bluuebunny/crossref_metadata_2025 huggingface dataset:
Care and cost trajectories of asylum seekers in a nurse-led, patient centered, care network in Switzerland
Authors: Spycher Jacques , Bodenmann Patrick , Bize Raphaël , Marti Joachim
Published: July 2021

Background

Switzerland, with its decentralized health system, has seen the emergence of a variety of care models to meet the complex needs of asylum seekers. A network of public and private providers was designed in the canton Vaud, in which a nurse-led team acts as a first contact point to the health system and provides health checks, preventive care, and health education to this population. In addition, the service plays a case management role for more complex and vulnerable patients. While the network has been examined from a clinical angle, we provide the first descriptive evidence on the care and cost trajectories of asylum seekers in the canton.

Methods

We used routinely collected administrative, patient-level data in a Swiss region responsible for 10% of the asylum seekers in the country. We extracted data on all asylum seekers aged 18 or older who entered the network between 2012 and 2015. The data covered all healthcare costs during the period until they left the network, either because they were granted residence, they left the country, or until 31 December 2018. We estimated random effects regression models for costs and consultations within and outside the network for each month of stay in the network. We investigated language barriers in access to care by stratifying the analysis between patients who spoke one of the official Swiss languages or English and patients who did not speak any of these languages.

Principal findings

We found that both overall health care costs and contacts with the nurse-led team were relatively high during the first year of stay. Asylum seekers then progressively integrated into the regular health system. Individuals who did not speak the language generally had more contacts with the network and fewer contacts outside.

Conclusions

In this exploratory study, we observe a transition from nurse-led specific care with frequent contacts to care in the regular health system. This leads us to generate the hypothesis that a nurse-led, patient-centered care network for asylum seekers can play an important role in providing primary care during the first year after their arrival and can subsequently help them navigate autonomously within the conventional healthcare system.
Co-designing a methodology for workforce development during the personalisation of allied health service funding for people with disability in Australia
Authors: Foley Kristen , Attrill Stacie , Brebner Chris
Published: July 2021

Background

Internationally, health and social services are undergoing creative and extensive redesign to meet population demands with rationed budgets. This has critical implications for the health workforces that serve such populations. Within the workforce literature, few approaches are described that enable workforce development for health professions in the service contexts that emerge from large scale service redesign in times of industry shift. We contribute an innovative and robust methodology for workforce development that was co-designed by stakeholders in allied health during the personalisation of disability funding in Australia (the introduction of the National Disability Insurance Scheme).

Methods

In the context of a broad action research project, we used program logic modelling to identify and enact opportunities for sustainable allied health education and workforce integration amidst the changed service provision context. We engaged with 49 industry stakeholders across 92 research engagements that included interviews (n = 43), a workshop explicitly for model development (n = 8) and a Project Advisory Group (n = 15). Data from these activities were inductively coded, analysed, and triangulated against each other. During the program logic modelling workshop, we worked with involved stakeholders to develop a conceptual model which could be used to guide trial and evaluation of allied health education which was fit-for-purpose to emerging workforce requirements.

Results

Stakeholder interviews showed that drivers of workforce design during industry shift were that (1) service provision was happening in turbulent times; (2) new concerns around skills and professional engagement were unfolding for AHP in the NDIS; and (3) impacts to AHP education were being experienced. The conceptual model we co-designed directly accounted for these contextual features by highlighting five underpinning principles that should inform methodologies for workforce development and AHP education in the transforming landscape: being (1) pedagogically sound; (2) person- or family-centred; (3) NDIS compliant; (4) informed by evidence and (5) having quality for all. We use a case study to illustrate how the co-designed conceptual model stimulated agility and flexibility in workforce and service redesign.

Conclusions

Proactive and situated education of the emerging workforce during policy shift is essential to realise future health workforces that can appropriately and effectively service populations under a variety of changing service and funding structures – as well as their transitions. We argue that collaborative program logic modelling in partnership with key stakeholders including existing workforce can be useful for broad purposes of workforce (re)design in diverse contexts.
Diabetic ketoacidosis presentations in a low socio-economic area: are services suitable?
Authors: James Steven , Annetts Kylie , Frakking Thuy , Broadbent Marc , Waugh John , Perry Lin , Lowe Julia , Clark Sean
Published: July 2021

Background

Diabetic ketoacidosis causes a significant number of hospitalisations worldwide, with rates tending to increase with remoteness and socioeconomic disadvantage. Our study aimed to explore healthcare professionals’ perceptions of factors affecting presentation of people with type 1 diabetes in a low socioeconomic area of Queensland, Australia.

