bluuebunny/crossref_metadata_2025 huggingface dataset:
Annona muricata Linn and Khaya grandifoliola C.DC. Reduce Oxidative Stress In Vitro and Ameliorate Plasmodium berghei-Induced Parasitemia and Cytokines in BALB/c Mice
Authors: Onohuean Hope , Alagbonsi Abdullateef I. , Usman Ibe M. , Iceland Kasozi Keneth , Alexiou Athanasios , Badr Reem H. , Batiha Gaber El-Saber , Ezeonwumelu Joseph O. C.
Published: August 2021

Background.

Annona muricata and Khaya grandifoliola are ethnomedicinally used for the treatment of malaria and have been experimentally shown to have an anti-plasmodial effect, but the mechanisms involved are not fully understood. This study investigated the effect of the ethanol extracts of their leaves on parasitemia, radical scavenging and cytokines in Plasmodium berghei ANKA-infected BALB/c mice.

Methods.

BALB/c mice were infected with P. berghei and treated with chloroquine, A. muricata or K. grandifoliola extract for 4 days. The percentage of parasitemia and the level of cytokine expression were determined after treatment. Trace element, phytochemical and nitric oxide (NO) scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties assays were done to study the antioxidant effects of AN and KG in vitro.

Results.

P. berghei consistently increased parasitemia in BALB/c mice. The tested doses (100-, 200-, and 400 mg/kg) of A. muricata and K. grandifoliola attenuated the P. berghei-induced elevation of parasitemia and cytokines (TNF-α, IL-5, and IL-6) in vivo during the experimental period, though not as much as chloroquine. Moreover, both extracts scavenged the DPPH and NO radicals, though A. muricata had more anti-oxidant effect than K. grandifoliola in-vitro.

Conclusion.

The ethanol extracts of A. muricata and K. grandifoliola reduce parasitemia in P. berghei-treated mice BALB/c by scavenging free radicals and reducing cytokines, though the extracts were not as effective as chloroquine.
Burnout: A Review of the Literature
Authors: Nápoles Jessica
Published: August 2021

In this review of literature related to burnout, I compiled definitions of the term, discussed factors contributing to burnout, effects of burnout, and prevention/possible remedies for burnout. Although there is no consensus on the term’s definition, it is well understood that burnout has three dimensions: emotional exhaustion, depersonalization/cynicism, and personal accomplishment. There are personal (internal) and organizational (external) factors that contribute to burnout. When teachers feel lack of control, overloaded, and underresourced, the potential for burnout is amplified. Burnout is manifested in physical (poor health) and psychological ways (detachment, boredom, and rigidity). Prevention strategies generally fall into the categories of (a) in-school interventions (including being more prepared and developing high quality interpersonal relationships), (b) out of school interventions (better work–life balance), and (c) mentoring. Given that engagement is the antithesis of burnout, keeping teachers engaged and feeling valued are mitigating factors for burnout.
Utility of High-Resolution Sonography for Evaluation of Knee Joint Pathologies as a Screening Tool
Authors: Singh Atul Pratap , Chandak Shruti , Agarwal Arjit , Malhotra Ankur , Jain Ashwani , Khan Adil Ali
Published: August 2021

Objective:

Magnetic resonance imaging (MRI) has been established as the gold standard imaging technique for assessing knee joint pathologies. However, high-resolution sonography (HRS) is affordable, easily available, cost-effective, and can be used for knee joint assessment. This study was conducted to assess the diagnostic yield of HRS in the evaluation of knee joint pathologies compared with MRI.

Materials and Methods:

In the study, 103 patients, with symptomatic knee pain, were included. HRS was performed followed by MRI. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Kappa values were calculated to assess the performance of HRS compared with MRI.

Results:

The most frequent pathologies observed on HRS were knee joint effusion (84%) followed by medial meniscal (43%) and lateral meniscal (26%) tear.

Conclusion:

HRS demonstrated good diagnostic accuracy in diagnosis of knee joint pathologies as compared with MRI. Therefore, HRS could be utilized as a screening tool for detection of knee joint pathologies.
Integrative, multi-omics, analysis of blood samples improves model predictions: applications to cancer
Authors: Ponzi Erica , Thoresen Magne , Haugdahl Nøst Therese , Møllersen Kajsa
Published: August 2021

Background

Cancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific (“individual”) patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as “shared” or “joint”. In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case–control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case–control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas.

Results

Our results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development.

