bluuebunny/crossref_metadata_2025 huggingface dataset:
A library of coiled-coil domains: from regular bundles to peculiar twists
Authors: Szczepaniak Krzysztof , Bukala Adriana , da Silva Neto Antonio Marinho , Ludwiczak Jan , Dunin-Horkawicz Stanislaw
Published: December 2020

Motivation

Coiled coils are widespread protein domains involved in diverse processes ranging from providing structural rigidity to the transduction of conformational changes. They comprise two or more α-helices that are wound around each other to form a regular supercoiled bundle. Owing to this regularity, coiled-coil structures can be described with parametric equations, thus enabling the numerical representation of their properties, such as the degree and handedness of supercoiling, rotational state of the helices, and the offset between them. These descriptors are invaluable in understanding the function of coiled coils and designing new structures of this type. The existing tools for such calculations require manual preparation of input and are therefore not suitable for the high-throughput analyses.

Results

To address this problem, we developed SamCC-Turbo, a software for fully automated, per-residue measurement of coiled coils. By surveying Protein Data Bank with SamCC-Turbo, we generated a comprehensive atlas of ∼50 000 coiled-coil regions. This machine learning-ready dataset features precise measurements as well as decomposes coiled-coil structures into fragments characterized by various degrees of supercoiling. The potential applications of SamCC-Turbo are exemplified by analyses in which we reveal general structural features of coiled coils involved in functions requiring conformational plasticity. Finally, we discuss further directions in the prediction and modeling of coiled coils.

Availability and implementation

SamCC-Turbo is available as a web server (https://lbs.cent.uw.edu.pl/samcc_turbo) and as a Python library (https://github.com/labstructbioinf/samcc_turbo), whereas the results of the Protein Data Bank scan can be browsed and downloaded at https://lbs.cent.uw.edu.pl/ccdb.

Supplementary information

Supplementary data are available at Bioinformatics online.
Minimally overlapping words for sequence similarity search
Authors: Frith Martin C , Noé Laurent , Kucherov Gregory
Published: December 2020

Motivation

Analysis of genetic sequences is usually based on finding similar parts of sequences, e.g. DNA reads and/or genomes. For big data, this is typically done via ‘seeds’: simple similarities (e.g. exact matches) that can be found quickly. For huge data, sparse seeding is useful, where we only consider seeds at a subset of positions in a sequence.

Results

Here, we study a simple sparse-seeding method: using seeds at positions of certain ‘words’ (e.g. ac, at, gc or gt). Sensitivity is maximized by using words with minimal overlaps. That is because, in a random sequence, minimally overlapping words are anti-clumped. We provide evidence that this is often superior to acclaimed ‘minimizer’ sparse-seeding methods. Our approach can be unified with design of inexact (spaced and subset) seeds, further boosting sensitivity. Thus, we present a promising approach to sequence similarity search, with open questions on how to optimize it.

Availability and implementation

Software to design and test minimally overlapping words is freely available at https://gitlab.com/mcfrith/noverlap.

Supplementary information

Supplementary data are available at Bioinformatics online.
Successful long-term management of recurrent focal segmental glomerulosclerosis after kidney transplantation with costimulation blockade
Authors: Mühlbacher Thomas , Amann Kerstin , Mahling Moritz , Nadalin Silvio , Heyne Nils , Guthoff Martina
Published: December 2020

Recurrence of primary focal segmental glomerulosclerosis (FSGS) occurs in up to 50% of patients after kidney transplantation and is associated with poor allograft outcome. Novel therapeutic concepts directly target podocyte function via B7-1 with inconsistent response. We present the case of a 19-year-old patient with recurrent primary FSGS early after living donor kidney transplantation. Plasmapheresis and rituximab did not induce remission. Repetitive abatacept administration was able to achieve partial remission. Maintenance immunosuppression was subsequently switched to a belatacept-based calcineurin inhibitor-free immunosuppression, resulting in sustained complete remission with excellent allograft function throughout a follow-up of >56 months.
Real-time observation of a high-echoic mass in the left ventricle during transcatheter aortic valve implantation: a case report
Authors: Masumoto Akiko , Kitai Takeshi , Ota Mitsuhiko , Kim Kitae , Ehara Natsuhiko , Furukawa Yutaka
Published: December 2020

Background

Increasing number of symptomatic patients with severe aortic stenosis is treated with transcatheter aortic valve implantation (TAVI). Stroke is one of the most serious complications of TAVI, and the majority of cerebral events in patients undergoing TAVI have an embolic origin.

Case summary

A 90-year-old female underwent trans-femoral TAVI for symptomatic severe aortic stenosis. Just before the implantation of the transcatheter heart valve (THV), transoesophageal echocardiography (TOE) showed a mobile, high-echoic mass attached to the THV, which gradually enlarged to 26 mm, then spontaneously detached from the THV and flowed up the ascending aorta, disappearing from the TOE field of. After the procedure, the patient presented with ischaemic stroke. The patient’s stroke was thought to have resulted from the embolism migrating to the distal cerebral arteries.

Discussion

The detailed images acquired with TOE during TAVI enabled the prompt identification of the unusual intracardiac mass.
Reverse takotsubo cardiomyopathy caused by patent foramen ovale-related cryptogenic stroke: a case report
Authors: Takafuji Hiroya , Arai Junya , Saigusa Kuniyasu , Obunai Kotaro
Published: December 2020

Background

Reverse takotsubo cardiomyopathy (rTTC) is recognized as an atypical type of TTC. It has been suggested that neurological events are typical trigger of rTTC, especially in young individuals.

