bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment
Authors: Kawachi Yusuke , Fujishima Yuya , Nishizawa Hitoshi , Nagao Hirofumi , Nakamura Takashi , Akari Seigo , Murase Takayo , Taya Naohiro , Omori Kazuo , Miyake Akimitsu , Fukuda Shiro , Takahara Mitsuyoshi , Kita Shunbun , Katakami Naoto , Maeda Norikazu , Shimomura Iichiro
Published: November 2020

Aims/Introduction

Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine and xanthine to xanthine and uric acid, respectively. Plasma XOR activity has recently been measured in humans. However, limited information is known about plasma XOR activity in patients with type 2 diabetes mellitus, and its changes after short‐term glycemic control treatment.

Materials and Methods

We enrolled 28 Japanese patients (10 men/18 women) with type 2 diabetes mellitus who were hospitalized to undergo medical treatment for diabetes. Plasma XOR activity, quantified using triple quadrupole mass spectrometry and liquid chromatography, and other clinical parameters were examined at admission and 2 weeks after treatment during hospitalization. Changes in plasma XOR activity after treatment during hospitalization and associated clinical parameters were assessed.

Results

At the time of admission, the median plasma XOR activity was 83.1 pmol/h/mL, with a wide range of 14.4–1150 pmol/h/mL. Multiple regression analysis identified serum aspartate transaminase and alanine transaminase levels as significant and independent factors correlating with the baseline plasma XOR. Two weeks of treatment during hospitalization was associated with a significant decrease in plasma XOR activity. Changes in serum aspartate transaminase were also the only significant and independent factor correlating with changes in plasma XOR activity.

Conclusions

A close relationship was observed between plasma XOR activity and liver transaminases in patients with type 2 diabetes mellitus, cross‐sectionally, and also across treatment during hospitalization.
A nationwide initiative to increase nursing and midwifery research leadership: overview of year one programme development, implementation and evaluation
Authors: Henshall Catherine , Greenfield Diana M. , Jarman Heather , Rostron Heather , Jones Helen , Barrett Sharon
Published: November 2020

Aims and objectives

To report on the development, implementation and evaluation of the first year of the National Institute for Health Research 70@70 Senior Nurse Research Leader Programme.

Background

Internationally, there is a lack of nursing and midwifery research and policy contribution to healthcare sectors. To address this, funding was obtained for a Senior Nurse and Midwife Research Leader Programme in England. The programme aimed to increase nursing and midwifery research capacity and capability and support the development of future research leaders.

Design

The programme had three phases: development, implementation and evaluation. The cohort study's evaluation phase consisted of a survey and qualitative written feedback.

Methods

An online survey was sent to cohort members (n = 66). Quantitative survey data was analysed in Survey Monkey. Written feedback asked cohort members to summarise their activities and any challenges. Data were thematically analysed. The “Strengthening the Reporting of Observational Studies in Epidemiology” reporting checklist was used.

Results

Thirty‐nine (59%) cohort members responded to the survey. Responders valued being part of a network (46%), having protected time (22%) and having workplace autonomy (13%). Challenges reported included difficulties accessing online resources (32%), lack of collaborative opportunities (17%) and organisational barriers (10%). Fifty‐six (85%) cohort members submitted the written report. The main themes were “relationship and profile building”, “developing capability and capacity”, “developing the workforce”, “patient and public involvement and engagement” and “quality improvement.”

Conclusions

The 70@70 programme has increased the research profile of the nursing and midwifery professions at a local and national level. International healthcare systems can learn from this, by considering optimal ways to provide nurses and midwives with the tools, resources and confidence to actively contribute to research policy and practice.

Relevance to Clinical Practice

The initiatives undertaken through year 1 of the programme have created a platform through which research can be incorporated into clinical practice, education and teaching.
Effect of preventing air intrusion on silent strokes during atrial fibrillation ablation using a mini‐basket catheter
Authors: Nakamura Kohki , Sasaki Takehito , Take Yutaka , Minami Kentaro , Sasaki Wataru , Kishi Shohei , Yoshimura Shingo , Okazaki Yoshinori , Miki Yuko , Goto Koji , Kaseno Kenichi , Yamashita Eiji , Koyama Keiko , Funabashi Nobusada , Naito Shigeto
Published: November 2020

Background

Air bubble intrusion through transseptal sheaths during left atrial (LA) catheter ablation can cause cerebral embolisms, especially when using complex‐shape catheters. This study aimed to compare the incidence of silent cerebral events (SCEs) after atrial fibrillation (AF) catheter ablation using a mini‐basket catheter (IntellaMap Orion; Boston Scientific) between the following groups: group SP, strict prevention of LA air intrusion and group CP, conventional air intrusion prevention.

Methods

We enrolled 123 consecutive AF patients (group SP, n = 61 and group CP, n = 62) who underwent brain magnetic resonance imaging after a local‐impedance‐guided ablation using one mini‐basket catheter and one circular mapping catheter. The preventive strategy in group SP included (a) the insertion of the mini‐basket catheter into the transseptal sheaths in a container filled with heparinized saline and (b) no exchange of all catheters over the sheaths.