Conclusions

In the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.
Gastrointestinal bleeding with Klippel–Trenaunay syndrome: a case report
Authors: Han Lin , Chen Shifeng , Jiang Shengping
Published: August 2021

Background

Gastrointestinal bleeding caused by gastrointestinal tract involvement in patients with Klippel–Trenaunay syndrome (KTS) is extremely rare and often overlooked.

Case presentation

A 9-year-old girl who presented with chronic gastrointestinal bleeding was admitted to our hospital. Laboratory examinations revealed microcytic hypochromic anemia and a positive fecal occult blood test. Computed tomography (CT) of the lower limbs combined with physical examination confirmed KTS. The pelvic CT showed concentric thickening of the sigmoid colon and rectum, with progressive enhancement after the administration of a contrast agent. Colonoscopy demonstrated vascular malformations of the sigmoid colon and rectum. The patient was finally diagnosed with KTS with gastrointestinal tract involvement. The patient improved after receiving conservative treatment.

Conclusions

A suspicion of gastrointestinal tract involvement as an etiology for gastrointestinal bleeding should not be overlooked in patients with KTS. Endoscopy and imaging modalities can synergistically help diagnose this condition.
Towards improving edge quality using combinatorial optimization and a novel skeletonize algorithm
Authors: Arnold Marvin , Speidel Stefanie , Hattab Georges
Published: August 2021

Background

Object detection and image segmentation of regions of interest provide the foundation for numerous pipelines across disciplines. Robust and accurate computer vision methods are needed to properly solve image-based tasks. Multiple algorithms have been developed to solely detect edges in images. Constrained to the problem of creating a thin, one-pixel wide, edge from a predicted object boundary, we require an algorithm that removes pixels while preserving the topology. Thanks to skeletonize algorithms, an object boundary is transformed into an edge; contrasting uncertainty with exact positions.

Methods

To extract edges from boundaries generated from different algorithms, we present a computational pipeline that relies on: a novel skeletonize algorithm, a non-exhaustive discrete parameter search to find the optimal parameter combination of a specific post-processing pipeline, and an extensive evaluation using three data sets from the medical and natural image domains (kidney boundaries, NYU-Depth V2, BSDS 500). While the skeletonize algorithm was compared to classical topological skeletons, the validity of our post-processing algorithm was evaluated by integrating the original post-processing methods from six different works.

Results

Using the state of the art metrics, precision and recall based Signed Distance Error (SDE) and the Intersection over Union bounding box (IOU-box), our results indicate that the SDE metric for these edges is improved up to 2.3 times.

Conclusions

Our work provides guidance for parameter tuning and algorithm selection in the post-processing of predicted object boundaries.
Rehabilitation interventions to support return to work for women with breast cancer: a systematic review and meta-analysis
Authors: Algeo Naomi , Bennett Kathleen , Connolly Deirdre
Published: August 2021

Background

Research recommends the development and evaluation of interventions to support women with breast cancer in returning to, or managing, work. Despite this, there has historically been a paucity of rehabilitation interventions to support women with breast cancer to maintain or return to their work role. The aim of this systematic review was to examine key characteristics of rehabilitation interventions, and their effectiveness on work outcomes for women with breast cancer, compared to usual care.

Methods

A systematic review was conducted of controlled studies of rehabilitation interventions with work outcomes for women with breast cancer. Six databases were systematically searched: EMBASE, Web of Science, MEDLINE (OVID), CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL). Results are presented either as pooled odds ratio (OR) or pooled effect size (hedges g) between groups, with 95% confidence intervals (CI). Narrative synthesis was conducted on intervention outcomes not suitable for meta-analysis.

Results

Five thousand, five hundred and thirty-five studies were identified. Nine out of 28 abstracts met inclusion criteria. Heterogeneity of interventions and outcomes precluded meta-analysis for most outcomes. Of the interventions included in meta-analysis, no significant differences compared to usual care were found for sick leave (2 studies (12 months); OR 1.11 (95% CI: 0.66 to 1.87), number of sick days taken (2 studies (six months); difference in effect: − 0.08, (95% CI: − 0.48 to 0.38) or working hours (2 studies (12 months); 0.19, (95% CI: − 0.20 to 0.64). Only one study, with a multidisciplinary intervention, showed a significant difference for work outcomes when compared to usual care. Work-specific content featured in three interventions only, none of which provided conclusive evidence for improvement in work outcomes. Enhanced physical and psychological sequalae, and quality of life was observed in some studies.

