Positive Signals Research Articles

Benchmarking of corporate social responsibility in China

This study explores the underexplored application of benchmarking in Corporate Social Responsibility (CSR) among Chinese A-listed companies from 2010 to 2020. The results reveal a positive relationship between CSR performance and local best practices, indicating benchmarking’s influence on CSR activities. Notably, benefits like increased market value, robust revenue, and heightened analyst attention signify positive market signals, motivating companies to enhance their CSR performance. The impacts on CSR performance varies significantly based on leader companies’ CSR scores, ages, and follower companies’ ownership properties, sizes, and locations. Our findings offer valuable insights into CSR motivations and the performance effects of best practices.

PENGARUH PENGUNGKAPAN ENVIRONMENTAL COST DAN CORPORATE SOCIAL RESPONSIBILITY TERHADAP PROFITABILITAS PERUSAHAAN MANUFAKTUR SEKTOR INDUSTRI DASAR DAN KIMIA YANG TERDAFTAR PADA BURSA EFEK INDONESIA PERIODE TAHUN 2018-2022

This study aims to evaluate the impact of environmental cost disclosure and corporate social responsibility (CSR) on the profitability of manufacturing companies in the basic and chemical industries listed on the Indonesia Stock Exchange (IDX) during the period 2018-2022. Utilizing a quantitative approach with data analysis through Eviews software, the research explores the effects of these variables on company profitability. The findings reveal that environmental cost disclosure does not have a significant effect on company profitability. The level of environmental cost allocation does not influence market reactions or investor interest in the company. Conversely, CSR has a positive impact on profitability. CSR is seen as providing a positive signal to investors as it demonstrates the company’s responsibility towards its operational impacts. Simultaneously, the independent variables, namely environmental cost disclosure and CSR, significantly affect profitability, indicating that while environmental cost disclosure does not have a direct impact, CSR plays a crucial role in enhancing company profitability and attracting investor attention. This study aims to provide insights into how environmental cost disclosure and CSR affect company financial performance and how companies can leverage this information for strategic advantages in the capital market.

Molecular and serological investigation of Francisella tularensis among wild animals in Yamaguchi prefecture.

Francisella tularensis is an intracellular gram-negative bacterium known as the causative agent of tularemia, which can be transmitted to humans by direct contact with wild animals or by tick bites. Although F. tularensis is highly pathogenic, its recent prevalence in Japan is underreported due to the small number of reported cases. To clarify the current situation of F. tularensis in wild animals, we conducted surveillance on various species of wild animals in Yamaguchi prefecture. In this study, we screened 809 samples collected from 90 Japanese black bears, 105 Japanese monkeys, 168 sika deer, 205 wild boars, and 84 bats. For seroprevalence analysis, we tested 177 serum samples from 75 black bears and 102 monkeys using the microagglutination test. The results showed that serums from five black bears exhibited slight agglutination. Western blot was performed as a confirmatory test on these five samples, but no positive signals were detected. Additionally, molecular surveillance was conducted using DNA extracted from 464 whole blood and 168 tissues, targeting the gene encoding 23 KDa hypothetical protein by real-time PCR and outer membrane protein A gene by conventional PCR. No positive samples of F. tularensis were detected by either real-time or conventional PCR. Although we did not detect any F. tularensis-positive samples through serological and molecular analyses, continuous surveillance studies are necessary since sporadic human cases have been reported in Japan.

Positive feed-forward regulation of nitrate uptake by rice roots and its molecular mechanism

To investigate the positive feed-forward regulatory mechanism of nitrate uptake by rice, its responses to various light and carbohydrates were compared. In order to measure nitrate uptake in real time, the non-invasive method was used. The results showed that net nitrate uptake increased in the light and decreased in the dark, and finally reached a steady state after about 5 h. Based on it, carbohydrates effects could be investigated without considering light effects. After sucrose addition for 2 h, net nitrate uptake increased by about 80% without a lag, while glucose, fructose and raffinose had a slight effect with a lag and other sugars had no effect. It provided an evidence that sucrose was a positive feed-forward signal molecule of nitrate uptake by rice roots. To further analyze the effect of sucrose on the expression of high affinity nitrate transporter genes OsNRT2.1, OsNRT2.2, OsNRT2.3a and OsNRT2.3b, qRT-PCR was used to further verify after treated with 10 mM sucrose. The results revealed that these genes expression was immediately up-regulated, which indicated that these genes were post transcriptionally regulated. Further, 15N exchange dynamics analyzed N transport. It is benefit for increasing nitrate uptake by rice and improving its yield.

Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device

The sensitivity and responsiveness of living cells to environmental changes are enabled by dynamic protein structures, inspiring efforts to construct artificial supramolecular protein assemblies. However, despite their sophisticated structures, designed protein assemblies have yet to be incorporated into macroscale devices for real-life applications. We report a 2D crystalline protein assembly of C98/E57/E66L-rhamnulose-1-phosphate aldolase (CEERhuA) that selectively blocks or passes molecular species when exposed to a chemical trigger. CEERhuA crystals are engineered via cobalt(II) coordination bonds to undergo a coherent conformational change from a closed state (pore dimensions <1 nm) to an ajar state (pore dimensions ~4 nm) when exposed to an HCN(g) trigger. When layered onto a mesoporous silicon (pSi) photonic crystal optical sensor configured to detect HCN(g), the 2D CEERhuA crystal layer effectively blocks interferents that would otherwise result in a false positive signal. The 2D CEERhuA crystal layer opens in selective response to low-ppm levels of HCN(g), allowing analyte penetration into the pSi sensor layer for detection. These findings illustrate that designed protein assemblies can function as dynamic components of solid-state devices in non-aqueous environments.

Adverse drug events associated with fluorouracil use in patients with metastatic colorectal cancer: a real-world pharmacovigilance study based on the FDA adverse event reporting system

ABSTRACT Background Fluorouracil (5-FU) is widely used to treat metastatic colorectal cancer (mCRC), but real-world safety data is limited. Our study aimed to evaluate 5-FU’s safety profile in a large mCRC population using the FAERS database. Research design and methods We conducted disproportionality analyses to identify adverse drug events associated with 5-FU use in mCRC patients from 2004 to 2023. Subgroup analyses, gender difference analyses, and logistic regression were also performed. Results We identified 1,458 reports with 5-FU as the primary suspected drug, with males accounting for 48.8% of reports. Gastrointestinal disorders were the most common adverse event (864 cases), while pregnancy-related conditions showed the strongest signal intensity (ROR = 2.97). We found 19 preferred terms with positive signals, including ischemic hepatitis (ROR = 59.32), blood iron increased (ROR = 59.32), and stress cardiomyopathy (ROR = 51.94). Males were more susceptible to weight loss and skin toxicity. Most adverse events occurred within the first month of 5-FU administration. Conclusion Our study provides a comprehensive analysis of 5-FU’s safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

Adverse events related to neuromuscular blocking agents: a disproportionality analysis of the FDA adverse event reporting system.

Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in "cardiac disorders," "immune system disorders," "respiratory, thoracic and mediastinal disorders" and "vascular disorders." At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study.

CD2AP is Co-Expressed with Tropomyosin-Related Kinase A and Ras-Related Protein Rab-5A in Cholinergic Neurons of the Murine Basal Forebrain.

