bluuebunny/crossref_metadata_2025 huggingface dataset:
PaSiT: a novel approach based on short-oligonucleotide frequencies for efficient bacterial identification and typing
Authors: Goussarov Gleb , Cleenwerck Ilse , Mysara Mohamed , Leys Natalie , Monsieurs Pieter , Tahon Guillaume , Carlier Aurélien , Vandamme Peter , Van Houdt Rob
Published: December 2019

Motivation

One of the most widespread methods used in taxonomy studies to distinguish between strains or taxa is the calculation of average nucleotide identity. It requires a computationally expensive alignment step and is therefore not suitable for large-scale comparisons. Short oligonucleotide-based methods do offer a faster alternative but at the expense of accuracy. Here, we aim to address this shortcoming by providing a software that implements a novel method based on short-oligonucleotide frequencies to compute inter-genomic distances.

Results

Our tetranucleotide and hexanucleotide implementations, which were optimized based on a taxonomically well-defined set of over 200 newly sequenced bacterial genomes, are as accurate as the short oligonucleotide-based method TETRA and average nucleotide identity, for identifying bacterial species and strains, respectively. Moreover, the lightweight nature of this method makes it applicable for large-scale analyses.

Availability and implementation

The method introduced here was implemented, together with other existing methods, in a dependency-free software written in C, GenDisCal, available as source code from https://github.com/LM-UGent/GenDisCal. The software supports multithreading and has been tested on Windows and Linux (CentOS). In addition, a Java-based graphical user interface that acts as a wrapper for the software is also available.

Supplementary information

Supplementary data are available at Bioinformatics online.
Improved Proofs Of Retrievability And Replication For Data Availability In Cloud Storage
Authors: Guo Wei , Qin Sujuan , Lu Jun , Gao Fei , Jin Zhengping , Wen Qiaoyan
Published: December 2019

For a high level of data availability and reliability, a common strategy for cloud service providers is to rely on replication, i.e. storing several replicas onto different servers. To provide cloud users with a strong guarantee that all replicas required by them are actually stored, many multi-replica integrity auditing schemes were proposed. However, most existing solutions are not resource economical since users need to create and upload replicas of their files by themselves. A multi-replica solution called Mirror is presented to overcome the problems, but we find that it is vulnerable to storage saving attack, by which a dishonest provider can considerably save storage costs compared to the costs of storing all the replicas honestly—while still can pass any challenge successfully. In addition, we also find that Mirror is easily subject to substitution attack and forgery attack, which pose new security risks for cloud users. To address the problems, we propose some simple yet effective countermeasures and an improved proofs of retrievability and replication scheme, which can resist the aforesaid attacks and maintain the advantages of Mirror, such as economical bandwidth and efficient verification. Experimental results show that our scheme exhibits comparable performance with Mirror while achieving high security.
A Decade of Varicella Screening Within a Paediatric Inflammatory Bowel Disease Population
Authors: Harris Rachel E , Curtis Lee , Hegde Vikas , Garrick Vikki , Gervais Lisa , Armstrong Lawrence , Delahunty Caroline , Eccleston Andrew , Al-Hourani Ghassan , Flynn Diana M , Merrick Victoria , Barclay Andrew R , Tayler Rachel , Hansen Richard , Russell Richard K
Published: December 2019

Introduction

Increased risk of opportunistic infection—e.g., varicella zoster infection—secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population.

Methods

Data regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009–2018].

Results

In all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; p <0.00001). Median diagnosis age of naïve patients was lower [8.3 years versus 12.8 years; p <0.00001]. Where vaccination was feasible, 21/31 [68%] had two and 7/31 [23%] one immunisation. Prednisolone induction led to lower rates of vaccination (5/13 [39%] versus 23/33 [70%] for other induction therapies; p =0.02). Of 28 vaccinated patients, 5 [18%] had suspected breakthrough varicella; and 6/18 [33%] unimmunised patients required post-exposure prophylaxis or treatment for varicella. Immunisation was associated with a decrease in patients requiring post-exposure prophylaxis (0/28 [0%] versus 5/18 [28%]; p =0.0006) and varicella-related hospital admission (1/28 [4%] versus 4/18 [22%]; p =0.01).