Results

SCEs were detected in 67 patients (54.5%), and the incidence of SCEs did not significantly differ between groups SP and CP (55.7% vs 53.2%; P = .780). A multivariate analysis demonstrated that an older age, non‐paroxysmal AF, and radiofrequency (RF) power output were independent positive predictors of SCEs (odds ratios: 1.079, 5.613, and 1.405; P = .005, <.001, and .012). On the follow‐up MR imaging, 83.5% of the SCEs in group SP and 87.7% in group CP disappeared (P = .398).

Conclusions

Strict prevention of LA air intrusion may have no additional effect for reducing the incidence of SCEs after local impedance‐guided AF ablation using a mini‐basket catheter. An older age, non‐paroxysmal AF, and high‐power RF applications may increase the risk of SCEs.
Plant sugars: Homeostasis and transport under abiotic stress in plants
Authors: Saddhe Ankush A. , Manuka Rakesh , Penna Suprasanna
Published: November 2020

The sessile nature of plants' life is endowed with a highly evolved defense system to adapt and survive under environmental extremes. To combat such stresses, plants have developed complex and well‐coordinated molecular and metabolic networks encompassing genes, metabolites, and acclimation responses. These modulate growth, photosynthesis, osmotic maintenance, and carbohydrate homeostasis. Under a given stress condition, sugars act as key players in stress perception, signaling, and are a regulatory hub for stress‐mediated gene expression ensuring responses of osmotic adjustment, scavenging of reactive oxygen species, and maintaining the cellular energy status through carbon partitioning. Several sugar transporters are known to regulate carbohydrate partitioning and key signal transduction steps involved in the perception of biotic and abiotic stresses. Sugar transporters such as SUGARS WILL EVENTUALLY BE EXPORTED TRANSPORTER (SWEETs), SUCROSE TRANSPORTERS (SUTs), and MONOSACCHARIDE TRANSPORTERS (MSTs) are involved in sugar loading and unloading as well as long‐distance transport (source to sink) besides orchestrating oxidative and osmotic stress tolerance. It is thus necessary to understand the structure–function relationship of these sugar transporters to fine‐tune the abiotic stress‐modulated responses. Advances in genomics have unraveled many sugars signaling components playing a key role in cross‐talk in abiotic stress pathways. An integrated omics approach may aid in the identification and characterization of sugar transporters that could become targets for developing stress tolerance plants to mitigate climate change effects and improve crop yield. In this review, we have presented an up‐to‐date analysis of the sugar homeostasis under abiotic stresses as well as describe the structure and functions of sugar transporters under abiotic stresses.
Plasma polymerization of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl in a collisional, capacitively coupled radio frequency discharge
Authors: Barnes Michael J. , Robson Alexander J. , Naderi Javad , Short Robert D. , Bradley James W.
Published: November 2020

Plasma polymerization of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) yields thin films containing stable nitroxide radicals that have properties analogous to that of nitric oxide (NO) without short lifetimes. This property gives TEMPO films a wide variety of potential applications. Typically, control of the final film chemistry is difficult and the plasma discharge conditions must be tailored to in order to maximize the retention of these nitroxide groups during the polymerization and deposition process. In this study, plasma diagnostics and surface analysis of the deposited films were carried out to determine the optimal plasma conditions for the retention of nitroxide groups. These techniques included energy-resolved mass spectrometry, heated planar probe ion current measurements, deposition rate measurements, and x-ray photoelectron spectroscopy (XPS). Results show that operating the plasma with a combination of low input powers and high pressures produces a collisional discharge in which fragmentation of the TEMPO molecule is suppressed, leading to good retention of nitroxide groups. Ion energy distribution functions and quartz crystal microbalance measurements support the soft landing theory of ion deposition on the substrate within this γ-mode, in which the flux of low energy, soft landed ions form the primary contribution to film growth. XPS analysis of deposited polymers shows 75.7% retention of N—O groups in the polymer films deposited in a 25 Pa 5 W discharge.
Assessment of the frequency and nature of erroneous x-ray photoelectron spectroscopy analyses in the scientific literature
Authors: Major George H. , Avval Tahereh G. , Moeini Behnam , Pinto Gabriele , Shah Dhruv , Jain Varun , Carver Victoria , Skinner William , Gengenbach Thomas R. , Easton Christopher D. , Herrera-Gomez Alberto , Nunney Tim S. , Baer Donald R. , Linford Matthew R.
Published: November 2020

This study was undertaken to understand the extent and nature of problems in x-ray photoelectron spectroscopy (XPS) data reported in the literature. It first presents an assessment of the XPS data in three high-quality journals over a six-month period. This analysis of 409 publications showing XPS spectra provides insight into how XPS is being used, identifies the common mistakes or errors in XPS analysis, and reveals which elements are most commonly analyzed. More than 65% of the 409 papers showed fitting of XP spectra. An ad hoc group (herein identified as “the committee”) of experienced XPS analysts reviewed these spectra and found that peak fitting was a common source of significant errors. The papers were ranked based on the perceived seriousness of the errors, which ranged from minor to major. Major errors, which, in the opinion of the ad hoc committee, can render the interpretation of the data meaningless, occurred when fitting protocols ignored underlying physics and chemistry or contained major errors in the analysis. Consistent with other materials analysis data, ca. 30% of the XPS data or analysis was identified as having major errors. Out of the publications with fitted spectra, ca. 40% had major errors. The most common elements analyzed by XPS in the papers sampled and researched at an online database, include carbon, oxygen, nitrogen, sulfur, and titanium. A scrutiny of the papers showing carbon and oxygen XPS spectra revealed the classes of materials being studied and the extent of problems in these analyses. As might be expected, C 1s and O 1s analyses are most often performed on sp2-type materials and inorganic oxides, respectively. These findings have helped focus a series of XPS guides and tutorials that deal with common analysis issues. The extent of problematic data is larger than the authors had expected. Quantification of the problem, examination of some of the common problem areas, and the development of targeted guides and tutorials may provide both the motivation and resources that enable the community to improve the overall quality and reliability of XPS analysis reported in the literature.
China set to bring back rocks from the Moon
Authors: Normile Dennis
Published: November 2020

