Disease Management Strategies Research Articles

How Tea Plant Defends Against Blister Blight Disease: Facts Revealed and Unexplored Horizons.

Tea (Camellia sinensis [L.] O. Kuntze) is cultivated as a beverage crop. Despite being a hardy perennial, the tea plant is susceptible to various biotic stresses. Among them, the foliar disease blister blight (BB) is considered the most serious threat to the tea industry, particularly in Asia. BB caused by Exobasidium vexans (Basidiomycetes) was first reported from Northern India in 1868 and gradually established in other tea-growing countries. The fungus E. vexans attacks young harvestable shoots and causes 20 to 50% crop loss. Over the past 150 years, scientific research has delved into various aspects of BB disease, including pathogen biology, disease cycle, epidemiology, disease forecasting, crop loss assessment, and disease management strategies. In a recent shift in research focus, scientists have begun to investigate the resistance mechanisms of tea plants against BB and apply this knowledge to commercial tea cultivation. Although progress has been significant in understanding the fundamental aspects of BB resistance, the detailed molecular mechanisms driving this resistance remain under investigation. This paper focuses on the current understanding of defense mechanisms employed by tea plants against E. vexans and, conversely, how E. vexans overcomes these defenses. Furthermore, we discuss the application of plant resistance strategies in commercial tea cultivation. Lastly, we identify existing research gaps and propose future research directions in the field.

First report of sweet cherry root rot caused by Fusarium solani in China.

Sweet cherry (Prunus avium L.) has become an economically important fruit in China. And its cultivation area has significantly expanded over the last three decades (Wang et al. 2020; Zhao et al. 2023). In July 2023, wilting of cherry trees was observed in a cherry plantation in Wenchuan County (31°51'N, 103°56'E, altitude: 1,510 m) in Sichuan Province and approximately 27% of the trees showed symptoms of root rot including soft roots, dark brown to black lesions, yellowing and wilted leaves, and a distinct yellow-brown core discoloration of the inner root core when cut in cross-section. To isolate the causal pathogens, six infected sweet cherry plants with rootstock 'Daqingye' from Cerasus pseudocerasus were randomly selected from the orchard and then the intertwined diseased and healthy roots (5mm× 5mm × 2mm) were washed with sterile water to remove surface soil. The root samples were surface sterilized with 75% ethanol for 30 seconds and NaClO for 30 seconds and washed three times with distilled water. The disinfected tissues were placed on potato dextrose agar (PDA) and incubated at 27°C in darkness for 5 days (Zhao et al. 2024). A total of nine fungal isolates with similar morphological characteristics were obtained. The colony obtained through single-spore purification displays a red reverse side and a concentric ring pattern on the front, with a sparse surface. Macroconidia were relatively slender with a curve, like sickle shape, 0 to 3 septate measuring (25.8 to 46.1) μm× (4.2 to 7.5) μm, respectively (n=20). The morphological characteristics were consistent with the description of Fusarium spp. (Li et al. 2021). Among these isolates, only HB5 was selected for additional molecular identification. Three target genes, including the internal transcribed spacer (ITS), partial translation elongation factor 1-alpha (TEF), and RNA polymerase second largest subunit (RPB2) were amplified using the primers ITS1/ITS4, TEF1-728/FTEF1-re, and fRPB2-5F/fRPB2-7r, respectively (Groenewald et al. 2013; Carbone and Kohn 1999; Reeb et al. 2004). Sequences of HB5 was deposited in GenBank (ITS, PP388208; TEF, PP580036; RPB2, PP580035). A BLAST search revealed high similarity to those of F. solani sequences with 99%, 100% and 100% respectively (MN013858.1, JF740846.1, OR371902.1), and a multilocus phylogenetic tree was generated to represent the molecular identification results. Pathogenicity studies were conducted on the rootstocks from 'Daqingye' of Cerasus pseudocerasus in 1 liter plastic flowerpots. The seedlings were incubated in a constant temperature incubator at 25°C with a humidity level of 65% for two weeks. Following the growth of green leaves, 200ml (1x106 spores/ml) of spore suspensions were poured into pots. After 4 weeks of inoculation, the same symptoms of the inoculated plants were observed consistent with those shown in the field , while control plants were inoculated with distill water with asymptomatic. The inoculated pathogen was confirmed both morphologically and molecularly as described earlier, thereby fulfilling Koch's postulates. It has been reported that Fusarium solani has been reported to cause root rot in various plants in China, including Actinidia sppt, Zanthoxylum bungeanum, Fragaria×ananassa Duch (Song et al.2022; Li et al. 2023; Zhao et al. 2024). To our knowledge, this is the first report of Fusarium solani causing root rot in sweet cherry (Prunus avium). We here also report the severity and outbreak of this disease, which has been found in other regions in recent years and may become prevalent. Further research on disease management strategies is urgently needed to protect sweet cherry production.