Conclusion

There remains a lack of effective and methodologically rigorous rehabilitation intervention studies for breast cancer survivors. The development and evaluation of effective rehabilitation interventions to support return to work is warranted.
A randomised controlled trial of the Nextdoor Kind Challenge: a study protocol
Authors: Lim Michelle H. , Qualter Pamela , Hennessey Alexandra , Smith Ben J. , Argent Taylah , Holt-Lunstad Julianne
Published: August 2021

Background

Community interventions are often promoted as a way of reducing loneliness and social isolation in our neighbourhoods. However, those community interventions are rarely examined within rigorous study designs. One strategy that holds the potential to reduce loneliness and can promote health and wellbeing is doing acts of kindness. The current study involves evaluating the impact of kindness acts on loneliness in community-dwelling individuals using an online social networking platform.

Methods

This study is made up of three randomised controlled trials conducted in three countries. Each randomised controlled trial has two arms (intervention vs waitlist control) and is designed to compare the effectiveness of the KIND challenge, which involves doing at least one act of kindness per week within a four-week period. This study will recruit users of an online community, be randomised online, and will be conducted using online assessments. We will first explore the effects of the intervention on the primary outcome of loneliness, followed by secondary outcomes, social isolation, neighbour relationship quality and contact, mental health symptoms, stress, quality of life, and positive affect. Further, we will assess the feasibility, acceptability, and safety of the KIND Challenge.

Discussion

This study, designed to evaluate the impact of kindness on the community, will be the first large scale randomised control trial conducted across three countries, Australia, UK, and USA. It will examine the potential of community-led interventions to reduce loneliness, improve social isolation, and promote neighbourhood cohesion, health, and wellbeing, which is especially crucial during the COVID-19 public health crisis.

Trial registration

Clinical Trials Registry. NCT04398472. Registered 21st May 2020.
A three-armed randomised controlled trial investigating the comparative impact of guidance on the efficacy of a web-based stress management intervention and health impairing and promoting mechanisms of prevention
Authors: Nixon Patricia , Boß Leif , Heber Elena , Ebert David Daniel , Lehr Dirk
Published: August 2021

Background

Web-based stress management interventions (SMI) fit increasingly digital lifestyles, reduce barriers of uptake and are easily scalable. SMIs might lower levels of stress in employees and thereby contribute to the prevention of depressive symptomatology. Different guidance formats can impact the efficacy of SMIs, with higher intensity assumed to result in larger effects. However, head-to-head comparisons of guidance formats are rare. This is the first trial to examine the impact of adherence-focused guidance compared to self-help on the efficacy of an occupational SMI compared to a wait list control condition. Additionally, it will be investigated if the SMI enfolds its impact on preventing depressive symptomatology by different pathways through reducing health impairing and increasing promoting factors.

Methods

A three-armed randomised controlled trial (RCT) on an occupational SMI was conducted. 404 employees with elevated levels of perceived stress (PSS-10 ≥ 22) were randomly assigned to: adherence-focused guidance (AFG), self-help (SH) or a wait list control group (WLC). The primary outcome was perceived stress (PSS-10). Secondary outcomes included health- and work-related measures. A parallel mediation analysis with stress and resilience as mediators for the effect on depression (CES-D) was carried out. Data collection took place at baseline (T1), after 7 weeks (T2) and 6 months (T3).

Results

The SMI was effective for all groups on the primary and secondary outcomes. For stress, analyses of covariance (ANCOVA) revealed significant group effects at T2 (F2,400 = 36.08, P < .001) and T3 (F2,400 = 37.04, P < .001) with large effect sizes for AFG (T2: d = 0.83; T3: d = 0.85) and SH (T2: d = 0.88; T3: d = 0.91) compared to WLC. No significant group differences were found for the efficacy between AFG and SH on the outcomes. Adherence in terms of completed modules was significantly higher for AFG compared to SH. The SMI’s impact on depression was mediated by perceived stress: a1b1 = − 0.77, 95% CI [− 1.26, − 0.34] and resilience: a2b2 = − 0.62, 95% CI [− 1.05, − 0.26].

Conclusions

The SMI was effective for reducing stress and improving other health- and work-related outcomes, irrespective of the guidance format. Results did not demonstrate superiority of adherence-focused guidance for the efficacy but for adherence in terms of completed modules. Among other reasons, better communication strategies about offered guidance and awareness-raising measures are discussed. Results from mediation analysis suggest that preventive SMIs should be designed to reach two goals: reducing the risk factor of stress and simultaneously increasing health promoting factors such as resilience.