Chang'e-5's lunar samples could firm up shaky crater count dating system for the rocky planets.
Tissue topography steers migrating
Drosophila
border cells
Authors: Dai Wei , Guo Xiaoran , Cao Yuansheng , Mondo James A. , Campanale Joseph P. , Montell Brandon J. , Burrous Haley , Streichan Sebastian , Gov Nir , Rappel Wouter-Jan , Montell Denise J.
Published: November 2020

Cells and the path of least resistance

For processes encompassing proper embryonic development, adult homeostasis, tumor cell dissemination, and immunity, certain cells must translocate from their site of origin. Migrating cells navigate physical features of their microenvironment; however, the in vivo importance of tissue topography for pathfinding is mostly unknown. Studying fruit flies, Dai
et al.
used border cells within the ovarian egg chamber to study path selection. Live imaging, genetics, mathematical modeling, and simulations showed that tissue microtopography provides an energetically favorable path of least resistance, whereas chemoattractants supply orthogonal guidance information and cell-cell adhesion contributes traction. The results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many.

Science
, this issue p.
987
Fire and biodiversity in the Anthropocene
Authors: Kelly Luke T. , Giljohann Katherine M. , Duane Andrea , Aquilué Núria , Archibald Sally , Batllori Enric , Bennett Andrew F. , Buckland Stephen T. , Canelles Quim , Clarke Michael F. , Fortin Marie-Josée , Hermoso Virgilio , Herrando Sergi , Keane Robert E. , Lake Frank K. , McCarthy Michael A. , Morán-Ordóñez Alejandra , Parr Catherine L. , Pausas Juli G. , Penman Trent D. , Regos Adrián , Rumpff Libby , Santos Julianna L. , Smith Annabel L. , Syphard Alexandra D. , Tingley Morgan W. , Brotons Lluís
Published: November 2020

Fire's growing impacts on ecosystems

Fire has played a prominent role in the evolution of biodiversity and is a natural factor shaping many ecological communities. However, the incidence of fire has been exacerbated by human activity, and this is now affecting ecosystems and habitats that have never been fire prone or fire adapted. Kelly
et al.
review how such changes are already threatening species with extinction and transforming terrestrial ecosystems and discuss the trends causing changes in fire regimes. They also consider actions that could be taken by conservationists and policy-makers to help sustain biodiversity in a time of changing fire activity.

Science
, this issue p.
eabb0355
Experimental observation of the liquid-liquid transition in bulk supercooled water under pressure
Authors: Kim Kyung Hwan , Amann-Winkel Katrin , Giovambattista Nicolas , Späh Alexander , Perakis Fivos , Pathak Harshad , Parada Marjorie Ladd , Yang Cheolhee , Mariedahl Daniel , Eklund Tobias , Lane Thomas. J. , You Seonju , Jeong Sangmin , Weston Matthew , Lee Jae Hyuk , Eom Intae , Kim Minseok , Park Jaeku , Chun Sae Hwan , Poole Peter H. , Nilsson Anders
Published: November 2020

Liquid-liquid transitions under pressure

Theoretical simulations suggest that deeply supercooled water undergoes a transition between high- and low-density forms, but this transition is difficult to study experimentally because it occurs under conditions in which ice crystallization is extremely rapid. Kim
et al.
combined x-ray lasers for rapid structure determination with infrared femtosecond pulses for rapid heating of amorphous ice layers formed at about 200 kelvin. The heating process created high-density liquid water at increased pressures. As the layer expanded and decompressed, low-density liquid domains appeared and grew on time scales between 20 nanoseconds and 3 microseconds, which was much faster than competing ice crystallization.

Science
, this issue p.
978
Comment on “Ancient origins of allosteric activation in a Ser-Thr kinase”
Authors: Park Yeonwoo , Patton Jaeda E. J. , Hochberg Georg K. A. , Thornton Joseph W.
Published: November 2020

Hadzipasic
et al
. (Reports, 21 February 2020, p. 912) used ancestral sequence reconstruction to identify historical sequence substitutions that putatively caused Aurora kinases to evolve allosteric regulation. We show that their results arise from using an implausible phylogeny and sparse sequence sampling. Addressing either problem reverses their inferences: Allostery and the amino acids that confer it were not gained during the diversification of eukaryotes but were lost in a subgroup of Fungi.
Oceanic plateau of the Hawaiian mantle plume head subducted to the uppermost lower mantle
Authors: Wei Songqiao Shawn , Shearer Peter M. , Lithgow-Bertelloni Carolina , Stixrude Lars , Tian Dongdong
Published: November 2020

Finding the Emperor's head

Volcanic island and seamount chains form from deep-seated plumes of hot material upwelling through the mantle. The most famous of these is the Hawaiian-Emperor seamount chain. However, a large volcanic structure associated with a plume head that should precede the chain has long been missing. Wei
et al.
finally identified the likely location of this structure in the mantle under eastern Russia. The structure was likely subducted 20 million to 30 million years ago, and the location helps constrain several geodynamic processes.

