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Mitochondrial abnormalities in lung epithelial cells have been associated with chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke (CS) can induce alterations in the molecular pathways regulating mitochondrial function in lung epithelial cells. Recently, heated tobacco products (HTPs) have been marketed as harm reduction products compared with regular cigarettes. However, the effects of HTP emissions on human alveolar epithelial cell metabolism and on the molecular mechanisms regulating mitochondrial content and function are unclear. In this study, human alveolar epithelial cells (A549) were exposed to cigarette or HTP emissions in the form of liquid extracts. The oxygen consumption rate of differently exposed cells was measured, and mRNA and protein abundancy of key molecules involved in the molecular regulation of mitochondrial metabolism were assessed. Furthermore, we used a mitophagy detection probe to visualize mitochondrial breakdown over time in response to the extracts. Both types of extracts induced increases in basal-, maximal- and spare respiratory capacity, as well as in cellular ATP production. Moreover, we observed alterations in the abundancy of regulatory molecules controlling mitochondrial biogenesis and mitophagy. Mitophagy was not significantly altered in response to the extracts, as no significant differences compared to vehicle-treated cells were observed., Competing Interests: Declaration of Competing Interest The authors of the manuscript: ‘Alterations in the molecular regulation of mitochondrial metabolism in human alveolar epithelial cells in response to cigarette- and heated tobacco product emissions’ have declared no conflict of interest and no present or past affiliation with the tobacco industry., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The hypothalamus-pituitary-adrenal axis (HPA axis) and the sympathetic-adrenal-medullary system (SAM system), two neuroendocrine systems associated with the stress response, have often been implicated to modulate decision-making in various domains. This systematic review summarizes the scientific evidence on the effects of pharmacological HPA axis and SAM system modulation on decision-making. We found 6375 references, of which 17 studies fulfilled our inclusion criteria. We quantified the risk of bias in our results with respect to missing outcome data, measurements, and selection of the reported results. The included studies administered hydrocortisone, fludrocortisone (HPA axis stimulants), yohimbine, reboxetine (SAM system stimulants), and/or propranolol (SAM system inhibitor). Integrating the evidence, we found that SAM system stimulation had no impact on risk aversion, loss aversion or intertemporal choice, while SAM system inhibition showed a tentative reduction in sensitivity to losses. HPA axis stimulation had no effect on loss aversion or reward anticipation but likely a time-dependent effect on decision under risk. Lastly, combined stimulation of both systems exhibited inconsistent results that could be explained by dose differences (loss aversion) and sex differences (risk aversion). Future research should address time-, dose-, and sex-dependencies of pharmacological effects on decision-making., (© The Author(s) 2024. Published by Oxford University Press.)

Phytoplasmas are obligate phytopathogenic bacteria belonging to the class Mollicutes. The pathogens, transmitted by insect vectors, associated with hundreds of plant diseases worldwide. Due to the regulation on banning use of antibiotics and limited efficacy of the traditional disease management manners, an eco-friendly alternative is needed. Given that terpene and probiotics have antibiotic activity and the ability to induce systemic resistance, in this study, the effectiveness of orange terpene and a Bacillus mycoides strain, BM103, was evaluated in periwinkle plants infected with periwinkle leaf yellowing (PLY) phytoplasma derived from a shoot-tip tissue culture system. Weekly drenching of 1,000 ppm diluted orange terpene emulsion or pre-activated strain BM103 liquid culture dilution exhibited the ability to inhibit PLY phytoplasma accumulation. The expression of the genes associated with plant defense response and flower development was upregulated after treatment. Moreover, pre-treatment of orange terpene or strain BM103 delayed PLY infection via cleft-grafting inoculation. While orange terpene did not suppress the symptoms, strain BM103 did result in a milder symptom expression that might partially attribute to its plant growth-promoting characteristics. Additionally, the pre-activation of strain BM103 may contribute to its efficacy. Taken together, this research indicates that orange terpene and B. mycoides BM103, with the ability to rapidly induce plant defense responses, could potentially be developed into biological control materials as preventive agents or biofertilizers.

Introduction: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers., Objectives: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population., Methods: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy ® OMNI ® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching., Results: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes., Conclusions: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization., (© 2024. The Author(s).)

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment., (© 2024. The Author(s).)

A comprehensive evaluation, including symptoms, medical history, C-peptide levels, and anti-GAD antibodies, is essential for distinguishing between diabetes' types, particularly in cases of diagnostic uncertainty. While obesity is often associated with T2DM, BMI should be viewed as a factor rather than a criterion for the exclusion of diabetes type., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: Achieving urinary continence is a key goal in children born with the bladder exstrophy-epispadias complex (BEEC). Unfortunately, this goal is only moderately achieved despite sometimes extensive surgical treatment. Undergoing repeated hospitalization and operations may consequently have a negative impact on quality of life. We therefore believe that other, conservative treatment options should be explored in an earlier stage of incontinence treatment in BEEC patients. As part of this, an intensive urotherapy program based on was offered to patients with persistent incontinence after reconstructive surgery for BEEC., Objective: The aim of this study is to evaluate the benefits of intensive urotherapy on incontinence after reconstructive surgery in children with BEEC., Study Design: A retrospective chart study was performed including all children who were enrolled in an intensive urotherapy program because of persistent incontinence after reconstructive surgery for BEEC. Urotherapy consisted of a ten-day inpatient training program based on cognitive behavioral therapy, with intensive follow-up by experienced urotherapists. Main outcome measurement was continence, expressed as the percentage of children that achieved complete continence (good result; 100% dry) or 50-99% decrease of wet days a week (improved result) after treatment., Results: Data of 33 patients with a mean age of 10.6 years were analyzed. In 61% of cases (20/33) an improved or good result was reported on incontinence after urotherapy. Children with classic bladder exstrophy more often achieved a good or improved result (13/16; 81%), compared to children with epispadias (6/16; 38%). The only patient with a cloacal exstrophy completed treatment with an improved result. From the group of patients with persistent incontinence, 75% (12/16) reported that the complaints were socially acceptable at the end of follow-up., Discussion: By following our intensive urotherapy program the majority of patients achieved complete continence or improved incontinence. In addition, our results show that the inpatient training program has a positive impact on acceptance in cases of persistent incontinence. The urotherapists offer individualized care and clear guidance, which we deem essential elements of successful treatment. Considering that repeated surgery may impede progress and offers no guarantee of continence, we recommend giving preference to conservative treatment options., Conclusion: Our results show that 37% (12/33) of patients with BEEC who were enrolled in our intensive urotherapy program because of persistent incontinence after reconstructive surgery, achieved complete continence after urotherapy and 63% (21/33) still experienced some degree of incontinence. 75% of patients who did not achieve complete continence, described the remaining incontinence as socially acceptable. These findings strongly support counselling patients with BEEC to consider conservative treatment before opting for further surgery., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Our objective is to predict the cumulative live birth rate (CLBR) and identify the specific subset within the population undergoing preimplantation genetic testing for monogenic disorders (PGT-M) and chromosomal structural rearrangements (PGT-SR) which is likely to exhibit a diminished expected CLBR based on various patient demographics., Methods: We performed a single-centre retrospective cohort study including 1522 women undergoing 3130 PGT cycles at a referral centre for PGT. A logistic regression analysis was performed to predict the CLBR per ovarian stimulation in women undergoing PGT-M by polymerase chain reaction (PCR) or single-nucleotide polymorphism (SNP) array, and in women undergoing PGT-SR by SNP array, array comparative genomic hybridization (CGH) or next-generation sequencing (NGS)., Results: The mean age of women was 32.6 years, with a mean AMH of 2.75 µg/L. Female age and AMH significantly affected the expected CLBR irrespective of the inheritance mode or PGT technology. An expected CLBR < 10% was reached above the age of 42 years and AMH ≤ 1.25 µg/L. We found no significant difference in outcome per ovarian stimulation between the different PGT technologies, i.e. PCR, SNP array, array CGH and NGS. Whereas per embryo transfer, we noticed a significantly higher probability of live birth when SNP array, array CGH and NGS were used as compared to PCR., Conclusion: In a PGT-setting, couples with an unfavourable female age and AMH should be informed of the prognosis to allow other reproductive choices. The heatmap produced in this study can be used as a visual tool for PGT couples., (© 2024. The Author(s).)

