bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling blooms of Planktothrix rubescens by optimized metalimnetic water withdrawal: a modelling study on adaptive reservoir operation
Authors: Mi Chenxi , Hamilton David P. , Frassl Marieke A. , Shatwell Tom , Kong Xiangzhen , Boehrer Bertram , Li Yiping , Donner Jan , Rinke Karsten
Published: October 2022

Background

Aggregations of cyanobacteria in lakes and reservoirs are commonly associated with surface blooms, but may also occur in the metalimnion as subsurface or deep chlorophyll maxima. Metalimnetic cyanobacteria blooms are of great concern when potentially toxic species, such as Planktothrix rubescens, are involved. Metalimnetic blooms of P. rubescens have apparently increased in frequency and severity in recent years, so there is a strong need to identify reservoir management options to control it. We hypothesized that P. rubescens blooms in reservoirs can be suppressed using selective withdrawal to maximize its export from the reservoir. We also expect that altering the light climate can affect the dynamics of this species. We tested our hypothesis in Rappbode Reservoir (the largest drinking water reservoir in Germany) by establishing a series of withdrawal and light scenarios based on a calibrated water quality model (CE-QUAL-W2).

Results

The novel withdrawal strategy, in which water is withdrawn from a certain depth below the surface within the metalimnion instead of at a fixed elevation relative to the dam wall, significantly reduced P. rubescens biomass in the reservoir. According to the simulation results, we defined an optimal withdrawal volume to control P. rubescens blooms in the reservoir as approximately 10 million m3 (10% of the reservoir volume) during its bloom phase. The results also illustrated that P. rubescens growth can be most effectively suppressed if the metalimnetic withdrawal is applied in the early stage of its rapid growth, i.e., before the bloom occurs. In addition, our study showed that P. rubescens biomass gradually decreased with increasing light extinction and nearly disappeared when the extinction coefficient exceeded 0.55 m−1.

Conclusions

Our study indicates the rise in P. rubescens biomass can be effectively offset by selective withdrawal as well as by reducing light intensity beneath the water surface. Considering the widespread occurrence of P. rubescens in stratified lakes and reservoirs worldwide, we believe the results will be helpful for scientists and managers working on other water bodies to minimize the negative impacts of this harmful cyanobacteria. Our model may serve as a transferable tool to explore local dynamics in other standing waters.
Co-expression network analysis identifies potential candidate hub genes in severe influenza patients needing invasive mechanical ventilation
Authors: Chen Liang , Hua Jie , He Xiaopu
Published: October 2022

Background

Influenza is a contagious disease that affects people of all ages and is linked to considerable mortality during epidemics and occasional outbreaks. Moreover, effective immunological biomarkers are needed for elucidating aetiology and preventing and treating severe influenza. Herein, we aimed to evaluate the key genes linked with the disease severity in influenza patients needing invasive mechanical ventilation (IMV). Three gene microarray data sets (GSE101702, GSE21802, and GSE111368) from blood samples of influenza patients were made available by the Gene Expression Omnibus (GEO) database. The GSE101702 and GSE21802 data sets were combined to create the training set. Hub indicators for IMV patients with severe influenza were determined using differential expression analysis and Weighted correlation network analysis (WGCNA) from the training set. The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy. Different immune cells' infiltration levels in the expression profile and their correlation with hub gene markers were examined using single-sample gene set enrichment analysis (ssGSEA).

Results

In the present study, we evaluated a total of 447 differential genes. WGCNA identified eight co-expression modules, with the red module having the strongest correlation with IMV patients. Differential genes were combined to obtain 3 hub genes (HLA-DPA1, HLA-DRB3, and CECR1). The identified genes were investigated as potential indicators for patients with severe influenza who required IMV using the least absolute shrinkage and selection operator (LASSO) approach. The ROC showed the diagnostic value of the three hub genes in determining the severity of influenza. Using ssGSEA, it has been revealed that the expression of key genes was negatively correlated with neutrophil activation and positively associated with adaptive cellular immune response.

Conclusion

We evaluated three novel hub genes that could be linked to the immunopathological mechanism of severe influenza patients who require IMV treatment and could be used as potential biomarkers for severe influenza prevention and treatment.
Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain
Authors: Martens Gerrit A. , Geßner Cornelia , Osterhof Carina , Hankeln Thomas , Burmester Thorsten
Published: October 2022

Background

The hooded seal (Cystophora cristata) exhibits impressive diving skills and can tolerate extended durations of asphyxia, hypoxia and oxidative stress, without suffering from irreversible neuronal damage. Thus, when exposed to hypoxia in vitro, neurons of fresh cortical and hippocampal tissue from hooded seals maintained their membrane potential 4–5 times longer than neurons of mice. We aimed to identify the molecular mechanisms underlying the intrinsic neuronal hypoxia tolerance. Previous comparative transcriptomics of the visual cortex have revealed that S100B and clusterin (apolipoprotein J), two stress proteins that are involved in neurological disorders characterized by hypoxic conditions, have a remarkably high expression in hooded seals compared to ferrets. When overexpressed in murine neuronal cells (HN33), S100B and clusterin had neuroprotective effects when cells were exposed to hypoxia. However, their specific roles in hypoxia have remained largely unknown.

