bluuebunny/crossref_metadata_2025 huggingface dataset:
Branding, culture, and political ideology: Spanish patriotism as the identity myth of an iconic brand
Authors: Pineda Antonio , Sanz-Marcos Paloma , Gordillo-Rodríguez María-Teresa
Published: January 2020

The cultural aspects of brands, as well as their consideration as symbols in consumer cultures, are relevant elements of contemporary branding. This research relies on cultural branding as a theoretical framework that explains the role of brands as vessels of ideology. Such a role relates to the fact that brands can simultaneously reflect and smooth societal tensions – that is, the mechanics that turn brands into icons according to the theory of “iconic brands.” This article focuses on the Spanish fashion company Piel de Toro (“Bull Skin”) to illustrate the ideological role of brands, as well as the identity myths they convey to meet consumers’ anxieties. To study the way this brand formulated a patriotic identity myth in the context of the Catalonian separatist movement, Piel de Toro’s “Proudly Spanish” 2017 campaign is analyzed by putting together the brand genealogy method and different data sources. Results shed light on the scope and limits of the brand’s iconic status, and indicate the role of commercial brands as political–ideological actors in contemporary Spanish culture.
Balloon-assisted coiling of intracranial aneurysms using the Eclipse 2L double lumen balloon
Authors: Pop Raoul , Harsan Oana , Martin Ioan , Mihoc Dan , Richter Johann Sebastian , Manisor Monica , Simu Mihaela , Chibbaro Salvatore , Cebula Helene , Proust Francois , Beaujeux Rémy
Published: January 2020

Background

Eclipse 2L is a new double lumen balloon microcatheter for neurovascular use, with several design features that separate it from previous generation devices. We aimed to report our initial experience of balloon-assisted coiling of intracranial aneurysms using the Eclipse 2L balloon.

Materials and methods

Retrospective single-center review of patients who underwent balloon-assisted coiling with the Eclipse 2L balloon, for ruptured or unruptured intracranial aneurysms between 1 June 2016 and 31 December 2018. Cases with adjunctive use of stents and recurrences of previously embolized aneurysms were excluded. Patient files were used to extract aneurysm characteristics, complications, immediate and long-term results.

Results

We identified 120 patients with 126 aneurysms, of which 83 (65.8%) unruptured. Average aneurysm size was 5.9 mm (standard deviation 3.2 mm), with a dome-to neck-ratio of 1.7 (SD 0.6). Most aneurysms (79.3%) were wide necked. Immediate angiographic exclusion (Raymond-Roy grade I–II) was obtained in 95.1% of cases (81.7% grade I and 13.4% grade II). Procedural morbidity was 3.2% with no procedural mortality. Follow-up imaging was available for 115 aneurysms (91.2%). After an average follow-up period of 8.9 months (SD 7.3 months), 96.5% of aneurysms presented class I–II occlusion. Two aneurysms (1.7%) were retreated during follow-up.

Conclusion

Balloon-assisted coiling using the Eclipse 2L double lumen balloon is feasible for aneurysms in a wide range of locations in the anterior and posterior circulation. The angiographic results and complication rates compare favorably with previously published studies.
On Heat Transfer enhancement in Diesel Engine Cylinder Head Using γ-Al2O3/water nanofluid with different nanoparticle sizes
Authors: Radwan Mohsen Salem , Saleh Hosam E , Attai Youssef Ahmed , Elsherbiny Mohamed Salah
Published: January 2020

In the current work, an experimental investigation of γ-Al2O3/water characteristics nanofluid was performed for convective cooling of engine cylinder head for fully developed turbulent regime. Nanoparticles of different sizes were mixed in distilled water with constant volume fraction of 1% through the experiments. The cylinder head was simulated as a rectangular duct, of an aspect ratio of 0.8, with a cast iron test specimen from actual cylinder head of diesel engine. The effect of different nanoparticle sizes (30, 100, and 150 nm), bulk temperature (60°C, 70°C, and 80°C), and flow velocity (1, 1.5 and 2 m/s) were investigated at variable heat fluxes. The experimental results revealed that the obtained enhancement of convective heat transfer coefficient is inversely proportional to both nanoparticle diameter and bulk temperature and directly proportional to the coolant flow velocity. Also, the highest achieved enhancement over the pure base fluid in heat transfer coefficient is 88.74% at 30 nm particle size. The γ-Al2O3/water nanofluid showed promising results for intensive study with different operating conditions.
The alchemy of confirmation bias transmutes expectations into bilingual advantages: A tale of two new meta-analyses
Authors: Paap Kenneth R , Mason Lauren , Zimiga Brandon , Ayala-Silva Yocelyne , Frost Matthew
Published: January 2020