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications., Learning Points: The reduction in insulin doses combined with the introduction of an SGLT2 inhibitor in a patient with type 1 diabetes may lead to the development of a dangerous health complication known as euglycemic diabetic ketoacidosis.In cases of diagnostic uncertainty regarding the differentiation of diabetes types, measuring the levels of C-peptide and anti-GAD antibodies can be helpful.Abnormal glycaemic results in a patient using insulin may result from improper administration. During follow-up visits, it is worthwhile to check the subcutaneous tissue for lipodystrophy and also remind the patient about the necessity of rotating insulin injection sites., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Ipomoea biflora L., commonly known as morning glory, is an herbaceous vine plant in the Convolvulaceae family and is widespread at low elevations in Taiwan and other East Asian countries. In September 2023, six I. biflora plants exhibiting small leaves, leaf yellowing, and shoot proliferation were observed in a vacant lot in Taiwan Agricultural Research Institute (TARI), Wufeng District, Taichung, Taiwan, representing 100% disease incidence in the area. All the symptomatic morning glory climbed onto Murraya paniculata L. (common jasmine orange) which however showed no similar symptoms. The total DNA (two samples for each plant) from leaf tissues of three symptomatic morning glory plants, two asymptomatic morning glory plants, and one asymptomatic common jasmine orange was isolated by the CTAB method (Fulton et al. 1995) and used for PCR with the universal primers, P1 (Deng and Hiruki 1991)/P7 (Schneider et al. 1995), to amplify a fragment containing partial 16S rDNA. Expected 1.8-kb bands were amplified from DNA extracted from all symptomatic plants, whereas no PCR product was detected from that of the asymptomatic I.biflora and M. paniculata plants. Six PCR products were cloned and sequenced in the Biotechnology Center DNA-sequencing facility at National Chung Hsing University, and one representative sequence was selected and deposited in GenBank. BLAST analysis revealed that the obtained 16S rDNA sequence (PP230905) shared 99.92% identity with the following phytoplasma strains: rapeseed phyllody phytoplasma (CP055264), plumbago auriculata leaf yellowing phytoplasma (MN239503), and aster yellows phytoplasma (MK992774), which all belong to the 16SrI subgroup. The query 16S rDNA sequence shares 99.84% identity with that of the 'Candidatus Phytoplasma asteris' reference strain (M30790), suggesting that the phytoplasma is a 'Ca. Phytoplasma asteris'-related strain. A virtual restriction fragment length polymorphism (RFLP) analysis was conducted using iPhyClassifier tool (Zhao et al. 2009), and the pattern derived from the 16S rDNA fragment of the I. biflora phytoplasma was identical (similarity coefficient 1.00) to the reference pattern of 16SrI, subgroup B (onion yellows phytoplasma OY-M; AP006628). Six total DNA samples from symptomatic plants were used as templates to amplify 842 bp secA sequences with SecAfor1 and SecArev3 primers (Hodgetts et al. 2008), and one representative sequence was deposited in GenBank. The partial secA sequence (PP263636) showed 98.22% identity with that of Trema levigatum witches'-broom phytoplasma (MW032212) that also belongs to the 16SrI group (Wan et al. 2021). Phylogenetic analysis of both 16S rDNA and secA confirmed I. biflora phytoplasma as 16SrI, subgroup B. Taken together, we concluded that the morning glory phytoplasma in this study was a 'Ca. Phytoplasma asteris'-related strain belonging to the 16SrI group. To the best of our knowledge, this is the first report of a phytoplasma-infected I. biflora in Taiwan, suggesting morning glory as a new natural host of 16SrI phytoplasmas, alongside other plants like roselle and citrus (Tseng et al. 2014; Feng et al. 2015).

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. PSC is a complex disease of largely unknown aetiology that is strongly associated with inflammatory bowel disease (IBD). Diagnosis, especially at an early stage, is difficult and to date there is no diagnostic biomarker. The present study aimed to assess the diagnostic potential of volatile organic compounds (VOCs) in exhaled breath to detect (early) PSC in an IBD population., Methods: Breath samples were obtained from 16 patients with PSC alone, 47 with PSC and IBD, and 53 with IBD alone during outpatient clinic visits. Breath sampling was performed using the ReCIVA breath sampler and subsequently analysed by gas chromatography mass spectrometry. Random forest modelling was performed to find discriminatory VOCs and create a predictive model that was tested using an independent test set., Results: The final model to discriminate patients with PSC, with or without IBD, from patients with IBD alone included twenty VOCs and achieved a sensitivity, specificity, and area under the receiver-operating curve on the test set of 77%, 83%, and 0.84 respectively. Three VOCs (isoprene, 2-octanone and undecane) together correlated significantly with the Amsterdam-Oxford score for PSC disease prognosis. A sensitivity analysis showed stable results across early-stage PSC, including in those with normal alkaline phosphatase levels, as well as further progressed PSC., Conclusion: The present study demonstrates that exhaled breath can distinguish PSC cases from IBD and has potential as a non-invasive clinical breath test for (early) PSC., Impact and Implications: Primary sclerosing cholangitis is a complex chronic liver disease, which ultimately results in cirrhosis, liver failure, and death. Detection, especially in early disease stages, can be challenging, and therefore therapy typically starts when there is already some irreversible damage. The current study shows that metabolites in exhaled breath, so called volatile organic compounds, hold promise to non-invasively detect primary sclerosing cholangitis, including at early disease stages., (© 2024 The Author(s).)

Introduction: IQOS HEETS are promoted as reduced-risk alternatives to cigarettes. Although some studies have investigated the chemical composition of HEETS emissions, little is known on whether toxicant levels in such emissions are affected by different puffing parameters and flavor varieties. This has important implications when assessing actual human exposure, since IQOS users develop a specific and personalized puffing behavior and may use different HEETS variants., Methods: This study measured the levels of nicotine, total particulate matter, carbonyl compounds, and tobacco-specific nitrosamines (TSNAs) in the emissions of nine differently flavored HEETS and two cigarettes (1R6F and Marlboro Red, MR). Emissions from Yellow HEETS, 1R6F, and MR were collected using the World Health Organization Intense smoking regime and four more intense smoking regimes., Results: Yellow HEETS aerosol contained lower levels of toxicants compared to 1R6F and MR smoke. More intense smoking regimes increased carbonyl release in cigarette smoke, whereas only higher puff frequency led to lower levels of toxicants in Yellow HEETS aerosol. Some HEETS varieties exhibited higher levels of formaldehyde and TSNAs in their aerosols compared to Yellow HEETS., Conclusions: Puff frequency was identified as the only smoking parameter that significantly lowered the release of almost all toxicants in Yellow HEETS, whereas a combination of higher puff volume and puff duration led to increased levels of some carbonyls. Differences in toxicant levels between various commercially available HEETS have important implications when assessing their health impact, as their consumption might induce different toxicant exposure and health effects., Implications: HEETS release about half as much nicotine and substantially lower levels of toxicants compared to cigarettes. Literature data showed that puffing intensity is increased in cigarette smokers switching to HEETS, maybe in reaction to these lower nicotine levels. Our results show a differential impact of increased puff frequency, puff duration, and puff volume in the release of toxicants from HEETS. Thus, industry-independent studies on puff topography are critical to make choices for the most relevant puffing regime for heated tobacco product regulation. Regulators should consider evaluating the health impact of multiple HEETS varieties, as the tobacco filler composition significantly affects the release of certain toxicants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Owing to the high cost of recycling waste, underdeveloped countries discharge industrial, agricultural, and anthropogenic effluents without pretreatment. As a result, pollutant-loaded waste enters water bodies. Among the diverse toxic contaminants, heavy metal ions are the most detrimental because of their chronic toxicity, non-degradability, prevalence, and bioaccumulation. The growing shortage of water resources demands the removal of heavy metal ions from wastewater. Three SDGs of the sustainability agenda of the United Nations appeal for clean water to protect life beneath water and on land depending on the water sources. Therefore, efficient environmentally friendly approaches for wastewater treatment are urgently required. In this regard, several methods have been developed for the removal of heavy metal ions from wastewater, including adsorption as the most widely used method owing to its eco-friendly, cost-effective, and sustainable nature. The present review discusses the progress in the preparation and application of various adsorbents based on carbon, micro-organisms, agricultural waste and inorganic materials for the extraction of toxic metal ions such as Pb 2+ , Cr 6+ , As 3+ , As 5+ , Hg 2+ and Cd 2+ . Herein, we provide information on the role of the homogeneity and heterogeneity of adsorbents, kinetics of the adsorption of an adsorbate on the surface of an adsorbent, insights into adsorption reaction pathways, the mechanism of the sorption process, and the uptake of solutes from solution. The present review will be useful for researchers working on environmental protection and clean environment., Competing Interests: Authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4-7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established., (© 2024. The Author(s).)