Methods

In order to shed light on potential molecular pathways or interaction partners, we exposed HN33 cells transfected with either S100B, soluble clusterin (sCLU) or nuclear clusterin (nCLU) to normoxia, hypoxia and oxidative stress for 24 h. We then determined cell viability and compared the transcriptomes of transfected cells to control cells. Potential pathways and upstream regulators were identified via Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA).

Results

HN33 cells transfected with sCLU and S100B demonstrated improved glycolytic capacity and reduced aerobic respiration at normoxic conditions. Additionally, sCLU appeared to enhance pathways for cellular homeostasis to counteract stress-induced aggregation of proteins. S100B-transfected cells sustained lowered energy-intensive synaptic signaling. In response to hypoxia, hypoxia-inducible factor (HIF) pathways were considerably elevated in nCLU- and sCLU-transfected cells. In a previous study, S100B and sCLU decreased the amount of reactive oxygen species and lipid peroxidation in HN33 cells in response to oxidative stress, but in the present study, these functional effects were not mirrored in gene expression changes.

Conclusions

sCLU and S100B overexpression increased neuronal survival by decreasing aerobic metabolism and synaptic signaling in advance to hypoxia and oxidative stress conditions, possibly to reduce energy expenditure and the build-up of deleterious reactive oxygen species (ROS). Thus, a high expression of CLU isoforms and S100B is likely beneficial during hypoxic conditions.
What GPs do to meet accreditation standards – implementation activities and perceived improvements attributed to general practice accreditation
Authors: Mølgaard Cecilie , Bro Flemming , Mygind Anna
Published: October 2022

Background

Healthcare accreditation is a widely implemented tool used to enhance the quality of care and underpin quality control. However, research is sparse on the accreditation process in general practice. The aim of this study was to explore how team-based implementation activities preceding accreditation were associated with self-perceived improvements in emergency preparedness (preparedness for urgent disease and cardiac arrest) and handling of prescription renewals in Danish general practice.

Methods

GPs (general practitioners) completed a questionnaire exploring practice-team activities conducted to implement two specific accreditation standards and the related improvements as perceived by the GPs. The following implementation activities were selected, inspired by Normalization Process Theory: Common understanding (obtaining a common understanding of the purpose of implementing changes according to the accreditation standard), key person (assigning a key person responsible for working with the standard), and easy integration (finding it easy to integrate changes into existing working procedures). Data were analysed with logistic regression, and adjusted analyses included practice type, number of GP partners, number of staff, training site for junior GPs and administrative region.

Results

The total response rate was 74% (n = 920). Around 80% of the clinics reported having conducted team-based implementation activities. Almost half of the clinics (48%) reported perceived improvements in the emergency preparedness, and 30% reported perceived improvements in the handling of prescription renewals. Obtaining a common understanding was found to have a strong, significant association with perceived improvements in the emergency preparedness (OR = 5.07 (3.06–8.40)) and handling of prescription renewals (OR = 3.66 (2.07–6.46)). Easy integration of changes was also significantly associated with improvements in both emergency preparedness (OR = 1.88 (1.24–2.85)) and handling of prescription renewals (OR = 2.34 (1.44–3.79)), whereas assigning a key person was only significantly associated with improved emergency preparedness (OR = 1.95 (1.19–3.19)).

Conclusion

Clinical quality initiatives that involve collaboration within a practice team are more likely to cause improvements if specific team-based implementation activities are conducted. It is particularly important to facilitate a common understanding of the purpose of the initiative. Therefore, external support for quality initiatives aiming at the practice level in general practice should facilitate such team-based activities.
Perception of providers on use of the WHO mental health Gap Action Programme-Intervention Guide (mhGAP-IG) electronic version and smartphone-based clinical guidance in Nigerian primary care settings
Authors: Ojagbemi Akin , Daley Stephanie , Kola Lola , Taylor Salisbury Tatiana , Feeney Yvonne , Makhmud Akerke , Lempp Heidi , Thornicroft Graham , Gureje Oye
Published: October 2022

Background

Taking advantage of the rapidly increasing access to digital technology in low- and middle-income countries, the World Health Organization has launched an electronic version of the mental health Gap Action Programme intervention guide (emhGAP-IG). This is suitable for use on smartphones or tablets by non-specialist primary healthcare providers (PHCWs) to deliver evidence-based intervention for priority mental, neurological and substance use disorders. We assessed the perceptions of PHCWs on the feasibility, acceptability, and benefits of using smartphone-based clinical guidance and the emhGAP-IG in the management of people with mental health conditions in Nigeria. 

Methods

Exploration of the views of PHCWs from 12 rural and urban primary health clinics (PHCs) in South-Western Nigeria were carried out using 34 in-depth key informant qualitative interviews with nurses (n = 10), community health officers (n = 13) and community health extension workers (n = 11). An additional two focus group discussions, each comprising eight participants drawn from across the range of characteristics of PHCWs, were also conducted. Thematic analysis was conducted using a three-staged constant comparison technique to refine and categorise the data.

Results

Three overall themes were identified around the use of clinical guidance and mobile applications (apps) in PHCs. Apps were deployed for purposes other than clinical consultation and decision making. Although paper-based guidance was the expected practice, its utilization is not fully embedded in routine care. An app-based decision-making tool was preferred to paper by PHCWs. Future usage of the emhGAP-IG would be facilitated by training and supporting of staff, helpful design features, and obtaining patients’ buy-in.

