bluuebunny/crossref_metadata_2025 huggingface dataset:
WHO-led consensus statement on vaccine delivery costing: process, methods, and findings
Authors: Levin Ann , Boonstoppel Laura , Brenzel Logan , Griffiths Ulla , Hutubessy Raymond , Jit Mark , Mogasale Vittal , Pallas Sarah , Resch Stephen , Suharlim Christian , Yeung Karene Hoi Ting
Published: March 2022

Background

Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization’s (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement.

Methods

The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed.

Results

The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made.

Conclusions

Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context.
Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study
Authors: Miravitlles Marc , Soler-Cataluña Juan José , Soriano Joan B. , García-Río Francisco , de Lucas Pilar , Alfageme Inmaculada , Casanova Ciro , Rodríguez González-Moro José Miguel , Sánchez-Herrero M. Guadalupe , Ancochea Julio , Cosío Borja G.
Published: March 2022

Background

Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD.

Methods

EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed.

Results

A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC.

Conclusions

This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.
MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy
Authors: Hosseinzadeh Aysooda , Merikhian Parnaz , Naseri Nazanin , Eisavand Mohammad Reza , Farahmand Leila
Published: March 2022

Although resistance is its major obstacle in cancer therapy, trastuzumab is the most successful agent in treating epidermal growth factor receptor 2 positive (HER2 +) breast cancer (BC). Some patients show resistance to trastuzumab, and scientists want to circumvent this problem. This review elaborately discusses possible resistance mechanisms to trastuzumab and introduces mucin 1 (MUC1) as a potential target efficient for overcoming such resistance. MUC1 belongs to the mucin family, playing the oncogenic/mitogenic roles in cancer cells and interacting with several other oncogenic receptors and pathways, such as HER2, β-catenin, NF-κB, and estrogen receptor (ERα). Besides, it has been established that MUC1- Cytoplasmic Domain (MUC1-CD) accelerates the development of resistance to trastuzumab and that silencing MUC1-C proto-oncogene is associated with increased sensitivity of HER2+ cells to trastuzumab-induced growth inhibitors. We mention why targeting MUC1 can be useful in overcoming trastuzumab resistance in cancer therapy.
Implementation of community case management of malaria in malaria endemic counties of western Kenya: are community health volunteers up to the task in diagnosing malaria?
Authors: Marita Enock , Langat Bernard , Kinyari Teresa , Igunza Patrick , Apat Donald , Kimori Josephat , Carter Jane , Kiplimo Richard , Muhula Samuel
Published: March 2022

Background

Community case management of malaria (CCMm) is an equity-focused strategy that complements and extends the reach of health services by providing timely and effective management of malaria to populations with limited access to facility-based healthcare. In Kenya, CCMm involves the use of malaria rapid diagnostic tests (RDT) and treatment of confirmed uncomplicated malaria cases with artemether lumefantrine (AL) by community health volunteers (CHVs). The test positivity rate (TPR) from CCMm reports collected by the Ministry of Health in 2018 was two-fold compared to facility-based reports for the same period. This necessitated the need to evaluate the performance of CHVs in conducting malaria RDTs.

Methods

The study was conducted in four counties within the malaria-endemic lake zone in Kenya with a malaria prevalence in 2018 of 27%; the national prevalence of malaria was 8%. Multi-stage cluster sampling and random selection were used. Results from 200 malaria RDTs performed by CHVs were compared with test results obtained by experienced medical laboratory technicians (MLT) performing the same test under the same conditions. Blood slides prepared by the MLTs were examined microscopically as a back-up check of the results. A Kappa score was calculated to assess level of agreement. Sensitivity, specificity, and positive and negative predictive values were calculated to determine diagnostic accuracy.

Results

The median age of CHVs was 46 (IQR: 38, 52) with a range (26–73) years. Females were 72% of the CHVs. Test positivity rates were 42% and 41% for MLTs and CHVs respectively. The kappa score was 0.89, indicating an almost perfect agreement in RDT results between CHVs and MLTs. The overall sensitivity and specificity between the CHVs and MLTs were 95.0% (95% CI 87.7, 98.6) and 94.0% (95% CI 88.0, 97.5), respectively.

Conclusion

Engaging CHVs to diagnose malaria cases under the CCMm strategy yielded results which compared well with the results of qualified experienced laboratory personnel. CHVs can reliably continue to offer malaria diagnosis using RDTs in the community setting.
Quantification of the dynamics of antibody response to malaria to inform sero-surveillance in pregnant women
Authors: Dharmaratne A. D. V. Tharkeshi T. , Dini Saber , O’Flaherty Katherine , Price David J. , Beeson James , McGready Rose , Nosten Francois , Fowkes Freya J. I. , Simpson Julie A. , Zaloumis Sophie G.
Published: March 2022

Background

Malaria remains a major public health threat and tools sensitive to detect infections in low malaria transmission areas are needed to progress elimination efforts. Pregnant women are particularly vulnerable to malaria infections. Throughout pregnancy they access routine antenatal care, presenting a unique sentinel population to apply novel sero-surveillance tools to measure malaria transmission. The aim of this study was to quantify the dynamic antibody responses to multiple antigens during pregnancy so as to identify a single or multiple antibody response of exposure to malaria in pregnancy.