Chrysanthemum morifolium (Asteraceae) is commonly grown as commercial cut flowers or pot mums worldwide. Common diseases of chrysanthemum include bacterial blight, fungal diseases, viruses, and phytoplasmas (Verma et al. 2003; Taloh et al. 2020). In June 2022, C. morifolium plants showing virescence, stunting, witches' broom, and phyllody symptoms were observed in 10 plants representing 10% of the estimated 100 plants in a field in Taichung City, Taiwan (Fig. S1). Three symptomatic samples along with three asymptomatic ones were collected for further study. Nested PCR was performed with two primer sets, P1/P7 (Deng and Hiruki 1991; Schneider et al. 1995) and R16F2n/R16R2 (Gundersen and Lee 1996) to amplify nearly full-length of 16S rDNA from the collected samples. The target 1.2-kb DNA band was only amplified from the symptomatic chrysanthemum plants. The amplicons were sequenced and a representative sequence deposited in GenBank under accession number OR501416. This sequence was used to search GenBank database by the Basic Local Alignment Search Tool (BLAST) program through the web service of National Center for Biotechnology Information (NCBI). In the 16S rDNA analyses, the three randomly picked amplicons from chrysanthemum phyllody phytoplasma (CPP) shared 100% identity with one another, and all shared 99.5% identity with the, 'Candidatus Phytoplasma australasiae' reference phytoplasma strain (Y10097). Further analysis using iPhyClassifier (Wei et al. 2007) revealed that CPP was most similar to the pattern of the peanut witches' broom phytoplasma in the 16SrII-A subgroup (GenBank Acc. No. L33765), with a pattern similarity coefficient of 1.0. For confirmation, the secY gene was amplified by secY-F/R primers (Li et al. 2014), the 1.2-kb band was sequenced and deposit in GenBank (Acc. No. OR508986). BLAST analysis showed that the secY sequence of CPP shared 99.93% of sequence identities to several 'Ca. P. australasiaticum' strains (MN543069, CP097312, CP120449, KC953013, MW085916, MW070030, CP040925). The phylogenetic tree analysis based on the secY gene by MEGA11 employing maximum-likelihood algorithm was performed and the bootstrap value was set as 1000 times for support of the stability for the clades. The result showed that CPP is closely related to other strains in 16SrII group (Fig. S2). Taken together, CPP is a 'Ca. P. australasiaticum' related-strain in 16SrII-A subgroup. This is the first report of chrysanthemum as a host of this phytoplasma in Taiwan, and might have an impact to the horticultural industry and the growers.

Autosomal dominant variants in LRP10 have been identified in patients with Lewy body diseases (LBDs), including Parkinson's disease (PD), Parkinson's disease-dementia (PDD), and dementia with Lewy bodies (DLB). Nevertheless, there is little mechanistic insight into the role of LRP10 in disease pathogenesis. In the brains of control individuals, LRP10 is typically expressed in non-neuronal cells like astrocytes and neurovasculature, but in idiopathic and genetic cases of PD, PDD, and DLB, it is also present in α-synuclein-positive neuronal Lewy bodies. These observations raise the questions of what leads to the accumulation of LRP10 in Lewy bodies and whether a possible interaction between LRP10 and α-synuclein plays a role in disease pathogenesis. Here, we demonstrate that wild-type LRP10 is secreted via extracellular vesicles (EVs) and can be internalised via clathrin-dependent endocytosis. Additionally, we show that LRP10 secretion is highly sensitive to autophagy inhibition, which induces the formation of atypical LRP10 vesicular structures in neurons in human-induced pluripotent stem cells (iPSC)-derived brain organoids. Furthermore, we show that LRP10 overexpression leads to a strong induction of monomeric α-synuclein secretion, together with time-dependent, stress-sensitive changes in intracellular α-synuclein levels. Interestingly, patient-derived astrocytes carrying the c.1424 + 5G > A LRP10 variant secrete aberrant high-molecular-weight species of LRP10 in EV-free media fractions. Finally, we show that this truncated patient-derived LRP10 protein species (LRP10 splice ) binds to wild-type LRP10, reduces LRP10 wild-type levels, and antagonises the effect of LRP10 on α-synuclein levels and distribution. Together, this work provides initial evidence for a possible functional role of LRP10 in LBDs by modulating intra- and extracellular α-synuclein levels, and pathogenic mechanisms linked to the disease-associated c.1424 + 5G > A LRP10 variant, pointing towards potentially important disease mechanisms in LBDs., (© 2024. The Author(s).)

Disease detection and monitoring using volatile organic compounds (VOCs) is becoming increasingly popular. For a variety of (gastrointestinal) diseases the microbiome should be considered. As its output is to large extent volatile, faecal volatilomics carries great potential. One technical limitation is that current faecal headspace analysis requires specialized instrumentation which is costly and typically does not work in harmony with thermal desorption units often utilized in e.g. exhaled breath studies. This lack of harmonization hinders uptake of such analyses by the Volatilomics community. Therefore, this study optimized and compared two recently harmonized faecal headspace sampling platforms: High-capacity Sorptive extraction (HiSorb) probes and the Microchamber thermal extractor (Microchamber) . Statistical design of experiment was applied to find optimal sampling conditions by maximizing reproducibility, the number of VOCs detected, and between subject variation. To foster general applicability those factors were defined using semi-targeted as well as untargeted metabolic profiles. HiSorb probes were found to result in a faster sampling procedure, higher number of detected VOCs, and higher stability. The headspace collection using the Microchamber resulted in a lower number of detected VOCs, longer sampling times and decreased stability despite a smaller number of interfering VOCs and no background signals. Based on the observed profiles, recommendations are provided on pre-processing and study design when using either one of both platforms. Both can be used to perform faecal headspace collection, but altogether HiSorb is recommended., (Creative Commons Attribution license.)

Introduction: Early and reliable determination of bacterial strain specificity and antibiotic resistance is critical to improve sepsis treatment. Previous research demonstrated the potential of headspace analysis of volatile organic compounds (VOCs) to differentiate between various microorganisms associated with pulmonary infections in vitro. This study evaluates whether VOC analysis can also discriminate antibiotic sensitive from resistant bacterial strains when cultured on varying growth media., Methods: Both antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonia were cultured on 4 different growth media, i.e. Brain Heart Infusion, Marine Broth, Müller-Hinton and Trypticase Soy Agar. After overnight incubation at 37°C, the headspace air of the cultures was collected on stainless steel desorption tubes and analyzed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). Statistical analysis was performed using regularized multivariate analysis of variance and cross validation., Results: The three bacterial species could be correctly recognized based on the differential presence of 14 VOCs (p<0.001). This discrimination was not influenced by the different growth media. Interestingly, a clear discrimination could be made between the antibiotic-resistant and -sensitive variant of Pseudomonas aeruginosa (p<0.001) based on their species-specific VOC signature., Conclusion: This study demonstrates that isolated microorganisms, including antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, could be identified based on their excreted VOCs independent of the applied growth media. These findings suggest that the discriminating volatiles are associated with the microorganisms themselves rather than with their growth medium. This study exemplifies the potential of VOC analysis as diagnostic tool in medical microbiology. However, validation of our results in appropriate in vivo models is critical to improve translation of breath analysis to clinical applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hintzen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire., Method: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time., Results: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated ( r = -0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 ( SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [ B ] = -0.15, 95% confidence interval, 95% CI [-0.28, -0.03], effect size = -0.02), whereas CTT-based scores did not ( B = 0.20, 95% CI [-0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar., Conclusions: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores' superior suitability for use in preclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Up to 5% of inflammatory bowel disease patients may at some point develop primary sclerosing cholangitis (PSC). PSC is a rare liver disease that ultimately results in liver damage, cirrhosis and liver failure. It typically remains subclinical until irreversible damage has been inflicted. Hence, it is crucial to screen IBD patients for PSC, but its early detection is challenging, and the disease's etiology is not well understood. This current study aimed at the early detection of PSC in an IBD population using Volatile Organic Compounds in fecal headspace and exhaled breath. To this aim, fecal material and exhaled breath were collected from 73 patients ( n = 16 PSC/IBD; n = 8 PSC; n = 49 IBD), and their volatile profile were analyzed using Gas Chromatography-Mass Spectrometry. Using the most discriminatory features, PSC detection resulted in areas under the ROC curve (AUCs) of 0.83 and 0.84 based on fecal headspace and exhaled breath, respectively. Upon data fusion, the predictive performance increased to AUC 0.92. The observed features in the fecal headspace relate to detrimental microbial dysbiosis and exogenous exposure. Future research should aim for the early detection of PSC in a prospective study design.

