intervention(s): Repeated measures of electrically-evoked slow phase eye velocity and vestibular electrically-evoked compound action potentials (vECAP) over 2 to 4 years.

Main outcome measure(s): Slow phase eye velocity and N1-P1 vECAP amplitudes as a function of time.

Results:

There were statistically significant fluctuations in electrically evoked slow phase eye velocity over time in at least one semicircular canal of each subject. vECAP N1-P1 amplitudes measured at similar time intervals and stimulus intensities seem to show somewhat correlated fluctuations. One of the subjects had a single Menière's attack during this time period. The others did not.

Conclusions:

In these four subjects originally diagnosed with Menière's disease, there was fluctuating electrical excitability of the ampullar nerve of at least one canal in each subject. These fluctuations occurred without active symptoms of Menière's disease.
Prognostic Factors Associated With Progression for Advanced-Stage/G1 and G2 Small-Bowel Neuroendocrine Tumors After Multimodal Therapy
Authors: Khetan Prerna , Oyewole Femi , Wolin Edward , Kim Michelle Kang , Divino Celia M.
Published: March 2020

Objectives

Neuroendocrine tumors represent approximately 40% of primary small bowel malignancies. However, factors predictive of progression after multimodal surgical therapy have not been well described. We evaluated the characteristics of small bowel neuroendocrine tumor patients associated with progression after multimodal surgical resection.

Methods

A retrospective chart review identified 99 stage III and stage IV small bowel neuroendocrine tumor patients at Mount Sinai diagnosed and treated with surgery between 2005 and 2019. Progression-free survival (PFS) was defined as time from surgery until progression in surveillance radiologic imaging. Kaplan-Meier method was used to calculate PFS. Cox proportional hazard models were used to study the prognostic factors for PFS.

Results

Of 99 patients, 48 had tumor progression during the follow-up period. Median PFS was 5.7 years (95% confidence interval [CI], 3.73–8.66) for the entire cohort. Prognostic factors for PFS were age at diagnosis (hazard ratio [HR], 1.04; 95% CI, 1.01–1.07), perineural invasion (HR, 2.19; 95% CI, 1.13–4.23), and elevated preoperative chromogranin level (HR, 2.31; 95% CI, 1.01–5.27).

Conclusions

Age at diagnosis, perineural invasion, and elevated preoperative chromogranin level may play a prognostic role in PFS.
The infected fracture: can we agree on standard definitions?
Authors: Hak David J.
Published: March 2020

A precise definition of infection after fracture fixation is essential for the evaluation of published research data and for the future establishment of uniform treatment concepts. Recently, a multidisciplinary expert panel has developed a consensus definition that includes 4 confirmatory criteria for infection following fracture fixation. These criteria are: Fistula, sinus, or wound breakdown; purulent drainage or deep purulence at surgery; positive cultures from at least 2 separate deep tissue/implant specimens taken during an operative intervention; and microorganisms in deep tissue specimens confirmed by histopathological staining. The consensus panel also identified 6 categories of suggestive criteria which are features associated with infection that requires further investigation.
Acute and chronic infection: Is there a gold standard for management of the wound and bone defect?
Authors: Giannoudis Peter V. , Tosounidis Theodoros H.
Published: March 2020

Acute and chronic infections with bone involvement remain a challenge to manage. They pose a significant burden to the patient, the treating surgeon, and society. Multidisciplinary team involvement is mandatory for a successful outcome. Application of a gold standard approach is not possible due to the high heterogeneous patient population and the variable degree of severity of soft tissue and bone involvement. The mainstay of treatment remains the conversion of a septic environment to an aseptic one with aggressive debridement of the affected soft tissues and bone. Reconstruction of the soft tissue defect can be achieved using modern microsurgical techniques, whereas the induced membrane and distraction osteogenesis (bone transport) are currently the 2 most commonly used treatment modalities for bone loss.

The safest approach to deal successfully with this multifaceted clinical pathology is to always follow well-established principles of management and adapt treatment to the personalized needs of the patient.
Needle Heating During Interventional Magnetic Resonance Imaging at 1.5- and 3.0-T Field Strengths
Authors: Khodarahmi Iman , Bonham Luke W. , Weiss Clifford R. , Fritz Jan
Published: March 2020

Objectives

The aim of this study was to test the hypothesis that clinically used magnetic resonance (MR)–conditional needles of varying lengths, orientations, locations, and pulse sequences can result in excessive heating during MR imaging (MRI)–guided interventions that can be minimized to physiological ranges with proper selection of the needle length, needle position, and modification of pulse sequence parameters.