Methods

This was a qualitative study. Individual semi-structured face-to-face or telephone interviews were completed with patients with type 1 diabetes who had presented in diabetic ketoacidosis, and healthcare professionals who have experience in related care. Data were analysed using Gibbs’s framework of thematic analysis.

Results

Four patients with type 1 diabetes and 18 healthcare professionals were interviewed. Restricted access was identified as a factor contributing to diabetic ketoacidosis and delayed presentation, with ketone testing supplies, continuous glucose monitoring technology and transport considered barriers. Many of these factors were arguably preventable. Opportunities to improve the care available to patients with type 1 diabetes were detailed, with particularly strong support for dedicated out of hours telephone help lines for adults with type 1 diabetes.

Conclusions

Gaps in support for patient self-care to avoid diabetic ketoacidosis presentations and prevent late presentation of diabetic ketoacidosis revealed by this study require service reconfiguration to support care delivery. Until change is made, people with type 1 diabetes will continue to make both avoidable and delayed, acutely unwell, presentations to Emergency Departments.
Endometritis decreases the population of uterine neurons in the paracervical ganglion and changes the expression of sympathetic neurotransmitters in sexually mature gilts
Authors: Miciński Bartosz , Jana Barbara , Całka Jarosław
Published: July 2021

Background

The focus of the study was to examine the impact of the inflamed uterus on the population of the paracervical ganglion (PCG) uterus-innervating perikarya and their chemical coding. Fast Blue retrograde tracer was injected into the wall of uterine horns on the 17th day of the first studied estrous cycle. After 28 days, eitherEscherichia colisuspension or saline was applied to the horns of the uterus, whereas the control group received laparotomy only. Eight days after the above-mentioned procedures, uterine cervices with PCG were collected. Both macroscopic and histopathologic examinations confirmed severe acute endometritis in theEscherichia coli-injected uteri. The double immunofluorescence method was used to analyze changes in the PCG populations coded with dopamine-β‐hydroxylase (DβH) and/or neuropeptide Y (NPY), somatostatin (SOM), vasoactive intestinal polypeptide (VIP) and neuronal isoform of nitric oxide synthase (nNOS).

Results

The use ofEscherichia colilowered the total number of Fast Blue-positive neurons. Moreover, an increase in DβH+/VIP+, DβH+/NPY+, DβH+/SOM + and DβH+/nNOS + expressing perikarya was noted. A rise in non-noradrenergic VIP-, SOM- and nNOS-immunopositive populations was also recorded, as well as a drop in DβH-positive neurotransmitter-negative neurons.

Conclusions

To sum up, inflammation of the uterus has an impact on the neurochemical properties of the uterine perikarya in PCG, possibly affecting the functions of the organ.
Statins and clinical outcomes in hospitalized COVID-19 patients with and without Diabetes Mellitus: a retrospective cohort study with propensity score matching
Authors: Lohia Prateek , Kapur Shweta , Benjaram Sindhuri , Cantor Zachary , Mahabadi Navid , Mir Tanveer , Badr M. Safwan
Published: July 2021

Background

The pleiotropic effects of statins may reduce the severity of COVID-19 disease. This study aims to determine the association between inpatient statin use and severe disease outcomes among hospitalized COVID-19 patients, especially those with Diabetes Mellitus (DM).

Research design and methods

A retrospective cohort study on hospitalized patients with confirmed COVID-19 diagnosis. The primary outcome was mortality during hospitalization. Patients were classified into statin and non-statin groups based on the administration of statins during hospitalization. Analysis included multivariable regression analysis adjusting for confounders and propensity score matching to achieve a 1:1 balanced cohort. Subgroup analyses based on presence of DM were conducted.

Results

In the cohort of 922 patients, 413 had a history of DM. About 27.1% patients (n = 250) in the total cohort (TC) and 32.9% patients (n = 136) in DM cohort received inpatient statins. Atorvastatin (n = 205, 82%) was the most commonly prescribed statin medication in TC. On multivariable analysis in TC, inpatient statin group had reduced mortality compared to the non-statin group (OR, 0.61; 95% CI, 0.42–0.90; p = 0.01). DM modified this association between inpatient statins and mortality. Patients with DM who received inpatient statins had reduced mortality (OR, 0.35; 95% CI, 0.21–0.61; p < 0.001). However, no such association was noted among patients without DM (OR, 1.21; 95% CI, 0.67–2.17; p = 0.52). These results were further validated using propensity score matching.

