bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Features of Fibrolamellar Hepatocellular Carcinoma with Contrast-Enhanced Ultrasound
Authors: Dong Yi , Wang Wen-Ping , Mao Feng , Zhang Qi , Yang Daohui , Tannapfel Andrea , Meloni Maria Franca , Neye Holger , Clevert Dirk-André , Dietrich Christoph F.
Published: February 2020

Purpose Fibrolamellar hepatocellular carcinoma (f-HCC) is a rare primary liver tumor. Imaging plays an important role in diagnosis. The aim of this retrospective study was to analyze contrast-enhanced ultrasound (CEUS) features of histologically proven f-HCC in comparison to benign focal nodular hyperplasia (FNH).

Materials & Methods 16 patients with histologically proven f-HCC lesions and 30 patients with FNH lesions were retrospectively reviewed regarding CEUS features to determine the malignant or benign nature of the focal liver lesions (FLL). Five radiologists assessed the CEUS enhancement pattern and came to a consensus using the EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) guideline criteria.

Results Fibrolamellar hepatocellular carcinoma manifested as a single and huge FLL. On CEUS, f-HCC showed heterogeneous hyperenhancement in the arterial phase and hypoenhancement (16/16, 100 %) in the portal venous and late phases (PVLP) as a sign of malignancy. In contrast to the hypoenhancement of f-HCC in the PVLP, all patients with FNH showed hyperenhancement as the most distinctive feature (P < 0.01). 8 f-HCC lesions showed a central scar as an unenhanced area (8/16, 50.0 %), which could also be detected in 53.3 % (16/30) of FNH lesions (P > 0.05).

Conclusion By analyzing the hypoenhancement in the PVLP, CEUS imaging reliably diagnosed f-HCC as a malignant FLL. CEUS also showed differentiation between f-HCC and FNH lesions, showing similar non-enhanced central scars, whereas f-HCC lesions showed peripheral hyperenhancement in the arterial phase and early washout in the PVLP.
Unique Complications of Venous Anastomotic Couplers: A Systematic Review of the Literature
Authors: Wu Gerald J. , Loewenstein Scott N. , Mailey Brian A. , Sasor Sarah , Cook Julia , Hassanein Aladdin H.
Published: February 2020

Background Anastomotic couplers expedite venous microvascular anastomoses and have been established as an equivalent alternative to hand-sewn anastomoses. However, complications unique to the coupler such as palpability and extrusion can occur. The purpose of this study was to perform a systematic review of the literature to assess complications distinct to the venous anastomotic coupler.

Methods A Medline, PubMed, EBSCO host search of articles involving anastomotic venous couplers was performed. Studies involving arterial anastomotic couplers, end-to-side anastomoses, and reviews were excluded. Data points of interest were flap failure, venous thrombosis, hematoma, partial flap necrosis, infection, coupler extrusion, and coupler palpability.

Results The search identified 165 articles; 41 of these met inclusion criteria. A total of 8,246 patients underwent 8,955 venous-coupled anastomoses. Combined reoperation rate was 3.3% and all-cause unsalvageable flap failure was 1.0%. Complications requiring reoperation included venous thrombosis (2.0%), hematoma (0.4%), partial flap necrosis (0.4%), and infection (0.3%). Eight patients had palpable couplers and 11 patients had extrusion of couplers (head/neck, hand, and feet) and required operative management.

Conclusion Venous couplers remain an equivalent alternative to conventional hand-sewn anastomosis. However, venous coupler extrusion and palpability in the late postoperative period is a complication unique to anastomotic couplers, particularly in radiated head and neck, feet and hand free flaps. Removing extruded venous couplers is safe after tissue integration 3 weeks postoperatively. Coupler palpability and extrusion should be integrated into preoperative patient counseling and assessed in follow-up examinations.
Dynamically pre-compressed hydrocarbons studied by self-impedance mismatch
Authors: Hartley N. J. , Zhang C. , Duan X. , Huang L. G. , Jiang S. , Li Y. , Yang L. , Pelka A. , Wang Z. , Yang J. , Kraus D.
Published: February 2020

Using the SG-III prototype laser at China Academy of Engineering Physics, Mianyang, we irradiated polystyrene (CH) samples with a thermal radiation drive, reaching conditions on the principal Hugoniot up to P ≈ 1 TPa (10 Mbar), and away from the Hugoniot up to P ≈ 300 GPa (3 Mbar). The response of each sample was measured with a velocity interferometry diagnostic to determine the material and shock velocity, and hence the conditions reached, and the reflectivity of the sample, from which changes in the conductivity can be inferred. By applying the self-impedance mismatch technique with the measured velocities, the pressure and density of thermodynamic points away from the principal Hugoniot were determined. Our results show an unexpectedly large reflectivity at the highest shock pressures, while the off-Hugoniot points agree with previous work suggesting that shock-compressed CH conductivity is primarily temperature-dependent.
Using tellability to analyze entrepreneurial narratives in the classroom
Authors: Wang Longlong
Published: February 2020