Case summary

In this case report, we describe a 16-year-girl who presented with neurological deficits due to embolic stroke and acute heart failure. Transthoracic echocardiography on admission revealed a severely reduced left ventricular (LV) function with akinesis of basal to mid LV, but normal contraction in apex. Coronary computed tomography angiography confirmed unobstructed coronary arteries. Two weeks later, her LV wall motion and ejection fraction were completely normalized. Transthoracic echocardiography and transoesophageal echocardiography demonstrated no evidence of intracardiac thrombus but showed a patent foramen ovale (PFO) with large shunt. After thorough work-up and brain–heart team discussion, we concluded that the patient developed rTTC due to cryptogenic stroke related with her PFO. She underwent percutaneous PFO closure for secondary prevention with good clinical course.

Discussion

Reverse TTC is a rare condition. It should be considered in stroke patients with acute heart failure. Quick diagnosis and management with brain–heart team is crucial for better prognosis.
Aortic valve neocuspidization with autologous pericardium in adult patients: UK experience and meta-analytic comparison with other aortic valve substitutes
Authors: Benedetto Umberto , Sinha Shubhra , Dimagli Arnaldo , Dixon Lauren , Stoica Serban , Cocomello Lucia , Quarto Cesare , Angelini Gianni D , Dandekar Uday , Caputo Massimo
Published: December 2020

OBJECTIVES

We sought to provide further evidence on the safety and efficacy of aortic valve neocuspidization (AVNeo) using autologous pericardium in adult patients with aortic valve disease by reporting clinical and echocardiographic results from the first UK experience and performing a meta-analytic comparison with other biological valve substitutes.

METHODS

We reported clinical and echocardiographic outcomes of 55 patients (mean age 58 ± 15 years) undergoing AVNeo with autologous pericardium in 2 UK centres from 2018 to 2020. These results were included in a meta-analytic comparison between series on AVNeo (7 studies, 1205 patients, mean weighted follow-up 3.6 years) versus Trifecta (10 studies, 8705 patients, 3.8 years), Magna Ease (3 studies, 3137 patients, 4.1 years), Freedom Solo (4 studies, 1869 patients, 4.4 years), Freestyle (4 studies, 4307 patients, 7 years), Mitroflow (4 studies, 4760 patients, 4.1 years) and autograft aortic valve (7 papers, 3839 patients, 9.1 years).

RESULTS

In the present series no patients required intraoperative conversion. After mean follow-up of 12.5 ± 0.9 months, 3 patients presented with endocarditis and 1 required reintervention. The remaining patients had absent or mild aortic valve insufficiency with very low peak and mean transvalvular gradients (16 ± 3.7 and 9 ± 2.2 mmHg, respectively). Meta-analytic estimates showed non-significant difference between AVNeo and all but Magna Ease valves with regards to structural valve degeneration, reintervention and endocarditis. When compared Magna Ease valve, AVNeo and other valve substitutes showed an excess of valve-related events.

CONCLUSIONS

AVNeo is safe, associated with excellent haemodynamic profile. Its midterm risk of valve-related events is comparable to most biological valve substitutes. Magna Ease is potentially the best biological choice as far as risk of reintervention is concerned.
Sharing the Fun? How Social Information Affects Viewers’ Video Enjoyment and Video Evaluations
Authors: Möller A Marthe , Baumgartner Susanne E , Kühne Rinaldo , Peter Jochen
Published: December 2020

Online video platforms often present videos together with social information in the form of user comments and likes. This study tested two hypotheses about how this merger of mass and interpersonal communication on online video platforms shapes viewers’ evaluations and enjoyment of online videos. Whereas the judgement effect hypothesis states that social information alters viewers’ video evaluations, the processing effect hypothesis poses that it influences viewers’ enjoyment while they are watching videos. Using real-time response measures, this experiment pitted both hypotheses against each other. The results indicate that if viewers are exposed to social information before watching a video, a processing effect emerges on their enjoyment as they are watching. If viewers are exposed to social information after watching a video, a judgement effect on their retrospective video enjoyment occurs but not on their video evaluations. These new insights advance our understanding of how social information affects video viewers.
Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis
Authors: Kojima Kazuki , Ichijo Hidenori , Naguro Isao
Published: December 2020

VCells are constantly exposed to various types of stress, and disruption of the proper response leads to a variety of diseases. Among them, inflammation and apoptosis are important examples of critical responses and should be tightly regulated, as inappropriate control of these responses is detrimental to the organism. In several disease states, these responses are abnormally regulated, with adverse effects. Apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases that regulate inflammation and apoptosis after a variety of stimuli, such as oxidative stress and endoplasmic reticulum stress. In this review, we summarize recent reports on the ASK family in terms of their involvement in inflammatory diseases, focussing on upstream stimuli that regulate ASK family members.
Compliance with Short-Interval Follow-up MRI after Benign Concordant MRI-guided Breast Biopsy
Authors: Ram Shruthi , Regen-Tuero Helaina , Baird Grayson L , Lourenco Ana P
Published: December 2020

Objective

To evaluate compliance with short-interval follow-up MRI after benign concordant MRI-guided breast biopsy.

Methods

This institutional review board-approved retrospective study included all benign concordant MRI-guided biopsies performed between January 1, 2010, and May 1, 2018. The following was collected from the electronic medical record: patient and lesion characteristics, short-interval follow-up MRI recommendation, communication to referring physician, follow-up imaging, repeat biopsies, biopsy outcome, and patient insurance status. Compliance with recommendations was defined as follow-up MRI within 9 months of biopsy.