Conclusions

Inpatient statin use was associated with significant reduction in mortality among COVID-19 patients especially those with DM. These findings support the pursuit of randomized clinical trials and inpatient statin use appears safe among COVID-19 patients.
Integrative analysis the characterization of peroxiredoxins in pan-cancer
Authors: Gao Lei , Meng Jialin , Yue Chuang , Wu Xingyu , Su Quanxin , Wu Hao , Zhang Ze , Yu Qinzhou , Gao Shenglin , Fan Song , Zuo Li
Published: July 2021

Background

Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA).

Methods

A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA.

Result

Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines.

Conclusions

PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA.
Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample
Authors: Kvamme Sinikka L. , Pedersen Michael M. , Rømer Thomsen Kristine , Thylstrup Birgitte
Published: July 2021

Background

The use of cannabis as medicine (CaM) both prescribed and non-prescribed has increased markedly in the last decade, mirrored in a global shift in cannabis policy towards a more permissive stance. There is some evidence that cannabis functions as a substitute for prescription drugs, particularly opioids; however, more knowledge is needed on the motives of substitution users, their patterns of use, and perceived effects of substitution use.

Aims

To explore who substitutes prescription drugs with cannabis, the type of prescription drugs substituted and the type of cannabis used, and the impact that substitution with cannabis has on prescription drug use as well as the motives for substitution in terms of experienced effects and side effects.

Methods

A self-selected convenience sample was recruited through social media, public media, and patient organizations to take part in an anonymous online survey. Inclusion criteria were 18 years or older and use of cannabis (prescribed or non-prescribed) with a medical purpose.

Results

The final sample included 2.841 respondents of which the majority (91%) used non-prescribed cannabis, and more than half (54.6%) had used CaM with the purpose of replacing a prescribed drug. Compared to non-substitution users, substitution users were more likely to be women and to use CaM in the treatment of chronic pain and other somatic conditions. Pain medication (67.2%), antidepressants (24.5%), and arthritis medication (20.7%) were the most common types of drugs replaced with CaM. Among substitution users, 38.1% reported termination of prescription drug use, and 45.9% a substantial decrease in prescription drug use. The most frequent type of cannabis used as a substitute was CBD-oil (65.2%), followed by ‘hash, pot or skunk’ (36.6%). More than half (65.8%) found CaM much more effective compared to prescription drugs, and 85.5% that the side effects associated with prescription drug use were much worse compared to use of CaM.

Conclusion

CaM is frequently used as a substitute for prescription drugs, particularly opioids. More research is needed on the long-term consequences of use of CaM, including the impact from low and high THC cannabis products on specific somatic and mental health conditions.
Regulating the health workforce in Europe: implications of the COVID-19 pandemic
Authors: Panteli Dimitra , Maier Claudia B.
Published: July 2021

In the European free movement zone, various mechanisms aim to harmonize how the competence of physicians and nurses is developed and maintained to facilitate the cross-country movement of professionals. This commentary addresses these mechanisms and discusses their implications during the COVID-19 pandemic, drawing lessons for future policy. It argues that EU-wide regulatory mechanisms should be reviewed to ensure that they provide an adequate foundation for determining competence and enabling health workforce flexibility during health system shocks. Currently, EU regulation focuses on the automatic recognition of the primary education of physicians and nurses. New, flexible mechanisms should be developed for specializations, such as intensive or emergency care. Documenting new skills, such as the ones acquired during rapid training in the pandemic, in a manner that is comparable across countries should be explored, both for usual practice and in light of outbreak preparedness. Initiatives to strengthen continuing education and professional development should be supported further. Funding under the EU4Health programme should be dedicated to this endeavour, along with revisiting the scope of necessary skills following the experience of COVID-19. Mechanisms for cross-country sharing of information on violations of good practice standards should be maintained and strengthened to enable agile reactions when the need for professional mobility becomes urgent.
Depression among healthcare workers in the Eastern Mediterranean Region: a systematic review and meta-analysis
Authors: Abraham Amit , Chaabna Karima , Doraiswamy Sathyanarayanan , Bhagat Sapna , Sheikh Javaid , Mamtani Ravinder , Cheema Sohaila
Published: July 2021

Background

Depression is a major population health challenge globally. This systematic review and meta-analysis aims to (i) determine depression prevalence and (ii) identify the risk and protective factors of depression among healthcare workers (HCWs) in the Eastern Mediterranean Region (EMR).

Methods

The protocol was registered on Open Science Framework (registration ID:https://osf.io/rdv27). We searched five databases (PubMed, Embase, PsycINFO, Al Manhal, Google Scholar) till July 22, 2020 without language restrictions. We included studies from the EMR using a depression screening or diagnostic instrument to measure the depression prevalence among HCWs. Studies were assessed and data were pooled using random-effects meta-analysis based on the Cochrane handbook.