First Report of Klebsiella variicola Causing Tomato Pith Necrosis in Yunnan Province, China.

Tomato (Solanum lycopersicum L.) is a key vegetable crop in China. In August 2023, an outbreak of bacterial pith necrosis in tomato occurred in Lufeng County, Yunnan Province, China, affecting over 40% of the tomato plants in a greenhouse. The stems of infected plants developed a waterlogged soft rot and the disease progressed, the lower leaves and lateral branches of infected plants gradually wilted and died. A longitudinal cut of the stem revealed hollow pith with brown vascular tissue. To isolate the pathogen, the plant surface was disinfested with 75% ethanol. Then, a piece of infected tissue from the base of the stem was excised and immersed in sterile water for 2 min. A small amount of liquid was streaked onto TTC (2,3,5-triphenyltetrazolium chloride) agar medium using an inoculation loop, and plates were incubated at 28℃ for 24 h. Colonies on the TTC plate were white, indicating that the pathogen was not Ralstonia solanacearum. Colonies grown on LB (Luria-Bertani) agar medium were randomly selected and subjected to preliminary pathogenicity tests. Based on the results, a colony named Kv4 was selected and purified through six subcultures in LB agar medium. Biochemical tests showed the strain utilized D-sorbitol, raffinose and citrate but not adonitol, and was positive for methyl red, D-glucose (acid), urea hydrolysis, lysine decarboxylase, and motility, and negative for phenylalanine deaminase, H2S production, indole production, and ornithine decarboxylase. These characteristics align with Klebsiella species (Garrity et al. 2007). To determine the species of strain Kv4, partial sequences of the 16S rDNA, phoE, leuS, and rpoB genes were amplified (Barrios-Camacho et al. 2019) and sequenced. Through BLASTn analysis, strain Kv4 sequences of 16S rDNA (OR888750) had 99.47% identity (1488/1496 bp), phoE (OR899599) had 98.69% (605/613 bp) identity, leuS (OR899598) had 99.07% identity (959/968 bp), and rpoB (OR899597) had 97.69% (633/648 bp) identity with Klebsiella variicola strain FF0907. Using the ClustalW algorithm in MEGA11 for nucleotide sequence alignment, phylogenetic trees were constructed with 16S and phoE, leuS, and rpoB via the neighbor-joining method, confirming strain Kv4 as K. variicola. To test pathogenicity, the roots of 25 'Moneymaker' tomato plants with four to five true leaves were wounded, then each plant inoculated with a 15 mL bacterial suspension (OD600=0.6) of strain Kv4, while the control plants received sterile water. Plants were incubated at 28℃ with a 16 h photoperiod. Experiments were done twice. At 15 days after inoculation (DAI), all plants inoculated with Kv4 showed yellowing, unevenly distributed small black necrotic spots on the leaf surface, and purple-brown soft rot at the stem base. By 18 DAI, there was a gradual transformation of the stem bases from green to purplish brown. At 21 DAI, 60% of the inoculated plants displayed brownish soft rot at the stem base. In contrast, the control plants remained symptom-free. The pathogen was re-isolated from the stem and identified as K. variicola via sequence analysis of 16S, phoE, leuS, and rpoB. In recent years, several new bacterial pith necrosis diseases were reported in tomato (Guo et al. 2023; Ivić et al. 2023). This is the first study documenting K. variicola causing bacterial pith necrosis in tomato. Once considered a benign plant endophyte, Sun et al. (2023) reported K. variicola causing banana sheath rot in Guangdong and Guangxi Provinces, China. Malik et al. (2023) reported that K. variicola caused leaf streak in sorghum in India. This report of bacterial pith necrosis in tomato caused by K. variicola strain Kv4 underscores the escalating threat posed by emerging pathogens to agricultural production. The emergence of K. variicola as a tomato pathogen complicates plant disease management strategies.

First Report of Phytophthora cinnamomi causing root rot of avocado trees in Greece.