Trial registration

German Clinical Trial Registration (DRKS) DRKS00005687, 6/6/2014.
Infant processed food consumption and their interaction to breastfeeding and growth in children up to six months old
Authors: Neves Renata Oliveira , Guimarães Luciano Santos Pinto , Bosa Vera Lúcia , Nunes Leandro Meirelles , da Silva Clécio Homrich , Goldani Marcelo Zubaran , Bernardi Juliana Rombaldi
Published: August 2021

Background

Evidences suggest that early processed food (PF) consumption may cause harm to infant health. During the first 6 months of life, it is not known whether the timing and quantity of this food group can impact breastfeeding and growth. The aim of the study was to analyze the associations between time of introduction and quantity of infant PF consumption with duration of breastfeeding and infant growth at 6 months of age.

Methods

Data were longitudinally collected in six interviews, from birth to 6 months, in a sample of Brazilian newborns with adverse intrauterine environments. PF consumption was calculated by gravity score of processed foods (GSPF) in relation to feeding supply quality and time. For the analysis, the scores were divided into tertiles, making scores severities: Null, Mild, Moderate, and Severe. The interaction between GSPF and breastfeeding (exclusive and non-exclusive) and growth parameters (analyzed in Z-scores, by weight for height, weight for age, and body mass index for age) was tested.

Results

A total of 236 infants were included in the study. Greater GSPF were associated with better rates of breastfeeding practices and higher growth indicators scores in the sixth month of infants. These findings were confirmed after adjustment for family income, maternal age, pre-gestational body mass index, and growth z scores at birth.

Conclusion

The harms of eating PF in relation to breastfeeding and infant growth are more evident the greater and earlier they are consumed. Future studies should explore interventions to reduce and delay the consumption of these foods to prevent adverse health outcomes in later life.
Computer-aided diagnosis with a convolutional neural network algorithm for automated detection of urinary tract stones on plain X-ray
Authors: Kobayashi Masaki , Ishioka Junichiro , Matsuoka Yoh , Fukuda Yuichi , Kohno Yusuke , Kawano Keizo , Morimoto Shinji , Muta Rie , Fujiwara Motohiro , Kawamura Naoko , Okuno Tetsuo , Yoshida Soichiro , Yokoyama Minato , Suda Rumi , Saiki Ryota , Suzuki Kenji , Kumazawa Itsuo , Fujii Yasuhisa
Published: August 2021

Background

Recent increased use of medical images induces further burden of their interpretation for physicians. A plain X-ray is a low-cost examination that has low-dose radiation exposure and high availability, although diagnosing urolithiasis using this method is not always easy. Since the advent of a convolutional neural network via deep learning in the 2000s, computer-aided diagnosis (CAD) has had a great impact on automatic image analysis in the urological field. The objective of our study was to develop a CAD system with deep learning architecture to detect urinary tract stones on a plain X-ray and to evaluate the model’s accuracy.

Methods

We collected plain X-ray images of 1017 patients with a radio-opaque upper urinary tract stone. X-ray images (n = 827 and 190) were used as the training and test data, respectively. We used a 17-layer Residual Network as a convolutional neural network architecture for patch-wise training. The training data were repeatedly used until the best model accuracy was achieved within 300 runs. The F score, which is a harmonic mean of the sensitivity and positive predictive value (PPV) and represents the balance of the accuracy, was measured to evaluate the model’s accuracy.

Results

Using deep learning, we developed a CAD model that needed 110 ms to provide an answer for each X-ray image. The best F score was 0.752, and the sensitivity and PPV were 0.872 and 0.662, respectively. When limited to a proximal ureter stone, the sensitivity and PPV were 0.925 and 0.876, respectively, and they were the lowest at mid-ureter.

