bluuebunny/crossref_metadata_2025 huggingface dataset:
Particulate matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression
Authors: Choi Yong Jun , Han Heejae , Lee Jae-Hyun , Lee Jaeuk , Kim Chi Young , Byun Min Kwang , Cho Jae Hwa , Park Hye Jung
Published: March 2023

Background

Particulate matter10 (PM10) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM10-treated murine mice models.

Methods

In female BALB/c mice, PM10 was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways.

Results

PM10 and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM10 or PM10/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM10 and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway.

Conclusions

Chitinase-1 suppression by CPX can regulate PM10- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.
General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial
Authors: Franek Edward , Pais Prem , Basile Jan , Nicolay Claudia , Raha Sohini , Hickey Ana , Ahmad Nadia N. , Konig Manige , Kan Hong , Gerstein Hertzel C.
Published: March 2023

Background

In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D).

Methods

Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor.

Results

Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed.

Conclusions

In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.
Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients
Authors: Rea Federico , Savaré Laura , Valsassina Valeria , Ciardullo Stefano , Perseghin Gianluca , Corrao Giovanni , Mancia Giuseppe
Published: March 2023

Background

To evaluate the protective effect of oral antidiabetic drugs in a large cohort of elderly patients with type 2 diabetes differing for age, clinical status, and life expectancy, including patients with multiple comorbidities and short survival.

Methods

A nested case–control study was carried out by including the cohort of 188,983 patients from Lombardy (Italy), aged ≥ 65 years, who received ≥ 3 consecutive prescriptions of antidiabetic agents (mostly metformin and other older conventional agents) during 2012. Cases were the 49,201 patients who died for any cause during follow-up (up to 2018). A control was randomly selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antidiabetic drugs. The analysis was stratified according to four categories of the clinical status (good, intermediate, poor, and very poor) differing for life expectancy.

Results

There was a steep increase in comorbidities and a marked reduction of the 6-year survival from the very good to the very poor (or frail) clinical category. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of all-cause mortality in all clinical categories and at all ages (65–74, 75–84 and ≥ 85 years) except for the frail patient subgroup aged ≥ 85 years. The mortality reduction from lowest to highest adherence level showed a tendency to be lower in frail patients compared to the other categories. Similar although less consistent results were obtained for cardiovascular mortality.

Conclusions

In elderly diabetic patients, increased adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the patients’ clinical status and age, with the exception of very old patients (age ≥ 85 years) in the very poor or frail clinical category. However, in the frail patient category the benefit of treatment appears to be less than in patients in good clinical conditions.
Positive association of triglyceride-glucose index with new-onset hypertension among adults: a national cohort study in China
Authors: Gao Qi , Lin Yuxin , Xu Ruqi , Luo Fan , Chen Ruixuan , Li Pingping , Zhang Yuping , Liu Jiao , Deng Zhenan , Li Yanqin , Su Licong , Nie Sheng
Published: March 2023

Background

Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults.

Methods

A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension.

Results

The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0–6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07–1.55, Q2; aHR, 1.24, 95% CI 1.03–1.49, Q3; aHR, 1.50, 95% CI 1.22–1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04–1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose–response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension.

Conclusions

High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.
Improving the production of 9α-hydroxy-4-androstene-3,17-dione from phytosterols by 3-ketosteroid-Δ1-dehydrogenase deletions and multiple genetic modifications in Mycobacterium fortuitum
Authors: Liu Xiangcen , Zhang Jingxian , Yuan Chenyang , Du Guilin , Han Suwan , Shi Jiping , Sun Junsong , Zhang Baoguo
Published: March 2023

Background

9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol biotransformation to manufacture 9-OHAD, product degradation, and by-products restrict 9-OHAD output. In this study, to construct a stable and high-yield 9-OHAD producer, we investigated a combined strategy of blocking Δ1‑dehydrogenation and regulating metabolic flux.

