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We examine the dynamical properties of a single-layer convolutional recurrent network with a smooth sigmoidal activation function, for small values of the inputs and when the convolution kernel is unitary, so all eigenvalues lie exactly at the unit circle. Such networks have a variety of hallmark properties: the outputs depend on the inputs via compressive nonlinearities such as cubic roots and both the timescales of relaxation and the length scales of signal propagation depend sensitively on the inputs as power laws, both diverging as the input →0. The basic dynamical mechanism is that inputs to the network generate ongoing activity, which in turn controls how additional inputs or signals propagate spatially or attenuate in time. We present analytical solutions for the steady states when the network is forced with a single oscillation and when a background value creates a steady state of “ongoing activity” and derive the relationships shaping the value of the temporal decay and spatial propagation length as a function of this background value.

Abstract Aggregation‐induced emission has eliminated the problem of fluorescence quenching in the solid state, making molecules with this property excellent candidates for vapor sensing due to their portability and ease of interpretation. Here, films of polystyrene / 2‐[4‐vinyl(1,10‐biphenyl)‐40‐yl]‐cyanovinyljulolidine copolymers are reported that exhibit aggregation‐induced emission behavior for the detection of toluene, m‐xylene, dichloromethane, and chloroform. After exposure to the analytes, the emission of the copolymers shows significant changes in intensity and spectral shape corresponding to the reduced microviscosity of the molecular environment. However, these changes are similar for different analytes, resulting in low chemical selectivity. Therefore, label‐free selectivity is achieved by controlling the molecular diffusion of the four vapor analytes within the films using the Flory–Huggins solution theory with capping layers of cellulose acetate (CA) and poly(vinyl alcohol) (PVA) polymers.

Candida auris outbreaks are increasingly frequent worldwide. In our 1000-bed hospital, an endemic transmission of C. auris was established in two of five intensive care units (ICUs). Aims of our study were to describe the occurrence of new cases of C. auris colonization and infection outside the endemic ICUs, in order to add evidence for future policies on screening in patients discharged as negative from an endemic setting, as well as to propose a new algorithm for screening of such high-risk patients. From 26 March 2021 to 26 January 2023, among 392 patients who were diagnosed as colonized or infected with C. auris in our hospital, 84 (21.4%) received the first diagnosis of colonization or infection outside the endemic ICUs. A total of 68 patients out of 84 (81.0%) had a history of prior admission to the endemic ICUs. All were screened and tested negative during their ICU stay with a median time from last screening to discharge of 3 days. In 57/68 (83.8%) of patients, C. auris was detected through screening performed after ICU discharge, and 90% had C. auris colonization detected within 9 days from ICU discharge. In 13 cases (13/57 screened, 22.8%), the first post-ICU discharge screening was negative. In those not screened, candidemia was the most frequent event of the first C. auris detection (6/11 patients not screened). In settings where the transmission of C. auris is limited to certain wards, we suggest screening both at discharge from the endemic ward(s) even in case of a recent negative result, and at least twice after admission to nonendemic settings. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychosis., Study Design: This study included 4679 participants of European ancestry from the Adolescent Brain Cognitive Development Study. Persistent distressing PLE was derived from the Prodromal-Questionnaire-Brief Child Version using four years of data. Generalized linear mixed models tested the association between polygenic risk score for schizophrenia (PRS-SCZ), physical activities, and PLE. The models adjusted for age, sex, parental education, income-to-needs ratio, family history of psychosis, body mass index, puberty status, principal components for PRS-SCZ, study site, and family., Study Results: PRS-SCZ was associated with a greater risk for persistent distressing PLE (adjusted relative risk ratio (RRR) = 1.14, 95% CI [1.04, 1.24], P = .003). Physical activity was associated with less risk for persistent distressing PLE (adjusted RRR = 0.87, 95% CI [0.79, 0.96], P = .008). Moreover, physical activities moderated the association between PRS-SCZ and persistent distressing PLE (adjusted RRR = 0.89, 95% CI [0.81, 0.98], P = .015), such that the association was weaker as participants had greater participation in physical activities., Conclusions: These findings demonstrate that the interaction between genetic liability and physical activities is associated with trajectories of distressing PLE. Further research is needed to understand the mechanisms of physical activities and genetic liability for schizophrenia in the development of psychosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Advances in theoretical understanding are frequently unlocked by access to large, diverse experimental datasets. Our understanding of olfactory neuroscience and psychophysics remain years behind the other senses, in part because rich datasets linking olfactory stimuli with their corresponding percepts, behaviors, and neural pathways remain scarce. Here we present a concerted effort to unlock and unify dozens of stimulus-linked olfactory datasets across species and modalities under a unified framework called Pyrfume. We present examples of how researchers might use Pyrfume to conduct novel analyses uncovering new principles, introduce trainees to the field, or construct benchmarks for machine olfaction. [ABSTRACT FROM AUTHOR]