Five recent meta-analyses of the bilingual advantage in executive functioning hypothesis have converged on the outcome that the mean effect size is very small and that the incidence of statistically significant bilingual advantages is very low (about 15% of all comparisons). Those analyses that used the PET-PEESE method to correct for publication bias show mean effect sizes that are not different from zero and sometimes negative. In contrast, van den Noort and colleagues provide a sixth review of 46 studies published before October 31, 2018, that appears to produce a very different outcome, namely that more than half the studies yield clear support for the bilingual advantage hypothesis. We show that the deviance is due in part to search terms that yielded far fewer relevant studies, but more importantly to a subjective method of evaluating the results of each study that enables confirmation biases on the part of study authors and meta-analysts to substantially distort the objective pattern of results. A seventh meta-analysis, by Armstrong and colleagues, reports significant bilingual advantages of g = 0.48 for 32 samples using Simon and Stroop colour–word interference tasks that tested older adults. However, all effects were entered into the funnel plots as positive even though many were negative (bilingual disadvantages). This and other striking anomalies are consistent with the view that confirmation bias can suspend critical judgement and promulgate errors. Meta-analyses that use preregistration and a many-labs collaboration can better control for both publication and experimenter biases.
The influence of display-to-display feature changes on net cueing effects: Evidence for a contribution of object-file updating
Authors: Schoeberl Tobias , Goller Florian , Ansorge Ulrich
Published: January 2020

In spatial cueing, presenting a peripheral cue at the same position as a to-be-searched-for target (valid condition) facilitates search relative to a cue presented away from the target (invalid condition). It is assumed that this cueing effect reflects spatial attentional capture to the cued position that facilitates search in valid relative to invalid conditions. However, the effect is typically stronger for top-down matching cues that resemble the targets than for non-matching cues that are different from targets. One factor which could contribute to this effect is that in valid non-matching conditions, a cue-to-target colour difference could prompt an object-updating cost of the target that counteracts facilitative influences of attention capture by the valid cues (this has been shown especially in known-singleton search). We tested this prediction by introducing colour changes at target locations in valid and invalid conditions in feature search. This should compensate for selective updating costs in valid conditions and unmask the true capture effect of non-matching cues. In addition, in top-down matching conditions, colour changes at target positions in invalid conditions should increase the cueing effect, now by selective updating costs in addition to capture away from the targets in invalid conditions. Both predictions were borne out by the results, supporting a contribution of object-file updating to net cueing effects. However, we found little evidence for attentional capture by non-matching cues in feature search even when the selective cost by object-file updating in only valid conditions was compensated for.
The perceived duration of numerical and verbal digits: The independent effects of digit value and covered area
Authors: Pichelmann Stefan , Rammsayer Thomas H
Published: January 2020

Numerical digits influence perceived duration; specifically, higher numerical digit values are perceived to be longer than lower ones that are presented for the same duration of time. To examine the functional relationship between digit value and perceived duration further, three models based on digit value and covered area were tested in two experiments. Unlike previous studies, each experiment utilised the entire digit range that spans from 1 to 9. In both experiments, digit values were presented visually during the target interval of a time reproduction task. Although numerical digits (i.e., Arabic digits) were used in Experiment 1, verbal digits (i.e., number words) were utilised in Experiment 2. In the case of the numerical digits, perceived duration increased as a function of digit value, while the effect of covered area failed to reach statistical significance. For verbal digits, however, the effects of both digit value and covered area were statistically significant. Overall, our findings support the existence of two distinct nontemporal processes that are involved in the modulation of perceived duration: one process that is based on a digit’s surface characteristics (i.e., covered area) and another process that is based on the digit’s numerical meaning (i.e., digit value).
Resolving conflicting cues in processing of ambiguous words: The role of case, word order, and animacy
Authors: Edeleva Julia , Chrabaszcz Anna , Demareva Valeriia
Published: January 2020

We report results from a self-paced silent-reading study and a self-paced reading-aloud study examining ambiguous forms (heteronyms) of Russian animate and inanimate nouns which are differentiated in speech through word stress, for example, uCHItelja.TEACHER.GEN/ACC.SG and uchiteLJA.TEACHERS.NOM.PL.1 During reading, the absence of the auditory cue (word stress) to word identification results in morphologically ambiguous forms since both words have the same inflectional marking, -ja. Because word inflection is a reliable cue to syntactic role assignment, the ambiguity affects the level of morphology and of syntactic structure. However, word order constraints and frequency advantage of the GEN over both the NOM and the ACC noun forms with the - a/-ja inflection should pre-empt two different syntactic parses (OVS vs. SVO) when the heteronym is sentence-initial. We inquired into whether the parser is aware of the multi-level ambiguity and whether selected conflicting cues (case, word order, animacy) can prime parallel access to several structural parses. We found that animate and inanimate nouns patterned differently. The difference was consistent across the experiments. Against the backdrop of classical sentence processing dichotomies, the emergent pattern fits with the serial interactive or the parallel modular parser hypothesis.
HIV treatment non-adherence is associated with ICU mortality in HIV-positive critically ill patients
Authors: Neto Nelson BF , Marin Luiz G , de Souza Bruna G , Moro Ana LD , Nedel Wagner L
Published: January 2020

Introduction

Combined antiretroviral therapy has led to significant decreases in morbidity and mortality in acquired immunodeficiency syndrome patients. Survival among these patients admitted to intensive care units has also improved in the last years. However, the prognostic predictors of human immunodeficiency vírus patients in intensive care units have not been adequately studied. The main objective of this study was to evaluate if non-adherence to antiretroviral therapy is a predictor of hospital mortality.

