bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of atherosclerosis and association with 5-year outcome: The Norwegian Stroke in the Young Study
Authors: Nawaz Beenish , Fromm Annette , Øygarden Halvor , Eide Geir E , Saeed Sahrai , Meijer Rudy , Bots Michiel L , Sand Kristin M , Thomassen Lars , Næss Halvor , Waje-Andreassen Ulrike
Published: November 2021

Objectives:

We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up.

Methods:

Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle–arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied.

Results:

Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients ( p = 0.044, p = 0.020, p = 0.023 and p <0.001, respectively). Mean fIMT was higher in middle-aged female patients ( p <0.001). Cardiovascular events were associated with ischaemic ECG; AAI ≤0.9, fIMT ≥0.9 mm and increased number of areas with atherosclerosis (NAA) among patients, and with AAP, cIMT ≥0.9 mm, fIMT ≥0.9 mm and NAA among controls. Mortality was associated with higher age, ischaemic ECG and NAA among patients, and cIMT ≥0.9 mm among controls.

Conclusion:

Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.
‘Open Purpose’: Embracing Organizations as Expressive Systems
Authors: Clegg Stewart , Cunha Miguel Pina e , Rego Arménio , Santos Filipe
Published: November 2021

The concept of purpose gained prominence in organization theory in recent years but there are discrepant views of its meaning, which we review as evolving and different perspectives: economic theories of the firm; stakeholder approaches; integrative social contracts; and social mission. We elaborate these perspectives in terms of the ebb and flow of ideas and eras. Against these instrumental views, we revisit the work of Robert Cooper, namely the ever-open purpose of expressive organizations, and contrast this with fixist views of purpose in instrumental organizations. We engage with the logic of open purpose and sketch a way of rethinking purpose as a general orientation that constantly evolves and changes over time in interaction with its ecosystem.
The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia
Authors: Langerbeins Petra , Zhang Can , Robrecht Sandra , Cramer Paula , Fürstenau Moritz , Al-Sawaf Othman , von Tresckow Julia , Fink Anna-Maria , Kreuzer Karl-Anton , Vehling-Kaiser Ursula , Tausch Eugen , Müller Lothar , Eckart Michael Josef , Schlag Rudolf , Freier Werner , Gaska Tobias , Balser Christina , Reiser Marcel , Stauch Martina , Wendtner Clemens-Martin , Fischer Kirsten , Stilgenbauer Stephan , Eichhorst Barbara , Hallek Michael
Published: November 2021

Observation is the current standard of care for patients with early-stage asymptomatic chronic lymphocytic leukemia (CLL), as chemotherapy-based interventions have failed to prolong survival. We hypothesized that early intervention with ibrutinib would be well tolerated and lead to superior disease control in a subgroup of early-stage patients with CLL. The phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily. At a median follow-up of 31 months, the study met its primary endpoint by significantly improving event-free survival in the ibrutinib group (median, not reached vs 47.8 months; hazard ratio = 0.25; 95% confidence interval = 0.14-0.43, P < .0001). Compared with placebo, ibrutinib did not increase overall toxicity, yielding similar incidence and severity of adverse events (AEs). The most common serious AEs were atrial fibrillation, pneumonia, and rash in the ibrutinib group, and basal cell carcinoma, pneumonia, and myocardial infarction in the placebo group. Ibrutinib-associated risk for bleeding (33.5%) was decreased by prohibiting the use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug–drug interactions. Ibrutinib confirms efficacy in CLL patients at an early stage with an increased risk of progression. However, the results do not justify changing the current standard of “watch and wait.” This trial was registered at www.clinicaltrials.gov as #NCT02863718.
Right atrial function is associated with right venticular diastolic stiffness: RA–RV interaction in pulmonary arterial hypertension
Authors: Wessels Jeroen N. , Mouratoglou Sophia A. , van Wezenbeek Jessie , Handoko M. Louis , Marcus J. Tim , Meijboom Lilian J. , Westerhof Berend E. , Bogaard Harm Jan , Strijkers Gustav J. , Vonk Noordegraaf Anton , de Man Frances S.
Published: November 2021

Background

Pulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA–RV interaction.

Methods

PAH patients with low or high end-diastolic elastance (Eed) (n=94) were compared with controls (n=31). Treatment response was evaluated in 62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided into a passive and active phase. Vena cava backflow was calculated as RA active emptying−RV active filling and RA stroke work as RA active emptying×RV end-diastolic pressure.

