Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy.

Despite the remarkable clinical success of immunotherapies in a subset of cancer patients, many fail to respond to treatment and exhibit resistance. Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Genetic depletion or pharmacologic inhibition of PIKfyve elevated tumor-specific MHC-I surface expression, increased intratumoral functional CD8+ T cells, and slowed tumor progression in multiple syngeneic mouse models. Importantly, enhanced antitumor responses by Pikfyve-depletion were CD8+ T cell- and MHC-I-dependent, as CD8+ T cell depletion or B2m knockout rescued tumor growth. Furthermore, PIKfyve inhibition improved response to immune checkpoint blockade (ICB), adoptive cell therapy, and a therapeutic vaccine. High expression of PIKFYVE was also predictive of poor response to ICB and prognostic of poor survival in ICB-treated cohorts. Collectively, our findings show that targeting PIKfyve enhances immunotherapies by elevating surface expression of MHC-I in cancer cells, and PIKfyve inhibitors have potential as agents to increase immunotherapy response in cancer patients.

Main drivers of dragonflies and damselflies (Insecta; Odonata) metacommunities in streams inside protected areas in the Brazilian Amazon.

The evaluation of environmental and spatial influence in freshwater systems is crucial for the conservation of aquatic diversity. So, we evaluated communities of Odonata in streams inside and outside sustainable use areas in the Brazilian western Amazon. We predicted that these streams would differ regarding habitat integrity and species α and ß diversity. We also predict that environmental and spatial variables will be important for both suborders, but with more substantial effects on Zygoptera species, considering their nature of forest-specialist. The study was conducted in 35 streams, 19 inside and 16 outside sustainable use areas. The streams outside presented high species richness, abundance, and number of exclusive forest-specialist species from Zygoptera and higher scores of habitat integrity. In contrast, one sustainable use area presented the lowest values of these metrics. Besides, we found that environmental and spatial variables were significantly associated to Zygoptera species composition, but not with Anisoptera, which can be explained by their cosmopolitan nature. Our results indicated that an interplay between environmental and spatial processes determines the structure of the metacommunities of Zygoptera. The less effective dispersal rates and narrow ecological tolerance of Zygoptera species make them more influenced by local conditions and dispersal limitation, and more sensible to habitat modifications. We highlight the importance of improving the local management of the sustainable use areas by environmental agencies, mainly on areas that are losing their capacity to maintain the aquatic fauna, and implementation of social policies toward traditional people.

Evaluation of internal markers in digestibility estimation for sheep and goats.

The objective of this study was to compare the indirect methods of obtaining digestibility with the direct method of total fecal collection to estimate the apparent digestibility of nutrients in sheep and goats supplemented with non-protein nitrogen. Five goats and five sheep with no defined racial pattern were used, distributed in two 5 × 5 Latin squares, with split plots, considering the diets as plots and the apparent digestibility determination methodologies as subplots. The diets were composed of buffelgrass hay and the addition, via ruminal infusion, of increasing amounts of nitrogen supplementation in order to gradually raise the CP level of the basal diet in intervals of 2% points, that is, + 2, +4, + 6 and + 8%. Samples of the feeds offered, and the leftovers were collected daily during the five days of collection to determine the nutrient intake, as well as the total collection of feces to determine the apparent digestibility of the nutrients. The amount of fecal dry matter excreted was estimated by the concentration of Indigestible Acid Detergent Fiber (ADFi), Indigestible Neutral Detergent Fiber (NDFi), Indigestible Dry Matter at 244 h (DMi 244 h) and Indigestible Dry Matter at 264 h (DMi 264 h). Among the evaluated markers, DMi 264 h had the lowest accuracy in estimating fecal excretion and nutrient digestibility. For the goat species, the markers ADFi and DMi 244 h proved to be able to adequately predict fecal excretion and digestibility indices, while NDFi stood out for both species. Among the evaluated markers, NDFi is the one that most accurately estimates the nutrient digestibility of the diet for goats and sheep.

Human land-uses homogenize stream assemblages and reduce animal biomass production.

