Positive Signals Research Articles

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis. This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to December 2023. A disproportionality analysis was conducted to assess drug-related keratitis with positive signals, and drugs were classified and assessed with regard to their drug-induced timing and risk of drug-related keratitis. A total of 1606 drugs were reported to pose a risk of drug-related keratitis in the FAERS database, and, after disproportionality analysis and screening, 17 drugs were found to significantly increase the risk of drug-related keratitis. Among them, seven were ophthalmic medications, including dorzolamide (reporting odds ratio [ROR] = 3695.82), travoprost (ROR = 2287.27), and brimonidine (ROR = 2118.52), and 10 were non-ophthalmic medications, including tralokinumab (ROR = 2609.12), trazodone (ROR = 2377.07), and belantamab mafodotin (ROR = 680.28). The top three drugs having the highest risk of drug-related keratitis were dorzolamide (Bayesian confidence propagation neural network [BCPNN] = 11.71), trazodone (BCPNN = 11.11), and tralokinumab (BCPNN = 11.08). The drug-induced times for non-ophthalmic medications were significantly shorter than those for ophthalmic medications (mean days, 141.02 vs. 321.96, respectively; P < 0.001). The incidence of drug-related keratitis reached its peak in 2023. Prevention of drug-related keratitis is more important than treatment. Identifying the specific risks and timing of drug-induced keratitis can support the development of preventive measures. Identifying the specific drugs related to medication-related keratitis is of significant importance for drug vigilance in the occurrence of drug-related keratitis.

Too good to be true: A theory

We use a Gaussian mixture prior with two clusters to explain market fears. We show that a surprisingly positive signal can shake investors’ confidence in their understanding of the market, and in the process, potentially lower their expectation of an asset’s value.

Risk of Suicide, Hair Loss, and Aspiration with GLP1-Receptor Agonists and Other Diabetic Agents: A Real-World Pharmacovigilance Study.

With the increasing popularity of glucagon-like peptide 1 receptor agonists (GLP1-RAs), numerous safety concerns arose pertaining to suicide, hair loss, and aspiration risks. We attempted to validate these concerns. We queried four pharmacovigilance databases to compare GLP1-RAs to sodium-glucose transporter 2 inhibitors (SGLT2is) with respect to these adverse events (AE): the FDA Adverse Event Reporting System (FAERS), the Australian Database of Adverse Event Notifications (DAEN), the European Medicines Agency's (EudraVigilance), and the World Health Organization-Vigibase. OpenVigil 2.1 was utilized to perform a disproportionality analysis for GLP1-RAs, SGLT2is, dipeptidyl peptidase 4 inhibitors (DPP4is), sulfonylureas, metformin, and insulin. The following indices were extracted from the FAERS database from Q4/2003 until Q3/2023: relative reporting ratio (RRR), proportional reporting ratio (PRR), reporting odds ratio (ROR), and chi-squared (χ2). A positive signal was detected if PRR > 2 and χ2 > 4 for any drug-event pair. No positive signals were observed between GLP1-RAs and either suicide, hair loss, or aspiration risks. Semaglutide [ROR = 0.60 (0.51-0.71)] and liraglutide [ROR = 0.28 (0.23-0.35)] had higher suicidal events than DPP4is and SGLT2is. GLP1-RAs were the most reported class with hair loss [ROR = 0.61 (0.60-0.64)], and semaglutide, liraglutide, and dulaglutide were the three leading medications. GLP1-RAs ranked lower with aspiration events, which were led by sitagliptin and DPP4is as a group. GLP1-RAs exhibit higher reporting of suicide, hair loss, and aspiration events when compared to several other antidiabetic medications despite not meeting the criteria for positive signals yet. This warrants intensive monitoring and reporting.