Results

Among 98 patients, there were 107 lesions with benign concordant MRI-guided biopsy results that met study criteria. After excluding 7 patients who underwent subsequent mastectomy, 50/91 (54.9%) patients were recommended short-interval follow-up MRI. Of these, 33/50 (66.0%) had a short-interval follow-up MRI. Direct communication of the short-interval follow-up recommendation was documented in the biopsy report for 4/50 (8%) patients. Subsequent MRI was available for 77/107 (72%) lesions at a median of 29 months following MRI-guided biopsy (range, 3–96 months). Subsequent mammography was available for 21/30 (70%) remaining lesions at a median of 47 months following MRI-guided biopsy (range, 23–88 months). There were two repeat biopsies, with one subsequent malignancy, resulting in a false-negative rate of 0.9% (1/107).

Conclusion

When short-interval follow-up MRI was recommended following benign concordant MRI-guided breast biopsy, compliance was 66.0%. Lack of communication of the recommendation may at least partially explain the low compliance. The low false-negative rate (0.9%) suggests routine short-interval follow-up MRI may be unnecessary following benign concordant MRI-guided biopsy.
Overview of Pest Status, Potential Risk, and Management Considerations ofHelicoverpa armigera(Lepidoptera: Noctuidae) for U.S. Soybean Production
Authors: Haile Fikru , Nowatzki Tim , Storer Nicolas
Published: December 2020

Since its introduction and establishment in Brazil in 2013 and subsequent spread through most of Latin America, the Old World bollworm, Helicoverpa armigera (Hübner), has become an economically important pest of soybean, cotton, and other crops. Because this pest can migrate long distances aided by wind currents, it is expected to arrive and establish in the United States. There were reports of H. armigera moth incursions collected in pheromone traps from Puerto Rico and Florida, but no reports yet of field establishment in the United States. Although H. armigera is a polyphagous pest and poses threats to multiple crops, it has shown preference for and is considered a key pest of soybean and cotton in Brazil. Soybean and cotton in Mid-Southern states will be at greater risk for economic loss when this pest establishes in the United States due to similarities of H. armigera with the native sibling species, Helicoverpa zea (Lepidoptera: Noctuidae) (Boddie). Both are polyphagous, could damage the same crops, and have documented cases of resistance. Establishment of H. armigera in the United States presents uncertainty about how the two species may interact in U.S. agroecosystems. Management strategies for H. armigera consist of correct species identification, monitoring and early detection, and determining the susceptibility of populations to multiple control tactics to deploy effective management tools. Although it is expected to be a key pest of soybean and cotton, in this article, we discuss the overview of the potential threats which H. armigera poses to soybean production in Mid-Southern states when it establishes in the United States.
The Concept of ‘Principled Resistance’ to ECtHR Judgments: A Useful Tool to Analyse Implementation Deficits?
Authors: Breuer Marten
Published: December 2020

Recent years have seen a marked increase in ‘clashes’ between national courts on the one hand and international courts and tribunals on the other hand. This article introduces a new analytical pattern, called ‘principled resistance’, in order to analyse deficits occurring during the implementation phase of a Strasbourg judgment. This analytical concept is contrasted with other most recently developed scholarly concepts (‘reasonable resistance’: Palombino; ‘pushback’ and ‘backlash’: Madsen; ‘principled’ and ‘dilatory non-execution’: de Londras and Dzehtsiarou) in order to show differences and commonalities. Furthermore, the limits of (permissible) ‘disagreement’, as opposed to (impermissible) ‘principled resistance’, are explored from an international law point of view. It will be argued that although cases of principled resistance are extremely rare, the concept has an analytical value in that it prevents us from overestimating divergences between national and international courts and tribunals. At the same time, it will be shown that even where courts and other national actors employ legal arguments for their resistance to the ECtHR, those conflicts should be conceptualized as struggles over the proper allocation of powers between the national level and Strasbourg.
Rare synchronous caecal and sigmoid volvulus: management of two cases
Authors: Muhammad Butt , Alice Lee , Rabiya Aseem , Jason Smith
Published: December 2020

Colonic volvulus is one of leading causes of large bowel obstruction following colorectal cancer and diverticulitis, accounting for 5% of cases. Sigmoid volvulus is most common (75%) followed by volvulus of the caecum (15%), transverse colon (3%) and splenic flexure (2%). Synchronous volvulus of the caecum and sigmoid is very rare, with six reported cases in the literature to the best of our knowledge. We report two cases within 6 months. The key learning points include that classical radiological signs of both caecal and sigmoid volvulus may not be present, and that prompt, definitive management is necessary to prevent recurrence and morbidity.
Pretreatment of Body Fluid Specimens Using Hyaluronidase and Ultracentrifugation
Authors: La’ulu Sonia L , Turner Devon R , Zupan Emily , Genzen Jonathan R
Published: December 2020

Objective

Viscous body fluids present challenges during clinical laboratory testing. The present study was conducted to evaluate the effectiveness of hyaluronidase (HYAL) and ultracentrifugation (UC) pretreatment for a variety of body fluids before clinical chemistry testing.