In September 2023, thirty declining 30-year-old avocado (Persea americana) trees ('Hass' grafted on 'Zutano' seedlings) were detected in a 1.5-ha orchard in the island of Crete (Chania region). Crown symptoms encompassed wilting and leaf chlorosis, advancing to defoliation and extensive dieback. Tap and feeder roots decayed and brown discoloration of root tissues was evident on heavily infected trees. The disease was severe and widespread, resulting in a 5% mortality rate among 300 trees. The pathogen was isolated with a modified soil baiting technique (Ferguson and Jeffers, 1999). Surface disinfected avocado fruits were immersed in water containing soil samples. Following a period of 2 to 8 days, tissue fragments from the resulting necrotic lesions on the fruit surface were transferred on ΡΑRP medium and subsequently incubated at 20°C (Ferguson and Jeffers, 1999). Three isolates (AV2, AV12 and AV11a) were obtained by transferring single hyphal tips to new Petri dishes containing V8 juice agar. They were grown at 20˚C and used for identification after 10 days. Isolates formed coralloid colonies with abundant clustered spherical hyphal swellings and terminal or intercalary (ratio 1:5) thick-walled chlamydospores measuring 20 to 36 μm (avg 29±0.8 μm) with characteristic thick walls (avg 1.2±0.2 μm). Sporangia, produced in non-sterile soil-extract water, were ovoid to obpyriform, persistent, non-papillate, 32 to 81 μm (avg 56±4.8 μm) long and 20 to 42 μm (avg 31±3.2 μm) wide (n=100). Isolates were heterothallic as they did not produce oospores in single cultures. Based on the morphological traits the isolates were identified as Phytophthora cinnamomi (Erwin and Ribeiro 1996). The internal transcribe spacer region (ITS) including ITS1, 5.8S rDNA region, and ITS2 as well as the cytochrome c oxidase subunit I (coxI) gene of the three representative isolates wereamplified with ITS1/ITS4 and FM83/FM84 primers, respectively (White et al. 1990; Martin and Tooley 2003), and sequenced (GenBank acc. PP506613 to PP506615 and PQ063867 to PQ063869, respectively). BLAST search revealed almost 100% identity with the sequences of P. cinnamomi ex-isotype isolate (KC478663 and KU899315 respectively). Pathogenicity tests using isolate AV2 were conducted following the soil infestation method (Jung et al. 1996) using six-year-old avocado 'Zutano' seedlings. Six non-inoculated plants treated with vermiculite-multivitamin juice mixture were used as controls. Plants (1 m tall) were grown in pots under greenhouse conditions and watered regularly. Six weeks post inoculation, all inoculated trees showed chlorosis, wilting and root rot, while control plants remained symptomless. Symptoms were similar to those observed in the field and the pathogen was re-isolated and molecularly identified as previously described. This study presents the first documented occurrence of P. cinnamomi, widely regarded as the most destructive avocado pathogen globally, on avocado crops in Greece (Rodger et al. 2019). Additionally, this marks the first recorded presence of this pathogen on the island of Crete, regardless of the host species. The accurate identification of Phytophthora species associated with avocado root rot is essential for implementing an effective disease management strategy, particularly in the selection of appropriate disease-resistant rootstocks.

A systematic review and meta-analysis of cortisol levels in Plasmodium infections

Malaria has complex interactions with host physiology, including alterations in cortisol levels. Cortisol, a key hormone in the stress response, is known to be dysregulated in various infectious diseases. This systematic review and meta-analysis aimed to elucidate the relationship between Plasmodium infection and cortisol levels, shedding light on the intricate interplay between the parasite and the host’s endocrine system. The methodological protocol for assessing cortisol levels in malaria patients was registered in PROSPERO (CRD42024496578), a widely recognized international prospective register of systematic reviews. This registration ensures transparency and minimizes the risk of bias in our research. A comprehensive search strategy was employed across major databases, including Embase, PubMed, Scopus, and Medline, to include studies that reported cortisol levels in infected patients. The qualitative synthesis was undertaken to synthesize the difference in cortisol levels between malaria-infected and uninfected individuals. The meta-analysis employed the random effects model in the quantitative synthesis to calculate the effect estimate. The review included a total of 20 studies, with a substantial number conducted in Africa, followed by Asia and South America. Most included studies (13/20, 65%) reported higher cortisol levels in infected patients than in uninfected patients. The meta-analysis confirmed significantly higher cortisol levels in infected patients compared to uninfected individuals (P < 0.0001, standardized mean difference (SMD): 1.354, 95% confidence interval: 0.913 to 1.795, I2: 88.3%, across 15 studies). Notably, the method for cortisol measurement and the type of blood sample used (serum or plasma) were significant moderators in the analysis, indicating that these factors may influence the observed relationship between Plasmodium infection and cortisol levels. The systematic review and meta-analysis confirmed that Plasmodium infection is associated with increased cortisol levels, highlighting the intricate relationship between the disease and the host stress response. These findings underscore the potential of cortisol as a supplementary biomarker for understanding the pathophysiological impact of malaria. By providing insights into the stress-related mechanisms of malaria, this comprehensive understanding can inform future research and potentially enhance disease management and treatment strategies, particularly in regions heavily burdened by malaria.