Conclusion

CAD of a plain X-ray may be a promising method to detect radio-opaque urinary tract stones with satisfactory sensitivity although the PPV could still be improved. The CAD model detects urinary tract stones quickly and automatically and has the potential to become a helpful screening modality especially for primary care physicians for diagnosing urolithiasis. Further study using a higher volume of data would improve the diagnostic performance of CAD models to detect urinary tract stones on a plain X-ray.
Home blood pressure data visualization for the management of hypertension: using human factors and design principles
Authors: Wegier Pete , Belden Jeffery L. , Canfield Shannon M. , Shaffer Victoria A. , Patil Sonal J. , LeFevre Michael L. , Valentine K. D. , Popescu Mihail , Steege Linsey M. , Jain Akshay , Koopman Richelle J.
Published: August 2021

Background

Home blood pressure measurements have equal or even greater predictive value than clinic blood pressure measurements regarding cardiovascular outcomes. With advances in home blood pressure monitors, we face an imminent flood of home measurements, but current electronic health record systems lack the functionality to allow us to use this data to its fullest. We designed a data visualization display for blood pressure measurements to be used for shared decision making around hypertension.

Methods

We used an iterative, rapid-prototyping, user-centred design approach to determine the most appropriate designs for this data display. We relied on visual cognition and human factors principles when designing our display. Feedback was provided by expert members of our multidisciplinary research team and through a series of end-user focus groups, comprised of either hypertensive patients or their healthcare providers required from eight academic, community-based practices in the Midwest of the United States.

Results

A total of 40 participants were recruited to participate in patient (N = 16) and provider (N = 24) focus groups. We describe the conceptualization and development of data display for shared decision making around hypertension. We designed and received feedback from both patients and healthcare providers on a number of design elements that were reported to be helpful in understanding blood pressure measurements.

Conclusions

We developed a data display for substantial amounts of blood pressure measurements that is both simple to understand for patients, but powerful enough to inform clinical decision making. The display used a line graph format for ease of understanding, a LOWESS function for smoothing data to reduce the weight users placed on outlier measurements, colored goal range bands to allow users to quickly determine if measurements were in range, a medication timeline to help link recorded blood pressure measurements with the medications a patient was taking. A data display such as this, specifically designed to encourage shared decision making between hypertensive patients and their healthcare providers, could help us overcome the clinical inertia that often results in a lack of treatment intensification, leading to better care for the 35 million Americans with uncontrolled hypertension.
The presence and potential impact of psychological safety in the healthcare setting: an evidence synthesis
Authors: Grailey K. E. , Murray E. , Reader T. , Brett S. J.
Published: August 2021

Introduction

Psychological safety is the shared belief that the team is safe for interpersonal risk taking. Its presence improves innovation and error prevention. This evidence synthesis had 3 objectives: explore the current literature regarding psychological safety, identify methods used in its assessment and investigate for evidence of consequences of a psychologically safe environment.

Methods

We searched multiple trial registries through December 2018. All studies addressing psychological safety within healthcare workers were included and reviewed for methodological limitations. A thematic analysis approach explored the presence of psychological safety. Content analysis was utilised to evaluate potential consequences.

Results

We included 62 papers from 19 countries. The thematic analysis demonstrated high and low levels of psychological safety both at the individual level in study participants and across the studies themselves. There was heterogeneity in responses across all studies, limiting generalisable conclusions about the overall presence of psychological safety.

A wide range of methods were used. Twenty-five used qualitative methodology, predominantly semi-structured interviews. Thirty quantitative or mixed method studies used surveys.

Ten studies inferred that low psychological safety negatively impacted patient safety. Nine demonstrated a significant relationship between psychological safety and team outcomes.

The thematic analysis allowed the development of concepts beyond the content of the original studies. This analytical process provided a wealth of information regarding facilitators and barriers to psychological safety and the development of a model demonstrating the influence of situational context.

Discussion

This evidence synthesis highlights that whilst there is a positive and demonstrable presence of psychological safety within healthcare workers worldwide, there is room for improvement. The variability in methods used demonstrates scope to harmonise this. We draw attention to potential consequences of both high and low psychological safety.

We provide novel information about the influence of situational context on an individual’s psychological safety and offer more detail about the facilitators and barriers to psychological safety than seen in previous reviews. There is a risk of participation bias - centres involved in safety research may be more aligned to these ideals. The data in this synthesis are useful for institutions looking to improve psychological safety by providing a framework from which modifiable factors can be identified.
The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
Authors: Zeng Tiansheng , Cui Longzhen , Huang Wenhui , Liu Yan , Si Chaozeng , Qian Tingting , Deng Cong , Fu Lin
Published: August 2021

Background

The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest.

Methods

The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy.

Results

After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P< 0.001). Besides, the model can perform well in multiple datasets and could further stratify the cytogenetically normal AML patients and intermediate-risk AML population. Compared with the European Leukemia Net Risk Stratification System and other AML prognostic models, our model had the highest C-index and the largest AUC of the ROC curve, which demonstrated that our model had the best prognostic efficacy.