Conclusion

Our findings suggest that the emhGAP-IG could be a viable way to embed clinical guidance and decision-making tools in the management of people with mental health conditions in Nigerian PHCs.
Incidence and type of restrictive practice use in nursing homes in Ireland
Authors: Dunbar Paul , McMahon Martin , Durkan Ciara , Walsh Kieran A. , Keyes Laura M.
Published: October 2022

Background

Use of restrictive practices (RP) in care settings may sometimes be warranted but can also conflict with human rights. Research to date has focused primarily on physical and chemical RP, however other forms are also used. Better understanding of practice can inform RP reduction. This study describes the incidence of all types of RP use reported from nursing homes in Ireland.

Methods

RP notifications from nursing homes reported in 2020 were extracted from the Database of Statutory Notifications from Social Care in Ireland. The primary outcome measurement was the national incidence of use (frequency of RP/occupancy per 1000 residents) of categories and types of RP. Secondary outcome measurements such as percentage of facilities reporting use and quarterly median incidence of use in these facilities were calculated.

Results

Seventy thousand six hundred sixty-three RP uses were notified from 608 facilities (33,219 beds). National incidence of RP use per 1000 residents was, all categories: 2465.1, environmental: 1324.5, physical: 922.5, chemical: 141.1; ‘other’: 77.0. The most frequently used RPs per category were, environmental: door locks; physical: bedrails; chemical (where drug specified): antipsychotics; ‘other’: privacy. 90.5% of nursing homes reported using at least one type of RP in the 12-month period. Quarterly incidence of any RP use in these facilities was median 1.642 (IQR: 0.018 to 18.608) per bed.

Conclusions

Nursing homes in Ireland regularly use RP; only 9.5% reported no RP use in the 12-month period. A wide variety of types of RP were reported. Environmental and ‘other’ (largely psychosocial) RP contributed notably to total RP use and warrant attention alongside the traditional focus on physical and chemical RP. Policy implications include the need for more comprehensive RP definitions.
Computer-aided diagnostic for classifying chest X-ray images using deep ensemble learning
Authors: Visuña Lara , Yang Dandi , Garcia-Blas Javier , Carretero Jesus
Published: October 2022

Background

Nowadays doctors and radiologists are overwhelmed with a huge amount of work. This led to the effort to design different Computer-Aided Diagnosis systems (CAD system), with the aim of accomplishing a faster and more accurate diagnosis. The current development of deep learning is a big opportunity for the development of new CADs. In this paper, we propose a novel architecture for a convolutional neural network (CNN) ensemble for classifying chest X-ray (CRX) images into four classes: viral Pneumonia, Tuberculosis, COVID-19, and Healthy. Although Computed tomography (CT) is the best way to detect and diagnoses pulmonary issues, CT is more expensive than CRX. Furthermore, CRX is commonly the first step in the diagnosis, so it’s very important to be accurate in the early stages of diagnosis and treatment.

Results

We applied the transfer learning technique and data augmentation to all CNNs for obtaining better performance. We have designed and evaluated two different CNN-ensembles: Stacking and Voting. This system is ready to be applied in a CAD system to automated diagnosis such a second or previous opinion before the doctors or radiology’s. Our results show a great improvement, 99% accuracy of the Stacking Ensemble and 98% of accuracy for the the Voting Ensemble.

Conclusions

To minimize missclassifications, we included six different base CNN models in our architecture (VGG16, VGG19, InceptionV3, ResNet101V2, DenseNet121 and CheXnet) and it could be extended to any number as well as we expect extend the number of diseases to detected. The proposed method has been validated using a large dataset created by mixing several public datasets with different image sizes and quality. As we demonstrate in the evaluation carried out, we reach better results and generalization compared with previous works. In addition, we make a first approach to explainable deep learning with the objective of providing professionals more information that may be valuable when evaluating CRXs.
Gamma-secretase inhibitor does not induce cytotoxicity in adult T-cell leukemia cell lines despite NOTCH1 expression
Authors: Suzuki Shinsuke , Hourai Sawako , Uozumi Kimiharu , Uchida Yuichirou , Yoshimitsu Makoto , Miho Hachiman , Arima Naomichi , Ueno Shin-ichi , Ishitsuka Kenji
Published: October 2022

Background

Activated mutations in NOTCH1 are drivers of T-cell type acute lymphoblastic leukemia/lymphoma. The γ-secretase inhibitor (GSI), which suppresses the function of NOTCH1, is expected to be a molecular-targeted agent. NOTCH1 is also expressed in other malignant neoplasms. We aimed to determine the function of NOTCH1 expression and the effects of GSI on adult T-cell leukemia/lymphoma (ATL) caused by long-term human T-cell leukemia virus type I (HTLV-1) infection.

Methods

We analyzed the expression of NOTCH1 in six ATL- and HTLV-1-infected cell lines and investigated the influence of activated NOTCH1 (i.e., the cleaved form of NOTCH1) together with GSI on cell proliferation.

Results

Activated NOTCH1 found in ATL- and HTLV-1-infected cell lines was undetectable after incubation with GSI, regardless of Tax expression (HTLV-1-coded protein). Whole-exome sequencing revealed that activated NOTCH1 mutations were undetectable in six ATL- and HTLV-1-infected cell lines, regardless of abundant NOTCH1 expression. Moreover, GSI did not suppress the growth of ATL cell lines.