Results

With increased Eed, RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling but higher RA active emptying and RA stroke work. RV active filling was lower in patients with high Eed, resulting in higher vena cava backflow. Upon treatment, Eedwas reduced in ~50% of the patients with high Eed, which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison with patients in whom Eedremained high.

Conclusions

In PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of patients with high baseline Eed, diastolic stiffness remained high, despite treatment. A reduction in Eedcoincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow.
Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial
Authors: Godet Cendrine , Couturaud Francis , Marchand-Adam Sylvain , Pison Christophe , Gagnadoux Frédéric , Blanchard Elodie , Taillé Camille , Philippe Bruno , Hirschi Sandrine , Andréjak Claire , Bourdin Arnaud , Chenivesse Cécile , Dominique Stéphane , Bassinet Laurence , Murris-Espin Marlène , Rivière Frédéric , Garcia Gilles , Caillaud Denis , Blanc François-Xavier , Goupil François , Bergeron Anne , Gondouin Anne , Frat Jean-Pierre , Flament Thomas , Camara Boubou , Priou Pascaline , Brun Anne-Laure , Laurent François , Ragot Stéphanie , Cadranel Jacques ,   for the NebuLamB study group and GREPI network, Godet C. , Couturaud F. , Cadranel J. , Frat J-P. , Brun A-L. , Laurent F. , Marchand-Adam S. , Pison C. , Gagnadoux F. , Blanchard E. , Taillé C. , Philippe B. , Hirschi S. , Andréjak C. , Chenivesse C. , Dominique S. , Bassinet L. , Murris-Espin M. , Rivière F. , Garcia G. , Caillaud D. , Blanc F-X. , Goupil F. , Gondouin A. , Flament T. , Camara B. , Priou P. , Ragot S.
Published: November 2021

Background

In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

Methods

We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters.

Results

Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference −0.6%, 95% CI −16.8– +15.6%; OR 0.98, 95% CI 0.50–1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168–476 days)versus177 days (64–288 days). At the end of maintenance therapy, total immunoglobulin-E andAspergillusprecipitins were significantly decreased in the nebulised liposomal amphotericin-B group.

Conclusions

In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.
Changes in health-related quality of life as a marker in the prognosis in COPD patients
Authors: Esteban Cristóbal , Arostegui Inmaculada , Aramburu Amaia , Moraza Javier , Aburto Myriam , Aizpiri Susana , Chasco Leyre , Quintana José M.
Published: November 2021

Chronic obstructive pulmonary disease (COPD) is understood as a complex, heterogeneous and multisystem airway obstructive disease. The association of deterioration in health-related quality of life (HRQoL) with mortality and hospitalisation for COPD exacerbation has been explored in general terms. The specific objectives of this study were to determine whether a change in HRQoL is related, over time, to mortality and hospitalisation.

Overall, 543 patients were recruited through Galdakao Hospital's five outpatient respiratory clinics. Patients were assessed at baseline, and the end of the first and second year, and were followed up for 3 years. At each assessment, measurements were made of several variables, including HRQoL using the St George's Respiratory Questionnaire (SGRQ).

The cohort had moderate obstruction (forced expiratory volume in 1 s 55% of the predicted value). SGRQ total, symptoms, activity and impact scores at baseline were 39.2, 44.5, 48.7 and 32.0, respectively. Every 4-point increase in the SGRQ was associated with an increase in the likelihood of death: “symptoms” domain odds ratio 1.04 (95% CI 1.00–1.08); “activity” domain OR 1.12 (95% CI 1.08–1.17) and “impacts” domain OR 1.11 (95% CI 1.06–1.15). The rate of hospitalisations per year was 5% (95% CI 3–8%) to 7% (95% CI 5–10%) higher for each 4-point increase in the separate domains of the SGRQ.

Deterioration in HRQoL by 4 points in SGRQ domain scores over 1 year was associated with an increased likelihood of death and hospitalisation.
Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease
Authors: Boustani Karim , Ghai Poonam , Invernizzi Rachele , Hewitt Richard J. , Maher Toby M. , Li Quan-Zhen , Molyneaux Philip L. , Harker James A.
Published: November 2021

Background

Fibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD, and assessed association with disease severity and outcome.