Results

Five 3-Ketosteroid-Δ1-dehydrogenases (KstD) were identified in Mycobacterium fortuitum ATCC 35855. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4, and KstD5, respectively. In particular, KstD2 had a much higher catalytic activity for C9 hydroxylated steroids than for C9 non-hydroxylated steroids, whereas KstD3 showed the opposite characteristics. The deletion of kstDs indicated that KstD2 and KstD3 were the main causes of 9-OHAD degradation. Compared with the wild type M. fortuitum ATCC 35855, MFΔkstD, the five kstDs deficient strain, realized stable accumulation of 9-OHAD, and its yield increased by 42.57%. The knockout of opccr or the overexpression of hsd4A alone could not reduce the metabolic flux of the C22 pathway, while the overexpression of hsd4A based on the knockout of opccr in MFΔkstD could remarkably reduce the contents of 9,21 ‑dihydroxy‑20‑methyl‑pregna‑4‑en‑3‑one (9-OHHP) by-products. The inactivation of FadE28-29 leads to a large accumulation of incomplete side-chain degradation products. Therefore, hsd4A and fadE28-29 were co-expressed in MFΔkstDΔopccr successfully eliminating the two by-products. Compared with MFΔkstD, the purity of 9-OHAD improved from 80.24 to 90.14%. Ultimately, 9‑OHAD production reached 12.21 g/L (83.74% molar yield) and the productivity of 9-OHAD was 0.0927 g/L/h from 20 g/L phytosterol.

Conclusions

KstD2 and KstD3 are the main dehydrogenases that lead to 9-OHAD degradation. Hsd4A and Opccr are key enzymes regulating the metabolic flux of the C19- and C22-pathways. Overexpression of fadE28-29 can reduce the accumulation of incomplete degradation products of the side chains. According to the above findings, the MF-FA5020 transformant was successfully constructed to rapidly and stably accumulate 9-OHAD from phytosterols. These results contribute to the understanding of the diversity and complexity of steroid catabolism regulation in actinobacteria and provide a theoretical basis for further optimizing industrial microbial catalysts.
Changes in calpain-2 expression during glioblastoma progression predisposes tumor cells to temozolomide resistance by minimizing DNA damage and p53-dependent apoptosis
Authors: Stillger Maren Nicole , Chen Chia-Yi , Lai Zon Weng , Li Mujia , Schäfer Agnes , Pagenstecher Axel , Nimsky Christopher , Bartsch Jörg Walter , Schilling Oliver
Published: March 2023

Background

Glioblastoma multiforme (GBM) is characterized by an unfavorable prognosis for patients affected. During standard-of-care chemotherapy using temozolomide (TMZ), tumors acquire resistance thereby causing tumor recurrence. Thus, deciphering essential molecular pathways causing TMZ resistance are of high therapeutic relevance.

Methods

Mass spectrometry based proteomics were used to study the GBM proteome. Immunohistochemistry staining of human GBM tissue for either calpain-1 or -2 was performed to locate expression of proteases. In vitro cell based assays were used to measure cell viability and survival of primary patient-derived GBM cells and established GBM cell lines after TMZ ± calpain inhibitor administration. shRNA expression knockdowns of either calpain-1 or calpain-2 were generated to study TMZ sensitivity of the specific subunits. The Comet assay and ɣH2AX signal measurements were performed in order to assess the DNA damage amount and recognition. Finally, quantitative real-time PCR of target proteins was applied to differentiate between transcriptional and post-translational regulation.

Results

Calcium-dependent calpain proteases, in particular calpain-2, are more abundant in glioblastoma compared to normal brain and increased in patient-matched initial and recurrent glioblastomas. On the cellular level, pharmacological calpain inhibition increased the sensitivities of primary glioblastoma cells towards TMZ. A genetic knockdown of calpain-2 in U251 cells led to increased caspase-3 cleavage and sensitivity to neocarzinostatin, which rapidly induces DNA strand breakage. We hypothesize that calpain-2 causes desensitization of tumor cells against TMZ by preventing strong DNA damage and subsequent apoptosis via post-translational TP53 inhibition. Indeed, proteomic comparison of U251 control vs. U251 calpain-2 knockdown cells highlights perturbed levels of numerous proteins involved in DNA damage response and downstream pathways affecting TP53 and NF-κB signaling. TP53 showed increased protein abundance, but no transcriptional regulation.

