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Citrus yellow vein clearing virus (CYVCV) is the causative agent of citrus yellow vein clearing disease, and poses a serious threat to the lemon industry in Asia. The common symptoms of CYVCV-infected lemon plants are leaf crinkling, leaf chlorotic mottling, and yellow vein clearing. However, the molecular mechanisms underlying CYVCV-citrus interaction that responsible for symptom occurrence is still unclarified. In this study, RNA-seq was performed to analyze the gene expression patterns of 'Eureka' lemon (Citrus limon Burm. f.) plants in response to CYVCV infection. There were 3691 differentially expressed genes (DEGs) identified by comparison between mock and CYVCV-infected lemon plants through RNA-seq. Bioinformatics analyses revealed that these DEGs were components of different pathways involved in phenylpropanoid biosynthesis, brassinosteroid biosynthesis, flavonoid biosynthesis and photosynthesis. Among these, the DEGs related to phytohormone metabolism and photosynthesis pathways were further enriched and analyzed. This study showed that different phytohormone-related genes had different responses toward CYVCV infection, however almost all of the photosynthesis-related DEGs were down-regulated in the CYVCV-infected lemon plants. The obtained RNA-seq data were validated by RT-qPCR using 12 randomly chosen genes, and the results of mRNA expression analysis were consistent with those of RNA-seq. The phytohormone biosynthesis, signaling and photosynthesis-related genes of lemon plants were probably involved in systemic infection and symptom occurrence of CYVCV. Notably, CYVCV infection had regulatory effects on the biosynthesis and signaling of phytohormone, which likely improve systemic infection of CYVCV. Additionally, CYVCV infection could cause structural changes in chloroplast and inhibition of photosynthesis pathway, which probably contribute to the appearance of leaf chlorotic mottling and yellow vein clearing in CYVCV-infected lemon plants. This study illustrates the dynamic nature of the citrus-CYVCV interaction at the transcriptome level and provides new insights into the molecular mechanism underlying the pathogenesis of CYVCV in lemon plants.

Background Despite the increasing understanding of factors that might underlie psychiatric disorders, prospectively detecting shifts from a healthy towards a symptomatic state has remained unattainable. A complex systems perspective on psychopathology implies that such symptom shifts may be foreseen by generic indicators of instability, or early warning signals (EWS). EWS include, for instance, increasing variability, covariance, and autocorrelation in momentary affective states—of which the latter was studied. The present study investigated if EWS predict (i) future worsening of symptoms as well as (ii) the type of symptoms that will develop, meaning that the association between EWS and future symptom shifts would be most pronounced for congruent affective states and psychopathological domains (e.g., feeling down and depression). Methods A registered general population cohort of adolescents (mean age 18 years, 36% male) provided ten daily ratings of their affective states for 6 consecutive days. The resulting time series were used to compute EWS in feeling down, listless, anxious, not relaxed, insecure, suspicious, and unwell. At baseline and 1-year follow-up, symptom severity was assessed by the Symptom Checklist-90 (SCL-90). We selected four subsamples of participants who reported an increase in one of the following SCL-90 domains: depression ( N  = 180), anxiety ( N  = 192), interpersonal sensitivity ( N  = 184), or somatic complaints ( N  = 166). Results Multilevel models showed that EWS in feeling suspicious anticipated increases in interpersonal sensitivity, as hypothesized. EWS were absent for other domains. While the association between EWS and symptom increases was restricted to the interpersonal sensitivity domain, post hoc analyses showed that symptom severity at baseline was related to heightened autocorrelations in congruent affective states for interpersonal sensitivity, depression, and anxiety. This pattern replicated in a second, independent dataset. Conclusions The presence of EWS prior to symptom shifts may depend on the dynamics of the psychopathological domain under consideration: for depression, EWS may manifest only several weeks prior to a shift, while for interpersonal sensitivity, EWS may already occur 1 year in advance. Intensive longitudinal designs where EWS and symptoms are assessed in real-time are required in order to determine at what timescale and for what type of domain EWS are most informative of future psychopathology.

Background Despite the individual and economic relevance of irritable bowel syndrome (IBS), research on social inequalities in the development of IBS symptoms is lacking. Therefore, the aim of the study was to shed light on (1) IBS symptom development across different social identities, and (2) psychosocial influences on and impact of IBS symptom development to understand the processes by and the social contexts in which these experiences are created. Methods Analyses made use of a prospective longitudinal qualitative study with three serial time points (initial interview, three-months, and twelve-month follow-up). Interviews of n  = 20 participants were included capturing a variety of social identities (occupational status, gender, history of migration), symptom specifics, and experiences with and in relation to their IBS symptomatology. Following a longitudinal qualitative research (LQR) approach, deductive and optional inductive themes were extracted. Results Over the one-year study period, participants’ symptoms largely improved, undulated, remained mainly stagnant, or worsened. Social inequalities became apparent in that participants with a high occupational status and males experienced improvements in their symptoms compared to participants with a low occupational status and females, respectively. To understand these differences, the following deductive themes related to psychosocial influences on and impact of IBS symptom development were identified: stressors regarding private environment (e.g., life events, familial responsibilities) and livelihood, coping, and perceived stigma in medical contexts. Conclusions To mitigate social inequalities in IBS symptom development, both, individuals’ coping strategies and social power need to be strengthened, especially for those with intersecting social identities associated with oppression, like low socioeconomic status, female gender, or a history of migration. Thereby, work-related, medical, and psychoeducational interventions are needed addressing both the individual and structural level.