Conclusions

High rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies.
Deep structure of the Hellenic lithosphere from teleseismic Rayleigh-wave tomography
Authors: Kassaras I , Kapetanidis V , Karakonstantis A , Papadimitriou P
Published: December 2019

This research provides new constraints on the intermediate depth upper-mantle structure of the Hellenic lithosphere using a three-step Rayleigh-wave tomography. Broadband waveforms of about 1000 teleseismic events, recorded by ∼200 permanent broad-band stations between 2010 and 2018 were acquired and processed. Through a multichannel cross-correlation technique, the fundamental mode Rayleigh-wave phase-velocity dispersion curves in the period range 30–90 s were derived. The phase-velocities were inverted and a 3-D shear velocity model was obtained down to the depth of 140 km. The applied method has provided 3-D constraints on large-scale characteristics of the lithosphere and the upper mantle of the Hellenic region. Highlighted resolved features include the continental and oceanic subducting slabs in the region, the result of convergence between Adria and Africa plates with the Aegean. The boundary between the oceanic and continental subduction is suggested to exist along a trench-perpendicular line that connects NW Peloponnese with N. Euboea, bridging the Hellenic Trench with the North Aegean Trough. No clear evidence for trench-perpendicular vertical slab tearing was resolved along the western part of Hellenic Subduction Zone; however, subcrustal seismicity observed along the inferred continental–oceanic subduction boundary indicates that such an implication should not be excluded. The 3-D shear velocity model supports an N–S vertical slab tear beneath SW Anatolia that justifies deepening, increase of dip and change of dip direction of the Wadati-Benioff Zone. Low velocities found at depths <50 km beneath the island and the backarc, interrelated with recent/remnant volcanism in the Aegean and W. Anatolia, are explained by convection from a shallow asthenosphere.
Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank
Authors: Arthur Rhonda S , Wang Tao , Xue Xiaonan , Kamensky Victor , Rohan Thomas E
Published: December 2019

Background

Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal.

Methods

Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci.

Results

Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women.

Conclusion

Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.
Intranasal Methylprednisolone Effectively Reduces Neuroinflammation in Mice With Experimental Autoimmune Encephalitis
Authors: Rassy Dunia , Bárcena Brandon , Pérez-Osorio Iván Nicolás , Espinosa Alejandro , Peón Alberto N , Terrazas Luis I , Meneses Gabriela , Besedovsky Hugo O , Fragoso Gladis , Sciutto Edda
Published: December 2019

Relapsing-remitting multiple sclerosis, the most common form, is characterized by acute neuroinflammatory episodes. In addition to continuous disease-modifying therapy, these relapses require treatment to prevent lesion accumulation and progression of disability. Intravenous methylprednisolone (1–2 g for 3–5 days) is the standard treatment for relapses. However, this treatment is invasive, requires hospitalization, leads to substantial systemic exposure of glucocorticoids, and can only reach modest concentrations in the central nervous system (CNS). Intranasal delivery may represent an alternative to deliver relapse treatment directly to the CNS with higher concentrations and reducing side effects. Histopathological analysis revealed that intranasal administration of methylprednisolone to mice with experimental autoimmune encephalomyelitis (EAE) suppressed the neuroinflammatory peak, and reduced immune cell infiltration and demyelination in the CNS similarly to intravenous administration. Treatment also downregulated Iba1 and GFAP expression. A similar significant reduction of IL-1β, IL-6, IL-17, IFN-γ, and TNF-α levels in the spinal cord was attained in both intranasal and intravenously treated mice. No damage in the nasal cavity was found after intranasal administration. This study demonstrates that intranasal delivery of methylprednisolone is as efficient as the intravenous route to treat neuroinflammation in EAE.
Colliding winds in and around the stellar group IRS 13E at the galactic centre
Authors: Wang Q Daniel , Li Jun , Russell Christopher M P , Cuadra Jorge
Published: December 2019

IRS 13E is an enigmatic compact group of massive stars located in projection only 3.6 arcsec away from Sgr A*. This group has been suggested to be bounded by an intermediate-mass black hole (IMBH). We present a multiwavelength study of the group and its interplay with the environment. Based on Chandra observations, we find the X-ray spectrum of IRS 13E can be well characterized by an optically thin thermal plasma. The emission peaks between two strongly mass-losing Wolf–Rayet stars of the group. These properties can be reasonably well reproduced by simulated colliding winds of these two stars. However, this scenario underpredicts the X-ray intensity in outer regions. The residual emission likely results from the ram-pressure confinement of the IRS 13E group wind by the ambient medium and is apparently associated with a shell-like warm gas structure seen in Pa α and in ALMA observations. These latter observations also show strongly peaked thermal emission with unusually large velocity spread between the two stars. These results indicate that the group is colliding with the bar of the dense cool gas mini-spiral around Sgr A*. The extended X-ray morphology of IRS 13E and its association with the bar further suggest that the group is physically much farther away than the projected distance from Sgr A*. The presence of an IMBH, while favourable to keep the stars bound together, is not necessary to explain the observed stellar and gas properties of IRS 13E.
The Hubble Space Telescope UV Legacy Survey of Galactic globular clusters – XXI. Binaries among multiple stellar populations
Authors: Milone A P , Vesperini E , Marino A F , Hong J , van der Marel R , Anderson J , Renzini A , Cordoni G , Bedin L R , Bellini A , Brown T M , D’Antona F , Lagioia E P , Libralato M , Nardiello D , Piotto G , Tailo M , Cool A , Salaris M , Sarajedini A
Published: December 2019

