Advancements in Small Molecule Fluorescent Probes for Superoxide Anion Detection: A Review.

Superoxide anion (O2•-), a significant reactive oxygen species (ROS) within biological systems, plays a widespread role in cellular function regulation and is closely linked to the onset and progression of numerous diseases. To unveil the pathological implications of O2•- in these diseases, the development of effective monitoring techniques within biological systems is imperative. Small molecule fluorescent probes have garnered considerable attention due to their advantages: simplicity in operation, heightened sensitivity, exceptional selectivity, and direct applicability in monitoring living cells, tissues, and animals. In the past few years, few reports have focused on small molecule fluorescence probes for the detection of O2•-. In this small review, we systematically summarize the design and application of O2•- responsive small molecule fluorescent probes. In addition, we present the limitations of the current detection of O2•- and suggest the construction of new fluorescent imaging probes to indicate O2•- in living cells and in vivo.

Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Myofilaments promote wing expansion and maintain genitalia morphology in the American cockroach, Periplaneta americana.

Insects are the most widely distributed and successful animals on the planet. A large number of insects are capable of flight with functional wings. Wing expansion is an important process for insects to achieve functional wings after eclosion and healthy genital morphology is crucial for adult reproduction. Myofilaments are functional units that constitute sarcomeres and trigger muscle contraction. Here, we identified four myofilament proteins, including Myosin, Paramyosin, Tropomyosin and Troponin T, from the wing pads of nymphs in the American cockroach, Periplaneta americana. RNAi-mediated knockdown of Myosin, Paramyosin, Tropomyosin and Troponin T in the early stage of final instar nymphs caused a severely curly wing phenotype in the imaginal moult, especially in the Paramyosin and Troponin T knockdown groups, indicating that these myofilament proteins are involved in controlling wing expansion behaviours during the nymph-adult transition. In addition, the knockdown resulted in abnormal external genitalia, caused ovulation failure, and affected male accessory gland development. Interestingly, the expression of myofilament genes was induced by methoprene, a juvenile hormone (JH) analogue, and decreased by the depletion of the JH receptor gene Met. Altogether, we have determined that myofilament genes play an important role in promoting wing expansion and maintaining adult genitalia morphology, and their expression is induced by JH signalling. Our data reveal a novel mechanism by which wing expansion is regulated by myofilaments and the functions of myofilaments are involved in maintaining genitalia morphology.

An Optimized LC-MS/MS Method for Quantification of Sunitinib and N -Desethyl Sunitinib in Human Plasma and Its Application for Therapeutic Drug Monitoring.

BACKGROUND: Sunitinib (SUN) malate is an oral, multitargeted, tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. SUN has a narrow therapeutic window and high variability in interpatient pharmacokinetic parameters. Clinical detection methods for SUN and N -desethyl SUN limit the application of SUN to therapeutic drug monitoring. All published methods for quantifying SUN in human plasma require strict light protection to avoid light-induced isomerism or the use of additional quantitative software. To avoid these difficult processes in clinical routines, the authors propose a novel method that merges the peaks of the E -isomer and Z -isomer of SUN or N -desethyl SUN into a single peak. METHODS: The E -isomer and Z -isomer peaks of SUN or N -desethyl SUN were merged into a single peak by optimizing the mobile phases to decrease the resolution of the isomers. A suitable chromatographic column was selected to obtain a good peak shape. Thereafter, the conventional and single-peak methods (SPM) were simultaneously validated and compared according to the guidelines published by the Food and Drug Administration in 2018 and the Chinese Pharmacopoeia in 2020. RESULTS: The verification results showed that the SPM was superior to the conventional method in the matrix effect and met the requirements for biological sample analysis. SPM was then applied to detect the total steady-state concentration of SUN and N -desethyl SUN in tumor patients who received SUN malate. CONCLUSIONS: The established SPM makes the detection of SUN and N -desethyl SUN easier and faster without light protection or extra quantitative software, making it more appropriate for routine clinical use. The clinical application results showed that 12 patients took 37.5 mg per day, with a median total trough steady-state concentration of 75.0 ng/mL.