Conclusion

A prognostic model for AML based on the TIME classification was constructed in our study, which may provide a new strategy for precision treatment in AML.
Severe long-delayed malaria caused by Plasmodium malariae in an elderly French patient
Authors: Marteau Anthony , Ouedraogo Elise , Van der Meersch Guillaume , Akhoundi Mohammad , Souhail Berenice , Cohen Yves , Bouchaud Olivier , Izri Arezki
Published: August 2021

Background

Plasmodium malariae is the cause of the rare but severe form of malaria that sometimes affects individuals travelling to malaria-endemic regions. This report presents the unique case of a patient exhibiting severe malaria symptoms caused by P. malariae with no record of recent travel to any malaria-endemic areas.

Case presentation

An 81-year-old French woman was admitted to the emergency department with sustained fever and severe weakness for the past 5 days. She suffered from anaemia, thrombocytopenia, confusion, somnolence, pulmonary complications, and hypoxaemia. In the absence of any concrete aetiology that could explain the fever together with thrombocytopenia, physicians suspected malaria as a probable diagnosis.

The LAMP-PCR and lateral flow test confirmed the presence of malaria parasite, Plasmodium sp. Microscopic examination (May-Grünwald Giemsa-stained thin blood smear) revealed the presence of trophozoites, schizonts, and gametocytes with 0.93 % parasitaemia. Conventional PCR amplification targeting 510 bp DNA fragment of small subunit ribosomal RNA (ssrRNA) and bidirectional sequencing identified the parasite as Plasmodium malariae. The travel history of this patient revealed her visits to several countries in Europe (Greece), North Africa (Tunisia and Morocco), and the West Indies (Dominican Republic). Of these, the latter was the only country known to be endemic for malaria at the time (three malaria parasite species were prevalent: Plasmodium falciparum, Plasmodium vivax, and P. malariae). The patient had most likely got infected when she visited the Dominican Republic in the summer of 2002. This time interval between the initial parasite infection (2002) till the onset of symptoms and its subsequent diagnosis (2020) is a reminder of the ability of P. malariae to persist in the human host for many years.

Conclusions

This report highlights the persistent nature and ability of P. malariae to cause severe infection in the host even after a prolonged time interval.
CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer
Authors: Li Xianhuang , Guo Mingming , Hou Bei , Zheng Bin , Wang Zhiyun , Huang Mengqian , Xu Yanan , Chang Jin , Wang Tao
Published: August 2021

Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes.
A qualitative study on overdose response in the era of COVID-19 and beyond: how to spot someone so they never have to use alone
Authors: Perri Melissa , Kaminski Natalie , Bonn Matthew , Kolla Gillian , Guta Adrian , Bayoumi Ahmed M. , Challacombe Laurel , Gagnon Marilou , Touesnard Natasha , McDougall Patrick , Strike Carol
Published: August 2021

Background

Spotting is an informal practice among people who use drugs (PWUD) where they witness other people using drugs and respond if an overdose occurs. During COVID-19 restrictions, remote spotting (e.g., using a telephone, video call, and/or a social media app) emerged to address physical distancing requirements and reduced access to harm reduction and/or sexually transmitted blood borne infection (STBBI’s) prevention services. We explored spotting implementation issues from the perspectives of spotters and spottees.

Methods

Research assistants with lived/living expertise of drug use used personal networks and word of mouth to recruit PWUD from Ontario and Nova Scotia who provided or used informal spotting. All participants completed a semi-structured, audio-recorded telephone interview about spotting service design, benefits, challenges, and recommendations. Recordings were transcribed and thematic analysis was used.

Results

We interviewed 20 individuals between 08/2020–11/2020 who were involved in informal spotting. Spotting was provided on various platforms (e.g., telephone, video calls, and through texts) and locations (e.g. home, car), offered connection and community support, and addressed barriers to the use of supervised consumption sites (e.g., location, stigma, confidentiality, safety, availability, COVID-19 related closures). Spotting calls often began with setting an overdose response plan (i.e., when and who to call). Many participants noted that, due to the criminalization of drug use and fear of arrest, they preferred that roommates/friends/family members be called instead of emergency services in case of an overdose. Both spotters and spottees raised concerns about the timeliness of overdose response, particularly in remote and rural settings.