A number of scenarios for the formation of multiple populations in globular clusters (GCs) predict that second generation (2G) stars form in a compact and dense subsystem embedded in a more extended first-generation (1G) system. If these scenarios are accurate, a consequence of the denser 2G formation environment is that 2G binaries should be more significantly affected by stellar interactions and disrupted at a larger rate than 1G binaries. The fractions and properties of binary stars can thus provide a dynamical fingerprint of the formation epoch of multiple-population GCs and their subsequent dynamical evolution. We investigate the connection between binaries and multiple populations in five GCs, NGC 288, NGC 6121 (M 4), NGC 6352, NGC 6362, and NGC 6838 (M 71). To do this, we introduce a new method based on the comparison of Hubble Space Telescope observations of binaries in the F275W, F336W, F438W, F606W, and F814W filters with a large number of simulated binaries. In the inner regions probed by our data, we do not find large differences between the local 1G and the 2G binary incidences in four of the studied clusters, the only exception being M 4 where the 1G binary incidence is about three times larger than the 2G incidence. The results found are in general agreement with the results of simulations predicting significant differences in the global 1G and 2G incidences and in the local values in the clusters’ outer regions but similar incidences in the inner regions. The significant difference found in M 4 is consistent with simulations with a larger fraction of wider binaries. Our analysis also provides the first evidence of mixed (1G–2G) binaries, a population predicted by numerical simulations to form in a cluster’s inner regions as a result of stellar encounters during which one component of a binary is replaced by a star of a different population.
Firm Response to Competitive Shocks: Evidence from China’s Minimum Wage Policy
Authors: Hau Harald , Huang Yi , Wang Gewei
Published: December 2019

The large regional variation in minimum wage levels during the period 2002–8 in China implies that Chinese manufacturing firms experienced competitive shocks as a function of firm location and their low-wage employment share. We find that minimum wage hikes accelerate the input substitution from labour to capital, reduce employment growth and accelerate total factor productivity growth—particularly among the less productive firms under private Chinese or foreign ownership, but not among state-owned enterprises. The heterogeneous firm response to labour cost shocks can be explained by differences in management practices and suggests that management quality and competitive pressure are complementary.
The Segregation Premium: How Gender Shapes the Symbolic Valuation Process of Occupational Prestige Judgments
Authors: Valentino Lauren
Published: December 2019

Symbolic valuation is an important but overlooked aspect of gendered processes of inequality in the occupation structure. Prior work has largely focused on the material valuation of gendered work, such as how much predominantly-female versus predominantly-male occupations pay. Less research has examined the symbolic valuation of work, such as how prestigious predominantly-female versus predominantly-male occupations are. What research has examined this question has remained inconclusive at best. Drawing on insights into and techniques from the sociology of culture and cognition, this study examines the role of an occupation’s gender composition in how Americans judge the prestige of jobs, testing key predictions from theories of gender and status. Using 2012 General Social Survey and federal occupation-level data, it finds evidence for a segregation premium: people view gender-segregated occupations as the most symbolically valuable jobs. Both men and women reward gender-segregated occupations with symbolic value, although there is evidence of a gendered in-group bias in which women in particular see women’s work as more prestigious, while men see men’s work as more prestigious.
Diabetes-associated cardiac autonomic neuropathy
Authors: Wooton Angela K. , Melchior Lynne
Published: December 2019

Cardiac autonomic neuropathy (CAN) is an underdiagnosed cardiovascular complication associated with diabetes. NPs are in a pivotal position to screen patients for CAN. As the incidence of diabetes increases in an aging population, NPs can help prevent complications associated with diabetes and CAN.
Targeting BRAF and MEK inhibitors in melanoma in the metastatic, neoadjuvant and adjuvant setting
Authors: Tétu Pauline , Baroudjian Barouyr , Lebbe Céleste
Published: December 2019

Purpose of review

Better understanding of the biology of BRAF-mutated melanoma has led to the development of highly effective therapy, BRAF and MEK inhibitors, targeting abnormally activated protein kinases for patient with BRAF-mutated melanoma. The purpose of this article was to review the recent published data on BRAF and MEK inhibitors in melanoma in the metastatic, adjuvant and neoadjuvant setting to facilitate the management of melanoma patients in clinical practice.

Recent findings

The spectacular outcomes of targeted therapy in advanced melanoma patients have led to their development in the adjuvant setting with substantial improvements in recurrence-free and overall survival. The neoadjuvant strategy is already used in many cancers to decrease tumor load, improve resectability and prevent relapse. Targeted therapy in the neoadjuvant setting is a therapeutic approach being explored in subsequent studies.