Results

The systematic review identified 108 studies from 12 EMR countries with varying quality. Working long hours, poor sleep quality and being female were risk factors for depression in EMR HCWs. The meta-analysis comprised 77 studies providing 122 prevalence measures across 7 EMR countries. The pooled prevalence of depression among EMR HCWs was 33.03% (95% CI = 27.40–39.19%). Emergency HCWs had markedly higher rates of depression [53.14% (95% CI = 26.63–77.99%)] compared to HCWs of other specialties. Most studies had an appropriate sample size.

Conclusions

Depression among EMR HCWs is a major concern. Steps must be taken to prevent, identify, and manage depression among HCWs. Fostering a compassionate and empathetic environment is critically important to building a resilient healthcare system. Generating high-quality regional data from longitudinal studies on mental health will further contribute to a better understanding and management of depression among EMR HCWs.
Differential RNA packaging into small extracellular vesicles by neurons and astrocytes
Authors: Luo Xuan , Jean-Toussaint Renée , Sacan Ahmet , Ajit Seena K.
Published: July 2021

Background

Small extracellular vesicles (sEVs) mediate intercellular communication by transferring RNA, proteins, and lipids to recipient cells. These cargo molecules are selectively loaded into sEVs and mirror the physiological state of the donor cells. Given that sEVs can cross the blood–brain barrier and their composition can change in neurological disorders, the molecular signatures of sEVs in circulation can be potential disease biomarkers. Characterizing the molecular composition of sEVs from different cell types is an important first step in determining which donor cells contribute to the circulating sEVs.

Methods

Cell culture supernatants from primary mouse cortical neurons and astrocytes were used to purify sEVs by differential ultracentrifugation and sEVs were characterized using nanoparticle tracking analysis, transmission electron microscopy and western blot. RNA sequencing was used to determine differential expression and loading patterns of miRNAs in sEVs released by primary neurons and astrocytes. Motif analysis was conducted on enriched miRNAs in sEVs and their respective donor cells.

Results

Sequencing total cellular RNA, and miRNAs from sEVs isolated from culture media of postnatal mouse cortical neurons and astrocytes revealed a distinct profile between sEVs and their corresponding cells. Though the total number of detected miRNAs in astrocytes was greater than neurons, neurons expressed more sEV-associated miRNAs than astrocytes. Only 20.7% of astrocytic miRNAs were loaded into sEVs, while 41.0% of neuronal miRNAs were loaded into sEVs, suggesting differences in the cellular sorting mechanisms. We identified short RNA sequence motifs, or EXOmotifs, on the miRNAs that were differentially loaded or excluded from sEVs. A sequence motif GUAC was enriched in astrocytic sEVs. miRNAs preferably retained in neurons or astrocytes had a similar RNA motif CACACA, suggesting a cell-type-independent mechanism to maintain cellular miRNAs. mRNAs of five RNA-binding proteins associated with passive or active RNA sorting into sEVs were differentially expressed between neurons and astrocytes, one of which, major vault protein was higher in astrocytes than in neurons and detected in astrocytic sEVs.

Conclusions

Our studies suggest differences in RNA sorting into sEVs. These differences in miRNA signatures can be used for determining the cellular sources of sEVs altered in neurological disorders.
WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy
Authors: Hashemi Ehsan , Dehghanbanadaki Hojat , Baharanchi Alireza Abbasi , Forouzanfar Katayoon , Kakaei Ardeshir , Mohammadi Seyed Mohammad , Zeidi Saba , Razi Farideh
Published: July 2021

Background

Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN.

Methods

The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs.

Results

DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = − 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively.

Conclusions

WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.
A video game based hand grip system for measuring muscle force in children
Authors: Gotthelf Mark , Townsend DeWayne , Durfee William
Published: July 2021

Background

While new therapies are continuously introduced to treat muscular dystrophy, current assessment tests are challenging to quantify, cannot be used in non-ambulatory patients, or can de-motivate pediatric patients. We developed a simple, engaging, upper-limb assessment tool that measures muscle strength and fatigue in children, including children with muscular dystrophy. The device is a bio-feedback grip sensor that motivates children to complete maximal and fatiguing grip protocols through a game-based interface.

Methods

To determine if the new system provided the same maximum grip force as what is reported in the literature, data was collected from 311 participants without muscle disease (186 M, 125 F), ages 6 to 30, each of whom played the four minute grip game once. We compared maximum voluntary contraction at the start of the test to normative values reported in the literature using Welch’s unequal variances t-tests. In addition, we collected data on a small number of participants with muscle disease to determine if the assessment system could be used by the target patient population.