A comprehensive theoretical review suggests that tellability can be used to understand life stories, how stories are constructed, the social context shaping storytelling, and how stories function as a mode of thought. However, the complex and multi-dimensional nature of tellability has been overlooked. This study analyzes one Chinese teacher’s storytelling of six entrepreneurs’ stories as an example, aiming to demonstrate that tellability is structurally embedded within an entire story. Interpreting the stories with reference to the classroom setting reveals that entrepreneurial narratives are tellable because they institutionalize culturally salient values and beliefs about entrepreneurship, they are pedagogically meaningful, and they provide an epistemological tool for listeners to constitute their future reality. This paper argues that an analysis on tellability, informed by multiple theories and recognizant of its structural, social, ontological and epistemological nature, is effective to understand teachers’ storytelling in classrooms and unpack the meanings of stories in more detail.
Embedded sacrificial AlAs segments in GaAs nanowires for substrate reuse
Authors: Jafari Jam R , Beech Jason P , Zeng Xulu , Johansson Jonas , Samuelson Lars , Pettersson Håkan , Borgström Magnus T
Published: February 2020

We report on the use of a sacrificial AlAs segment to enable substrate reuse for nanowire synthesis. A silicon nitride template was deposited on a p-type GaAs substrate. Then a pattern was transferred to the substrate by nanoimprint lithography and reactive ion etching. Thermal evaporation was used to define Au seed particles. Metalorganic vapour phase epitaxy was used to grow AlAs–GaAs NWs in the vapour–liquid–solid growth mode. The yield of synthesised nanowires, compared to the number expected from the patterned template, was more than 80%. After growth, the nanowires were embedded in a polymer and mechanically removed from the parent substrate. The parent substrate was then immersed in an HCl:H2O (1:1) mixture to dissolve the remaining stub of the sacrificial AlAs segment. The pattern fidelity was preserved after peeling off the nanowires and cleaning, and the semiconductor surface was flat and ready for reuse. Au seed particles were then deposited on the substrate by use of pulse electrodeposition, which was selective to the openings in the growth template, and then nanowires were regrown. The yield of regrowth was less optimal compared to the first growth but the pattern was preserved. Our results show a promising approach to reduce the final cost of III–V nanowire based solar cells.
Molecular/Cytogenetic Education for Hematopathology Fellows
Authors: Beck Rose C , Kim Annette S , Goswami Rashmi S , Weinberg Olga K , Yeung Cecilia C S , Ewalt Mark D
Published: February 2020

Objectives

At a discussion on molecular/cytogenetic education for hematopathology fellows at the 2018 Society for Hematopathology Program Directors Meeting, consensus was that fellows should understand basic principles and indications for and limitations of molecular/cytogenetic testing used in routine practice. Fellows should also be adept at integrating results of such testing for rendering a final diagnosis. To aid these consensus goals, representatives from the Society for Hematopathology and the Association for Molecular Pathology formed a working group to devise a molecular/cytogenetic curriculum for hematopathology fellow education.

Curriculum Summary

The curriculum includes a primer on cytogenetics and molecular techniques. The bulk of the curriculum reviews the molecular pathology of individual malignant hematologic disorders, with applicable molecular/cytogenetic testing for each and following the 2017 World Health Organization classification of hematologic neoplasms. Benign hematologic disorders and bone marrow failure syndromes are also discussed briefly. Extensive tables are used to summarize genetics of individual disorders and appropriate methodologies.

Conclusions

This curriculum provides an overview of the current understanding of the molecular biology of hematologic disorders and appropriate ancillary testing for their evaluation. The curriculum may be used by program directors for training hematopathology fellows or by practicing hematopathologists.
Eco-geographical determinants of the evolution of ornamentation in vipers
Authors: Pizzigalli Cristian , Banfi Federico , Ficetola Gentile Francesco , Falaschi Mattia , Mangiacotti Marco , Sacchi Roberto , Zuffi Marco A L , Scali Stefano
Published: February 2020