We hope that this review will help clinicians to manage melanoma patients in routine practice.
Is Surgery-first Still a Reasonable Option in the Era of Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer?
Authors: Saharia Ashish , Potter Lucy M. , Baio Flavio , Elaileh Ahmed , Mobley Constance , Ghobrial Rafik M. , Abdelrahim Maen , Heyne Kirk
Published: December 2019

The incidence of pancreatic ductal adenocarcinoma has risen rapidly. By 2030, it is likely to be the second most prevalent cause of death by cancer, following cancer of the lung. Unfortunately, most patients present with advanced disease. In fact, only 20% of patients are candidates for surgery. More research is needed to find dependable treatment options for this disease. Although we wait for more effective treatments to be developed, we continue using chemotherapy, radiation, and surgery—all with less than optimal outcomes. There is a debate about using chemotherapy in the neoadjuvant setting and counter-debate about better outcomes in the adjuvant settings. In the neoadjuvant setting, not everyone is able to make it to surgery; conversely, in the adjuvant setting, not everyone is able to make it to chemotherapy. Drop-out data after surgery are widely available, but similar drop-out rates after neoadjuvant treatment are not widely published. Here, we will analyze the literature to better understand the treatment strategies and outcomes of pancreatic ductal adenocarcinoma. We argue in favor of an upfront surgery and adjuvant therapy strategy for better outcomes and patient quality of life.
Intrathoracic Breast Transposition: A New Method in the Treatment of Bronchopleural Fistula and Empyema
Authors: de Weerd Louis , Endresen Petter Cappelen , Numan Anmar Tabit , Weum Sven
Published: December 2019

A bronchopleural fistula (BF) is a life-threatening complication. Optimal management of a BF is still debated although surgery remains the preferred treatment. Usually, the fistula is a result of inadequate healing at the bronchial stump after pneumonectomy. Successful closure of a BF after pneumonectomy depends on evacuation of empyema, coverage of the suture line after fistula closure with vascularized tissue, and obliteration of the residual pleural cavity. Extrathoracic muscles and omentum are the first choice for intrathoracal transposition. We report a unique case of a cachectic female patient with a BF from the left main stem bronchus complicated with empyema following right-sided pneumonectomy. Previous surgeries excluded the use of extrathoracic muscles or only omentum. The BF could not be closed with sutures. Using a parachute technique, omentum was sutured into the fistula opening resulting in a tension-free fistula closure. A well-vascularized breast was transposed into the residual pleural cavity to obliterate dead space and to support the omentoplasty, so it would be able to withstand changes in intrathoracic pressure. The postoperative course was uneventful. Tension-free closure of a BF can be obtained by suturing well-vascularized tissue into the fistula opening using a parachute technique. Intrathoracic breast transposition could be a new option in the treatment of a BF and associated empyema in a female patient. In selected patients, a large breast can obliterate the dead space after pneumonectomy and support the omentoplasty.
Mechanical circulatory support in cardiogenic shock
Authors: Frost Andrew , Haddad Haissam , Shavadia Jay
Published: December 2019

Purpose of review

Cardiogenic shock remains a complex clinical syndrome with high morbidity and mortality. The purpose of this article is to review important landmark trials as well as the relevant recent literature for percutaneous mechanical circulatory support following acute myocardial infarction.

Recent findings

The sole use of intraaortic balloon pumps for cardiogenic shock following acute myocardial infarction continues to be questioned with downgrading of its recommendation in recent years, there however may remain a role in patients with mechanical complications of their myocardial infarction. The combined use of extracorporeal circulatory support and a ventricular unloading device appears to be promising with increasing data supporting this strategy.

Given the complex and heterogeneous nature of cardiogenic shock there remains somewhat limited robust data to guide clinical practice. Ongoing research is needed to help guide improvements in patient outcomes.
Airway fellowship: Royal Surrey County Hospital, Guildford, UK
Authors: King Wendy , Patel Bhavesh
Published: December 2019

This Advanced Airway Fellowship offered at a UK surgical oncology unit offers excellent anaesthetic experience, working alongside the maxillofacial and ENT surgical specialties. It offers a wide caseload of cancer, as well as benign orthognathic, ontological and nasal procedures frequently necessitating advanced airway techniques. Original research is supported, alongside teaching and presentation.
CHOROIDAL NEOVASCULAR MEMBRANE AFTER FINE-NEEDLE ASPIRATION BIOPSY OF VITREORETINAL LYMPHOMA
Authors: Mashayekhi Arman , Mazloumi Mehdi , Shields Carol L. , Shields Jerry A.
Published: December 2019

Purpose:

To report development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma.

Methods:

Case report. A 75-year-old white woman with 14-month history of bilateral vitritis.

Results:

Examination showed vitreous infiltration in both eyes and yellow-white subretinal pigment epithelial infiltrates temporally in the left eye. Visual acuity was 20/400 in both eyes. Transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrate in the left eye using a long 27-gauge needle attached to a 10-mL syringe revealed large B-cell lymphoma. Treatment was initiated with monthly intravitreal injections of melphalan (10 μg/0.05 mL) to both eyes. One month after first injection, visual acuity in the left eye had decreased to hand motion, and new ill-defined patches of retinal whitening were noticeable in the temporal macular area. Intravenous fluorescein angiography and optical coherence tomography angiography showed large choroidal neovascular membrane temporally at the site of previous fine-needle aspiration biopsy. Four monthly injections of intravitreal bevacizumab (1.25 mg/0.05 mL) resulted in complete regression of choroidal neovascular membrane with improvement of visual acuity to 20/100 in the left eye.