Results

Of the 311 participants without muscle disease that started the test, all but one completed the game. The maximum voluntary contraction data, when categorized by age, matched literature values for hand grip force within an acceptable range. Grip forced increased with age and differed by gender, and most participants exhibited fatigue during the game, including a degradation in tracking ability as the game progressed. Of the 13 participants with muscle disease, all but one completed the game.

Conclusions

The study demonstrated the technical feasibility and validity of the new hand grip device, and indicated that the device can be used to assess muscle force and fatigue in longitudinal studies of children with muscular dystrophy.
The prevalence of human herpesvirus 8 in normal, premalignant, and malignant cervical samples of Iranian women
Authors: Chavoshpour-Mamaghani Sara , Shoja Zabihollah , Mollaei-Kandelous Yaghoub , Sharifian Kimia , Jalilvand Somayeh
Published: July 2021

Background

Regard to this fact that the main transmission route of HPV and HHV-8 is via sexual activity, it is reasonable to speculate that coinfection of HPV and HHV-8 may have been played an important role in the development of cervical cancer. The aim of this study was to estimate the prevalence of HHV-8 and the frequency of HPV and HHV-8 coinfection in cervical samples of patients with cervical cancer and healthy individuals.

Methods

In total, 364 samples from 61 patients with cervical cancer, 124 women with premalignant lesions, and 179 healthy individuals were investigated by nested-PCR.

Results

The frequency of HHV-8 was found to be 22.9%, 17.7%, and 14.5% in cervical cancer, premalignant lesions, and normal specimens, respectively (P = 0.308). The overall prevalence of coinfection between HHV-8 and HPV was shown to be 16.2%. The HPV prevalence was higher in HHV-8 positive samples than HHV-8 negative specimens in all three studied groups and this difference was reached a statistically significant level (P = 0.002). However, no significant differences were found between HHV-8 positivity and HPV genotypes (P = 0.08).

Conclusions

Our results showed the higher rate of HHV-8 genome detection in cervical cancer group than control group. However, future studies with larger sample sizes and evaluation of expression of HHV-8 proteins are warranted.
Mapping patterns of para-aortic lymph node recurrence in cervical cancer: a retrospective cohort analysis
Authors: Bae Bong Kyung , Park Shin-Hyung , Jeong Shin Young , Chong Gun Oh , Kim Mi Young , Kim Jae-Chul
Published: July 2021

Background

To map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV).

Methods

Cervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTVRTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTVK was contoured as proposed by Keenan et al. CTVM was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12–L1 interspace. CTVnew was created by modifying CTVRTOG to obtain better coverage.

Results

We identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTVRTOG, CTVK, and CTVM covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTVnew to cover 96.7% of all PALNs and all nodes in 91.4% of patients.

Conclusion

CTVRTOG and CTVK encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered.
YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma
Authors: Chai Rui-Chao , Chang Yu-Zhou , Chang Xin , Pang Bo , An Song Yuan , Zhang Ke-Nan , Chang Yuan-Hao , Jiang Tao , Wang Yong-Zhi
Published: July 2021

Background

The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2′-O-dimethyladenosine (m6A) reader, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), in regulating the malignant progression of gliomas.

Methods

YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2.

Results

YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-κB activation. We further revealed that UBXN1 overexpression attenuated the oncogenic effect of YTHDF2 overexpression and was associated with better survival in patients with elevated YTHDF2 expression.

Conclusions

Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m6A modification.
Non‐pharmacological interventions and corticosteroid injections for the management of the Achilles tendon in inflammatory arthritis: a systematic review
Authors: Modi Shaily , Turner Deborah , Hennessy Kym
Published: July 2021

Background

Achilles tendon (AT) pathologies, particularly Achilles enthesitis, are common in inflammatory arthritis (IA). Although there are various non‐pharmacological interventions and injection therapies available, it is unknown if these interventions are effective for people with IA, as this population is often excluded from studies investigating the management of AT pathologies. This study aimed to identify and critically appraise the evidence for non‐pharmacological interventions and corticosteroid injections in the management of AT pathology in those with IA.