Basal forebrain cholinergic neurons project to the hippocampus and cortex, are critical for learning and memory, and are central to the pathogenesis of Alzheimer's disease (AD). GWAS have consistently shown that genomic variants at the CD2AP gene locus are associated with significant increased risk of AD. GWAS studies have also shown that genetic variants in endocytosis genes, including RAB5A , significantly increase susceptibility to AD. Previous work in our lab has shown that CD2AP functions as a docking-scaffold/adaptor protein as a coordinator of nerve growth factor (NGF) and trophic signaling in neurons. We have also demonstrated that CD2AP positively regulates Rab5-mediated mechanisms of endocytosis in primary sensory neurons. The purpose of this study was to perform an in vivo characterization of CD2AP expression in cholinergic neurons of the brain regions most relevant to AD pathogenesis and to investigate the colocalization of CD2AP and Rab5 in cholinergic neurons of the murine basal forebrain. Brain tissue was perfused, harvested from ChAT BAC -eGFP transgenic mice (N=4 male, N=4 female; aged 10 mo), where cholinergic neurons (co-) express green fluorescence protein (GFP) in central and peripheral neurons that express choline acetyltransferase (ChAT). Frozen tissue sections were used to assess the specificity of the reporter in mouse brain along with localization of both CD2AP and Rab5 (co-) expression using immunofluorescence (IF) analysis of ChAT-GFP+ neurons and primary antibodies against ChAT, CD2AP and Rab5. Image J software was used to develop and optimize a colocalization assay for CD2AP and Rab5 puncta. Experiments were repeated in a follow-up cohort of aged-adult mice (N=2 male, N=2 female; aged 18 mo). IF expression of CD2AP was quantified in the basal forebrain, diagonal band of Broca (vDB), and striatal regions and compared to results from the cortical regions of the adult mouse brain. Colocalization of CD2AP was observed in the cell bodies of ChAT-GFP+ neurons of the striatum, vDB and basal forebrain regions, where CD2AP expression intensity as well as the number of cell bodies with positive signal increased incrementally. Colocalization analyses revealed near-complete overlap of CD2AP and Rab5 expression in ChAT-GFP+ cholinergic neurons of the basal forebrain region. We conclude that cholinergic neurons express CD2AP in healthy adult and aged-adult mouse brains. These data provide the first evidence of quantifiable CD2AP protein expression of cholinergic neurons specific to the diagonal band of Broca (vDB) and basal forebrain. Together with previous research from our lab, these data support a role for CD2AP in the pathogenesis of AD through orchestration of endocytosis and retrograde signaling. Ongoing studies are underway to verify these findings in a novel AD mouse model that incorporates the humanized variant of CD2AP , created by MODEL-AD, where we aim to further investigate how CD2AP variants may affect mechanistic components of Rab5 endocytosis as well as subsequent survival of cholinergic neurons in the context of known amyloid beta and Tau pathologies.

Evaluation of BACTEC™ FX and BacT/Alert™ Automated Blood Culture Systems for Detection of Clinically Relevant Bacterial and Yeast Species

Background: Bloodstream infections (BSI) are a significant health concern, necessitating effective diagnostic tools. This study evaluates the performance of the BD Bactec FX system in comparison to the established BacT/Alert system, examining mean time till detection (TTD) across various blood culture bottles.Methods: The study involves 148 blood culture bottles, inoculated with representative bacterial ATCC strains (n= 15) and 04 yeast isolates. Parallel testing is conducted by seeding 10–30 colony-forming units (CFU) in duplicate in both BD Bactec FX and BacT/Alert systems. TTD is assessed across aerobic, anaerobic, and pediatric bottles for diverse microbial species.Results: All 148 bottles tested in parallel show positive signals in both systems. BD Bactec FX demonstrates significantly shorter TTD for adult-seeded cultures in aerobic and anaerobic bottles compared to BacT/Alert Similarly, pediatric bottles with BD Bactec FX exhibit a shorter TTD compared to BacT/Alert. The statistical significance of TTD, 95% confidence intervals (CI), and p-values is evident for Bactec FX aerobic, anaerobic, and pediatric bottles across tested organisms. Notable examples of faster TTD include; Bacteroides ovatus (16.6h by Bactec FX vs. 70.5h by Bact/Alert 3D), Stenotrophomonas maltophilia (33.7h vs. 72.5h), and Streptococcus pyogenes (8.1h vs. 11.9h).Conclusions: In conclusion, the study’s findings demonstrate that BD Bactec FX surpasses BacT/Alert in prompt microbial detection, showcasing potential for early identification of bacteremia and fungemia. Faster TTD implies the potential to initiate timely antimicrobial treatment, thereby reducing patient morbidity and mortality. However, exceptions in certain microbial species highlight the need for comprehensive clinical validation to establish the broad applicability of these findings.Keywords: Blood Culture System; Recovery Rate; Time to detection; Blood stream infection; BTA3D; Bactec FX

Influence of male’s facial attractiveness, vocal attractiveness and social interest on female’s decisions of fairness

The present study employed dictator game and ultimatum game to investigate the effect of facial attractiveness, vocal attractiveness and social interest in expressing positive (“I like you”) versus negative signals (“I don’t like you”) on decision making. Female participants played against male recipients in dictator game and ultimatum game while played against male proposers in ultimatum game. Results showed that participants offered recipients with attractive faces more money than recipients with unattractive faces. Participants also offered recipients with attractive voices more money than recipients with unattractive voices, especially under the positive social interest condition. Moreover, participants allocated more money to recipients who expressed positive social interest than those who expressed negative social interest, whereas they would also expect proposers who expressed positive social interest to offer them more money than proposers who expressed negative social interest. Overall, the results inform beauty premium for faces and voices on opposite-sex economic bargaining. Social interest also affects decision outcomes. However, the beauty premium and effect of social interest varies with participants’ roles.