Methods

A unicentric, retrospective, cohort study composed of patients admitted to a 59-bed mixed intensive care unit including all patients with human immunodeficiency vírus infection. Patients were excluded if exclusive palliative care was established before completing 48 h of intensive care unit admission. Clinical and treatment data were obtained, including demographic records, underlying diseases, Simplified Acute Physiology III score at the time of intensive care unit admission, CD4 lymphocyte count, antiretroviral therapy adherence, admission diagnosis, human immunodeficiency vírus-related diseases, sepsis and use of mechanical ventilation and hemodialysis. The outcome analyzed was hospital mortality.

Results

Overall, 167 patients were included in the study, and intensive care unit mortality was 34.7%. Multivariate analysis indicated that antiretroviral therapy adherence and the Simplified Acute Physiology 3 score were independently related to hospital mortality. antiretroviral therapy adherence was a protective factor (OR 0.2; 95% CI 0.05–0.71; P = 0.01), and Simplified Acute Physiology 3 (OR 1.04; 95% CI 1.01–1.08; P < 0.01) was associated with increased hospital mortality.

Conclusion

Non-adherence to antiretroviral therapy is associated with hospital mortality in this population. Highly active antiretroviral therapy non-adherence may be associated with other comorbidities that may be associated with a worst prognosis in this scenario.
Feasibility, tolerance and effectiveness of enteral feeding in critically ill patients in prone position
Authors: Savio Raymond Dominic , Parasuraman Rajalakshmi , Lovesly Daphnee , Shankar Bhuvaneshwari , Ranganathan Lakshmi , Ramakrishnan Nagarajan , Venkataraman Ramesh
Published: January 2020

Aim

To assess the feasibility, tolerance and effectiveness of enteral nutrition in critically ill patients receiving invasive mechanical ventilation in the prone position for severe Acute Respiratory Distress Syndrome (ARDS).

Methods

Prospective observational study conducted in a multidisciplinary critical care unit of a tertiary care hospital from January 2013 until July 2015. All patients with ARDS who received invasive mechanical ventilation in prone position during the study period were included. Patients’ demographics, severity of illness (Acute Physiology and Chronic Health Evaluation (APACHE II) score), baseline markers of nutritional status (subjective global assessment (SGA) and body mass index), details of nutrition delivery during prone and supine hours and outcomes (Length of stay and discharge status) were recorded.

Results

Fifty-one patients met inclusion criteria out of whom four patients were excluded from analysis since they did not receive any enteral nutrition due to severe hemodynamic instability. The mean age of patients was 46.4 ± 12.9 years, with male:female ratio of 7:3. On admission, SGA revealed moderate malnutrition in 51% of patients and the mean APACHE II score was 26.8 ± 9.2. The average duration of prone ventilation per patient was 60.2 ± 30.7 h. All patients received continuous nasogastric/orogastric feeds. The mean calories (kcal/kg/day) and protein (g/kg/day) prescribed in the supine position were 24.5 ± 3.8 and 1.1 ± 0.2 while the mean calories and protein prescribed in prone position were 23.5 ± 3.6 and 1.1 ± 0.2, respectively. Percentage of prescribed calories received by patients in supine position was similar to that in prone position (83.2% vs. 79.6%; P = 0.12). Patients received a higher percentage of prescribed protein in supine compared to prone position (80.8% vs. 75%, P = 0.02). The proportion of patients who received at least 75% of the caloric and protein goals was 37 (78.7%) and 37 (78.7%) in supine and 32 (68.1%) and 21 (44.6%) in prone position.

Conclusion

In critically ill patients receiving invasive mechanical ventilation in the prone position, enteral nutrition with nasogastric/orogastric feeding is feasible and well tolerated. Nutritional delivery of calories and proteins in prone position is comparable to that in supine position.
Evaluation of proprioception in denervated and healthy wrist joints
Authors: Rein Susanne , Winter Jochen , Kremer Thomas , Siemers Frank , Range Ursula , Euchner Nane
Published: January 2020

We recruited 25 patients after complete wrist denervation and 60 healthy adults to investigate conscious and unconscious proprioception of the wrist. Ipsi- and contralateral joint-position sense, force sense, and wrist reflexes were measured. The latter were triggered by a trapdoor, recording electromyographic signals from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris muscles. No significant differences were found for joint position sense, force sense, and wrist reflexes between both groups, except for reflex time of the flexor carpi ulnaris after denervation of the left wrist as compared with the left flexor carpi ulnaris in controls or in right operated wrists. At a mean follow-up of 32 months (range 8 to 133), we found no proprioceptive deficit of the conscious proprioceptive qualities of joint position sense, force sense, and the unconscious proprioceptive neuromuscular control of wrist reflex time for most muscles after complete wrist denervation. We conclude from this study that complete wrist denervation does not affect the proprioceptive senses of joint position, force sense, and reflex time of the wrist.
Frailty: Tackling the crisis
Authors: Ajayi Temitope O , Conroy Simon P
Published: January 2020