Methods

All studies which met the inclusion criteria (AT interventions in adults with a working clinical diagnosis of IA, English language) were identified from the following databases: Medline, Embase, CINAHL and the Cochrane Library. The search strategies used the search terms ‘spondyloarthropathies', ‘inflammatory arthritis', ‘achilles tendon’, ‘physical therapy’, ‘conservative management’, ‘injections', and related synonyms. Studies included were quantitative longitudinal design, such as randomised controlled trials, pseudo randomised and non‐randomised experimental studies, observational studies, cohort studies, and case control studies. All outcome measures were investigated, quality assessment to determine internal and external validity of included studies was undertaken, and qualitative data synthesis was conducted.

Results

Of the 10,911 articles identified in the search strategy, only two studies that investigated the efficacy of corticosteroid injections for the management of the AT in IA met the inclusion criteria, and no studies were identified for non‐pharmacological interventions. Both injection studies had low quality rating for internal and external validity, and thus overall validity. The included studies only investigated two outcome domains: pain and ultrasound (US) (B Mode and Doppler) identified abnormalities and vascularity in the AT. There is weak evidence suggesting a short‐term improvement (6–12 weeks) in pain and for the reduction in some abnormal US (B‐Mode and Doppler) detectable features (entheseal thickness, bursitis, and entheseal vascularity) at the AT and surrounding structures post‐corticosteroid injection.

Conclusion

Weak evidence is available regarding the efficacy of corticosteroid injections in reducing pain and inconclusive evidence for the improvement of abnormal US detectable features. No studies were identified for non‐pharmacological interventions. It is evident from the lack of relevant literature that there is an urgent need for more studies assessing non‐pharmacological interventions for the AT in people with IA.
Cycling in people with a lower limb amputation
Authors: Poonsiri Jutamanee , Dekker Rienk , Dijkstra Pieter U. , Hijmans Juha M. , Geertzen Jan H. B.
Published: July 2021

Background

To evaluate cycling participation and identify barriers and facilitators related to cycling participation in people with a lower limb amputation (LLA) in the Netherlands.

Methods

A questionnaire was sent to adults with a LLA between March and August 2019 to obtain information regarding prosthesis, individual’s characteristics, amputation, cycling barriers and facilitators, and prosthetic satisfaction. The questionnaires were distributed via 8 orthopedic workshops, post and were given directly. To find cycling predictors, variables associated with cycling (p < 0.1) were entered into a logistic regression analysis. Non-significant variables were removed manually.

Results

Participants (n = 207, 71% males) had a mean age of 62.0 ± 13.0 years. The most frequent level of amputation was transtibial (42%), and trauma was the most frequent cause of amputation (43%). After the LLA, 141 participants (68%) cycled for recreation (80%), physical fitness (74%), and transport (50%). In the past six months, cyclists cycled for recreation (79%) and transport (66%). Most cycled less than once a day. Recreational cyclists cycled alone (75%) for a median duration of 45 min or 14 km per ride. Cyclists with a transportation purpose usually cycled to go shopping (80%) or to visit friends (68%), with a median duration of 20 min or five kilometers per ride. Cyclists reported more facilitators (median (IQR) = 5 (3, 7) than non-cyclists 0 (0, 3). The majority of cyclists reported a positive attitude toward cycling (89%) and cycled because of health benefits (81%). A dynamic foot (odds ratio: 5.2, 95% CI 2.0, 13.3) and a higher number of facilitators (odds ratio: 1.3, 95% CI 1.2, 1.5) positively predicted cycling, whereas the presence of other underlying diseases (odds ratio: 0.4, 95% CI 0.2, 0.9) negatively predicted cycling (R2: 40.2%).

Conclusion

In the Netherlands, the majority of adults cycled after a LLA, mainly for recreational purposes. A dynamic foot, a higher number of facilitators, and no other underlying diseases increases the likelihood of cycling after a LLA. The results suggest that personal motivation and a higher mobility level could be the key to increasing cycling participation. Future research should determine the association between motivation, mobility levels, and cycling with a LLA.
Short-term effect of ovariohysterectomy on urine serotonin, cortisol, testosterone and progesterone in bitches
Authors: Hydbring-Sandberg Eva , Larsson Elin , Madej Andrzej , Höglund Odd Viking
Published: July 2021

Objective

This study aimed to investigate the short-term effect of ovariohysterectomy on urine levels of serotonin and its relation to levels of cortisol, testosterone and progesterone in female dogs. Seven bitches were studied before surgical ovariohysterectomy and then once a week during 4 weeks. Spontaneously voided urine samples were collected and concentration ratios of hormone/creatinine in urine were analysed.