The role of FraI in cell-cell communication and differentiation in the hormogonia-forming cyanobacterium Nostoc punctiforme.

The filament-forming cyanobacterium Nostoc punctiforme serves as a valuable model for studying cell differentiation, including the formation of nitrogen-fixing heterocysts and hormogonia. Hormogonia filaments play a crucial role in dispersal and plant colonization, providing a nitrogen source through atmospheric nitrogen fixation, thus holding promise for fertilizer-free agriculture. The coordination among the hormogonia cells enabling uniform movement toward the positive signal remains poorly understood. This study investigates the role of septal junction-mediated communication in hormogonia differentiation and motility, by studying a ΔfraI mutant with significantly impaired communication. Surprisingly, impaired communication does not abolish synchronized filament movement, suggesting an alternative coordination mechanism. These findings deepen our understanding of cyanobacterial biology and have broader implications for multicellular behavior in prokaryotes.

Background-free mid-infrared absorption spectroscopy using sub-cycle pulses

We have demonstrated highly sensitive single-shot based background-free mid-infrared (MIR) absorption spectroscopy using sub-cycle MIR pulses generated through filamentation. The MIR pulse transmitted through a sample was upconverted with a fast rising and long tailing gate pulse through four-wave difference frequency generation in a silicon membrane. By recording the upconverted spectrum of the free induction decay alone, we successfully measured the absorption spectrum as a positive signal in the wavenumber range from 500 to 4500 cm−1, which covers both the fingerprint and functional group regions. We obtained an absorption spectrum of ∼50 mM of aqueous glucose, which is not detectable with a standard Fourier transform infrared spectrometer.

Risk of drug-induced angioedema: a pharmacovigilance study of FDA adverse event reporting system database.

The purpose of this study is to explore and analyze the FDA Adverse Event Reporting System (FAERS) database to identify drug adverse reaction signals associated with angioedema. The findings aim to provide valuable insights for clinical drug safety considerations. The Open Vigil 2.1 data platform was utilized to collect adverse event reports related to angioedema from the first quarter of 2004 to the fourth quarter of 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were employed as disproportionality measures to detect adverse reaction signals Sof drugs associated with angioedema. A total of 38,921 reports were retrieved, with the majority being reported by healthcare professionals. The analysis included predominantly adult patients (≥18years of age), with slightly higher representation of females compared to males. Among the top 30 drugs associated with the occurrence of angioedema, 24 drugs showed positive signals in the risk analysis. Based on the individual drug reporting odds ratio (95% confidence interval) as a measure of risk signal strength, the top five drugs are as follows: lisinopril [ROR (95% CI): 46.43 (42.59-50.62)], enalapril [ROR (95% CI): 43.51 (39.88-47.46)], perindopril [ROR (95% CI): 31.17 (27.5-35.32)], alteplase [ROR (95% CI): 29.3 (26.95-31.85)], ramipril [ROR (95% CI): 20.93 (19.66-22.28)]. After categorizing the drugs, the strongest positive signal was observed in the antithrombotic agents [ROR (95% CI): 22.53 (21.16-23.99)], following that, cardiovascular drugs [ROR (95% CI): 9.17 (8.87-9.48)], antibiotics [ROR (95% CI): 6.42 (5.91-6.96)], immunosuppressors [ROR (95% CI): 5.95 (5.55-6.39)], anti-inflammatory analgesics [ROR (95% CI): 4.65 (4.45-4.86)], antiallergic drugs [ROR (95% CI): 4.47 (3.99-5)], antiasthmatics [ROR (95% CI): 2.49 (2.14-2.89)], blood sugar control drugs [ROR (95% CI): 1.65 (1.38-1.97)], and digestive system drugs [ROR (95% CI): 1.59 (1.45-1.74)] exhibited progressively decreasing ROR values. Many medications are associated with a high risk of angioedema. These medications play a crucial and potentially preventable role in controlling the occurrence of angioedema. It is essential to consider the risk level of drug-induced angioedema in clinical practice to optimize medication therapy.

Histopathologic Features and Viral Antigen Distribution of H5N1 Highly Pathogenic Avian Influenza Virus Clade 2.3.4.4b from the 2022-2023 Outbreak in Iowa Wild Birds.