Human land-use change is a major threat to natural ecosystems worldwide. Nonetheless, the effects of human land-uses on the structure of plant and animal assemblages and their functional characteristics need to be better understood. Furthermore, the pathways by which human land uses affect ecosystem functions, such as biomass production, still need to be clarified. We compiled a unique dataset of fish, arthropod and macrophyte assemblages from 61 stream ecosystems in two Neotropical biomes: Amazonian rainforest and Uruguayan grasslands. We then tested how the cover of agriculture, pasture, urbanization and afforestation affected the taxonomic richness and functional diversity of those three species assemblages, and the consequences of these effects for animal biomass production. Single trait categories and functional diversity were evaluated, combining recruitment and life-history, resource and habitat-use, and body size. The effects of intensive human land-uses on taxonomic and functional diversities were as strong as other drivers known to affect biodiversity, such as local climate and environmental factors. In both biomes, the taxonomic richness and functional diversity of animal and macrophyte assemblages decreased with increasing cover of agriculture, pasture, and urbanization. Human land-uses were associated with functional homogenization of both animal and macrophyte assemblages. Human land-uses reduced animal biomass through direct and indirect pathways mediated by declines in taxonomic and functional diversities. Our findings indicate that converting natural ecosystems to supply human demands results in species loss and trait homogenization across multiple biotic assemblages, ultimately reducing animal biomass production in streams.

Biochemical responses of the mussel Perna perna after exposure to environmental concentrations of the UV filter Benzophenone-3.

Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 µg.L-1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) activity and lipoperoxidation (MDA) were evaluated in the gills. A significant reduction (p < 0.05) in the activity of G6PDH and GPx was observed after exposure for 7 days to 0.1 µg.L-1. However, no significant differences were observed in GST activity and MDA levels, independently of the exposure time. Principal component analysis (PCA) showed an association of BP-3 highest concentration with GR and MDA at 72 h and only with GR at 7 days of exposure. Similarly, the integrated biomarker response (IBR) demonstrated GR and MDA alterations. In conclusion, environmentally relevant concentrations of BP-3 altered antioxidant and auxiliary enzymes, which could cause long-term damage to P.perna mussels. The need to implement more efficient techniques in wastewater treatment systems is pointed out, especially in summer, when UV filters are used more frequently and abundantly.

Study of Melipona quadrifasciata brain under operant learning using proteomic and phosphoproteomic analysis.

Learning to anticipate events based on the predictive relationship between an action and an outcome (operant conditioning) is a form of associative learning shared by humans and most of other living beings, including invertebrates. Several behavioral studies on the mechanisms of operant conditioning have included Melipona quadrifasciata, a honey bee that is easily manipulated due to lack of sting. In this work, brain proteomes of Melipona bees trained using operant conditioning and untrained (control) bees were compared by two-dimensional gel electrophoresis analysis within pI range of 3-10 and 4-7; in order to find proteins specifically related to this type of associative learning.One protein was detected with differential protein abundance in the brains of trained bees, when compared to not trained ones, through computational gel imaging and statistical analysis. This protein was identified by peptide mass fingerprinting and MS/MS peptide fragmentation using a MALDI-TOF/TOF mass spectrometer as one isoform of arginine kinase monomer, apparently dephosphorylated. Brain protein maps were obtained by 2-DE (Two-dimensional gel electrophoresis) from a total proteins and phosphoproteins extract of the bee Melipona quadrifasciata. One isoform of arginine kinase, probably a dephosphorylated isoform, was significantly more abundant in the brain of trained bees using operant conditioning. Arginine kinase has been reported as an important enzyme of the energy releasing process in the visual system of the bee, but it may carry out additional and unexpected functions in the bee brain for learning process.

Impact of FGFR2 gene fusions on survival of patients with intrahepatic cholangiocarcinoma following curative intent resection.

BACKGROUND: Intrahepatic Cholangiocarcinoma (iCCA) is an aggressive cancer with diverse mutational profiles. An important molecular subtype is fibroblast growth factor receptor 2 (FGFR2) fusion. The effect of FGFR2 fusions on prognosis is unknown. Our aim was to assess the outcomes in resected CCA patients in relation to FGFR2 status. METHODS: Surgically treated CCA patients from a single institution were retrospectively reviewed between 2008 and 2014. FGFR rearrangements were detected by fluorescence in situ hybridization (FISH). Data included patient demographics, tumor pathology, disease-free survival (DFS) and overall survival (OS). RESULTS: Ninety-five patients underwent surgical resection for iCCA. Twelve (13%) of these were found to have FGFR2 fusion, none of which were treated with FGFR targeted therapy. Patients with FGFR2 fusions were found to have a longer 5-year (83 vs. 32%, p = 0.01) and 10-year (46 vs. 22%, p = 0.04) OS. Five and 10-year DFS was also increased (68 vs. 33% p = 0.04) and (68 vs. 25 %, p = 0.02,). FGFR2 fusion status was the strongest independent factor associated with improved OS (HR 0.23, 0.09-0.62, p=0.003) and DFS (HR 0.18, 0.05-0.67, p=0.01). CONCLUSION: Patients with CCA FGFR2 fusion have improved OS and DFS following surgical resection.