Science
, this issue p.
983
How directed evolution reshapes the energy landscape in an enzyme to boost catalysis
Authors: Otten Renee , Pádua Ricardo A. P. , Bunzel H. Adrian , Nguyen Vy , Pitsawong Warintra , Patterson MacKenzie , Sui Shuo , Perry Sarah L. , Cohen Aina E. , Hilvert Donald , Kern Dorothee
Published: November 2020

Two steps forward—now look back

Whether designed computationally or uncovered in activity screening, enzymes repurposed for biocatalysis rarely start at the peak of proficiency. However, directed evolution can in some cases increase catalytic efficiency of a poor enzyme by many orders of magnitude. Otten
et al.
used a suite of biochemical techniques to investigate the origins of rate enhancement in a previously evolved model enzyme. Two conformational states are present in the initial, computationally designed enzyme, but only one is active. Shifting the population toward the active state is one factor in increasing catalytic efficiency during evolution. Single mutations do not greatly increase activity, but the synergistic combination of just two out of 17 substitutions can provide most of the rate enhancement seen in the final, evolved enzyme.

Science
, this issue p.
1442
The molecular wagon that stays on track
Authors: Esch Friedrich , Lechner Barbara A. J.
Published: November 2020

Single molecules are sent and received accurately over long distances across a surface
Alphabets and their origins
A to Z: The First Alphabet
David Sington, director
NOVA, 2020. 54 minutes.
A to Z: How Writing Changed the World
David Sington, director
NOVA, 2020. 54 minutes.
Authors: Robinson Andrew
Published: November 2020

A new documentary series surveys the inception and evolution of the written word
HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV
Authors: Milewska Aleksandra , Chi Ying , Szczepanski Artur , Barreto-Duran Emilia , Dabrowska Agnieszka , Botwina Pawel , Obloza Magdalena , Liu Kevin , Liu Dan , Guo Xiling , Ge Yiyue , Li Jingxin , Cui Lunbiao , Ochman Marek , Urlik Maciej , Rodziewicz-Motowidlo Sylwia , Zhu Fengcai , Szczubialka Krzysztof , Nowakowska Maria , Pyrc Krzysztof
Published: November 2020

The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats.
Cardiorespiratory monitoring in the delivery room using transcutaneous electromyography
Authors: van Leuteren Ruud W , Kho Eline , de Waal Cornelia G , te Pas Arjan B , Salverda Hylke H , de Jongh Frans H , van Kaam Anton H , Hutten Gerard J
Published: November 2020

Objective

To assess feasibility of transcutaneous electromyography of the diaphragm (dEMG) as a monitoring tool for vital signs and diaphragm activity in the delivery room (DR).

Design

Prospective observational study.

Setting

Delivery room.

Patients

Newborn infants requiring respiratory stabilisation after birth.

Interventions

In addition to pulse oximetry (PO) and ECG, dEMG was measured with skin electrodes for 30 min after birth.

Outcome measures

We assessed signal quality of dEMG and ECG recording, agreement between heart rate (HR) measured by dEMG and ECG or PO, time between sensor application and first HR read-out and agreement between respiratory rate (RR) measured with dEMG and ECG, compared with airway flow. Furthermore, we analysed peak, tonic and amplitude diaphragmatic activity from the dEMG-based respiratory waveform.

Results

Thirty-three infants (gestational age: 31.7±2.8 weeks, birth weight: 1525±661 g) were included.

18%±14% and 22%±21% of dEMG and ECG data showed poor quality, respectively. Monitoring HR with dEMG was fast (median 10 (IQR 10–11) s) and accurate (intraclass correlation coefficient (ICC) 0.92 and 0.82 compared with ECG and PO, respectively). RR monitoring with dEMG showed moderate (ICC 0.49) and ECG low (ICC 0.25) agreement with airway flow. Diaphragm activity started high with a decreasing trend in the first 15 min and subsequent stabilisation.

Conclusion

Monitoring vital signs with dEMG in the DR is feasible and fast. Diaphragm activity can be detected and described with dEMG, making dEMG promising for future DR studies.
Identifying opportunities for health promotion and intervention in the ED
Authors: Robson Simon , Stephenson Andrew , McCarthy Colm , Lowe David , Conlen Ben , Gray Alasdair James
Published: November 2020

Background

ED staff assess patients with modifiable risk factors for acute and chronic illness. Health promotion interventions delivered in the ED have been advocated for these patients. The engagement of staff is essential to provide effective screening and brief interventions for patients. This survey aimed to assess if staff support the ED as an environment for health promotion.

Methods

A multicentre, structured survey was conducted in four EDs in Scotland from 2017 to 2018. Physician and nursing staff at two teaching and two district general hospitals (n=423) were study eligible and offered a multicomponent survey. Outcomes measured included perceived barriers to practice and risk factor specific ED interventions.