In 2022, a new epornitic of H5N1 highly pathogenic avian influenza (HPAI) virus clade 2.3.4.4b emerged in U.S. domestic poultry with high prevalence in wild bird populations. We describe pathological findings of HPAI H5N1 in nine wild birds encompassing eight different species, including Accipitriformes (red-tailed hawk, bald eagle), Cathartiforme (turkey vulture), Falconiforme (peregrine falcon), Strigiforme (one adult great-horned owl, one juvenile great-horned owl), Pelecaniforme (American white pelican), and Anseriformes (American green-winged teal, trumpeter swan). All these birds died naturally (found dead, or died in transit to or within a rehabilitation center), except for the bald eagle and American green-winged teal, which were euthanized. Gross lesions were subtle, characterized by meningeal congestion observed in the turkey vulture, bald eagle, and adult great-horned owl. Histologically, encephalitis was observed in all cases (9/9, 100%). Leukocytoclastic and fibrinoid vasculitis with necrotizing encephalitis was observed in the red-tailed hawk, great-horned owls, and American white pelican (5/9, 55.6%), and perivascular lymphohistiocytic encephalitis was seen in the turkey vulture, peregrine falcon, green-winged teal, and bald eagle (4/9, 44.4%). Coagulative necrosis or lymphohistiocytic/lymphoplasmacytic inflammation was identified in the kidney (6/8, 75%), liver (6/9, 66.7%), heart (5/9, 55.6%), and lung (2/9, 22.2%). Immunopositive signals against Influenza virus A nucleoprotein were predominantly detected within the brain (9/9, 100%), air sac (7/9, 77.8%), lung (7/9, 77.8%), kidney (6/8, 75%), heart (6/9, 66.7%), and liver (5/9, 55.6%). Additionally, other organs, such as the pancreas, spleen, intestines, gonads, and adrenals occasionally exhibited positive viral protein signals. In these organs, in addition to parenchymal cells, viral protein signals were often identified in endothelial cells. Our results suggest that the 2022-2023 HPAIV H5N1 clade 2.3.4.4b replicated systemically in all examined birds, with brain lesions being the most prevalent and associated with a subset of birds displaying clinical signs observed perimortem.

Superimposed Positive Sequence Impedance for Detecting Unintentional Islanding in Microgrid

Incorporation of environmentally friendly energy sources (RESs) into the electricity grid has many benefits, including economic, technological, and environmental. However, excessive renewable energy sources (RES) in the power grid provide technical problems, including equipment protection, DG operation, and islanding detection. One of the most serious challenges is the islanding phenomenon. Islanding can cause several problems, such as frequency instability and voltage fluctuations resulting in damage to electrical equipment or threatening utility workers who may be working/accessing the equipment. This research proposes an efficient islanding detection algorithm to lessen the impact of such threats. This novel passive islanding detection scheme is based on superimposed positive sequence impedance (SPSI). For calculating the superimposed positive sequence impedance (SPSI), the voltage and current signals are obtained from targeted DG points. The scheme’s performance is tested on multiple bus systems across islanding and non-islanding conditions using a MATLAB/Simulink environment. It is shown that even in the presence of noise, the algorithm can determine an islanding decision with high accuracy and a short detection time of 84 ms. In comparison to other algorithms, it operates at zero power mismatch (ZPM) and does not affect power quality.

A Quasi Real-Time Evaluation of High-Resolution Mass Spectra of Complex Chlorinated Paraffin Mixtures and Their Transformation Products.

Chlorinated paraffins (CPs) are complex mixtures of polychlorinated n-alkanes with multiple carbon- (C-, nC = 9-30) and chlorine homologues (Cl-, nCl = 3-18). The mass spectrometric analysis of CPs is time-consuming and challenging, especially when interferences between CPs, their transformation products, or from the matrix are numerous. These analytical challenges and the lack of appropriate and accessible data evaluation tools are obstacles to their analysis. CP-Hunter is a web-based, open-access data processing platform for the automatic analysis of mass spectra of CPs and their transformation products. Extracts of two consumer plastic materials and sewage sludge were evaluated with CP-Hunter. C- and Cl-homologue distributions were obtained in quasi-real-time and the posterior calculated fingerprints were in agreement with the ones obtained by traditional methods. However, the data extraction and evaluation time were now reduced from several minutes to seconds. The implemented signal deconvolution method, i.e., to resolve mass spectrometric interferences, provides robust results, even when severe matrix effects are present. CP-Hunter facilitates the untargeted analysis of unknown products and the detection and elimination of false positive signals. Finally, data evaluation with CP-Hunter is performed locally without the transfer of data to external servers. The tool is safe, public, and accessible at https://cphunter.cheminfo.org/.