Conclusions

These findings suggested that NOTCH1 protein is constitutively activated but is likely a passenger during NOTCH1-mutation-negative ATL cell proliferation.
The frequencies of CYP2D6 alleles and their impact on clinical outcomes of adjuvant tamoxifen therapy in Syrian breast cancer patients
Authors: Ismail Al-khalil Wouroud , Al-Salhi Lana , Rijjal Sara , Aljamali Majd , Youssef Lama A.
Published: October 2022

Background

Tamoxifen is one of the fundamental pillars of adjuvant endocrine therapy for hormone receptor-positive breast cancer; however, 30–50% of patients receiving tamoxifen experience tumor relapse. CYP2D6, encoded by an extremely polymorphic CYP2D6 gene, is the rate-limiting enzyme of tamoxifen bioactivation. This study aimed at determining the frequencies of the most clinically relevant CYP2D6 alleles and evaluating their impact on the responsiveness to tamoxifen in a cohort of Syrian breast cancer patients.

Methods

This case–control study encompassed positive estrogen and/or progesterone receptor, stage 1–3 breast cancer female patients receiving tamoxifen at Al-Bairouni University Hospital, the major National Oncology Center in Syria. Successfully genotyped eligible patients (n = 97) were classified according to their response into; no recurrence group (n = 39) who had completed a five-year recurrence-free adjuvant tamoxifen therapy, and recurrence group (n = 58) who had experienced recurrence. Several star alleles including CYP2D6*4, CYP2D6*10, CYP2D6*41, and CYP2D6*69 were identified via targeted sequencing of specific polymerase chain reaction (PCR) products and phenotypes were assigned according to activity score (AS). The correlation between genotypes and disease-free survival (DFS) was assessed using Kaplan–Meier method and log-rank test. Hazard ratios were estimated using Cox proportional hazards regression models.

Results

The allelic frequencies of CYP2D6*41, CYP2D6*10, CYP2D6*4, and CYP2D6*69 were found to be 9.28%, 7.22%, 7.22%, and 2.58%, respectively. No statistically significant differences were observed in the frequencies of CYP2D6 phenotypes between the two arms (P = 0.24), nor the incidence of tamoxifen-induced hot flashes (P = 0.109). Poor metabolizers (PMs) tended to display shorter DFS than intermediate metabolizers (IMs) and normal metabolizers (NMs) combined (adjusted HR = 2.34, 95% CI = 0.84–6.55, P = 0.104). Notably, patients homozygous for the null CYP2D6*4 allele (1847A/A) had an elevated risk of disease recurrence compared to patients with 1847G/G genotype (adjusted HR = 5.23, 95% CI = 1.22–22.49, P = 0.026).

Conclusions

Our findings show no association between CYP2D6 phenotype and treatment outcomes of tamoxifen in Syrian breast cancer patients. Nevertheless, a worse DFS was revealed in patients with 1847A/A genotype (*4/*4).
PIK3CA mutations associated with a poor postoperative prognosis in patients with pulmonary pleomorphic carcinoma: a retrospective cohort study
Authors: Kojima Kensuke , Imai Saki , Samejima Hironobu , Fujiwara Ayako , Tokunaga Toshiteru , Yoon Hyungeun , Okishio Kyoichi
Published: October 2022

Background

Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small cell lung cancer characterized by high malignancy and a poor prognosis. PPC is associated with a high frequency of postoperative relapse, and shows resistance to chemotherapy. The high malignancy of cancers is associated with genomic instability, which is related to mutations of tumor suppressor genes, such as tumor protein p53 (TP53) and ataxia-telangiectasia mutated (ATM). In addition, signaling pathways involving the oncogenes such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and epidermal growth factor receptor (EGFR) are associated with resistance to chemotherapy. However, the association of PPC with these gene mutations remains unknown. We investigated the impact of TP53, ATM, PIK3CA, and EGFR mutations on the postoperative prognosis of PPC.

Methods

Fifty-five patients with PPC who underwent complete resection were studied. A gene mutation analysis was performed using next-generation sequencing. Postoperative overall survival of patients with gene mutations was evaluated using a multivariable Cox proportional hazards model in which the explanatory variables were the presence of each gene mutation, and the confounding factors were pathological stage and age. The robustness of the results was evaluated by a sensitivity analysis.

Results

The frequencies of pathogenic mutations in TP53, ATM, PIK3CA, and EGFR were 47, 0, 7, and 9%, respectively. A multivariable analysis adjusted for pathological stage and age showed a significant difference for only PIK3CA mutations. The hazard ratio (HR) for overall survival in cases with pathogenic mutations of PIK3CA for wild type or non-pathogenic mutations was 4.5 (95% confidence interval [CI] 1.1–18.8). Likewise, sensitivity analyses adjusted for pathological stage and sex (HR, 7.5; 95% CI 1.7–32.4) and for age and sex (HR, 5.4; 95% CI 1.4–21.7) resulted in similar findings. Although three patients with pathogenic mutations of PIK3CA that recurred postoperatively were treated by chemotherapy or immunotherapy, they survived for less than 2 years.

Conclusions

The postoperative prognosis of PPC with PIK3CA pathogenic mutations is particularly poor. Pathogenic mutations of PIK3CA may be a postoperative prognostic marker. Inhibition of signaling pathways associated with PIK3CA mutations may also be a target for chemotherapy after relapse of PPC.
The social and sexual lives of Black sexual minority men 30 years of age and older in South Africa
Authors: Crandall Amy , Phaleng Happy , Dacus Jagadīśa-devaśrī , Bista Oshin , Brouard Pierre , Nel Dawie , Reddy Vasu , Sandfort Theo , Knox Justin
Published: October 2022

Background

Black sexual minority men (SMM) ages 30 and older are under-represented in HIV studies in sub-Saharan Africa, despite being at increased risk of HIV infection and contributing to potential onward HIV transmission. To better understand the social and sexual lives of older Black South African SMM, we conducted in-depth interviews with SMM who were > 30 years old.

Methods

From March–September 2016, we recruited a convenience sample of 37 SMM ages 30 and older by partnering with an LGBTQ+ organization in Tshwane, Pretoria. Men were interviewed about various aspects of their lives, including their sexual orientation, social connectedness, experiences with stigma and perspectives on participating in research.

Results

Participants described their experiences with their sexual identities, cultural and social implications of disclosure, and their perspective on South Africa’s political perspectives on the LGBTQ+ community. Men described how these experiences influence their trust in research and comfort participating in studies.

Conclusions

Inferences drawn from these findings provide direction on how to improve middle-aged SMM’s representation in research, such as recruiting a higher proportion of older and middle-aged SMM to serve as seed participants and building stronger community partnerships to disseminate study findings to settings where data collection is conducted.
Effects of physiotherapeutic scoliosis-specific exercise in patients with mild juvenile scoliosis
Authors: Yuan Wangshu , Wang Hai , Yu Keyi , Shen Jianxiong , Chen Lixia , Liu Ying , Lin Youxi
Published: October 2022

Study design

A combined retrospective and prospective analysis on the therapeutic effect of physiotherapeutic scoliosis-specific exercise (PSSE) in mild juvenile idiopathic scoliosis (JIS) patients.

Background

At present, patients with mild JIS are generally treated by observation without any interventional treatment. This study analyzed the effects of PSSE on mild JIS, which provided a new approach for the treatment of JIS.

Method

A total of 52 patients with mild JIS (Cobb angle 10–19°), aged 4–9 years, self-selected into an observation group and a PSSE group. Patients performed the corrective posture exercises daily based on the Scientific Exercise Approach to Scoliosis (SEAS) to the best of their ability, and performed the over-corrective training based on Schroth methods for 30 min each day. Before and one year after the treatment, the Cobb angle and the angle of trunk rotation (ATR) were evaluated, and the results were compared between the two groups.

Results

After one year of treatment, the Cobb angle in the PSSE group decreased from 15.0(11.0–17.0)° to 5.0(2.0–12.0)°(p ≤ 0.001), while the Cobb angle in the observation group increased from 13.5(11.0–17.3)° to 16.0(10.8–20.0)° (p = 0.010). The ATR in the PSSE group decreased from 5.0(2.0–7.0)° to 3.0(2.0–4.0)° (p = 0.009), while the change of ATR in the observation group was not significant. Compared with the observation group, 69.57% of patients in PSSE group had a decreased Cobb angle of more than 5 degrees, which was statistically significant(p ≤ 0.001).

Conclusion

For mild JIS, PSSE decreased the Cobb angle and ATR.
Expiratory high-frequency percussive ventilation: a novel concept for improving gas exchange
Authors: Peták Ferenc , Fodor Gergely H. , Schranc Álmos , Südy Roberta , Balogh Ádám L. , Babik Barna , Dos Santos Rocha André , Bayat Sam , Bizzotto Davide , Dellacà Raffaele L. , Habre Walid
Published: October 2022

Background

Although high-frequency percussive ventilation (HFPV) improves gas exchange, concerns remain about tissue overdistension caused by the oscillations and consequent lung damage. We compared a modified percussive ventilation modality created by superimposing high-frequency oscillations to the conventional ventilation waveform during expiration only (eHFPV) with conventional mechanical ventilation (CMV) and standard HFPV.

Methods

Hypoxia and hypercapnia were induced by decreasing the frequency of CMV in New Zealand White rabbits (n = 10). Following steady-state CMV periods, percussive modalities with oscillations randomly introduced to the entire breathing cycle (HFPV) or to the expiratory phase alone (eHFPV) with varying amplitudes (2 or 4 cmH2O) and frequencies were used (5 or 10 Hz). The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined. Volumetric capnography was used to evaluate the ventilation dead space fraction, phase 2 slope, and minute elimination of CO2. Respiratory mechanics were characterized by forced oscillations.

Results

The use of eHFPV with 5 Hz superimposed oscillation frequency and an amplitude of 4 cmH2O enhanced gas exchange similar to those observed after HFPV. These improvements in PaO2 (47.3 ± 5.5 vs. 58.6 ± 7.2 mmHg) and PaCO2 (54.7 ± 2.3 vs. 50.1 ± 2.9 mmHg) were associated with lower ventilation dead space and capnogram phase 2 slope, as well as enhanced minute CO2 elimination without altering respiratory mechanics.

Conclusions

These findings demonstrated improved gas exchange using eHFPV as a novel mechanical ventilation modality that combines the benefits of conventional and small-amplitude high-frequency oscillatory ventilation, owing to improved longitudinal gas transport rather than increased lung surface area available for gas exchange.
Incorporating a gender lens into nutrition and health-related policies in Fiji: analysis of policies and stakeholder perspectives
Authors: McKenzie Briar L. , Waqa Gade , Mounsey Sarah , Johnson Claire , Woodward Mark , Buse Kent , Thow Anne Marie , McLean Rachael , Webster Jacqui
Published: October 2022

Background

Gender equality, zero hunger and healthy lives and well-being for all, are three of the Sustainable Development Goals (SDGs) that underpin Fiji’s National Development Plan. Work towards each of these goals contributes to the reduction of non-communicable diseases (NCDs). There are gender differences in NCD burden in Fiji. It is, however, unclear whether a gender lens could be more effectively included in nutrition and health-related policies.

Methods

This study consisted of three components: (i) a policy content analysis of gender inclusion in nutrition and health-related policies (n = 11); (ii) policy analysis using the WHO Gender Analysis tool to identify opportunities for strengthening future policy; and (iii) informant interviews (n = 18), to understand perceptions of the prospects for gender considerations in future policies.

Results

Gender equality was a goal in seven policies (64%); however, most focused on women of reproductive age. One of the policies was ranked as gender responsive. Main themes from key informant interviews were: 1) a needs-based approach for the focus on specific population groups in policies; 2) gender-related roles and responsibilities around nutrition and health; 3) what is considered “equitable” when it comes to gender, nutrition, and health; 4) current considerations of gender in policies and ideas for further gender inclusion; and 5) barriers and enablers to the inclusion of gender considerations in policies. Informants acknowledged gender differences in the burden of nutrition-related NCDs, yet most did not identify a need for stronger inclusion of gender considerations within policies.

Conclusions

There is considerable scope for greater inclusion of gender in nutrition and health-related policies in Fiji. This could be done by: 1) framing gender considerations in ways that are actionable and inclusive of a range of gender identities; 2) undertaking advocacy through actor networks to highlight the need for gender-responsive nutrition and health-related policies for key stakeholder groups; 3) ensuring that data collected to monitor policy implementation is disaggregated by sex and genders; and 4) promoting equitable participation in nutrition related issues in communities and governance processes. Action on these four areas are likely critical enablers to more gender equitable NCD reduction in Fiji.
Selling sex in the context of substance use: social and structural drivers of transactional sex among men who use opioids in Maryland
Authors: Rosen Joseph G. , Schneider Kristin E. , Allen Sean T. , Morris Miles , Urquhart Glenna J. , Rouhani Saba , Sherman Susan G.
Published: October 2022

Background

Transactional sex is an important driver of HIV risk among people who use drugs in the USA, but there is a dearth of research characterizing men’s selling and trading of sex in the context of opioid use. To identify contextually specific factors associated with selling or trading sex in a US population of men who use drugs, we cross-sectionally examined social and structural correlates of transactional sex among men who use opioids (MWUO) in Anne Arundel County and Baltimore City, Maryland.

Methods

Between July 2018 and March 2020, we used targeted sampling to recruit men reporting past-month opioid use from 22 street-level urban and suburban recruitment zones. MWUO completed a 30-min self-administered interview eliciting substance use histories, experiences with hunger and homelessness, criminal justice interactions, and transactional sex involvement. We identified correlates of recent (past 3 months) transactional sex using multivariable log-binomial regression with cluster-robust standard errors.

Results

Among 422 MWUO (mean age 47.3 years, 73.4% non-Hispanic Black, 94.5% heterosexual), the prevalence of recent transactional sex was 10.7%. In multivariable analysis, younger age (adjusted prevalence ratio [aPR] 0.98, 95% confidence interval [95% CI] 0.97–0.99, p < 0.001), identifying as gay/bisexual (aPR = 5.30, 95% CI 3.81–7.37, p < 0.001), past-month food insecurity (aPR = 1.77, 95% CI 1.05–3.00, p = 0.032), and injection drug use in the past 3 months (aPR = 1.75, 95% CI 1.02–3.01, p = 0.043) emerged as statistically significant independent correlates of transactional sex.

Conclusions

Synergistic sources of social and structural marginalization—from sexuality to hunger, homelessness, and injection drug use—are associated with transactional sex in this predominantly Black, heterosexual-identifying sample of MWUO. Efforts to mitigate physical and psychological harms associated with transactional sex encounters should consider the racialized dimensions and socio-structural drivers of transactional sex among MWUO.
A novel microRNA signature for the detection of melanoma by liquid biopsy
Authors: Sabato Claudia , Noviello Teresa Maria Rosaria , Covre Alessia , Coral Sandra , Caruso Francesca Pia , Besharat Zein Mersini , Splendiani Elena , Masuelli Laura , Battistelli Cecilia , Vacca Alessandra , Catanzaro Giuseppina , Po Agnese , Anichini Andrea , Maio Michele , Ceccarelli Michele , Di Giacomo Anna Maria , Ferretti Elisabetta
Published: October 2022

Background

Melanoma is the deadliest form of skin cancer and metastatic disease is associated with a significant survival rate drop. There is an urgent need for consistent tumor biomarkers to scale precision medicine and reduce cancer mortality. Here, we aimed to identify a melanoma-specific circulating microRNA signature and assess its value as a diagnostic tool.

Methods

The study consisted of a discovery phase and two validation phases. Circulating plasma extracellular vesicles (pEV) associated microRNA profiles were obtained from a discovery cohort of metastatic melanoma patients and normal subjects as controls. A pEV-microRNA signature was obtained using a LASSO penalized logistic regression model. The pEV-microRNA signature was subsequently validated both in a publicly available dataset and in an independent internal cohort.

Results

We identified and validated in three independent cohorts a panel of melanoma-specific circulating microRNAs that showed high accuracy in differentiating melanoma patients from healthy subjects with an area under the curve (AUC) of 1.00, 0.94 and 0.75 respectively. Investigation of the function of the pEV-microRNA signature evidenced their possible immune suppressive role in melanoma patients.

Conclusions

We demonstrate that a blood test based on circulating microRNAs can non-invasively detect melanoma, offering a novel diagnostic tool for improving standard care. Moreover, we revealed an immune suppressive role for melanoma pEV-microRNAs.
Circular RNA hsa_circ_0000144 aggravates ovarian Cancer progression by regulating ELK3 via sponging miR-610
Authors: Wu Dandan , Liu Jia , Yu Liji , Wu Shaofang , Qiu Xiaomei
Published: October 2022

Background

Ovarian cancer is a common cause of death among women and a health problem worldwide. Circ_0000144 has been confirmed to be an oncogene involved in cancer progression, such as gastric cancer. However, the role of circ_0000144 in ovarian cancer remains unclear and needs to be elucidated. This retrospective study aimed to investigate the underlying mechanism of circ_0000144 in ovarian cancer.

Methods

Differentially expressed circ_0000144 expression in ovarian cancer and normal tissues was identified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In vitro assays were performed to explore the biological functions of circ_0000144 in ovarian cancer cells. An in vivo xenograft model was used to investigate the efficacy of circ_0000144 in the progression of ovarian cancer.

Results

Circ_0000144 was significantly upregulated in ovarian cancer cells and tissues. Circ_0000144 overexpression significantly promoted ovarian cancer cell proliferation, migration, and invasion. This study further demonstrated that circ_0000144 downregulated ELK3 levels by sponging miR-610 in ovarian cancer cells. Moreover, circ_0000144 significantly promotes ovarian cancer tumorigenesis in vivo.

Conclusion

Our data indicate that circ_0000144 could enhance the carcinogenesis of ovarian cancer by specifically targeting miR-610, which may serve as a novel target for the diagnosis and prognosis of ovarian cancer.
mRNAs encoding neurodevelopmental regulators have equal N6-methyladenosine stoichiometry in Drosophila neuroblasts and neurons
Authors: Sami Josephine D. , Spitale Robert C. , Cleary Michael D.
Published: October 2022

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in metazoans and is particularly abundant in the central nervous system. The extent to which m6A is dynamically regulated and whether m6A contributes to cell type-specific mRNA metabolism in the nervous system, however, is largely unknown. To address these knowledge gaps, we mapped m6A and measured mRNA decay in neural progenitors (neuroblasts) and neurons of the Drosophila melanogaster larval brain. We identified 867 m6A targets; 233 of these are novel and preferentially encode regulators of neuroblast proliferation, cell fate-specification and synaptogenesis. Comparison of the neuroblast and neuron m6A transcriptomes revealed that m6A stoichiometry is largely uniform; we did not find evidence of neuroblast-specific or neuron-specific m6A modification. While m6A stoichiometry is constant, m6A targets are significantly less stable in neuroblasts than in neurons, potentially due to m6A-independent stabilization in neurons. We used in vivo quantitative imaging of m6A target proteins in Mettl3 methyltransferase null brains and Ythdf m6A reader overexpressing brains to assay metabolic effects of m6A. Target protein levels decreased in Mettl3 null brains and increased in Ythdf overexpressing brains, supporting a previously proposed model in which m6A enhances translation of target mRNAs. We conclude that m6A does not directly regulate mRNA stability during Drosophila neurogenesis but is rather deposited on neurodevelopmental transcripts that have intrinsic low stability in order to augment protein output.
Disrupted methylation patterns at birth persist in early childhood: a prospective cohort analysis
Authors: Dolinko Andrey V. , Schultz Bryant M. , Ghosh Jayashri , Kalliora Charikleia , Mainigi Monica , Coutifaris Christos , Sapienza Carmen , Senapati Suneeta
Published: October 2022

Background

Alterations in the epigenome are a risk factor in multiple disease states. We have demonstrated in the past that disruption of the epigenome during early pregnancy or periconception, as demonstrated by altered methylation, may be associated with both assisted reproductive technology and undesirable clinical outcomes at birth, such as low birth weight. We have previously defined this altered methylation, calculated based on statistical upper and lower limits of outlier CpGs compared to the population, as an ‘outlier methylation phenotype’ (OMP). Our aim in this study was to determine whether children thus identified as possessing an OMP at birth by DNA methylation in cord blood persist as outliers in early childhood based on salivary DNA methylation.