Multiple hypotheses have been proposed to explain the variation of dorsal patterns observed in snakes, but no studies yet have tested them over broad taxonomic and geographical scales. The Viperidae offer a powerful model group to test eco-evolutionary processes that lead to disruptive and cryptic ornaments. We developed a database reporting dorsal ornamentation, ecological habitus, habitat features and climatic parameters for 257 out of 341 recognized species. Three patterns of dorsal ornamentation were considered: “zig-zag”, “blotchy” and “uniform” patterns. Phylogenetic comparative analyses were based on 11 mitochondrial and nuclear genes. Forty-eight species presented a zig-zag pattern type, 224 a blotchy pattern type and 32 a uniform pattern type. All the patterns showed a strong phylogenetic signal. Character phylogenetic reconstruction analyses suggested an ancestral state for blotchy ornamentation, with multiple independent evolutions of the other patterns. The blotchy pattern was more frequent in terrestrial species living in warm climates and sandy habitats, supporting the hypothesis of a disruptive function. The zig-zag pattern evolved independently in several isolated taxa, particularly in species living in cold climates and in dense vegetation or water-related habitats, supporting the hypothesis of disruptive and aposematic functions. Uniform coloration was particularly frequent in arboreal species, supporting the hypothesis of a cryptic function.
De-escalation of Empiric Antibiotics Following Negative Cultures in Hospitalized Patients With Pneumonia: Rates and Outcomes
Authors: Deshpande Abhishek , Richter Sandra S , Haessler Sarah , Lindenauer Peter K , Yu Pei-Chun , Zilberberg Marya D , Imrey Peter B , Higgins Thomas , Rothberg Michael B
Published: February 2020

Background

For patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized patients with pneumonia with negative cultures.

Methods

We included adults admitted with pneumonia in 2010–2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS), and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles.

Results

Of 14 170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2–35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were <50%. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to ICU (adjusted odds ratio, .38; 95% CI, .18–.79), LOS (adjusted ratio of means, .76; .75–.78), and costs (.74; .72–.76).

Conclusions

A minority of eligible patients with pneumonia had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice.
Heparin ‘flush’ induced thrombocytopenia triggered by total hip replacement: a case report
Authors: Yoshida Ruka , Tanaka Akihito , Yoshioka Naoki , Yokote Jun
Published: February 2020

Background

Heparin-induced thrombocytopenia (HIT) typically responds to heparin termination. Some types of HIT can persist after heparin discontinuation.

Case summary

A 95-year-old woman was referred to the cardiology from orthopaedics because of acute limb ischaemia (ALI) 1 day after surgery of a femoral neck fracture. Despite thrombectomy, ALI relapsed the next day. She had been treated with intravenous antibiotics with a diagnosis of aspiration pneumonia for 1 week until 3 days before surgery, together with heparin flush twice a day. Of note, no intra-/post-operative heparin was administered, no cell salvage device, central venous, nor arterial catheters were used before development of ALI. The patient and her family refused reattempting invasive therapies; consequently, the patient continued to worsen and died on post-operative day 3. Diagnosis of autoimmune HIT, which was prompted by surgery without re-exposure to heparin, was confirmed posthumously.

Discussion

This case emphasizes the significance of suspecting autoimmune HIT in any patient presenting with thrombosis, even if the heparin exposure dates back more than a few days or even without heparin exposure.
Concept for a Multinational Patent Search using Elements of Blockchain Technology
Authors: Marschall Stefan
Published: February 2020

Blockchain Elements Integrated Multinational Search (BEIMS) is a response to an ongoing discussion about the search and examination procedures employed in patent offices, relaunched in 2018 when German law firms sent an open letter to the President of the European Patent Office.

The BEIMS concept turns away from patent examiners working by themselves in isolation, and instead involves experts from different offices working in close co-operation.

BEIMS integrates elements of Blockchain Technology – such as decentralized network, competition and consensus building – with the participation of several national and/or regional patent offices, and involves financial incentives. The co-operating patent offices are coequal and, as a consequence, a multinational search report is generated with cited prior art determined and evaluated by patent examiners of different patent offices in due time.
Does lobar or size-reduced lung transplantation offer satisfactory early and late outcomes?
Authors: Santos Silva João , Olland Anne , Massard Gilbert , Falcoz Pierre-Emmanuel
Published: February 2020

A best evidence topic was constructed according to a structured protocol. The question addressed was whether size-reduced or lobar lung transplantation (LLTx) offers the same benefit as classic lung transplantation (LTx). Of the 147 papers found using the reported search, 9 were selected to provide the best evidence. Details of the studies regarding authors, date, journal, country of publication, study type, group studied, relevant outcomes and results are given. All studies reported survival rates of LLTx and most compared it with classical LTx. No statistical differences were reported in medium term and long term. Two of the studies reported a higher incidence of postoperative complications, such as the need for cardiopulmonary bypass, reperfusion oedema or primary graft dysfunction, and longer intubation or intensive care unit stay times. Although the largest study showed a significantly worse 1-year survival in LLTx, a sub-analysis considering patients successfully discharged showed similar outcomes at 1, 3 and 5 years when compared with classic LTx patients. We conclude that LLTx is a valid therapeutic option for recipients with significant donor size mismatch, offering similar outcomes as classical LTx in the medium term and long term.
Calcaneal Quantitative Ultrasonography and Urinary Retinol-Binding Protein in Antiretroviral-Treated Patients With Human Immunodeficiency Virus in Uganda: A Pilot Study
Authors: Costa Cecilia , Scabini Silvia , Kaimal Arvind , Kasozi William , Cusato Jessica , Kafufu Bosco , Borderi Marco , Mwaka Erisa , Di Perri Giovanni , Lamorde Mohammed , Calcagno Andrea , Castelnuovo Barbara
Published: February 2020