COVID-19 and automation in a developing economy: Evidence from Chile.

This paper analyzes the Covid-19 pandemic impact of the global process of automation on employment in a developing economy. This is particularly interesting because developing economies characteristics, such as having larger informal sectors and weaker social safety nets, shapes the impact of automation on labor markets. We show that occupations with a higher risk of automation exhibit the most significant employment contraction. More specifically, we find that one standard deviation higher in sectoral share of employment in occupations at risk of automation (OaRA) implied around 7% less employment on average between the last quarter of 2019 and the first quarter of 2021. The effect on informal employees is three times more in comparison to formal employees, and the estimation for self-employed workers is not statistically significant. We also find that employees in sector with relatively low compared to high wages, both vis-à-vis the US, exhibit a 20% smaller reaction on employment due to the pandemic restrictions. We do not find robust evidence showing that the employment contraction has been larger among female workers or in jobs with higher at-work physical proximity, but we do find a positive relationship related to the capacity of working remotely.

Response of aquatic insects to an environmental gradient in Amazonian streams.

The increasing land use in the Amazon region has resulted in the widespread substitution of forest areas with pasture and bauxite mining. These land uses reduce the forest cover of streams and modify their characteristics, reducing the diversity of aquatic insect assemblages. In the present study, we aimed to identify the threshold of the assemblages of the larvae of insects of the orders Ephemeroptera, Plecoptera, and Trichoptera (collectively known as EPT), and adults of the order Odonata, along an environmental gradient of land use and land cover (LULC). We sampled 30 streams along an environmental gradient determined by the proportion of forest, pasture, and bauxite mining observed within the catchment of each stream. We identified 12 taxa associated with forest (nine positively and three negatively) and four negatively associated with pasture. However, no taxa were associated explicitly with the bauxite mining gradient. As forest is converted to pasture, the abundance and frequency of occurrence of the taxa sensitive to pasture are reduced, reflecting their environmental sensitivity and their potential as sentinels of preserved streams. The identification of the thresholds of the EPT and odonates taxa allowed us to determine which of these organisms are positively or negatively associated with the environmental gradient of LULC in Amazonian streams. We hope that the results of the present study can be applied in future biomonitoring programs, particularly for monitoring the response of aquatic insects to the degradation of streams.

Spineless cactus use management on microbiological quality, performance, and nutritional disorders in sheep.

The physically effective neutral detergent fiber content alone has not been able to explain the appearance of diarrhea in ruminants fed diets with large volumes of spineless cactus, so the proliferation of enterobacteria in spineless cactus may be associated with cases of diarrhea in sheep. In the in vitro test, used two varieties of spineless cactus, both of which were chopped to particles of 4 and 2 cm2. For the in vivo test, 15 lambs were allocated to three treatment groups, namely, spineless cactus crushed and immediately supplied to the animals; spineless cactus crushed 8 h before supply; and silage of spineless cactus. The variables evaluated were dry matter intake, weight gain, fecal score, hemogram, and fecal colony count. In the in vitro test, higher Enterobacteriaceae and lactic acid bacteria counts were found both at 12 h and 24 h when the spineless cactus was crushed to 2 cm2 in both varieties. The sheep fed the spineless cactus crushed 8 h prior to supply showed the highest Enterobacteriaceae count in the feces (8.48 CFU/g), compared to animals fed silage of spineless cactus (4.95 CFU/g). It can thus be concluded that the management of spineless cactus influences the development of total and fecal coliforms, especially when it is chopped to 2 cm2 and exposed to the environment for periods longer than 7 h, and that the bacterial population can be controlled by administering the spineless cactus in the form of silage.

Percutaneous treatments of primary aneurysmal bone cysts: systematic review and meta-analysis.