Methods

Bronchoalveolar lavage (BAL) fluid was collected from a cohort of fILD patients and total BAL antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 122 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.

Results

A subset of patients with fILD but not healthy controls had a local autoimmune signature in their BAL that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased BAL total IgA and IgG1while subjects with CHP had increased BAL IgA, IgG1and IgG4. In patients with CHP, increased BAL total IgA was associated with reduced survival probability.

Conclusion

Airway autoantibodies that are not present systemically identify a group of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.
Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge
Authors: Jha Akhilesh , Chen Fangyue , Mann Sam , Shah Ravi , Abu-Youssef Randa , Pavey Holly , Lin-Jia-Qi Helen , Cara Josh , Cunningham Daniel , Fitzpatrick Kate , Goh Celine , Ma Renee , Mookerjee Souradip , Nageshwaran Vaitehi , Old Timothy , Oxley Catherine , Jordon Louise , Selvan Mayurun , Wood Anna , Ying Andrew , Zhang Chen , Wozniak Dariusz , Goodhart Iain , Early Frances , Fisk Marie , Fuld Jonathan
Published: November 2021

Background

Prone positioning has a beneficial role in coronavirus disease 2019 (COVID-19) patients receiving ventilation but lacks evidence in awake non-ventilated patients, with most studies being retrospective, lacking control populations and information on subjective tolerability.

Methods

We conducted a prospective, single-centre study of prone positioning in awake non-ventilated patients with COVID-19 and non-COVID-19 pneumonia. The primary outcome was change in peripheral oxygenation in proneversussupine position. Secondary outcomes assessed effects on end-tidal CO2, respiratory rate, heart rate and subjective symptoms. We also recruited healthy volunteers to undergo proning during hypoxic challenge.

Results

238 hospitalised patients with pneumonia were screened; 55 were eligible with 25 COVID-19 patients and three non-COVID-19 patients agreeing to undergo proning – the latter insufficient for further analysis. 10 healthy control volunteers underwent hypoxic challenge. Patients with COVID-19 had a median age of 64 years (interquartile range 53–75). Proning led to an increase in oxygen saturation measured by pulse oximetry (SpO2) compared to supine position (difference +1.62%; p=0.003) and occurred within 10 min of proning. There were no effects on end-tidal CO2, respiratory rate or heart rate. There was an increase in subjective discomfort (p=0.003), with no difference in breathlessness. Among healthy controls undergoing hypoxic challenge, proning did not lead to a change in SpO2or subjective symptom scores.

Conclusion

Identification of suitable patients with COVID-19 requiring oxygen supplementation from general ward environments for awake proning is challenging. Prone positioning leads to a small increase inSpO2within 10 min of proning though is associated with increased discomfort.
Laboratory methods to decipher epigenetic signatures: a comparative review
Authors: Halabian Raheleh , Valizadeh Arshad  , Ahmadi Ali , Saeedi Pardis , Azimzadeh Jamalkandi Sadegh , Alivand Mohammad Reza
Published: November 2021

Epigenetics refers to nucleotide sequence-independent events, and heritable changes, including DNA methylation and histone modification (as the two main processes), contributing to the phenotypic features of the cell. Both genetics and epigenetics contribute to determining the outcome of regulatory gene expression systems. Indeed, the flexibility of epigenetic effects and stability of genetic coding lead to gene regulation complexity in response signals. Since some epigenetic changes are significant in abnormalities such as cancers and neurodegenerative diseases, the initial changes, dynamic and reversible properties, and diagnostic potential of epigenomic phenomena are subject to epigenome-wide association studies (EWAS) for therapeutic aims. Based on recent studies, methodological developments are necessary to improve epigenetic research. As a result, several methods have been developed to explore epigenetic alterations at low, medium, and high scales, focusing on DNA methylation and histone modification detection. In this research field, bisulfite-, enzyme sensitivity- and antibody specificity-based techniques are used for DNA methylation, whereas histone modifications are gained based on antibody recognition. This review provides a mechanism-based understanding and comparative overview of the most common techniques for detecting the status of epigenetic effects, including DNA methylation and histone modifications, for applicable approaches from low- to high-throughput scales.
Integration of adeno-associated virus (AAV) into the genomes of most Thai and Mongolian liver cancer patients does not induce oncogenesis
Authors: Schäffer Alejandro A. , Dominguez Dana A. , Chapman Lesley M. , Gertz E. Michael , Budhu Anuradha , Forgues Marshonna , Chaisaingmongkol Jittiporn , Rabibhadana Siritida , Pupacdi Benjarath , Wu Xiaolin , Bayarsaikhan Enkhjargal , Harris Curtis C. , Ruchirawat Mathuros , Ruppin Eytan , Wang Xin Wei
Published: November 2021