Methods

This study involved a secondary analysis of antibody responses to six parasite antigens [five commonly studied merozoite antigens and the variant surface antigen 2-chondroitin sulphate A (VAR2CSA), a pregnancy-specific erythrocytic antigen] measured by enzyme-linked immunosorbent assay (ELISA) over the gestation period until delivery (median of 7 measurements/woman) in 250 pregnant women who attended antenatal clinics located at the Thai-Myanmar border. A multivariate mixture linear mixed model was used to cluster the pregnant women into groups that have similar longitudinal antibody responses to all six antigens over the gestational period using a Bayesian approach. The variable-specific entropy was calculated to identify the antibody responses that have the highest influence on the classification of the women into clusters, and subsequent agreement with grouping of women based on exposure to malaria during pregnancy.

Results

Of the 250 pregnant women, 135 had aPlasmodiuminfection detected by light microscopy during pregnancy (39%Plasmodium falciparumonly, 33%Plasmodium vivaxonly and 28% mixed/other species), defined as cases. The antibody responses to all six antigens accurately identified the women who did not have a malaria infection detected during pregnancy (93%, 107/115 controls). Antibody responses toP. falciparummerozoite surface protein 3 (PfMSP3) andP. vivaxapical membrane antigen 1 (PvAMA1) were the least dynamic. Antibody responses to the antigensP. falciparumapical membrane antigen 1 (PfAMA1) andPfVAR2CSA were able to identify the majority of the cases more accurately (63%, 85/135).

Conclusion

These findings suggest that the combination of antibodies,PfAMA1 andPfVAR2CSA, may be useful for sero-surveillance of malaria infections in pregnant women, particularly in low malaria transmission settings. Further investigation of other antibody markers is warranted considering these antibodies combined only detected 63% of the malaria infections during pregnancy.
Super-resolution imaging of Douglas fir xylem cell wall nanostructure using SRRF microscopy
Authors: Donaldson Lloyd A.
Published: March 2022

Background

The nanostructure of plant cell walls is of significant biological and technological interest, but methods suited to imaging cell walls at the nanoscale while maintaining the natural water-saturated state are limited. Light microscopy allows imaging of wet cell walls but with spatial resolution limited to the micro-scale. Most super-resolution techniques require expensive hardware and/or special stains so are less applicable to some applications such as autofluorescence imaging of plant tissues.

Results

A protocol was developed for super-resolution imaging of xylem cell walls using super-resolution radial fluctuations (SRRF) microscopy combined with confocal fluorescence imaging (CLSM). We compared lignin autofluorescence imaging with acriflavin or rhodamine B staining. The SRRF technique allows imaging of wet or dry tissue with moderate improvement in resolution for autofluorescence and acriflavin staining, and a large improvement for rhodamine B staining, achieving sub 100 nm resolution based on comparison with measurements from electron microscopy. Rhodamine B staining, which represents a convolution of lignin staining and cell wall accessibility, provided remarkable new details of cell wall structural features including both circumferential and radial lamellae demonstrating nanoscale variations in lignification and cell wall porosity within secondary cell walls.

Conclusions

SRRF microscopy can be combined with confocal fluorescence microscopy to provide nanoscale imaging of plant cell walls using conventional stains or autofluorescence in either the wet or dry state.
LncRNA HOTAIR facilitates proliferation and represses apoptosis of retinoblastoma cells through the miR-20b-5p/RRM2/PI3K/AKT axis
Authors: Fu Ke , Zhang Ke , Zhang Xiaoyu
Published: March 2022

Purpose

Retinoblastoma (RB) represents an adolescent eye malignancy. Long non-coding RNA (LncRNA) HOTAIR shows aberrant expression in many malignancies. This research investigated the mechanism of HOTAIR in RB.

Methods

Normal retinal cell lines (ARPE-19 and RPE-1) and RB cell lines (ORB50, Y79, HXO-RB44, and WERI-RB) were selected for detection of HOTAIR expression by qRT-PCR. sh-HOTAIR was delivered into Y79 and HXO-RB44 cells. Cell-cycle distribution, proliferation, and apoptosis were detected by CCK-8 assay and flow cytometry. Binding relationships among HOTAIR, miR-20b-5p, and RRM2 were confirmed using dual-luciferase assay. Roles of miR-20b-5p and RRM2 in RB cell-cycle distribution, proliferation, and apoptosis were ascertained by functional rescue experiments. Murine model of xenograft tumor was established, followed by detection of tumor growth and counting of Ki67-positive cells. Expressions of proliferation- and apoptosis-associated proteins and PI3K/AKT pathway-related proteins were determined by Western blot.

