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Item Determinants of Campylobacter species diversity in infants and association with family members, livestock, and household environments in rural Eastern Ethiopia(BioMed Central Ltd, 2025-12-01) Ojeda A; Deblais L; Mummed B; Brhane M; Hassen KA; Ahmedo BU; Weldesenbet YD; Chen D; Li X; Saleem C; Manary MJ; Roesch LFW; McKune SL; Havelaar AH; Rajashekara G; CAGED Research TeamBackground: Campylobacter infections pose a significant challenge in low- and middle-income countries, contributing to child mortality. Campylobacter is linked to acute gastrointestinal illness and severe long-term consequences, including environmental enteric dysfunction (EED) and stunting. In 2018, our cross-sectional study in Ethiopia detected Campylobacter in 88% of stools from children aged 12–15 months, with an average of 11 species per stool using meta-total RNA sequencing. Building on these findings, we conducted a longitudinal study (December 2020–June 2022) to investigate Campylobacter colonization of infants and identify reservoirs and risk factors in rural eastern Ethiopia. Results: After a preliminary screening of 15 Campylobacter species using species-specific quantitative PCR, we analyzed four target species in 2045 samples from infants (first month to just one year of life) and biannual samples from mothers, siblings, and livestock (goats, cattle, sheep, and chickens). Candidatus C. infans (41%), C. jejuni (26%), and C. upsaliensis (13%) were identified as the predominant in the infant gut. Colonization of C. infans and C.jejuni increased (C. infans: 0.85%, C. jejuni-0.98% increase/ day in the odds of colonization) and abundance (P = 0.027, 0.024) with age. Enteric symptoms were strongly associated with C. infans (diarrhea: OR = 2.02 [95%CI: 35%,100%]; fever: OR = 1.62 [95%CI: 14%, 83%]) and C. jejuni (diarrhea: OR = 2.29 [95%CI: 46%,100%], fever: OR = 2.53 [95%CI: 56%,100%]). Based on linear mixed models, we found elevated cumulative loads of C. infans load in infants (especially females OR = 1.5 [95%CI: 10%, 67%]), consuming raw milk (OR = 2.3 [95%CI: 24%,100%]) or those exposed to areas contaminated with animal droppings (OR = 1.6 [95%CI: 7%,93%]), while C. jejuni cumulative loads were higher in infants ingesting soil or animal feces (OR = 2.2 [95%CI: 23%,100%]). C. infans was also prevalent in siblings (56%) and mothers (45%), whereas C. jejuni was common in chickens (38%) and small ruminants (goats 27%, sheep 21%). Conclusions: Campylobacter was highly prevalent in rural Ethiopian infants. C. infans was primarily associated with human hosts, and C. jejuni was mainly linked to zoonotic sources. Our findings emphasize the need for targeted interventions addressing environmental, dietary, and behavioral factors to reduce Campylobacter transmission in resource-limited settings.Item Comprehensive analysis of molecular characteristics between primary and breast-derived metastatic ovarian cancer(AME Publishing Company, 2025-03-30) Long J; Liu B; Li J; Ji X; Zhu N; Zhuang X; Wang H; Li L; Chen Y; Li X; Zhao SBackground: The molecular basis for the disparities between primary ovarian cancer (POC) and ovarian cancer secondary to breast cancer (OCSTBC) remains poorly understood. This study aimed to explore the different characteristics between them through genomic analysis. Methods: We performed differentially expressed genes (DEGs) analysis between POC (n=96) and OCSTBC (n=44) groups with transcriptome data and revealed the enriched biological pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Hallmark gene sets between these two groups. Then, the Microenvironment Cell Populations (MCP)-counter and Cell-type Identification by Estimating Relative Subsets of RNA Transcript (CIBERSORT) algorithms were applied to evaluate the immune infiltration in tumor microenvironment (TME) between them. Finally, we performed the association analysis within single nucleotide polymorphism (SNP) data and obtained some meaningful SNPs and candidate genes for further transcriptomic analysis. Results: We identified a total of 13 cancer-related genes including GATA3, FOXA1, CCND1, and TTK between POC (n=96) and OCSTBC (n=44) groups with DEGs analysis. Integrated analysis revealed more significant immune-enriched pathways in the POC than in the OCSTBC group. Most immune cells had higher infiltration abundance in POC, except M2 macrophages, which was higher in OCSTBC. In SNP analysis, four SNP regions (8q12.1, 11q21, 11q24.3, and 17q25.3) were found to be significantly