Background

Engineered versions of adeno-associated virus (AAV) are commonly used in gene therapy but evidence revealing a potential oncogenic role of natural AAV in hepatocellular carcinoma (HCC) has raised concerns. The frequency of potentially oncogenic integrations has been reported in only a few populations. AAV infection and host genome integration in another type of liver cancer, cholangiocarcinoma (CCA), has been studied only in one cohort. All reported oncogenic AAV integrations in HCC come from strains resembling the fully sequenced AAV2 and partly sequenced AAV13. When AAV integration occurs, only a fragment of the AAV genome is detectable in later DNA or RNA sequencing. The integrated fragment is typically from the 3’ end of the AAV genome, and this positional bias has been only partly explained. Three research groups searched for evidence of AAV integration in HCC RNAseq samples in the Cancer Genome Atlas (TCGA) but reported conflicting results.

Results

We collected and analyzed whole transcriptome and viral capture DNA sequencing in paired tumor and non-tumor samples from two liver cancer Asian cohorts from Thailand (N = 147, 47 HCC and 100 intrahepatic cholangiocarcinoma (iCCA)) and Mongolia (N = 70, all HCC). We found only one HCC patient with a potentially oncogenic integration of AAV, in contrast to higher frequency reported in European patients. There were no oncogenic AAV integrations in iCCA patients. AAV genomic segments are present preferentially in the non-tumor samples of Thai patients.

By analyzing the AAV genome positions of oncogenic and non-oncogenic integrated fragments, we found that almost all the putative oncogenic integrations overlap the X gene, which is present and functional only in the strain AAV2 among all fully sequenced strains. This gene content difference could explain why putative oncogenic integrations from other AAV strains have not been reported.

We resolved the discrepancies in previous analyses of AAV presence in TCGA HCC samples and extended it to CCA. There are 12 TCGA samples with an AAV segment and none are in Asian patients. AAV segments are present in preferentially in TCGA non-tumor samples, like what we observed in the Thai patients.

Conclusions

Our findings suggest a minimal AAV risk of hepatocarcinogenesis in Asian liver cancer patients. The partial genome presence and positional bias of AAV integrations into the human genome has complicated analysis of possible roles of AAV in liver cancer.
Oxytocin administration for induction and augmentation of labour in polish maternity units – an observational study
Authors: Baranowska Barbara , Kajdy Anna , Kiersnowska Iwona , Sys Dorota , Tataj-Puzyna Urszula , Daly Déirdre , Rabijewski Michał , Bączek Grażyna , Węgrzynowska Maria
Published: November 2021

Background

There is not enough data regarding practices and protocols on the dose of oxytocin administrated to women during labour. Empirical evidence indicates that compliance with the guidelines improves the quality of healthcare and reduces adverse effects. The study aimed to evaluate practices of oxytocin provision for labour induction and augmentation in two maternity units in Poland.

Methods

The article presents a prospective observational study. Data from 545 (n = 545) labours was collected in two maternity units. First, the total dose (the total amount of oxytocin provided from the beginning in the labour ward until delivery including the III and IV stage of labour) and cumulative dose of oxytocin (the amount of oxytocin given until the birth of the neonate) administered to women during labour was calculated. Then, the relationship between the cumulative dose of oxytocin and short term perinatal outcomes (mode of delivery, use of epidural anaesthesia, Apgar scores, birth weight and postpartum blood loss) was analysed. Finally, the compliance of oxytocin supply during labour with national guidelines in the following five criteria: medium, start dose, escalation rate, interval, the continuation of infusion after established labour was examined.

Results

The average cumulative dose of oxytocin administrated to women before birth was 4402 mU following labour induction and 2366 mU following labour augmentation. The actual administration of oxytocin deviated both from the unit and national guidelines in 93.6% of all observed labours (mainly because of continuation of infusion after established labour). We found no statistically significant correlation between the cumulative dose of oxytocin administered and mode of delivery, immediate postpartum blood loss or Apgar scores. There was no observed effect of cumulative dose oxytocin on short-term perinatal outcomes. The two units participating in the study had similar protocols and did not differ significantly in terms of total oxytocin dose, rates of induction and augmentation - the only observed difference was the mode of delivery.