Results

Of the 283 respondents, 116 (41%) were physicians and 167 (59%) were nurses. More physicians (86.1%) than nurses (49.7%) reported offering health promotion interventions. Time constraints and a lack of health promotion infrastructure in the ED were cited as challenges to intervention delivery. Staff believed that alcohol (n=170/283, 60.1%) and drug misuse (n=173/283, 61.1%) were more appropriately managed in the ED than primary care. ED staff believed same day brief interventions were more appropriate when alcohol/drug misuse and smoking were directly related to ED presentations.

Discussion and conclusions

Staff support the concept of the ED as a potential environment for offering health promotion interventions. ED physicians and nurses have different perspectives on the delivery of health promotion. The role of the ED in health promotion is likely to be multimodal and dependant on the reason for ED attendance.
RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer
Authors: Sun Lei , Wan Arabella , Zhou Zhuolong , Chen Dongshi , Liang Heng , Liu Chuwei , Yan Shijia , Niu Yi , Lin Ziyou , Zhan Siyue , Wang Shanfeng , Bu Xianzhang , He Weiling , Lu Xiongbin , Xu Anlong , Wan Guohui
Published: November 2020

Objective

Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood.

Design

We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models.

Results

We identified a novel RNA-binding protein, RALY (also known as hnRNPCL2), that is highly associated with colorectal tumour aggressiveness. RALY acts as a key regulatory component in the Drosha complex, and promotes the post-transcriptional processing of a specific subset of miRNAs (miR-483, miR-676 and miR-877). These miRNAs systematically downregulate the expression of the metabolism-associated genes (ATP5I, ATP5G1, ATP5G3 and CYC1) and thereby reprogramme mitochondrial metabolism in the cancer cell. Analysis of The Cancer Genome Atlas (TCGA) reveals that increased levels of RALY are associated with poor prognosis in the patients with CRC expressing low levels of mitochondrion-associated genes. Mechanistically, induced processing of these miRNAs is facilitated by their N6-methyladenosine switch under reactive oxygen species (ROS) stress. Inhibition of the m6A methylation abolishes the RALY recognition of the terminal loop of the pri-miRNAs. Knockdown of RALY inhibits colorectal tumour growth and progression in vivo and in organoid models.

Conclusions

Collectively, our results reveal a critical metabolism-centric role of RALY in tumour progression, which may lead to cancer therapeutics targeting RALY for treating CRC.
Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial)
Authors: Kandiah Kesavan , Subramaniam Sharmila , Thayalasekaran Sreedhari , Chedgy Fergus JQ , Longcroft-Wheaton Gaius , Fogg Carole , Brown James F , Smith Samuel CL , Iacucci Marietta , Bhandari Pradeep
Published: November 2020

Background

Longstanding colonic IBD increases the risk of developing colorectal cancer. The utility of chromoendoscopy with standard-definition white light technology has been established. However, the use of high-definition virtual chromoendoscopy (HDV) in colitis surveillance remains undefined.

Objective

To compare the performance of HDV (i-scan OE mode 2) with high-definition white light (HDWL) for detection of neoplasia in patients with IBD undergoing surveillance colonoscopy. Additionally, we assessed the utility of protocol-guided quadrantic non-targeted biopsies.

Design

A multioperator randomised controlled trial was carried out in two centres in the UK. Total of 188 patients (101 men, mean age 54) with longstanding ulcerative or Crohn’s colitis were randomised, prior to starting the surveillance colonoscopy, to using either HDV (n=94) or HDWL (n=94) on withdrawal. Targeted and quadrantic non-targeted biopsies were taken in both arms per-randomisation protocol. The primary outcome was the difference in neoplasia detection rate (NDR) between HDV and HDWL.

Results

There was no significant difference between HDWL and HDV for neoplasia detection. The NDR was not significantly different for HDWL (24.2%) and HDV (14.9%) (p=0.14). All intraepithelial neoplasia (IEN) detected contained low-grade dysplasia only. A total of 6751 non-targeted biopsies detected one IEN only. The withdrawal time was similar in both arms of the study; median of 24 min (HDWL) versus 25.5 min (HDV).

Conclusion

HDV and HDWL did not differ significantly in the detection of neoplasia. Almost all neoplasia were detected on targeted biopsy or resection. Quadrantic non-targeted biopsies have negligible additional gain.

Trial registration number

Clinical Trial.gov IDNCT02822352.
Integration of computer-aided automated analysis algorithms in the development and validation of immunohistochemistry biomarkers in ovarian cancer
Authors: Gentles Lucy , Howarth Rachel , Lee Won Ji , Sharma-Saha Sweta , Ralte Angela , Curtin Nicola , Drew Yvette , O'Donnell Rachel Louise
Published: November 2020

In an era when immunohistochemistry (IHC) is increasingly depended on for histological subtyping, and IHC-determined biomarker informing rapid treatment choices is on the horizon; reproducible, quantifiable techniques are required. This study aimed to compare automated IHC scoring to quantify 6 DNA damage response protein markers using a tissue microarray of 66 ovarian cancer samples. Accuracy of quantification was compared between manual H-score and computer-aided quantification using Aperio ImageScope with and without a tissue classification algorithm. High levels of interobserver variation was seen with manual scoring. With automated methods, inclusion of the tissue classifier mask resulted in greater accuracy within carcinomatous areas and an overall increase in H-score of a median of 11.5% (0%–18%). Without the classifier, the score was underestimated by a median of 10.5 (5.2–25.6). Automated methods are reliable and superior to manual scoring. Fixed algorithms offer the reproducibility needed for high-throughout clinical applications.
Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma
Authors: Kim Jung Hee , Kim Man Jin , Kong Sung Hye , Kim Su Jin , Kang Hyein , Shin Chan Soo , Park Sung Sup , Lee Kyu Eun , Seong Moon-Woo
Published: November 2020

Background

Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing neuroendocrine tumours. PPGLs are a rare but important cause of secondary hypertension owing to their high morbidity and mortality. Patients with PPGL exhibit an increased prevalence of mutations in one of the PPGL susceptibility genes according to previous studies. We aimed to investigate the characteristics of germline mutations in the largest number of Korean patients with PPGL.