Background

Data on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infected  individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein–urinary creatinine ratio (uRBP/uCr) and reduced BMD.

Methods

We conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infected adults who had been receiving continuous antiretroviral therapy for ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection.

Results

DXA BMD measurements were significantly associated (P < .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [P = .03], femoral neck [P < .001], and total hip [P = .002]).

Conclusions

Calcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate–sparing regimens in resource-limited settings.
Changing Contact Patterns Over Disease Progression: Nipah Virus as a Case Study
Authors: Lee Kyu Han , Nikolay Birgit , Sazzad Hossain M S , Hossain M Jahangir , Khan A K M Dawlat , Rahman Mahmudur , Satter Syed Moinuddin , Nichol Stuart T , Klena John D , Pulliam Juliet R C , Kilpatrick A Marm , Sultana Sharmin , Afroj Sayma , Daszak Peter , Luby Stephen , Cauchemez Simon , Salje Henrik , Gurley Emily S
Published: February 2020

Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1642 contacts of 94 Nipah virus case patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case patients who died, peaked on the day of death. Given transmission has only been observed among fatal cases of Nipah virus infection, our findings suggest that changes in contact patterns during illness contribute to risk of infection.
Order polarities
Authors: Egrot Rob
Published: February 2020

We define an order polarity to be a polarity $(X,Y,{\operatorname{R}})$ where $X$ and $Y$ are partially ordered, and we define an extension polarity to be a triple $(e_X,e_Y,{\operatorname{R}})$ such that $e_X:P\to X$ and $e_Y:P\to Y$ are poset extensions and $(X,Y,{\operatorname{R}})$ is an order polarity. We define a hierarchy of increasingly strong coherence conditions for extension polarities, each equivalent to the existence of a preorder structure on $X\cup Y$ such that the natural embeddings, $\iota _X$ and $\iota _Y$, of $X$ and $Y$, respectively, into $X\cup Y$ preserve the order structures of $X$ and $Y$ in increasingly strict ways. We define a Galois polarity to be an extension polarity satisfying the strongest of these coherence conditions and where $e_X$ and $e_Y$ are meet- and join-extensions, respectively. We show that for such polarities the corresponding preorder on $X\cup Y$ is unique. We define morphisms for polarities, providing the class of Galois polarities with the structure of a category, and we define an adjunction between this category and the category of $\varDelta _1$-completions and appropriate homomorphisms.
Ectopic RNF168 expression promotes break-induced replication-like DNA synthesis at stalled replication forks
Authors: Krais John J , Johnson Neil
Published: February 2020

The RNF168 E3 ubiquitin ligase is activated in response to double stranded DNA breaks (DSBs) where it mono-ubiquitinates γH2AX (ub-H2AX). RNF168 protein expression and ubiquitin signaling are finely regulated during the sensing, repair and resolution of DNA damage in order to avoid excessive spreading of ubiquitinated chromatin. Supra-physiological RNF168 protein expression levels have been shown to block DNA end resection at DSBs and increase PARP inhibitor (PARPi) sensitivity. In this study, we examined the impact of ectopic RNF168 overexpression on hydroxyurea (HU)-induced stalled replication forks in the setting of BRCA1 deficiency. Surprisingly, RNF168 overexpression resulted in the extension of DNA fibers, despite the presence of HU, in BRCA1 deficient cells. Mechanistically, RNF168 overexpression recruited RAD18 to ub-H2AX at HU-induced DNA breaks. Subsequently, a RAD18-SLF1 axis was responsible for initiating DNA synthesis in a manner that also required the break-induced replication (BIR) factors RAD52 and POLD3. Strikingly, the presence of wild-type BRCA1 blocked RNF168-induced DNA synthesis. Notably, BIR-like repair has previously been linked with tandem duplication events found in BRCA1-mutated genomes. Thus, in the absence of BRCA1, excessive RNF168 expression may drive BIR, and contribute to the mutational signatures observed in BRCA1-mutated cancers.
Impact of acute kidney injury on anticancer treatment dosage and long-term outcomes: a pooled analysis of European Organisation for Research and Treatment of Cancer trials
Authors: Péron Julien , Neven Anouk , Collette Laurence , Launay-Vacher Vincent , Sprangers Ben , Marreaud Sandrine
Published: February 2020

Background

The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear.