Conclusions

The study showed no effect of the mean cumulative oxytocin dose on short-term perinatal outcomes and high rate of non-compliance of the practice of oxytocin administration for labour induction and augmentation with the national recommendations. Cooperation between different professional groups of maternity care providers should be considered in building national guidelines for maternity care.. Further studies investigating possible long-term effects of the meant cumulative dose of oxytocin and the reasons for non-compliance of practice with guidelines should be carried out.
Construction of a microenvironment immune gene model for predicting the prognosis of endometrial cancer
Authors: Wang Yichen , Zhang Jingkai , Zhou Yijun , Li Zhiguang , Lv Dekang , Liu Quentin
Published: November 2021

Background

Infiltrating immune and stromal cells are important components of the endometrial cancer (EC) microenvironment, which has a significant effect on the biological behavior of EC, suggesting that unique immune-related genes may be associated with the prognosis of EC. However, the association of immune-related genes with the prognosis of EC has not been elucidated. We attempted to identify immune-related genes with potentially prognostic value in EC using The Cancer Genome Atlas database and the relationship between immune microenvironment and EC.

Methods

We analyzed 578 EC samples from TCGA database and used weighted gene co-expression network analysis to screen out immune-related genes. We constructed a protein–protein interaction network and analyzed it using STRING and Cytoscape. Immune-related genes were analyzed through conjoint Cox regression and random forest algorithm analysis were to identify a multi-gene prediction model and stratify low-risk and high-risk groups of EC patients. Based on these data, we constructed a nomogram prediction model to improve prognosis assessment. Evaluation of Immunological, gene mutations and gene enrichment analysis were applied on these groups to quantify additional differences.

Results

Using conjoint Cox regression and random forest algorithm, we found that TRBC2, TRAC, LPXN, and ARHGAP30 were associated with the prognosis of EC and constructed four gene risk models for overall survival and a consistent nomogram. The time-dependent receiver operating characteristic curve analysis revealed that the area under the curve for 1-, 3-, and 5-y overall survival was 0.687, 0.699, and 0.76, respectively. These results were validated using a validation cohort. Immune-related pathways were mostly enriched in the low-risk group, which had higher levels of immune infiltration and immune status.

Conclusion

Our study provides new insights for novel biomarkers and immunotherapy targets in EC.
Co-design of a digital dietary intervention for adults at risk of type 2 diabetes
Authors: Tay Brenda S. J. , Edney Sarah M. , Brinkworth Grant D. , Cox David N. , Wiggins Bonnie , Davis Aaron , Gwilt Ian , Haveman-Nies Annemien , Ryan Jillian C.
Published: November 2021

Background

Co-design has the potential to create interventions that lead to sustainable health behaviour change. Evidence suggests application of co-design in various health domains has been growing; however, few public-facing digital interventions have been co-designed to specifically address the needs of adults at risk of Type 2 diabetes (T2D). This study aims to: (1) co-design, with key stakeholders, a digital dietary intervention to promote health behaviour change among adults at risk of T2D, and (2) evaluate the co-design process involved in developing the intervention prototype.

Methods

The co-design study was based on a partnership between nutrition researchers and designers experienced in co-design for health. Potential end-users (patients and health professionals) were recruited from an earlier stage of the study. Three online workshops were conducted to develop and review prototypes of an app for people at risk of T2D. Themes were inductively defined and aligned with persuasive design (PD) principles used to inform ideal app features and characteristics.

Results

Participants were predominantly female (range 58–100%), aged 38 to 63 years (median age = 59 years), consisting of a total of 20 end-users and four experts. Participants expressed the need for information from credible sources and to provide effective strategies to overcome social and environmental influences on eating behaviours. Preferred app features included tailoring to the individual’s unique characteristics, ability to track and monitor dietary behaviour, and tools to facilitate controlled social connectivity. Relevant persuasive design principles included social support, reduction (reducing effort needed to reach target behaviour), tunnelling (guiding users through a process that leads to target behaviour), praise, rewards, and self-monitoring. The most preferred prototype was the Choices concept, which focusses on the users’ journey of health behaviour change and recognises progress, successes, and failures in a supportive and encouraging manner. The workshops were rated successful, and feedback was positive.