Customized multiple sequence alignment as an effective strategy to improve performance of Taq DNA polymerase.

Engineering Taq DNA polymerase (TaqPol) for improved activity, stability and sensitivity was critical for its wide applications. Multiple sequence alignment (MSA) has been widely used in engineering enzymes for improved properties. Here, we first designed TaqPol mutations based on MSA of 2756 sequences from both thermophilic and non-thermophilic organisms. Two double mutations were generated including a variant H676F/R677G showing a decrease in both activity and stability, and a variant Y686R/E687K showing an improved activity, but a decreased stability. Mutations targeted on coevolutionary residues of Arg677 and Tyr686 were then applied to rescue stability or activity loss of the double mutants, which achieved a partial success. Sequence analysis revealed that the two mutations are abundant in non-thermophilic sequences but not in thermophilic homologues. Then, a small-scale MSA containing sequences from only thermophilic organisms was applied to predict 13 single variants and two of them, E507Q and E734N showed a simultaneous increase in both stability and activity, even in sensitivity. A customized MSA was hence more effective in engineering a thermophilic enzyme and could be used in engineering other enzymes. Molecular dynamics simulations revealed the impact of mutations on the protein dynamics and interactions between TaqPol and substrates. KEY POINTS: • The pool of sequence for alignment is critical to engineering Taq DNA polymerase. • The variants with low properties can be rescued by mutations in coevolving network. • Improving binding with DNA can improve DNA polymerase stability and activity.

Network Analysis of Health-related Behaviors, Insomnia, and Depression Among Urban Left-behind Adolescents in China.

Mental health of urban left-behind adolescents (LBA) is a public issue of growing concern. This study aims to examine the symptom level associations among multiple health-related behaviors, insomnia, and depression in urban LBA. Data on a sample of urban LBA aged 11-19 (N = 3,601) from the Adolescent Mental Health Survey in Shenzhen, China, were used. Health-related behaviors (i.e., Internet use, physical inactivity, social jetlag, smoking, and alcohol consumption), insomnia, and depressive symptoms were assessed using a self-administered questionnaire. Graphical Gaussian Model (GGM) was used to describe key bridging nodes in an undirected network. Directed Acyclic Graph (DAG) was used to construct a directed network and estimate the most likely causal associations among behaviors/symptoms. In the undirected network, Internet use was identified as the key bridging node most strongly associated with insomnia and depression. Two other key bridging nodes include difficulty initiating sleep and appetite change. In the directed network, anhedonia emerged as the most pivotal symptom, which could cause insomnia symptoms and behavioral changes, either directly, or through triggering other depressive symptoms, such as low energy and appetite change. These findings have implications for understanding the occurrence and maintenance process of health-related behaviors, insomnia, and depression in urban LBA. In practice, Internet use should be considered a priority in targeting multiple health behavior interventions. Meanwhile, early screening and treatment for anhedonia are of great significance as well.

DeepMPM: a mortality risk prediction model using longitudinal EHR data.

BACKGROUND: Accurate precision approaches have far not been developed for modeling mortality risk in intensive care unit (ICU) patients. Conventional mortality risk prediction methods can hardly extract the information in longitudinal electronic medical records (EHRs) effectively, since they simply aggregate the heterogeneous variables in EHRs, ignoring the complex relationship and interactions between variables and the time dependence in longitudinal records. Recently deep learning approaches have been widely used in modeling longitudinal EHR data. However, most existing deep learning-based risk prediction approaches only use the information of a single disease, neglecting the interactions between multiple diseases and different conditions. RESULTS: In this paper, we address this unmet need by leveraging disease and treatment information in EHRs to develop a mortality risk prediction model based on deep learning (DeepMPM). DeepMPM utilizes a two-level attention mechanism, i.e. visit-level and variable-level attention, to derive the representation of patient risk status from patient's multiple longitudinal medical records. Benefiting from using EHR of patients with multiple diseases and different conditions, DeepMPM can achieve state-of-the-art performances in mortality risk prediction. CONCLUSIONS: Experiment results on MIMIC III database demonstrates that with the disease and treatment information DeepMPM can achieve a good performance in terms of Area Under ROC Curve (0.85). Moreover, DeepMPM can successfully model the complex interactions between diseases to achieve better representation learning of disease and treatment than other deep learning approaches, so as to improve the accuracy of mortality prediction. A case study also shows that DeepMPM offers the potential to provide users with insights into feature correlation in data as well as model behavior for each prediction.