Methods

In this study, 161 patients with PPGL were evaluated. Phenotype data, including biochemical, pathological and anatomical imaging results, were collected. Germline mutations in 10 PPGL-related genes were tested by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification.

Results

Approximately 21% of apparently sporadic PPGLs harboured germline mutations of the PPGL-related genes. The mutation carriers were younger at the first diagnosis and had more bilateral (28.6% vs 4.0%, p<0.001) and multifocal (11.4% vs 1.6%, p=0.027) PPGLs, but showed no metastatic risk (17.1% vs 11.1%, p=0.504), than non-mutation carriers. Missense mutation ofSDHDp.V111I was found in this cohort of Asian patients, which was associated with unilateral pheochromocytoma with dominantly epinephrine production.

Conclusion

This study covered the largest number of Korean patients with PPGL. To our knowledge, it is the first to compare results of targeted NGS panel with those of conventional sequencing methods in Asia. We demonstrated that the variant type, as well as the mutated gene, may determine the phenotype and prognosis of PPGLs.
Fully automated cognitive screening tool based on assessment of speech and language
Authors: O'Malley Ronan Peter Daniel , Mirheidari Bahman , Harkness Kirsty , Reuber Markus , Venneri Annalena , Walker Traci , Christensen Heidi , Blackburn Dan
Published: November 2020

Introduction

Recent years have seen an almost sevenfold rise in referrals to specialist memory clinics. This has been associated with an increased proportion of patients referred with functional cognitive disorder (FCD), that is, non-progressive cognitive complaints. These patients are likely to benefit from a range of interventions (eg, psychotherapy) distinct from the requirements of patients with neurodegenerative cognitive disorders. We have developed a fully automated system, ‘CognoSpeak’, which enables risk stratification at the primary–secondary care interface and ongoing monitoring of patients with memory concerns.

Methods

We recruited 15 participants to each of four groups: Alzheimer’s disease (AD), mild cognitive impairment (MCI), FCD and healthy controls. Participants responded to 12 questions posed by a computer-presented talking head. Automatic analysis of the audio and speech data involved speaker segmentation, automatic speech recognition and machine learning classification.

Results

CognoSpeak could distinguish between participants in the AD or MCI groups and those in the FCD or healthy control groups with a sensitivity of 86.7%. Patients with MCI were identified with a sensitivity of 80%.

Discussion

Our fully automated system achieved levels of accuracy comparable to currently available, manually administered assessments. Greater accuracy should be achievable through further system training with a greater number of users, the inclusion of verbal fluency tasks and repeat assessments. The current data supports CognoSpeak’s promise as a screening and monitoring tool for patients with MCI. Pending confirmation of these findings, it may allow clinicians to offer patients at low risk of dementia earlier reassurance and relieve pressures on specialist memory services.
Suggestibility in functional neurological disorder: a meta-analysis
Authors: Wieder Lillian , Brown Richard , Thompson Trevor , Terhune Devin B.
Published: November 2020

Objective

Responsiveness to direct verbal suggestions (suggestibility) has long been hypothesised to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether patients with FND display elevated suggestibility relative to controls via meta-analysis.

Methods

Four electronic databases were searched in November 2019, with the search updated in April 2020, for original studies assessing suggestibility using standardised behavioural scales or suggestive symptom induction protocols in patients with FND (including somatisation disorder) and controls. The meta-analysis followed Cochrane, Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Data extraction and study quality coding were performed by two independent reviewers. Standardised suggestibility scores and responsiveness to symptom induction protocols were used to calculate standardised mean differences (SMDs) between groups.

Results

Of 26 643 search results, 19 articles presenting 11 standardised suggestibility data sets (FND: n=316; control: n=360) and 11 symptom suggestibility data sets (FND: n=1285; control: n=1409) were included in random-effect meta-analyses. Meta-analyses revealed that patients with FND displayed greater suggestibility than controls on standardised behavioural scales (SMD, 0.48 (95% C, 0.15 to 0.81)) and greater responsiveness to suggestive symptom induction (SMD, 1.39 (95% CI 0.92 to 1.86)). Moderation analyses presented mixed evidence regarding the extent to which effect sizes covaried with methodological differences across studies. No evidence of publication bias was found.