Conclusions

The study’s co-design methods were successful in developing a functionally appealing and relevant digital health promotion intervention. Continuous engagement with stakeholders such as designers and end-users is needed to further develop a working prototype for testing.
Impacts of chronic disease prevention programs implemented by private health insurers: a systematic review
Authors: Wanni Arachchige Dona Sithara , Angeles Mary Rose , Hall Natasha , Watts Jennifer J. , Peeters Anna , Hensher Martin
Published: November 2021

Background

Chronic diseases contribute to a significant proportion (71%) of all deaths each year worldwide. Governments and other stakeholders worldwide have taken various actions to tackle the key risk factors contributing to the prevalence and impact of chronic diseases. Private health insurers (PHI) are one key stakeholders, particularly in Australian health system, and their engagement in chronic disease prevention is growing. Therefore, we investigated the impacts of chronic disease prevention interventions implemented by PHI both in Australia and internationally.

Method

We searched multiple databases (Business Source Complete, CINAHL, Global Health, Health Business Elite, Medline, PsycINFO, and Scopus) and grey literature for studies/reports published in English until September 2020 using search terms on the impacts of chronic disease prevention interventions delivered by PHIs. Two reviewers assessed the risk of bias using a quality assessment tool developed by Effective Public Healthcare Panacea Project. After data extraction, the literature was synthesised thematically based on the types of the interventions reported across studies. The study protocol was registered in PROSPERO, CRD42020145644.

Results

Of 7789 records, 29 studies were eligible for inclusion. There were predominantly four types of interventions implemented by PHIs: Financial incentives, health coaching, wellness programs, and group medical appointments. Outcome measures across studies were varied, making it challenging to compare the difference between the effectiveness of different intervention types. Most studies reported that the impacts of interventions, such as increase in healthy eating, physical activity, and lower hospital admissions, last for a shorter term if the length of the intervention is shorter.

Interpretation

Although it is challenging to conclude which intervention type was the most effective, it appeared that, regardless of the intervention types, PHI interventions of longer duration (at least 2 years) were more beneficial and outcomes were more sustained than those PHI interventions that lasted for a shorter period.

Funding

Primary source of funding was Geelong Medical and Hospital Benefits Association (GMHBA), an Australian private health insurer.
Accelerating Sustainable Development Goals for South African adolescents from high HIV prevalence areas: a longitudinal path analysis
Authors: Meinck Franziska , Orkin Mark , Cluver Lucie
Published: November 2021

Background

Adolescents experience a multitude of vulnerabilities which need to be addressed in order to achieve the Sustainable Development Goals (SDGs). In sub-Saharan Africa, adolescents experience high burden of HIV, violence exposure, poverty, and poor mental and physical health. This study aimed to identify interventions and circumstances associated with three or more targets (“accelerators”) within multiple SDGs relating to HIV-affected adolescents and examine cumulative effects on outcomes.

Methods

Prospective longitudinal data from 3401 adolescents from randomly selected census enumeration areas in two provinces with > 30% HIV prevalence carried out in 2010/11 and 2011/12 were used to examine six hypothesized accelerators (positive parenting, parental monitoring, free schooling, teacher support, food sufficiency and HIV-negative/asymptomatic caregiver) targeting twelve outcomes across four SDGs, using a multivariate (multiple outcome) path model with correlated outcomes controlling for outcome at baseline and socio-demographics. The study corrected for multiple-hypothesis testing and tested measurement invariance across sex. Percentage predicted probabilities of occurrence of the outcome in the presence of the significant accelerators were also calculated.

Results

Sample mean age was 13.7 years at baseline, 56.6% were female. Positive parenting, parental monitoring, food sufficiency and AIDS-free caregiver were variously associated with reductions on ten outcomes. The model was gender invariant. AIDS-free caregiver was associated with the largest reductions. Combinations of accelerators resulted in a percentage reduction of risk of up to 40%.