Efficacy of music therapy and predictors of sleep disturbance among patients with chronic schizophrenia: A prospective study.

STUDY OBJECTIVES: Patients with schizophrenia often suffer from sleep disturbance. Music therapy, as a non-invasive intervention, may have benefit on sleep problem in such population. Our study aimed to investigate the efficacy of music therapy on sleep disturbance among patients with schizophrenia. METHOD: This prospective study recruited participants with schizophrenia along with sleep disturbances in the chronic wards. Patients in the control group received standard care, and those in the intervention group received additional music therapy before sleeping at night for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the severity of sleep disturbance. The generalized estimating equation (GEE) was used to analyze measure the difference of change in PSQI scores between both groups at the baseline and four weeks later. It was also applied to find the predictors of treatment efficacy within intervention group. FINDINGS: A total of 66 (31 in control group and 35 in intervention group) participants were recruited. After adjusting with the demographic variables, the change of PSQI among intervention group was significantly more than the change among control group (Group × time; Estimate = -7.05, p < 0.001), indicating the efficacy of music therapy. In addition, irreligious patients and those with chronic medical disease predicted better efficacy. Whereas, elderly patients had compromising efficacy of music therapy. CONCLUSION: Music therapy demonstrated its merit on sleep disturbance among patients with schizophrenia. Whereas, healthcare workers should consider the variability of severity in schizophrenia during clinical practice.

Risk factors of falls and the gender differences in older adults with diabetes at outpatient clinics.

AIMS: To explore the risk factors of falls and the gender differences based on demographic and disease characteristics, physical capability, and fear of falling in older adults with diabetes visiting outpatient clinics in Taiwan. DESIGN: Cross-sectional design. METHODS: A total of 485 patients with type 2 diabetes aged between 65 and 80 years were recruited from three endocrine outpatient clinics in Taiwan. Demographic and disease characteristics, fall history in the previous one year and fear of falling were collected by a self-reported questionnaire. Calf circumference, handgrip strength, one-leg standing and time up-and-go tests were all performed to assess the physical capability of participants. Data were collected from May 2019 to May 2020. RESULTS: Female gender (OR = 1.75), handgrip strength (OR = 2.43) and fear of falling (OR = 3.38) were important risk factors of falls overall, although fear of falling (OR = 4.69) was the only important risk factor of falls in males, while handgrip strength (OR = 3.48) and fear of falling (OR = 2.86) were important risk factors of falls in females. The sensitivity of simultaneous screening handgrip strength and fear of falling were 85.7, 86.4 and 86.2 in males, females and older adults overall with diabetes, respectively. CONCLUSION: Fear of falling was an important risk factor of falls in both genders, especially in males. Handgrip strength was an important risk factor of falls specifically for females. By simultaneously screening fear of falling and handgrip strength, risk of falls in older adults with diabetes at outpatient clinics could be identified in a more timely manner. Impact Nurses could periodically and simultaneously assess fear of falling and handgrip strength of older adults with diabetes at outpatient clinics. For those are identified at risk of falls on either fear of falling or handgrip strength, nurses could provide corresponding interventions to reduce the fear of falling or improve muscle strength to prevent such falls.

Pathways of diabetes distress, decisional balance, self-efficacy and resilience to quality of life in insulin-treated patients with type 2 diabetes: A 9-month prospective study.