correlated with phenotypes (POC/OCSTBC), and importantly, some new susceptibility genes such as ETS1, CWC15, and XKR4 were revealed to potentially be associated with distinction between POC and OCSTBC. Conclusions: Our study provides a systematic molecular characteristic between POC and OCSTBC and suggests a pressing need to develop some specific therapeutic strategies in certain types of ovarian cancer.Item Transmission pathways of Campylobacter jejuni between humans and livestock in rural Ethiopia are highly complex and interdependent(BioMed Central Limited, London, United Kingdom, 2025-12-01) Singh N; Thystrup CAN; Hassen BM; Bhandari M; Rajashekara G; Hald TM; Manary MJ; McKune SL; Hassen JY; Smith HL; Marshall JC; French NP; Havelaar AH; Mekuria ZH; Weldesenbet YD; Yang Y; Li X; Gebreyes W; Shaikh N; Bhrane M; Dawid MM; Usmail MM; Deblais L; Mechlowitz K; Umer KA; Roba KT; Hassen KA; Amin JK; Usmane IA; Ahmed IA; Yimer G; Yusuf EA; Chen D; Saleem C; Ahmedo BU; Ojeda AE; Ibrahim AM; Seran AJBackground: Campylobacter jejuni and C. coli are the most common causes of bacterial enteritis worldwide whereas symptomatic and asymptomatic infections are associated with stunting in children in low- and middle-income countries. Little is known about their sources and transmission pathways in low- and middle-income countries, and particularly for infants and young children. We assessed the genomic diversity of C. jejuni in Eastern Ethiopia to determine the attribution of infections in infants under 1 year of age to livestock (chickens, cattle, goats and sheep) and other humans (siblings, mothers). Results: Among 287 C. jejuni isolates, 48 seven-gene sequence types (STs), including 11 previously unreported STs were identified. Within an ST, the core genome STs of multiple isolates differed in fewer than five alleles. Many of these isolates do not belong to the most common STs reported in high-resource settings, and of the six most common global STs, only ST50 was found in our study area. Isolates from the same infant sample were closely related, while those from consecutive infant samples often displayed different STs, suggesting rapid clearance and new infection. Four different attribution models using different genomic profiling methods, assumptions and estimation methods predicted that chickens are the primary reservoir for infant infections. Infections from chickens are transmitted with or without other humans (mothers, siblings) as intermediate sources. Model predictions differed in terms of the relative importance of cattle versus small ruminants as additional sources. Conclusions: The transmission pathways of C. jejuni in our study area are highly complex and interdependent. While chickens are the most important reservoir of C. jejuni, ruminant reservoirs also contribute to the infections. The currently nonculturable species Candidatus C. infans is also highly prevalent in infants and is likely anthroponotic. Efforts to reduce the colonization of infants with Campylobacter and ultimately stunting in low-resource settings are best aimed at protecting proximate sources such as caretakers’ hands, food and indoor soil through tight integration of the currently siloed domains of nutrition, food safety and water, sanitation and hygiene.Item Campylobacter colonization and undernutrition in infants in rural eastern Ethiopia - a longitudinal community-based birth cohort study.(Frontiers Media S.A., 2025-01-07) Chen D; McKune SL; Yang Y; Usmane IA; Ahmed IA; Amin JK; Ibrahim AM; Seran AJ; Shaik N; Ojeda A; Hassen BM; Deblais L; Ahmedo BU; Hassen KA; Bhrane M; Li X; Singh N; Roba KT; French NP; Rajashekara G; Manary MJ; Hassen JY; Havelaar AH; CAGED Research TeamBackground: Campylobacter is associated with environmental enteric dysfunction (EED) and malnutrition in children. Campylobacter infection could be a linchpin between livestock fecal exposure and health outcomes in low-resource smallholder settings. Methods: We followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and Campylobacter spp. was quantified using genus-specific qPCR. In month 13, we collected stool and urine samples to assay for EED biomarkers. We employed regression analyses to assess the associations of household determinants with Campylobacter colonization, EED, and growth faltering. Results: The Campylobacter load in infant stools increased with age. The mean length-for-age Z-score (LAZ) decreased from −0.45 at 3–4 months of age to −2.06 at 13 months, while the prevalence of stunting increased from 3 to 51%. The prevalence of