Objective: This study explores the risk factors for low-level viremia (LLV) occurrence after ART and develops a risk prediction model. Method: Clinical data and laboratory indicators of people living with HIV (PLWH) at Hangzhou Xixi Hospital from 5 April 2011 to 29 December 2022 were collected. LASSO Cox regression and multivariate Cox regression analysis were performed to identify laboratory indicators and establish a nomogram for predicting LLV occurrence. The nomogram's discrimination and calibration were assessed via ROC curve and calibration plots. The concordance index (C-index) and decision curve analysis (DCA) were used to evaluate its effectiveness. Result: Predictive factors, namely, age, ART delay time, white blood cell (WBC) count, baseline CD4+ T-cell count (baseline CD4), baseline viral load (baseline VL), and total bilirubin (TBIL), were incorporated into the nomogram to develop a risk prediction model. The optimal model (which includes 6 variables) had an AUC for LLV after 1-year, 3-year, and 5-year of listing of 0.68 (95% CI, 0.61–0.69), 0.69 (95% CI, 0.65–0.70), and 0.70 (95% CI, 0.66–0.71), respectively. The calibration curve showed high consistency between predicted and actual observations. The C-index and DCA indicated superior prediction performance of the nomogram. There was a significant difference in CD4 levels between LLV and non-LLV groups during the follow-up time. The dynamic SCR, ALT, TG and BG levels and occurrence of complications differed significantly between the high- and low-risk groups. Conclusion: A simple-to-use nomogram containing 6 routinely detected variables was developed for predicting LLV occurrence in PLWH after ART. [ABSTRACT FROM AUTHOR]