Methods

Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using serum creatinine levels and using adverse events reported by investigators. The impact of baseline estimated glomerular filtration rates (eGFRs) on progression-free survival (PFS) and overall survival (OS) was investigated. Pooled estimates of the impact of AKI on dose intensity, treatment duration, PFS and OS were obtained following a meta-analytic process.

Results

Nine trials were included in this study, totalling 2872 metastatic patients with various tumour types and various systemic treatment types. Baseline eGFR had homogeneously no impact on PFS or OS. Most Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) events occurred early during the course of the treatment. AKI was not associated with an increased rate of treatment discontinuation, while it decreased the study treatment dose intensity. Occurrence of a first RIFLE event significantly and homogeneously reduced PFS (pooled hazard ratio = 1.18, 95% confidence interval 1.07–1.30; P = 0.0012), while its impact on OS was more heterogeneous across trials.

Conclusion

AKI is associated with reduced treatment dose intensity and reduced PFS. Therefore, close monitoring of the kidney function during the first months of treatment should be included in clinical trial protocols and probably also in daily practice to enable early AKI diagnosis and management. Collaboration between oncologists and nephrologists is needed to reduce the risk of undertreatment of patients experiencing AKI.
Imaging and histopathologic correlates of plasma cell-free DNA concentration and circulating tumor DNA in adult patients with newly diagnosed glioblastoma
Authors: Nabavizadeh Seyed Ali , Ware Jeffrey B , Guiry Samantha , Nasrallah MacLean P , Mays Jazmine J , Till Jacob E , Hussain Jasmin , Abdalla Aseel , Yee Stephanie S , Binder Zev A , O’Rourke Donald M , Brem Steven , Desai Arati S , Wolf Ronald , Carpenter Erica L , Bagley Stephen J
Published: February 2020

Background

Plasma cell-free DNA (cfDNA) concentration is lower in glioblastoma (GBM) compared to other solid tumors, which can lead to low circulating tumor DNA (ctDNA) detection. In this study, we investigated the relationship between multimodality magnetic resonance imaging (MRI) and histopathologic features with plasma cfDNA concentration and ctDNA detection in patients with treatment-naive GBM.

Methods

We analyzed plasma cfDNA concentration, MRI scans, and tumor histopathology from 42 adult patients with newly diagnosed GBM. Linear regression analysis was used to examine the relationship of plasma cfDNA concentration before surgery to imaging and histopathologic characteristics. In a subset of patients, imaging and histopathologic metrics were also compared between patients with and without a detected tumor somatic mutation.

Results

Tumor volume with elevated (>1.5 times contralateral white matter) rate transfer constant (Kep, a surrogate of blood–brain barrier [BBB] permeability) was independently associated with plasma cfDNA concentration (P = .001). Histopathologic characteristics independently associated with plasma cfDNA concentration included CD68+ macrophage density (P = .01) and size of tumor vessels (P = .01). Patients with higher (grade ≥3) perivascular CD68+ macrophage density had lower volume transfer constant (Ktrans, P = .01) compared to those with lower perivascular CD68+ macrophage density. Detection of at least 1 somatic mutation in plasma cfDNA was associated with significantly lower perivascular CD68+ macrophages (P = .01).

Conclusions

Metrics of BBB disruption and quantity and distribution of tumor-associated macrophages are associated with plasma cfDNA concentration and ctDNA detection in GBM patients. These findings represent an important step in understanding the factors that determine plasma cfDNA concentration and ctDNA detection.
Navigating the Intersection Between Persistent Pain and the Opioid Crisis: Population Health Perspectives for Physical Therapy
Authors: Davenport Todd E , DeVoght Andra C , Sisneros Holly , Bezruchka Stephen
Published: February 2020

The physical therapy profession has recently begun to address its role in preventing and managing opioid use disorder (OUD). This topic calls for discussion of the scope of physical therapist practice, and the profession’s role, in the prevention and treatment of complex chronic illnesses, such as OUD. OUD is not just an individual-level problem. Abundant scientific literature indicates OUD is a problem that warrants interventions at the societal level. This upstream orientation is supported in the American Physical Therapy Association’s vision statement compelling societal transformation and its mission of building communities. Applying a population health framework to these efforts could provide physical therapists with a useful viewpoint that can inform clinical practice and research, as well as develop new cross-disciplinary partnerships. This Perspective discusses the intersection of OUD and persistent pain using the disease prevention model. Primordial, primary, secondary, and tertiary preventive strategies are defined and discussed. This Perspective then explains the potential contributions of this model to current practices in physical therapy, as well as providing actionable suggestions for physical therapists to help develop and implement upstream interventions that could reduce the impact of OUD in their communities.
Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry
Authors: Sag Erdal , Akal Fuat , Atalay Erdal , Akca Ummusen Kaya , Demir Selcan , Demirel Dilara , Batu Ezgi Deniz , Bilginer Yelda , Ozen Seza
Published: February 2020

Objectives

FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry.