Conclusion

TMZ-induced cell death in the presence of calpain-2 expression appears to favor DNA repair and promote cell survival. We conclude from our experiments that calpain-2 expression represents a proteomic mode that is associated with higher resistance via “priming” GBM cells to TMZ chemotherapy. Thus, calpain-2 could serve as a prognostic factor for GBM outcome.
BRF2 is mediated by microRNA-409-3p and promotes invasion and metastasis of HCC through the Wnt/β-catenin pathway
Authors: Chang Jian-Hua , Xu Bo-Wen , Shen Di , Zhao Wei , Wang Yue , Liu Jia-liang , Meng Guang-Xiao , Li Guang-Zhen , Zhang Zong-Li
Published: March 2023

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. BRF2 has been shown to be an oncogene in a number of tumors; however, its role in HCC has not yet been thoroughly examined. In this study, we identified and validated BRF2 as an oncogene in HCC, providing a new insight into HCC pathogenesis and therapeutic possibilities. We showed that BRF2 expression was significantly upregulated in HCC cell lines and tissues, while BRF2 depletion suppressed HCC metastasis and invasion. We then examined the upstream regulation of BRF2 and identified miR-409-3p as being predicted to bind to the 3′ UTR of BRF2. We used a luciferase activity assay and functional verification to show that BRF2 is downregulated by miR-409-3p. Finally, we used bioinformatic analysis to show that BRF2 may be related to early HCC development through the Wnt/β-catenin signaling pathway.
Species composition and insecticide resistance in malaria vectors in Ellibou, southern Côte d’Ivoire and first finding of Anopheles arabiensis in Côte d’Ivoire
Authors: N’Dri Bédjou P. , Wipf Nadja C. , Saric Jasmina , Fodjo Behi K. , Raso Giovanna , Utzinger Jürg , Müller Pie , Mouhamadou Chouaïbou S.
Published: March 2023

Background

Knowing the species composition and insecticide resistance status of the target vector population is important to guide malaria vector control. The aim of this study was to characterize the malaria vector population in terms of species composition, insecticide susceptibility status and potential underlying resistance mechanisms in Ellibou, southern Côte d’Ivoire.

Methods

A 1-year longitudinal entomological survey was conducted using light traps and pyrethroid spray catches to sample adult mosquitoes in combination with larval sampling. The susceptibility status of Anopheles gambiae sensu lato (s.l.) to bendiocarb, deltamethrin, DDT and malathion was assessed using the World Health Organization insecticide susceptibility test. Additionally, An. gambiae specimens were screened for knockdown (kdr) and acetylcholineesterase (ace1) target site resistance alleles, and the expression levels of eight metabolic resistance genes, including seven cytochrome P450 monooxygenases (P450s) and one glutathione S-transferase (GST), measured with reverse transcription quantitative real-time polymerase chain reaction (qPCR).

Results

Overall, 2383 adult mosquitoes from 12 different taxa were collected with Culex quinquefasciatus and An. gambiae being the predominant taxa. Molecular identification of An. gambiae s.l. revealed the presence of Anopheles arabiensis, Anopheles coluzzii, An. gambiae sensu stricto (s.s.) and Anopheles coluzzii/An. gambiae s.s. hybrids. Anopheles gambiae mosquitoes were resistant to all insecticides except malathion. PCR diagnostics revealed the presence of ace1-G280S and the kdr L995F, L995S and N1570Y target-site mutations. Additionally, several genes were upregulated, including five P450s (i.e., CYP6P3, CYP6M2, CYP9K1, CYP6Z1, CYP6P1) and GSTE2.

Conclusion

This is the first documented presence of An. arabiensis in Côte d’Ivoire. Its detection – together with a recent finding further north of the country – confirms its existence in the country, which is an early warning sign, as An. arabiensis shows a different biology than the currently documented malaria vectors. Because the local An. gambiae population was still susceptible to malathion, upregulation of P450s, conferring insecticide resistance to pyrethroids, together with the presence of ace1, suggest negative cross-resistance. Therefore, organophosphates could be an alternative insecticide class for indoor residual spraying in the Ellibou area, while additional tools against the outdoor biting An. arabiensis will have to be considered.
A review of efficacy and safety of Ugandan anti-malarial plants with application of RITAM score
Authors: Angupale Jimmy R. , Tusiimire Jonans , Ngwuluka Ndidi C.
Published: March 2023

Background

Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants.