Data mining study on adverse events of tirzepatide based on FAERS database

ABSTRACT Background Tirzepatide is a novel dual gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 receptor agonist (GLP-1 RA) for type 2 diabetes or obesity. To explore the safety profile of tirzepatide in real-world clinical applications. Research design and methods A retrospective analysis of adverse events (AEs) reports associated with tirzepatide was conducted from the second quarter of 2022 through the fourth quarter of 2023, utilizing the FDA Adverse Event Reporting System (FAERS) database. Signal mining utilized the reporting odds ratio (ROR) method, and onset time was analyzed utilizing the Weibull Shape Parameter (WSP). Results We identified 25,215 AE reports related to tirzepatide, predominantly in the 65 to 85 age group. Four positive signals were found at the system organ classes level. Additionally,109 AEs at the preferred terms level with positive signals were indicated. Included among these are novel signals, such as the presence of thyroid mass, medullary thyroid carcinoma, and conditions affecting the reproductive system and breast. Most AEs occurred within the first 30 days. The WSP was 0.66, indicating a propensity for early failure type. Conclusions This study identified several novel AE signals for tirzepatide, highlighting the need for careful monitoring, especially in the early stages of treatment.

Evaluating drug withdrawal syndrome risks through food and drug administration adverse event reporting system: a comprehensive disproportionality analysis.

The study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome. All the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome. A total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs. Our analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications.

Biomarker Multiplexing with Rational Design of Nucleic Acid Probe Complex

AbstractThe expression profiles of intracellular biomarkers hold significance for understanding cellular biological functions and tracking pathological activities. Due to its programmability and biocompatibility, extensive efforts have been devoted to design various kinds of nucleic acid probes for biomarker detection. However, pinpointing a single biomarker could end up in a false positive signal, delaying diagnosis. In this review, we present an overview of current advances in biomarker detection and signal amplification techniques. We highlight strategies for biomarker multiplexing and signal amplification with combination of isothermal approaches. High specificity and sensitivity are the two criteria for a desired probe, as are the challenges encountered by a probe that operates efficiently in biological systems. With higher biomarker identification accuracy, we may be able to move one step closer to precision medicine.

Gray-tone appearances on 4-hour delayed gadolinium-enhanced magnetic resonance imaging indicate severe inner ear pathology and symptoms in sudden sensorineural hearing loss.

Hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) in delayed gadolinium-enhanced magnetic resonance imaging (MRI) typically depicts normal inner ear as "white-tone" and endolymphatic hydrops as "black-transparent" appearances, whereas ears with auditory and vestibular disorders are occasionally depicted as "gray-tone." This study aimed to investigate the pathological basis of sudden sensorineural hearing loss (SSNHL) patients with "gray-tone" appearances on HYDROPS. Delayed gadolinium-enhanced MRI examinations were conducted on 29 subjects with unilateral SSNHL. We mainly analyzed positive perilymph image (PPI) and positive endolymph image (PEI), which were components HYDROPS. On PPI, signal intensity (SI) values extracted from the cochlear and vestibular region of interest (ROI) were higher in the SSNHL ears with dizziness/vertigo symptom at the first visit compared to the healthy ear. Additionally, the PPI/PEI enhancement pattern in the vestibule was associated with a high prevalence of hearing and vestibular deteriorations at the first visit and poor hearing improvement after treatment. Enhancement on PPI/PEI may result from leakage of gadolinium into the inner ear following breakdown of the blood-labyrinth barrier, with high SI being correlated with the amount of leakage. Particularly, a significant leakage into the endolymphatic space, defined as PPI+/PEI+, indicates severe inner ear pathology. Ultimately, we emphasize that the "gray-tone" appearance in the inner ear on HYDROPS comprises enhancements on both PPI and PEI and propose a new classification for evaluating SSNHL Peri- and Endolymphatic image Enhancement pattern in Delayed gadolinium-enhanced MRI (SPEED). 4.