Intracellular abundance, localization, and enzymatic activity of a saxitoxin biosynthesis enzyme, SxtG, in two sister subclones of the dinoflagellate Alexandrium catenella with extremely different levels of paralytic shellfish toxins

Paralytic shellfish poisoning is caused by saxitoxin (STX), and its analogues (paralytic shellfish toxins (PSTs)) produced by marine dinoflagellates. SxtA and SxtG are the most essential enzymes in STX biosynthesis. Previous studies investigated the abundance and subcellular localization (i.e., chloroplasts) of SxtA in dinoflagellates using immunostaining. The present study characterized SxtG, and positive signals were detected in sister subclones of Alexandrium catenella (Group I) with extremely different levels of PSTs. Multiplex fluorescence immunostaining detection of a PST-positive subclone revealed co-localization of SxtA and SxtG, suggesting that SxtG localizes to chloroplasts. In vitro amidino-transfer from arginine to Int-A’, the first intermediate product in the biosynthesis, was presumed to be catalyzed by SxtG, and the reaction was established using crude extracts of PST-positive and negative A. catenella subclones. These analyses suggested that the PST-negative subclone expresses active SxtG but not SxtA. These findings support our hypothesis that decrease of SxtA leads to the loss of toxicity in the PST-negative subclone of A. catenella. Our results identified a key reaction that could enhance understanding of the biochemistry of STX biosynthesis in dinoflagellates.

Effects of anti-rainbow trout germ-cell monoclonal antibody on germ cells and gonadal tissues in rainbow trout (Oncorhynchus mykiss)

The development of sterilization technology is important to improve the production efficacy of aquaculture and prevent genetically modified fish from escaping. Immunosterilization is a novel sterilization method that has already been used in mammals. In this study, anti-rainbow trout germ-cell monoclonal antibodies (anti-GC mAbs) were injected into immature rainbow trout Oncorhynchus mykiss, and their effects were analyzed. First, anti-GC mAbs labeled with Alexa Fluor 488 were injected into the body cavity of larvae 20 days (group 1) and 102 days (group 2) after fertilization. Second, anti-GC mAbs were injected into the body cavity of yearling trout (group 3), and their impacts on gonadal tissue were analyzed in terms of histology and gene expression levels. As a result, anti-GC mAbs were observed to bind to some primordial GCs in group 1, whereas there were no obvious positive cells in male testes of group 2. In contrast, green fluorescent signals were observed in an arrangement parallel to the ovarian lamina in female ovaries of group 2, which was similar to the arrangement of positive signals on ovarian tissue sections immunostained with anti-GC mAbs. GCs in group 1 were observed again after 76 days, and double-positive cells remained. In group 3, there were changes in the expression levels of GC-specific genes, but the changes were not seen as biologically meaningful. Moreover, there was no histological abnormality in gonadal tissues after immunization. In conclusion, these results suggested that anti-GC mAbs could only reach GCs in early developmental stages or in the ovary, and injection of anti-GCs mAbs did not have harmful effects on GCs after binding.

A national analysis of systemic adverse events of beta-blockers used for glaucoma therapy

Purpose To evaluate systemic complications for timolol, carteolol, levobunolol, and/or betaxalol by using an FDA Federal Adverse Event Reporting System (FAERS) Methods We evaluated FAERS for adverse events associated with β-blocker use for glaucoma. All reported symptoms were reviewed to identify systemic adverse events and to detect safety signals, defined as information on a new or known side effect that may be caused by a medicine. We used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis comparing the frequency of β-blocker symptoms with all other adverse event reports. We considered a signal to be detected when all four disproportionality analysis metrics were positive. Results We found 10,500,309 total adverse event reports from the FAERS database 2004-2022Q3, which included 8,793 case reports with a primary suspect of a β-blocker use for glaucoma. 1,838 unique adverse symptoms were reported were associated with β-blocker. Regarding outcomes, there were 165 (1.88%) reports of disability, 671 (7.63%) reports of hospitalisation, and 1,934 (21.99%) reports of some other unspecified complication. Regarding adverse events, the most reported general, cardiac, and respiratory symptoms were respectively dizziness (n = 281), bradycardia (n = 145), and dyspnoea (n = 195). 256 (2.91%) cases of death were reported. We found significant signals on bradycardia (n = 145), complete atrioventricular block (n = 38), and bronchospasm (n = 23). No allergic, endocrine, constitutional, or gastrointestinal symptoms generated positive signals. Conclusion β-blocker use in glaucoma therapy can be rarely associated with serious systemic and life-threatening complications.