AIMS AND OBJECTIVES: To construct a path model addressing influences of diabetes distress, self-efficacy of injecting insulin, resilience and decisional balance of injecting insulin to quality of life (QoL) in insulin-treated patients with type 2 diabetes (T2DM). BACKGROUND: Insulin regimens more negatively impact QoL than oral medication treatments in patients with T2DM. Understanding the factors and influencing pathways associated with subsequent QoL will help nurses design timely interventions to improve QoL of insulin-treated T2DM patients. DESIGN: A 9-month prospective design was employed in this study. METHODS: Self-reported questionnaires were used to collect data from 185 insulin-treated T2DM patients. At baseline, diabetes distress and self-efficacy of injecting insulin were collected, while QoL, resilience and decisional balance of injecting insulin were collected 9 months later. Data were collected from February 2017 to February 2018. Structural equation modelling was used for analysis. This study was conducted based on the STROBE. RESULTS: Low baseline diabetes distress and high 9-month decisional balance of injecting insulin directly associated with high 9-month QoL. High baseline self-efficacy of injecting insulin and high 9-month resilience directly associated with high 9-month decisional balance of insulin injection and indirectly associated with high 9-month QoL. High baseline diabetes distress directly and indirectly associated with poor 9-month QoL. CONCLUSIONS: Diabetes distress, self-efficacy of injecting insulin, resilience and decisional balance of injecting insulin play different roles in associating with QoL in insulin-treated T2DM patients. RELEVANCE TO CLINICAL PRACTICE: Nurses could provide educational programs focusing on enhancing decisional balance of injecting insulin to improve QoL in insulin-treated patients. Improving self-efficacy of injecting insulin and resilience could be promising strategies to improve the decisional balance of injecting insulin. More timely assessment of diabetes distress and intervention might be powerful strategies to improve subsequent QoL in these patients.

Mother's exposure to domestic and community violence and its association with child's behavioral outcomes.

This study investigated the potential cumulative effect of maternal exposure to violence both at home and in community on children. This study used the data (N = 2506) from the Fragile Families and Child Wellbeing study. We found that maternal nonphysical victimization, either by witnessing violence in the community or by experiencing psychological domestic violence, had a direct negative effect on children's depression and anxiety. Maternal nonphysical victimization also indirectly elevated child's aggression through mother's use of psychological and physical aggression toward the child. Witnessing community violence by mothers, directly and indirectly, worsened the child's withdrawal behaviors through the mother's psychological aggression toward the child. Mother's direct victimization by community violence and physical domestic violence was not related to child's behavioral outcomes after controlling for other risk factors. This study points to important considerations for devising intervention and prevention for mothers and children. Implications for research and practice are discussed.

The effects of emergency department crowding on triage and hospital admission decisions.

BACKGROUND: Emergency department (ED) crowding is a recognized issue and it has been suggested that it can affect clinician decision-making. OBJECTIVES: Our objective was to determine whether ED census was associated with changes in triage or disposition decisions made by ED nurses and physicians. METHODS: We performed a retrospective study using one year of data obtained from a US academic center ED (65,065 patient encounters after cleaning). Using a cumulative logit model, we investigated the association between a patient's acuity group (low, medium, and high) and ED census at triage time. We also used multivariate logistic regression to investigate the association between the disposition decision for a patient (admit or discharge) and the ED census at the disposition decision time. In both studies, control variables included census, age, gender, race, place of treatment, chief complaint, and certain interaction terms. RESULTS: We found statistically significant correlation between ED census and triage/disposition decisions. For each additional patient in the ED, the odds of being assigned a high acuity versus medium or low acuity at triage is 1.011 times higher (95% confidence interval [CI] for Odds Ratio [OR] = [1.009,1.012]), and the odds of being assigned medium or high acuity versus low acuity at triage is 1.009 times higher (95% CI for OR = [1.008,1.010]). Similarly, the odds of being admitted versus discharged increases by 1.007 times (95% CI for OR = [1.006,1.008]) per additional patient in the ED at the time of disposition decision. CONCLUSION: Increased ED occupancy was found to be associated with more patients being classified as higher acuity as well as higher hospital admission rates. As an example, for a commonly observed patient category, our model predicts that as the ED occupancy increases from 25 to 75 patients, the probability of a patient being triaged as high acuity increases by about 50% and the probability of a patient being categorized as admit increases by around 25%.

Diversity of Conopeptides and Their Precursor Genes of Conus Litteratus.