Results

A total of 31 children were included in the analysis. Among 24 children for whom both cord blood DNA and salivary DNA were available, DNA methylation patterns, analyzed using the Illumina Infinium MethylationEPIC BeadChip (850 K), between cord blood at birth and saliva in childhood at age 6–12 years remain stable (R2 range 0.89–0.97). At birth, three out of 28 children demonstrated an OMP in multiple cord blood datasets and hierarchical clustering. Overall DNA methylation among all three OMP children identified as outliers at birth was remarkably stable (individual R2 0.908, 0.92, 0.915), even when only outlier CpG sites were considered (R2 0.694, 0.738, 0.828).

Conclusions

DNA methylation signatures in cord blood remain stable over time as demonstrated by a strong correlation with epigenetic salivary signatures in childhood. Future work is planned to identify whether a clinical phenotype is associated with OMP and, if so, could undesirable clinical outcomes in childhood and adulthood be predicted at birth.
COVID-19 prevalence and infection control measures at homeless shelters and hostels in high-income countries: a scoping review
Authors: Levesque Justine , Babando Jordan , Loranger Nathaniel , Johnson Shantel , Pugh David
Published: October 2022

Background

The COVID-19 pandemic has disproportionately impacted homeless populations and service workers, especially within homeless shelter/hostel settings. To date, there have been few evidence syntheses examining outbreaks of COVID-19 among both homeless shelter residents and service workers and no critical review of infection control and prevention (IPAC) measures. This scoping review offers a much-needed synthesis of COVID-19 prevalence within homeless shelters and a review of pertinent IPAC measures. 

Methods

We conducted a scoping review that aimed to synthesize academic and gray literature published from March 2020 to July 2021 pertaining to (1) the prevalence of COVID-19 among both residents and staff in homeless shelters and hostels in high-income countries and (2) COVID-19 IPAC strategies applied in these settings. Two reviewers independently screened the literature from several databases that included MEDLINE, PsycInfo, and the WHO’s COVID-19 Global Health Portal. The extracted data was mapped, categorized, and thematically discussed.

Results

Thematic analysis of 77 academic and gray literature documents revealed four key themes: (1) the demographics of COVID-19 in homeless shelters, (2) asymptomatic spread, (3) pre-existing vulnerability of people experiencing homelessness and shelters, and (4) the inconsistency and ineffectiveness of IPAC implementation.

Conclusion

This review offers a useful glimpse into the landscape of COVID-19 outbreaks in homeless shelters/hostels and the major contributing factors to these events. This review revealed that there is no clear indication of generally accepted IPAC standards for shelter residents and workers. This review also illustrated a great need for future research to establish IPAC best practices specifically for homeless shelter/hostel contexts. Finally, the findings from this review reaffirm that homelessness prevention is key to limiting disease outbreaks and the associated negative health outcomes in shelter populations. Limitations of this review included the temporal and database constraints of the search strategy, the exclusion of quality assessments of the literature, and the absence of investigation on the influence of emerging variants on public health policy.

Systematic review registration

This scoping review has not been registered on any database; the protocol is available on York University’s Institutional Repository https://dx.doi.org/10.25071/10315/38513.
Suboptimal blood pressure control and its associated factors among people living with diabetes mellitus in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Akalu Yonas , Yeshaw Yigizie , Tesema Getayeneh Antehunegn , Tiruneh Sofonyas Abebaw , Teshale Achamyeleh Birhanu , Angaw Dessie Abebaw , Gebrie Misganew , Dagnew Baye
Published: October 2022

Background

Suboptimal blood pressure control among people living with diabetes mellitus (DM) is one of the primary causes of cardiovascular complications and death in sub-Saharan Africa (SSA). However, there is a paucity of evidence on the prevalence and associated factors of suboptimal blood pressure control in SSA. Therefore, this review aimed to estimate its pooled prevalence and associated factors among people living with DM in SSA. 

Methods

We systematically searched PubMed, African Journals OnLine, HINARI, ScienceDirect, Google Scholar, and direct Google to access observational studies conducted in SSA. Microsoft Excel spreadsheet was used to extract the data, which was exported into STATA/MP version 16.0 for further analyses. Heterogeneity across studies was checked using Cochran’s Q test statistics and I2 test, and small study effect was checked using Funnel plot symmetry and Egger’s statistical test at a 5% significant level. A random-effects model was used to estimate the pooled prevalence and associated factors of suboptimal blood pressure control at a 95% confidence interval (CI) and significance level of p < 0.05.

Results

Of the 7329 articles retrieved, 21 articles were eligible for the meta-analysis. After performing random-effects model, the pooled prevalence of suboptimal blood pressure control was 69.8% (95% CI: 63.43, 76.25%). Poor adherence to antihypertensive treatment (OR = 1.7; 95% CI: 1.03–2.80, I2 = 0.0%, p = 0.531) and overweight (OR = 2.4, 95% CI: 1.57–3.68, I2 = 0.00%, p = 0.47) were significantly associated with suboptimal blood pressure control.

Conclusions

The prevalence of suboptimal blood pressure control among diabetic patients in SSA was high, and poor adherence to antihypertensive treatment and overweight were significantly associated with suboptimal blood pressure control. Hence, there is an urgent need for initiatives to improve and control hypertension, and preventive measures should concentrate on modifiable risk factors.

Systematic review registration

PROSPERO CRD42020187901.