Results

The bitches had significantly lower levels of cortisol, testosterone, and progesterone 1 week after ovariohysterectomy compared with before and the levels stayed low throughout the study (P ≤ 0.05). Interestingly, serotonin levels tended to increase 4 weeks after surgery (P = 0.08). A positive correlation between cortisol and progesterone was found before and after surgery. After surgery, serotonin was positively correlated with cortisol and progesterone (P ≤ 0.05).
Genome sequence analysis of new plum pox virus isolates from Japan
Authors: Mori Tomoaki , Warner Chiaki , Ohno Serika , Mori Koichi , Tobimatsu Takamasa , Sera Takashi
Published: July 2021

Objective

To find mutations that may have recently occurred in Plum pox virus (PPV), we collected six PPV-infected plum/peach trees from the western part of Japan and one from the eastern part. After sequencing the full-length PPV genomic RNAs, we compared the amino acid sequences with representative isolates of each PPV strain.

Results

All new isolates were found to belong to the PPV-D strain: the six isolates collected from western Japan were identified as the West-Japan strain while the one collected from eastern Japan as the East-Japan strain. Amino acid sequence analysis of these seven isolates suggested that the 1407th and 1529th amino acid residues are characteristic of the West-Japan and the East-Japan strains, respectively. Comparing them with the corresponding amino acid residues of the 47 non-Japanese PPV-D isolates revealed that these amino acid residues are undoubtedly unique. A further examination of the relevant amino acid residues of the other 210 PPV-D isolates collected in Japan generated a new hypothesis regarding the invasion route from overseas and the subsequent diffusion route within Japan: a PPV-D strain might have invaded the western part of Japan from overseas and spread throughout Japan.
DNA methylation analysis reveals epimutation hotspots in patients with dilated cardiomyopathy-associated laminopathies
Authors: Morival Julien L. P. , Widyastuti Halida P. , Nguyen Cecilia H. H. , Zaragoza Michael V. , Downing Timothy L.
Published: July 2021

Background

Mutations inLMNA, encoding lamin A/C, lead to a variety of diseases known as laminopathies including dilated cardiomyopathy (DCM) and skeletal abnormalities. Though previous studies have investigated the dysregulation of gene expression in cells from patients with DCM, the role of epigenetic (gene regulatory) mechanisms, such as DNA methylation, has not been thoroughly investigated. Furthermore, the impact of family-specificLMNAmutations on DNA methylation is unknown. Here, we performed reduced representation bisulfite sequencing on ten pairs of fibroblasts and their induced pluripotent stem cell (iPSC) derivatives from two families with DCM due to distinctLMNAmutations, one of which also induces brachydactyly.

Results

Family-specific differentially methylated regions (DMRs) were identified by comparing the DNA methylation landscape of patient and control samples. Fibroblast DMRs were found to enrich for distal regulatory features and transcriptionally repressed chromatin and to associate with genes related to phenotypes found in tissues affected by laminopathies. These DMRs, in combination with transcriptome-wide expression data and lamina-associated domain (LAD) organization, revealed the presence of inter-family epimutation hotspots near differentially expressed genes, most of which were located outside LADs redistributed inLMNA-related DCM. Comparison of DMRs found in fibroblasts and iPSCs identified regions where epimutations were persistent across both cell types. Finally, a network of aberrantly methylated disease-associated genes revealed a potential molecular link between pathways involved in bone and heart development.

Conclusions

Our results identified both shared and mutation-specific laminopathy epimutation landscapes that were consistent with lamin A/C mutation-mediated epigenetic aberrancies that arose in somatic and early developmental cell stages.
Initial action output and feedback-guided motor behaviors in autism spectrum disorder
Authors: Unruh Kathryn E. , McKinney Walker S. , Bojanek Erin K. , Fleming Kandace K. , Sweeney John A. , Mosconi Matthew W.
Published: July 2021

Background

Sensorimotor issues are common in autism spectrum disorder (ASD), related to core symptoms, and predictive of worse functional outcomes. Deficits in rapid behaviors supported primarily by feedforward mechanisms, and continuous, feedback-guided motor behaviors each have been reported, but the degrees to which they are distinct or co-segregate within individuals and across development are not well understood.

Methods

We characterized behaviors that varied in their involvement of feedforward control relative to feedback control across skeletomotor (precision grip force) and oculomotor (saccades) control systems in 109 individuals with ASD and 101 age-matched typically developing controls (range: 5–29 years) including 58 individuals with ASD and 57 controls who completed both grip and saccade tests. Grip force was examined across multiple force (15, 45, and 85% MVC) and visual gain levels (low, medium, high). Maximum grip force also was examined. During grip force tests, reaction time, initial force output accuracy, variability, and entropy were examined. For the saccade test, latency, accuracy, and trial-wise variability of latency and accuracy were examined.