EED at 13 months of age was 56%. A higher Campylobacter load was associated with more frequent diarrhea. Prelacteal feeding significantly increased Campylobacter load in the first month of life. Over the whole follow-up period, Campylobacter load was increased by keeping chickens unconfined at home and unsanitary disposal of infant stools while decreased by mothers’ handwashing with soap. Longitudinally, Campylobacter load was positively associated with food insecurity, introduction of complementary foods, and raw milk consumption. There were no significant associations between Campylobacter load, EED, and LAZ. Conclusion: This study found that most determinants associated with increased Campylobacter infection were related to suboptimal feeding practices and hygiene. The findings related to livestock-associated risks were inconclusive. Although stunting, EED, and Campylobacter prevalence rates all increased to high levels by the end of the first year of life, no significant association between them was identified. While additional research is needed to investigate whether findings from this study are replicable in other populations, community efforts to improve infant and young child feeding practices and food hygiene, and water, sanitation, and hygiene (WaSH) at the household level, could reduce (cross-)contamination at the point of exposure.Item Simultaneous Whole-Chamber Non-contact Mapping of Highest Dominant Frequency Sites During Persistent Atrial Fibrillation: A Prospective Ablation Study(Frontiers Media S.A., 2022-03-16) Chu GS; Li X; Stafford PJ; Vanheusden FJ; Salinet JL; Almeida TP; Dastagir N; Sandilands AJ; Kirchhof P; Schlindwein FS; Ng GA; Ng FSPURPOSE: Sites of highest dominant frequency (HDF) are implicated by many proposed mechanisms underlying persistent atrial fibrillation (persAF). We hypothesized that prospectively identifying and ablating dynamic left atrial HDF sites would favorably impact the electrophysiological substrate of persAF. We aim to assess the feasibility of prospectively identifying HDF sites by global simultaneous left atrial mapping. METHODS: PersAF patients with no prior ablation history underwent global simultaneous left atrial non-contact mapping. 30 s of electrograms recorded during AF were exported into a bespoke MATLAB interface to identify HDF regions, which were then targeted for ablation, prior to pulmonary vein isolation. Following ablation of each region, change in AF cycle length (AFCL) was documented (≥ 10 ms considered significant). Baseline isopotential maps of ablated regions were retrospectively analyzed looking for rotors and focal activation or extinction events. RESULTS: A total of 51 HDF regions were identified and ablated in 10 patients (median DF 5.8Hz, range 4.4-7.1Hz). An increase in AFCL of was seen in 20 of the 51 regions (39%), including AF termination in 4 patients. 5 out of 10 patients (including the 4 patients where AF termination occurred with HDF-guided ablation) were free from AF recurrence at 1 year. The proportion of HDF occurrences in an ablated region was not associated with change in AFCL (τ = 0.11, p = 0.24). Regions where AFCL decreased by 10 ms or more (i.e., AF disorganization) after ablation also showed lowest baseline spectral organization (p < 0.033 for any comparison). Considering all ablated regions, the average proportion of HDF events which were also HRI events was 8.0 ± 13%. Focal activations predominated (537/1253 events) in the ablated regions on isopotential maps, were modestly associated with the proportion of HDF occurrences represented by the ablated region (Kendall's τ = 0.40, p < 0.0001), and very strongly associated with focal extinction events (τ = 0.79, p < 0.0001). Rotors were rare (4/1253 events). CONCLUSION: Targeting dynamic HDF sites is feasible and can be efficacious, but lacks specificity in identifying relevant human persAF substrate. Spectral organization may have an adjunctive role in preventing unnecessary substrate ablation. Dynamic HDF sites are not associated with observable rotational activity on isopotential mapping, but epi-endocardial breakthroughs could be contributory.Item Clonostachys rosea Promotes Root Growth in Tomato by Secreting Auxin Produced through the Tryptamine Pathway(MDPI (Basel, Switzerland), 2022-11-04) Han Z; Ghanizadeh H; Zhang H; Li X; Li T; Wang Q; Liu J; Wang A; Feng M-GClonostachys rosea (Link) Schroers is a filamentous fungus that has been widely used for biological control, biological fermentation, biodegradation and bioenergy. In this research, we