bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of the Wound Edge Gene Signature “WD14” in Responding to Clinical Change: A Longitudinal Cohort Study
Authors: Bosanquet David C. , Laloo Ryan , Sanders Andrew J. , Ruge Fiona , Lane Jane , Morris Ceri A. , Jiang Wen G. , Harding Keith G.
Published: November 2021

Introduction: WounD14 (WD14) gene signature is a recently developed tool derived from genetic interrogation of wound edge biopsies of chronic venous leg ulcers to identify heard-to-heal wounds and enable clinicians to target aggressive therapies to promote wound healing. This study aimed to evaluate if changes in wound clinical healing status were detected by the WD14 gene signature over time as this is currently poorly understood. Material and methods: WD14 was developed through gene screening and subsequent validation in 3 patient cohorts involving 85 consecutive patients with chronic venous leg ulcers referred to a tertiary wound healing unit. Patients underwent a wound edge biopsy to interrogate for a “healing” or “non-healing” genotype. A smaller cohort (18%) underwent a second biopsy, which comprised this pilot cohort reported herein. Twelve weeks following biopsy, wounds were clinically assessed for healing status based on reduction in size and compared to WD14 genotype. Results: Sequential biopsies and WD14 scores were derived from 16 patients. WD14 signature predicted wound healing status among this cohort at either visit (32 wound edge biopsies) with a positive predictive value (PPV) of 85.2% (95% CI 74.1%-92.0%) and negative predictive value (NPV) of 80.0% (95% CI 34.2%-96.9%). A total of 6 wounds underwent altered clinical status between the 2 visits. In this cohort, WD14 has a PPV of 66.7% (95% CI 47.3%-81.7%) and NPV of 100%. Conclusion: Although the WD14 gene signature did change with wound healing status, larger studies are required to precisely clarify its role and ability to prognosticate wounds of differing clinical status over time.
Region-Wise Brain Response Classification of ASD Children Using EEG and BiLSTM RNN
Authors: Manoharan Thanga Aarthy , Radhakrishnan Menaka
Published: November 2021

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in sensory modulation. These sensory modulation deficits would ultimately lead them to difficulties in adaptive behavior and intellectual functioning. The purpose of this study was to observe changes in the nervous system with responses to auditory/visual and only audio stimuli in children with autism and typically developing (TD) through electroencephalography (EEG). In this study, 20 children with ASD and 20 children with TD were considered to investigate the difference in the neural dynamics. The neural dynamics could be understood by non-linear analysis of the EEG signal. In this research to reveal the underlying nonlinear EEG dynamics, recurrence quantification analysis (RQA) is applied. RQA measures were analyzed using various parameter changes in RQA computations. In this research, the cosine distance metric was considered due to its capability of information retrieval and the other distance metrics parameters are compared for identifying the best biomarker. Each computational combination of the RQA measure and the responding channel was analyzed and discussed. To classify ASD and TD, the resulting features from RQA were fed to the designed BiLSTM (bi-long short-term memory) network. The classification accuracy was tested channel-wise for each combination. T3 and T5 channels with neighborhood selection as FAN (fixed amount of nearest neighbors) and distance metric as cosine is considered as the best-suited combination to discriminate between ASD and TD with the classification accuracy of 91.86%, respectively.
How to Problematise Categories: Building the Methodological Toolbox for Linguistic Reflexivity
Authors: Alejandro Audrey
Published: November 2021

Following qualitative researchers’ growing interest in reflexivity, a body of scholarship has emerged that aims to turn informal practices for reflexivity into methods that can be learnt and taught alongside other research practices. This literature, however, has focused on helping researchers become more reflexive toward their situatedness and positionality, rather than toward their use of language and its effects on knowledge production – a process I refer to as ‘linguistic reflexivity’. This article addresses this gap by formalising a method for ‘problematising categories’, an informal approach familiar to qualitative researchers as a promising solution to the analytical and ethical blinders that result from scholars’ unconscious use of language. I proceed in three steps. First, I review the literature to show the analytical, empirical and ethical rationales behind this approach and offer a definition of problematising categories as the practice of making conscious how socio-linguistic units of categorisation unconsciously organise our perception and can represent a problem for knowledge production. This practice, I argue, enables us to decentre ourselves from the taken-for-granted nature of those categories. Second, I develop a three-stage research method for problematising categories: noticing ‘critical junctures' when problematisation is called for, identifying the categorical problem through sensitising questions and reconstructing an alternative. Third, I demonstrate how problematising categories contributes to the research process by applying this method to my experience in problematising the binary pair ‘local’ versus ‘international’ in a research project on the environmental impact of Chinese investment in the Senegalese fishery sector. I show that problematising categories leads to more rigorous empirical findings and nuanced analysis in a way that is feasible within the frame of qualitative research projects. Overall, this article expands the practical tools for linguistic reflexivity and heeds the methodological call to make conscious and explicit choices for every dimension of our research.
Inventing hell: how the Ethiopian and Eritrean regimes produced famine in Tigray
Authors: Weldemichel Teklehaymanot G.
Published: November 2021

It has been a year since a devastating war broke out in the Tigray region, Northern Ethiopia, where hundreds of thousands of Tigrayan civilians are killed, millions internally displaced and tens of thousands have fled to seek refuge in neighboring Sudan. An alarming development linked to this war is the manmade famine in Tigray that now threatens the lives of the millions of civilians who survived the horrific atrocities during the war. This piece is an attempt to explain why millions of Tigrayans from all walks of life face famine and concludes that famine was from the start an end goal of the Ethiopian and Eritrean regimes and they employed different tactics to ensure that it unfolds the way it does now. Among others, the tactics include (1) the systematic looting and destruction of Tigray’s basic economic infrastructures, (2) implementation of different financial measures to deprive people in the region of access to cash, and imposition of a complete siege that hindered access to supplies including lifesaving humanitarian assistance.
Severe COVID-19 and long COVID in a 31-year-old woman with incontinentia pigmenti: A case report
Authors: Rheault Sylvie
Published: November 2021

Incontinentia pigmenti is a rare genetic disease affecting the skin, microvasculature, and central nervous system, in which a hyperactive inflammatory response is observed. Due to the inflammatory phase of COVID-19 and associated cytokine storm, infection with SARS-CoV-2 in individuals with incontinentia pigmenti is a concern. Furthermore, type I interferon autoantibodies are found in life-threatening COVID-19 pneumonia and in 25% of individuals with incontinentia pigmenti. The present case report describes a 31-year-old Caucasian woman with incontinentia pigmenti and severe COVID-19. She was hospitalized for oxygen therapy, intravenous antibiotics, and corticosteroids. Eight months later, she is still symptomatic. To our knowledge, she is the first reported case of long COVID in incontinentia pigmenti. Increased autoimmunity may be implicated in both incontinentia pigmenti and long COVID. Pending evidence-based guidelines, COVID-protective measures including vaccination should be recommended to all patients with incontinentia pigmenti. Specific interferon therapy may be considered along with usual COVID treatment.
Effects of Desensitizers, Temporary Cements, and Dentin Cleaning Methods on the Bond Strength of Self-Etch/ Adhesive Resin Cements to Dentin: An In Vitro Study
Authors: Uğur Mehmet , Kavut I˙dris , Külünk Şafak , Akdeniz Mehmet Şerif , Tanrıkut Özgür Ozan
Published: November 2021

Aim:

The aim of this study was to evaluate the effect of desensitizer, temporary cements, dentin cleaning methods on shear bond strength (SBS) of self-etch and self-adhesive resin cements to dentin.

Materials and Methods:

Four hundred eighty buccal or lingual/palatine coronal portions of human molar teeth were mounted in the acrylic blocks. Teeth surfaces were prepared until the dentin was exposed. Specimens were divided into four groups. One group separated as control and three groups of teeth were treated with a desensitizing agent containing calcium-phosphate desensitizer (Teethmate Desensitizer, TMD), resin-based self-reinforcing monomer (Shield Force Plus, SFP) and 2-hydroxyethyl methacrylate and glutaraldehyde (Gluma Desensitizer). Two different temporary cement containing calcium hydroxide (Dycall) and zinc oxide based (Rely X Temp NE) temporary cement were applied to the dentin surfaces. Temporary cement was removed with one of three cleansing techniques: 2% chlorhexidine digluconate and glass particles containing agent (Consepsis Scrub), cleansing bur (OptiClean), and ıntra/extracoronal rotary brush (Starbrush). All groups were further divided into two cementation subgroups (Panavia V5 and Panavia SA). The SBS (MPa) was measured using a universal testing machine at 0.5 mm/min crosshead speed. The data were analyzed statistically with a four-way analysis of variance and Tukey’s Honest Significant Difference test ( α = 0.05).

Results:

Although SFP showed higher SBS, there was no statistically significant difference between other groups ( P > .05). There were no significant differences between temporary cements ( P > .05). OptiClean rotary bur showed higher mean SBS values in all groups. The dual-polymerized Panavia V5 showed the highest SBS values in all groups ( P <.05).

Conclusion:

Cleaning of dentin surface from temporary cement remnants with a silicon bur and dual-cure resin cement showed the highest bond strength values.
Book review: Sanjib Baruah, In the Name of the Nation
Authors: Sharma Samir
Published: November 2021

Sanjib Baruah, In the Name of the Nation (New Delhi: Navayana Publishers, 2020), 278 pp. ₹599.
Book review: Shirin M. Rai and Carole Spary. Performing Representation: Women Members in the Indian Parliament
Authors: Nanda Bijayalaxmi
Published: November 2021

Shirin M. Rai and Carole Spary. Performing Representation: Women Members in the Indian Parliament. New Delhi: Oxford University Press. 2019. 398 pages. ₹995.
Aspects of Women’s Leadership in the Organisation: Systematic Literature Review
Authors: Kulkarni Aparna , Mishra Mahima
Published: November 2021

In most organisations, women are underrepresented in top positions. Many aspects of Women’s Leadership are studied in the literature for underrepresentation of women leaders. This study aims to analyse and consolidate the insights about those aspects of Women’s Leadership, which gives them a stable and secure position in the organisation, beyond the unseen walls of gender discrimination. These aspects are barriers, enablers, strengths and weaknesses of Women’s Leadership. The research method used for the study is a systematic literature review method. Peer-reviewed, scholarly journal articles and book references between 1990 and 2021 identified from the Scopus and Web of Sciences databases are considered for the study. The result showed much uniformity in the ‘Women’s Leadership’ phenomenon, globally. This research found that Women’s Leadership studies are mostly conducted in areas such as social sciences, business and management, medicine, education, etc. It also found that most women-leadership-related studies are conducted in developed countries where the percentage of women leaders is comparatively higher than in other industries. Still, women leaders in both developed and developing countries face similar barriers during their careers. The gender gap and the glass ceiling they have to break are some of the issues experienced by women in any organisation. Organisational bias, lack of assertiveness and poor networking also pose barriers to Women’s Leadership. Yet, there are some enablers for Women’s Leadership, such as mentoring, good training programmes and workplace culture. However, maintaining a work–life balance, working under pressure and excluding informal communication are considered as limitations for Women’s Leadership. Strengths, such as high emotional intelligence, empathy, democratic leadership style, sincerity and ability to make decisions under critical circumstances benefit the organisation. This study will help to get an integrated and consolidated theoretical review of different aspects of Women’s Leadership in the organisation. Moreover, the study can help to implement various organisational policies to increase the percentage of women in leadership roles.
Are Baseball Statistics an Appropriate Tool for Assessing Return to Play in Injured Pitchers? Analysis of Statistical Variability in Healthy Players
Authors: Pareek Ayoosh , Parkes Chad W. , Leontovich Alexey A. , Krych Aaron J. , Conte Stan , Steubs John A. , Wulf Corey A. , Camp Christopher L.
Published: November 2021

Background:

Basic pitcher statistics have been used to assess performance in pitchers after injury or surgery without being validated. Even among healthy pitchers, the normal variability of these parameters has not yet been established.

Purpose:

To determine (1) the normal variability of basic and advanced pitcher statistics in healthy professional baseball pitchers and (2) the minimum pitches needed to predict these parameters.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Publicly available data from the MLB Statcast and PITCHf/x databases were used to analyze MLB pitchers during the 2015 and 2016 seasons who recorded a minimum of 100 innings without injury. Basic and advanced baseball pitcher statistics were analyzed. The variability of each parameter was assessed by computing the coefficient of variation (CV) between individual pitchers and across all pitchers. A CV <10 was indicative of a relatively constant parameter, and parameters with a CV >10 were generally considered inconsistent and unreliable. The minimum number of pitches needed to be followed for each variable was also analyzed.

Results:

A total of 118 pitchers, 55 baseball-specific statistical metrics (38 basic and 17 advanced), and 7.5 million pitches were included and analyzed. Of the 38 basic pitcher statistics, only fastball velocity demonstrated a CV <10 (CV = 1.5), while 6 of 17 (35%) advanced metrics demonstrated acceptable consistency (CV <10). Release position from plate and velocity from the plate were the 2 most consistent advanced parameters. When separated by pitch type, these 2 parameters were the most constant (lowest CV) across every pitch type.

Conclusion:

We recommend against utilizing nonvalidated statistical measures to assess performance after injury, as they demonstrated unacceptably high variability even among healthy, noninjured professional baseball pitchers. It is our hope that this study will serve as the foundation for the identification and implementation of validated pitcher-dependent statistical measures that can be used to assess return-to-play performance after injury in the future.
IgM-MM is predominantly a pre–germinal center disorder and has a distinct genomic and transcriptomic signature from WM
Authors: Bazarbachi Abdul Hamid , Avet-Loiseau Hervé , Szalat Raphael , Samur Anil Aktas , Hunter Zachary , Shammas Masood , Corre Jill , Fulciniti Mariateresa , Anderson Kenneth C. , Parmigiani Giovanni , Treon Steven P. , Mohty Mohamad , Munshi Nikhil C. , Samur Mehmet Kemal
Published: November 2021

Immunoglobulin M (IgM) multiple myeloma (MM) is a rare disease subgroup. Its differentiation from other IgM-producing gammopathies such as Waldenström macroglobulinemia (WM) has not been well characterized but is essential for proper risk assessment and treatment. In this study, we investigated genomic and transcriptomic characteristics of IgM-MM samples using whole-genome and transcriptome sequencing to identify differentiating characteristics from non–IgM-MM and WM. Our results suggest that IgM-MM shares most of its defining structural variants and gene-expression profiling with MM, but has some key characteristics, including t(11;14) translocation, chromosome 6 and 13 deletion as well as distinct molecular and transcription-factor signatures. Furthermore, IgM-MM translocations were predominantly characterized by VHDHJH recombination-induced breakpoints, as opposed to the usual class-switching region breakpoints; coupled with its lack of class switching, these data favor a pre–germinal center origin. Finally, we found elevated expression of clinically relevant targets, including CD20 and Bruton tyrosine kinase, as well as high BCL2/BCL2L1 ratio in IgM-MM, providing potential for targeted therapeutics.
Advanced Atomic Layer Deposition Technologies for Micro-LEDs and VCSELs
Authors: Yeh Yen-Wei , Lin Su-Hui , Hsu Tsung-Chi , Lai Shouqiang , Lee Po-Tsung , Lien Shui-Yang , Wuu Dong-Sing , Li Guisen , Chen Zhong , Wu Tingzhu , Kuo Hao-Chung
Published: November 2021

In recent years, the process requirements of nano-devices have led to the gradual reduction in the scale of semiconductor devices, and the consequent non-negligible sidewall defects caused by etching. Since plasma-enhanced chemical vapor deposition can no longer provide sufficient step coverage, the characteristics of atomic layer deposition ALD technology are used to solve this problem. ALD utilizes self-limiting interactions between the precursor gas and the substrate surface. When the reactive gas forms a single layer of chemical adsorbed on the substrate surface, no reaction occurs between them and the growth thickness can be controlled. At the Å level, it can provide good step coverage. In this study, recent research on the ALD passivation on micro-light-emitting diodes and vertical cavity surface emitting lasers was reviewed and compared. Several passivation methods were demonstrated to lead to enhanced light efficiency, reduced leakage, and improved reliability.
Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan
Authors: Bhat Mamatha , Clotet-Freixas Sergi , Baciu Cristina , Pasini Elisa , Hammad Ahmed , Ivanics Tommy , Reid Shelby , Azhie Amirhossein , Angeli Marc , Ghanekar Anand , Fischer Sandra , Sapisochin Gonzalo , Konvalinka Ana
Published: November 2021

Background and aims

Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches.

Methods

Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry.

Results

Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples.

Conclusions

Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.
Learning from diagnostic errors to improve patient safety when GPs work in or alongside emergency departments: incorporating realist methodology into patient safety incident report analysis
Authors: Cooper Alison , Carson-Stevens Andrew , Cooke Matthew , Hibbert Peter , Hughes Thomas , Hussain Faris , Siriwardena Aloysius , Snooks Helen , Donaldson Liam J. , Edwards Adrian
Published: November 2021

Background

Increasing demand on emergency healthcare systems has prompted introduction of new healthcare service models including the provision of GP services in or alongside emergency departments. In England this led to a policy proposal and £100million (US$130million) of funding for all emergency departments to have co-located GP services. However, there is a lack of evidence for whether such service models are effective and safe. We examined diagnostic errors reported in patient safety incident reports to develop theories to explain how and why they occurred to inform potential priority areas for improvement and inform qualitative data collection at case study sites to further refine the theories.

Methods

We used a mixed-methods design using exploratory descriptive analysis to identify the most frequent and harmful sources of diagnostic error and thematic analysis, incorporating realist methodology to refine theories from an earlier rapid realist review, to describe how and why the events occurred and could be mitigated, to inform improvement recommendations. We used two UK data sources: Coroners’ reports to prevent future deaths (30.7.13–14.08.18) and National Reporting and Learning System (NRLS) patient safety incident reports (03.01.05–30.11.15).

Results

Nine Coroners’ reports (from 1347 community and hospital reports, 2013–2018) and 217 NRLS reports (from 13 million, 2005–2015) were identified describing diagnostic error related to GP services in or alongside emergency departments. Initial theories to describe potential priority areas for improvement included: difficulty identifying appropriate patients for the GP service; under-investigation and misinterpretation of diagnostic tests; and inadequate communication and referral pathways between the emergency and GP services. High-risk presentations included: musculoskeletal injury, chest pain, headache, calf pain and sick children.

Conclusion

Initial theories include the following topics as potential priority areas for improvement interventions and evaluation to minimise the risk of diagnostic errors when GPs work in or alongside emergency departments: a standardised initial assessment with streaming guidance based on local service provision; clinical decision support for high-risk conditions; and standardised computer systems, communication and referral pathways between emergency and GP services. These theories require refinement and testing with qualitative data collection from case study (hospital) sites.
Miller Fisher syndrome following BNT162b2 mRNA coronavirus 2019 vaccination
Authors: Nishiguchi Yamato , Matsuyama Hirofumi , Maeda Kuniko , Shindo Akihiro , Tomimoto Hidekazu
Published: November 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. One of the vaccines approved against COVID-19 is the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech).

Case presentation

We present the case of a 71-year-old man with no history of the SARS-CoV-2 infection or any recent viral or bacterial illnesses who presented with bilateral oculomotor palsy and limb ataxia after BNT162b2 mRNA COVID-19 vaccination. The diagnosis of Miller Fisher syndrome (MFS) was established based on physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF), and positron emission tomography (PET). There was no evidence of other predisposing infectious or autoimmune factors, and the period from COVID-19 vaccination to the appearance of neurological symptoms was similar to that of other vaccines and preceding events, such as infection.

Conclusion

Guillain–Barré syndrome (GBS) and its variants after COVID-19 vaccination are extremely rare. Note that more research is needed to establish an association between MFS and COVID-19 vaccines. In our opinion, the benefits of COVID-19 vaccination largely outweigh its risks.
Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies
Authors: Poon Michael T. C. , Bruce Morgan , Simpson Joanne E. , Hannan Cathal J. , Brennan Paul M.
Published: November 2021

Background

Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.

Methods

We searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC50).

Results

We included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0–27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3–277.7 μM), 223.1 μM (IQR 92.0–590.1 μM) and 230.0 μM (IQR 34.1–650.0 μM), respectively. The median IC50 at 72 h for patient-derived cell lines was 220 μM (IQR 81.1–800.0 μM).

Conclusion

Temozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.
Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)
Authors: Kurul Serife , Taal H. Rob , Flint Robert B. , Mazela Jan , Reiss Irwin K. M. , Allegaert Karel , Simons Sinno H. P.
Published: November 2021

Background

Late onset sepsis is a leading cause of death and morbidity in preterm infants. Despite optimal antibiotic treatment, sepsis related mortality and morbidity is still high. Pentoxifylline (PTX) is a methylxanthine with promising immunomodulatory properties, which can be used as an additional therapy next to antibiotics in preterm infants. PTX is increasingly used off-label in neonatal intensive care units, however up till now no dose finding study has been done for PTX in this specific population. The aim of this study (PTX-trial) is to determine the optimal dose of PTX in preterm infants (gestational age < 30 weeks) with (suspected) late onset sepsis. Dose finding in this particular population is unique, since for most drugs used in neonates the optimal dosage has not been investigated in phase II dose-seeking studies.

Methods

The PTX-trial is a prospective open label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design will be used, with dose step-up and step-down titration after every 3 patients. The PTX starting dosage will be 30 mg/kg/day in 6 hours as described in most previous neonatal studies. Efficacy is defined by means of biochemical and clinical parameters. Toxicity in these vulnerable patients is unwarranted. The optimal dose is defined as the ED75 (i.e., clinically and chemically effective dose for 75% of patients) in preterm neonates with late onset sepsis. We plan to include 30 neonates to determine the optimal dose using this study design. Subsequently, the optimal dose will be validated in 10 additional preterm neonates. In parallel, pharmacokinetics of PTX and its metabolites will be described as well as longitudinal evaluation of metabolomics and proteomics.

Discussion

The study has been approved by the Regional Medical Ethics Board of Erasmus Medical Center University Rotterdam (MEC 2019-0477) and registered at Clinicaltrials.gov (NCT04152980). Results of the main trial and each of the secondary endpoints will be submitted for publications in peer-reviewed journals.

Trial registration

Clinicaltrials.gov, NCT04152980, Registered November 6th, 2019
Users’ perceptions about receiving personalized depression risk information: findings from a qualitative study
Authors: Eccles Heidi , Nadouri Doaa , Nannarone Molly , Lashewicz Bonnie , Schmitz Norbert , Patten Scott B. , Manuel Douglas G. , Wang JianLi
Published: November 2021

Objectives

To understand users’ perceptions about receiving their personalized depression risk score and to gain an understanding about how to improve the efficiency of risk communication from the user perspective.

Methods

A qualitative study embedded in a randomized controlled trial (RCT) on evaluating the impact of providing personalized depression risk information on psychological harms and benefits. The participants (20 males and 20 females) were randomly selected from the intervention arm of the RCT after the 12-month assessment. The qualitative interviews were conducted through telephone, audio recorded and transcribed verbatim. We conducted a content analysis to describe the content and contextual meaning of data collected from participants.

Results

The first theme explained the motivation for receiving a risk score. Most participants chose to receive their personalised depression risk score with the goal of improving their self-awareness. The results revealed three sub-themes surrounding perceptions and implication of receiving their risk score: positive, negative, and neutral. Most participants found that receiving their score was positive because it improved their awareness of their mental health, but some participants could see that some people would have negative feelings when getting the score causing them to be more likely to get depression. The final theme focussed on improvements including: the best delivery methods, having resources and strategies, and targeting younger people.

Conclusion

The most significant motivation for, and benefit of receiving one’s personalized depression risk score was improved awareness of one’s mental health. A comprehensive risk communication program may improve the uptake and maximize the impact on behavior changes and risk reduction.
Knowledge of mothers regarding children’s vaccinations in Greece: an online cross-sectional study
Authors: Giannakou Konstantinos , Kyprianidou Maria , Hadjikou Andria , Fakonti Georgia , Photiou Galatia , Tzira Eleana , Heraclides Alexandros
Published: November 2021

Background

One of the main reasons that influence parental choice to postpone or avoid children’s vaccination is insufficient knowledge. Mothers’ knowledge can be considered as an important factor when determining childcare, as they are often the primary decision maker for their children’s healthcare issues. This study aimed to assess the level of mothers’ knowledge and practice on certain aspects of vaccination for their child/children in Greece.

Methods

This was an online cross-sectional survey, which collected information about mother’s socio-demographic characteristics, vaccination-related information, and vaccine knowledge using a self-administered questionnaire. The survey was conducted between April 2020 and June 2020 and the study population included mothers over 18 years old with at least one child (< 18 years old), living in four broad geographical areas of Greece (Attica, Central Greece, North Greece, and Crete/Aegean Islands).

Results

A total of 1885 Greek mothers participated in the study. The majority stated that they vaccined their child/children (98%), and the most popular source of information about vaccination was their child’s pediatrician (89%). About half of participants (52%) have delayed their child/children vaccination with their pediatrician’s suggestion being the main driver. The median knowledge score was 11 which indicates a high knowledge level for childhood vaccination among Greek mothers. Multiple linear regression analysis identified an inverse association between education and knowledge score, characterized by higher knowledge scores among individuals with secondary and even higher among those with higher education. Multiple logistic regression analysis showed that the strict adherence to the prescribed dosage as indicated by the local recommendations for each vaccine, was associated with most of the knowledge items included in the study.

Conclusions

Our findings show that the vast majority of mothers in Greece did vaccinate their child/children, while pediatricians appear to have a very influential role in mothers’ decision making. High knowledge around vaccination was associated with mothers’ educational attainment, being particularly high among those who completed higher education. Considerable attention is required from public health authorities to promote vaccination through educational programs and campaigns, particularly aimed at people with lower educational attainment. Additionally, improving communication between pediatricians and mothers to reach those women who have not decided to vaccinate or delayed vaccination for their children, may prove to be very beneficial.
Community perceptions of vaccination among influential stakeholders: qualitative research in rural India
Authors: Dhaliwal Baldeep K. , Chandrashekhar Riti , Rattani Ananya , Seth Rajeev , Closser Svea , Jain Anika , Bloom David E. , Shet Anita
Published: November 2021

Background

In India and other low- and middle-income countries, multiple family and community members are influential in caregivers’ perceptions of vaccination. Existing literature indicates the primary caregiver, typically the mother, is instrumental in vaccine decision-making, but this may vary in contexts. We investigated the role of stakeholders in India who influence caregivers’ vaccination perceptions, as this is essential to developing strategies to promote vaccine acceptance and improve uptake.

Methods

This research was conducted in 2019 in Mewat District in Haryana, an area in India with extremely low vaccination coverage. We conducted six focus group discussions with 60 participants in the following categories: fathers of children under-5 years old, expectant mothers, mothers-in-law, community health workers, and community influencers such as locally elected officials and religious leaders.

Results

Our results highlighted four themes that influence vaccine uptake. First, while caregivers associated vaccination with reductions in specific diseases, they also noted that vaccination services brought broad health gains, including improved nutrition, antenatal guidance, and social support. Second, community health workers critically influenced, positively or negatively, caregivers’ vaccination perceptions. Third, community health workers faced gaps in their education such as limited training on vaccine side-effects, placing them at a disadvantage when dealing with families. Finally, we found that mothers-in-law, fathers, and religious leaders influence caregivers’ perceptions of vaccination.

Conclusions

Communication of broader benefits of vaccines and vaccination services by community health workers could be impactful in increasing vaccine acceptance. Vaccine uptake could potentially be improved by facilitating community health workers’ ownership over vaccine acceptance and uptake by involving them in the design and implementation of interventions to target mothers and mothers-in-law. A ‘bottom-up’ approach, leveraging community health workers’ knowledge to design interventions, and giving a voice to key members of the household and society beyond mothers alone, may sustain health improvement in low vaccine coverage areas.
C-EBPβ mediates in cigarette/IL-17A-induced bronchial epithelial–mesenchymal transition in COPD mice
Authors: Chu Shuyuan , Ma Libing , Wu Yashan , Zhao Xiaoli , Xiao Bo , Pan Qilu
Published: November 2021

Background

Cigarettes smoking and IL-17A contribute to chronic obstructive pulmonary disease (COPD), and have synergistical effect on bronchial epithelial cell proliferation. CCAAT/enhancer-binding protein β (C-EBPβ) could be induced by IL-17A and is up-regulated in COPD. We explored the effect of cigarettes and IL-17 on bronchial epithelial–mesenchymal transition (EMT) in COPD mice and potential mechanism involved with C-EBPβ in this study.

Methods

COPD model was established with mice by exposing to cigarettes. E-Cadherin, Vimentin, IL-17A and C-EBPβ distributions were detected in lung tissues. Primary bronchial epithelial cells were separated from health mice and cocultured with cigarette smoke extract (CSE) or/and IL-17A. E-Cadherin, Vimentin and IL-17 receptor (IL-17R) expressions in vitro were assessed. When C-EBPβ were silenced by siRNA in cells, E-Cadherin, Vimentin and C-EBPβ expressions were detected.

Results

E-Cadherin distribution was less and Vimentin distribution was more in bronchus of COPD mice than controls. IL-17A and C-EBPβ expressions were higher in lung tissues of COPD mice than controls. In vitro, C-EBPβ protein expression was highest in CSE + IL-17A group, followed by CSE and IL-17A groups. E-cadherin expression in vitro was lowest and Vimentin expression was highest in CSE + IL-17A group, followed by CSE or IL-17A group. Those could be inhibited by C-EBPβ silenced.

Conclusions

C-EBPβ mediates in cigarette/IL-17A-induced bronchial EMT in COPD mice. Our findings contribute to a better understanding on the progress from COPD to lung cancers, which will provide novel avenues in preventing tumorigenesis of airway in the context of cigarette smoking.
Potential biomarkers of abnormal osseointegration of implants in type II diabetes mellitus
Authors: Wang Lingxiao , Gao Zhenhua , Liu Changying , Li Jun
Published: November 2021

Background

Type II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants. The aim of this study was to explore key genes of T2DM affecting bone metabolism through bioinformatic analysis of published RNA sequencing data, identify potential biomarkers, and provide a reference for finding the molecular mechanism of abnormal osseointegration caused by T2DM.

Methods

We identified differentially expressed mRNAs and miRNAs from the Gene Expression Omnibus database using the R package ‘limma’ and analysed the predicted target genes using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis. At the same time, miRNA–mRNA interactions were explored using miRWalk 2.0.