Methods

The following body fluids were evaluated: biliary/hepatic, cerebrospinal, dialysate, drain, pancreatic, pericardial, peritoneal/ascites, pleural, synovial, and vitreous. Analytes assessed included amylase, total bilirubin, cancer antigen 19-9, carcinoembryonic antigen, cholesterol, chloride, creatinine, glucose, lactate dehydrogenase, lipase, potassium, rheumatoid factor, sodium, total protein, triglycerides, urea nitrogen, and uric acid.

Results

Observed percentage differences between HYAL treated and untreated fluids were less than ±15% for all analytes investigated, with a small number showing statistical significance (P <.05). In addition, UC showed increased variability for limited body fluid/analyte combinations.

Conclusion

The HYAL treatment effectively reduced viscosity for body fluids. Validation of specimen pretreatment processes ensures acceptable analytical performance and the absence of unanticipated interferences.
Novel Beta-Lactam/Beta-Lactamase Plus Metronidazole vs Carbapenem for Complicated Intra-abdominal Infections: A Meta-analysis of Randomized Controlled Trials
Authors: Che Haoyue , Wang Jin , Wang Rui , Cai Yun
Published: December 2020

Background

Complicated intra-abdominal infections (cIAIs) remain a leading cause of death in surgical wards, in which antibiotic treatment is crucial. We aimed to compare the efficacy and safety of novel β-lactam/β-lactamase inhibitors (BL/BLIs) in combination with metronidazole and carbapenems in the treatment of cIAIs.

Methods

A comprehensive search of randomized controlled trials (RCTs) was performed using Medline, Embase, and Cochrane Library, which compared the efficacy and safety of novel BL/BLIs and carbapenems for the treatment of cIAIs.

Results

Six RCTs consisting of 2254 patients were included. The meta-analysis showed that novel BL/BLIs in combination with metronidazole had a lower clinical success rate (risk difference [RD], –0.05; 95% CI, –0.07 to –0.02; I2 = 0%) and a lower microbiological success rate (RD, –0.04; 95% CI, –0.08 to –0.00; I2 = 0%). No difference was found between the 2 groups in incidence of adverse events (RD, 0.02; 95% CI, –0.01 to 0.06; I2 = 0%), serious adverse events (SAEs; RD, 0.01; 95% CI, –0.02 to 0.03; I2 = 0%), or mortality (RD, 0.01; 95% CI, –0.00 to 0.02). However, ceftazidime/avibactam had a higher risk of vomiting (RD, 0.03; 95% CI, 0.01 to 0.05; I2 = 47%), and the ceftolozane/tazobactam subgroup showed a higher incidence of SAEs (RD, 0.12; 95% CI, 0.01 to 0.03).

Conclusions

The efficacy of novel BL/BLIs in combination with metronidazole was not as high as that of carbapenems. Although no significant differences were found with respect to overall adverse events, SAEs, or mortality, the novel BL/BLIs has a higher risk of vomiting. We still need to be cautious about the clinical application of a new anti-infective combination.

Trial registration

PROSPERO ID: 42020166061.
A Type II Split Cord Malformation in an Adult Patient: An Operative Case Report
Authors: Oh Taemin , Avalos Lauro Nathaniel , Burke John Frederick , Mummaneni Nikhil , Safaee Michael , Gupta Nalin , Clark Aaron J
Published: December 2020

BACKGROUND AND IMPORTANCE

Split cord malformations (SCMs) are rare conditions in which the spinal cord is split into two hemicords within either a single thecal sac or two separate thecal sacs. The hemicords are typically split by a bony or fibrous structure. We present an adult patient who presented with a type II SCM with tethered cord. This is the first case of such a presentation with an accompanying intraoperative video. Unusual features of the case were the presence of an incomplete fibrous septum and lack of a discrete filum terminale.

CLINICAL PRESENTATION

A 50-yr-old woman presented with back pain, radiculopathy, urinary urgency, and episodic fecal incontinence. Her exam was notable for weakness of the right extensor hallicus longus. Imaging showed an SCM extending from L3 to S1, a fibrous septum located at L4-5, and a low-lying conus at S4. She was treated with a decompressive L3-S4 laminectomy and disconnection of all the dural attachment points. She required lumbar drain placement postoperatively and reoperation for wound dehiscence and persistent pseudomeningocele. At the time of last follow-up, she was neurologically intact with improvement in bowel/bladder function.

CONCLUSION

SCM is an uncommon presentation in adults and is often accompanied by findings of skin stigmata, tethered cord, and other central nervous system/skeletal anomalies. Obtaining full multimodal imaging is critical to understanding subtle anatomic variations that can pose operative challenges. We report the treatment of an adult patient with type II SCM, and provide an intraoperative video demonstrating the removal of an incomplete midline fibrous septum.
The Effectiveness of Anti-Nerve Growth Factor Monoclonal Antibodies in the Management of Pain in Osteoarthritis of the Hip and Knee: A PRISMA Systematic Review and Meta-Analysis
Authors: Seah K T Matthew , Rammanohar Jashmitha , Sutton James , To Kendrick , Khan Wasim S
Published: December 2020

Objective

To conduct a systematic review and meta-analysis of the efficacy of anti-nerve growth factor (NGF) monoclonal antibodies in osteoarthritis pain (hip and knee).

Design

Grade the evidence for anti-NGF use.

Methods

An interdisciplinary work group conducted a literature search for anti-NGF use in osteoarthritis. The systematic review was performed in accordance with methods described by the Cochrane collaboration. General inclusion criteria included all osteoarthritis trials studying any monoclonal anti-NGF antibody at any dose/phase. Excluded studies were those where participants received NSAIDs or analgesics other than anti-NGF antibodies. The Jadad Scale score was used to assess the quality of the included studies.