Methods

HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents.

Results

Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions.

Conclusion

Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.
Gender Mainstreaming as a Universal Tool for Constitution Writing: The Case of Iraq
Authors: Forman-Rabinovici Aliza
Published: February 2020

In light of postcolonial feminist criticisms, this article asks how does gender mainstreaming function as a strategy for introducing a gender perspective into the constitution writing process and constitutional text? The 2005 Iraqi Constitution is used to explore the method outside of its usual Western-dominated intergovernmental organization (IGO) context. Three main questions guide the analysis: Did gender mainstreaming promote gender equality effectively? Were there any shortcomings that were a result of a failure to account for intersectionality? Was the association of gender mainstreaming with Western-dominated IGOs a hindrance to the advancement of gender equality?
Assessment of hand function using the functional dexterity test after opponensplasty in young children with Blauth type 2 hypoplastic thumb
Authors: Iba Kousuke , Takayama Shinichiro , Kawabata Hidehiko , Horii Emiko , Kazuki Kenichi
Published: February 2020

The functional dexterity test (FDT) is a timed pegboard test based on the manipulation of each peg and suitable for young children as it is both simple and quick to perform. We assessed the postoperative FDT values for children with Blauth type 2 hypoplastic thumbs after opponensplasty. We evaluated hand function using FDT for 12 hands of 11 patients with Blauth type 2 hypoplastic thumbs. Opponensplasty was performed in all hands following by Huber’s procedure. All patients were evaluated from 6 to 12 months after surgery for hand function using three types of FDT scores: time in seconds to complete the test (FDT time), combined total time with penalty seconds added to the initial time (FDT total), and the number of pegs per second to complete the task as a percentage against normative values (FDT speed). We compared the postoperative FDT scores with those for Blauth type 1 or 2 hypoplastic thumb patients without surgical treatment. FDT time and FDT total for the patients postoperatively were both significantly shorter than those in the type 2 patients without surgical treatment. FDT speed was significantly higher than that for the patients without surgical treatment. There were no significant differences in the three FDT scores between the postoperative patients and the type 1 patients. There were several limitations including small sample size, large ranges of the data, and high number of variables. FDT reflected postopponensplasty improvement in hand dexterity in young children with Blauth type 2 hypoplastic thumb.
Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives
Authors: Haas David W. , Cramer Yoninah S. , Godfrey Catherine , Rosenkranz Susan L. , Aweeka Francesca , Berzins Baiba , Coombs Robert , Coughlin Kristine , Moran Laura E. , Gingrich David , Zorrilla Carmen D. , Baker Paxton , Cohn Susan E. , Scarsi Kimberly K.
Published: February 2020

Objective

In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions.

Methods

In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 μg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed.

Results

The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure (P = 3.2 × 10−3), decreased plasma concentrations of etonogestrel (P = 1.7 × 10−3), and decreased ethinyl estradiol (P = 6.7 × 10−4). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers.

Conclusion

CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.
A Randomized, Active-Controlled, 52-Week Study of Hyaluronic Acid Fillers for Anteromedial Malar Region Augmentation
Authors: Huh Chang-Hun , Eom Yunae , Yang So Dam , Shin Jung Won , Seo Kyle Koo-il
Published: February 2020

Background:

Hyaluronic acid (HA) fillers for volume augmentation in the anteromedial malar region of Asians have been popular for many years. However, studies on their long-term effectiveness are lacking. This study aimed to evaluate the effectiveness and safety of HA fillers injected into the anteromedial malar region for volume augmentation for up to 52 weeks.

Methods:

Each anteromedial malar region of the subjects was treated with YVOIRE Contour (YVOC) in one side and Restylane Sub-Q (RESS) in the other and followed up at weeks 2, 14, 26, and 52. The volume using the mid-face aesthetic scale (MFAS) ranging from 0 (full) to 4 (very severely sunken) and the subject’s satisfaction and adverse events were evaluated.