Materials and Methods

We simulated a clinical interventional MRI setting with 2 standard American Society for Testing and Materials F2182-11A phantoms and measured temperatures with fiber optic sensors. Temperature profiles were monitored for commercial 10, 15 and 20 cm MR-conditional cobalt-chromium needles in clinically relevant perpendicular, 45-degree oblique, and parallel orientations relative to the static magnetic field (B0) and center, right off-center, and left off-center needle tip locations in the z = 0 plane. Clinically available interventional MRI pulse sequences including turbo spin echo (TSE), fast TSE, slice encoding for metal artifact correction, compressed sensing slice encoding for metal artifact correction, half-Fourier acquisition single-shot TSE (HASTE), HASTE inversion recovery, fluoroscopic steady-state gradient echo (3.0 T only), fast low-angle shot gradient echo, and volumetric interpolated breath-hold examination gradient echo pulse sequences were tested at 1.5 and 3.0 T field strengths. Acquired temperature data were analyzed using Friedman and Wilcoxon signed-rank tests with Bonferroni correction.

Results

After 5-minute of continuous MRI, less than 2.5°C heating occurred when needles were oriented perpendicular and 45-degree oblique to B0, regardless of field strengths. Higher temperature rises capable of causing permanent tissue damage were observed when needles were oriented in parallel to B0 (1.5 T: 22°C with 20 cm needles, 3.0 T: 8°C with 10 and 15 cm needles) using higher radiofrequency energy pulse sequences, such as TSE and HASTE. Left off-center location, parallel orientation, and needle lengths close to half of the radiofrequency pulse wavelength were positively associated with higher temperature rises.

Conclusions

Under the herein used experimental conditions, clinically used MR-conditional needles can heat to supraphysiologic temperatures during prolonged MRI at 1.5 and 3.0 T field strengths; however, the temperature rise can be balanced to physiological ranges with proper selection of needle length, needle orientation, and pulse sequence parameters. Caution must be exercised when using different MRI systems, as results may not directly translate.
Lesion Detectability and Radiation Dose in Spiral Breast CT With Photon-Counting Detector Technology
Authors: Shim Sojin , Saltybaeva Natalia , Berger Nicole , Marcon Magda , Alkadhi Hatem , Boss Andreas
Published: March 2020

Objectives

The aim of the article was to evaluate the lesion detectability, image quality, and radiation dose of a dedicated clinical spiral breast computed tomography (CT) system equipped with a photon-counting detector, and to propose optimal scan parameter settings to achieve low patient dose levels and optimal image quality.

Methods

A breast phantom containing inserts mimicking microcalcifications (diameters 196, 290, and 400 μm) and masses (diameters 1.8, 3.18, 4.76, and 6.32 mm) was examined in a spiral breast CT system with systematic variations of x-ray tube currents between 5 and 125 mA, using 2 slabs of 100 and 160 mm. Signal-to-noise ratio and contrast-to-noise ratio measurements were performed by region of interest analysis. Two experienced radiologists assessed the detectability of the inserts. The average absorbed dose was calculated in Monte Carlo simulations.

Results

Microcalcifications in diameters of 290 and 400 μm and masses in diameters of 3.18, 4.76, and 6.32 mm were visible for all tube currents between 5 and 125 mA. Soft tissue masses in a diameter of 1.8 mm were visible at tube currents of 25 mA and higher. Microcalcifications with a diameter of 196 μm were detectable at a tube current of 25 mA and higher in the small, and at a tube current of 40 mA and higher in the large slab. For the small and large breast, at a tube current of 25 and 40 mA, an average dose value of 4.30 ± 0.01 and 5.70 ± 0.02 mGy was calculated, respectively.

Conclusions

Optimizing tube current of spiral breast CT according to the breast size enables the visualization of microcalcifications as small as 196 μm while keeping dose values in the range of conventional mammography.
The Future of Computed Tomography
Authors: Alkadhi Hatem , Euler André
Published: March 2020

Modern medicine cannot be imagined without the diagnostic capabilities of computed tomography (CT). Although the past decade witnessed a tremendous increase in scan speed, volume coverage, and temporal resolution, along with a considerable reduction of radiation dose, current trends in CT aim toward more patient-centric, tailored imaging approaches that deliver diagnostic information being personalized to each individual patient. Functional CT with dual-and multienergy, as well as dynamic, perfusion imaging became clinical reality and will further prosper in the near future, and upcoming photon-counting detectors will deliver images at a heretofore unmatched spatial resolution.

This article aims to provide an overview of current trends in CT imaging, taking into account the potential of photon-counting detector systems, and seeks to illustrate how the future of CT will be shaped.
Continuum thermomechanics of nonlinear micromorphic, strain and stress gradient media
Authors: Forest Samuel
Published: March 2020

A comprehensive constitutive theory for the thermo-mechanical behaviour of generalized continua is established within the framework of continuum thermodynamics of irreversible processes. It represents an extension of the class of generalized standard materials to higher order and higher grade continuum theories. It reconciles most existing frameworks and proposes some new extensions for micromorphic and strain gradient media. The special case of strain gradient plasticity is also included as a contribution to the current debate on the consideration of energetic and dissipative mechanisms. Finally, the stress gradient continuum theory emerges as a new research field for which an elastic-viscoplastic theory at finite deformations is provided for the first time.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Relationships between rational extended thermodynamics and extended irreversible thermodynamics
Authors: Jou David
Published: March 2020