Conclusion

Positive parenting, parental monitoring, food sufficiency and AIDS-free caregivers by themselves and in combination improve adolescent outcomes across ten SDG targets. These could translate to the corresponding real-world interventions parenting programmes, cash transfers and universal access to antiretroviral treatment, which when provided together, may help governments in sub-Saharan Africa more economically to reach their SDG targets.
Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses
Authors: Tanha Kiarash , Mottaghi Azadeh , Nojomi Marzieh , Moradi Marzieh , Rajabzadeh Rezvan , Lotfi Samaneh , Janani Leila
Published: November 2021

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer.
ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma
Authors: Babikir Husam , Wang Lin , Shamardani Karin , Catalan Francisca , Sudhir Sweta , Aghi Manish K. , Raleigh David R. , Phillips Joanna J. , Diaz Aaron A.
Published: November 2021

Background

Recent single-cell transcriptomic studies report that IDH-mutant gliomas share a common hierarchy of cellular phenotypes, independent of genetic subtype. However, the genetic differences between IDH-mutant glioma subtypes are prognostic, predictive of response to chemotherapy, and correlate with distinct tumor microenvironments.

Results

To reconcile these findings, we profile 22 human IDH-mutant gliomas using scATAC-seq and scRNA-seq. We determine the cell-type-specific differences in transcription factor expression and associated regulatory grammars between IDH-mutant glioma subtypes. We find that while IDH-mutant gliomas do share a common distribution of cell types, there are significant differences in the expression and targeting of transcription factors that regulate glial identity and cytokine elaboration. We knock out the chromatin remodeler ATRX, which suffers loss-of-function alterations in most IDH-mutant astrocytomas, in an IDH-mutant immunocompetent intracranial murine model. We find that both human ATRX-mutant gliomas and murine ATRX-knockout gliomas are more heavily infiltrated by immunosuppressive monocytic-lineage cells derived from circulation than ATRX-intact gliomas, in an IDH-mutant background. ATRX knockout in murine glioma recapitulates gene expression and open chromatin signatures that are specific to human ATRX-mutant astrocytomas, including drivers of astrocytic lineage and immune-cell chemotaxis. Through single-cell cleavage under targets and tagmentation assays and meta-analysis of public data, we show that ATRX loss leads to a global depletion in CCCTC-binding factor association with DNA, gene dysregulation along associated chromatin loops, and protection from therapy-induced senescence.

Conclusions

These studies explain how IDH-mutant gliomas from different subtypes maintain distinct phenotypes and tumor microenvironments despite a common lineage hierarchy.
The Alzheimer’s disease drug development landscape
Authors: van Bokhoven Pieter , de Wilde Arno , Vermunt Lisa , Leferink Prisca S. , Heetveld Sasja , Cummings Jeffrey , Scheltens Philip , Vijverberg Everard G. B.
Published: November 2021

Background

Alzheimer’s disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Numerous genetic risk factors for sporadic AD have been identified, providing further insight into the molecular underpinnings of the disease. For the last two decades, however, drug development for AD has been proven to be particularly challenging. Here, we provide a unique overview of the drug development landscape for AD. By comparing preclinical and clinical drug development pipelines, we aim to describe trends and differences regarding target classes and therapeutic modalities in preclinical and clinical development.

Methods

We analyzed proprietary and public databases and company websites for drugs in preclinical development for AD by the pharmaceutical industry and major clinical trial registries for drugs in clinical development for AD. Drugs were categorized by target class and treatment modality.

Results

We found a higher proportion of preclinical interventions targeting molecular pathways associated with sporadic AD genetic risk variants, compared to clinical stage interventions. These include apolipoprotein E (ApoE) and lipids, lysosomal/endosomal targets, and proteostasis. Further, we observed a trend suggesting that more traditional therapeutic modalities are developed for these novel targets, while more novel treatment modalities such as gene therapies and enzyme treatments are in development for more traditional targets such as amyloid β and tau. Interestingly, the percentage of amyloid β targeting therapies in preclinical development (19.2%) is even higher than the percentage in clinical development (10.7%), indicating that diversification away from interventions targeting amyloid-beta has not materialized. Inflammation is the second most popular target class in both preclinical and clinical development.

Conclusions

Our observations show that the AD drug development pipeline is diversifying in terms of targets and treatment modalities, while amyloid-targeting therapies remain a prominent avenue of development as well. To further advance AD drug development, novel companion diagnostics are needed that are directed at disease mechanisms related to genetic risk factors of AD, both for patient stratification and assessment of therapeutic efficacy in clinical trials.
A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites
Authors: Shi Hongli , Ge Xing , Ma Xi , Zheng Mingxuan , Cui Xiaoying , Pan Wei , Zheng Peng , Yang Xiaoying , Zhang Peng , Hu Minmin , Hu Tao , Tang Renxian , Zheng Kuiyang , Huang Xu-Feng , Yu Yinghua
Published: November 2021

Background

Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis.