Conclusion:

This case demonstrates the rare development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma.
Contemporary management of refractory pediatric glaucoma
Authors: Malik Rizwan , AlDarrab Abdulrahman , Edward Deepak P.
Published: December 2019

Purpose of review

The management of pediatric glaucoma poses a unique challenge in terms of maintaining lifelong vision and combating an aggressive scarring response from surgery. Contemporary literature regarding the surgical management of children with pediatric glaucoma who fail, or are at a high risk of failure, from conventional surgery is limited. The aim of this review is to highlight recent developments in relation to the current opinion regarding the management of children with refractory pediatric glaucoma.

Recent findings

Some studies have reported impressive success rates with circumferential trabeculotomy, even in eyes with previous failed surgery. Early results of deep sclerectomy in populations which may not respond well to conventional angle surgery are encouraging but data is limited for the pediatric age group. In compliant patients in whom multiple postoperative examinations under anesthesia are possible, trabeculectomy remains an effective procedure. Multiple recent studies have demonstrated that glaucoma drainage device (GDD) surgery is associated with 5-year success rates of over 70% in primary childhood glaucomas.

Glaucoma drainage device surgery is likely to remain a mainstay of surgical management for refractory glaucoma in older children. More prospective data are needed on the success of circumferential trabeculotomy, deep sclerectomy and micropulse laser in pediatric eyes with previous failed surgery.

Video abstract

http://links.lww.com/COOP/A34.
Epigenetic upregulation of acid-sensing ion channel 1 contributes to gastric hypersensitivity in adult offspring rats with prenatal maternal stress
Authors: Wang Hong-Jun , Xu Xue , Zhang Ping-An , Li Meng , Zhou You-Lang , Xu Yu-Cheng , Jiang Xing-Hong , Xu Guang-Yin
Published: December 2019

Functional dyspepsia is a common functional gastrointestinal disorder. Gastric hypersensitivity (GHS) is a hallmark of this disorder, but the cellular mechanisms remain largely unknown. Stressors during gestational period could have effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. The aim of this study was to test whether prenatal maternal stress (PMS) induces GHS and to investigate role of acid-sensing ion channel (ASIC)/nuclear factor-κB (NF-κB) signaling by examining Asic1 methylation status in adult offspring rats. Gastric hypersensitivity in response to gastric distension was examined by electromyography recordings. Changes in neuronal excitability were determined by whole-cell patch-clamp recording techniques. Demethylation of CpG islands of Asic1 was determined by methylation-specific PCR and bisulfite sequencing assay. Prenatal maternal stress produced GHS in adult offspring rats. Treatment with amiloride, an inhibitor of ASICs, significantly attenuated GHS and reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI. Expression of ASIC1 and NF-κBp65 was markedly enhanced in T7 to T10 DRGs. Furthermore, PMS led to a significant demethylation of CpG islands in the Asic1 promoter. A chromatin immunoprecipitation assay showed that PMS also enhanced the ability of NF-κBp65 to bind the promoter of Asic1 gene. Blockade of NF-κB using lentiviral-p65shRNA reversed upregulation of ASIC1 expression, GHS, and the hyperexcitability of DRG neurons. These data suggest that upregulation of ASIC1 expression is attributed to Asic1 promoter DNA demethylation and NF-κB activation, and that the enhanced interaction of the Asic1 and NF-κBp65 contributes to GHS induced by PMS.
Informal caring for back pain: overlooked costs of back pain and projections to 2030
Authors: Schofield Deborah , Zeppel Melanie J.B. , Tanton Robert , Veerman Jacob , Kelly Simon , Passey Megan E. , Shrestha Rupendra N.
Published: December 2019

This study models the economic costs of informal caring for people with back pain, using a microsimulation model, Care&WorkMOD, from 2015 to 2030. Care&WorkMOD was based on 3 national Australian Surveys of Disability, Ageing and Carers (2003, 2009, 2012) data sets for individuals aged 15 to 64 years. Estimated national income loss due to caring for people with back pain was AU$258 million in 2015, increasing to $398 million in 2030 (54% increase). Lost income tax revenue to the Australian government due to informal care of people with back pain was estimated to be AU$78 million in 2015, increasing to AU$118 million in 2030 (50% increase), and additional welfare payments were estimated to rise from $132 million in 2015 to AU$180 in 2030 (36% increase). Larger growth in lost income, compared with the increase in welfare payments, means that there would be an increasing income gap between those out of the labour force providing informal care and noncarers who are in the labour force, leading to increased inequality. Informal carers are defined as providers of informal, unpaid assistance to someone with a health condition, for at least 6 months. Informal carers of people with back pain who are out of the labour force incur substantial economic costs. Furthermore, back pain is a large economic burden on national governments. Policies addressing back pain prevention and treatment, and supporting carers, may offset government welfare expenditure, while improving the socioeconomic well-being of carers and patients.
PCL Transtibial Tunnel Reconstruction
Authors: Fanelli Gregory C.
Published: December 2019