Conclusion

Spotting is a novel addition to, but not replacement for, existing harm reduction services. To optimize overdose/COVID-19/STBBI’s prevention services, additional supports (e.g., changes to Good Samaritan Laws) are needed. The criminalization of drug use may limit uptake of formal spotting services.
Family reported outcomes, an unmet need in the management of a patient's disease: appraisal of the literature
Authors: Shah R. , Ali F. M. , Finlay A. Y. , Salek M. S.
Published: August 2021

Background

A person’s chronic health condition or disability can have a huge impact on the quality of life (QoL) of the whole family, but this important impact is often ignored. This literature review aims to understand the impact of patients' disease on family members across all medical specialities, and appraise existing generic and disease-specific family quality of life (QoL) measures.

Methods

The databases Medline, EMBASE, CINHAL, ASSIA, PsycINFO and Scopus were searched for original articles in English measuring the impact of health conditions on patients' family members/partner using a valid instrument.

Results

Of 114 articles screened, 86 met the inclusion criteria. They explored the impact of a relative's disease on 14,661 family members, mostly 'parents' or 'mothers', using 50 different instruments across 18 specialities including neurology, oncology and dermatology, in 33 countries including the USA, China and Australia. These studies revealed a huge impact of patients' illness on family members. An appraisal of family QoL instruments identified 48 instruments, 42 disease/speciality specific and six generic measures. Five of the six generics are aimed at carers of children, people with disability or restricted to chronic disease. The only generic instrument that measures the impact of any condition on family members across all specialities is the Family Reported Outcome Measure (FROM-16). Although most instruments demonstrated good reliability and validity, only 11 reported responsiveness and only one reported the minimal clinically important difference.

Conclusions

Family members' QoL is greatly impacted by a relative's condition. To support family members, there is a need for a generic tool that offers flexibility and brevity for use in clinical settings across all areas of medicine. FROM-16 could be the tool of choice, provided its robustness is demonstrated with further validation of its psychometric properties.
MYBL2-induced PITPNA-AS1 upregulates SIK2 to exert oncogenic function in triple-negative breast cancer through miR-520d-5p and DDX54
Authors: Liu Bolong , Yao Pingbo , Xiao Feng , Guo Jianjin , Wu Lianghui , Yang Yong
Published: August 2021

Background

In recent years, long non-coding RNAs (lncRNAs) have attracted much attention because of its regulatory role in occurrence and progression of tumors, including triple-negative breast cancer (TNBC). LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) has been explored in some cancers, whereas its function and molecular mechanism in TNBC remain unclear.

Methods

PITPNA-AS1 expression in TNBC tissues and cells was determined by RT-qPCR. TNBC cell viability, proliferation, migration, invasion were assessed with CCK-8, colony formation, wound healing, transwell assays. Cell apoptosis was evaluated by flow cytometry. Expression of EMT-related markers was detected by western blot analyses. The molecular mechanism of PITPNA-AS1 was explored by RNA pull down, luciferase reporter, RIP and ChIP assays.

Results

PITPNA-AS1 showed high expression levels in TNBC tissues and cells. PITPNA-AS1 knockdown suppressed TNBC cell viability, proliferation, migration, invasion in vitro and inhibited xenograft tumor growth in mice. Mechanistically, PITPNA-AS1 upregulated SIK2 expression by sponging miR-520d-5p and recruiting DDX54 protein. Results of rescue assays suggested that the inhibitive effects of silenced PITPNA-AS1 on TNBC cellular processes were partially rescued by overexpressing SIK2 or combination of miR-520d-5p inhibition and DDX54 overexpression. More importantly, we found that the upregulation of PITPNA-AS1 in TNBC cells was attributed to transcription factor MYBL2.

Conclusion

PITPNA-AS1 activated by MYBL2 plays an oncogenic role in TNBC through upregulating SIK2.
Natural variation in yolk fatty acids, but not androgens, predicts offspring fitness in a wild bird
Authors: Mentesana Lucia , Andersson Martin N. , Casagrande Stefania , Goymann Wolfgang , Isaksson Caroline , Hau Michaela
Published: August 2021

Background

In egg-laying animals, mothers can influence the developmental environment and thus the phenotype of their offspring by secreting various substances into the egg yolk. In birds, recent studies have demonstrated that different yolk substances can interactively affect offspring phenotype, but the implications of such effects for offspring fitness and phenotype in natural populations have remained unclear. We measured natural variation in the content of 31 yolk components known to shape offspring phenotypes including steroid hormones, antioxidants and fatty acids in eggs of free-living great tits (Parus major) during two breeding seasons. We tested for relationships between yolk component groupings and offspring fitness and phenotypes.