PURPOSE: To systematically review the literature to determine recurrence rates of percutaneous treatments for primary aneurysmal bone cysts (ABC). METHODS: Search strategies were performed in the following databases: PubMed, SCIELO, LILACS and BVS, using terms in English, Spanish and Portuguese (PROSPERO Registration Number: CRD42020170340). Longitudinal studies, either observational or clinical trials, with at least five patients and with a mean of 18 months of follow-up were included. Studies had to use any type of percutaneous treatments and report the recurrence rates of primary ABC treatment. Studies selection, data extraction and risk of bias assessment were performed independently by two researchers. A global meta-analysis was carried out to assess the proportion of recurrence. Studies were categorized into two subgroups: selective arterial embolization and sclerotherapy. RESULTS: Thirteen studies were included in the present study. The average success rate of percutaneous treatments for ABC was 91.11%, with a total of 37 lesions recurrences in the 416 patients. The sex ratio was 1:1. The subgroup of sclerotherapies presented a lower proportion of recurrence. The proportion of recurrence in the subgroup of selective arterial embolization was 19% (95%IC 12.11-27.54) and that of sclerotherapies was 6% (95%IC 3.65-9.19). CONCLUSIONS: Both percutaneous treatments for ABC are effective, showing a lower rate of recurrence. Sclerotherapy treatments seem to be promising, but further clinical trials must be conducted with a longer follow-up.

Ruminal and histological characteristics and nitrogen balance in lamb fed diets containing cactus as the only roughage.

This study examined rumen fermentation, histological, blood, and urinary characteristics as well as ammoniacal nitrogen concentration, pH, nitrogen balance, and microbial protein in lamb fed diets containing spineless cactus as the sole roughage source plus levels of wheat bran (WB) in comparison with a control diet based on spineless cactus and buffelgrass. Twenty-eight uncastrated, crossbreed lambs with an average initial weight of 22.6 ± 2.37 kg were used in the experiment. The treatments consisted of a standard diet (control) containing buffelgrass and spineless cactus and three diets containing cactus as the only roughage source plus varied concentrations of WB (30, 37, and 44%, on a dry matter basis). Results were evaluated by analysis of variance, and contrasts were applied at the 5% probability level for mean comparison. Rumen villus height and width were greater and musculature was lower in the lamb fed diets containing 37% and 44% WB compared with those fed control diet. In the intestine, the crypts were smaller in the animals which consumed the diets with 30, 44, and 37% WB. All WB levels resulted in lower nitrogen intake and retention. Microbial protein concentration, microbial protein efficiency, microbial nitrogen, urea, and glucose were not significantly affected. Feeding lamb with diets containing levels of wheat bran, with cactus as the only roughage source, does not negatively affect their ruminal-fermentation, blood, and urinary characteristics; ammoniacal nitrogen concentration; pH; or microbial protein. However, nitrogen balance and ruminal and intestinal morphometric characteristics are impaired.

Robot-Enabled Support of Daily Activities in Smart Home Environments.

Smart environments offer valuable technologies for activity monitoring and health assessment. Here, we describe an integration of robots into smart environments to provide more interactive support of individuals with functional limitations. RAS, our Robot Activity Support system, partners smart environment sensing, object detection and mapping, and robot interaction to detect and assist with activity errors that may occur in everyday settings. We describe the components of the RAS system and demonstrate its use in a smart home testbed. To evaluate the usability of RAS, we also collected and analyzed feedback from participants who received assistance from RAS in a smart home setting as they performed routine activities.

Toxic effects of antiparasitic pesticides used by the salmon industry in the marine amphipod Monocorophium insidiosum.

The use of antiparasitic pesticides (APs) has been widely required by the salmon industry to treat diseases. The direct emission of chemicals in the seawater has produced uncertainty about the potential effects on nontarget organisms, such as crustaceans. The aim of this study was to assess the toxicity of three APs used by the salmon farm industry, such as emamectin benzoate (EB), cypermethrin (CP), and deltamethrin (DE), in the amphipod Monocorophium insidiosum during 10 days through whole-sediment bioassay tests. Lethal concentration by 50 % (LC50-10d) and biochemical responses, such as glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), were measured as exposure and effects end points, respectively. Acute assays for DE (7.8 µg kg(-1), confidence interval, CI95% 5-11) and CP (57 µg kg(-1), CI95% 41-77) showed more mortality than EB (890 µg kg(-1), CI95% 672-1,171). In this study, it was possible to observe sublethal responses in amphipods after 2 days of exposure to APs. Significant induction in GST and TBARS (p < 0.05) were measured for CP and EB. Lower DE concentrations showed no significant biochemical responses. M. insidiosum was sensitive to AP concentrations at µg kg(-1) in sediments. This information would allow considering the possible consequences of detected concentrations for APs in areas with intensive salmon farming activity.