Multifunctional spatial-potential resolved electrochemiluminescence biosensor for dual-channel simultaneous detection of hepatitis A virus and hepatitis C virus DNA

Highly sensitive simultaneous detection of dual-target is one of the main research directions of electrochemiluminescence (ECL), but the traditional three-electrode system makes it difficult to realize this aim. This work designed a multifunctional spatial-potential resolved ECL biosensor for dual-channel simultaneous detection of hepatitis A virus (HAV) and hepatitis C virus (HCV) DNA. Self-luminescent dual-ligand metal organic framework (D-MOF) and cerium MOF (Ce-MOF) were modified on two parts of the ITO electrode to achieve dual-channel simultaneous detection. One ligand of D-MOF acted as the luminophore and the other as the co-reactant, so D-MOF could emit excellent positive potential ECL signal without requiring external co-reactants. In channel A, the Ag nanoparticles (Ag NPs) quenching probes were introduced to D-MOF through hybridization of HAV with “Y” type DNA. Positive potential signal of D-MOF was decreased for HAV DNA detection based on resonance energy transfer (RET). In channel B, the CdSe quantum dots (QDs) were introduced to Ce-MOF through hybridization of HCV with “Y” type DNA. Due to the excellent ECL performance of CdSe QDs, negative potential signal was increased for HCV DNA detection. In this work, an ingenious spatial-potential resolved ECL biosensor was developed for simultaneous detection of dual-target by simple sealing film isolation, which opened a new strategy for dual-target detection in general ECL assays with three-electrode system.

Pyrroloquinoline Quinone Alleviates Intestinal Inflammation and Cell Apoptosis via the MKK3/6-P38 Pathway in a Piglet Model.

This study investigates the underlying mechanism through which dietary supplementation of pyrroloquinoline quinone disodium (PQQ) alleviates intestinal inflammation and cell apoptosis in piglets challenged with lipopolysaccharide (LPS). Seventy-two barrows were divided into three groups: control (CTRL), LPS challenged (LPS), and LPS challenged with PQQ supplementation (PQQ + LPS). On d 7, 11, and 14, piglets received intraperitoneal injections of LPS or 0.9% of NaCl (80 μg/kg). After a 4 h interval following the final LPS injection on d 14, blood samples were obtained, and all piglets were euthanized for harvesting jejunal samples. The results showed that dietary supplementation of PQQ improved the damage of intestinal morphology, increased the down-regulated tight junction proteins, and reduced the increase of serum diamine oxidase activity, the intestinal fatty acid binding protein, and TNF-α levels in piglets challenged with LPS (p < 0.05). The proteomics analysis revealed a total of 141 differentially expressed proteins (DEPs), consisting of 64 up-regulated DEPs and 77 down-regulated DEPs in the PQQ + LPS group compared to the LPS group. The KEGG pathway analysis indicated enrichment of the tight junction pathway and the apoptosis pathway (p < 0.05). Compared to the LPS group, the piglets in the PQQ + LPS group had increased levels of Bcl-2 protein, reduced positive apoptosis signals, and a decrease in the abundance of MKK 3/6 and p-p38 proteins (p < 0.05). In conclusion, dietary supplementation of PQQ could alleviate jejunal inflammatory damage and cell apoptosis in piglets challenged with LPS through the MKK3/6-p38 signaling pathway.

Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified. Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined. A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation. In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation.

A gut-brain-gut interoceptive circuit loop gates sugar ingestion in Drosophila.

The communication between the brain and digestive tract is critical for optimising nutrient preference and food intake, yet the underlying neural mechanisms remain poorly understood1-7. Here, we show that a gut-brain-gut circuit loop gates sugar ingestion in flies. We discovered that brain neurons regulating food ingestion, IN18, receive excitatory input from enteric sensory neurons, which innervate the oesophagus and express the sugar receptor Gr43a. These enteric sensory neurons monitor the sugar content of food within the oesophagus during ingestion and send positive feedback signals to IN1s, stimulating the consumption of high-sugar foods. Connectome analyses reveal that IN1s form a core ingestion circuit. This interoceptive circuit receives synaptic input from enteric afferents and provides synaptic output to enteric motor neurons, which modulate the activity of muscles at the entry segments of the crop, a stomach-like food storage organ. While IN1s are persistently activated upon ingestion of sugar-rich foods, enteric motor neurons are continuously inhibited, causing the crop muscles to relax and enabling flies to consume large volumes of sugar. Our findings reveal a key interoceptive mechanism that underlies the rapid sensory monitoring and motor control of sugar ingestion within the digestive tract, optimising the diet of flies across varying metabolic states.