investigated the impact of this fungus on root growth in tomato and the underlying mechanisms. The results showed that C. rosea can promote root growth in tomato, and tryptophan enhances its growth-promoting impacts. The results also showed that tryptophan increases the abundance of metabolites in C. rosea, with auxin (IAA) and auxin-related metabolites representing a majority of the highly abundant metabolites in the presence of tryptophan. It was noted that C. rosea could metabolize tryptophan into tryptamine (TRA) and indole-3-acetaldehyde (IAAId), and these two compounds are used by C. rosea to produce IAA through the tryptamine (TAM) pathway, which is one of the major pathways in tryptophan-dependent IAA biosynthesis. The IAA produced is used by C. rosea to promote root growth in tomato. To the best of our knowledge, this is the first report on IAA biosynthesis by C. rosea through the TAM pathway. More research is needed to understand the molecular mechanisms underlying IAA biosynthesis in C. rosea, as well as to examine the ability of this fungus to boost plant development in the field.Item Evaluating spatial disparities of rotor sites and high dominant frequency regions during catheter ablation for PersAF patients targeting high dominant frequency sites using non-contacting mapping(Frontiers Media S.A., 2022-08-05) Ehnesh M; Li X; Almeida TP; Chu GS; Dastagir N; Stafford PJ; Ng GA; Schlindwein FS; Martínez JPPurpose: Several studies have emphasised the significance of high dominant frequency (HDF) and rotors in the perpetuation of AF. However, the co-localisation relationship between both attributes is not completely understood yet. In this study, we aim to evaluate the spatial distributions of HDF regions and rotor sites within the left atrium (LA) pre and post HDF-guided ablation in PersAF. Methods: This study involved 10 PersAF patients undergoing catheter ablation targeting HDF regions in the LA. 2048-channels of atrial electrograms (AEG) were collected pre- and post-ablation using a non-contact array (EnSite, Abbott). The dominant frequency (DF, 4-10 Hz) areas with DF within 0.25 Hz of the maximum out of the 2048 points were defined as "high" DF (HDF). Rotors were defined as PSs that last more than 100 ms and at a similar location through subsequent phase frames over time. Results: The results indicated an extremely poor spatial correlation between the HDF regions and sites of the rotors in pre-versus post-ablation cases for the non-terminated (pre: CORR; 0.05 ± 0.17. vs. post: CORR; -0.030 ± 0.19, and with terminated patients (pre: CORR; -0.016 ± 0.03. post: CORR; -0.022 ± 0.04). Rotors associated with AF terminations had a long-lasting life-span post-ablation (non-terminated vs. terminated 120.7 ± 6.5 ms vs. 139.9 ± 39.8 ms), high core velocity (1.35 ± 1.3 mm/ms vs. 1.32 ± 0.9 mm/ms), and were less meandering (3.4 ± 3.04 mm vs. 1.5 ± 1.2 mm). Although the results suggest a poor spatial overlapping between rotors' sites and sites of AFCL changes in terminated and non-terminated patients, a higher correlation was determined in terminated patients (spatial overlapping percentage pre: 25 ± 4.2% vs. 17 ± 3.8% vs. post: 8 ± 4.2% vs. 3.7 ± 1.7% p < 0.05, respectively). Conclusion: Using non-contact AEG, it was noted that the correlation is poor between the spatial distribution of HDF regions and sites of rotors. Rotors were longer-lasting, faster and more stationary in patients with AF termination post-ablation. Rotors sites demonstrated poor spatial overlapping with sites of AFCL changes that lead to AF termination.Item A Study of the Interaction, Morphology, and Structure in Trypsin-Epigallocatechin-3-Gallate Complexes(MDPI (Basel, Switzerland), 2021-07-28) Liu J; Ghanizadeh H; Li X; Han Z; Qiu Y; Zhang Y; Chen X; Wang A; Tresserra-Rimbau A; Bresciani LUnderstanding the interaction between proteins and polyphenols is of significance to food industries. The aim of this research was to investigate the mode of aggregation for trypsin-EGCG (Epigallocatechin-3-gallate) complexes. For this, the complex was characterized by fluorescence spectroscopy, circular dichroism (CD) spectra, small-angel X-ray scattering (SAXS), and atomic force microscope (AFM) techniques. The results showed that the fluorescence intensity of trypsin-EGCG complexes decreased with increasing the concentration of EGCG, indicating that the interaction between trypsin and EGCG resulted in changes in the microenvironment around fluorescent amino acid residues. The results of CD analysis showed conformational changes