Conclusions

These results corroborate the hypothesis that FND is characterised by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.
Neuromyelitis optica spectrum disorder: pregnancy-related attack and predictive risk factors
Authors: Wang Liang , Zhou Lei , ZhangBao Jingzi , Huang Wenjuan , Chang Xuechun , Lu Chuanzhen , Wang Min , Li Wenyu , Xia Junhui , Li Xiang , Chen Lilin , Qiu Wei , Lu Jiahong , Zhao Chongbo , Quan Chao
Published: November 2020

Objectives

To investigate the influence of pregnancy on patients with neuromyelitis optica spectrum disorder (NMOSD) and to identify risk factors that predict pregnancy-related attack.

Methods

From January 2015 to April 2019, 418 female patients with NMOSD were registered at Huashan Hospital. We retrospectively reviewed their medical records and identified 110 patients with 136 informative pregnancies, of whom 83 were aquaporin-4 antibody (AQP4-ab)-positive and 21 were myelin oligodendrocyte glycoprotein-antibody-positive. Pregnancy-related attack was deﬁned as an attack that occurred during pregnancy or within 1 year after delivery/abortion. We compared annualised relapse rate (ARR) during 12 months before pregnancy with that during every trimester of pregnancy and after delivery/abortion. Multivariate analyses were used to explore the independent risk factors involved and a nomogram was generated for the prediction of pregnancy-related attack. Thirty-five female patients from 3 other centres formed an external cohort to validate this nomogram.

Results

ARR increased significantly during the first trimester after delivery (p<0.001) or abortion (p=0.019) compared with that before pregnancy. Independent risk factors predicting pregnancy-related attack included age at delivery/abortion (20–26.5, p=0.018; 26.5–33, p=0.001), AQP4-ab titre (≥1:100, p=0.049) and inadequate treatment during pregnancy and postpartum period (p=0.004). The concordance index of nomogram was 0.87 and 0.77 using bootstrap resampling in internal and external validation.

Conclusions

The first trimester post partum is a high-risk period for NMOSD recurrence. Patients with younger age, higher AQP4-ab titre and inadequate treatment are at higher risk for pregnancy-related attack.
Anti-MOG antibody–associated disorders: differences in clinical profiles and prognosis in Japan and Germany
Authors: Liu Jia , Mori Masahiro , Zimmermann Hanna , Brandt Alexander , Havla Joachim , Tanaka Satoru , Sugimoto Kazuo , Oji Satoru , Uzawa Akiyuki , Asseyer Susanna , Cooper Graham , Jarius Sven , Bellmann-Strobl Judith , Ruprecht Klemens , Siebert Nadja , Masuda Hiroki , Uchida Tomohiko , Ohtani Ryohei , Nomura Kyoichi , Meinl Edgar , Kuempfel Tania , Paul Friedemann , Kuwabara Satoshi
Published: November 2020

Background

Neurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder.

Objective

The study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG–associated disorders between East Asian (Japanese) and Caucasian (German) patients.

Methods

Demographic, clinical and therapeutic data from 68 MOG-IgG–positive adults were collected (Japanese, n=44; German, n=24).

Results

Age and sex were similar between cohorts, with optic neuritis occurring most frequently at onset (Japanese: 61%; German: 58%). However, Japanese patients had a lower annualised relapse rate (0.4 vs 0.8, p=0.019; no relapse, 64% vs 25%, p=0.002) and lower Expanded Disability Status Scale score at the last visit (1.0 vs 2.0; p=0.008), despite similar follow-up periods (mean, 73.9 months vs 73.4 months), than those of German patients, respectively. Cerebral syndromes were more common (27% vs 4%; p=0.021) and myelitis less common (21% vs 50%; p=0.012) in Japanese than in German patients, respectively. Japanese patients were more commonly treated with long-term corticosteroids (73%), whereas German patients were more commonly treated with rituximab or other immunosuppressants (63%).

Conclusions

Among patients with MOG-IgG, Japanese tended to have a monophasic milder disease, whereas the majority of German patients had a relapsing course and more frequent myelitis, findings compatible with neuromyelitis optica spectrum disorder. Although the attack-prevention treatment regimens were considerably different, genetic and environmental factors may be important to determine clinical phenotypes and disease activity.
Experiences, patient interactions and knowledge regarding the use of cannabis as a medicine in a cohort of New Zealand doctors in an oncology setting
Authors: Oldfield Karen , Eathorne Allie , Tewhaiti-Smith Jordan , Beasley Richard , Semprini Alex , Braithwaite Irene
Published: November 2020

Purpose of Study

To explore the experiences, patient interactions and knowledge regarding the use of cannabis as a medicine in New Zealand doctors in an oncology setting.

Study Design

An observational cross-sectional survey undertaken between November 2019 and January 2020 across four secondary-care hospital oncology departments within New Zealand (Auckland, Wellington, Christchurch and Dunedin). Participants were a convenience sample of doctors; consultants, registrars, medical officers of special status and house surgeons working in oncology departments. Of 53 individuals approached, 45 participated (85% Response Rate). The primary outcome was reporteddoctor-patient interactions. Secondary outcomes included knowledge of cannabis-based products, their efficacy, prescribing regulations and educational access.

Results

Of 44 doctors, 37 (84%, 95% CI: 70 to 93) reported patient requests to prescribe cannabis-based products and 43 (98%, 95% CI: 88 to 100) reported patients using illicit cannabis for medical symptoms. Primary request reasons were pain, nausea/vomiting and cancer treatment. 33/45 (73%, 95% CI: 58 to 85) cited knowledge of at least one cannabis-based product and 27/45 (60%, 95% CI: 44 to 74) indicated at least one condition that had evidence of efficacy. 36/44 (82%, 95% CI: 67 to 92) expressed future prescribing concerns but all were willing to use a cannabis-based product developed with traditional medical provenance.