Results

Thirteen studies were included in the analysis, involving 8145 participants with a diagnosis of hip and/or knee osteoarthritis. Anti-NGF antibody treatment was associated with a significant improvement in all Western Ontario and McMaster Universities Arthritis Index (WOMAC) indices when compared to placebo. These agents were not associated with a significantly increased incidence of serious adverse events but were associated with significant increases in therapy discontinuation due to adverse events or side effects (e.g., peripheral neuropathy).

Conclusions

Future randomized clinical trials are needed to characterize the overall risk-to-benefit ratio of anti-NGF antibodies in managing pain associated with OA, particularly with long-term use, in order to verify their efficacy and safety in clinical practice.
An international patient-centred study of retroperitoneal fibrosis
Authors: Dattani R , Barwick T D , El Wardany G , Gibbons N , Mason J C , Morgan P , Pusey C D , Tam F W K , Tomlinson J A P ,   for the RaDaR Rare Disease Group (RDG)
Published: December 2020

Background

The impact that rare chronic disorders, such as retroperitoneal fibrosis (RPF), can have on the physical and psychological aspects of a patient’s health is poorly understood. Patient-related outcome measures and experiences provide a unique opportunity to understand the impact rare chronic disorders have on a patient’s life as well as allowing healthcare providers to compare and improve performance.

Aim

To understand the physical and psychosocial impact that RPF has upon peoples’ lives.

Design

An international online questionnaire was therefore created to gain insights into how patients with RPF, a rare fibro-inflammatory condition, viewed their health and experiences.

Methods

An international online questionnaire comprising 62 questions/free text options, was designed in collaboration with two patient advocates and the multi-disciplinary Renal Association Rare Disease Registry (RaDaR) RPF Group the questionnaire was anonymous and freely accessible on a GOOGLE Form online platform for 6 months.

Results

A total of 229 patients from 30 countries across 5 continents responded. Four key issues were identified; (i) pain; (ii) therapy-related side effects; (iii) lack of informed doctors/information about their condition and its management; and (iv) psychological burden. Variations in diagnosis and management are highlighted with 55% undergoing a biopsy to reach a diagnosis of RPF; 75% of patients underwent a further interventional procedure with 60% concurrently treated medically.

Conclusion

This study will guide further development of clinical and academic multi-disciplinary activity and shows the importance of trying to understand the impact of rare chronic disorders on the physical and psychological aspects of a patient’s health.
The incidence of clinical fractures in adults aged 50 years and older in Spain
Authors: Gomez-Vaquero Carmen , Valencia Lidia , Nolla Joan M , Boquet Dolors , Martínez Pardo Silvia , Mihaylov Grigorov Mihail , Lafont Anna , Segalés Nuria , Roig Vilaseca Daniel , Cerdà Dacia , Casado Enrique , Oncins Xavier , Sallés Meritxell , Mínguez Sonia , García Mira Yaiza , Holgado Susana , López Louzao Ana , Pitarch Conxita , Castellanos Moreira Raúl , Florez Helena , Tebé Cristian
Published: December 2020

Objective

The aim of this study was to quantify the incidence of all clinical fractures, including traumatic and fragility fractures, in patients aged 50 years and older, and to describe their distribution by fracture location, sex and age.

Methods

The incidence of clinical fractures at 10 hospitals in Catalonia, with a reference population of 3 155 000 inhabitants, was studied. For 1 week, from 30 May to 5 June 2016, we reviewed the discharge reports of the Traumatology section of the Emergency Department to identify all fractures diagnosed in patients ≥50 years of age. As a validation technique, data collection was carried out for 1 year at one of the centres, from 1 December 2015 to 30 November 2016. The fracture incidence, including the 95% CI, was estimated for the entire sample and grouped by fracture type, location, sex and age.

Results

A total of 283 fractures were identified. Seventy per cent were in women, with a mean age of 72 years. The overall fracture incidence was 11.28 per 1000 person-years (95% CI: 11.10, 11.46), with an incidence of traumatic and fragility fractures of 4.15 (95% CI: 4.04, 4.26) and 7.13 per 1000 person-years (95% CI: 6.99, 7.28), respectively. The incidence of fractures observed in the validation sample coincided with that estimated for the whole of Catalonia. The most common fragility fractures were of the hip, forearm, humerus and vertebrae.

Conclusion

The results of this study are the first to estimate the incidence of clinical fragility fractures in Spain, grouped by location, age and sex.
GRACy: A tool for analysing human cytomegalovirus sequence data
Authors: Camiolo Salvatore , Suárez Nicolás M , Chalka Antonia , Venturini Cristina , Breuer Judith , Davison Andrew J
Published: December 2020

Modern DNA sequencing has instituted a new era in human cytomegalovirus (HCMV) genomics. A key development has been the ability to determine the genome sequences of HCMV strains directly from clinical material. This involves the application of complex and often non-standardized bioinformatics approaches to analysing data of variable quality in a process that requires substantial manual intervention. To relieve this bottleneck, we have developed GRACy (Genome Reconstruction and Annotation of Cytomegalovirus), an easy-to-use toolkit for analysing HCMV sequence data. GRACy automates and integrates modules for read filtering, genotyping, genome assembly, genome annotation, variant analysis, and data submission. These modules were tested extensively on simulated and experimental data and outperformed generic approaches. GRACy is written in Python and is embedded in a graphical user interface with all required dependencies installed by a single command. It runs on the Linux operating system and is designed to allow the future implementation of a cross-platform version. GRACy is distributed under a GPL 3.0 license and is freely available at https://bioinformatics.cvr.ac.uk/software/ with the manual and a test dataset.
Development and Evaluation of a Model that Predicts Grapevine Anthracnose Caused by Elsinoë ampelina
Authors: Ji Tao , Caffi Tito , Carisse Odile , Li Ming , Rossi Vittorio
Published: December 2020