Results:

Total 83 subjects were randomized and treated with YVOC and RESS. The LS means (standard error) of MFAS score in the YVOC and RESS groups were both 2.56 (0.05) at baseline, 1.32 (0.07) and 1.39 (0.07) at week 26, and 1.84 (0.10) and 1.89 (0.10) at week 52, respectively. The difference in the LS mean of MFAS score between the groups at week 26 was 0.07 (95% confidence interval, 0.01–0.12), showing the non-inferiority of YVOC to RESS. About 70% of subjects were still satisfied with the results at week 52. No specific safety concern was detected.

Conclusions:

The HA fillers injected for the anteromedial malar augmentation maintained the volume well for up to 52 weeks. Additionally, both YVOC and RESS show similar effectiveness and safety profiles.
Modeling Cerebral Hemodynamics Using BOLD Magnetic Resonance Imaging and its Application in Mild Cognitive Impairment
Authors: Henley B.C. , Okafor M.O. , Hajjar I.
Published: February 2020

Objective

This study develops a procedure and related analytical methods for deriving indices of cerebral hemodynamics in the magnetic resonance imaging (MRI) setting using resting state recordings of systemic blood pressure, pulse rate, and end-tidal CO2 synchronized with the MRI image acquisitions of blood oxygenation level dependent (BOLD) data as a measure of cerebral perfusion.

Methods

We employed the concept of Principal Dynamic Modes (PDM) to model the effect of three determinants of cerebral perfusion: mean arterial blood pressure (MABP), end-tidal CO2 (PETCO2), and pulse rate (PR). The relation between these signals and the BOLD signal were used respectively to quantify cerebral autoregulation (CA), CO2 vasoreactivity (CVR), and pulse rate reactivity (PRR).

Results

Hemodynamic indices were obtained from 129 participants with normal cognition (NC) and mild cognitive impairment (MCI). CA was reduced in MCI compared to NC in the parietal lobe, CVR was reduced in MCI in the occipital and temporal lobes, and PRR was reduced in the frontal, parietal, occipital and temporal lobes. Reduced CVR and PRR were associated with worse cognitive scores including memory and executive function.

Conclusion

Employed acquisition and analysis of MRI hemodynamic identified cerebral hemodynamic alterations in MCI, related to PR and ETCO2 changes.

Significance

This modeling approach may offer a novel way to clinically assess cerebral hemodynamics during MRI.
A systematic review and meta-analysis considering the SSRI, SNRI and TCA classes of antidepressants and the risk for congenital heart defects
Authors: De Vries Courtney , Gadzhanova Svetla , Sykes Matthew J. , Ward Michael , Roughead Elizabeth
Published: February 2020

Background

Antidepressant use during the first trimester is reported in 4% to 8% of pregnancies. The use of some selective serotonin reuptake inhibitors (SSRI) during this stage of gestation has been identified as increasing the odds for congenital heart defects, however little is known about the safety of non-SSRI antidepressants.

Objective

To assess the odds of congenital heart defects associated with the use of any antidepressant during the first trimester of pregnancy. To investigate individual classes of antidepressants: SSRIs, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and individual antidepressants.

Data sources

PubMed and Embase were searched without restrictions from inception till 2 January 2020.

Study selection

Prospective and retrospective cohort and case-control studies were included if they documented the maternal usage of antidepressants during the first trimester of pregnancy and assessed the presence of congenital heart defects.

Data extraction and meta-analysis

Data were extracted by two independent reviewers and the endpoint assessed was congenital heart defects. Where studies reported multiple results for different types of heart defects or individual antidepressants, results were combined when possible. Analyses assessing individual antidepressants and classes of antidepressants (SSRIs, SNRIs and TCAs) were undertaken.

Results

A total of 16 studies were identified, encompassing 4,564,798 pregnancy outcomes. The odds ratio for maternal use of any antidepressant and the presence of congenital heart defects from the mixed-methods meta-analysis was 1.22 (95% confidence interval (CI): 1.11 to 1.33).

Analyses of antidepressants by class produced an odds ratio of 1.50 (95% CI: 1.19 to 1.89) for maternal SNRI use during the first trimester of pregnancy and the formation of congenital heart defects. A significant odds ratio of 1.22 (95% CI: 1.12 to 1.33) was reported for SSRIs. For the TCA class, no increased odds ratio was found.

Analyses of individual antidepressants produced significant odds ratios of 1.53 (95% CI: 1.25 to 1.88), 1.28 (95% CI: 1.01 to 1.62), 1.28 (95% CI: 1.14 to 1.45) and 1.23 (95% CI: 1.01 to 1.50) for paroxetine, fluoxetine, sertraline and bupropion respectively.