Even though evidence-based treatments are generally effective in reducing post-traumatic stress disorder (PTSD) in youth, many still experience elevated symptoms after treatment. A better understanding of how PTSD develops throughout treatment can increase efficiency and reduce residual symptoms. This study investigated which PTSD symptom clusters and symptoms within these clusters changed the most and least through trauma-focused cognitive behavioural therapy (TF-CBT), and identified common residual symptoms after treatment. Latent growth curve modelling was used to identify differences in intercepts and slopes of symptoms, and residual symptoms were identified with McNemar tests in a sample of 517 youth (aged 6-19 years, 75.6% girls) receiving TF-CBT. We found small but statistically significant differences in slopes across clusters. Avoidance both reduced the most and demonstrated most residual symptoms. Also, within clusters, many of the symptoms that reduced the most, such as psychological cue reactivity, persistent negative emotional state, and difficulties sleeping and concentrating, had the highest symptom levels before treatment and the most residual symptoms after treatment. Overall, symptoms of PTSD were reduced throughout TF-CBT. Symptoms rated highest at treatment start decreased the most but also tended to persist as common residual symptoms. Symptoms such as psychological cue reactivity, persistent negative emotional state, and negative beliefs that were common residual symptoms and are known to be central in the development and maintenance of PTSD are of particular clinical relevance. Research based on frequent symptom measurements during treatment could capture subtler changes, increasing understanding of the mechanisms of effective trauma treatment.

Viral infections cause plant chlorosis, stunting, necrosis or other symptoms. The down‐regulation of chloroplast‐related genes (ChRGs) is assumed to be responsible for chlorosis. We identified the differentially expressed genes (DEGs) in Rice stripe virus (RSV)‐infected Nicotiana benthamiana, and examined the contribution of 75 down‐regulated DEGs to RSV symptoms by silencing them one by one using Tobacco rattle virus (TRV)‐induced gene silencing. Silencing of 11 of the 75 down‐regulated DEGs caused plant chlorosis, and nine of the 11 were ChRGs. Silencing of a down‐regulated DEG encoding the eukaryotic translation initiation factor 4A (eIF4A) caused leaf‐twisting and stunting that were visible on RSV‐infected N. benthamiana. A region of RSV RNA4 was complementary to part of eIF4A mRNA and virus‐derived small interfering (vsiRNAs) from that region were present in infected N. benthamiana. When expressed as artificial microRNAs, those vsiRNAs could target NbeIF4A mRNA for regulation. We provide experimental evidence supporting the association of ChRGs with chlorosis and show that eIF4A is involved in RSV symptom development. This is also the first report demonstrating that siRNA derived directly from a plant virus can target a host gene for regulation.

Potato mop-top virus (PMTV) is an emerging viral pathogen that causes tuber necrosis in potatoes. PMTV is composed of three single-stranded RNA segments: RNA1 encodes RNA-dependent RNA polymerase, RNA2 contains the coat protein (CP), and RNA3 harbors a triple gene block (TGB 1, TGB2, and TGB3). CP plays a role in viral transmission, while TGB is known to facilitate cell-to-cell and long-distance systemic movement. The role of CP in symptom development, specifically in the presence of TGB genes, was investigated using potato virus X (PVX) as a delivery vehicle to express PMTV genes in the model plant Nicotiana benthamiana. Plants expressing individual genes showed mild symptoms that included leaf curling and crumpling. Interestingly, symptom severity varied among plants infected with three different combinations: CP with TGB1, CP with TGB2, and CP with TGB3. Notably, the combination of CP and TGB3 induced a hypersensitive response, accompanied by stunted growth and downward curling and crumpling. These results suggest the potential role of TGB co-expressed with CP in symptom development during PMTV infection. Additionally, this study demonstrates the use of the PVX-based expression system as a valuable platform for assessing the role of unknown genes in viral pathogenicity.