The UK has an ageing population and this is reflected in increasingly higher rates of consultations with GPs; these consultations often relate to complex and interdependent needs. Older people are more likely to be frail, relative to the general population, and the General Medical Service contract aims for a proactive identification of older people with moderate or severe frailty, and then their risk stratification using an evidence-based tool: the electronic frailty index. This article reflects on best practice in the assessment of older people in primary care and what interventions are in place to improve their outcomes.
Writing and sharing care plans in general practice
Authors: Jackson Darren P
Published: January 2020

Sharing a well-written care plan allows individuals, carers, emergency care providers and primary care teams to access information about managing patients’ problems in line with their wishes. It allows the documentation and sharing of information from conversations with patients, relatives and carers. There are multiple formats for patient care plans, but this article will focus on care planning for patients with frailty or in end of life care. A care plan is only as good as the conversation that informs it. A good care plan requires clear documentation and effective sharing of the information with easy access for all care givers.
Instant messaging or face-to-face? How choice of communication medium affects team collaboration environments
Authors: Tang Chun M , Bradshaw Adrian
Published: January 2020

Working on team projects is a common feature in higher education as a way to foster team learning and collaboration. For a team to work well towards achieving project objectives, it is important that there is effective team communication. Conventionally, face-to-face interactions allow students to interact with each other in multiple communication channels, simultaneously sending and receiving verbal and nonverbal messages in real time. Today, modern mobile technology offers students a variety of alternative digital communication media for collaboration. Unlike a full-channel communication medium such as the face-to-face interaction, a digital communication medium like instant messaging does not normally transmit nonverbal cues. As a result, to compensate for insufficient nonverbal cues, users of instant messaging services have to put more effort and time into understanding each other. If more effort and time is required to understand each other better, then why is it that today’s students prefer instant messaging to face-to-face interactions for collaborative project work? To answer this question, this study conducted a questionnaire survey to collect responses from university students who have been involved in team projects. This study analysed students’ copresence (a second-order formative construct consisting of two first-order constructs: self-copresence and partner-copresence) and its relationships with media satisfaction and communication effectiveness. It investigated whether these relationships differed between the students who used instant messaging and those who used face-to-face interactions. In addition, this study also examined whether media satisfaction played a mediating role between copresence and communication effectiveness. The findings of this study could help explain how different communication media can facilitate teamwork in collaborative learning environments.
Associations of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Garg Parveen K , Claxton J’Neka S , Soliman Elsayed Z , Chen Lin Y , Lewis Tené T , Mosley Thomas , Alonso Alvaro
Published: January 2020

Background

We examined the relationships of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation in a biracial cohort of middle and older-aged adults.

Methods

This analysis included 11,445 Atherosclerosis Risk in Communities Study participants who were free of atrial fibrillation at baseline in 1990–1992. Vital exhaustion was assessed at baseline and defined as a score in the highest quartile on the 21-item Vital Exhaustion Questionnaire. Baseline anti-depressant use was self-reported. The Spielberger Trait Anger Scale to assess anger and both the Interpersonal Support Evaluation List and the Lubben Social Network Scale to assess social ties were also administered at baseline. The primary outcome was incident atrial fibrillation throughout 2016, identified by electrocardiogram, hospital discharge coding of atrial fibrillation, and death certificates.

Results

A total of 2220 incident atrial fibrillation cases were detected over a median follow-up of 23.4 years. After adjusting for age, race-center, sex, education, and height, participants in the 4th Vital Exhaustion Questionnaire quartile (referent = 1st Vital Exhaustion Questionnaire quartile) and those reporting anti-depressant use were at increased risk for atrial fibrillation (hazard ratio = 1.45, 95% confidence interval 1.29–1.64 for Vital Exhaustion Questionnaire; hazard ratio = 1.37, 95% confidence interval 1.11–1.69 for anti-depressant use). The increased atrial fibrillation risk observed for 4th Vital Exhaustion Questionnaire quartile participants remained significant after additional adjustment for relevant comorbidities (hazard ratio = 1.20; confidence interval 1.06–1.35). No significant associations were observed for anger or poor social ties with development of atrial fibrillation.

Conclusions

Vital exhaustion is associated with an increased risk of incident atrial fibrillation.
Metachronous testicular tumour recurrence in extra-gonadal germ cell tumour: A case report and review of the literature
Authors: Storey Benjamin , Raman Avi , Grant Alexander
Published: January 2020

A 24-year-old male presented in 2014 with left sided abdominal pain and a palpable abdominal mass. After appropriate investigation a diagnosis of an extra-gonadal germ cell tumour was made and he was treated with platinum based chemotherapy. He then underwent retroperitoneal lymph node dissection due to residual disease identified on imaging with no specific tissue type identified on the histological sample. In early 2019 he presented to his General Practitioner with a left sided testicular lump and was diagnosed with non-seminomatous germ cell tumour of the testis, an uncommon condition; metachronous testicular tumour.