Calyceal Rupture Secondary to Nephrolithiasis: A Case Report Emphasizing Early Diagnosis and Management.

Calyceal rupture, defined as the extravasation of urine from the renal calyces into the perinephric or paranephric spaces, typically results from increased intrapelvic pressure due to urinary tract obstruction. This condition can lead to the formation of a perinephric urinoma and severe complications, such as infection, abscess formation, and impaired renal function. Timely diagnosis and management are crucial to prevent these adverse outcomes. Calyceal rupture often results from urolithiasis, with other causes including strictures, tumors, and congenital abnormalities. The rupture occurs when intrapelvic pressure exceeds the tensile strength of the calyceal walls, leading to urine leakage and potential inflammation or sepsis. Calyceal ruptures are quite rare, with their exact incidence not well-documented due to the infrequency of the condition and potential underreporting. Although relatively uncommon, the condition is more prevalent in individuals with recurrent nephrolithiasis and other predisposing factors. Timely recognition and intervention, guided by imaging studies such as non-contrast CT scans, are essential. Conservative management with medical therapy is effective in many cases, but surgical intervention may be necessary for larger stones or complications. This report presents the case of a 36-year-old female with calyceal rupture secondary to nephrolithiasis, presenting with severe flank pain. Upon initial presentation, the patient underwent a thorough workup, including imaging studies, appropriate medical management, and continuous monitoring. She was stabilized, her pain was effectively managed, and she was discharged with a scheduled outpatient follow-up. This case highlights the importance of early diagnosis, comprehensive management, and vigilant monitoring in preventing complications and promoting favorable outcomes.

Fruquintinib-Induced Cerebellar Hemorrhage in Left-Sided Descending Metastatic Colorectal Adenocarcinoma: A Case Report and Risk Assessment.

Colorectal adenocarcinoma is the most prevalent form of colorectal cancer, representing the majority of cases in the United States. The disease is driven by a series of genetic mutations, including alterations in the adenomatous polyposis coli (APC), Kirsten rat sarcoma viral oncogene homolog G12D (KRAS), human epidermal growth factor receptor 2 immunohistochemistry 3+ (HER-2 IHC3+), checkpoint kinase 2 (CHEK-2) and tumor protein P53 (TP53) genes, which lead to malignant transformation. While the standard treatment for metastatic colorectal cancer (mCRC) typically involves chemotherapy and targeted therapies, many patients experience disease progression, necessitating the exploration of novel treatments. Fruquintinib, a highly selective vascular endothelial growth factor (VEGFR) inhibitor, has emerged as a promising option for mCRC patients who have exhausted conventional therapies. However, its use is associated with significant bleeding risks, including rare but severe complications such as cerebellar hemorrhage. This case report presents a patient with mCRC who developed a cerebellar hemorrhage shortly after initiating fruquintinib therapy, highlighting the need for careful patient monitoring and individualized risk assessment to mitigate such serious adverse events.

Severe Pneumatosis Intestinalis and Hepatic Portal Venous Gas in a Patient With Methamphetamine Use: Early Recognition and Management.

Pneumatosis intestinalis (PI) and hepatic portal venous gas (HPVG) are rare but potentially life-threatening conditions characterized by the presence of gas within the bowel wall and portal venous system, respectively. This case report presents a 45-year-old male with a history of methamphetamine use who developed severe metabolic and hemodynamic instability, marked by altered mental status, metabolic acidosis, and ST elevations. Despite aggressive resuscitation and intensive care, the patient unfortunately succumbed to his condition, highlighting the gravity of these complications. This report underscores the importance of early recognition, comprehensive management, and timely surgical consultation to improve outcomes. It also emphasizes the need for a multidisciplinary approach and further research to better understand these conditions and the significant role of methamphetamine use as a contributing factor.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells. CDK12/13 degradation rapidly triggers gene-length-dependent transcriptional elongation defects, leading to DNA damage and cell-cycle arrest. In vivo, YJ9069 significantly suppresses prostate tumor growth. Modifications of YJ9069 yielded an orally bioavailable CDK12/13 degrader, YJ1206, which exhibits comparable efficacy with significantly less toxicity. To identify pathways synthetically lethal upon CDK12/13 degradation, phosphorylation pathway arrays were performed using cell lines treated with YJ1206. Interestingly, degradation or genetic knockdown of CDK12/13 led to activation of the AKT pathway. Targeting CDK12/13 for degradation, in conjunction with inhibiting the AKT pathway, resulted in a synthetic lethal effect in preclinical prostate cancer models.