Conclusion

In the oncology setting, patients are asking doctors about symptomatic and curative treatment with cannabis-based products. Doctors are not biased against the use of products showing medical provenance; however, NZ-specific clinical and regulatory guidelines are essential to support patient discussions and appropriate prescribing.
Are all blood-based postal sampling kits the same? A comparative service evaluation of the performance of dried blood spot and mini tube sample collection systems for postal HIV and syphilis testing
Authors: Page Matthew , Atabani Sowsan , Arumainayagam Joseph , Wilson Steven , Hartland Daniel , Taylor Stephen
Published: November 2020

Objectives

We comparatively evaluated two HIV and syphilis blood sampling kits (dried blood spot (DBS) and mini tube (MT)) as part of an online STI postal sampling service that included tests for chlamydia and gonorrhoea. We aimed to see how the blood collection systems compared regarding sample return rates and result rates. Additionally, we aimed to observe differences in false-positive results and describe a request-to-result ratio (RRR)—the required number of kit requests needed to obtain one successful result.

Methods

We reviewed data from an online postal STI kit requesting service for a client transitioning from MT to DBS blood collection systems. We described service user baseline characteristics and compared kit requests, kit and blood sample return rates, and the successful resulting rates for HIV and syphilis for MT and DBS. Pearson’s χ
2
and Fisher’s exact test were used to determine statistical differences, and statistical formulae were applied to produce CIs for differences in proportions.

Results

5670 STI postal kit requests from a Midlands region were reviewed from 6 September 2016–2 January 2019 (1515 MT and 4155 DBS). Baseline characteristics between the two groups were comparable (68.0% female, 74.0% white British and 87.5% heterosexual, median age 26 years). Successful processing rates for DBS were 94.6% and 54.4% for MT (p<0.001) with a percentage difference of 40.2% (95% CI 36.9% to 43.4%). The RRR for MT was 2.9 cf. 1.6 for DBS. False-positive results for MT samples were 5.2% (HIV) and 0.4% (syphilis), and those for DBS were 0.4% (HIV) and 0.0% (syphilis).

Conclusions

This comparative analysis demonstrated the superior successful processing rates for postal DBS collection systems compared with MT. Reasons for this included insufficient volumes, high false-positive rates and degradation of blood quality in MT samples. A postal sampling service using DBS to screen for HIV, syphilis and other blood-borne viruses could be a viable alternative.
Effect of syphilis infection on HIV acquisition: a systematic review and meta-analysis
Authors: Wu Meng Yin , Gong Hui Zi , Hu Kui Ru , Zheng He-yi , Wan Xia , Li Jun
Published: November 2020

Objectives

Co-infection of syphilis and HIV remains hard to manage and its morbidity shows a rising tendency. Syphilis has been associated with increased risk of HIV acquisition in high-risk groups, especially in men who have sex with men (MSM). This systematic review and meta-analysis estimates the effect of syphilis infection on subsequent HIV acquisition, and assesses its difference between MSM and other high-risk populations.

Methods

Five electronic databases were searched for literature published to 21 September 2019 without language restrictions. Longitudinal studies that enrolled key populations to compare the incidence of HIV with and without syphilis exposure were included. We used a random-effects model to estimate the effect of syphilis infection on HIV acquisition among high-risk populations, which include MSM, sex workers, serodiscordant couples, people who inject drugs and attendees of STD clinics.

Results

A total of 17 cohorts and 5 case-control studies involving 65 232 participants were included. HIV incidence showed a two-time increase after syphilis exposure, compared with a control group (relative risk (RR) 2.67 (95% CI 2.05 to 3.47); p<0.05 for prevalence; RR 3.21 (95% CI 2.26 to 4.57); p=0.419 for incidence). No significant differences were observed between MSM and other high-risk groups in syphilis infection prevalence (RR 2.60 (95% CI 1.78 to 3.80); p<0.05 vs RR, 2.98 (95% CI 2.15 to 4.14); p<0.05; ratio of relative risk 0.76 (95% CI 0.49 to 1.17)).

Conclusions

Syphilis infection increases the risk of HIV acquisition in high-risk populations. There is no evidence to suggest MSM are at greater risk than other high-risk populations. Prompt diagnosis, timely treatment, preventive interventions against syphilis infection would be a worthwhile investment for reducing HIV incidence. Strategies to combat stigma and discrimination targeted at MSM are pragmatically needed.
User-centric genomics infrastructure: trends and technologies
Authors: Krishna Ritesh , Elisseev Vadim
Published: November 2020

Genomics is both a data- and compute-intensive discipline. The success of genomics depends on an adequate informatics infrastructure that can address growing data demands and enable a diverse range of resource-intensive computational activities. Designing a suitable infrastructure is a challenging task, and its success largely depends on its adoption by users. In this article, we take a user-centric view of the genomics, where users are bioinformaticians, computational biologists, and data scientists. We try to take their point of view on how traditional computational activities for genomics are expanding due to data growth, as well as the introduction of big data and cloud technologies. The changing landscape of computational activities and new user requirements will influence the design of future genomics infrastructures.