Level of Evidence: 5
Epidemiology and phenotypes of multiple sclerosis in the Middle East North Africa (MENA) region
Authors: Yamout Bassem I , Assaad Wassim , Tamim Hani , Mrabet Saloua , Goueider Riyad
Published: January 2020

The Middle East North Africa (MENA) region falls in the low-to-moderate multiple sclerosis (MS) prevalence zone, with prevalence rates slightly lower than Southern Europe but much higher than sub-Saharan Africa. However, there is clearly a trend toward increased MS prevalence over the last few decades, consistent with the globally rising prevalence of the disease. We analyzed all data collected from the MENACTRIMS (Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis) registry by the end of December 2018. A total of 6885 patients were eligible for the study. Overall, the clinical phenotype of MS in the MENA region was not different from the Western phenotype except for earlier age at onset and a more aggressive clinical course leading to earlier disability.
Clinical Value of an Acute Popping Sensation in Throwing Athletes With Medial Elbow Pain for Ulnar Collateral Ligament Injury
Authors: Molenaars Rik J. , van den Bekerom Michel P.J. , Nazal Mark R. , Eygendaal Denise , Oh Luke S.
Published: January 2020

Background:

Throwing athletes sustaining an ulnar collateral ligament (UCL) injury may recall a popping sensation originating from the medial elbow at the time of injury. There are no studies available that inform clinicians how to utilize this salient anamnestic information and what amount of diagnostic weight to afford to it.

Purpose:

To assess the diagnostic value of a popping sensation for significant UCL injury in throwing athletes who sustained an injury causing medial elbow pain.

Study Design:

Cohort study (prognosis); Level of evidence, 3.

Methods:

A total of 207 consecutive patients with throwing-related medial elbow pain were evaluated for UCL injury by the senior author between 2011 and 2016. The presence or absence of a popping sensation was routinely reported by the senior author. Magnetic resonance imaging was evaluated for UCL injury severity and classified into intact, edema/low-grade partial-, high-grade partial-, and full-thickness tears.

Results:

The overall frequency of a pop was 26%. The proportion of patients who reported a pop significantly increased with UCL tear severity ( P < .001), from 13% in patients with low-grade UCL injuries to 26% in patients with high-grade partial-thickness tears and 51% in patients with full-thickness tears. The positive likelihood ratio, negative likelihood ratio, and odds ratio of a popping sensation for significant UCL injury were 3.2, 0.7, and 4.4 ( P < .001), respectively ( P < .001). A pop was not associated with either distal or proximal UCL tears ( P ≥ .999).

Conclusion:

A popping sensation at the time of injury in throwing athletes with medial elbow pain was associated with UCL injury severity. When a throwing athlete reports a pop, this should moderately increase a clinician’s suspicion for a significant UCL injury. Conversely, absence of a pop should not substantially decrease suspicion for significant UCL injury. The findings of this study allow for the clinical interpretation of the salient anamnestic finding of a pop at the time of injury, which can be used for diagnostic purposes as well as patient counseling. This study provides reference foundation for future studies of predictive and diagnostic factors for UCL injury in throwing athletes.
From Democratic to “Need to Know”: Linking Distributed Leadership to Data Cultures in the Florida College System
Authors: Brower Rebecca L. , Mokher Christine G. , Bertrand Jones Tamara , Cox Bradley E. , Hu Shouping
Published: January 2020

This multiple case study examines the extent and ways in which leaders and administrators in Florida College System (FCS) institutions engage in distributed leadership through data sharing with frontline staff. Based on focus groups and individual interviews with administrators, faculty, and staff (659 participants) from 21 state colleges, we found a continuum of three data cultures ranging from democratic data cultures to blended data cultures to “need to know” data cultures. We triangulate these results with survey data from FCS institutional leaders and find considerable variation in the extent of data sharing and perceptions of effectiveness of institutional data use. Institutions with democratic data cultures tended to have distributed leadership that encouraged information sharing and collaboration among staff to use data to inform change. Need-to-know institutions faced challenges, including weak data quality, concerns about adequate time and resources among staff for reviewing data, and perceptions that staff lack data literacy skills.
Biomechanical Evaluation With a Novel Cadaveric Model Using Supination and Pronation Testing of a Lisfranc Ligament Injury
Authors: Wagner Emilio , Wagner Pablo , Baumfeld Tiago , Prado Marcelo Pires , Baumfeld Daniel , Nery Caio
Published: January 2020

Background:

Lisfranc joint injuries can be due to direct or indirect trauma and while the precise mechanisms are unknown, twisting or axial force through the foot is a suspected contributor. Cadaveric models are a useful way to evaluate injury patterns and models of fixation, but a frequent limitation is the amount of joint displacement after injury. The purpose of this study was to test a cadaveric model that includes axial load, foot plantarflexion and pronation-supination motion, which could re-create bone diastasis similar to what is seen in subtle Lisfranc injuries. Our hypothesis was that applying pronation and supination motion to a cadaveric model would produce reliable and measurable bone displacements.

Methods:

Twenty-four fresh-frozen lower leg cadaveric specimens were used. The medial (C1) and intermediate (C2) cuneiforms and the first (M1) and second (M2) metatarsal bones were marked. A complete ligament injury was performed between C1-C2 and C1-M2 in 12 specimens (group 1), and between C1-C2, C1-M2, C1-M1, and C2-M2 in 12 matched specimens (group 2). Foot pronation and supination in addition to an axial load of 400 N was applied to the specimens. A 3D digitizer was used to measure bone distances.