Self-Administered Interventions Based on Natural Language Processing Models for Reducing Depressive and Anxiety Symptoms: Systematic Review and Meta-Analysis.

BACKGROUND: The introduction of natural language processing (NLP) technologies has significantly enhanced the potential of self-administered interventions for treating anxiety and depression by improving human-computer interactions. Although these advances, particularly in complex models such as generative artificial intelligence (AI), are highly promising, robust evidence validating the effectiveness of the interventions remains sparse. OBJECTIVE: The aim of this study was to determine whether self-administered interventions based on NLP models can reduce depressive and anxiety symptoms. METHODS: We conducted a systematic review and meta-analysis. We searched Web of Science, Scopus, MEDLINE, PsycINFO, IEEE Xplore, Embase, and Cochrane Library from inception to November 3, 2023. We included studies with participants of any age diagnosed with depression or anxiety through professional consultation or validated psychometric instruments. Interventions had to be self-administered and based on NLP models, with passive or active comparators. Outcomes measured included depressive and anxiety symptom scores. We included randomized controlled trials and quasi-experimental studies but excluded narrative, systematic, and scoping reviews. Data extraction was performed independently by pairs of authors using a predefined form. Meta-analysis was conducted using standardized mean differences (SMDs) and random effects models to account for heterogeneity. RESULTS: In all, 21 articles were selected for review, of which 76% (16/21) were included in the meta-analysis for each outcome. Most of the studies (16/21, 76%) were recent (2020-2023), with interventions being mostly AI-based NLP models (11/21, 52%); most (19/21, 90%) delivered some form of therapy (primarily cognitive behavioral therapy: 16/19, 84%). The overall meta-analysis showed that self-administered interventions based on NLP models were significantly more effective in reducing both depressive (SMD 0.819, 95% CI 0.389-1.250; P<.001) and anxiety (SMD 0.272, 95% CI 0.116-0.428; P=.001) symptoms compared to various control conditions. Subgroup analysis indicated that AI-based NLP models were effective in reducing depressive symptoms (SMD 0.821, 95% CI 0.207-1.436; P<.001) compared to pooled control conditions. Rule-based NLP models showed effectiveness in reducing both depressive (SMD 0.854, 95% CI 0.172-1.537; P=.01) and anxiety (SMD 0.347, 95% CI 0.116-0.578; P=.003) symptoms. The meta-regression showed no significant association between participants' mean age and treatment outcomes (all P>.05). Although the findings were positive, the overall certainty of evidence was very low, mainly due to a high risk of bias, heterogeneity, and potential publication bias. CONCLUSIONS: Our findings support the effectiveness of self-administered NLP-based interventions in alleviating depressive and anxiety symptoms, highlighting their potential to increase accessibility to, and reduce costs in, mental health care. Although the results were encouraging, the certainty of evidence was low, underscoring the need for further high-quality randomized controlled trials and studies examining implementation and usability. These interventions could become valuable components of public health strategies to address mental health issues. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42023472120; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023472120.

Pesticide Exposure in the Cultivation of Carica papaya L. and Capsicum annuum L. in Rural Areas of Oaxaca, Mexico.

This study focuses on describing the diversity of pesticides, the knowledge and behaviors of their use, and the acute poisoning symptoms (APS) derived from their exposure from two agricultural production systems (papaya-Carica papaya L.- and chili-Capsicum annuum L.-) in Oaxaca, Mexico. Through surveys, sociodemographic information, characteristics of the production system, knowledge and behaviors in the handling of pesticides, and APS perceived by users were captured. Papaya producers are younger, have fewer years of activity, and have larger agricultural areas than chili producers. Insect attacks and diseases are an essential factor for the application of pesticides. Thirty-one active ingredients (Ais) were identified in papaya and thirty-seven in chili, predominantly insecticides and fungicides of toxicological category IV. Approximately 50% of users apply mixtures of different Ais, have little knowledge and inappropriate behavior in their handling, and report up to five acute pesticide poisoning symptoms, mainly burning and irritation of the skin, burning eyes, itchy skin, runny nose, headache, and watery eyes. The production of papaya and chili are relevant activities for generating economic income, but they risk the producer's and their family's health. Both systems are a potential scenario for the manifestation of diseases due to exposure to pesticides in the medium and long term.