We consider a few conceptual questions on extended thermodynamics, with the aim to contribute to a higher contact between rational extended thermodynamics and extended irreversible thermodynamics. Both theories take a number of fluxes as independent variables, but they differ in the formalism being used to deal with the exploitation of the second principle (rational thermodynamics in the first one and classical irreversible thermodynamics in the second one). Rational extended thermodynamics is more restricted in the range of systems to be analysed, but it is able to obtain a wider number of restrictions and deeper specifications from the second law. By contrast, extended irreversible thermodynamics is more phenomenological, its mathematical formalism is more elementary, but it may deal with a wider diversity of systems although with less detail. Further comparison and dialogue between both branches of extended thermodynamics would be useful for a fuller deployment and deepening of extended thermodynamics. Besides these two approaches, one should also consider the Hamiltonian approach, formalisms with internal variables, and more microscopic approaches, based on kinetic theory or on non-equilibrium ensemble formalisms.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution
Authors: Kumar Roshan , Verma Helianthous , Singhvi Nirjara , Sood Utkarsh , Gupta Vipin , Singh Mona , Kumari Rashmi , Hira Princy , Nagar Shekhar , Talwar Chandni , Nayyar Namita , Anand Shailly , Rawat Charu Dogra , Verma Mansi , Negi Ram Krishan , Singh Yogendra , Lal Rup
Published: March 2020

The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.
Mitigation and herd immunity strategy for COVID-19 is likely to fail
Authors: Adamik Barbara , Bawiec Marek , Bezborodov Viktor , Bock Wolfgang , Bodych Marcin , Burgard Jan Pablo , Götz Thomas , Krueger Tyll , Migalska Agata , Pabjan Barbara , Ożański Tomasz , Rafajłowicz Ewaryst , Rafajłowicz Wojciech , Skubalska-Rafajłowicz Ewa , Ryfczyńska Sara , Szczurek Ewa , Szymański Piotr
Published: March 2020

On the basis of a semi-realistic SIR microsimulation for Germany and Poland, we show that the R0 parameter interval for which the COVID-19 epidemic stays overcritical but below the capacity limit of the health care system to reach herd immunity is so narrow that a successful implementation of this strategy is likely to fail, which is in contrast to results obtained from classical differential equation models. Our microsimulation is based on official census data and involves household composition and age distribution as the main population structure variables. Outside household contacts are characterised by an out-reproduction number R* which is the only free parameter of the model. For a subcritical domain we compute the time till extinction and prevalence as a function of the initial number of infected individuals and R*. For the Polish city of Wrocław we also discuss the combined impact of testing coverage and contact reduction. For both countries we estimate R* for disease progression until 20th of March 2020.
A novel full-reduced HMGB1 and kartogenin-containing bio-active scaffold for meniscus regeneration
Authors: Xu Hongyao , Dai Zhihong , Zou Xiangjie , Xia Pengcheng , Aboudi Mohammad Ahmad , Wang Jingwen , Foon Warren Alexander Lam Sung , Huang He
Published: March 2020

A novel bio-active scaffold for enhancing wounded meniscus healing has been developed by combination of High mobility group box 1 protein (HMGB1) and kartogenin (KGN) with alginate gel. The properties of the bio-active scaffold were also investigated using anin vitrocell culture model andin vivorat wounded meniscus healing model. This HMGB1-KGN-containing bioactive scaffold released HMGB1 and KGN into wound area and kept high concentrations of HMGB1 and KGN in the system for more than two weeks. This HMGB1-KGN-containing bioactive scaffold also activated rat bone marrow stem cells (BMSCs) from G0to GAlertstage and promoted cell proliferation as evidenced by 5-bromo-2-deoxyuridine (BrdU) incorporation testing. Our results also demonstrated that the HMGB1-KGN-containing bioactive scaffold induced cell migrationin vitroand recruited the cells to wound area to promote wounded rat meniscus healingin vivo.
First month of the epidemic caused by COVID-19 in Italy: current status and real-time outbreak development forecast
Authors: Megna Rosario
Published: March 2020

Background

The first outbreaks of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people, Italy has become in a few weeks the country with the greatest number of infected people after China. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service.

Methods

We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 26 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative logistic distribution. We then produced an estimate of the overall number of potentially infected individuals and epidemic duration at a national and Regional level, for the most affected Regions.

Results

We reported the daily distribution of performed swabs and confirmed cases, and the cumulative distribution of confirmed cases, of patients quarantined at home (42%), hospitalized in non-intensive care (31%), recovered or discharged (13%), deceased (10%), and hospitalized in intensive care (4%). The forecast model estimated a number of infected persons for Italy of 115,000 about, and a duration of the epidemic not less than 2 months.

Conclusions

Once month after the first outbreaks there seems to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic.