bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Early Eukaryotic Integration of Mitochondria and Chloroplasts in the Light of Internal ROS Challenges: Timing is of the Essence
Authors: Speijer Dave , Hammond Michael , Lukeš Julius
Published: May 2020

The early eukaryotic evolution was deeply influenced by the acquisition of two endosymbiotic organelles - the mitochondrion and the chloroplast. Here we discuss the possibly important role of reactive oxygen species in these processes.
Overexpression of the Small RNA PA0805.1 in Pseudomonas aeruginosa Modulates the Expression of a Large Set of Genes and Proteins, Resulting in Altered Motility, Cytotoxicity, and Tobramycin Resistance
Authors: Coleman Shannon R. , Smith Maren L. , Spicer Victor , Lao Ying , Mookherjee Neeloffer , Hancock Robert E. W.
Published: May 2020

P. aeruginosa
is an opportunistic pathogen of humans. With roughly 10% of its genes encoding transcriptional regulators, and hundreds of small noncoding RNAs (sRNAs) interspersed throughout the genome,
P. aeruginosa
is able to fine-tune its response to adapt and survive in the host and resist antimicrobial agents. Understanding mechanisms of genetic regulation is therefore crucial to combat pathogenesis. The previously uncharacterized sRNA PA0805.1 was overexpressed in
P. aeruginosa
strain PAO1, resulting in decreased motility, increased adherence, cytotoxicity, and tobramycin resistance. In contrast, a ΔPA0805.1 deletion mutant had increased susceptibility to tobramycin under swarming conditions. Omic approaches uncovered 1,121 transcriptomic and 258 proteomic changes in the overexpression strain compared with the empty-vector strain, which included 106 regulatory factors. Downstream of these regulators were upregulated adherence factors, multidrug efflux systems, and virulence factors in both transcriptomics and proteomics. This study provides insights into the role of the sRNA PA0805.1 in modulating bacterial adaptations.
Cellular and Structural Basis of Synthesis of the Unique Intermediate Dehydro-F
420
-0 in Mycobacteria
Authors: Grinter Rhys , Ney Blair , Brammananth Rajini , Barlow Christopher K. , Cordero Paul R. F. , Gillett David L. , Izoré Thierry , Cryle Max J. , Harold Liam K. , Cook Gregory M. , Taiaroa George , Williamson Deborah A. , Warden Andrew C. , Oakeshott John G. , Taylor Matthew C. , Crellin Paul K. , Jackson Colin J. , Schittenhelm Ralf B. , Coppel Ross L. , Greening Chris
Published: May 2020

Mycobacteria are major environmental microorganisms and cause many significant diseases, including tuberculosis. Mycobacteria make an unusual vitamin-like compound, F
420
, and use it to both persist during stress and resist antibiotic treatment. Understanding how mycobacteria make F
420
is important, as this process can be targeted to create new drugs to combat infections like tuberculosis. In this study, we show that mycobacteria make F
420
in a way that is different from other bacteria. We studied the molecular machinery that mycobacteria use to make F
420
, determining the chemical mechanism for this process and identifying a novel chemical intermediate. These findings also have clinical relevance, given that two new prodrugs for tuberculosis treatment are activated by F
420
.
Supplemental Material: The Chief Joseph dike swarm of the Columbia River flood basalts, and the legacy data set of William H. Taubeneck
Authors: Morriss M.C.
Published: May 2020

Supplemental Tables. Table S1: Location of Dr. William H. Taubeneck’s (WHT) mapped dike midpoints, each dike’s host rock, bearing, azimuthal direction, and segment length. Table S2: Digitized WHT journal entries denoting each dike observation made during his 50-year career. Table S3: Geochemical re-analysis results from Washington State University X-ray fluorescence laboratory. Table S4: Dike width measurements from original field work and WHT notebooks. Tables S5−S7: Locations of mapped bearing, azimuthal direction, and segment length for Ice Harbor (Table S5), Monument (Table S6), and Steens Dikes (Table S7).
Supplemental Material: Three-dimensional shape and structure of the Susitna basin, south-central Alaska, from geophysical data
Authors: Shah A.K.
Published: May 2020

Figure S1 showing locations of magnetic high-low
anomalies that exhibit total gradient highs, numbered 1–3 as described in the
text with: (A) simplified surface geology (colors as in Fig. 2), arrow marks an area
near metavolcanic rock described as Triassic to Pennsylvanian? by Wilson et al.
(2015); (B) reduced-to-pole
magnetic field; and (C) total gradient and thick black lines delineate faults
interpreted in this study and by Haeussler and Saltus (2011).
Supplemental Material: Intrarift fault fabric, segmentation, and basin evolution of the Lake Malawi (Nyasa) Rift, East Africa
Authors: Scholz C.A. , al. et
Published: May 2020

Contains mapping files in GIS formats of 1) the basement structure contour grid for Lake Malawi (Nyasa); 2) the sediment thickness grid for Lake Malawi (Nyasa); and 3) fault heaves for major basement-involved faults observed in the Lake Malawi (Nyasa) Rift
Glycated hemoglobin (HbA1c) as diagnostic criteria for diabetes: the optimal cut-off points values for the Pakistani population; a study from second National Diabetes Survey of Pakistan (NDSP) 2016–2017
Authors: Basit Abdul , Fawwad Asher , Abdul Basit Khalid , Waris Nazish , Tahir Bilal , Siddiqui Iftikhar Ahmed
Published: May 2020

Aim

Glycated hemoglobin (HbA1c) cut-off values as diagnostic tool in diabetes and prediabetes with its concordance to oral glucose tolerance test (OGTT) in Pakistani population.

Methodology

Data for this substudy was obtained from second National Diabetes Survey of Pakistan (NDSP) 2016–2017. With this survey, 10 834 individuals were recruited and after excluding known subjects with diabetes, 6836 participants fulfilled inclusion criteria for this study. Demographic, anthropometric and biochemical parameters were obtained. OGTT was used as standard diagnostic tool to screen population and HbA1c for optimal cut-off values. Participants were categorized into normal glucose tolerance (NGT), newly diagnosed diabetes (NDD) and prediabetes.

Results

Out of 6836 participants, 4690 (68.6%) had NGT, 1333 (19.5%) had prediabetes and 813 (11.9%) had NDD by OGTT criteria with median (IQR) age of 40 (31–50) years. Optimal HbA1c cut-off point for identification of diabetes and prediabetes was observed as 5.7% ((AUC (95% CI)=0.776 (0.757 to 0.795), p<0.0001)) and 5.1% ((AUC (95% CI)=0.607 (0.590 to 0.624), p<0.0001)), respectively. However, out of 68.6% NGT subjects identified through OGTT, 24.1% and 9.3% participants were found to have prediabetes and NDD, respectively by using HbA1c criteria. By using both OGTT and HbA1c criteria, only 7.9% and 7.3% were observed as prediabetes and diabetes, respectively.

Conclusion

Findings from second NDSP demonstrated disagreement between findings of OGTT and HbA1c as diagnostic tool for Pakistani population. As compared with international guidelines, HbA1c threshold for prediabetes and NDD were lower in this part of world. HbA1c as diagnostic tool might require ethnic or regional-based modification in cut-off points, validated by relevant community-based epidemiological surveys.
Universal access to essential health information: accelerating progress towards universal health coverage and other SDG health targets
Authors: Royston Geoff , Pakenham-Walsh Neil , Zielinski Chris
Published: May 2020

The information that people need to protect and manage their own health and the health of those for whom they are responsible is a fundamental element of an effective people-centred healthcare system. Achieving universal health coverage (UHC) requires universal access to essential health information. While it was recently recognised by the World Medical Association, universal access to essential health information is not yet reflected in official monitoring of progress on UHC for the sustainable development goals (SDGs). In this paper, we outline key features that characterise universal access to essential health information and indicate how it is increasingly achievable. We highlight the growing evidence of the impact of wider access to practical and actionable information on health for the public, carers and frontline health workers and provide illustrative, evidence-based, examples of how increasing access to essential health information can accelerate the achievement of UHC and other health targets of the SDGs. The paper ends with an assessment of reasons why universal access to essential health information has not yet been achieved, and an associated call to action to key stakeholders—such as governments, multilaterals, funding bodies, policy-makers, health professionals and knowledge intermediaries—to explicitly recognise the foundational role of universal access to essential health information for achieving UHC and the rest of the health SDGs, to include it in the relevant SDG target and associated monitoring indicators, and to incorporate actions in their own policies and programmes to promote and enable this access.
Mental health interventions for suicide prevention among indigenous adolescents: a systematic review protocol
Authors: Grande Antonio José , Elia Christelle , Peixoto Clayton , Jardim Paulo de Tarso Coelho , Dazzan Paola , Veras Andre Barciela , Cruickshank John Kennedy , Harding Seeromanie
Published: May 2020

Introduction

There are more than 370 million indigenous people from 5000 cultures living in 90 countries worldwide. Although they make up 5% of the global population, they account for 15% of the extreme poor. Youth suicide is the second leading cause of mortality among 15–29 years old and disproportionately affects indigenous youth. This research protocol pertains to a systematic review of studies that use a comparator/control group to evaluate the effectiveness of suicide interventions targeting indigenous adolescents (aged 10–19 years).

Methods and analysis

We will conduct a systematic search on MEDLINE, EMBASE, CINAHL, LILACS and PsycINFO from inception to September 2019 to identify articles that compare mental health interventions for suicide prevention among indigenous adolescents. Two reviewers will independently determine the eligibility of each study. Studies will be assessed for methodological quality using the risk of bias tool to assess non-randomised studies of interventions. We will conduct a meta-analysis if possible and use established statistical methods to identify and control for heterogeneity where appropriate.

Ethics and dissemination

This systematic review will use published data and does not require ethics approval. However, this review is in preparation of a feasibility study that will examine how best to support the physical and mental health of indigenous adolescents in Brazil. Ethics approval for the feasibility study was obtained from National Research Ethics Commission. Findings will be disseminated through a peer-reviewed publication and will be made available to key decision-makers with authority for indigenous health and other relevant stakeholders.

PROSPERO registration number

CRD42019141754.
How self-stigma affects patient activation in persons with type 2 diabetes: a cross-sectional study
Authors: Kato Asuka , Fujimaki Yuko , Fujimori Shin , Isogawa Akihiro , Onishi Yukiko , Suzuki Ryo , Ueki Kohjiro , Yamauchi Toshimasa , Kadowaki Takashi , Hashimoto Hideki
Published: May 2020

Objectives

Self-stigma is associated with lower patient activation levels for self-care in persons with type 2 diabetes mellitus (T2DM). However, the causal pathway linking self-stigma with patient activation for self-care has not been shown. In order to determine how self-stigma affects patient activation for self-care, we tested a two-path hypothetical model both directly and as mediated by self-esteem and self-efficacy.

Design

A cross-sectional study.

Setting

Two university hospitals, one general hospital and one clinic in Japan.

Participants

T2DM outpatients receiving treatment (n=209) completed a self-administered questionnaire comprising the Self-Stigma Scale, Patient Activation Measure, Rosenberg Self-Esteem Scale, General Self-Efficacy Scale, Patient Health Questionnaire, haemoglobin A1c test, age, sex and body mass index.

Primary and secondary outcome measures

Self-stigma levels were measured by using the Self-Stigma Scale. Patient activation levels were measured by the Patient Activation Measure.

Results

Path analysis showed a strong relationship between self-stigma and patient activation (χ2=27.55, p=0.120; goodness-of-fit index=0.97; adjusted goodness-of-fit index=0.94; comparative fit index=0.98; root mean square error of approximation=0.04). Self-stigma had a direct effect on patient activation (β=−0.20; p=0.002). Indirectly, self-stigma affected patient activation along two paths (β=0.31; p<0.001) by reducing self-esteem (β=−0.22; p<0.001) and self-efficacy (β=−0.36; p<0.001).

Conclusions

Due to the cross-sectional design of the study, longitudinal changes between all the variables cannot be established. However, the findings indicate that self-stigma affected patient activation for self-care, both directly and as mediated by self-esteem and self-efficacy. Interventions that increase self-esteem and self-efficacy may decrease self-stigma in patients with T2DM, thus increasing patient activation for self-care.
Effectiveness and acceptability of metformin in preventing the onset of type 2 diabetes after gestational diabetes in postnatal women: a protocol for a randomised, placebo-controlled, double-blind feasibility trial — Optimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA)
Authors: Amaefule Chiamaka Esther , Bolou Angeliki , Drymoussi Zoe , Gonzalez Carreras Francisco Jose , Pardo Llorente Maria del Carmen , Lanz Doris , Dodds Julie , Sweeney Lorna , Pizzo Elena , D’Amico Maria , Thomas Amy , Heighway James , Daru Jahnavi , Sobhy Soha , Robson John , Sanghi Anita , Zamora Javier , Harden Angela , Hitman Graham , Khan Khalid , Pérez Teresa , Huda Mohammed SB , Thangaratinam Shakila
Published: May 2020

Introduction

Up to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial.

Methods and analysis

Optimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA) is a multicentre placebo-controlled double-blind randomised feasibility trial, where we will randomly allocate 160 postnatal women with gestational diabetes treated with medication to either metformin (intervention) or placebo (control) tablets to be taken until 1 year after delivery. The primary outcomes are rates of recruitment, randomisation, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes in both arms, and acceptability of the study and intervention, which will be evaluated through a nested qualitative study. Feasibility outcomes will be summarised using descriptive statistics, point estimates and 95% CIs.

Ethics and dissemination

The OMAhA study received ethics approval from the London-Brent Research Ethics Committee (18/LO/0505). Trial findings will be published in a peer-reviewed journal, disseminated at conferences, through our Patient and Public Involvement advisory group (Katie’s Team) and through social media platforms.

Trial registration number

ISRCTN20930880
Improving the use of the ‘COUGH’ bundle in Surgical High Dependency Unit, Ninewells Hospital, Dundee
Authors: Livie Victoria , Livie Jennifer , Hilton-Christie Sharon
Published: May 2020

Developing respiratory complications postoperatively is one of the major determinants of longer hospital stay, morbidity, mortality and increased healthcare costs. The incidence of postoperative respiratory complications varies from 1% to 23%. Given that postoperative respiratory complications are relatively common and costly, there have been various studies which look at ways to reduce the risk of these occurring. One such protocol is the ICOUGH bundle which stands for Incentive spirometry, Coughing and deep breathing, Oral care, patient Understanding, Getting out of bed and Head of bed elevation. This has been adapted locally to the Coughing and deep breathing, Oral care, patient Understanding, Getting out of bed and Head of bed elevation (COUGH) bundle which consists of these components excluding incentive spirometry. Within our surgical high dependency unit (HDU), the COUGH bundle should be implemented in patients who have a moderate or high risk of developing postoperative respiratory complications with an Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score of 26 or above. Studies have shown that the ICOUGH bundle has reduced rates of pneumonia and unplanned intubation in general surgical and vascular patients. Baseline data taken from surgical HDU showed that the COUGH bundle was not well implemented. One out of eight patients who had an ARISCAT score greater than 26 had the COUGH bundle implemented on admission to the unit. Three out of eight patients had the ARISCAT score documented in their admission medical review. One patient who should have received the bundle, but did not, developed a hospital acquired pneumonia postoperatively. To address this issue, we aimed to increase awareness surrounding the COUGH bundle and to increase the number of patients who had the COUGH bundle started on admission. This quality improvement project had four cycles (plan, do, study, act) and after these, 100% of patients who had an ARISCAT score of 26 or more had the COUGH bundle implemented.
Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial
Authors: Arai Toru , Kida Hiroshi , Ogata Yoshitaka , Marumo Satoshi , Matsuoka Hiroto , Gohma Iwao , Yamamoto Suguru , Mori Masahide , Sugimoto Chikatoshi , Tachibana Kazunobu , Akira Masanori , Inoue Yoshikazu
Published: May 2020

Background

Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP.

Methods

In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP.

Results

We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0).

Conclusions

Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.

Trial registration number

UMIN000014969, date: 28 August 2014.
Selecting esophageal cancer patients for lymphadenectomy after neoadjuvant chemoradiotherapy: a modeling study
Authors: Scholte Mirre , de Gouw Didi JJM , Klarenbeek Bastiaan R , Grutters Janneke PC , Rosman Camiel , Rovers Maroeska M
Published: May 2020

Objectives

Two-thirds of patients do not harbor lymph node (LN) metastases after neoadjuvant chemoradiotherapy (nCRT). Our aim was to explore under which circumstances a selective lymph node dissection (LND) strategy, which selects patients for LND based on the restaging results after nCRT, has added value compared with standard LND in esophageal cancer.

Design

A decision tree with state-transition model was developed. Input data on short-term and long-term consequences were derived from literature. Sensitivity analyses were conducted to assess promising scenarios and uncertainty.

Setting

Dutch healthcare system.

Participants

Hypothetical cohort of esophageal cancer patients who have already received nCRT and are scheduled for esophagectomy.

Interventions

A standard LND cohort was compared with a cohort of patients that received selective LND based on the restaging results after nCRT.

Main outcome measures

Quality-adjusted life years (QALYs), residual LN metastases and LND-related complications.

Results

Selective LND could have short-term benefits, that is, a decrease in the number of performed LNDs and LND-related complications. However, this may not outweigh a slight increase in residual LN metastases which negatively impacts QALYs in the long-term. To accomplish equal QALYs as with standard LND, a new surgical strategy should have the same or higher treatment success rate as standard LND, that is, should show equal or less recurrences due to residual LN metastases.

Conclusions

The reduction in LND-related complications that is accomplished by selecting patients for LND based on restaging results after nCRT seems not to outweigh a QALY loss in the long-term due to residual LN metastases. Despite the short-term advantages of selective LND, this strategy can only match long-term QALYs of standard LND when its success rate equals the success rate of standard LND.
Telementoring for remote simulation instructor training and faculty
development using telesimulation
Authors: Gross Isabel Theresia , Whitfill Travis , Auzina Luize , Auerbach Marc , Balmaks Reinis
Published: May 2020

Introduction

Simulation-based training is essential for high-quality medical care, but
it requires access to equipment and expertise. Technology can facilitate
connecting educators to training in simulation. We aimed to explore the use of
remote simulation faculty development in Latvia using telesimulation and
telementoring with an experienced debriefer located in the USA.

Methods

This was a prospective, simulation-based longitudinal study. Over the
course of 16 months, a remote simulation instructor (RI) from the USA and a
local instructor (LI) in Latvia cofacilitated with teleconferencing.
Responsibility gradually transitioned from the RI to the LI. At the end of each
session, students completed the Debriefing Assessment for Simulation in
Healthcare (DASH) student version form (DASH-SV) and a general feedback form,
and the LI completed the instructor version of the DASH form (DASH-IV). Outcome
measures were the changes in DASH scores over time.

Results

A total of eight simulation sessions were cofacilitated of 16 months. As
the role of the LI increased over time, the debrief quality measured with the
DASH-IV did not change significantly (from 89 to 87), although the DASH-SV
score decreased from a total median score of 89 (IQR 86–98) to 80 (IQR 78–85)
(p=0.005).

Conclusion

In this study, telementoring with telesimulations resulted in high-quality
debriefing. The quality—perceived by the students—was higher with the
involvement of the remote instructor and declined during the transition to the
LI. This concept requires further investigation and could potentially build
local simulation expertise promoting sustainability of high-quality
simulation.
Comorbid psoriasis-bipolar disorder successfully treated with apremilast: much more than a mere coincidence?
Authors: Uvais N A , Rakhesh S V , Afra T P , Hafi N A Bishurul , Razmi T Muhammed
Published: May 2020

Psoriasis is a chronic, immune mediated, systemic inflammatory skin disease with a reported prevalence of 0.6%–4.8% in the general population. Bipolar disorder (BP) is a severe episodic psychiatric disorder that ranks as the fourth leading cause of disability. Recent evidence suggests that genetic and immunological factors play a significant role in the development of both disorders. Studies have also shown a higher association of psychiatric disorders among patients with psoriasis. Moreover, several autoimmune comorbidities have been reported in association with BP. Here, we describe a young woman with BP who developed psoriasis after 1 year of developing BP and showed exacerbations in psoriasis lesions with each manic episode. We also highlight the safe and efficacious use of apremilast for psoriatic lesions in the woman.
Bystanders’ behaviours and associated factors in cyberbullying
Authors: Panumaporn Jidapa , Hongsanguansri Sirichai , Atsariyasing Wanlop , Kiatrungrit Komsan
Published: May 2020

Background

Cyberbullying is presently an alarming problem worldwide due to its impact on the emotions, behaviour and psychological well-being of not only the victims, but the bullies themselves and also bystanders.

Aim

This study aims to investigate bystanders’ behaviours in cyberbullying and associated factors.

Methods

This research is a cross-sectional study of 578 secondary school students in Bangkok, Thailand. Simple random sampling was used to select four secondary schools. Data were collected through online questionnaires which included four sections: (1) demographic data, (2) bystanders’ behaviour in cyberbullying (cyberbullying experience and attitude towards cyberbullying were included in this section), (3) parental attachment (Inventory of Parent Attachment-Revised), and (4) self-esteem (Rosenberg Self-Esteem Scale-Revised).

Results

It was found that most occurrences of bystanders’ behaviour were: (a) willing to intervene or help victims (34.6%), (b) ignoring the cyberbullying (28%) or (c) partaking in cyberbullying (26.3%). Participants who either were victims of cyberbullying or knew of cyberbullying happening to friends or relatives and had high parental attachment would intervene more than those who never had such experiences. Participants who knew of cyberbullying happening to the general public had tendencies towards ignoring the cyberbullying. Participants who indicated they were bullies and had positive attitude towards joining in tended to partake in the cyberbullying more than those who were not.

Conclusion

Factors relating to the behaviours of bystanders in cyberbullying should be further explored to provide support in the discouragement of ignoring and averting participation in cyberbullying. Secure parental attachment is one important factor that should be instilled during childhood years.
Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer
Authors: Knudsen Erik S , Kumarasamy Vishnu , Chung Sejin , Ruiz Amanda , Vail Paris , Tzetzo Stephanie , Wu Jin , Nambiar Ram , Sivinski Jared , Chauhan Shailender S , Seshadri Mukund , Abrams Scott I , Wang Jianmin , Witkiewicz Agnieszka K
Published: May 2020

Objective

This study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer.

Design

Patient-derived cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic syngeneic models. Single-cell RNA sequencing and multispectral imaging were employed to delineate effects on the immunological milieu in the tumour microenvironment.

Results

We found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumour progression. These effects were associated with stable cell-cycle arrest, as well as the induction of multiple genes associated with interferon response and antigen presentation in an RB-dependent fashion. Using single-cell sequencing and complementary approaches, we found that the combination of CDK4/6 and MEK inhibition had a significant impact on increasing T-cell infiltration and altering myeloid populations, while potently cooperating with immune checkpoint inhibitors.

Conclusions

Together, these data indicate that there are canonical and non-canonical features of CDK4/6 and MEK inhibition that impact on the tumour and immune microenvironment. This combination-targeted treatment can promote robust tumour control in combination with immune checkpoint inhibitor therapy.
Global epidemiology of
Neisseria gonorrhoeae
in infertile populations: systematic review, meta-analysis and metaregression
Authors: Chemaitelly Hiam , Majed Alzahraa , Abu-Hijleh Farah , Blondeel Karel , Matsaseng Thabo Christopher , Kiarie James , Toskin Igor , Abu-Raddad Laith J
Published: May 2020

Objective

To provide an in-depth systematic assessment of the global epidemiology of gonorrhoea infection in infertile populations.

Methods

A systematic literature review was conducted up to 29 April 2019 on international databases and WHO regional databases, and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All prevalence measures of gonorrhoea infection among infertile populations, based on primary data, qualified for inclusion. Infertile populations were broadly defined to encompass women/men undergoing infertility evaluation or treatment (infertility clinic attendees and partners). Pooled mean prevalence by relevant strata was estimated using random-effects meta-analysis. Associations with prevalence and sources of heterogeneity were explored using metaregression. Risk of bias was assessed using four quality domains.

Findings

A total of 147 gonorrhoea prevalence studies were identified from 56 countries. The pooled mean prevalence of current gonorrhoea infection was estimated globally at 2.2% (95% CI 1.3% to 3.2%), with the highest prevalence in Africa at 5.0% (95% CI 1.9% to 9.3%). The mean prevalence was higher for populations with tubal factor infertility (3.6%, 95% CI 0.9%–7.7%) and mixed cause and unexplained infertility (3.6%, 95% CI 0.0% to 11.6%) compared with other diagnoses, such as ovarian and non-tubal infertility (0.1%, 95% CI 0.0% to 0.8%), and for secondary (2.5%, 95% CI 0.2% to 6.5%) compared with primary (0.5%, 95% CI 0.0% to 1.7%) infertility. Metaregression identified evidence of variations in prevalence by region and by infertility diagnosis, higher prevalence in women than men and a small-study effect. There was a trend of declining prevalence by about 3% per year over the last four decades (OR=0.97, 95% CI 0.95 to 0.99).

Conclusions

Gonorrhoea prevalence in infertile populations is several folds higher than that in the general population, with even higher prevalence in women with tubal factor infertility and in individuals with secondary infertility. These findings support the potential role of gonorrhoea in infertility and suggest that some infertility is possibly preventable by controlling gonorrhoea transmission.

PROSPERO registration number

CRD42018102934.
SINGAPORE ENGAGES THE BELT AND ROAD INITIATIVE: PERCEPTIONS, POLICIES, AND INSTITUTIONS
Authors: LIU HONG , FAN XIN , LIM GUANIE
Published: May 2020

This article argues that Singapore, courtesy of its strong state capacity and long-standing connections with China, has promoted effective polices and coordinated mutually reinforcing institutional mechanisms in engaging with the Belt and Road Initiative (BRI). While some of these institutions predate the BRI, they have been continuously enhanced or modified to meaningfully foster Singapore-China cooperation. In certain cases, new institutions have been created to fulfill specific demands the existing institutions cannot adequately serve. These two types of institutions not only complement each other but also promote cooperation between the bureaucrats, politicians, transnational corporations, government-linked corporations, small- and medium-sized private firms and business associations. The article also illustrates the flexibility of the ‘networked state’ in formulating collaborative ties linking key international and domestic actors, demonstrating how a small state like Singapore can partner China effectively and deepen its strategic importance to the BRI to enhance its own strategic and economic interests. Lastly, the article highlights the two key conditions in BRI-related nations for their successful engagement: the existence of mutual interests between China and a counterpart nation bolstered by conducive perceptions and policies, and the institutionalization of competent mechanisms to materialize and operationalize these interests.
Multi-Modal Image Fusion via Convolutional Morphological Component Analysis and Guided Filter
Authors: Guo Peng , Xie Guoqi , Li Renfa , Hu Hui
Published: May 2020

In feature-level image fusion, deep learning technology, particularly convolutional sparse representation (SR) theory, has emerged as a new topic over the past three years. This paper proposes an effective image fusion method based on convolution SR, namely, convolutional sparsity-based morphological component analysis and guided filter (CS-MCA-GF). The guided filter operator and choose-max coefficient fusion scheme introduced in this method can effectively eliminate the artifacts generated by the morphological components in the linear fusion, and maintain the pixel saliency of the source images. Experiments show that the proposed method can achieve an excellent performance in multi-modal image fusion, which includes medical image fusion.
Restrictions on Homflypt and Kauffman polynomials arising from local moves
Authors: Ganzell Sandy , Gonzalez Mercedes V. , Marcum Chloe’ , Ryalls Nina , Santos Mariel
Published: May 2020

We study the effects of certain local moves on Homflyptand Kauffman polynomials. We show that all Homflypt(or Kauffman) polynomials are equal in a certain nontrivial quotient of the Laurent polynomial ring. As a consequence, we discover some new properties of these invariants.
Damping Characteristics of Bending Vibration of Thick-Walled CFRP Hollow Shafts
Authors: Yang Mo , Zhou Xian , Zhou Yuebin , Qin Tao , Ye Jianmin , Lyu Xujun
Published: May 2020

The damping characteristics of the composite thick-walled hollow shaft directly affect its amplitude of rotational vibration at low speeds and stability at high speeds. In this study, the shaft is made of carbon fiber reinforced plastic (CFRP) material. In order to study the damping characteristics of the composite hollow shaft, a 3D numerical damping model was established based on finite element method and strain energy expression. In this regard, both the contributions of in-plane and out-of-plane strain energy dissipation were studied. Then, the validity of 3D damping model in bending was verified by experiments. On this basis, the flexural damping characteristics of the thick-walled composite shaft were studied, and the effects of orientation angle and stacking sequences on the flexural damping were obtained.
The Impact of Cultural Intelligence on Organisational Performance: Applied Study in Sample of Jordanian Pharmaceutical Companies
Authors: Najm Najm Abood , Zaghari Aya Y.
Published: May 2020

The aim of this study is to determine the impact of cultural intelligence in its four dimensions (metacognitive, cognitive, motivational and behavioural) on organisational performance based on three criteria: productivity, profitability and market share in Jordanian pharmaceutical companies. The study is sought to provide a broad review of the literature of cultural intelligence and administrative practices in the field of business administration and research in different parts. The results of the study confirmed that there is an impact of three dimensions of cultural intelligence (metacognitive, cognitive, behavioural) on organisational performance (productivity, profitability, market share), while the motivational dimension has no impact on all three performance criteria in Jordanian pharmaceutical companies.
A tree-based dictionary learning framework
Authors: Budinich Renato , Plonka Gerlind
Published: May 2020

We propose a new outline for adaptive dictionary learning methods for sparse encoding based on a hierarchical clustering of the training data. Through recursive application of a clustering method, the data is organized into a binary partition tree representing a multiscale structure. The dictionary atoms are defined adaptively based on the data clusters in the partition tree. This approach can be interpreted as a generalization of a discrete Haar wavelet transform. Furthermore, any prior knowledge on the wanted structure of the dictionary elements can be simply incorporated. The computational complexity of our proposed algorithm depends on the employed clustering method and on the chosen similarity measure between data points. Thanks to the multiscale properties of the partition tree, our dictionary is structured: when using Orthogonal Matching Pursuit to reconstruct patches from a natural image, dictionary atoms corresponding to nodes being closer to the root node in the tree have a tendency to be used with greater coefficients.
Climate Change Litigation
Authors: Peel Jacqueline , Osofsky Hari M.
Published: May 2020

Climate change litigation has grown exponentially in the last decade, paralleled by the emergence of a rich legal and social sciences literature assessing these cases. Building on a recent review in WIRES Climate Change, this article evaluates the growth of this literature and the key themes it highlights. In 2019, climate litigation literature experienced substantial growth, with a focus on multiple novel dimensions: new high-profile judgments; emerging legal avenues, types of actors, litigation objectives, and jurisdictions, especially those in the Global South; and additional interdisciplinary analyses. Just as in the underlying case law, climate litigation scholarship shows evidence of distinct but overlapping waves that build together in a manner similar to a harmonic chord. Even so, this literature has not yet engaged deeply with questions about the effectiveness of climate litigation as a governance tool, particularly in the context of the decentralized system formalized with the 2015 Paris Agreement.
Statins activate the NLRP3 inflammasome and impair insulin signaling via p38 and mTOR
Authors: Henriksbo Brandyn D. , Tamrakar Akhilesh K. , Phulka Jobanjit S. , Barra Nicole G. , Schertzer Jonathan D.
Published: May 2020

Statins lower cholesterol and risk of cardiovascular disease. Statins can increase blood glucose and risk of new-onset diabetes. It is unclear why statins can have opposing effects on lipids versus glucose. Statins have cholesterol-independent pleiotropic effects that influence both insulin and glucose control. Statin lowering of isoprenoids required for protein prenylation promotes pancreatic β-cell dysfunction and adipose tissue insulin resistance. Protein prenylation influences immune function and statin-mediated adipose tissue insulin resistance involves the NLR family pyrin domain-containing 3 (NLRP3) inflammasome and IL-1β. However, the intracellular cues that statins engage to activate the NLRP3 inflammasome and those responsible for IL-1β-mediated insulin resistance in adipose tissue have not been identified. We hypothesized that stress kinases or components of the insulin signaling pathway mediated statin-induced insulin resistance. We tested the associations of p38, ERK, JNK, phosphatase, and tensin homolog (PTEN), and mTOR in statin-exposed adipose tissue from WT and IL-1β−/− mice. We found that statins increased phosphorylation of p38 in WT and IL-1β−/− mice. Statin activation of p38 upstream of IL-1β led to priming of this NLRP3 inflammasome effector in macrophages. We found that mTORC1 inhibition with low doses of rapamycin (2 or 20 nM) lowered macrophage priming of IL-1β mRNA and secretion of IL-1β caused by multiple statins. Rapamycin (20 nM) or the rapalog everolimus (20 nM) prevented atorvastatin-induced lowering of insulin-mediated phosphorylation of Akt in mouse adipose tissue. These results position p38 and mTOR as mediators of statin-induced insulin resistance in adipose tissue and highlight rapalogs as candidates to mitigate the insulin resistance and glycemic side effects of statins.
A Novel PRRT2 Variant in Chinese Patients Suffering from Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsion
Authors: Baldi Salem , Zhu Jin-Ling , Hu Qing-Yun , Wang Ju-Li , Zhang Jin-Bo , Zhang Shu-Hong
Published: May 2020

PRRT2 mutations are the major causative agent of paroxysmal kinesigenic dyskinesia with infantile convulsion (PKD/IC). The study is aimed at screening PRRT2 gene mutations in patients who suffered from PKD/IC in Chinese population. Thirteen Chinese patients with PKD/IC were screened randomly for coding exons of the PRRT2 gene mutation along with 50 ethnically coordinated control people. Nine (2 unaffected) and 4 of the patients showed familial PKD/IC and apparently sporadic cases, respectively. We identified 5 different PRRT2 mutations in 10 individuals, including 8 familial and 2 apparently sporadic cases. However, no mutations were found in the 50 ethnically matched controls. Unknown (novel) NM_145239.2:c.686G>A and previously reported NM_145239.2:c.743G>C variants were identified in two familial and sporadic patients. All affected members of family A showed mutation NM_145239.2:c.650_670delinsCAATGGTGCCACCACTGGGTTA. The previously identified NM_145239.2:c.412 C>G and NM_145239.2:c.709G>A variants are seen in two individuals assessed in family B. Other than the previously identified variants, some of the patients with PRRT2-PKD/IC showed a new PRRT2 substitution variant. Thus, the spectrum of PRRT2 variants is expanded. The possible role and probability of PRRT2 variants involved in PKD/IC are highlighted.
Protective Effects of Biscoclaurine Alkaloids on Leukopenia Induced by 60Co‐γ Radiation
Authors: Wang Min , Xie Xueheng , Du Yuyang , Ma Guoxu , Xu Xudong , Sun Guibo , Sun Xiaobo
Published: May 2020

Objective. Leukopenia, a common complication of tumor chemoradiotherapy, contributes serious damage to the hematopoietic, gastrointestinal, and immune systems of the body and can cause delay, discontinuation, or even failure to tumor treatment, thereby greatly threatening human health. The present study aims to investigate the protective effects of biscoclaurine alkaloids (BA) on leukopenia. Methods. This study was conducted on 60 Kunming mice, which were randomly divided into six groups containing 10 animals each. A hematology analyzer was used to count white blood cells (WBC) in the peripheral blood cell. Mice serum was collected, and the granulocyte‐macrophage colony‐stimulating factor, vascular cell adhesion molecule 1 (VCAM‐1), and interferon‐γ (IFN‐γ) were detected by enzyme‐linked immunosorbent assays. Pathological changes were detected through hematoxylin and eosin staining in the liver and spleen of mice. The spleen and liver ultrastructures were observed via electron microscopy. Results. Results showed that BA ameliorated WBC, PLT reduction in the peripheral blood and significantly increased the levels of IFN‐γ and VCAM‐1 in mice serum. BA reduced ionizing radiation‐induced injuries to spleen, mitigated the reduction of superoxide dismutase (SOD), and significantly decreased the malonaldehyde (MDA) and xanthine oxidase (XOD) levels in the liver. Conclusion. BA enhanced the immune and hematopoietic functions and ameliorated the oxidative stress induced by 60Co‐γ radiation, revealing its therapeutic potential both as a radioprotector and as a radiation mitigator for leukopenia induced by 60Co‐γ radiation.
A New Continuum Model considering Driving Behaviors and Electronic Throttle Effect on a Gradient Highway
Authors: Jiao Yulei , Cheng Rongjun , Ge Hongxia
Published: May 2020

In order to explore the potential impact of sloping road on traffic flow, an improved car-following model considering electronic throttle (ET) dynamics and driver’s driving characteristics on slope is proposed. Based on the improved car-following model, a new continuum model is established through the conversion relationship between microscopic variables and macroscopic variables. Firstly, the stability condition of the model is obtained by using the linear stability theory, after that the evolution process of traffic flow density wave near the neutral stability curve is studied by using the nonlinear analysis method, and we also get the improved KdV-Burgers equation. At the same time, numerical experiments and experimental verification of the model are carried out; the theoretical analysis and numerical results show that the ET effect and aggressive driving of drivers play an important role in alleviating traffic congestion to a certain extent.
Two Parallel-Machine Scheduling Problems with Function Constraint
Authors: Hsu Chia-Lun , Liao Jan-Ray
Published: May 2020

The objective of this paper is to minimize both the makespan and the total completion time. Since parallel-machine scheduling which contains the function constraint problem has been a new issue, this paper explored two parallel-machine scheduling problems with function constraint, which refers to the situation that the two machines have a same function but one of the machines has another. We pointed out that the function constraint occurs not only in the manufacturing system but also in the service system. For the makespan problem, we demonstrated that it is NP-hard in the ordinary sense. In addition, we presented a polynomial time heuristic for this problem and have proved its worst-case ratio is not greater than 5/4. Furthermore, we simulated the performance of the algorithm through computational testing. The overall mean percent error of the heuristic is 0.0565%. The results revealed that the proposed algorithm is quite efficient. For the total completion time problem, we have proved that it can be solved in On4 time.
Effect ofMoringa oleiferaSeed Powder on the Clarity, Colloidal Particles, and Nutritional Contents of Cashew Apple Juice
Authors: Ugwuoke Cajethan U. , Ugwuoke Felicitas G. , Omeje Benedicta A. , Eze Godwin E. , Monwuba Nnennaya S. , Ifeanyieze Florence O. , Ukonze Juliana A.
Published: May 2020

Cashew apple juice is a good source of vitamins, minerals, and other nutrients. Cashew apples are being wasted due to lack of processing and are not much cherished because of its astringency. Some of the available clarifying agents are costly and are mainly imported. The study was, therefore, aimed at finding out the effect ofM. oleiferaseed powder on the clarity and phytochemical and nutritional contents of cashew apple juice. The study adopted an experimental design where 5 g, 10 g, 15 g, and 20 g ofM. oleiferaseed powder were used to clarify 250 cm3of cashew apple juice. The setups were filtered using a filter paper after standing for an hour to get the clarified juice. The clarity of each filtrate was determined using an atomic absorption spectrometer (AAS). Similarly, the tannin, lignin, pectin, protein, starch, calcium, zinc, copper, magnesium, and vitamin C were determined following the procedure of the Association of Official Analytical Chemists (AOAC). Results showed that cashew apple juice clarified with 10 g/250 cm3gave the best clarity. The colloidal particle contents of cashew apple juice were significantly reduced by the use ofM. oleiferaseed powder. It was equally found out that the clarified cashew apple juice contained an appreciable amount of nutrients. The flavour, colour, and general acceptability of the clarified cashew apple juice were very much liked by the panellist while the aroma was moderately liked. The study recommended thatM. oleiferaseed powder should be used for clarifying cashew apple juice and be included at the rate of 10 g/250 cm3.