The comet assay-based in vitro DNA repair assay has become a common tool for quantifying base excision repair (BER) activity in human lymphocytes or cultured cells. Here, we optimized the protocol for studying BER in human placental tissue because the placenta is a non-invasive tissue for biomonitoring of early-life exposures, and it can be used to investigate molecular mechanisms associated with prenatal disorders. The optimal protein concentration of placental protein extracts for optimal damage recognition and incision was 2 mg protein/mL. The addition of aphidicolin did not lead to reduced non-specific incisions and was, therefore, not included in the optimized protocol. The interval between sample collection and analysis did not affect BER activity up to 70 min. Finally, this optimized protocol was tested on pre-eclamptic (PE) placental tissues ( n = 11) and significantly lower BER activity in PE placentas compared to controls ( n = 9) was observed. This was paralleled by a significant reduction in the expression of BER-related genes and increased DNA oxidation in PE placentas. Our study indicates that BER activity can be determined in placentas, and lower activity is present in PE compared with healthy. These findings should be followed up in prospective clinical investigations to examine BER's role in the advancement of PE.

Background: Organ donation after euthanasia (ODE) has been performed over 100 times in the Netherlands, primarily involving patients suffering from a neurodegenerative or psychiatric disease. In recent years, the number of euthanasia cases related to dementia has increased in the Netherlands, with some patients living with dementia expressing a wish for organ donation after euthanasia., Methods: We describe a unique case of a 67-year-old female diagnosed with primary progressive aphasia as part of frontotemporal dementia who requested and underwent organ donation after euthanasia., Results: The patient had expressed her explicit wishes for both euthanasia and organ donation, which were discussed with her family physician, the Euthanasia Expertise Center (EE), and an organ donation coordinator. The patient was informed that to proceed with ODE, she should still be capable of voicing a voluntary and well-considered request for organ donation. The legally required euthanasia assessment procedure was carefully completed before ODE. Multiple healthcare professionals assessed the patient's competence, voluntariness, and unbearable suffering. Thereafter the patient's ODE request was granted, and both lungs and kidneys were successfully donated and transplanted. Post hoc analysis confirmed that all due diligence criteria for euthanasia were met, and the patient's relatives received an anonymous letter of gratitude from one of the organ recipients., Conclusions: This unique case demonstrates that ODE is feasible from medical, ethical, and legal perspectives in patients living with dementia. This case highlights several aspects essential to enable an ODE request by a patient living with dementia to be granted, such as the role of the physician performing euthanasia, the relevance of the decision-making capacity of the patient, the presence of an advance directive, and the involvement of and support by relatives and caregivers. However, several unresolved ethical issues surrounding ODE in patients with dementia, especially in patients with advanced stages of dementia, warrant further exploration, including the timing of discussing organ donation after the initial euthanasia request., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 van Dijk, Vliegen, Ham, de Jongh, Berkhout, Blankevoort, ten Hoopen, Bollen and van Mook.)

DNA repair is an essential agent in cancer development, progression, prognosis, and response to therapy. We have adapted a cellular repair assay based on the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay to assess DNA repair kinetics. The removal of oxidized nucleobases over time (0-480 min) was analyzed in peripheral blood mononuclear cells (PBMCs) and 8 cell lines. DNA damage was induced by exposure to either Ro19-8022 plus visible light or potassium bromate (KBrO 3 ). The initial amount of damage induced by Ro 19-8022 plus light varied between cell lines, and this was apparently associated with the rate of repair. However, the amount of DNA damage induced by KBrO 3 varied less between cell types, so we used this agent to study the kinetics of DNA repair. We found an early phase of ca. 60 min with fast removal of Fpg-sensitive sites, followed by slower removal over the following 7 h. In conclusion, adjusting the initial damage at T 0 to an equal level can be achieved by the use of KBrO 3 , which allows for accurate analysis of subsequent cellular DNA repair kinetics in the first hour after exposure., (© 2023. The Author(s).)

Background: Despite optimizations of coronary stenting technology, a residual risk of in-stent restenosis (ISR) remains. Vessel wall injury has important impact on the development of ISR. While injury can be assessed in histology, there is no injury score available to be used in clinical practice., Methods: Seven rats underwent abdominal aorta stent implantation. At 4 weeks after implantation, animals were euthanized, and strut indentation, defined as the impression of the strut into the vessel wall, as well as neointimal growth were assessed. Established histological injury scores were assessed to confirm associations between indentation and vessel wall injury. In addition, stent strut indentation was assessed by optical coherence tomography (OCT) in an exemplary clinical case., Results: Stent strut indentation was associated with vessel wall injury in histology. Furthermore, indentation was positively correlated with neointimal thickness, both in the per-strut analysis (r = 0.5579) and in the per-section analysis (r = 0.8620; both p ≤ 0.001). In a clinical case, indentation quantification in OCT was feasible, enabling assessment of injury in vivo., Conclusion: Assessing stent strut indentation enables periprocedural assessment of stent-induced damage in vivo and therefore allows for optimization of stent implantation. The assessment of stent strut indentation might become a valuable tool in clinical practice., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Xylella taiwanensis (Xt) is a nutritionally fastidious bacterial pathogen causing pear leaf scorch disease (PLSD) in Taiwan. The disease causes early defoliation, loss of tree vigor, and reduction in fruit yield and quality. No cure for PLSD is available. The only option for growers to control the disease is to use pathogen-free propagation material, which requires early and accurate detection of Xt. Currently, only one simplex PCR method is available for the diagnosis of PLSD. We developed five Xt-specific TaqMan quantitative PCR (TaqMan qPCR) systems (primers-probe sets) for the detection of Xt. The PCR systems target three conserved genomic loci commonly used in bacterial pathogen detection: the 16S rRNA gene ( rrs ), the 16S-23S rRNA intergenic transcribed sequence (16S-23S rRNA ITS), and the DNA gyrase gene ( gyrB ). BLAST analysis using the GenBank nr sequence database, including whole genome sequences of 88 Xanthomonas campestris pv. campestris (Xcc) strains, 147 X. fastidiosa (Xf) strains, and 32 Xt strains, showed that all primer and probe sequences were specific only to Xt. Single nucleotide polymorphisms (SNPs) provided the primer/probe specificity to Xt. The PCR systems were evaluated by using DNA samples from pure cultures of two Xt strains, one Xf strain, one Xcc strain, and 140 plant samples collected from 23 pear orchards in four counties in Taiwan. The two-copy rrs and 16S-23S rRNA ITS-based PCR systems (Xt803-F/R, Xt731-F/R, and Xt16S-F/R) showed higher detection sensitivity than the two single-copy gyrB -based systems (XtgB1-F/R and XtgB2-F/R). A metagenomic analysis of a representative PLSD leaf sample detected the presence of non-Xt proteobacteria and fungal pathogens that should be taken into consideration in PLSD, as they might interfere with diagnosis., Competing Interests: The author(s) declare no conflict of interest.