Buyer-initiated knowledge payment facilitates free knowledge contribution in knowledge-sharing platforms: an integration of relational signaling theory and attribution theory

PurposeThe model of pay-for-knowledge incentivizes individuals with financial rewards for sharing their expertise, facilitating a transactional exchange between knowledge providers (sellers) and seekers (buyers). While this model is effective in promoting paid contributions, its influence on free knowledge exchanges remains ambiguous, creating uncertainty about its overall impact on platform knowledge ecosystems. This study aims to explore the mechanim of how knowledge payment influences free knowledge contribution. Based on relational signaling theory, this study posits that a buyer’s payment for knowledge acts as a positive relational signal in the buyer–seller relationship and examines how the signaling effect varies across different social contexts through attribution theory.Design/methodology/approachThis paper empirically tests the hypotheses by analyzing a data set comprising 630 instances from 359 unique knowledge sellers on Zhihu, a prominent knowledge-sharing platform in China. This paper use zero-inflated negative binomial models to conduct this analysis.FindingsThe findings reveal that when buyers pay for knowledge, this action positively influences sellers to contribute knowledge for free. However, the strength of this influence is moderated by the platform’s social functions: appreciation feedback tends to weaken this effect, while social network ties enhance it.Originality/valuePrior research has predominantly focused on the financial incentives of pay-for-knowledge and its spillover effects on unpaid users’ activities. This study shifts the focus to the social dimensions of pay-for-knowledge, arguing that buyer-initiated knowledge payments signal buyers’ commitment to foster reciprocal relationships with sellers. It expands the literature on the relationship between knowledge payment and contribution, moving beyond financial incentives to include social factors, thus enriching our understanding of the interplay between paid and free knowledge activities. Additionally, the empirical evidence supports the efficacy of pay-for-knowledge in promoting both free and paid contributions within knowledge-sharing platforms.

All-optical organic photochemical integrated nanophotonic memory: low-loss, continuously tunable, non-volatile

Controlling changes in the optical properties of photonic devices allows photonic integrated circuits (PICs) to perform useful functions, leading to a large breadth of applications in communications, computing, and sensing. Many mechanisms to change optical properties exist, but few allow doing so in a reversible, non-volatile manner. Without such mechanisms, power inefficiencies and use of external memory are inevitable. In this work, we propose and experimentally demonstrate reversible, non-volatile phase actuation of a silicon nitride PIC with thermally stable photochromic organic molecules vapor-deposited within a slot waveguide structure. The use of a high-core-index platform allows the photochemical phase actuation of a planar-resonator-based photonic memory unit, which enables positive and negative signal weighting and permits integrated spectroscopic analysis. We show properties of this all-optical memory for a silicon photonics platform, including low loss in the optical C-band, first-order photokinetics of the photoconversion, bidirectional scalable switching, and continuous tuning. Such features are critical for memories in analog applications such as quantum, microwave, and neuromorphic photonics, where bipolar weights, low loss, and precision are paramount. More generally, this work suggests that back-end-of-line-compatible vapor deposition of organic molecules into silicon photonic circuits is promising to introduce non-silicon-native functionality.

Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database.