Results:

After ligament injury, distances changed as follows: C1-C2 increased 3 mm (23%) with supination; C1-M2 increased 4 mm (21%) with pronation (no differences between groups). As expected, distances between C1-M1 and C2-M2 only changed in group 2, increasing 3 mm (14%) and 2 mm (16%), respectively (no differences between pronation and supination). M1-M2 and C2-M1 distances did not reach significant difference for any condition.

Conclusions:

Pronation or supination in addition to axial load produced measurable bone displacements in a cadaveric model of Lisfranc injury using sectioned ligaments. Distances M1-M2 and C2-M1 were not reliable to detect injury in this model.

Clinical Relevance:

This new cadaveric Lisfranc model included foot pronation-supination in addition to axial load delivering measurable bone diastasis. It was a reliable Lisfranc cadaveric model that could be used to test different Lisfranc reconstructions.
IGHV sequencing reveals acquired N-glycosylation sites as a clonal and stable event during follicular lymphoma evolution
Authors: Odabashian Mariette , Carlotti Emanuela , Araf Shamzah , Okosun Jessica , Spada Filomena , Gribben John G. , Forconi Francesco , Stevenson Freda K. , Calaminici Mariarita , Krysov Sergey
Published: January 2020

Follicular lymphoma B cells undergo continuous somatic hypermutation (SHM) of their immunoglobulin variable region genes, generating a heterogeneous tumor population. SHM introduces DNA sequences encoding N-glycosylation sites asparagine-X-serine/threonine (N-gly sites) within the V-region that are rarely found in normal B-cell counterparts. Unique attached oligomannoses activate B-cell receptor signaling pathways after engagement with calcium-dependent lectins expressed by tissue macrophages. This novel interaction appears critical for tumor growth and survival. To elucidate the significance of N-gly site presence and loss during ongoing SHM, we tracked site behavior during tumor evolution and progression in a diverse group of patients through next-generation sequencing. A hierarchy of subclones was visualized through lineage trees based on SHM semblance between subclones and their discordance from the germline sequence. We observed conservation of N-gly sites in more than 96% of subclone populations within and across diagnostic, progression, and transformation events. Rare N-gly-negative subclones were lost or negligible from successive events, in contrast to N-gly-positive subclones, which could additionally migrate between anatomical sites. Ongoing SHM of the N-gly sites resulted in subclones with different amino acid compositions across disease events, yet the vast majority of resulting DNA sequences still encoded for an N-gly site. The selection and expansion of only N-gly-positive subclones is evidence of the tumor cells’ dependence on sites, despite the changing genomic complexity as the disease progresses. N-gly sites were gained in the earliest identified lymphoma cells, indicating they are an early and stable event of pathogenesis. Targeting the inferred mannose-lectin interaction holds therapeutic promise.
External validation of models for KIR2DS1/KIR3DL1-informed selection of hematopoietic cell donors fails
Authors: Schetelig Johannes , Baldauf Henning , Heidenreich Falk , Massalski Carolin , Frank Sandra , Sauter Jürgen , Stelljes Matthias , Ayuk Francis Ayuketang , Bethge Wolfgang A. , Bug Gesine , Klein Stefan , Wendler Sarah , Lange Vinzenz , de Wreede Liesbeth C. , Fürst Daniel , Kobbe Guido , Ottinger Hellmut D. , Beelen Dietrich W. , Mytilineos Joannis , Fleischhauer Katharina , Schmidt Alexander H. , Bornhäuser Martin
Published: January 2020

Several studies suggest that harnessing natural killer (NK) cell reactivity mediated through killer cell immunoglobulin-like receptors (KIRs) could reduce the risk of relapse after allogeneic hematopoietic cell transplantation. Based on one promising model, information on KIR2DS1 and KIR3DL1 and their cognate ligands can be used to classify donors as KIR-advantageous or KIR-disadvantageous. This study was aimed at externally validating this model in unrelated donor hematopoietic cell transplantation. The impact of the predictor on overall survival (OS) and relapse incidence was tested in a Cox regression model adjusted for patient age, a modified disease risk index, Karnofsky performance status, donor age, HLA match, sex match, cytomegalovirus match, conditioning intensity, type of T-cell depletion, and graft type. Data from 2222 patients with acute myeloid leukemia or myelodysplastic syndrome were analyzed. KIR genes were typed by using high-resolution amplicon-based next-generation sequencing. In univariable analyses and subgroup analyses, OS and the cumulative incidence of relapse of patients with a KIR-advantageous donor were comparable to patients with a KIR-disadvantageous donor. The adjusted hazard ratio from the multivariable Cox regression model was 0.99 (Wald test, P = .93) for OS and 1.04 (Wald test, P = .78) for relapse incidence. We also tested the impact of activating donor KIR2DS1 and inhibition by KIR3DL1 separately but found no significant impact on OS and the risk of relapse. Thus, our study shows that the proposed model does not universally predict NK-mediated disease control. Deeper knowledge of NK-mediated alloreactivity is necessary to predict its contribution to graft-versus-leukemia reactions and to eventually use KIR genotype information for donor selection.
Clinical diagnostics and treatment strategies for Philadelphia chromosome–like acute lymphoblastic leukemia
Authors: Harvey Richard C. , Tasian Sarah K.
Published: January 2020

Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children, adolescents, and adults and is associated with high rates of conventional treatment failure and relapse. Current clinical trials are assessing the efficacy of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy for children and adults with Ph-like ALL harboring ABL class translocations or CRLF2 rearrangements and other JAK pathway alterations. However, real-time diagnosis of patients can be quite challenging given the genetic heterogeneity of this disease and the often cytogenetically cryptic nature of Ph-like ALL-associated alterations. In this review, we discuss the complex biologic and clinical features of Ph-like ALL across the age spectrum, available diagnostic testing modalities, and current clinical treatment strategies for these high-risk patients. We further propose a practical and step-wise approach to Ph-like ALL genetic testing to facilitate the identification and allocation of patients to appropriate clinical trials of TKI-based therapies or commercially available drugs. Although the majority of patients with Ph-like ALL can be successfully identified via current clinical assays by the end of induction chemotherapy, increasing diagnostic efficiency and sensitivity and decreasing time to test resulting will facilitate earlier therapeutic intervention and may improve clinical outcomes for these high-risk patients.
A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
Authors: Du Zhaohui , Weinhold Niels , Song Gregory Chi , Rand Kristin A. , Van Den Berg David J. , Hwang Amie E. , Sheng Xin , Hom Victor , Ailawadhi Sikander , Nooka Ajay K. , Singhal Seema , Pawlish Karen , Peters Edward S. , Bock Cathryn , Mohrbacher Ann , Stram Alexander , Berndt Sonja I. , Blot William J. , Casey Graham , Stevens Victoria L. , Kittles Rick , Goodman Phyllis J. , Diver W. Ryan , Hennis Anselm , Nemesure Barbara , Klein Eric A. , Rybicki Benjamin A. , Stanford Janet L. , Witte John S. , Signorello Lisa , John Esther M. , Bernstein Leslie , Stroup Antoinette M. , Stephens Owen W. , Zangari Maurizio , Van Rhee Frits , Olshan Andrew , Zheng Wei , Hu Jennifer J. , Ziegler Regina , Nyante Sarah J. , Ingles Sue Ann , Press Michael F. , Carpten John David , Chanock Stephen J. , Mehta Jayesh , Colditz Graham A. , Wolf Jeffrey , Martin Thomas G. , Tomasson Michael , Fiala Mark A. , Terebelo Howard , Janakiraman Nalini , Kolonel Laurence , Anderson Kenneth C. , Le Marchand Loic , Auclair Daniel , Chiu Brian C.-H. , Ziv Elad , Stram Daniel , Vij Ravi , Bernal-Mizrachi Leon , Morgan Gareth J. , Zonder Jeffrey A. , Huff Carol Ann , Lonial Sagar , Orlowski Robert Z. , Conti David V. , Haiman Christopher A. , Cozen Wendy
Published: January 2020

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
Expression of the prosurvival kinase HCK requires PAX5 and mutated MYD88 signaling in MYD88-driven B-cell lymphomas
Authors: Liu Xia , Chen Jiaji G. , Munshi Manit , Hunter Zachary R. , Xu Lian , Kofides Amanda , Tsakmaklis Nickolas , Demos Maria G. , Guerrera Maria Luisa , Chan Gloria G. , Jimenez Cristina , Patterson Christopher J. , Meid Kirsten , Keezer Andrew , Castillo Jorge J. , Treon Steven P. , Yang Guang
Published: January 2020

Hematopoietic cell kinase (HCK) is an SRC family member that is aberrantly upregulated in B-cell neoplasms dependent on MYD88-activating mutations and supports their growth and survival. We showed herein that activation of Toll-like receptor (TLR) signaling in MYD88 wild-type B cells also triggered HCK expression, denoting on path regulatory function for HCK by MYD88. To clarify the signaling cascades responsible for aberrant HCK expression in MYD88-mutated B-cell lymphomas, we performed promoter-binding transcription factor (TF) profiling, PROMO weighted TF consensus binding motif analysis, and chromatin immunoprecipitation studies. We identified PAX5, and the mutated MYD88 downstream signaling mediators STAT3, NF-κB, and AP-1, as important drivers of HCK transcription. Knockdown of PAX5, a crucial regulatory factor required for B-cell commitment and identity, abrogated HCK transcription in MYD88-mutated lymphoma cells. Among AP-1 complex components, JunB showed greatest relevance to TLR/MYD88 signaling and HCK transcription regulation. In MYD88-mutated Waldenström macroglobulinemia and activated B-cell-diffuse large B-cell lymphoma cells, knockdown of MYD88 reduced phosphorylation of JunB but not c-Jun, and knockdown of JunB reduced HCK protein levels. Deletion of STAT3, NF-κB, and AP-1 binding sites reduced corresponding TFs binding and HCK promoter activity. Moreover, inhibitors to STAT3, NF-κB, and AP-1 reduced HCK promoter activity and messenger RNA levels, particularly in combination, in MYD88-mutated lymphoma cells. The findings provide new insights into the transcriptional regulation of HCK prosurvival signaling by mutated MYD88, and the importance of JunB as a downstream mediator of the MYD88-directed signaling apparatus.
Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma
Authors: Santoro Armando , Mazza Rita , Pulsoni Alessandro , Re Alessandro , Bonfichi Maurizio , Zilioli Vittorio Ruggero , Zanni Manuela , Merli Francesco , Anastasia Antonella , Luminari Stefano , Annechini Giorgia , Gotti Manuel , Peli Annalisa , Liberati Anna Marina , Di Renzo Nicola , Castagna Luca , Giordano Laura , Ricci Francesca , Carlo-Stella Carmelo
Published: January 2020