A Novel Plant-Derived Biopesticide Mitigates Fusarium Root Rot of Angelica sinensis by Modulating the Rhizosphere Microbiome and Root Metabolome

Fusarium root rot caused by the Fusarium species complex significantly affects the yield and quality of Angelica sinensis, a valuable medicinal herb. Traditional management primarily relies on chemical fungicides, which have led to pathogen resistance, environmental hazards, and concerns regarding public health and the active components in A. sinensis. This study explores the efficacy of a novel plant-derived biopesticide Shi Chuang Zhi Feng Ning (T1; SCZFN), alongside Bacillus subtilis wettable powder (T2) and a chemical fungicide (T3), in controlling root rot and understanding their impacts on the rhizosphere microbial community and root metabolome. Results of the field experiment demonstrated that treatments T1 and T3 achieved control efficiencies of 73.17% and 75.45%, respectively, significantly outperforming T2 (39.99%) and the control. High-throughput sequencing revealed that all treatments altered the diversity and structure of microbial communities, with T1 and T2 reducing the abundance of taxa linked to root rot, such as Muribaculaceae spp., Humicola spp., Fusarium spp., and Mycochlamys spp. Treatment T1 notably enhanced beneficial bacterial taxa, including Acidobacteria spp., Nitrospira spp., and Pedosphaeraceae spp., involved in carbon cycling and plant growth promotion. Metabolomic analysis identified 39, 105, and 45 differentially expressed metabolites (DEMs) across the treatments, demonstrating T1’s potential to modulate the root metabolome effectively. Further, a correlation analysis demonstrated a stronger correlation between distinct microorganisms with significant influence and DEMs of T1 treatment compared to other treatments. These findings underscore biopesticide SCZFN’s role in enhancing plant health and disease suppression in A. sinensis, providing insights into its biocontrol mechanisms and supporting the development of sustainable disease management strategies in its cultivation.

Adaptive interventions for advancing in situ wildlife disease management.

There is a critical need for advancements in disease management strategies for wildlife, but free-living animals pose numerous challenges that can hinder progress. Most disease management attempts involve fixed interventions accompanied by post hoc outcome assessments focused on success or failure. Though these approaches have led to valuable management advances, there are limitations to both the rate of advancement and amount of information that can be gained. As such, strategies that support more rapid progress are required. Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei mites, is a globally emerging and re-emerging panzootic that exemplifies this problem. The bare-nosed wombat (Vombatus ursinus), a marsupial endemic to southeastern Australia, is impacted by sarcoptic mange throughout its geographic range and enhanced disease management capabilities are needed to improve upon existing in situ methods. We sought to advance in situ wildlife disease management for sarcoptic mange in free-living bare-nosed wombats, implementing an adaptive approach using fluralaner (Bravecto, MSD Animal Health) and a structured process of learning and method-optimisation. By using surveillance of treated wombats to inform real-time management changes, we have demonstrated the efficacy of topically administered fluralaner at 45 and 85 mg/kg against sarcoptic mange. Importantly, we observed variation in the effects of 45 mg/kg doses, but through our adaptive approach found that 85 mg/kg doses consistently reduced mange severity. Through modifying our surveillance program, we also identified individual-level variation in wombat observability and used this to quantify the level of surveillance needed to assess long-term management success. Our adaptive intervention represents the first report of sarcoptic mange management with fluralaner in free-living wildlife and evaluation of its efficacy in situ. This study illustrates how adapting interventions in real time can advance wildlife disease management and may be applicable to accelerating in situ improvements for other host-pathogen systems.

Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration.

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Sterility Mosaic Disease of Pigeonpea (Cajanus cajan (L.) Huth): Current Status, Disease Management Strategies, and Future Prospects

Pigeonpea (Cajanus cajan) is one of the important grain legume crops cultivated in the semi-arid tropics, playing a crucial role in the economic well-being of subsistence farmers. India is the major producer of pigeonpea, accounting for over 75% of the world’s production. Sterility mosaic disease (SMD), caused by Pigeonpea sterility mosaic virus (PPSMV) and transmitted by the eriophyid mite (Aceria cajani), is a major constraint to pigeonpea cultivation in the Indian subcontinent, leading to potential yield losses of up to 100%. The recent characterization of another Emaravirus associated with SMD has further complicated the etiology of this challenging viral disease. This review focuses on critical areas, including the current status of the disease, transmission and host-range, rapid phenotyping techniques, as well as available disease management strategies. The review concludes with insights into the future prospects, offering an overview and direction for further research and management strategies.

The mortality burden of cachexia or weight loss in patients with colorectal or pancreatic cancer: A systematic literature review.

Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (n=23) or univariate (n=3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.

Resistance of Ascochyta rabiei isolates from chickpeas (Cicer arietinum L.) to fungicides

Ascochyta blight is a disease that causes significant yield losses in chickpea crops in Turkey under favorable environmental conditions. The fungal pathogen Ascochyta rabiei is the causative agent of this disease. The antifungal activity of previous fungicides against A. rabiei was not effective due to the heterothallic nature of the fungus. The aim of this study was to determine the sensitivity of A. rabiei to fungicides (25.2 g kgˉ1 boscalid + 12.8 g kgˉ1 pyraclostrobin; 50% tebuconazole + 25% trifloxystrobin; 62.5 g Lˉ1 propiconazole + 37.5 g Lˉ1 azoxystrobin; 80% thiram; 80% kükürt (sulphur); 80% mancozeb; 80% maneb) under in vitro and field conditions. Pure cultures of A. rabiei were isolated from infected chickpea plants collected in Boğazlayan, Sarıkaya, Sorgun, Merkez and Yerköy. A total of 14 A. rabiei isolates and 4 references were evaluated. The field test was conducted at Yozgat Bozok University, Yerköy Agricultural Application and Research Center Station. The trials began on March 14, 2021. The experimental area was divided into plots and the susceptible chickpea variety Sarı98 was used for the study. Two artificial inoculations were carried out approximately on the 40th and 80th days after sowing. Twenty-four hours after inoculation, the chickpea plants were sprayed with the fungicides Nativo® WG 75, Bellis®, Dikotan® M45 and Thiovit Jet® using a handheld sprayer. In vitro testing revealed that A. rabiei was resistant to kükürt (sulphur), thiram, maneb, and mancozeb. A field study showed that the percentage of A. rabiei isolates treated with the mancozeb fungicide was between 14 and 21% of the control. Therefore, effective disease management strategies should include not only the use of fungicides, but also alternative approaches such as the use of resistant varieties. Moreover, the study focused on phenotypic resistance and suggests that future research should investigate the genetic and molecular mechanisms underlying A. rabiei resistance to enable better resistance management.

DenseNet201Plus: Cost-effective transfer-learning architecture for rapid leaf disease identification with attention mechanisms

Plant leaf diseases are a significant concern in agriculture due to their detrimental impact on crop productivity and food security. Effective disease management depends on the early and accurate detection and diagnosis of these conditions, facilitating timely intervention and mitigation strategies. In this study, we address the pressing need for accurate and efficient methods for detecting leaf diseases by introducing a new architecture called DenseNet201Plus. DenseNet201 was modified by including superior data augmentation and pre-processing techniques, an attention-based transition mechanism, multiple attention modules, and dense blocks. These modifications enhance the robustness and accuracy of the proposed DenseNet201Plus model in diagnosing diseases related to plant leaves. The proposed architecture was trained using two distinct datasets: Banana Leaf Disease and Black Gram Leaf Disease. Through extensive experimentation, we evaluated the performance of DenseNet201Plus in terms of various classification metrics and achieved values of 0.9012, 0.9012, 0.9012, and 0.9716 for accuracy, precision, recall, and AUC for the banana leaf disease dataset, respectively. Similarly, the black gram leaf disease dataset model provides values of 0.9950, 0.9950, 0.9950, and 1.0 for accuracy, precision, recall, and AUC. Compared to other well-known pre-trained convolutional neural network (CNN) architectures, our proposed model demonstrates superior performance in both utilized datasets. Last but not least, we combined the strength of Grad-CAM++ with our proposed model to enhance the interpretability and localization of disease areas, providing valuable insights for agricultural practitioners and researchers to make informed decisions and optimize disease management strategies.