Grapevine anthracnose caused by Elsinoë ampelina is a serious threat in many vineyards, and its control requires repeated application of fungicides, usually on a calendar basis. A better understanding of the pathogen life cycle would help growers manage anthracnose more safely and effectively. After conducting a systematic literature search of grape anthracnose, we used the retrieved information and data to develop a mechanistic model based on systems analysis. The model simulates production and maturation of primary inoculum, infection caused by both primary and secondary conidia, and lesion formation and production of secondary inoculum. The model was validated for its ability to predict first seasonal onset of anthracnose lesions by using 8 years of data collected at Auckland, New Zealand, and disease progress during the season by using 3 years of data collected at Frelighsburg, Canada. Overall, the model provided accurate predictions of infection occurrence, with 0.96 accuracy, 0.91 sensitivity, and 0.97 specificity. The model also showed good accuracy for predicting disease progress, with a concordance correlation coefficient between observed and predicted disease severities of 0.92, a root mean square error of 0.14, and a coefficient of residual mass of 0.06. Although the model failed to predict 10 of 110 real infection periods, these missed infections led to only mild disease symptoms. We therefore conclude that the model is reliable and can be used to reduce the costs of anthracnose management by improving the timing of fungicide applications.
Association Between Text Neck and Neck Pain in Adults
Authors: Correia Igor Macedo Tavares , Ferreira Arthur de Sá , Fernandez Jessica , Reis Felipe José Jandre , Nogueira Leandro Alberto Calazans , Meziat-Filho Ney
Published: December 2020

Study Design.

Observational cross-sectional study.

Objective.

The aim of this study was to investigate the association between text neck and neck pain (NP) in adults.

Summary of Background Data.

It has been hypothesized that the inappropriate neck posture adopted when texting and reading on a smartphone, called text neck, is related to the increased prevalence of NP.

Methods.

The sample was composed of 582 volunteers aged between 18 and 65 years. Sociodemographics, anthropometrics, lifestyle, psychosocial, NP, and smartphone use-related questions were assessed by a self-reported questionnaire. Text neck was assessed by measuring the cervical flexion angle of the participants standing and sitting while typing a text on their smartphones, using the Cervical Range of Motion (CROM) device.

Results.

Multiple logistic regression analysis and linear regression analysis showed the cervical flexion angle of the standing participant using a smartphone did not associate with the prevalence of NP (odds ratio [OR] = 1.00; 95% confidence interval [CI]: 0.98–1.02; P = 0.66), NP frequency (OR = 1.01; 95% CI: 1.00–1.03; P = 0.056), or maximum NP intensity (beta coefficient = −5.195 × 10−5; 95% CI: −0.02 to 0.02; P = 0.99). Also, the cervical flexion angle of the sitting participant using the smartphone did not associate with NP (OR = 0.99; 95% CI: 0.98–1.01; P = 0.93), NP frequency (OR = 1.01; 95% CI: 0.99–1.02; P = 0.13), or maximum NP intensity (beta coefficient = 0.002; 95% CI: −0.002 to 0.02; P = 0.71).

Conclusion.

Text neck was not associated with prevalence of NP, NP frequency, or maximum NP intensity in adults.

Level of Evidence: 4
Prognostic and predictive factors to nivolumab in patients with metastatic renal cell carcinoma: a single center study
Authors: Mollica Veronica , Rizzo Alessandro , Tassinari Elisa , Giunchi Francesca , Schiavina Riccardo , Fiorentino Michelangelo , Brunocilla Eugenio , Ardizzoni Andrea , Massari Francesco
Published: December 2020

Renal cell carcinoma (RCC) scenario has radically changed with the advent of immunotherapy; in this setting, the identification of predictive and prognostic factors represents an urgent clinical need to evaluate which patients are the best candidate for an immunotherapy approach. The aim of our study was to analyze the association between nivolumab in pretreated patients with metastatic RCC and clinicopathological features, metastatic sites, and clinical outcomes. A total of 37 patients treated between January 2017 and April 2020 in our institution were retrospectively evaluated. All patients received nivolumab as second- or later-line of therapy after progression on previous tyrosine kinase inhibitors. The primary outcomes were overall survival (OS) from immunotherapy start and OS from first-line start. Univariate analysis was performed through the log-rank test and a Cox regression proportional hazards model was employed in multivariable analysis. Of the 12 variables analyzed, 4 were significantly associated with prognoses at multivariate analysis. Cox proportional hazard ratio models confirmed that International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk group, liver metastases at diagnosis, and central nervous system (CNS) metastases at diagnosis were associated with worse OS with an estimated hazard ratio of 4.76 [95% confidence interval (CI), 2.05–19.8] for liver metastases and 2.27 (95% CI, 1.13–28.9) for CNS metastases. Pancreatic metastases at diagnosis were correlated to a better prognosis with an estimated hazard ratio of 0.15 (95% CI, 0.02–0.38). IMDC risk group, liver metastases at diagnosis, and CNS metastases at diagnosis may identify a population of patients treated with immunotherapy in second- or later-line associated with worse prognosis.
A PI3K inhibitor-induced growth inhibition of cancer cells is linked to MEK-ERK pathway
Authors: Duff Angela , Kavege Llona , Baquier Jocelyn , Hu Tang
Published: December 2020

Phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3Ks) regulate several important cellular and subcellular processes including cell proliferation and differentiation. LY294002 was originally reported to be a selective inhibitor of PI3K-Akt. Later, it showed that this compound also inhibits several other molecules. In this study, we investigated the effect of LY294002 on the growth of suspension (MV4-11 and TF-1a) and tissue (Hep-G2) cells. In exponential phase, MV4-11 cells, but not TF-1a and Hep-G2 cells, expressed a low level of PI3Kp85 and addition of LY294002 inhibited the phosphorylation of PI3Kp85. LY294002 also significantly inhibited the proliferation of MV4-11, TF-1a and Hep-G2 cell and caused formation of cell clusters/aggregates measured by MTT and BrdU assays, and observed under an inverted microscope, respectively. Surprisingly, we found that LY294002 markedly repressed the activation of mitogen-activated protein kinase (MAPK) signal molecules, MEK and ERK, in all these cells. The inhibition of MEK and ERK was confirmed by using MEK stimulators, GM-CSF and phorbol 12-myristate 13-acetate, and MEK-specific inhibitor, PD98059. Although transforming growth factor beta (TGFβ) also inhibited the growth of Hep-G2 cells, it had no effect on the activity of MEK and ERK. The clusters/aggregates found in LY294002-treated cells were not detectable in TGFβ-treated cells. Our data suggest that LY294002 may directly inhibit the activation of MEK and ERK by its ability to bind to the ATP-binding site of the MAPK molecules.
Thickness and Curvature Changes of Human Corneal Grafts in Dextran-Containing Organ Culture Medium Before Keratoplasty
Authors: Hamon Loïc , Daas Loay , Mäurer Stephanie , Weinstein Isabel , Quintin Adrien , Schulz Katja , Langenbucher Achim , Seitz Berthold
Published: December 2020

Purpose:

To determine the changes of corneal thickness and curvature of human corneal grafts in organ culture medium II, containing dextran T500 6%, before keratoplasty.

Methods:

We examined the tomography of 24 corneas from our eye bank transferred from medium I into medium II. Images were repeated hourly during 24 hours using an anterior segment optical coherence tomography. The central corneal thickness (CCT) was measured with the manual measurement tool of the anterior segment optical coherence tomography. The radii of curvature (anterior flat and steep and posterior flat and steep) were measured with a MATLAB self-programmed software for “sterile donor tomography.”

Results:

The mean CCT (±SD) at baseline (T0) was 727 ± 156 μm. It reached 581 ± 103, 506 ± 84, 472 ± 79, and 456±7 μm after 6, 12, 18, and 24 hours, respectively. After 12 hours, 83% of the final deswelling was achieved. The radii of curvature (±SD) at baseline (T0) were (posterior flat, posterior steep, anterior flat, and anterior steep) 6.6 ± 0.5, 6.2 ± 0.5, 7.7 ± 0.4, and 7.4 ± 0.4 mm, respectively. After 24 hours, the radii of curvature reached 6.8 ± 0.1, 6.6 ± 0.3, 7.6 ± 0.1, and 7.4 ± 0.2 mm, respectively.

Conclusions:

The kinetics of the deswelling process in medium II follow a hyperbolic curve. Considering a CCT of 506 μm at T12, we assume that a time interval of 12 hours in medium II might be enough for clinical purposes. This result might help to keep storage in medium II as short as possible to escape potential toxic effects of dextran in medium II. The radius of curvature does not seem to change within 24 hours for all measured surfaces.
Cost-related Medication Nonadherence and Its Risk Factors Among Medicare Beneficiaries
Authors: Nekui Farrah , Galbraith Alison A. , Briesacher Becky A. , Zhang Fang , Soumerai Stephen B. , Ross-Degnan Dennis , Gurwitz Jerry H. , Madden Jeanne M.
Published: December 2020

Background:

Unaffordability of medications is a barrier to effective treatment. Cost-related nonadherence (CRN) is a crucial, widely used measure of medications access.

Objectives:

Our study examines the current national prevalence of and risk factors for CRN (eg, not filling, skipping or reducing doses) and companion measures in the US Medicare population.

Research Design:

Survey-weighted analyses included logistic regression and trends 2006–2016.

Subjects:

Main analyses used the 2016 Medicare Current Beneficiary Survey. Our study sample of 12,625 represented 56 million community-dwelling beneficiaries.

Measures:

Additional outcome measures were spending less on other necessities in order to pay for medicines and use of drug cost reduction strategies such as requesting generics.

Results:

In 2016, 34.5% of enrollees under 65 years with disability and 14.4% of those 65 years and older did not take their medications as prescribed due to high costs; 19.4% and 4.7%, respectively, experienced going without other essentials to pay for medicines. Near-poor older beneficiaries with incomes $15–25K had 50% higher odds of CRN (vs. >$50K), but beneficiaries with incomes <$15K, more likely to be eligible for the Part D Low-Income Subsidy, did not have significantly higher risk. Three indicators of worse health (general health status, functional limits, and count of conditions) were all independently associated with higher risk of CRN.