PurposeTo study the use of interventions and symptom relief for adult patients with incurable cancer admitted to an acute palliative care unit providing integrated oncology and palliative care services.MethodsAll admissions during 1 year were assessed. The use of interventions was evaluated for all hospitalizations. Patients with assessments for worst and average pain intensity, tiredness, drowsiness, nausea, appetite, dyspnea, depression, anxiety, well-being, constipation, and sleep were evaluated for symptom development during hospitalization. Descriptive statistics was applied for the use of interventions and the paired sample t-test to compare symptom intensities (SIs).ResultsFor 451 admissions, mean hospital length of stay was 7.0 days and mean patient age 69 years. More than one-third received systemic cancer therapy. Diagnostic imaging was performed in 66% of the hospitalizations, intravenous rehydration in 45%, 37% received antibiotics, and 39% were attended by the multidisciplinary team. At admission and at discharge, respectively, 55% and 44% received oral opioids and 27% and 45% subcutaneous opioids. For the majority, opioid dose was adjusted during hospitalization. Symptom registrations were available for 180 patients. Tiredness yielded the highest mean SI score (5.6, NRS 0–10) at admission and nausea the lowest (2.2). Significant reductions during hospitalization were reported for all assessed SIs (p ≤ 0.01). Patients receiving systemic cancer therapy reported symptom relief similar to those not on systemic cancer therapy.ConclusionClinical practice and symptom relief during hospitalization were described. Symptom improvements were similar for oncological and palliative care patients.

Tomato leaf curl New Delhi virus-ES (ToLCNDV-ES), a high threat to cucurbits in the Mediterranean Basin, is listed as a different strain from the Asian ToLCNDV isolates. In this study, the infectivity of two clones previously isolated from Italy and Pakistan were compared in cucumbers, which resulted in the opposite symptom appearance. The swapping subgenome was processed; however, the mechanisms related to the disease phenotype remain unclear. To identify the disease-associated genes that could contribute to symptom development under the two ToLCNDV infections, the transcriptomes of ToLCNDV-infected and mock-inoculated cucumber plants were compared 21 days postinoculation. The number of differentially expressed genes in ToLCNDV-India-infected plants was 10 times higher than in ToLCNDV-ES-infected samples. The gene ontology (GO) and pathway enrichment were analyzed using the Cucurbits Genomics Database. The flavonoid pathway-related genes were upregulated in ToLCNDV-ES, but some were downregulated in ToLCNDV-India infection, suggesting their role in resistance to the two ToLCNDV infections. The relative expression levels of the selected candidate genes were validated by qRT-PCR under two ToLCNDV-infected conditions. Our results reveal the different infectivity of the two ToLCNDVs in cucumber and also provide primary information based on RNA-seq for further analysis related to different ToLCNDV infections.

Pepino mosaic virus (PepMV) is a significant threat to global tomato production, with symptom severity varying widely among strains and often leading to significant economic losses. Despite extensive studies on aggressive variants, the molecular determinants of mild symptomatology in field isolates, particularly from Korea, remain underexplored. In this study, we characterized a mildly infecting PepMV isolate from asymptomatic tomato plants during a field survey in Jeonju, South Korea. The full-length genome sequence and phylogenetic analysis classified it as a CH2 strain. A full-length cDNA infectious clone of this isolate was constructed and confirmed to induce no mosaic symptoms in tomato plants. To identify symptom determinants, targeted mutagenesis was performed in the coat protein (CP) open reading frame. Substitution mutations at CP position 236 or combined 6/155 substitutions converted the mild isolate into a severe variant, inducing strong mosaic symptoms and significantly higher viral accumulation (up to tenfold). These results demonstrated that specific CP residues act as key regulators of symptom severity in PepMV CH2 strains and provide defined severe mutants as useful tools for screening resistance in tomatoes. Although the mechanism underlying symptom modulation remains unclear, this work advanced our understanding of molecular differences between mild and severe strains and supported targeted strategies for managing this economically important virus.

Decision-making for antibiotic therapy in palliative cancer care implies avoiding futile interventions and to identify patients who benefit from treatment. We evaluated patient-reported outcome-measures (PROMs), physiological findings, and survival in palliative cancer care patients hospitalized with an infection. All acute admissions during one year, directly to a University Hospital unit that provided integrated services, were included. Serious infection was defined as a need to start intravenous antibiotics. PROMs, clinical and paraclinical variables, and survival were obtained. Sixty-two of 257 patients received intravenous antibiotic treatment. PROMs were generally similar in the infection group and the non-infection group, both in respect to intensities at admission and improvements during the stay. There were more physiological and paraclinical deviations at admission in patients in the infection group. These deviations improved during the stay. Survival was not poorer in the infection group compared to the non-infection group. Patients in integrated cancer care were as likely to be put on intravenous antibiotics but had longer survival. In integrated oncology and palliative cancer services, patients with an infection had similar outcomes as those without an infection. This argues that the use of intravenous antibiotics is appropriate in many patients admitted to palliative care.