Results

We constructed an miRNA-gene regulatory network and a protein–protein interaction network. The enrichment pathways of differentially expressed mRNAs included extracellular matrix receptor interactions, protein digestion and absorption, the PI3K-Akt signalling pathway, cytokine–cytokine receptor interactions, chemokine signalling pathways, and haematopoietic cell lineage functions. We analysed the expression of these differentially expressed mRNAs and miRNAs in T2DM rats and normal rats with bone implants and identified Smpd3, Itga10, and rno-mir-207 as possible key players in osseointegration in T2DM.

Conclusion

Smpd3, Itga10, and rno-mir-207 are possible biomarkers of osseointegration in T2DM. This study sheds light on the possible molecular mechanism of abnormal osseointegration caused by bone metabolism disorder in T2DM.
Clinicians’ experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making
Authors: Carlisle N. , Watson H. A. , Carter J. , Kuhrt K. , Seed P. T. , Tribe R. M. , Sandall J. , Shennan A. H.
Published: November 2021

Background

As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth.

Methods

Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians’ (obstetricians’ and midwives’) experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach.

Results

Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: ‘experience of using the app’, ‘how QUiPP risk changes practice’ and ‘successfully adopting QUiPP: context is everything’. With these final themes we appeared to have achieved our aim of exploring the clinicians’ experiences of using and implementing the QUiPP app.

Conclusion

This study explored different clinician’s experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL.

Clinical trial registry and registration number

ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337.
Assessment, referral and management of obstructive sleep apnea by Australian general practitioners: a qualitative analysis
Authors: Grivell Nicole , Haycock Jenny , Redman Anne , Vakulin Andrew , Zwar Nicholas , Stocks Nigel , Frank Oliver , Reed Richard , Chai-Coetzer Ching Li , Grunstein Ronald R. , McEvoy R. Doug , Hoon Elizabeth
Published: November 2021

Background

The high and increasing demand for obstructive sleep apnea (OSA) care has exceeded the capacity of specialist sleep services prompting consideration of whether general practitioners could have an enhanced role in service delivery. However, little is known about the current involvement, experiences and attitudes of Australian general practitioners towards OSA. The purpose of this study was to provide an in-depth analysis of Australian general practitioners’ experiences and opinions regarding their care of patients with OSA to inform the design and implementation of new general practice models of care.

Methods

Purposive sampling was used to recruit participants with maximum variation in age, experience and location. Semi-structured interviews were conducted and were analysed using Thematic Analysis.

Results

Three major themes were identified: (1) General practitioners are important in recognising symptoms of OSA and facilitating a diagnosis by others; (2) Inequities in access to the assessment and management of OSA; and (3) General practitioners currently have a limited role in the management of OSA.

Conclusions

When consulting with patients with symptoms of OSA, general practitioners see their primary responsibility as providing a referral for diagnosis by others. General practitioners working with patients in areas of greater need, such as rural/remote areas and those of socio-economic disadvantage, demonstrated interest in being more involved in OSA management. Inequities in access to assessment and management are potential drivers for change in future models of care for OSA in general practice.
The role of noncoding RNAs in Parkinson’s disease: biomarkers and associations with pathogenic pathways
Authors: Kuo Ming-Che , Liu Sam Chi-Hao , Hsu Ya-Fang , Wu Ruey-Meei
Published: November 2021

The discovery of various noncoding RNAs (ncRNAs) and their biological implications is a growing area in cell biology. Increasing evidence has revealed canonical and noncanonical functions of long and small ncRNAs, including microRNAs, long ncRNAs (lncRNAs), circular RNAs, PIWI-interacting RNAs, and tRNA-derived fragments. These ncRNAs have the ability to regulate gene expression and modify metabolic pathways. Thus, they may have important roles as diagnostic biomarkers or therapeutic targets in various diseases, including neurodegenerative disorders, especially Parkinson’s disease. Recently, through diverse sequencing technologies and a wide variety of bioinformatic analytical tools, such as reverse transcriptase quantitative PCR, microarrays, next-generation sequencing and long-read sequencing, numerous ncRNAs have been shown to be associated with neurodegenerative disorders, including Parkinson’s disease. In this review article, we will first introduce the biogenesis of different ncRNAs, including microRNAs, PIWI-interacting RNAs, circular RNAs, long noncoding RNAs, and tRNA-derived fragments. The pros and cons of the detection platforms of ncRNAs and the reproducibility of bioinformatic analytical tools will be discussed in the second part. Finally, the recent discovery of numerous PD-associated ncRNAs and their association with the diagnosis and pathophysiology of PD are reviewed, and microRNAs and long ncRNAs that are transported by exosomes in biofluids are particularly emphasized.