The keys to successful posterior cruciate ligament (PCL) reconstruction are to identify and treat all pathology, use strong graft material, accurately place tunnels in anatomic insertion sites, minimize graft bending, mechanical graft tensioning, secure graft fixation, and the appropriate postoperative rehabilitation program. Adherence to these technical principles results in successful single and double bundle arthroscopic transtibial tunnel PCL reconstruction based upon stress radiography, arthrometer, knee ligament rating scales, and patient satisfaction measurements. The purpose of this article is to describe the arthroscopic transtibial tunnel PCL reconstruction surgical technique.
Anatomy and Biomechanics of the Posterior Cruciate Ligament and Their Surgical Implications
Authors: Arthur Jaymeson R. , Haglin Jack M. , Makovicka Justin L. , Chhabra Anikar
Published: December 2019

Knowledge and understanding of the complex anatomy and biomechanical function of the native posterior cruciate ligament (PCL) is vitally important when evaluating PCL injury and possible reconstruction. The PCL has important relationships with the anterior cruciate ligament, menisci, tibial spines, ligament of Humphrey, ligament of Wrisberg, and the posterior neurovascular structures. Through various experimental designs, the biomechanical role of the PCL has been elucidated. The PCL has its most well-defined role as a primary restraint/stabilizer to posterior stress and it seems this role is greatest at higher degrees of knee flexion. The natural history of high-grade deficiency leads to increased contact pressures and degeneration of both the medial and patellofemoral compartments. There is still considerable debate regarding whether high-level athletes can return to sport at the same level with conservative treatment of a high-grade PCL tear, and whether greater laxity in the knee correlates with decreased subjective and objective outcomes. Poor surgical outcomes after PCL reconstruction have been attributed to many factors, the most common of which include: additional intra-articular pathology, poor fixation methods, insufficient knowledge of PCL anatomy, improper tunnel placement, and poor surgical candidates.
Intrahepatic biliary strictures after liver transplantation are morphologically similar to primary sclerosing cholangitis but immunologically distinct
Authors: Zhou Taotao , Bartelheimer Katja , Ruping Fabian , Rupp Christian , Sauer Peter , Koschny Ronald , Mehrabi Arianeb , Mieth Markus , von Haken Rebecca , Weiss Karl Heinz , Gotthardt Daniel Nils , Rauber Conrad
Published: December 2019

Objective

Biliary strictures are an important cause of morbidity and mortality in primary hepatic disease and after liver transplantation (LT). We aimed to characterize inflammatory cytokines in biliary fluids in biliary strictures to investigate their immunological origin.

Methods

We conducted a retrospective study on 72 patients with strictures after LT, eight patients with primary sclerosing cholangitis (PSC) and 15 patients with secondary sclerosing cholangitis (SSC). We measured cytokines interleukin (IL)-2, -4, -6, -10, -17, monocyte chemoattractant protein (MCP)-1, fibroblast growth factor (FGF)-2 and interferon (IFN)-γ as well as biochemical components such as protein and phospholipids in biliary fluid obtained from endoscopic retrograde cholangiography (ERC). Cell viability assays were performed on human cholangiocytes (H69) after being treated with IL-6, IL-4 and IFN-γ.

Results

Bile of patients with diffuse strictures after LT or due to SSC showed low values of all measured cytokines except for IL-6 levels, which were largely elevated in patients with diffuse strictures after LT. Patients high in biliary IL-6 showed an increase in profibrotic markers FGF-2 and MCP-1. In contrast, PSC bile was dominated by a Th1/Th17 profile with elevated IL-2, IL-17 and IFN-γ. In LT patients with biliary strictures, biliary IL-6 negatively predicted retransplantation-free survival after ERC.

Conclusion

PSC patients showed a biliary Th1/Th17 cytokine profile, while SSC and diffuse strictures showed low values of cytokines except IL-6. In diffuse intrahepatic strictures after LT, biliary IL-6 is strongly associated with retransplantation-free survival after ERC.
Qualitative and quantitative reproducibility of [18]fluoromethycholine PET/computed tomography in prostate cancer
Authors: Pinto-Leite Thomas , Tixier Florent , Upadhaya Taman , Gallais Christelle , Perdrisot Remy , Cheze Le Rest Catherine
Published: December 2019

Background

Recurrence occurs in more than 50% of prostate cancer. To be effective, treatments require precise localization of tumor cells. [18F]fluoromethylcholine ([18F]FCH) PET/computed tomography (CT) is currently used to restage disease in cases of biochemical relapse. To be used for therapy response as has been suggested, repeatability limits of PET derived indices need to be established.