Conclusions:

Changes in the risk profile for CRN since Part D reflect the effectiveness of targeted policies. The persistent prevalence of CRN and associated risks for sicker people in Medicare demonstrate the consequences of high cost-sharing for prescription fills.
The role of antioxidants in restoring MAPK 14 and a DNA damage marker level following autophagy suppression
Authors: Elbialy Abdalla
Published: December 2020

Autophagy is a lysosomal degradation mechanism for elimination and recycling of damaged intracellular organelles and proteins. Recent studies have shown that autophagy could help reduce oxidative stress by removing oxidized proteins and damaged mitochondria. Autophagy deficiency is associated with the disruption of many intracellular biological processes. Using bioinformatics tools and fibroblast immunostaining technology, I tried to investigate whether oxidative stress is involved in mediating the effect of autophagy suppression on certain cell biological processes and signalling pathways. Many pharmaceutical components have different modes of action to suppress autophagy. In this study, I performed analysis on autophagy suppression induced by neutralizing lysosomal pH (NH
4
Cl and bafilomycin A1). Bioinformatics analysis of GEO data, GSE60570 accession number, revealed that p38 signalling induction and DNA damage response are among the main disrupted signalling pathways in bafilomycin A1-treated RPE-1 cells. Likewise, fibroblast immunostaining showed that autophagy deficiency established by ammonium chloride (NH
4
Cl) has significantly increased P38 signalling, DNA damage marker (H2A.X), and oxidative stress marker (dityrosine). I therefore investigated the role of oxidative stress and whether antioxidants treatment could reverse autophagy suppression effects on p38 signalling and DNA damage response. Importantly, antioxidant treatment clearly restored P38 signalling and H2A.X levels in autophagy-suppressed fibroblast cells. Indicating that oxidative stress might be associated with the harmful effect of autophagy suppression.
Planar cell polarity in the larval epidermis of
Drosophila
and the role of microtubules
Authors: Pietra Stefano , Ng KangBo , Lawrence Peter A. , Casal José
Published: December 2020

We investigate planar cell polarity (PCP) in the
Drosophila
larval epidermis. The intricate pattern of denticles depends on only one system of PCP, the Dachsous/Fat system. Dachsous molecules in one cell bind to Fat molecules in a neighbour cell to make intercellular bridges. The disposition and orientation of these Dachsous–Fat bridges allows each cell to compare two neighbours and point its denticles towards the neighbour with the most Dachsous. Measurements of the amount of Dachsous reveal a peak at the back of the anterior compartment of each segment. Localization of Dachs and orientation of ectopic denticles help reveal the polarity of every cell. We discuss whether these findings support our gradient model of Dachsous activity. Several groups have proposed that Dachsous and Fat fix the direction of PCP via oriented microtubules that transport PCP proteins to one side of the cell. We test this proposition in the larval cells and find that most microtubules grow perpendicularly to the axis of PCP. We find no meaningful bias in the polarity of microtubules aligned close to that axis. We also reexamine published data from the pupal abdomen and find no evidence supporting the hypothesis that microtubular orientation draws the arrow of PCP.
The social function of the feeling and expression of guilt
Authors: Julle-Danière Eglantine , Whitehouse Jamie , Vrij Aldert , Gustafsson Erik , Waller Bridget M.
Published: December 2020

Humans are uniquely cooperative and form crucial short- and long-term social bonds between individuals that ultimately shape human societies. The need for such intense cooperation may have provided a particularly powerful selection pressure on the emotional and communicative behaviours regulating cooperative processes, such as guilt. Guilt is a social, other-oriented moral emotion that promotes relationship repair and pro-sociality. For example, people can be more lenient towards wrongdoers who display guilt than towards those who do not. Here, we examined the social consequences of guilt in a novel experimental setting with pairs of friends differing in relationship quality. Pairs of participants took part in a cooperative game with a mutual goal. We then induced guilt in one of the participants and informed the other participant of their partner's wrongdoing. We examined the outcome using a dictator game to see how they split a joint reward. We found that guilty people were motivated to repair wrongdoing regardless of friendship. Observing guilt in others led to a punishment effect and a victim of wrongdoing punished close friends who appeared guilty more so than acquaintances. We suggest, therefore, that guilt has a stronger function between close friends as the costs of relationship breakdown are greater. Relationship context, therefore, is crucial to the functional relevance of moral emotions.
Macroscopic permeability of doubly porous solids with spheroidal macropores: closed-form approximate solutions of the longitudinal permeability
Authors: monchiet Vincent
Published: December 2020

The presence of macropores and fractures significantly affects the effective transport properties of porous solids such as concrete and rocks. The dimensions of the fractures are generally large behind that of the initial porosity, so that the problem contains two porosities. The influence of the macroporosity is studied in the homogenization framework by solving at the intermediate scale, that of the macropores, a coupled Darcy/Stokes problem with the Beavers–Joseph–Saffman (BJS) interface condition. We derive analytic expressions of the macroscopic permeability in the case of an isotropic permeable matrix containing spheroidal-shaped macropores. To this aim, we consider a representative volume element (RVE) on which uniform boundary conditions are considered for the velocity and pressure fields. The local problem is written as minimum principles; kinematic and static approaches are developed to derive rigorous bounds for the macroscopic permeability. Closed-form expressions of the longitudinal permeability (along the revolution axe of the spheroid) are determined by considering a simplified RVE constituted of two confocal spheroids. They depend on the volume fraction and the eccentricity of the spheroidal macropores, the scale factor between the two porosities and the slip coefficient of the BJS model. Illustrations show the influence of these parameters.