Results

HOTAIR was elevated in RB cells relative to that in normal retinal cells and showed relatively high expression in Y79 and HXO-RB44 cells. sh-HOTAIR induced RB cell-cycle arrest, restrained proliferation, and strengthened apoptosis. HOTAIR functioned as the ceRNA of miR-20b-5p and targeted RRM2. RB cells had poorly-expressed miR-20b-5p and highly-expressed RRM2. miR-20b-5p downregulation or RRM2 overexpression facilitated RB cell-cycle and proliferation, suppressed apoptosis, and reversed the protective effect of sh-HOTAIR on RB. sh-HOTAIR reduced tumor growth and Ki67-positive cells in vivo and inactivated PI3K/AKT pathway.

Conclusion

LncRNA HOTAIR upregulated RRM2 by competitively binding to miR-20b-5p and activated PI3K/AKT pathway, thereby facilitating proliferation and repressing apoptosis of RB cells.
Heterogeneous clinical features in Cockayne syndrome patients and siblings carrying the same CSA mutations
Authors: Chikhaoui Asma , Kraoua Ichraf , Calmels Nadège , Bouchoucha Sami , Obringer Cathy , Zayoud Khouloud , Montagne Benjamin , M’rad Ridha , Abdelhak Sonia , Laugel Vincent , Ricchetti Miria , Turki Ilhem , Yacoub-Youssef Houda
Published: March 2022

Background

Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in the transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and that cannot be anticipated in the diagnostic phase. In addition, little data is available for affected siblings, and this disease is largely undiagnosed in North Africa.

Methods

We report here the clinical description as well as genetic and functional characterization of eight Tunisian CS patients, including siblings. These patients, who belonged to six unrelated families, underwent complete clinical examination and biochemical analyses. Sanger sequencing was performed for the recurrent mutation in five families, and targeted gene sequencing was done for one patient of the sixth family. We also performed Recovery RNA Synthesis (RRS) to confirm the functional impairment of DNA repair in patient-derived fibroblasts.

Results

Six out of eight patients carried a homozygous indel mutation (c.598_600delinsAA) in exon 7 of ERCC8, and displayed a variable clinical spectrum including between siblings sharing the same mutation. The other two patients were siblings who carried a homozygous splice-site variant in ERCC8 (c.843+1G>C). This last pair presented more severe clinical manifestations, which are rarely associated with CSA mutations, leading to gastrostomy and hepatic damage. Impaired TC-NER was confirmed by RRS in six tested patients.

Conclusions

This study provides the first deep characterization of case series of CS patients carrying CSA mutations in North Africa. These mutations have been described only in this region and in the Middle-East. We also provide the largest characterization of multiple unrelated patients, as well as siblings, carrying the same mutation, providing a framework for dissecting elusive genotype–phenotype correlations in CS.
Treating rare diseases with the cinema: Can popular movies enhance public understanding of rare diseases?
Authors: Domaradzki Jan
Published: March 2022

Background

Rare diseases (RDs) constitute an important public health issue. However, although public awareness campaigns focus on the improvement of undergraduate and postgraduate education, also popular culture may serve as an educational tool in this field. This study aims to analyse how rare genetic diseases are depicted in popular movies.

Methods

Twenty popular movies on RDs were analysed quantitatively. The main categories included in the coding frame were: disease, patient, physician/scientist and psychosocial issuses related to RDs.

Results

The majority of movies do not contain adequate scientific information on RDs. Consequently, their cinematic image is either inaccurate or simplified. However, the cinema does take up some important topics in the field of RDs and highlight their ethical, psychosocial, legal or economic dimension: the diagnostic and therapeutic odyssey, the role of RD patients’ advocacy groups in the production of scientific knowledge, the problem of orphan drugs, the stigmatisation of and discrimination against RD patients, and the impact of diagnosis on one’s concept of self and parents’ feelings of guilt.

Conclusion

Although popular movies mostly focus on RD patients’ problems of daily living and rarely describe clinical aspects of RDs, they do have an educational potential. Thus, movies can help to raise the public’s awareness on the psychospocial and economic problems faced by RD patients and their families.
Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease
Authors: Bairamian Diane , Sha Sha , Rolhion Nathalie , Sokol Harry , Dorothée Guillaume , Lemere Cynthia A. , Krantic Slavica
Published: March 2022

Background

The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve.

Main messages

The putative mechanisms of the indirect and direct impact of microbiota on neuronal activity are discussed by focusing on Alzheimer’s disease, one of the most studied neurodegenerative disorders and the prime cause of dementia worldwide. More specifically, the mechanisms of microbiota-mediated microglial alterations are discussed in the context of the peripheral and central inflammation cross-talk. Next, we highlight the role of microbiota in the regulation of humoral mediators of peripheral immunity and their impact on vagus nerve stimulation. Finally, we address whether and how microbiota perturbations could affect synaptic neurotransmission and downstream cognitive dysfunction.