Background: Analysis of volatile organic compounds (VOCs) in exhaled breath has the potential to serve as an accurate diagnostic tool for gastro-intestinal diseases. Animal studies could be instrumental as a preclinical base and subsequent clinical translation to humans, as they are easier to standardize and better equipped to relate specific VOCs to metabolic and pathological processes. This review provides an overview of the study design, characteristics and methodological quality of previously published animal studies on analysis of exhaled breath in gastrointestinal and hepatic diseases. Guidelines are provided for standardization in study design and breath collection methods to improve comparability, avoid duplication of research and reduce discomfort of animals in future studies., Methods: PubMed and Embase database were searched for animal studies using exhaled breath analysis to detect gastro-intestinal diseases. Risk of bias was assessed using the SYRCLE's risk of bias tool for animal studies. Information on study design, standardization methods, animal models, breath collection methods and identified VOCs were extracted from the included studies., Results: 10 studies were included (acute liver failure n = 1, non-alcoholic steatohepatitis n = 1, hepatic ischemia n = 2, mesenteric ischemia n = 2, sepsis and peritonitis n = 3, colitis n = 1). Rats were used in most of the studies. Exhaled breath was mostly collected using invasive procedures as tracheal cannulation or tracheostomy. Poor reporting on standardization, breath collection methods, analytical techniques, as well as heterogeneity of the studies, complicate comparison of the different studies., Conclusion: Poor reporting of essential methodological details impaired comprehensive summarizing the various studies on exhaled breath in gastrointestinal and hepatic diseases. Potential pitfalls in study design, and suggestions for improvement of study design are discussed which, when applied, lead to consistent and generalizable results and a reduction in the use of laboratory animals. Refining the methodological quality of animal studies has the potential to improve subsequent clinical trial design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hintzen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A hyperspectral field sensor (FloX) was installed in Adventdalen (Svalbard, Norway) in 2019 as part of the Svalbard Integrated Arctic Earth Observing System (SIOS) for monitoring vegetation phenology and Sun-Induced Chlorophyll Fluorescence (SIF) of high-Arctic tundra. This northernmost hyperspectral sensor is located within the footprint of a tower for long-term eddy covariance flux measurements and is an integral part of an automatic environmental monitoring system on Svalbard (AsMovEn), which is also a part of SIOS. One of the measurements that this hyperspectral instrument can capture is SIF, which serves as a proxy of gross primary production (GPP) and carbon flux rates. This paper presents an overview of the data collection and processing, and the 4-year (2019-2021) datasets in processed format are available at: https://thredds.met.no/thredds/catalog/arcticdata/infranor/NINA-FLOX/raw/catalog.html associated with https://doi.org/10.21343/ZDM7-JD72 under a CC-BY-4.0 license. Results obtained from the first three years in operation showed interannual variation in SIF and other spectral vegetation indices including MERIS Terrestrial Chlorophyll Index (MTCI), EVI and NDVI. Synergistic uses of the measurements from this northernmost hyperspectral FLoX sensor, in conjunction with other monitoring systems, will advance our understanding of how tundra vegetation responds to changing climate and the resulting implications on carbon and energy balance., (© 2023 The Authors.)

Introduction: Acute mesenteric ischaemia (AMI) is a life-threatening condition with short-term mortality of up to 80%. The diagnosis of AMI has remained troublesome due to the non-specific clinical presentation, symptoms and laboratory findings. Early unambiguous diagnosis of AMI is critical to prevent progression from reversible to irreversible transmural intestinal damage, thereby decreasing morbidity and improving survival. The present study aims to validate a panel of plasma biomarkers and investigate volatile organic compound (VOC) profiles in exhaled air as a tool to timely and accurately diagnose AMI., Methods and Analysis: In this international multicentre prospective observational study, 120 patients (>18 years of age) will be recruited with clinical suspicion of AMI. Clinical suspicion is based on: (1) clinical manifestation, (2) physical examination, (3) laboratory measurements and (4) the physician's consideration to perform a CT scan. The patient's characteristics, repetitive blood samples and exhaled air will be prospectively collected. Plasma levels of mucosal damage markers intestinal fatty acid-binding protein and villin-1, as well as transmural damage marker smooth muscle protein 22-alpha, will be assessed by ELISA. Analysis of VOCs in exhaled air will be performed by gas chromatography time-of-flight mass spectrometry. Diagnosis of AMI will be based on CT, endovascular and surgical reports, clinical findings, and (if applicable) verified by histopathological examination., Ethics and Dissemination: The study protocol was approved by the Medical Research Ethics Committee (METC) of Maastricht University Medical Centre+ and Maastricht University (METC azM/UM), the Netherlands (METC19-010) and the Ethics Committee Research UZ/KU Leuven, Belgium (S63500). Executive boards and local METCs of other Dutch participating centres Gelre Ziekenhuizen (Apeldoorn), Medisch Spectrum Twente (Enschede), and University Medical Centre Groningen have granted permission to carry out this study. Study results will be disseminated via open-access peer-reviewed scientific journals and national/international conferences., Trial Registration Number: NCT05194527., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

DNA repair plays an essential role in maintaining genomic stability, and can be assessed by various comet assay-based approaches, including the cellular repair assay and the in vitro repair assay. In the cellular repair assay, cells are challenged with a DNA-damaging compound and DNA damage removal over time is assessed. In the in vitro repair assay, an early step in the repair process is assessed as the ability of a cellular extract to recognize and incise damaged DNA in substrate nucleoids from cells treated with a DNA-damaging compound. Our direct comparison of both assays in eight cell lines and human peripheral blood lymphocytes indicated no significant relationship between these DNA repair assays (R 2  = 0.084, P = 0.52). The DNA incision activity of test cells measured with the in vitro repair assay correlated with the background level of DNA damage in the untreated test cells (R 2  = 0.621, P = 0.012). When extracts were prepared from cells exposed to DNA-damaging agents (10 mM KBrO 3 or 1 µM Ro 19-8022 plus light), the incision activity was significantly increased, which is in line with the notion that base excision repair is inducible. The data presented suggest that the two assays do not measure the same endpoint of DNA repair and should be considered as complementary., (© 2023. The Author(s).)

Understanding the seedborne nature of plant viruses is essential for developing disease control strategies and is impactful to the seed market. Here, we investigated seed transmissibility of tomato leaf curl New Delhi virus-cucumber isolate (ToLCNDV-CB) and -oriental melon isolate (ToLCNDV-OM) in cucumber and seed transmissibility of tomato leaf curl Taiwan virus (ToLCTV) and tomato yellow leaf curl Thailand virus (TYLCTHV) in tomato. Parent plants were inoculated using agroinfiltration with virus infectious clones, and virus infection was confirmed by PCR with virus-specific primers. ToLCNDV-CB and ToLCNDV-OM were detected in different parts of the female and male flowers and the fruits of cucumbers. ToLCNDV-CB and ToLCNDV-OM were also detected in cucumber seed coats and seedlings with an infection rate higher than 79%. Similar results were observed with ToLCTV and TYLCTHV as they were detected in different parts of the female and male flowers and fruits of three tomato cultivars. ToLCTV and TYLCTHV were also detected in tomato seed coats and seedlings with an infection rate higher than 36%. In addition, pollen-mediated transmission assays of these four begomoviruses were conducted with pollen derived from virus-infected plants to healthy plants. Results showed that ToLCNDV-CB and ToLCNDV-OM were detected in cross-pollinated cucumber progenies with an infection rate higher than 70%. ToLCTV and TYLCTHV were also detected in cross-pollinated tomato progenies with an infection rate higher than 77%. Our results indicated that ToLCNDV, ToLCTV, and TYLCTHV can be transmitted via seeds or pollens of cucumber and tomato plants. To our knowledge, this is the first report documenting the pollen-mediated transmission of begomoviruses., Competing Interests: The author(s) declare no conflict of interest.