in trypsin after binding with EGCG. The results from SAXS analysis showed that the addition of EGCG results in the formation of aggregates of trypsin-EGCG complexes, and increasing the concentration of EGCG resulted in larger aggregates. AFM images showed that the trypsin-EGCG complex formed aggregates of irregular ellipsoidal shapes with the size of about 200 × 400 × 200 nm, with EGCG interconnecting the trypsin particles. Overall, according to these results, it was concluded that the large aggregates of trypsin-EGCG complexes are formed from several small aggregates that are interconnected. The results of this study shed some light on the interaction between digestive enzymes and EGCG.Item Biochar and soil properties limit the phytoavailability of lead and cadmium by Brassica chinensis L. in contaminated soils(Springer Nature on behalf of the Shenyang Agricultural University, 2022-12) Houssou AA; Jeyakumar P; Niazi NK; Van Zwieten L; Li X; Huang L; Wei L; Zheng X; Huang Q; Huang Y; Huang X; Wang H; Liu Z; Huang ZThe current study investigated the effect of biochars derived from cinnamomum woodchip, garden waste and mulberry woodchip on soil phytoavailable lead (Pb), cadmium (Cd) pools, and their uptake by Chinese cabbage (Brassica chinensis L.). The biochars were produced at 450 °C of pyrolysis temperature. The contaminated soils were collected from Yunfu (classified as Udept), Jiyuan (Ustalf) and Shaoguan (Udult) cities in China at the depth of 0–20 cm and amended with biochars at the rate of 3% w/w. After mixing the soil with biochar for 14 days, the Chinese cabbage was planted in the amended soils. Then, it was harvested on the 48th day after sowing period. In Udult soil, Chinese cabbage died 18 days after sowing period in control and soils amended with cinnamomum and mulberry biochars. Although only plants grown with the garden waste biochar treatment survived in Udult soil, amendment of garden waste or mulberry biochars at 3% w/w (450 °C) to Udult soil significantly increased (4.95–6.25) soil pH compared to other biochar treatments. In Udept and Ustalf soils, the application of garden waste and mulberry biochars significantly improved plant biomass compared to control, albeit it was dependent on both biochar and soil properties. Garden waste biochar significantly decreased soil Cd phytoavailable concentration by 26% in the Udult soil, while a decrease of soil Cd phytoavailable concentration by 16% and 9% was observed in Ustalf and Udept soils, respectively. The available phosphorus in biochar and soil pH were important factors controlling toxic metal phytouptake by the plant. Thus, the amendment of soil with biochar at 3% can effectively reduce the mobility of Cd and Pb in soil and plant uptake. However, biochar and soil properties should be well-known before being used for soil toxic metal immobilization.Item Tsunami or storm deposit? A late Holocene sedimentary record from Swamp Bay, Rangitoto ki te Tonga/D’Urville Island, Aotearoa–New Zealand(Taylor and Francis Group, 2023) King DN; Clark K; Chagué C; Li X; Lane E; McFadgen BG; Hippolite J; Meihana P; Wilson B; Dobson J; Geiger P; Robb H; Hikuroa D; Williams S; Morgenstern R; Scheele FInformed by Māori oral histories that refer to past catastrophic marine inundations, multi-proxy analysis of stratigraphic records from Swamp Bay, Rangitoto ki te Tonga (D’Urville Island) shows evidence of an anomalous deposit extending some 160 m inland. The deposit includes two distinct lithofacies. The lower sand unit is inferred to have been transported from the marine environment, with corresponding increases in the percentages of benthic marine and brackish–marine diatoms, and geochemical properties indicative of sudden changes in environmental conditions. Radiocarbon dating indicates the deposit formation is less than 402 yrs BP, and pollen indicates it is unlikely to be younger than 1870 CE. Core stratigraphy age models and co-seismic chronologies point to the marine unit most likely being emplaced by tsunami transport associated with rupture of the Wairarapa Fault in 1855 CE. The overlying unit of gravel and silt is inferred to be fluvial deposit and slope-wash from the surrounding hills, loosened by ground-shaking following the earthquake. These findings indicate the 1855 CE earthquake may have been more complex than previously thought and, or, available tsunami modelling does not fully capture the local complexities in bathymetry and topography that can cause hazardous and localized tsunami amplification in embayments like Swamp Bay.