Objective

The aim of our study was to prospectively assess the qualitative and quantitative reproducibility [18F]FCH PET/CT in prostate cancer.

Methods

Patients with histologically proven prostate cancer referred for initial staging or restaging were prospectively included. All patients underwent two [18F]FCH PET/CTs in the same conditions within a maximum of 3 weeks’ time. We studied the repeatability of the visual report and the repeatability of SUVmax and its evolution over the acquisition time in lesions, liver and vascular background. Statistical analysis was performed using the Bland–Altman approach.

Results

Twenty-one patients were included. Reporting repeatability was excellent with 97.8% of concordance. Mean repeatability of SUVmax considering all times and all lesions was 2.2% ± 20. Evolution of SUVmax was unpredictable, either increasing or decreasing over the acquisition time, both for lesions and for physiological activity.

Conclusion

Our study demonstrated that visual report of [18F]FCH PET/CT was very reproducible and that the repeatability limits of SUVmax was similar to those of other PET radiotracers. An SUVmax difference of more than 40% should be considered as representing a treatment response effect. Change of SUVmax during the acquisition time varied and should not be considered as an interpretation criterion.
Immune contexture of cholangiocarcinoma
Authors: Paillet Juliette , Kroemer Guido , Pol Jonathan G.
Published: December 2019

Purpose of review

Considering the failure of standard treatments (i.e. surgery, radiotherapy, chemotherapy) in treating cholangiocarcinoma (CCA), introduction of alternative interventions is urgently needed. During the past 2 decades, discoveries of the mechanisms of cancer immunosurveillance and tumor immune evasion have precipitated the emergence and clinical approval of immunotherapies in multiple malignant indications. Interest in their introduction for the care of CCA is recent and several immunotherapeutic approaches are undergoing a clinical evaluation. Undoubtedly, their efficient application, as monotherapy or in combination regimens, will rely on a deeper understanding of CCA immune contexture.

Recent findings

CCA cells appeared very potent in recruiting protumorigenic cells and shaping an immunosuppressive microenvironment. Elevated densities of several immune cells with immunoinhibitory activities within the malignant bed have been associated with poor prognosis in patients. Particularly, macrophages and neutrophils (especially in their alternatively activated phenotype) were pointed out for their role in cancer progression. Dendritic cells were described as ineffective in priming CCA-specific T-cell responses.

Quantitative and qualitative assessment of the innate and adaptive immune compartments of the CCA immune contexture, as well as their prognostic value, will benefit to the development of improved immunotherapeutic strategies.
Detection and management of acute myeloid leukemia measurable residual disease: is it standard of care?
Authors: Paterno Giovangiacinto , Del Principe Maria Ilaria , Venditti Adriano
Published: December 2019

Purpose of review

In the present manuscript, we will review the current approaches to investigate measurable residual disease (MRD) and its clinical applications in AML management.

Recent findings

Over the last decades, several methods have been developed to trace MRD, with flow cytometry and polymerase chain reaction (PCR) being the most reliable. However, new technologies, such as digital PCR and Next-Generation Sequencing are emerging as particularly useful in AML. The 2017 European LeukemiaNet (ELN) recommendations have incorporated MRD assessment to define the response criteria to therapy, and more recently, the ELN MRD Working Party has published guidelines for the use of MRD in clinical practice.

Morphologic complete remission (mCR) after induction therapy, has been consistently shown not only to have a critical prognostic role but also to fail in predicting relapse on an individual basis. Major attempts to improve our prediction capability have been made by measuring the residual levels of leukemic cells that persist in the bone marrow after chemotherapy. This number of cells, also called MRD, harbors in the bone marrow below the threshold of morphology and is responsible for leukemia recurrence. Therefore, the detection of MRD promises to help predict the risk of relapse, allowing a more proper patients’ risk-stratification and the use of risk-tailored therapeutic strategy.
Lasers for stone treatment: how safe are they?
Authors: Noureldin Yasser A. , Kallidonis Panagiotis , Liatsikos Evangelos N.
Published: December 2019

Purpose of review

To update laser lithotripsy advances in regard to new laser types and technologies as well as review contemporary laser safety concerns.

Recent findings

The high prevalence of urolithiasis and the continuing miniaturization of scopes has encouraged the growth of laser lithotripsy technology. The holmium:yttrium-aluminum-garnet (Ho:YAG) laser has been used for over 20 years in endourology and has been extensively studied. Holmium laser power output is affected by a number of factors, including pulse energy, pulse frequency, and pulse width. Several recent experimental studies suggest that the new dual-phase Moses ‘pulse modulation’ technology, introduced in high-power laser machines, carries a potential to increase stone ablation efficiency and decrease stone retropulsion. A newly introduced thulium fiber laser (TFL) has been adapted to a very small laser fiber size and is able to generate very low pulse energy and very high pulse frequency. Both of these technologies promise to play a larger role in laser lithotripsy in the near future. However, more experimental and clinical studies are needed to expand on these early experimental findings. Even though laser lithotripsy is considered safe, precautions should be taken to avoid harmful or even catastrophic adverse events to the patient or the operating room staff.