Methods

Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020–December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (µg/ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety (LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development.

Results

Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 – 0.05 µg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation.

Conclusion

There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed.
Anopheles rufipes implicated in malaria transmission both indoors and outdoors alongside Anopheles funestus and Anopheles arabiensis in rural south-east Zambia
Authors: Saili Kochelani , de Jager Christiaan , Sangoro Onyango P. , Nkya Theresia E. , Masaninga Freddie , Mwenya Mwansa , Sinyolo Andy , Hamainza Busiku , Chanda Emmanuel , Fillinger Ulrike , Mutero Clifford M.
Published: March 2023

Background

The primary malaria vector-control interventions, indoor residual spraying and long-lasting insecticidal nets, are effective against indoor biting and resting mosquito species. Consequently, outdoor biting and resting malaria vectors might elude the primary interventions and sustain malaria transmission. Varied vector biting and resting behaviour calls for robust entomological surveillance. This study investigated the bionomics of malaria vectors in rural south-east Zambia, focusing on species composition, their resting and host-seeking behaviour and sporozoite infection rates.

Methods

The study was conducted in Nyimba District, Zambia. Randomly selected households served as sentinel houses for monthly collection of mosquitoes indoors using CDC-light traps (CDC-LTs) and pyrethrum spray catches (PSC), and outdoors using only CDC-LTs for 12 months. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were further identified using molecular techniques. Plasmodium falciparum sporozoite infection was determined using sandwich enzyme-linked immunosorbent assays.

Results

From 304 indoor and 257 outdoor light trap-nights and 420 resting collection, 1409 female Anopheles species mosquitoes were collected and identified morphologically; An. funestus (n = 613; 43.5%), An. gambiae sensu lato (s.l.)(n = 293; 20.8%), Anopheles pretoriensis (n = 282; 20.0%), Anopheles maculipalpis (n = 130; 9.2%), Anopheles rufipes (n = 55; 3.9%), Anopheles coustani s.l. (n = 33; 2.3%), and Anopheles squamosus (n = 3, 0.2%). Anopheles funestus sensu stricto (s.s.) (n = 144; 91.1%) and Anopheles arabiensis (n = 77; 77.0%) were the dominant species within the An. funestus group and An. gambiae complex, respectively. Overall, outdoor CDC-LTs captured more Anopheles mosquitoes (mean = 2.25, 95% CI 1.22–3,28) than indoor CDC-LTs (mean = 2.13, 95% CI 1.54–2.73). Fewer resting mosquitoes were collected with PSC (mean = 0.44, 95% CI 0.24–0.63). Sporozoite infectivity rates for An. funestus, An. arabiensis and An. rufipes were 2.5%, 0.57% and 9.1%, respectively. Indoor entomological inoculation rates (EIRs) for An. funestus s.s, An. arabiensis and An. rufipes were estimated at 4.44, 1.15 and 1.20 infectious bites/person/year respectively. Outdoor EIRs for An. funestus s.s. and An. rufipes at 7.19 and 4.31 infectious bites/person/year, respectively.

Conclusion

The findings of this study suggest that An. rufipes may play an important role in malaria transmission alongside An. funestus s.s. and An. arabiensis in the study location.

Graphical Abstract
Distribution of Anopheles gambiae thioester-containing protein 1 alleles along malaria transmission gradients in The Gambia
Authors: Hamid-Adiamoh Majidah , Jabang Abdoulie Mai Janko , Opondo Kevin Ochieng , Ndiath Mamadou Ousmane , Assogba Benoit Sessinou , Amambua-Ngwa Alfred
Published: March 2023

Background

Thioester-containing protein 1 (TEP1) is a highly polymorphic gene playing an important role in mosquito immunity to parasite development and associated with Anopheles gambiae vectorial competence. Allelic variations in TEP1 could render mosquito either susceptible or resistant to parasite infection. Despite reports of TEP1 genetic variations in An. gambiae, the correlation between TEP1 allelic variants and transmission patterns in malaria endemic settings remains unclear.