Results

Relative to controls, individuals with ASD showed similar accuracy of initial grip force but reduced accuracy of saccadic eye movements specific to older ages of our sample. Force variability was greater in ASD relative to controls, but saccade gain variability (across trials) was not different between groups. Force entropy was reduced in ASD, especially at older ages. We also find reduced grip strength in ASD that was more severe in dominant compared to non-dominant hands.

Limitations

Our age-related findings rely on cross-sectional data. Longitudinal studies of sensorimotor behaviors and their associations with ASD symptoms are needed.

Conclusions

We identify reduced accuracy of initial motor output in ASD that was specific to the oculomotor system implicating deficient feedforward control that may be mitigated during slower occurring behaviors executed in the periphery. Individuals with ASD showed increased continuous force variability but similar levels of trial-to-trial saccade accuracy variability suggesting that feedback-guided refinement of motor commands is deficient specifically when adjustments occur rapidly during continuous behavior. We also document reduced lateralization of grip strength in ASD implicating atypical hemispheric specialization.
Zinc oxide nanoparticles conjugated with clinically-approved medicines as potential antibacterial molecules
Authors: Akbar Noor , Aslam Zara , Siddiqui Ruqaiyyah , Shah Muhammad Raza , Khan Naveed Ahmed
Published: July 2021

At present, antibiotic resistance is one of the most pressing issues in healthcare globally. The development of new medicine for clinical applications is significantly less than the emergence of multiple drug-resistant bacteria, thus modification of existing medicines is a useful avenue. Among several approaches, nanomedicine is considered of potential therapeutic value. Herein, we have synthesized Zinc oxide nanoparticles (ZnO-NPs) conjugated with clinically-approved drugs (Quercetin, Ceftriaxone, Ampicillin, Naringin and Amphotericin B) with the aim to evaluate their antibacterial activity against several Gram-positive (Methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes) and Gram-negative (Escherichia coli K1, Serratia marcescens and Pseudomonas aeruginosa) bacteria. The nanoparticles and their drug conjugates were characterized using UV-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy and atomic force microscopy. Antibacterial activity was performed by dilution colony forming unit method and finally 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine their cytotoxic effects against human cell lines. ZnO-NPs revealed maxima surface plasmon resonance band at 374 and after conjugation with beta-cyclodextrin at 379 nm, polydispersity with size in range of 25–45 nm with pointed shaped morphology. When conjugated with ZnO-NPs, drug efficacy against MDR bacteria was enhanced significantly. In particular, Ceftriaxone- and Ampicillin-conjugated ZnO-NPs exhibited potent antibacterial effects. Conversely, ZnO-NPs and drugs conjugated NPs showed negligible cytotoxicity against human cell lines except Amphotericin B (57% host cell death) and Amphotericin B-conjugated with ZnO-NPs (37% host cell death). In conclusion, the results revealed that drugs loaded on ZnO-NPs offer a promising approach to combat increasingly resistant bacterial infections.
The growth of plants and indigenous bacterial community were significantly affected by cadmium contamination in soil–plant system
Authors: Du Yunyan , Zhang Dawei , Zhou Dinggang , Liu Lili , Wu Jinfeng , Chen Hongsong , Jin Decai , Yan Mingli
Published: July 2021

Concentrations of heavy metals continue to increase in soil environments as a result of both anthropogenic activities and natural processes. Cadmium (Cd) is one of the most toxic heavy metals and poses health risks to both humans and the ecosystem. Herein, we explore the impacts of Cd on a soil–plant system composed of oilseed rapes (Brassica napus and Brassica juncea) and bacteria. The results showed that Cd accumulation within tissues of two species of oilseed rapes enhanced with increasing concentrations of Cd in soils, and Cd treatment decreased their chlorophyll content and suppressed rapeseeds growth. Meanwhile, Cd stress induced the changes of antioxidative enzymes activities of both B. napus and B. juncea. Response to Cd of bacterial community was similar in soil-two species of oilseed rapes system. The impact of Cd on the bacterial communities of soils was greater than bacterial communities of plants (phyllosphere and endophyte). The α-diversity of bacterial community in soils declined significantly under higher Cd concentration (30 mg/kg). In addition, soil bacterial communities composition and structure were altered in the presence of higher Cd concentration. Meanwhile, the bacterial communities of bulk soils were significantly correlated with Cd, while the variation of rhizosphere soils bacterial communities were markedly correlated with Cd and other environmental factors of both soils and plants. These results suggested that Cd could affect both the growth of plants and the indigenous bacterial community in soil–plant system, which might further change ecosystem functions in soils.