The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemotherapy regimen prior to ASCT. Presented here are the 5-year results of BEGEV followed by ASCT in R/R cHL. With a median follow-up of 5 years, progression-free survival (PFS) and overall survival (OS) for the whole series (n = 59) were 59% and 78%, respectively. ASCT was performed in 43 of 49 responding patients (73% by intention to treat [ITT]; 88% by response to BEGEV) and resulted in 33 with continuous CR (56% by ITT; 77% of transplanted patients), 7 with disease relapse, and 3 with nonrelapse mortality. For patients who received transplants, the 5-year PFS and OS were 77% and 91%, respectively, with no significant difference between relapsed and refractory patients. No patient experienced secondary leukemia or myelodysplasia. In summary, the long-term efficacy data, the benefits for both relapsed and refractory patients, and the excellent safety profile provide a strong rationale for further development of the BEGEV regimen. This trial was registered at EudraCT as #2010-022169-91 and at www.clinicaltrials.gov as #NCT01884441.
Maximum tumor diameter is associated with event-free survival in PET-negative patients with stage I/IIA Hodgkin lymphoma
Authors: Illidge Tim M. , Phillips Elizabeth H. , Counsell Nicholas , Pettengell Ruth , Johnson Peter W. M. , Culligan Dominic J. , Popova Bilyana , Clifton-Hadley Laura , McMillan Andrew , Hoskin Peter , Barrington Sally F. , Radford John
Published: January 2020

Key Points

Baseline maximum tumor diameter is an important predictor of relapse for patients with ES-HL achieving complete metabolic remission. Patients with baseline tumor size ≥5 cm have worse outcomes with ABVD alone and are likely to benefit from consolidation radiotherapy.
Enhanced genome assembly and a new official gene set for Tribolium castaneum
Authors: Herndon Nicolae , Shelton Jennifer , Gerischer Lizzy , Ioannidis Panos , Ninova Maria , Dönitz Jürgen , Waterhouse Robert M. , Liang Chun , Damm Carsten , Siemanowski Janna , Kitzmann Peter , Ulrich Julia , Dippel Stefan , Oberhofer Georg , Hu Yonggang , Schwirz Jonas , Schacht Magdalena , Lehmann Sabrina , Montino Alice , Posnien Nico , Gurska Daniela , Horn Thorsten , Seibert Jan , Vargas Jentzsch Iris M. , Panfilio Kristen A. , Li Jianwei , Wimmer Ernst A. , Stappert Dominik , Roth Siegfried , Schröder Reinhard , Park Yoonseong , Schoppmeier Michael , Chung Ho-Ryun , Klingler Martin , Kittelmann Sebastian , Friedrich Markus , Chen Rui , Altincicek Boran , Vilcinskas Andreas , Zdobnov Evgeny , Griffiths-Jones Sam , Ronshaugen Matthew , Stanke Mario , Brown Sue J. , Bucher Gregor
Published: January 2020

Background

The red flour beetleTribolium castaneumhas emerged as an important model organism for the study of gene function in development and physiology, for ecological and evolutionary genomics, for pest control and a plethora of other topics. RNA interference (RNAi), transgenesis and genome editing are well established and the resources for genome-wide RNAi screening have become available in this model. All these techniques depend on a high quality genome assembly and precise gene models. However, the first version of the genome assembly was generated by Sanger sequencing, and with a small set of RNA sequence data limiting annotation quality.

Results

Here, we present an improved genome assembly (Tcas5.2) and an enhanced genome annotation resulting in a new official gene set (OGS3) forTribolium castaneum, which significantly increase the quality of the genomic resources. By adding large-distance jumping library DNA sequencing to join scaffolds and fill small gaps, the gaps in the genome assembly were reduced and the N50 increased to 4753kbp. The precision of the gene models was enhanced by the use of a large body of RNA-Seq reads of different life history stages and tissue types, leading to the discovery of 1452 novel gene sequences. We also added new features such as alternative splicing, well defined UTRs and microRNA target predictions. For quality control, 399 gene models were evaluated by manual inspection. The current gene set was submitted to Genbank and accepted as a RefSeq genome by NCBI.

Conclusions

The new genome assembly (Tcas5.2) and the official gene set (OGS3) provide enhanced genomic resources for genetic work inTribolium castaneum. The much improved information on transcription start sites supports transgenic and gene editing approaches. Further, novel types of information such as splice variants and microRNA target genes open additional possibilities for analysis.