Methods

TEP1 allelic variants were characterized by PCR from archived genomic DNA of > 1000 An. gambiae mosquitoes collected at 3 time points between 2009 and 2019 from eastern Gambia, where malaria transmission remains moderately high, and western regions with low transmission.

Results

Eight common TEP1 allelic variants were identified at varying frequencies in An. gambiae from both transmission settings. These comprised the wild type TEP1, homozygous susceptible genotype, TEP1s; homozygous resistance genotypes: TEP1rA and TEP1rB, and the heterozygous resistance genotypes: TEP1srA, TEP1srB, TEP1rArB and TEP1srArB. There was no significant disproportionate distribution of the TEP1 alleles by transmission setting and the temporal distribution of alleles was also consistent across the transmission settings. TEP1s was the most common in all vector species in both settings (allele frequencies: East = 21.4–68.4%. West = 23.5–67.2%). In Anopheles arabiensis, the frequency of wild type TEP1 and susceptible TEP1s was significantly higher in low transmission setting than in high transmission setting (TEP1: Z = − 4.831, P < 0.0001; TEP1s: Z = − 2.073, P = 0.038).

Conclusions

The distribution of TEP1 allele variants does not distinctly correlate with malaria endemicity pattern in The Gambia. Further studies are needed to understand the link between genetic variations in vector population and transmission pattern in the study settings. Future studies on the implication for targeting TEP1 gene for vector control strategy such as gene drive systems in this settings is also recommended.
Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome
Authors: Li Yuchun , Huang Xiaomin , Qing Ling , Zeng Wen , Zeng Xiangjie , Meng Feng , Wang GuangZe , Chen Yan
Published: March 2023

Background

Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear.

Methods

Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program.

Results

In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China’s Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China’s others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation.

Conclusions

Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China’s other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.
Community case management of malaria in Western Kenya: performance of community health volunteers in active malaria case surveillance
Authors: Otambo Wilfred Ouma , Ochwedo Kevin O. , Omondi Collince J. , Lee Ming-Chieh , Wang Chloe , Atieli Harrysone , Githeko Andew K. , Zhou Guofa , Kazura James , Githure John , Yan Guiyun
Published: March 2023

Background

In western Kenya, not all malaria cases are reported as stipulated in the community case management of malaria (CCMm) strategy. This underreporting affects the equity distribution of malaria commodities and the evaluation of interventions. The current study aimed to evaluate the effectiveness of community health volunteers’ active case detection and management of malaria in western Kenya.

Methods

Cross-sectional active case detection (ACD) of malaria survey was carried out between May and August 2021 in three eco-epidemiologically distinct zones in Kisumu, western Kenya: Kano Plains, Lowland lakeshore and Highland Plateau. The CHVs conducted biweekly ACD of malaria household visits to interview and examine residents for febrile illness. The Community Health Volunteers (CHVs) performance during the ACD of malaria was observed and interviews done using structured questionnaires.

Results

Of the total 28,800 surveyed, 2597 (9%) had fever and associated malaria symptoms. Eco-epidemiological zones, gender, age group, axillary body temperature, bed net use, travel history, and survey month all had a significant association with malaria febrile illness (p < 0.05). The qualification of the CHV had a significant influence on the quality of their service. The number of health trainings received by the CHVs was significantly related to the correctness of using job aid (χ2 = 6.261, df = 1, p = 0.012) and safety procedures during the ACD activity (χ2 = 4.114, df = 1, p = 0.043). Male CHVs were more likely than female CHVs to correctly refer RDT-negative febrile residents to a health facility for further treatment (OR = 3.94, 95% CI = 1.85–5.44, p < 0.0001). Most of RDT-negative febrile residents who were correctly referred to the health facility came from the clusters with a CHV having 10 years of experience or more (OR = 1.29, 95% CI = 1.05–1.57, p = 0.016). Febrile residents in clusters managed by CHVs with more than 10 years of experience (OR = 1.82, 95% CI = 1.43–2.31, p < 0.0001), who had a secondary education (OR = 1.53, 95% CI = 1.27–1.85, p < 0.0001), and were over the age of 50 (OR = 1.44, 95% CI = 1.18–1.76, p < 0.0001), were more likely to seek malaria treatment in public hospitals. All RDT positive febrile residents were given anti-malarial by the CHVs, and RDT negatives were referred to the nearest health facility for further treatment.