The venom of various Conus species is composed of a rich variety of unique bioactive peptides, commonly referred to as conotoxins (conopeptides). Most conopeptides have specific receptors or ion channels as physiologically relevant targets. In this paper, high-throughput transcriptome sequencing was performed to analyze putative conotoxin transcripts from the venom duct of a vermivorous cone snail species, Conus litteratus native to the South China Sea. A total of 128 putative conotoxins were identified, most of them belonging to 22 known superfamilies, with 43 conotoxins being regarded as belonging to new superfamilies. Notably, the M superfamily was the most abundant in conotoxins among the known superfamilies. A total of 15 known cysteine frameworks were also described. The largest proportion of cysteine frameworks were VI/VII (C-C-CC-C-C), IX (C-C-C-C-C-C) and XIV (C-C-C-C). In addition, five novel cysteine patterns were also discovered. Simple sequence repeat detection results showed that di-nucleotide was the major type of repetition, and the codon usage bias results indicated that the codon usage bias of the conotoxin genes was weak, but the M, O1, O2 superfamilies differed in codon preference. Gene cloning indicated that there was no intron in conotoxins of the B1- or J superfamily, one intron with 1273-1339 bp existed in a mature region of the F superfamily, which is different from the previously reported gene structure of conotoxins from other superfamilies. This study will enhance our understanding of conotoxin diversity, and the new conotoxins discovered in this paper will provide more potential candidates for the development of pharmacological probes and marine peptide drugs.

Longitudinal Trajectory of Adolescent Exposure to Community Violence and Depressive Symptoms Among Adolescents and Young Adults: Understanding the Effect of Mental Health Service Usage.

Research on the impact of exposure to community violence tends to define victimization as a single construct. This study differentiates between direct and indirect violence victimization in their association with mental health problems and mental health service use. This study includes 8947 individuals from four waves of the National Longitudinal Study of Adolescent to Adult Health and examines (1) whether sub-types of adolescent victimization are linked to depressive symptoms; (2) whether adolescent victimization is linked with mental health service use; and (3) the role of mental health service use in attenuating symptoms arising from victimizations. Adolescents witnessing community violence were more likely to experience depressive symptoms during adolescence but not during their young adulthood; direct exposure to violence during adolescence does not predict depressive symptoms in adolescence but does in adulthood. Use of mental health service mediates report of depressive symptoms for adolescent witnessing community violence.

Diversity of Cronobacter spp. isolates from the vegetables in the middle-east coastline of China.

Cronobacter spp. has caused life-threatening neonatal infections mainly resulted from consumption of contaminated powdered infant formula. A total of 102 vegetable samples from retail markets were evaluated for the presence of Cronobacter spp. Thirty-five presumptive Cronobacter isolates were isolated and identified using API 20E and 16S rDNA sequencing analyses. All isolates and type strains were characterized using enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR), and genetic profiles of cluster analysis from this molecular typing test clearly showed that there were differences among isolates from different vegetables. A polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) based on the amplification of the gyrB gene (1258 bp) was developed to differentiate among Cronobacter species. A new PCR-RFLP assay based on the amplification of the gyrB gene using Alu I and Hinf I endonuclease combination is established and it has been confirmed an accurate and rapid subtyping method to differentiate Cronobacter species. Sequence analysis of the gyrB gene was proven to be suitable for the phylogenetic analysis of the Cronobacter strains, which has much better resolution based on SNPs in the identification of Cronobacter species specificity than PCR-RFLP and ERIC-PCR. Our study further confirmed that vegetables are one of the most common habitats or sources of Cronobacter spp. contamination in the middle-east coastline of China.

[Exploration of the Care Needs of Post-Chemotherapy Lung Cancer Patients and Related Factors].