Conclusions

There is strong increasing evidence supporting a role for the gut microbiome in the pathogenesis of Alzheimer’s disease, including effects on synaptic dysfunction and neuroinflammation, which contribute to cognitive decline. Putative early intervention strategies based on microbiota modulation appear therapeutically promising for Alzheimer’s disease but still require further investigation.
Alzheimer’s disease – the journey of a healthy brain into organ failure
Authors: Golde Todd E.
Published: March 2022

As the most common dementia, Alzheimer’s disease (AD) exacts an immense personal, societal, and economic toll. AD was first described at the neuropathological level in the early 1900s. Today, we have mechanistic insight into select aspects of AD pathogenesis and have the ability to clinically detect and diagnose AD and underlying AD pathologies in living patients. These insights demonstrate that AD is a complex, insidious, degenerative proteinopathy triggered by Aβ aggregate formation. Over time Aβ pathology drives neurofibrillary tangle (NFT) pathology, dysfunction of virtually all cell types in the brain, and ultimately, overt neurodegeneration. Yet, large gaps in our knowledge of AD pathophysiology and huge unmet medical need remain. Though we largely conceptualize AD as a disease of aging, heritable and non-heritable factors impact brain physiology, either continuously or at specific time points during the lifespan, and thereby alter risk for devolvement of AD. Herein, I describe the lifelong journey of a healthy brain from birth to death with AD, while acknowledging the many knowledge gaps that remain regarding our understanding of AD pathogenesis. To ensure the current lexicon surrounding AD changes from inevitable, incurable, and poorly manageable to a lexicon of preventable, curable, and manageable we must address these knowledge gaps, develop therapies that have a bigger impact on clinical symptoms or progression of disease and use these interventions at the appropriate stage of disease.
Promising practices for the monitoring and evaluation of gender-based violence risk mitigation interventions in humanitarian response: a multi-methods study
Authors: Sharma Vandana , Ausubel Emily , Heckman Christine , Rastogi Sonia , Kelly Jocelyn T. D.
Published: March 2022

Background

Risks of gender-based violence (GBV) are exacerbated in humanitarian crises. GBV risk mitigation interventions aim to reduce exposure to GBV and ensure that humanitarian response actions and services themselves do not cause harm or increase the risk of violence. The 2015 IASC Guidelines for Integrating Gender-Based Violence Interventions in Humanitarian Action (‘GBV Guidelines’) are a globally endorsed resource that provides comprehensive guidance for all humanitarian actors and sectors on GBV risk mitigation. While uptake of GBV risk mitigation approaches across multiple humanitarian sectors has occurred, there is limited understanding of how to monitor and evaluate GBV risk mitigation interventions.

Methods

A multi-methods study was conducted in 2019 to identify promising practices for the monitoring and evaluation (M&E) of GBV risk mitigation interventions in non-GBV sectors and to develop a set of illustrative case examples. The study included a comprehensive desk review of 145 articles, documents and resources from the published and grey literature, as well as 11 in-depth interviews and five focus group discussions with humanitarian practitioners. Using Dedoose software and a codebook developed a priori, qualitative data were transcribed and coded and a content analysis was conducted. Excerpts focusing on promising practices from the qualitative data and the desk review were analyzed together and grouped by thematic area. Similar promising practices were combined and consolidated to create a final list, and case examples were identified.

Results

Current promising practices for M&E of GBV risk mitigation activities in the following categories are described: (1) Coordination and collaboration, (2) Designing M&E approaches and tools for GBV risk mitigation activities, (3) Contextualization, (4) Developing and selecting indicators, (5) Data collection, (6) Data analysis and use of findings, (7) Potential safety concerns for affected populations and staff, and (8) Staff capacity and engagement. These are supplemented with seven diverse case examples to illustrate application of the promising practices using real-world examples.

Conclusion

This paper highlights current promising practices for M&E of GBV risk mitigation interventions in humanitarian response. Further application of these practices—alongside ongoing documentation of emerging approaches—will be critical to ensuring that GBV risk mitigation interventions are more rigorously tested with the aim of building the evidence base on the effectiveness of different GBV risk mitigation interventions within specific humanitarian sectors.
Targeting CRABP-II overcomes pancreatic cancer drug resistance by reversing lipid raft cholesterol accumulation and AKT survival signaling
Authors: Yu Shuiliang , Wang Lei , Che Danian , Zhang Mei , Li Ming , Naito Mikihiko , Xin Wei , Zhou Lan
Published: March 2022

Background

Resistance to standard therapy is a major reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Developing novel therapy to overcome PDAC drug-resistance is urgently needed. CRABP-II was highly expressed in all PDAC but not expressed in normal pancreatic tissues and chronic pancreatitis. CRABP-II was shown to promote PDAC migration and metastasis while its potential role in promoting PDAC drug-resistance was not known.