Conclusions

The CHV’s years of experience, education level, and age had a significant influence on their service quality. Understanding the qualifications of CHVs can assist healthcare systems and policymakers in designing effective interventions that assist CHVs in providing high-quality services to their communities.
Anti-malarial drug use, appropriateness and associated factors among children under-five with febrile illnesses presenting to a tertiary health facility: a cross sectional study
Authors: Nyeko Richard , Otim Felix , Obiya Evelyn Miriam , Abala Catherine
Published: March 2023

Background

Malaria is endemic in 95% of Uganda and constitutes the country’s most significant public health problem—being the leading cause of morbidity and mortality, especially among children under five years of age. The current national malaria treatment policy is to use artemisinin-based combination therapy (ACT) as first-line treatment, and recommends parasitological confirmation of malaria before therapy. Adherence to this policy, however, remains suboptimal, with the self-initiated home-based therapy being common—posing undue exposures to, and pressure on the current artemisinin-based combinations, with the danger of emergence of drug resistance. The study evaluated the anti-malarial use and its appropriateness among febrile children under five presenting to a tertiary health facility in northern Uganda in light of the current malaria treatment policy.

Methods

This was a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6–59 months with fever were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect clinical data from the caregivers. Data were analysed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance.

Results

Seventy-two (34.3%) of the 210 children with fever in this study used anti-malarials prior to the hospital visit, 29.2% (21/72) of which were on a self-medication basis, 22.2% (16/72) were empiric prescriptions—all of which inappropriate, and only 48.6% (35/72) were prescribed based on a parasitological diagnosis of malaria. The most commonly used anti-malarials were artemether-lumefantrine 60/72 (88.3%), while a lesser proportion of quinine 7/72 (9.7%), artesunate 3/72 (4.2%) and dihydroartemisinin-piperaquine 2/72 (2.8%) were used. The factors independently associated with anti-malarial use among the children with febrile illnesses were duration of fever (p = 0.001); level of the nearest facility (p = 0.027), distance from the nearest health facility (p = 0.025), and caregivers’ age (p = 0.038).

Conclusions

Inappropriate use of anti-malarials for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of over-the-counter access, empiric prescription and use of leftover anti-malarials. This calls for a need to address communities’ health-seeking behaviour and the health providers’ practice alike.
Patterns and correlates of nutrition knowledge across five countries in the 2018 international food policy study
Authors: Bhawra Jasmin , Kirkpatrick Sharon I. , Hall Marissa G. , Vanderlee Lana , White Christine M. , Hammond David
Published: March 2023

Background

Nutrition knowledge is an important determinant of diet-related behaviour; however, the use of disparate assessment tools creates challenges for comparing nutrition knowledge levels and correlates across studies, geographic contexts, and populations. Using the Food Processing Knowledge (FoodProK) score – a measure of nutrition knowledge based on consumers’ ability to understand and apply the concept of food processing in a functional task – nutrition knowledge levels and associated correlates were assessed in five countries.

Methods

Adults, aged ≥18 years, were recruited through the Nielsen Consumer Insights Global Panel in Australia (n = 3997), Canada (n = 4170), Mexico (n = 4044), the United Kingdom (UK) (n = 5363), and the United States (US) (n = 4527). Respondents completed web-based surveys in November–December 2018. Functional nutrition knowledge was measured using the FoodProK score. Linear regression models examined associations between FoodProK score and sociodemographic, dietary behaviours, and knowledge-related characteristics.