Objective: To improve our transitional care, we explored how childhood dysfunctional voiding (DV) develops into adulthood. DV is a common condition in both children and adults. However, the long-term course of childhood DV into adulthood is unknown and treatment over the ages differs., Methods: A cross-sectional follow-up was performed in a cohort of 123 females treated from 2000 to 2003 for childhood DV with urinary tract infections (UTIs) and/or daytime urinary incontinence (DUI). The main outcome was a staccato or intermittent urinary flow pattern, possibly indicating persistent or recurred DV according to the International Continence Society criteria. Flow patterns of healthy women were used to compare results., Results: Twenty-five patients participated in this study, with a mean duration of 20.8 years after urotherapy. In 10/25 (40%) cases, a staccato or interrupted urinary flow pattern was found on the current measurement, compared to 5/47 (10.6%) in the control group. Around 50% (5/10) of the patients with a dysfunctional flow pattern reported UTIs and 50% (5/10) experienced DUI. In the group with a normal flow pattern, 2/15 (13%) reported UTIs and 9/15 (60%) DUI. The impact of DUI on quality of life was moderate to high in both groups., Conclusion: Our results show that 40% of females who had extensive urotherapy for DV in childhood, still have DV according to International Continence Society criteria as an adult, 56% still experience DUI, and 28% UTIs. These data should be taken into account in the counseling of patients and for guiding the process of transition into adulthood., Competing Interests: DECLARATION OF COMPETING INTEREST None Declared., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered intestinal tryptophan metabolism in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls. Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites. Integration of the transcriptome and metabolome identified various alterations in intestinal tryptophan metabolism during active disease in IBD patients, including decreased intestinal tryptophan absorption, enhanced kynurenine pathway, increased interstitial serotonin availability, changed indole pathway, and activated aryl hydrocarbon receptor signaling. Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.

Phase transitions and collective dynamics of active colloidal suspensions are fascinating topics in soft matter physics, particularly for out-of-equilibrium systems, which can lead to rich rheological behaviours in the presence of steady shear flow. Here the role of self-propulsion in the rheological response of a dense colloidal suspension is investigated by using particle-resolved Brownian dynamics simulations. First, the combined effect of activity and shear in the solid on the disordering transition of the suspension is analyzed. While both self-propulsion and shear destroy order and melt the system if critical values are exceeded, self-propulsion largely lowers the stress barrier needed to be overcome during the transition. We further explore the rheological response of the active sheared system once a steady state is reached. While passive suspensions show a solid-like behaviour, turning on particle motility fluidises the system. At low self-propulsion, the active suspension behaves in the steady state as a shear-thinning fluid. Increasing the self-propulsion changes the behaviour of the liquid from shear-thinning to shear-thickening. We attribute this to clustering in the sheared suspensions induced by motility. This new phenomenon of motility-induced shear thickening (MIST) can be used to tailor the rheological response of colloidal suspensions.

Introduction: Begomoviruses are mainly transmitted by whiteflies. However, a few begomoviruses can be transmitted mechanically. Mechanical transmissibility affects begomoviral distribution in the field., Materials and Methods: In this study, two mechanically transmissible begomoviruses, tomato leaf curl New Delhi virus-oriental melon isolate (ToLCNDV-OM) and tomato yellow leaf curl Thailand virus (TYLCTHV), and two nonmechanically transmissible begomoviruses, ToLCNDV-cucumber isolate (ToLCNDV-CB) and tomato leaf curl Taiwan virus (ToLCTV), were used to study the effects of virus-virus interactions on mechanical transmissibility., Results: Nicotiana benthamiana and host plants were coinoculated through mechanical transmission with inoculants derived from plants that were mix-infected or inoculants derived from individually infected plants, and the inoculants were mixed immediately before inoculation. Our results showed that ToLCNDV-CB was mechanically transmitted with ToLCNDV-OM to N. benthamiana , cucumber, and oriental melon, whereas ToLCTV was mechanically transmitted with TYLCTHV to N. benthamiana and tomato. For crossing host range inoculation, ToLCNDV-CB was mechanically transmitted with TYLCTHV to N. benthamiana and its nonhost tomato, while ToLCTV with ToLCNDV-OM was transmitted to N. benthamiana and its nonhost oriental melon. For sequential inoculation, ToLCNDV-CB and ToLCTV were mechanically transmitted to N. benthamiana plants that were either preinfected with ToLCNDV-OM or TYLCTHV. The results of fluorescence resonance energy transfer analyses showed that the nuclear shuttle protein of ToLCNDV-CB (CBNSP) and the coat protein of ToLCTV (TWCP) localized alone to the nucleus. When coexpressed with movement proteins of ToLCNDV-OM or TYLCTHV, CBNSP and TWCP relocalized to both the nucleus and the cellular periphery and interacted with movement proteins., Discussion: Our findings indicated that virus-virus interactions in mixed infection circumstances could complement the mechanical transmissibility of nonmechanically transmissible begomoviruses and alter their host range. These findings provide new insight into complex virus-virus interactions and will help us to understand the begomoviral distribution and to reevaluate disease management strategies in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Gustian, Chang and Jan.)

Scope: Western type of diets are characterized by high animal protein intake and are associated with various chronic inflammatory diseases. With a higher protein consumption, excess undigested protein will reach the colon and be subsequently metabolized by gut microbiota. Depending on the type of protein, fermentation in the colon generates different metabolites with varying biological effects. This study aims to compare the impact of protein fermentation products from different sources on gut health., Methods and Results: Three high protein diets (vital wheat gluten [VWG], lentil, or casein) are submitted to the in vitro model of colon. Fermentation of excess lentil protein for 72 h results in highest production of short-chain fatty acids and lowest production of branched-chain fatty acids. Exposure of Caco-2 monolayers or Caco-2 monolayers co-cultured with THP-1 macrophages to luminal extracts of fermented lentil protein results in less cytotoxicity of Caco-2 monolayers and less damage to barrier integrity, when compared to VWG and casein. Lowest induction of interleukin-6 is observed in THP-1 macrophages after treatment with lentil luminal extracts, which is identified to be regulated by aryl hydrocarbon receptor signaling., Conclusion: The findings indicate that protein sources affect the health effects of high protein diet in the gut., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Combining experimental observations of Quincke roller clusters with computer simulations and a stability analysis, we explore the formation and stability of two interlocked self-propelled dumbbells. For large self-propulsion and significant geometric interlocking, there is a stable joint spinning motion of two dumbbells. The spinning frequency can be tuned by the self-propulsion speed of a single dumbbell, which is controlled by an external electric field for the experiments. For typical experimental parameters the rotating pair is stable with respect to thermal fluctuations but hydrodynamic interactions due to the rolling motion of neighboring dumbbells leads to a breakup of the pair. Our results provide a general insight into the stability of spinning active colloidal molecules, which are geometrically locked.

Breaking the in-plane geometric symmetry of dielectric metasurfaces allows us to access a set of electromagnetic states termed symmetry-protected quasi -bound states in the continuum ( q BICs). Here we demonstrate that q BICs can also be accessed by a symmetry breaking in the permittivity of the comprising materials. While the physical size of atoms imposes a limit on the lowest achievable geometrical asymmetry, weak permittivity modulations due to carrier doping, and electro-optical Pockels and Kerr effects, usually considered insignificant, open the possibility of infinitesimal permittivity asymmetries for on-demand, dynamically tunable resonances of extremely high quality factors. As a proof-of-principle, we probe the excitation of permittivity-asymmetric q BICs (ε- q BICs) using a prototype Si/TiO 2 metasurface, in which the asymmetry in the unit cell is provided by the permittivity contrast of the materials. ε- q BICs are also numerically demonstrated in 1D gratings, where quality-factor enhancement and tailored interference phenomena of q BICs are shown via the interplay of geometrical and permittivity asymmetries.

Background: The prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof-MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children., Methods: This study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath., Discussion: The potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies., Trial Registration: Netherlands Trial Register, NL7336, Date registered 11-10-2018., (© 2023. The Author(s).)

Biosensors are analytical tools that can be used as simple, real-time, and effective devices in clinical diagnosis, food analysis, and environmental monitoring. Nanoscale functional materials possess unique properties such as a large surface-to-volume ratio, making them useful for biomedical diagnostic purposes. Nanoengineering has resulted in the increased use of nanoscale functional materials in biosensors. Various types of nanostructures i.e., 0D, 1D, 2D, and 3D, have been intensively employed to enhance biosensor selectivity, limit of detection, sensitivity, and speed of response time to display results. In particular, carbon nanotubes and nanofibers have been extensively employed in electrochemical biosensors, which have become an interdisciplinary frontier between material science and viral disease detection. This review provides an overview of the current research activities in nanofiber-based electrochemical biosensors for diagnostic purposes. The clinical applications of these nanobiosensors are also highlighted, along with a discussion of the future directions for these materials in diagnostics. The aim of this review is to stimulate a broader interest in developing nanofiber-based electrochemical biosensors and improving their applications in disease diagnosis. In this review, we summarize some of the most recent advances achieved in point of care (PoC) electrochemical biosensor applications, focusing on new materials and modifiers enabling biorecognition that have led to improved sensitivity, specificity, stability, and response time.

The comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility., (© 2023. Springer Nature Limited.)

Photodynamic therapy (PDT) is a process in which a photosensitizer (PS) is exposed to specific wavelengths and generates reactive oxygen species (ROS) which act within nanometers. The low invasive nature and directed cytotoxicity of this approach render it attractive to the treatment of different conditions, including the ones that affect the central nervous system (CNS). The effect of PDT on healthy neurons is one main concern over its use in the CNS, since neuronal-like cells were shown to be particularly sensitive to certain PSs. Among available PSs, 1,9-dimethyl-methylene blue (DMMB) stands out as being resistant to reduction to its inactive leuco form and by being able to produce high levels of singlet‑oxygen. In this study, we aimed to investigate DMMB photodamage mechanisms in the hippocampal cell line HT22. Our results demonstrate that DMMB-PDT decrease in cell viability was linked with an increase in cell death and overall ROS production. Besides, it resulted in a significant increase in mitochondrial ROS production and decreased mitochondria membrane potential. Furthermore, DMMB-PDT significantly increased the presence of acidic autolysosomes, which was accompanied by an increase in ATG1 and ATG8 homologue GaBarap1 expression, and decreased DRAM1 expression. Taken together our results indicated that mitochondrial and autophagic dysfunction underlie DMMB-PDT cytotoxicity in neuronal cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Stachytarpheta jamaicensis (L.) Vahl, also known as snack weed, is an exotic plant in Taiwan. In April 2021, severe golden yellow mosaic leaves (Fig. S1) were observed on S. jamaicensis plants in Taichung City, Taiwan. Samples from eight symptomatic and two asymptomatic plants were collected from the public flowerbed. Total DNA was extracted from each of the collected samples by using a modified CTAB method (Echevarría-Machado et al. 2005). PCR with Begomovirus degenerate primers (PAL1v1978/PAR1c715; Rojas et al. 1993) was conducted. The expected 1.5-kb fragment was amplified only from the 8 symptomatic samples. Two randomly selected amplicons were cloned on pCRII-TOPO TA vector (Invitrogen Co., San Diego, CA, USA) and sequenced with the ABI3730 automatic sequencer (Applied Biosystems, Hammonton, NJ, USA) at National Chung Hsing University (NCHU). After NCBI BLASTn analysis, the sequences were shown to be most closely related to tomato leaf curl Cebu virus (ToLCCeV) isolates (EU487042, EU487025, KU946997), with 92.4-92.5% nucleotide sequence identity by using the CLUSTAL W method of MegAlign program (DNASTAR, Inc., Madison, WI, USA). A ToLCCeV specific primer pair (FJJ2021-165 /166 5'-ACTTACAGGCCCATGTATCG-3' / 5'-GAATGGGTATCCGAGCACG-3') was designed to amplify and sequence the remaining half of viral DNA. The expected 1.6-kb amplicon was amplified only from the symptomatic samples. The full-length of DNA-A consisted of 2.7-kb nucleotides (ToLCCeV isolate stachy, ON525110 and ON525111) and contained six open reading frames (two in viral sense, V1 to V2 and four in the viral complementary sense, C1 to C4) and the conserved nonanucleotide motif (TAATATTAC). The full-length DNA-A of ToLCCeV stachy isolates shared 99.9% nucleotide identity to each other and 91.2-92.4% and 91.3-92.5% nucleotide identities to other ToLCCeV isolates (EU487042, EU487025, KU946997) available in NCBI GenBank. Besides, ToLCCeV is a monopartite begomovirus that harbors no DNA-B. Thus, there were no bands amplified from the degenerate primer pair for DNA-B (DNABLC2 / DNABLV2; Green et al. 2001). Furthermore, the infectious clone was constructed by using phi29 DNA polymerase (New England Biolabs, Ipswich, MA, USA) for rolling circle amplification (RCA). The RCA product was partially digested with ApaI (NEB) and ligated into the binary vector pCambia0380 (AF234290). The resulting recombinant vector was transformed into Agrobacterium tumefaciens C58. A. tumefaciens C58, containing the infectious ToLCCeV-Stachy DNA-A vector, was grown overnight in LB broth containing kanamycine (50 μg/ml) at 28°C. S. jamaicensis and Nicotiana benthamiana (Nb, four to six leaf stage) plants were agroinoculated to confirm the infectivity of the ToLCCeV clone. The leaf curling and blister symptoms were observed on the Nb systemic leaves 17-day post inoculation (dpi) and the golden yellow mosaic symptom noticed on S. jamaicensis systemic leaves 30-dpi. The presence of the viral DNA in the inoculated plants was confirmed by PCR using the specific primer pair of ToLCCeV. To the best of our knowledge, this is the first report of the monopartite begomovirus, ToLCCeV, associated with golden yellow mosaic disease in S. jamaicensis in Taiwan. The existence of ToLCCeV might severely impact the tomato and pepper industry because they are the natural hosts of ToLCCeV (Tsai et al. 2011) and ToLCCeV may be transmitted by the whitefly, Bemisia tabaci, in Taiwan (Ko et al. 2005).

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease for which cigarette smoking is the main risk factor. Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known to be formed during pyrolysis and combustion of tobacco and have been linked to respiratory toxicity. Mitochondrial dysfunction is suggested to be mechanistically and causally involved in the pathogenesis of smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has been shown to impair the molecular regulation of mitochondrial metabolism and content in epithelial cells of the airways and lungs. Although it is unknown which specific chemicals present in CS are responsible for this, it has been suggested that aldehydes may be involved. Therefore, it has been proposed by the World Health Organization to regulate aldehydes in commercially-available cigarettes. In this review, we comprehensively describe and discuss the impact of acetaldehyde, acrolein, and formaldehyde on mitochondrial function and content and the molecular pathways controlling this (biogenesis versus mitophagy) in epithelial cells of the airways and lungs. In addition, potential therapeutic applications targeting (aldehyde-induced) mitochondrial dysfunction, as well as regulatory implications, and the necessary required future studies to provide scientific support for this regulation, have been covered in this review.

Background: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented., Objective: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic., Methods: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12)., Results: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs., Conclusion: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention.

Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. This systematic review provides an overview of the current understanding of this topic. A systematic search using PubMed, Embase, Medline, Cochrane Library, and the Web of Science according to PRISMA guidelines resulted in seventy-one included studies. In addition, a systematic search was conducted that identified five systematic reviews from which CRC-associated gut microbiota data were extracted. The included studies analyzed VOCs in feces, urine, breath, blood, tissue, and saliva. Eight studies performed microbiota analysis in addition to VOC analysis. The most frequently reported dysregulations over all matrices included short-chain fatty acids, amino acids, proteolytic fermentation products, and products related to the tricarboxylic acid cycle and Warburg metabolism. Many of these dysregulations could be related to the shifts in CRC-associated microbiota, and thus the gut microbiota presumably contributes to the metabolic fingerprint of VOC in CRC. Future research involving VOCs analysis should include simultaneous gut microbiota analysis.