Methods

A paired cohort of human primary and relapsing PDAC tissues was assessed for CRABP-II expression by immunohistochemistry. CRISPR/cas9 gene editing was used to establish CRABP-II knockout cell lines and MTT assays were performed to assess gemcitabine sensitivity in vitro. Cleaved caspase-3/PARP blots and Annexin V staining were conducted to detect cell apoptosis. Gene expression microarray, Q-PCR, western blots, Co-IP and RNA-IP were used to study the molecular function of CRABP-II. Sucrose gradient ultracentrifugation was applied to isolate lipid rafts and LC–MS-MS was used to assess cholesterol content. Both subcutaneous CDX models and orthotopic PDX models were established to examine the efficacy of SNIPER-11 and the synergistic effect between SNIPER-11 and gemcitabine in vivo.

Results

A higher expression of CRABP-II was found in relapsing PDAC tissue and was associated with poor prognosis. Gemcitabine-resistant cell lines exhibited increased level of CRABP-II, while CRABP-II knockout resensitized PDAC cells to gemcitabine. Mechanistically, aberrant expression of CRABP-II increased the stability of SREBP-1c mRNA through cooperation with HuR and upregulated the downstream genes of SREBP-1c to favor cholesterol uptake and accumulation in lipid rafts. Increased lipid raft cholesterol accumulation facilitated ATK survival signaling and PDAC drug resistance. The small compound SNIPER-11 treatment effectively induced CRABP-II protein degradation, induced apoptosis, and suppressed tumor growth. Combination of SNIPER-11 and gemcitabine significantly reduced the lipid raft cholesterol content in CDX/PDX and profoundly inhibited tumor progression.

Conclusions

These findings identified CRABP-II as a novel regulator of cholesterol metabolism and suggested that CRABP-II is a selective target for overcoming PDAC drug resistance.
miR-3189-targeted GLUT3 repression by HDAC2 knockdown inhibits glioblastoma tumorigenesis through regulating glucose metabolism and proliferation
Authors: Kwak Sungmin , Park Seung-Ho , Kim Sung-Hak , Sung Gi-Jun , Song Ji-Hye , Jeong Ji-Hoon , Kim Hyunhee , Ha Chang Hoon , Kim Seong Who , Choi Kyung-Chul
Published: March 2022

Background

Epigenetic regulations frequently appear in Glioblastoma (GBM) and are highly associated with metabolic alterations. Especially, Histone deacetylases (HDACs) correlates with the regulation of tumorigenesis and cell metabolism in GBM progression, and HDAC inhibitors report to have therapeutic efficacy in GBM and other neurological diseases; however, GBM prevention and therapy by HDAC inhibition lacks a mechanism in the focus of metabolic reprogramming.

Methods

HDAC2 highly express in GBM and is analyzed in TCGA/GEPIA databases. Therefore, HDAC2 knockdown affects GBM cell death. Analysis of RNA sequencing and qRT-PCR reveals that miR-3189 increases and GLUT3 decreases by HDAC2 knockdown. GBM tumorigenesis also examines by using in vivo orthotopic xenograft tumor models. The metabolism change in HDAC2 knockdown GBM cells measures by glucose uptake, lactate production, and OCR/ECAR analysis, indicating that HDAC2 knockdown induces GBM cell death by inhibiting GLUT3.

Results

Notably, GLUT3 was suppressed by increasing miR-3189, demonstrating that miR-3189-mediated GLUT3 inhibition shows an anti-tumorigenic effect and cell death by regulating glucose metabolism in HDAC2 knockdown GBM.

Conclusions

Our findings will demonstrate the central role of HDAC2 in GBM tumorigenesis through the reprogramming of glucose metabolism by controlling miR-3189-inhibited GLUT3 expression, providing a potential new therapeutic strategy for GBM treatment.
The impact of COVID-19 continuous containment and mitigation strategy on the epidemic of vector-borne diseases in China
Authors: Guo Xiangyu , Ma Chenjin , Wang Lan , Zhao Na , Liu Shelan , Xu Wangli
Published: March 2022

Background

This study explored the effect of a continuous mitigation and containment strategy for coronavirus disease 2019 (COVID-19) on five vector-borne diseases (VBDs) in China from 2020 to 2021.

Methods

Data on VBDs from 2015 to 2021 were obtained from the National Health Commission of the People’s Republic of China, and the actual trend in disease activity in 2020–2021 was compared with that in 2015–2019 using a two-ratio Z-test and two proportional tests. Similarly, the estimated trend in disease activity was compared with the actual trend in disease activity in 2020.

Results

There were 13,456 and 3684 average yearly cases of VBDs in 2015–2019 and 2020, respectively. This represents a decrease in the average yearly incidence of total VBDs of 72.95% in 2020, from 0.9753 per 100,000 population in 2015–2019 to 0.2638 per 100,000 population in 2020 (t = 75.17, P < 0.001). The observed morbidity rates of the overall VBDs were significantly lower than the predicted rates (47.04% reduction; t = 31.72, P < 0.001). The greatest decline was found in dengue, with a 77.13% reduction (observed rate vs predicted rate: 0.0574 vs. 0.2510 per 100,000; t = 41.42, P < 0.001). Similarly, the average yearly mortality rate of total VBDs decreased by 77.60%, from 0.0064 per 100,000 population in 2015–2019 to 0.0014 per 100,000 population in 2020 (t = 6.58, P < 0.001). A decreasing trend was also seen in the monthly incidence of total VBDs in 2021 compared to 2020 by 43.14% (t = 5.48, P < 0.001).

Conclusions

The results of this study verify that the mobility and mortality rates of VBDs significantly decreased from 2015–2019 to 2020–2021, and that they are possibly associated to the continuous COVID-19 mitigation and contamination strategy implemented in China in 2020–2021.

Graphical Abstract
Data mining of bulk and single-cell RNA sequencing introduces OBI1-AS1 as an astrocyte marker with possible role in glioma recurrence and progression
Authors: Mamivand Ali , Bayat Shiva , Maghrouni Abolfazl , Shabani Sasan , Khoshnevisan Alireza , Saffar Hiva , Tabrizi Mina
Published: March 2022

Long non-coding RNAs (LncRNAs) are widely known for their various functions in cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classified into grades I to IV according to their malignant histological features with grade IV, also known as glioblastoma multiforme (GBM), displaying the highest level of malignancy. Thus, the search for differentially expressed LncRNAs in GBM versus low-grade glioma to uncover new insights into the molecular mechanisms of glioma progression have intensified. Bulk RNA sequencing pinpointed decreased expression ofOBI1-AS1in GBM compared to low-grade glioma samples. Subsequent single nuclei RNA sequencing revealedOBI1-AS1to be a super-exclusive astrocyte marker with AUC = 0.99 and the potential to fully differentiate astrocytes from other brain cell types. Additional supplementary bioinformatics analysis exhibitedOBI1-AS1role in synaptic signal transduction and glutamatergic signaling. In addition, ChIP-Seq data were analyzed to explore transcription factors that can regulateOBI1-AS1expression in neural cells. Results of Hi-C, methylation and ChIP-Seq analysis strongly suggest methylation of the CTCF binding site serving a central role in regulation ofOBI1-AS1expression via managing chromatin interactions. Our study indicated that lncRNAs, likeOBI1-AS1,could be extremely precise in identifying the astrocyte cluster in the single-cell transcriptome and demonstrating superiority to well-established astrocyte markers such asGFAP,S100B,ALDH1L1, and AQP4.

Graphical abstract
Improving the energy performance of the typical multi-family buildings in Amman, Jordan
Authors: Abu Qadourah Jenan , Al-Falahat Ala’a M. , Alrwashdeh Saad S. , Nytsch‐Geusen Christoph
Published: March 2022

In this paper, the possibility of reducing the energy demand of the typical multi-family buildings in Amman, Jordan utilizing passive design strategies are investigated through a parametric simulation study. Firstly, the energy demand of the multi-family buildings under the typical practice is evaluated, after that several design strategies are proposed such as wall and roof insulation, shading device, ventilation, etc. The effect of each strategy on the multi-family buildings’ energy demands is assessed alone and then in combination with the other strategies, to find the optimum solution to reduce the energy demand. This is beneficial for architects, engineers, and decisions makers involved in the design of energy-efficient multifamily buildings. The result proves that it’s possible to reduce the annual energy demand by 53, 71, and 78% of the cooling, heating, and lighting, respectively, by introducing passive design strategies. Around 45% savings of the heating demand are achieved due to adding wall insulation. Regarding the cooling demand about 17%, and 14% are saved due to applying a ventilated blind shading device and using a nighttime ventilation strategy.
Predation preference and nutritional values of four different aphid species for Orius sauteri (Hemiptera: Anthocoridae)
Authors: Zhang Liu , Li Tao , Qin Zifang , Cao Kaili , Gao Yifan , Wang Jingyi , Ge Yang , Shi Wangpeng
Published: March 2022

Background

Orius sauteri (Poppius) is one of the important natural enemies of aphids in Asia. Understanding its predation preference and efficiency can help improve its effectiveness as a biological control agent. Here, the predation preference of O. sauteri adults toward Aphis craccivora Koch, Rhopalosiphum maidis (Fitch), Myzus persicae Sulzer, and Aphis gossypii Glover was studied.

Results

The research found that O. sauteri had good predation efficiency on four important aphid species. Orius sauteri killed a similar number of four aphids in non-selective tests, but it preferred to eat more R. maidis and A. gossypii, and fewer A. craccivora in selective tests. The main biochemical components of the four aphid species were analyzed, including water content and nutritional components along with body mass. Rhopalosiphum maidis had a significantly lower water content than A. craccivora. Orius sauteri preferred R. maidis and A. gossypii, which harbored higher lipid and trehalose content, while preying on fewer A. craccivora, which had a larger body weight for the supplement of water and nutrition. The predation preference may be due to the closest nutrition composition to the optimal intake of O. sauteri.

Conclusions

This study showed that the predatory selection of O. sauteri was closely associated with the water content, bodyweight, lipid, and trehalose levels of prey, while the glycogen content and protein level might be less determinant. The high predation capacity on four aphids of O. sauteri indicated the great potential to integrate this predator into biological control strategies against aphids.
Study of the association between GLIS3 rs10758593 and type 2 diabetes mellitus in Egyptian population
Authors: Farid Mai Mohamed Mohamed , Abdel-Mageed Abeer Ibrahim , El-sherbini Aliaa , Mohamed Noha Refaat , Mohsen Manal
Published: March 2022

Background

GLIS3 (Gli-similar 3), a transcription factor, is involved in the maturation of pancreatic beta cells in fetal life, maintenance of cell mass as well as the control of insulin gene expression in adults. As a result, GLIS3 was reported as a susceptibility gene for type 1 diabetes, type 2 diabetes, and neonatal diabetes. Therefore, the goal of this study was to look into the association between the rs10758593 single nucleotide polymorphism (SNP) in the GLIS3 gene and T2DM in the Egyptian population.

Methods

Frequencies of the rs10758593 (A/G) SNPs were determined in 100 T2DM patients (cases) and in 100 non-diabetic healthy subjects (controls) using real-time PCR.

Results

The prevalence of the mutant genotypes, AA and AG, differed significantly between patients and controls. The AA genotype was more prevalent in the patients' group. The (AA) was found in 39% of the patients and 18% of the controls. While AG (heterozygous) genotype was found in 61% of the patients and 81% of the controls (p = 0.003). The AA genotype was significantly associated with T2DM. Moreover, The GLIS3 rs 10758593 mutation was found to be associated with the presence of diabetic retinopathy and nephropathy. In diabetic patients, a significant correlation between HbA1c with fasting glucose, fasting insulin, and HOMA-IR was found.

Conclusion

The rs10758593 polymorphism of the GLIS3 gene was found to be significantly associated with T2DM in an Egyptian population sample. Additionally, significant association between GLIS3 rs 10758593 mutation and the glycemic control was found.
Hematological indices in pediatric patients with acyanotic congenital heart disease: a cross-sectional study of 248 patients
Authors: Mohammadi Hanieh , Mohammadpour Ahranjani Behzad , Aghaei Moghadam Ehsan , Kompani Farzad , Mirbeyk Mona , Rezaei Nima
Published: March 2022

Background

Congenital heart disease CHD is a significant cause of mortality and morbidity in children worldwide. Patients with congenital heart disease may develop hematological problems, including thrombocytopenia and neutropenia. In addition, several studies indicate the higher frailty of patients with CHDs to infections and malignancies. Nevertheless, the mechanisms of immune system changes in these patients have remained in the shadow of uncertainty. Moreover, very few studies have worked on cytopenia in CHD. This study has assessed the frequency of thrombocytopenia, neutropenia, lymphopenia, and anemia in pediatric patients with acyanotic congenital heart disease ACHD prior to open-heart surgery.

Methods

This cross-sectional study was handled in the Pediatric Cardiology Clinic, Tehran University of Medical Sciences, during pre-operation visits from 2014 till 2019. Two hundred forty-eight children and adolescents with acyanotic congenital heart disease before open-heart surgery met the criteria to enter the study.

Results

A total of 191 (76.7%) patients with Ventricular Septal Defects (VSD), 37 (14.85%) patients with Atrial Septal Defects (ASD), and 20 (8.11%) patients with Patent Ductus Arteriosus (PDA) were enrolled in this study. The median age was 23.87 months. Thrombocytopenia and neutropenia were found, respectively, in 3 (1.2) and 23 (9.2%) patients. Hemoglobin level and lymphocyte count were significantly lower in patients with neutropenia than patients with normal neutrophil count (P value = 0.024 and P value = 0.000). Significant positive correlations were found between neutropenia and anemia. There were no correlations between neutrophil count and Platelets. Also, anemia was found in 48 patients (19.3%). The study also found a statistically significant correlation between the co-existence of VSD and neutropenia in the patients (P value = 0.000).

Conclusion

Although most were mildly neutropenic, there was a significant correlation between neutropenia and Ventricular Septal Defect compared to PDA and ASD groups. Regarding the importance of neutropenia to affect the prognosis of congenital heart defects in infections, it is important to consider further studies on the status of immune system function in these patients.
Association of methyltetrahydrofolate reductase gene mutation, homocysteine level with semen quality of Iraqi infertile males
Authors: Al-janabi Anwar Madlool , Al-Khafaji Salih Mahdi , Faris Shehab Ahmed
Published: March 2022

Background

Infertility is very common condition and almost 50% of cases are due to male factors. Several genetic and environmental factors are responsible for the poor quality and reduced number of sperms in several cases of infertility. The present study was designed to investigate the association between semen parameters, homocysteine, and the risk of C677T polymorphism of MTHFR gene in infertile males of Iraqi population.

Methods

This Case–control study has been conducted from February 2019 to July 2021 at a molecular laboratory in the Anatomy and Histology Department/college of Medicine/University of Kufa/Najaf/Iraq. It was composed of 353 infertile male patients. They were divided into five groups: 90 azoospermic, 84 oligospermia, 64 asthenospermic, 50 oligoasthenospermic, and 65 teratospermic with an age range 20–46 years compared with 100 fertile males as control with age range 21–49 years. In order to detect homocysteine levels, we used Hcy ELISA Kit. C677T mutation of MTHFR gene was employed by PCR–RFLP technique.

Results

Our data revealed three genotypes of MTHFR C677T, 167 (47.3%) subjects had CC genotype, 116 (32.9%) subjects had CT genotype and 70 (21.1%) subjects had TT genotype. Furthermore, T allele was associated with higher risk of infertility in all patients groups for any genetic model. In total infertile subjects (codominant model: CT vs. CC, OR = 2.0, 95% C.I = 1.2–3.3, P = 0.011; TT vs. CC, OR = 4.8, 95% C.I = 3.3–8.2, P = 0.0003; dominant model: CT + TT vs. CC, OR = 2.8, 95% C.I = 1.7–4.5, P = 0.0001). Oligoasthenospermic patients associated with higher risk in CT heterozygous genotype (OR = 2.8, 95% C.I = 1.0–4.9, P = 0.03) and TT homozygous of mutant allele (OR = 6.3, 95% C.I = 1.9–9.2, P = 0.002). Homocystein level was elevated in all infertile groups when compared with control group (P < 0.01), but the elevation was marked in oligoasthenospermia group. As well as, the level of Serum Hcy exhibited the highest value in TT mutant genotype (39.7 µmol/ml) followed by CT genotype (28.5 µmol/ml) while the lowest level of Hcy recorded in CC genotype (14.6 µmol/ml) for oligoasthenospermia group.

Conclusions

By relating the MTHFR C677T gene mutation with a higher homocystein level, the results showed that Iraqi males with this mutation are more likely to suffer from infertility.
Occurrence of gastrointestinal (GI) parasites in captive Olive Baboon and Common Langur in Bangladesh
Authors: Tabasshum Taniza , Liza Fahmida Tasnim , Rabbe Md. Fazle , Mukutmoni Mandira , Alam Md. Mahabub , Begum Aleya
Published: March 2022

Non-human primates (NHPs) serve as necessary reservoir hosts of parasites that create diseases to human. A close interaction between human and NHP can make a pathway for transmission of zoonotic diseases. To prevent zoonotic infection of zoo keepers, park visitors as well as keeping the captive NHPs in healthy state, it is necessary to carry out regular parasitological examination and treatment. A total of 72 fecal samples of Olive Baboon (n = 39) and Common Langur (n = 33) irrespective of their age and sex were collected from two zoological gardens of Bangladesh. Eggs and oocysts of seven gastrointestinal (GI) parasites were observed and identified in samples of both host species. The prevalence of GI parasites recorded was 100%. In case of Olive Baboon, the protozoan prevalence was higher (53.83%) than that of helminths, but opposite scenario was seen in case of Common Langur. Besides, higher intensity of coccidian oocysts in both hosts was recorded in the study.
Evolving Effect of the COVID-19 Pandemic on Cancer-Related Encounters
Authors: London Jack W. , Fazio-Eynullayeva Elnara , Palchuk Matvey B. , McNair Christopher
Published: March 2022

PURPOSE

This is an update to a previously published report characterizing the impact that efforts to control the COVID-19 pandemic have had on the normal course of cancer-related encounters.

METHODS

Data were analyzed from 22 US health care organizations (members of the TriNetX global network) having relevant, up-to-date encounter data. Although the original study compared encounter data pre–COVID-19 (January-April 2019) with the corresponding months in 2020, this update considers data through April 2021. As before, cohorts were generated for all neoplasm patients (malignant, benign, in situ, and of unspecified behavior), all new incidence neoplasm patients, exclusively malignant neoplasm patients, and new incidence malignant neoplasm patients. Data on the initial cancer stage were available for calendar year 2020 from about one third of the study's organizations.

RESULTS

Although COVID-19 cases fluctuated through 2021, newly diagnosed cancers closely paralleled the prepandemic base year 2019. Similarly, screening for breast, colorectal, and cervical cancers quickly recovered beginning in May 2020 to prepandemic numbers. Preliminary data for the initial cancer stage showed no significant difference ( P > .10) in distribution for breast or colon cancers between 2019 and 2020.

CONCLUSION

Although the number of COVID-19 cases fluctuated, the steep declines observed during March and April 2020 in screening for breast and colon cancer and patients with newly diagnosed cancer did not continue through the rest of 2020 and into April 2021. Screening and new incidence cancer numbers quickly rose compared with prepandemic levels. The concern that more patients with advanced-stage cancer would be seen in the months following the drastic dips of March-April 2020 was not realized as the major disruption to normal cancer care was limited to these 2 months.