Conclusion

While some insight has been gained into which classes of antidepressant and individual antidepressants pose more risk than others for causing congenital heart defects, information regarding some antidepressants is still lacking.
Estimating the causal effect of hearing loss on Alzheimer’s disease: a Mendelian randomisation study
Authors: Jacobs Benjamin M , Noyce Alastair J , Hardy Christopher JD , Warren Jason D , Marshall Charles R
Published: February 2020

Background

Hearing loss has been identified as one of the most important risk factors for Alzheimer’s disease (AD). However, the causality of this association has not been established.

Methods

We used publicly available GWAS summary statistics to construct instrumental variables for age-related hearing difficulty. We tested these genetic instruments for association with the outcome of AD using AD GWAS summary statistics in a two-sample Mendelian randomisation analysis. We used inverse-variance weighted meta-analysis to estimate the causal effect of hearing-related traits on AD, followed by secondary sensitivity analyses including a mixture of experts approach.

Results

There was no strong evidence for a causal relationship between genetically-determined hearing difficulty (ORFE-IVW 1.27, 95% CI 0.89 to 1.82, p=0.189) and AD risk. There was no evidence to suggest that unbalanced horizontal pleiotropy was biasing the result. Power calculations indicated our instruments were sufficiently powered to detect the magnitude of effect described in case-control and cohort settings.

Conclusions

Our results suggest that the size of the observed relationship between hearing loss and AD cannot be completely accounted for by a direct causal influence. Hearing loss may have more utility as a risk marker for AD than as a modifiable risk factor.
Visual Experience is not Necessary for the Development of Face Selectivity in the Lateral Fusiform Gyrus
Authors: Ratan Murty N. Apurva , Teng Santani , Beeler David , Mynick Anna , Oliva Aude , Kanwisher Nancy
Published: February 2020

Here we show robust face-selectivity in the lateral fusiform gyrus of congenitally blind participants during haptic exploration of 3D-printed stimuli, indicating that neither visual experience, nor fovea-biased input, nor visual expertise is necessary for face-selectivity to arise in its characteristic location. Similar resting fMRI correlation fingerprints in individual blind and sighted participants suggest a role for long-range connectivity in the specification of the cortical locus of face-selectivity.
Accurate localization of linear probe electrodes across multiple brains
Authors: Liu Liu D , Chen Susu , Economo Michael N , Li Nuo , Svoboda Karel
Published: February 2020

Recently developed silicon probes have large numbers of recording electrodes on long linear shanks. Specifically, Neuropixels probes have 960 recording electrodes distributed over 9.6 mm shanks. Because of their length, Neuropixels probe recordings in rodents naturally span multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals have to be aligned to each other and to a standardized brain coordinate system. Here we report a workflow for accurate localization of individual electrodes in standardized coordinates and aligned across individual brains. This workflow relies on imaging brains with fluorescent probe tracks and warping 3-dimensional image stacks to standardized brain atlases. Electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed ground-truth experiments, in which motor cortex outputs are labelled with ChR2 and a fluorescence protein. Recording from brain regions targeted by these outputs reveals better than 100 μm accuracy for electrode localization.
Nicotine exposure and neuronal activity regulate Golgi membrane dispersal and distribution
Authors: Govind Anitha P. , Jeyifous Okunola , Russell Theron A. , Vaasjo Lee O. , Yi Zola , Weigel Aubrey V. , Newell Luke , Koranda Jessica L. , Singh Karanveer , Valbuena Fernando , Glick Benjamin S. , Mukherjee Jogeshwar , Lippincott-Schwartz Jennifer , Zhuang Xiaoxi , Green William N.
Published: February 2020

How nicotine exposure produces long-lasting changes that remodel neural circuits with addiction is unknown. Here, we report that long-term nicotine exposure alters the trafficking of α4β2-type nicotinic acetylcholine receptors (α4β2Rs) by dispersing and redistributing the Golgi apparatus. In cultured neurons, dispersed Golgi membranes were distributed throughout somata, dendrites and axons. Small, mobile vesicles in dendrites and axons lacked standard Golgi markers and were identified by other Golgi enzymes that modify glycans. Nicotine exposure increased levels of dispersed Golgi membranes, which required α4β2R expression. Similar nicotine-induced changes occurredin vivoat dopaminergic neurons at mouse nucleus accumbens terminals, consistent with these events contributing to nicotine’s addictive effects. Characterizationin vitrodemonstrated that dispersal was reversible, that dispersed Golgi membranes were functional, and that membranes were heterogenous in size, with smaller vesicles emerging from larger “ministacks”, similar to Golgi dispersal induced by nocadazole. Protocols that increased cultured neuronal synaptic excitability also increased Golgi dispersal, without the requirement of α4β2R expression. Our findings reveal novel activity- and nicotine-dependent changes in neuronal intracellular morphology. These changes regulate levels and location of dispersed Golgi membranes at dendrites and axons, which function in local trafficking at subdomains.