Unravelling the complex interplay of age, comorbidities, and multimorbidities in COVID-19 disease progression: Clinical implications and future perspectives

IntroductionThe COVID-19 infection as an inflammatory disease has posed significant challenges to global public health due to multi-factor risks associated with it leading to disease severity and mortality. Understanding the effect of age and comorbidities on overall disease progression is crucial to identify highly susceptible individuals and to develop effective disease management strategies in a resource limited country like Pakistan. MethodologyA retrospective study was conducted on hospitalized COVID-19 patients to assess the prevalence of various comorbidities among different age groups and their effect on disease severity and mortality rate. ResultsIn this retrospective study, a cohort of 618 hospitalized COVID-19 patients was analyzed, consisting of 387 males (62.6 %) and 231 females (37.4 %). Notably, the young age group (15–24 years), had the lowest frequency of hospitalized COVID-19 patients, while no case was observed in children (≤14 years) showing a significant association (p < 0.001) of age and disease prevalence. Comorbidities were observed in 63.9 % of COVID-19 patients including hypertension (HTN), diabetes mellitus (DM), ischemic heart diseases (IHD), asthma, chronic kidney disease (CKD) and tuberculosis (TB). The most common comorbidities were HTN (42.1 %) followed by DM (33.8 %), IHD (16.5 %), asthma (11.2 %), CKD (7.9 %) and TB (1.9 %).Furthermore, the study revealed a significant association between comorbidities, age groups, and the need for non-invasive ventilation (NIV) (p < 0.001), mechanical ventilation (MV) (p < 0.001), and intensive care unit (ICU) admission (p < 0.001). Patients with specific comorbidities and those in the older age group (≥65 years) demonstrated a higher need for these interventions. However, patients without any comorbidity consistently exhibited the highest cumulative proportion of survival at each time point, indicating better overall survival outcomes. In contrast, patients with multimorbidities of DM/HTN/IHD, HTN/IHD, and DM/HTN/CKD had comparatively lower survival rates and higher mortality rates (p < 0.001). ConclusionThis research highlights the significant impact of age, comorbidities and multimorbidities on the severity and mortality of COVID-19 patients. It highlights the importance of considering these factors in tailoring effective management strategies for patients with COVID-19 or other infectious respiratory diseases.

Machine Learning Investigation of Tuberculosis with Medicine Immunity Impact

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions.

Molecular detection of avian pathogens in poultry red mite (Dermanyssus gallinae) in Algerian layer farms as a potential predictive tool

The poultry red mite Dermanyssus gallinae is a hematophagous ectoparasite of layer hens. Infestations with poultry red mites pose an increasing threat to the egg production industry, causing serious problems to animal health and welfare, directly or indirectly as a vector of several infectious agents. In this study, we aimed to investigate common avian pathogens in mites. The mite samples were collected from 58 poultry farms in 7 regions accounting for more than 70 % of the national egg production in Algeria. The presence of 13 avian pathogens was detected using DNA and RNA samples from mites collected. Results revealed significant associations between PRM and potential pathogens such as Escherichia coli, Salmonella enterica, fowlpox virus, and gallid herpesvirus 1. Pathogen detection in Dermanyssus gallinae could serve as an early diagnostic or a risk analysis tool for infectious diseases in poultry farms, facilitating effective disease management strategies. Despite further research being necessary to address uncertainties, such a strategy could be used to enhance the integrated management of poultry health.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1–9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Altering cold-regulated gene expression decouples the salicylic acid-growth trade-off in Arabidopsis.