On April 18, 2024, the U.S. Food and Drug Administration officially required updating of the "boxed warning" for T cell malignancies for all chimeric antigen receptor T cell (CAR-T) therapies. Given the clinical significance of these therapies, a rigorous safety assessment is paramount. However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. Therefore, we aimed to thoroughly analyze the adverse events (AEs) information in the FDA Adverse Event Reporting System (FAERS) database to comprehensively understand the safety risks of ide-cel and cilta-cel. We extracted AE reports related to ide-cel and cilta-cel from the FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.) from January 1, 2019 to December 31, 2023. Disproportionality analysis and Bayesian analysis were used to identify risk signals across subgroups and specific cases (including for death and secondary malignancies). Weibull distribution analysis was employed to determine the time to AE onset. A total of 695 AE reports for ide-cel and 848 for cilta-cel were included in the FAERS database. This analysis identified 81 positive signals for ide-cel and 74 for cilta-cel. Notably, comparisons with the drug labels revealed "unexpected signals," including febrile bone marrow aplasia (reporting odds ratio=69.10; confidence interval 39.12-122.03) and plasma cell myeloma (12.45; 8.18-18.95) for ide-cel, and increased serum ferritin (24.98; 8.0-77.58) and large intestine perforation (18.57; 5.98-57.69) for cilta-cel. Both drugs showed a higher AE incidence among male recipients and patients aged ≥65 years, although female recipients faced a greater risk. Most AEs occurred at the early stage of administration. However, secondary malignancies were detected for both drugs, primarily occurring one-year post-administration. This study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents.

The Impact of Environmental, Social, and Governance Disclosure on the Performance of Saudi Arabian Companies: Evidence from the Top 100 Non-Financial Companies Listed on Tadawul

This study investigated the relationship between environmental, social, and governance (ESG) disclosure and the performance of Saudi Arabian companies. We analysed panel data from the 100 non-financial companies listed on the Saudi stock exchange (Tadawul) from 2017 to 2022. Using fixed effects, random effects, and generalised method of moments (GMM) models to account for endogeneity concerns, we examined the impact of ESG disclosure on the return on assets (ROA), return on equity (ROE), and Tobin’s Q. An ESG index was constructed through a principal component analysis of individual environmental, social, and governance scores. Our results indicate a significant positive relationship between ESG disclosure and companies’ key performance variables across all models. These findings are consistent with stakeholder theory and signalling theory, suggesting that comprehensive ESG practices can lead to better financial performance and serve as a positive signal to stakeholders. The study also reveals sector-specific differences, with non-manufacturing firms showing stronger positive relationships between ESG disclosure and performance measures compared to manufacturing firms. Additionally, we find that firm size, age, and liquidity are important factors influencing the ESG–performance relationship. This research contributes to the growing literature on ESG and corporate performance in emerging markets, offering valuable insights for policymakers, investors, and corporate practitioners in Saudi Arabia’s evolving sustainable business landscape. Our findings underscore the importance of ESG disclosure in driving sustainable and responsible business practices in the region.

The Use of IPO Fund, Underpricing, and Survival: ESG-Driven Insights from Indonesian Firms

The IPO prospectus should disclose information on the use of IPO proceeds, which can be a reference for investors in making investment decisions. Companies conduct IPOs for investment, working capital, and debt repayment purposes. The use of IPO fund for investment and working capital gives a positive signal, while debt repayment gives a negative signal. Some companies also implement ESG (Environmental, Social, and Governance) policies after conducting an IPO. This research aims to test whether companies with ESG scores have different underpricing and survival phenomena compared to companies in general. This research was conducted on 148 Indonesian companies that conducted IPOs in the period 2008-2021. The results suggest that the use of IPO proceeds for investment and working capital has a positive effect on underpricing and survival. However, the use of IPO proceeds for debt repayment has no effect on underpricing. Moreover, the use of IPO proceeds for debt repayment in companies that obtain ESG scores has a positive effect on underpricing. Underpricing strengthens the effect of the use of IPO fund for investment on survival occurs in the sample of companies in general as well as companies that obtain ESG scores. The implication of this research suggests that investors do not consider IPOs as a return on debt in companies that obtain ESG scores as a negative signal to invest.

Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database.