The Ho:YAG laser remains the clinical gold standard for laser lithotripsy for over the last two decades. High-power Ho:YAG laser machines with Moses technology have the potential to decrease stone retropulsion and enhance efficiency of laser ablation. The new TFL has a potential to compete with and perhaps even replace the Ho:YAG laser for laser lithotripsy. Safety precautions should be taken into consideration during laser lithotripsy.
Risk factors and molecular characterization of penile cancer: impact on prognosis and potential targets for systemic therapy
Authors: Thomas Anita , Vanthoor Joren , Vos Gigi , Tsaur Igor , Albersen Maarten
Published: December 2019

Purpose of review

To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa).

Recent findings

E2F, LAMC2, MAML2, ID1 and IGFBP2 proteins were demonstrated to play a critical role for aggressive tumor behavior and might predict poor survival in PeCa. PD-L1 axis was confirmed as a promising pathway to serve as a therapeutic target. A number of genetic alterations were illuminated. In clinical testing, pan-HER tyrosine kinase inhibitor dacomitinib provided promising results in chemo-naïve and EGFR monoantibody nimotuzumab in chemotherapy-failed PeCa patients.

Knowledge of prognosis-relevant altered molecular pathways in PeCa is expanding paving the way for identification of potential therapeutic targets. Multicenter clinical trials in the setting of centralized PeCa care are warranted to foster effective marker-based individualized treatment strategies.
Evaluation of the Coagulation Profile With Rotational Thromboelastometry in Children With Hereditary Spherocytosis
Authors: Özdemir Zeynep C. , Kar Yeter Düzenli , Gündüz Eren , Bör Özcan
Published: December 2019

Hereditary spherocytosis (HS) is a familial hemolytic disorder associated with a variety of mutations that lead to defects in red blood cell (RBC) membrane proteins. There is increasing evidence that hypercoagulability occurs in chronic hemolytic anemia. In this study, changes in the coagulation profile in children with HS were investigated using rotational thromboelastometry. A total of 21 children with HS and 28 healthy children were enrolled in the study between October 2010 and October 2018. Complete blood count, prothrombin time, activated partial thromboplastin time, and fibrinogen level were ascertained, while rotational thromboelastometry assays were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. There was no difference between the 2 groups in terms of age and sex. The values of hemoglobin and RBC in the patient group were statistically significantly lower than those in the control group (P<0.01, <0.0001, respectively), and the values of platelet count, mean corpuscular hemoglobin concentration, and RBC distribution width were statistically significantly higher than those in the control group (P<0.05, 0.001, <0.0001, respectively). There was no statistically significant difference between the 2 groups in terms of prothrombin time, activated partial thromboplastin time, fibrinogen levels, coagulation time, clot formation time, and maximum clot firmness values. In contrast to other chronic hemolytic anemias, no predisposition to hypercoagulability has been shown in the coagulation profile of children with HS without splenectomy.
Evaluating Dimensions of Fatigue in Men With Prostate Cancer Receiving Radiation Therapy
Authors: Dickinson Kristin , Kupzyk Kevin , Saligan Leorey
Published: December 2019

Background

Cancer-related fatigue (CRF) is a complex multidimensional symptom. Identifying the fatigue dimension that may be most bothersome can guide in the development of individualized management strategies.

Objective

The purpose of this article is to describe the multidimensional fatigue experience of men with prostate cancer.

Methods

Data for this study were obtained from an ongoing descriptive longitudinal study at the National Institutes of Health, involving men diagnosed with nonmetastatic prostate cancer scheduled to receive external beam radiation therapy. Data were analyzed at 7 time points: baseline, before treatment initiation (T1), treatment midpoint (T2), treatment completion (T3), and 1 month (T4), 3 months (T5), 6 months (T6), and 12 months (T7) after treatment completion. Study data were obtained from medical records and self-report (fatigue, depressive symptoms, and sleep disturbance) questionnaires.

Results

Scores for total fatigue peaked at T2 and remained significantly different from baseline at T3. After T3, total fatigue scores were not significantly different from baseline. Affective fatigue had the highest scores (worst fatigue) reported during treatment, sensory fatigue scores were highest from T4 to T6, and cognitive fatigue scores were highest at T7. Affective and sensory fatigue scores peaked at T2, whereas behavioral and cognitive fatigue scores peaked at T3.

Conclusion

Independent changes in specific dimensions of CRF were observed during and post treatment.

Implications for Practice

Understanding the specific dimensions of CRF and how they change during and post treatment can help guide clinicians to recommend targeted and personalized management strategies.