Results

Variation in hatchling and fledgling numbers was primarily explained by yolk fatty acids (including saturated, mono- and polyunsaturated fatty acids) - but not by androgen hormones and carotenoids, components previously considered to be major determinants of offspring phenotype. Fatty acids were also better predictors of variation in nestling oxidative status and size than androgens and carotenoids.

Conclusions

Our results suggest that fatty acids are important yolk substances that contribute to shaping offspring fitness and phenotype in free-living populations. Since polyunsaturated fatty acids cannot be produced de novo by the mother, but have to be obtained from the diet, these findings highlight potential mechanisms (e.g., weather, habitat quality, foraging ability) through which environmental variation may shape maternal effects and consequences for offspring. Our study represents an important first step towards unraveling interactive effects of multiple yolk substances on offspring fitness and phenotypes in free-living populations. It provides the basis for future experiments that will establish the pathways by which yolk components, singly and/or interactively, mediate maternal effects in natural populations.
Retained particle surface area dose drives inflammation in rat lungs following acute, subacute, and subchronic inhalation of nanomaterials
Authors: Cosnier Frédéric , Seidel Carole , Valentino Sarah , Schmid Otmar , Bau Sébastien , Vogel Ulla , Devoy Jérôme , Gaté Laurent
Published: August 2021

Background

An important aspect of nanomaterial (NM) risk assessment is establishing relationships between physicochemical properties and key events governing the toxicological pathway leading to adverse outcomes. The difficulty of NM grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response.

Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. Inhalation studies were performed in rats with three classes of NMs: titanium dioxides (TiO2) and carbon blacks (CB) as poorly soluble particles of low toxicity (PSLT), and multiwall carbon nanotubes (MWCNTs). We compared our results to published data from nearly 30 rigorously selected articles.

Results

This analysis combined data specially generated for this work on three benchmark materials - TiO2P25, the CB Printex-90 and the MWCNT MWNT-7 - following subacute (4-week) inhalation with published data relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation.

A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship takes the form of sigmoid curves, and is independent of the post-exposure time. Curve fitting equations depended on the class of NM considered, and sometimes on the duration of exposure. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 5 cm2/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm2/g lung were required for PSLT.

Conclusions

Retained surface area is a useful metric for hazard grouping purposes. This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. Indeed, it could alternatively be estimated from dosimetry models using the aerosol parameters (rigorously determined following a well-defined aerosol characterization strategy).
Hearing characteristics of infantile-onset Pompe disease after early enzyme-replacement therapy
Authors: Hsueh Chien-Yu , Huang Chii-Yuan , Yang Chia-Feng , Chang Chia-Chen , Lin Wei-Sheng , Cheng Hsiu-Lien , Wu Shang-Liang , Cheng Yen-Fu , Niu Dau-Ming
Published: August 2021

Background

Studies suggest that enzyme-replacement therapy (ERT) is crucial to the survival of patients with infantile-onset Pompe disease (IOPD). Hearing impairment (HI) is one of the clinical sequelae observed in long-term survivors. However, the benefits of early ERT for hearing outcomes have not yet been reported. This study aimed to investigate the impact of early ERT on IOPD patients.

Methods

This retrospective longitudinal study recruited IOPD patients who were referred by newborn screening for confirmatory diagnosis based on our rapid diagnostic criteria and received early ERT treatment between January 1, 2010, and January 31, 2018. The hearing test battery included a tympanogram, otoacoustic emission, auditory brainstem evoked response (ABR), pure-tone audiometry or conditioned play audiometry.

Results

Nineteen patients with IOPD were identified, 6 of whom had hearing impairment (HI); 1 had conductive HI, 2 had sensorineural HI (one had bilateral mild HI and one had mild HI in a single ear) and 1 had moderate mixed-type HI. Two patients failed the newborn screening test and had mild HI in the ABR. The mean age of the initial time to ERT was 11.05 ± 4.31 days, and the HI rate was 31.6% (6/19).

Conclusion

Our study is the largest cohort to show the characteristic hearing outcomes of IOPD patients after ERT. Early ERT within 2 weeks after birth may contribute to better hearing outcomes. Clinicians should be vigilant in testing for the hearing issues associated with IOPD and should intervene early if any HI is detected.