In Arabidopsis (Arabidopsis thaliana), overproduction of salicylic acid (SA) increases disease resistance and abiotic stress tolerance but penalizes growth. This growth-defense trade-off has hindered the adoption of SA-based disease management strategies in agriculture. However, investigation of how SA inhibits plant growth has been challenging because many SA-hyperaccumulating Arabidopsis mutants have developmental defects due to the pleiotropic effects of the underlying genes. Here, we heterologously expressed a bacterial SA synthase gene in Arabidopsis and observed that elevated SA levels decreased plant growth and reduced the expression of cold-regulated (COR) genes in a dose-dependent manner. Growth suppression was exacerbated at below-ambient temperatures. Severing the SA-responsiveness of individual COR genes was sufficient to overcome the growth inhibition caused by elevated SA at ambient and below-ambient temperatures while preserving disease- and abiotic-stress-related benefits. Our results show the potential of decoupling SA-mediated growth and defense trade-offs for improving crop productivity.

Unveiling the adverse events of Nusinersen in spinal muscular atrophy management based on FAERS database

This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

First Report of Colletotrichum gigasporum causing Anthracnose of chili pepper in South Korea.

Anthracnose, a destructive fungal disease, poses a significant threat to chili pepper (Capsicum annuum L.) production worldwide (de Silva et al. 2019). In South Korea, anthracnose outbreaks have traditionally been attributed to several Colletotrichum species such as C. gloeosporioides and C. acutatum. About 10% of the yield (chili production) is lost annually in South Korea due to chili anthracnose (Oo et al. 2020). During field surveys conducted in August 2017, symptomatic lesions resembling anthracnose were observed on chili pepper in two farmer's fields (Gochang and Cheongyang) in South Korea. Affected fruits exhibited characteristic symptoms, including circular sunken lesions with dark margins and abundant orange spore masses on the surface. About 20% of chili pepper fruit were affected in each field with an area of about 0.2 ha. Five putative Colletotrichum spp. isolates were obtained from six affected fruits (three from each field) following the procedure described by Cai et el. (2009). Three isolates (C01049, C01111, and C01115), representing each location, were selected to identify at the species level. Colonies on potato dextrose agar (incubated at 25°C in the dark for 7 days) were cottony with entire margins, white aerial mycelium and dark gray in the center. Conidia were hyaline, aseptate, cylindrical with bothnds round, and 17.8 - 30.5 × 6.0 -10.0 µm (mean 23.8 ×7.9 μm, n = 30). Appressoria were dark brown, irregular but mostly ovoid with smooth walls. These morphological features align with those of Colletotrichum spp. within the Colletotrichum gigasporum species (Liu et al. 2014). The identity of the pathogen was further confirmed through multi-locus phylogenetic analysis. The target genes including ITS, ACT, CHS-1, GAPDH, TUB2, and GS were amplified and sequenced using the primer sets ITS1/ITS4, ACT 512F/ ACT-783R, CHS-79F/ CHS-345R, GDF/GDR, T1/Bt2b, and GSF1/GSR1, respectively (Weir et al. 2012; Liu et al. 2014). The resulting sequences were deposited in GenBank (accession no: ITS: MT605261, MT605262, LC823714; ACT: MT612991, MT612992, LC823718; CHS-1: MT612993, MT612994, LC823717; GAPDH: LC811375, LC811376, LC823716; TUB2: MT612997, MT612998, LC823715; GS: LC811377, LC811378, LC823719). The constructed Bayesian and maximum likelihood tree based on combined sequences of ITS, ACT, CHS-1, GAPDH, TUB2, and GS confirmed the identification of the isolates (C01049, C01111, C01115) as C. gigasporum. Pathogenicity tests were conducted by inoculating healthy chili fruit with 70 µL of a conidial suspension (1×106 conidia /mL) of pure cultures of the isolates. The conidial suspension was applied on 10 wounded or 10 non-wounded fruit. The same number of fruit were treated with sterile distilled water as controls. Within 5 days of inoculation, symptoms consistent with anthracnose developed on the inoculated wounded fruit, whereas non-wounded and control fruit remained asymptomatic. This experiment was repeated twice. Colletotrichum gigasporum was re-isolated from diseased tissue of inoculated fruit. Colletotrichum gigasporum has been identified as the cause of anthracnose on Dalbergia odorifera, Carica papaya in China, and Brassica oleracea in India (Wan et al., 2018; Saini et al. 2022; He et al. 2023). To the best of our knowledge, this report marks the first documented instance of C. gigasporum causing anthracnose of chili pepper in South Korea. These results indicate that various species of Colletotrichum can be the fungi causing chili pepper anthracnose. The findings of this study emphasize the need for effective disease management strategies to mitigate impact of C. gigasporum on chili pepper cultivation in the region.