BACKGROUND: Chemotherapy (CT) is the first priority treatment for advanced stage lung cancer. However, symptom distress, impaired ability to conduct daily activities, and post-CT care needs are potential side effects of CT. PURPOSE: To explore the factors related to the care needs of post-chemotherapy lung cancer patients. METHODS: A cross-sectional study was used. One hundred and twenty-one adult patients who had been diagnosed with advanced-stage lung cancer and who had undergone CT using the Platinum and Docetaxel doublet regimen were recruited from a medical center in southern Taiwan. The instruments used included a nursing care needs survey, symptoms distress scale, daily activity interference scale, and patient characteristics datasheet. RESULTS: Participants self-prioritized their emergency management, health consultation, and emotional support activities based on their perceived care needs. The top three post-CT symptoms in terms of severity were: fatigue, appetite change, and sleep disorder. Primary disruptions in daily activities during the post-CT period related to: holding social activities, work, and stair climbing. Significant and positive correlations were found among daily activity interference (r = .30, p < .01), symptoms distress (r = .23, p < .01), and care needs. The regression model indicated daily activity interference as a predictor of care needs, accounting for 10.7% of the total variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: These results highlight the relationships among care needs, symptom distress, and daily activity interference in post-chemotherapy lung-cancer patients. The present study provides a reference for nursing care to reduce the symptom distress, to enhance the performance of daily activities, and to meet the care needs of lung-cancer patients.

Comparative Genomic Analysis of Two-Component Signal Transduction Systems in Probiotic Lactobacillus casei.

Lactobacillus casei has traditionally been recognized as a probiotic, thus needing to survive the industrial production processes and transit through the gastrointestinal tract before providing benefit to human health. The two-component signal transduction system (TCS) plays important roles in sensing and reacting to environmental changes, which consists of a histidine kinase (HK) and a response regulator (RR). In this study we identified HKs and RRs of six sequenced L. casei strains. Ortholog analysis revealed 15 TCS clusters (HK-RR pairs), one orphan HKs and three orphan RRs, of which 12 TCS clusters were common to all six strains, three were absent in one strain. Further classification of the predicted HKs and RRs revealed interesting aspects of their putative functions. Some TCS clusters are involved with the response under the stress of the bile salts, acid, or oxidative, which contribute to survive the difficult journey through the human gastrointestinal tract. Computational predictions of 15 TCSs were verified by PCR experiments. This genomic level study of TCSs should provide valuable insights into the conservation and divergence of TCS proteins in the L. casei strains.

The Role of Cells and Cytokines in Male Infertility Induced by Orchitis.

Recent studies on male infertility reveal a growing worry: more infertile men are dealing with inflammation in the testis. Analyzing testicular biopsies from infertile men highlights a significant presence of inflammation. This connection, supported by clinical and pathological evidence, emphasizes that testicular inflammation hampers sperm production, leading to lasting declines in sperm count and quality. However, the exact reasons behind male infertility due to orchitis, a type of testicular inflammation, are still uncertain. Understanding these fundamental aspects of molecular signals and cellular mechanisms in testicular inflammation is crucial. Our review delves into recent literature with a dual objective: elucidating potential mechanisms involving immune cells, non-immune cells, and cytokines that link orchitis to male infertility, while also paving the way for precise interventions and solutions to address the challenges of male infertility.

Case Report: Successful Treatment of Cerebral Phaeohyphomycosis with Voriconazole: A Case Report and Literature Review.

Fonsecaea monophora is a species of Fonsecaea that belongs to Chaetothyriales. It is usually isolated from tropical and subtropical regions, causing reactive inflammation, skin abscesses, and pain. Cerebral infection caused by F. monophora is rare but often fatal. Diagnosing this disease at an early stage is difficult, and appropriate antifungal therapy is often delayed as a result. We report the case of a 53-year-old woman with type 2 diabetes who presented with a headache 2 months ago and progressive right-sided weakness of 1 month's duration. Magnetic resonance imaging revealed a space-occupying lesion in the left frontal lobe and corpus callosum. The cystic mass was removed by surgical intervention, and the identification of the sample based on sequencing of the internal transcribed spaced region in BLAST-N search showed that the sequences producing most significant alignments were F. monophora or similar (query cover 99%, E value 0.0, per ident 99.84). The patient was treated with a 3-month course of twice daily voriconazole, leading to complete recovery.

Cardiovascular adverse events associated with antibody-drug conjugates (ADCs): a pharmacovigilance study based on the FAERS database.

Objective: As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events. Research design and methods: We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated. Results: In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure (n = 277) and embolic and thrombotic events, venous (n = 446) were the most frequently reported CVD-related AEs in ADCs. Conclusion: By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.