Hypertension is a common complication in patients with osteoarthritis (OA). There is increasing interest in the relationship between hypertension and OA. However, hypertension has been reported to negatively affect symptoms and quality of life in patients with OA. Therefore, treating hypertension is crucial for patients with OA. However, there is a lack of real-world studies on the effects of medications for treating hypertension on OA. Data from the FAERS database from January 2004 to December 2023 were extracted for disproportionality analyses, and proportional reporting ratios (PRRs) were used to assess the association between medications for hypertension and all types of arthritis. Adverse event signals were identified and determined using reporting odds ratios (RORs) Adverse event signals were considered to have occurred if a drug-induced adverse event was recorded more than or equal to 3 and the lower limit of the ROR confidence interval was more than 1. We selected five classes of drugs including, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics and β-blockers and representative drugs were analysed for osteoarthritis-related adverse reactions, and age and gender subgroups were analysed for drugs of significance. We also analysed the occurrence of AEs in relation to time using the Weibull distribution. In terms of overall data, we found significant OA adverse reaction signals only for ARBs among the five drug classes.ARB AEs for spinal osteoarthritis (ROR 4.64, 95% CI 3.62-5.94), osteoarthritis (ROR 3.24 95% CI 2.82-3.72) and gouty arthritis (ROR 3.27 95% CI 1.22-8.75) were the three adverse reactions with the loudest signals. Next, we found that valsartan had strong osteoarthritis adverse reaction signals among the three ARBs, namely, irbesartan, cloxartan, and valsartan. We also analysed age and gender subgroups and found that osteoarthritis signals were strongest in the 18-65 and 65+ population, while females seem to be more prone to valsartan-related OA AEs. ARBs, especially valsartan, have significant positive signals for OA AEs. Therefore, ARB drugs, especially valsartan, should be used with caution when treating patients with OA combined with hypertension.

Comparison of Zybio Kit and saponin in-house method in rapid identification of bacteria from positive blood cultures by EXS2600 matrix-assisted laser desorption ionization time-of-flightmass spectrometry system.

We evaluated the performance of Zybio EXS2600 matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Zybio Inc., Chongqing, China) for the identification of bacteria from positive blood culture (BC) bottles using Blood Culture Positive Sample Pretreatment Kit (Zybio Inc., Chongqing, China) in comparison to an in-house saponin method. Following a positive signal by the BACTEC™ FX system, confirmation of identification was achieved using subcultured growing biomass used for MALDI-TOF MS analysis. A total of 94 positive BC bottles with 97 bacterial isolates were analyzed. The overall identification rates at the genus and species levels for the saponin method were 89.7% (87/97) and 74.2% (72/97), respectively. With the Zybio Kit, 88.7% (86/97) and 80.4% (78/97) of microorganisms were correctly identified to the genus and species levels, respectively. The saponin method identified 65.3% (32/49) of Gram-positive bacteria at the species level, whereas the Zybio Kit achieved a higher species-level identification rate of 79.6% (39/49) (p= 0.1153). The saponin method with additional on-plate formic acid extraction showed a significantly higher overall identification rate in comparison to the saponin method without that step for both genus (87.6% [85/97] vs. 70.1% [68/97], p= 0.0029) and species level (70.1% [68/97] vs. 46.4% [45/97], p= 0.0008). Identification rates of Gram-negative bacteria showed a higher identification rate, however, not statistically significant with additional Zybio Kit protocol step on both genus (85.4% [41/48] vs. 81.3% [39/48], p= 0.5858) and species level (77.1% [37/48] vs. 75% [36/48], p= 0.8120). Zybio Kit could offer an advantage in species-level identification, particularly for Gram-positive bacteria. The inclusion of on-plate formic acid extraction in the saponin method notably enhanced identification at both genus and species levels for Gram-positive bacteria. The extended protocol provided by the Zybio Kit could potentially offer an advantage in the identification of Gram-negative bacteria at both genus and species levels. Enhancements to the Zybio EXS2600 MALDI-TOF instrument software database are necessary.