Results

FoodProK scores (maximum, 8 points) were highest in Canada (mean: 5.1) and Australia (5.0), followed by the UK (4.8), Mexico (4.7), and the US (4.6). Health literacy and self-rated nutrition knowledge were positively associated with FoodProK scores (p < .001). FoodProK scores were higher among those who reported vegetarian/other dietary practices (p < .001); made efforts to consume less sodium, trans fats, or sugars (p < .001); ≥60 years (p = 0.002), female (p < .001), and ‘majority’ ethnic group respondents in their respective countries (p < .001).

Conclusions

This study found differences in consumers’ ability to distinguish levels of food processing for common foods, with somewhat lower levels of nutrition knowledge in countries with the highest intake of highly processed foods. Nutrition knowledge differences based on consumer characteristics highlight the need for accessible policy interventions that support uptake of healthy eating efforts across populations to avoid exacerbating nutrition-related disparities. Tools such as the FoodProK can be used to evaluate the impact of policies targeting nutrition knowledge across contexts.
ECG signal feature extraction trends in methods and applications
Authors: Singh Anupreet Kaur , Krishnan Sridhar
Published: March 2023

Signal analysis is a domain which is an amalgamation of different processes coming together to form robust pipelines for the automation of data analysis. When applied to the medical world, physiological signals are used. It is becoming increasingly common in today’s day and age to be working with very large datasets, on the scale of having thousands of features. This is largely due to the fact that the acquisition of biomedical signals can be taken over multi-hour timeframes, which is another challenge to solve in and of itself. This paper will focus on the electrocardiogram (ECG) signal specifically, and common feature extraction techniques used for digital health and artificial intelligence (AI) applications. Feature extraction is a vital step of biomedical signal analysis. The basic goal of feature extraction is for signal dimensionality reduction and data compaction. In simple terms, this would allow one to represent data with a smaller subset of features; these features could then later be leveraged to be used more efficiently for machine learning and deep learning models for applications, such as classification, detection, and automated applications. In addition, the redundant data in the overall dataset is filtered out as the data is reduced during feature extraction. In this review, we cover ECG signal processing and feature extraction in the time domain, frequency domain, time–frequency domain, decomposition, and sparse domain. We also provide pseudocode for the methods discussed so that they can be replicated by practitioners and researchers in their specific areas of biomedical work. Furthermore, we discuss deep features, and machine learning integration, to complete the overall pipeline design for signal analysis. Finally, we discuss future work that can be innovated upon in the feature extraction domain for ECG signal analysis.
Strengthening and expanding health inequality monitoring for the advancement of health equity: a review of WHO resources and contributions
Authors: Hosseinpoor Ahmad Reza , Bergen Nicole , Kirkby Katherine , Schlotheuber Anne
Published: March 2023

As part of its commitment to advance health equity, the World Health Organization (WHO) has a developed area of work to promote and strengthen health inequality monitoring. This includes an emphasis on the collection, analysis and use of disaggregated health data, which are central to evidence-informed decision making. The aim of this paper is to review WHO's work on health inequality monitoring, namely the 2022–27 Inequality monitoring and analysis strategy and corresponding activities, resources and tools. The strategy has three goals pertaining to: strengthening capacity for health inequality monitoring; generating and disseminating the latest evidence on health inequality and supporting data disaggregation; and developing and refining health inequality monitoring methods, resources and best practices. In alignment with these goals, WHO has published reference materials focused on conceptual approaches to health inequality monitoring, which are applied in the global State of Inequality report series. The Health Inequality Monitoring eLearning channel on OpenWHO and capacity building workshops and webinars facilitate the uptake and application of inequality monitoring practices across diverse settings and stakeholders. A key tool available to support the analysis and reporting aspects of health inequality monitoring is the Health Equity Assessment Toolkit (HEAT) application, which allows users to explore data interactively. The Health Inequality Data Repository, a collection of the largest publicly available database of disaggregated data from around the globe, further enables inequality monitoring and analyses. This collection of resources is an important contribution to promote health inequality monitoring across diverse settings. The uptake of evidence from health inequality monitoring remains crucial to the advancement of equity as part of global health and development initiatives.
Social capital and women’s narratives of homelessness and multiple exclusion in northern England
Authors: McGrath Joanne , Crossley Stephen , Lhussier Monique , Forster Natalie
Published: March 2023