Results

In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment.

Conclusions

This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.
Heavy metal contamination and health risk assessment of mechanically milled delicacy called fufu
Authors: Nkansah Marian Asantewah , Agorsor Patrica-Ivy , Opoku Francis
Published: November 2021

Contamination of food by heavy metals is a concern as consumption of contaminated food is one of the most likely human exposure routes to metals. Fufu is a delicacy in Ghana consumed mainly by the Akans. Human exposure to some heavy metals (Cr, Fe, Zn, Mn and Ni) through mechanically processed fufu consumption was analysed by atomic absorption spectrophotometer and ascertaining consumer awareness of potential exposure by questionnaire administration. A total of 30 milled and un-milled fufu samples (cassava and plantain) were sampled from Bomso, Kotei, Ayeduase, Ayigya and Kentikrono, all within Kumasi. The results showed that Fe and Zn levels after milling were elevated in the range: 2.816–7.297 and 0.753–7.529 mg/kg, respectively. The concentrations of Fe and Zn were below the Food and Agriculture Organization/World Health Organization (FAO/WHO) permissible limits except Zn concentration at Bomso. Cr, Mn and Ni were below the detection limit (0.05). Hazard quotients and indices were less than the US Environmental Protection Agency’s permitted level of one, indicating no possible harm to consumers. Findings from the questionnaire administration indicated a complete lack of knowledge on consumer exposure due to the food processing method.
An investigation of latent fingerprinting techniques
Authors: Dhaneshwar Ritika , Kaur Mandeep , Kaur Manvjeet
Published: November 2021

Background

Latent fingerprints are the unintentional impressions that are left at crime scenes, which are considered to be highly significant in forensic analysis and authenticity verification. It is an extremely crucial tool used by law enforcement and forensic agencies for the conviction of criminals. However, due to the accidental nature of these impressions, the quality of prints uplifted is generally inferior.

Main body

In order to improve the overall fingerprint recognition performance, there is an insistent need to design novel methods to improve the reliability and robustness of the existing techniques. Therefore, a systematic review is presented to study the existing methods for latent fingerprint acquisition, enhancement, reconstruction, and matching, along with various benchmark datasets available for research purposes.

Conclusion

The paper highlights multiple challenges and research gaps using comparative analysis of existing enhancement, reconstruction and matching approaches in order to augment the research in this direction that has become imperative in this digital era.
(Trans) Sex Sells
Authors: Goldberg RL
Published: November 2021

In this article the author considers the vexed relationship that Star Distributors' trans sleaze had with taxonomy. The author argues that linguistic slippage and the inability to define a precise trans identity as object speaks not only, or exclusively, to a sloppiness on the part of sleaze writers but is also a deliberate illumination of the degree to which white trans is not reducible to something known or necessarily stable. Because it is irreducible to knowledge and finality, these texts delight in the possibilities of plurality, in teaching, and in learning to work one's gender in excess of cis practice. Finally, this article explores the bifurcated way these novels depict pedagogy for white and Black trans characters.
A method for selective stimulation of leg chemoreceptors in whole crustaceans
Authors: Solari Paolo , Sollai Giorgia , Palmas Francesco , Sabatini Andrea , Crnjar Roberto
Published: November 2021

The integration of sensory information with adequate motor outputs is critical for animal survival. Here, we present an innovative technique based on a non-invasive closed-circuit device consisting of a perfusion/stimulation chamber chronically applied on a single leg of the crayfish Procambarus clarkii. Using this technique, we focally stimulated the leg inside the chamber and studied the leg-dependent sensory–motor integration involving other sensory appendages, such as antennules and maxillipeds, which remain unstimulated outside the chamber. Results show that the stimulation of a single leg with chemicals, such as disaccharides, is sufficient to trigger a complex search behaviour involving locomotion coupled with the reflex activation of antennules and maxillipeds. This technique can be easily adapted to other decapods and/or other sensory appendages. Thus, it has opened possibilities for studying sensory–motor integration evoked by leg stimulation in whole aquatic animals under natural conditions to complement, with a direct approach, current ablation or silencing techniques.