Stachytarpheta jamaicensis, a traditional herbal pharmacological plant in the Family Verbenaceae that produces purplish-blue flowers, is mainly used as a garden plant in tropical and subtropical areas, including Taiwan. A begomovirus, stachytarpheta leaf curl virus (StaLCV) that caused disease on S. jamaicensis, has been reported (Xiong et al. 2005). In 2021, five symptomatic plants with mild mottle and leaf distortion (Fig. S1A, B) and three asymptomatic plants were collected in Taichung City, Taiwan. Polymerase chain reaction (PCR) and reverse transcription (RT)-PCR assays using degenerate primer pairs with expected amplicon sizes of 1.2-1.3 kb (PAL1v1978/PAR1c715; Rojas et al. 1993), 312 bp (dTospo-F2/dTospo-R2; Huang et al. 2018), and 600-750 kb (Hrp5/Pot1; Chen et al. 2006, Colinet and Kummert 1993) for Begomovirus, Orthotospovirus, and Potyvirus, respectively were performed using total DNA and total RNA plant extracts. Results showed the expected fragments were only amplified from the 5 symptomatic plants using Potyvirus degenerate primers. Three out of five randomly picked amplicons, coding the 3'-end of nuclear inclusion b protein (NIb) and 5'-end coat protein (CP) genes, were cloned and sequenced with the ABI3730 automatic sequencer (Applied Biosystems, Hammonton, NJ, USA) in Biotechnology Centre DNA-sequencing facility at National Chung Hsing University (NCHU). After NCBI BLASTN analysis, the sequences were shown to be most closely related to bidens mottle virus (BiMoV). The nucleotide sequence identities analyzed using the CLUSTAL W Methods of MegAlign program (DNASTAR, Inc., Madison, WI, USA), showed the three amplicons shared 95.8-99.8% to each other and 94.3-97.1% with 18 BiMoV isolates available in NCBI GenBank. Further RT-PCR with a specific primer (FJJ2021-278) designed from the CP of previously amplified amplicons, paired with oligo d(T) primer, were used for amplification of the 3'-CP gene and 3'-untranslated region (UTR) from total RNAs purified from symptomatic plants. The full-length CPs (804-nt and 268-aa) of the BiMoV isolates described here (Acc. Nos. OM406329 and OM406330; designated as isolate Stachy3 and Stachy7, respectively) shared 96.5-98.5% nucleotide and 97.8-99.3% amino acid identity to other BiMoV isolates. The isolate used for back-inoculation to S. jamaicensis was selected after the completion of triple single chlorotic local lesion isolation in Chenopodium quinoa. Two mechanically-inoculated S. jamaicensis plants exhibited symptoms 14-16 days post-inoculation similar to those observed in field plants and tested positive in RT-PCR using BiMoV-specific primers. In transmission electron microscopy, crude sap extracted from mechanically-inoculated C. quinoa and stained with uranyl acetate (UA) revealed flexuous filamentous virions of approximately 720 × 12 nm (Fig. S1C). A western blot assay using BiMoV antiserum (Chen and Lee 2012) revealed bands of about 34 KDa only from the mechanically-inoculated C. quinoa and the five symptomatic S. jamaicensis plants collected from the field. Taken together, we believe this is the first report of BiMoV infecting and causing mild chlorotic mottle and leaf distortion on S. jamaicensis. S. jamaicensis may serve as a new alternative host of BiMoV that can spread the disease, and consequently may directly impact the producers of horticultural or economical crops, such as lettuce, calendula, sunflower, lisianthus, and garland chrysanthemum in Taiwan.

Phalaenopsis orchids are one of the most important exporting commodities for Taiwan. Most orchids are planted and grown in greenhouses. Early detection of orchid diseases is crucially valuable to orchid farmers during orchid cultivation. At present, orchid viral diseases are generally identified with manual observation and the judgment of the grower's experience. The most commonly used assays for virus identification are nucleic acid amplification and serology. However, it is neither time nor cost efficient. Therefore, this study aimed to create a system for automatically identifying the common viral diseases in orchids using the orchid image. Our methods include the following steps: the image preprocessing by color space transformation and gamma correction, detection of leaves by a U-net model, removal of non-leaf fragment areas by connected component labeling, feature acquisition of leaf texture, and disease identification by the two-stage model with the integration of a random forest model and an inception network (deep learning) model. Thereby, the proposed system achieved the excellent accuracy of 0.9707 and 0.9180 for the image segmentation of orchid leaves and disease identification, respectively. Furthermore, this system outperformed the naked-eye identification for the easily misidentified categories [cymbidium mosaic virus (CymMV) and odontoglossum ringspot virus (ORSV)] with the accuracy of 0.842 using two-stage model and 0.667 by naked-eye identification. This system would benefit the orchid disease recognition for Phalaenopsis cultivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Huang, Wu, Lin, Lee, Yu, Chan and Jan.)

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease primarily caused by exposure to cigarette smoke (CS). During the pyrolysis and combustion of tobacco, reactive aldehydes such as acetaldehyde, acrolein, and formaldehyde are formed, which are known to be involved in respiratory toxicity. Although CS-induced mitochondrial dysfunction has been implicated in the pathophysiology of COPD, the role of aldehydes therein is incompletely understood. To investigate this, we used a physiologically relevant in vitro exposure model of differentiated human primary bronchial epithelial cells (PBEC) exposed to CS (one cigarette) or a mixture of acetaldehyde, acrolein, and formaldehyde (at relevant concentrations of one cigarette) or air, in a continuous flow system using a puff-like exposure protocol. Exposure of PBEC to CS resulted in elevated IL-8 cytokine and mRNA levels, increased abundance of constituents associated with autophagy, decreased protein levels of molecules associated with the mitophagy machinery, and alterations in the abundance of regulators of mitochondrial biogenesis. Furthermore, decreased transcript levels of basal epithelial cell marker KRT5 were reported after CS exposure. Only parts of these changes were replicated in PBEC upon exposure to a combination of acetaldehyde, acrolein, and formaldehyde. More specifically, aldehydes decreased MAP1LC3A mRNA (autophagy) and BNIP3 protein (mitophagy) and increased ESRRA protein (mitochondrial biogenesis). These data suggest that other compounds in addition to aldehydes in CS contribute to CS-induced dysregulation of constituents controlling mitochondrial content and function in airway epithelial cells.

Objectives: We aimed to determine how cognitive impairment relates to the extent of the presumed epileptogenic zone in pediatric focal epilepsies. We analyzed the cognitive functions in unilobar compared to multilobar focal epilepsy patients that underwent neuropsychological testing at a tertiary epilepsy center., Methods: We assessed cognitive functions of pediatric focal epilepsy patients with the German version of the Wechsler Intelligence Scales that measures full-scale IQ and subcategories. We assessed differences in IQ and epilepsy-related variables between unilobar and multilobar epilepsy patients., Results: We included 62 patients (37 unilobar, 25 multilobar), aged 10.6 ± 3.7 years. Full-scale IQ values were significantly higher in unilobar (93.6 ± 17.7, 95% CI 87.7-99.6) than in multilobar epilepsy patients (77.3 ± 17.2, 95% CI 69.3-85.0; p = 0.001). In all but one IQ subcategory (working memory), significantly higher values were measured in unilobar than in multilobar epilepsy patients. The proportion of unilobar epilepsy patients with severe cognitive impairment (8.3%) and below-average intelligence (30.5%) was lower compared to multilobar epilepsy patients (47.6% and 61.9%; p = 0.002 and p = 0.021, respectively). Epilepsy onset occurred earlier in multilobar (4.0 years, 95% CI 2.6-5.5, SD ± 3.4 years) than in unilobar epilepsy patients (7.0 years, 95% CI 5.5-8.5, SD ± 4.4 years, p = 0.008)., Conclusions: Pediatric multilobar epilepsy patients face more cognitive issues than unilobar epilepsy patients on average. Our findings should help to identify children and adolescents who are most at risk for impaired cognitive development. A limitation of our study is the simple division into unilobar and multilobar epilepsies, with no specific account being taken of etiology/epilepsy syndrome, which can have a profound effect on cognition., Competing Interests: Declaration of competing interest None., (© 2022 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

We study a one-dimensional three-state run-and-tumble model motivated by the bacterium Caulobacter crescentus which displays a cell cycle between two non-proliferating mobile phases and a proliferating sedentary phase. Our model implements kinetic transitions between the two mobile and one sedentary states described in terms of their number densities, where mobility is allowed with different running speeds in forward and backward direction. We start by analyzing the stationary states of the system and compute the mean and squared-displacements for the distribution of all cells, as well as for the number density of settled cells. The latter displays a surprising super-ballistic scaling [Formula: see text] at early times. Including repulsive and attractive interactions between the mobile cell populations and the settled cells, we explore the stability of the system and employ numerical methods to study structure formation in the fully nonlinear system. We find traveling waves of bacteria, whose occurrence is quantified in a non-equilibrium state diagram., (© 2022. The Author(s).)