Women experiencing three or more co-occurring issues (homelessness, substance misuse, mental health) are a highly vulnerable population associated with multimorbidity. Taking women’s life stories of trajectories into social exclusion in the north of England as its focus, this paper aims to explore the complexity of social contexts in which women navigate extreme health inequalities. Of the few studies that have examined women’s experiences of homelessness through the lens of social capital, most have focused on network size, rather than the quality and influence of the relationships which precipitate or contextualise experiences of social exclusion. We utilise case studies to offer a theoretically-grounded analysis which illustrates the relationship between social capital and homelessness within this population. Our results illustrate how structural contexts, and specifically social capital accrual and social bonding processes particularly pertinent to women can act to both ameliorate and perpetuate social exclusion. We conclude by arguing that health inequalities cannot be tackled as single-issue processes but instead are multi-layered and complex.
Health equity related challenges and experiences during the rapid implementation of virtual care during COVID-19: a multiple case study
Authors: Shahid Simone , Hogeveen Sophie , Sky Philina , Chandra Shivani , Budhwani Suman , de Silva Ryan , Bhatia R. Sacha , Seto Emily , Shaw James
Published: March 2023

Background

Virtual care quickly became of crucial importance to health systems around the world during the COVID-19 pandemic. Despite the potential of virtual care to enhance access for some communities, the scale and pace at which services were virtualized did not leave many organizations with sufficient time and resources to ensure optimal and equitable delivery of care for everyone. The objective of this paper is to outline the experiences of health care organizations rapidly implementing virtual care during the first wave of the COVID-19 pandemic and examine whether and how health equity was considered.

Methods

We used an exploratory, multiple case study approach involving four health and social service organizations providing virtual care services to structurally marginalized communities in the province of Ontario, Canada. We conducted semi-structured qualitative interviews with providers, managers, and patients to understand the challenges experienced by organizations and the strategies put in place to support health equity during the rapid virtualization of care. Thirty-eight interviews were thematically analyzed using rapid analytic techniques.

Results

Organizations experienced challenges related to infrastructure availability, digital health literacy, culturally appropriate approaches, capacity for health equity, and virtual care suitability. Strategies to support health equity included the provision of blended models of care, creation of volunteer and staff support teams, participation in community engagement and outreach, and securement of infrastructure for clients. We put our findings into the context of an existing framework conceptualizing access to health care and expand on what this means for equitable access to virtual care for structurally marginalized communities.

Conclusion

This paper highlights the need to pay greater attention to the role of health equity in virtual care delivery and situate that conversation around existing inequitable structures in the health care system that are perpetuated when delivering care virtually. An equitable and sustainable approach to virtual care delivery will require applying an intersectionality lens on the strategies and solutions needed to address existing inequities in the system.
Equity in the public social healthcare protection in Tanzania: does it matter on household healthcare financing?
Authors: Kitole Felician Andrew , Lihawa Robert Michael , Mkuna Eliaza
Published: March 2023

Efforts to promote equity in healthcare involve implementing policies and programs that address the root causes of healthcare disparities and promote equal access to care. One such program is the public social healthcare protection schemes. However, like many other developing countries, Tanzania has low health insurance coverage, hindering its efforts to achieve universal health coverage. This study examines the role of equity in public social healthcare protection and its effects on household healthcare financing in Tanzania. The study used secondary data collected from the National Bureau of Statistics' National Panel Survey 2020/21 and stratified households based on their place of residence (rural vs. urban). Moreover, the logit regression model, ordered logit, and the endogenous switching regression model were used to provide counterfactual estimates without selection bias and endogeneity problems. The results showed greater variations in social health protection across rural and urban households, increasing disparities in health outcomes between these areas. Rural residents are the most vulnerable groups. Furthermore, education, income, and direct healthcare costs significantly influence equity in healthcare financing and the ability of households to benefit from public social healthcare protection schemes. To achieve equity in healthcare in rural and urban areas, developing countries need to increase investment in health sector by reducing the cost of healthcare, which will significantly reduce household healthcare financing. Furthermore, the study recommends that social health protection is an essential strategy for improving fair access to quality healthcare by removing differences across households and promoting equality in utilizing healthcare services.