A disproportionality analysis of sunitinib in the FDA adverse event reporting system (FAERS)

ObjectiveThis study aimed to analyze the FAERS database to identify adverse event associated with sunitinib to offer valuable insights for the judicious utilization of medication in clinical settings. MethodsVarious disproportionality analysis techniques, such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPN), and multi-gamma Poisson shrinkage (MGPS), were employed to analyze adverse drug reaction (ADR) reports pertaining to sunitinib in the FAERS database from its market introduction up to the first quarter of 2023. Subsequently, a secondary screening process was conducted to identify reliable positive signals. ResultsThe analysis of sunitinib adverse event signals at the system-organ classification level encompassed 27 organ systems, with gastrointestinal and endocrine disorders emerging as the predominant SOCs. A total of 237 significant adverse events meeting all four algorithms were detected. Notably, this study revealed previously unreported adverse events, including pleural effusion and ascites, while potential adrenal toxicity-related adverse events, highlighted in the drug's specification, were not identified in this analysis. The study examined the relationship between the duration of sunitinib dosing and the onset of adverse events, revealing a median onset of 48 days (IQR, 15–160 days). The findings indicated that a majority of adverse events manifested early in the dosing period, with tumor progression, disease progression, and mortality becoming more prevalent after one year of treatment. ConclusionIn the clinical utilization of sunitinib, vigilant monitoring of potential adverse reactions is imperative during the initial phase of drug administration. In addition to the documented adverse reactions outlined in the drug specification, healthcare providers should remain attentive to potential adverse reactions such as pleural effusion, ascites, and tumor development.

Complete organelle genomes of the threatened aquatic species Scheuchzeria palustris (Scheuchzeriaceae): Insights into adaptation and phylogenomic placement.

Scheuchzeria palustris, the only species in the Scheuchzeriaceae family, plays a crucial role in methane production and transportation, influencing the global carbon cycle and maintaining ecosystem stability. However, it is now threatened by human activities and global warming. In this study, we generated new organelle genomes for S. palustris, with the plastome (pt) measuring 158,573 bp and the mitogenome (mt) measuring 420,724 bp. We predicted 296 RNA editing sites in mt protein-coding genes (PCGs) and 142 in pt-PCGs. Notably, abundant RNA editing sites in pt-PCGs likely originated from horizontal gene transfer between the plastome and mitogenome. Additionally, we identified positive selection signals in four mt-PCGs (atp4, ccmB, nad3, and sdh4) and one pt-PCG (rps7), which may contribute to the adaptation of S. palustris to low-temperature and high-altitude environments. Furthermore, we identified 35 mitochondrial plastid DNA (MTPT) segments totaling 58,479 bp, attributed to dispersed repeats near most MTPT. Phylogenetic trees reconstructed from mt- and pt-PCGs showed topologies consistent with the APG IV system. However, the conflicting position of S. palustris can be explained by significant differences in the substitution rates of its mt- and pt-PCGs (p < .001). In conclusion, our study provides vital genomic resources to support future conservation efforts and explores the adaptation mechanisms of S. palustris.

Relationship between MRI findings and renal histopathology in IgG4-related tubulointerstitial nephritis.

MRI is expected to be a valuable tool for evaluating disease activity in immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis (IgG4-TIN). However, the correlation between MRI findings and renal histopathological findings remains to be elucidated. This study aimed to clarify the correlation between MRI findings and renal histopathological findings in IgG4-TIN. This retrospective cross-sectional study investigated 26 patients with biopsy-proven IgG4-TIN who underwent simultaneous percutaneous kidney biopsies and abdominal MRI examinations at Toranomon Hospital or Toranomon Hospital Kajigaya between December 2007 and November 2022. We reviewed kidney biopsy specimens and scored the degree of inflammatory cell infiltration and interstitial fibrosis. We assessed abdominal MRI, specifically examining T1WI, T2WI, and DWI, for the presence of abnormal signals in the inferior pole of the kidney on the side where the kidney biopsy was performed. Spearman's correlation coefficient test was conducted to examine the relationship between the images and histological findings. For T1WI, eight cases showed a positive low-intensity signal, and 18 cases were negative. For T2WI, 19 cases were positive for a low-intensity signal, and seven cases were negative. In DWI, 23 cases were positive for a high-intensity signal, and one was negative. T1WI low-intensity signal and T2WI low-intensity signal were significantly correlated with interstitial fibrosis score (correlation coefficient 0.52 and 0.64). DWI revealed IgG4-TIN detected IgG4-TIN lesions with the highest sensitivity; however, the correlation with inflammatory cell infiltration score was not significant. Low-intensity signal on T2WI is useful for predicting the degree of fibrosis in IgG4-TIN.