Introduction: Candida auris is an emerging pathogen that represents a worldwide health problem due to its global expansion, multidrug resistance, and difficult laboratory identification. Among the risk factors for colonization/infection by C. auris , a stay in an intensive care unit (ICU) stands out. This prospective multicenter study aimed to monitor the trend of the local epidemiology of Candida spp. and unveil the prevalence of C. auris. Methods: From 2020 to 2022, axillar/inguinal swabs were collected from adult patients at three points: upon admission (D1) and on the fifth (D5) and eighth (D8) days of their ICU stay. We employed culture-based screening methods combined with molecular techniques to identify Candida spp. down to the species level. Specific screening for Candida auris was conducted using a real-time PCR assay in combination with an improved selective culture medium, mannitol salt agar auris (MSAA). To validate the effectiveness of MSAA, a collection of reference C. auris strains representing the four major geographical clades was used. Results: We enrolled 675 patients, and 355 Candida isolates were retrieved from the 988 swab samples collected. From those, 185/355 (52.1%) were identified as C. albicans and 170/355 (47.9%) as non- albicans Candida (NAC). MSAA medium showed a specificity of 94.8%, albeit C. auris was not detected in this cohort. The dynamics of Candida spp. colonization by ICU were significant at the three collection points. Upon admission, C. albicans was associated with the Beatriz Ângelo Hospital ICU (p =0.003) and C. tropicalis with the general Hospital Professor Doutor Fernando Fonseca (FFH) ICU (p =0.006). C. parapsilosis and C. lusitaniae were associated with FFH ICUs, with the general ICU at D5 (p =0.047) and surgical ICU at D8 (p =0.012). The dynamics of NAC colonization by ICU were significantly different at D1 (p =0.011), D5 (p =0.047), and D8 (p =0.012). Conclusion: We developed and implemented a screening protocol for C. auris while uncovering the colonization patterns of Candida in the ICU. Our findings contribute to the optimization of overall patient management, ensuring that ICU protocols are resilient and adaptive to emerging fungal threats. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a potentially life-threatening condition with significant mortality and morbidity. An estimated 48.9 million cases and 11 million deaths occur due to sepsis worldwide. The gold standard for the diagnosis of suspected sepsis patients is blood culture. Aims and Objectives: The aims and objectives of the study are to evaluate the growth of rare microorganisms in blood cultures of intensive care unit (ICU) patients, to determine their antimicrobial susceptibility patterns, and also to assess the associated risk factors in those patients. Materials and Methods: This study was conducted for 1 year (August 2023-July 2024) in our department including blood culture samples from ICU patients and relatively rare microorganisms isolated were included in the study accounting for 40 cases. Blood specimens were cultured in automated BD BACTECTM Fx40 blood culture system and identification of microorganisms and their antimicrobial susceptibility pattern were detected by Vitek2 system. Results: Female patients were more in number than male patients and patients of 0--20 years' age group were most commonly affected. Staphylococcus hominis was most commonly isolated out of all rarely isolated microorganisms. The different parameters for the assessment of sepsis severity in our study were C-reactive protein (CRP), Neutrophil count, D-dimer, Procalcitonin, and quick sequential organ failure assessment (qSOFA) score. Out of all, CRP was most commonly raised among sepsis patients. The most common risk factor involved was prolonged ICU stay. Conclusion: Appropriate collection and processing of blood culture samples can reduce sepsis-related morbidity and mortality manifold. Combination of biomarkers study and qSOFA scoring system can improve diagnosis and monitoring of sepsis patients. [ABSTRACT FROM AUTHOR]

Background: This article employs bibliometric methods and visual maps to delineate the research background, collaborative relationships, hotspots, and trends in the study of gut fungi in human diseases and health. Methods: Publications related to human gut fungi were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, R software and Microsoft Excel were employed to generate visual representations illustrating the contributions made by countries/regions, authors, organizations, and journals. Employing VOSviewer and CiteSpace, we conducted a comprehensive analysis of the retrieved publications, revealing underlying tendencies, research hotspots, and intricate knowledge networks. Results: This study analyzed a total of 3,954 publications. The United States ranks first in the number of published papers and has the highest number of citations and h-index. Mostafa S Elshahed is the most prolific author. The University of California System is the institution that published the most papers. Frontiers In Microbiology is the journal with the largest number of publications. Three frequently co-cited references have experienced a citation burst lasting until 2024. Conclusion: Advancements in sequencing technologies have intensified research into human gut fungi and their health implications, shifting the research focus from gut fungal infections towards microbiome science. Inflammatory bowel diseases and Candida albicans have emerged as pivotal areas of interest in this endeavor. Through this study, we have gained a deeper insight into global trends and frontier hotspots within this field, thereby enhancing our understanding of the intricate relationship between gut fungi and human health. [ABSTRACT FROM AUTHOR]

The capabilities of the human ear are remarkable. We can normally detect acoustic stimuli down to a threshold sound-pressure level of 0 dB (decibels) at the entrance to the external ear, which elicits eardrum vibrations in the picometer range. From this threshold up to the onset of pain, 120 dB, our ears can encompass sounds that differ in power by a trillionfold. The comprehension of speech and enjoyment of music result from our ability to distinguish between tones that differ in frequency by only 0.2%. All these capabilities vanish upon damage to the ear’s receptors, the mechanoreceptive sensory hair cells. Each cochlea, the auditory organ of the inner ear, contains some 16,000 such cells that are frequency-tuned between ∼20 Hz (cycles per second) and 20,000 Hz. Remarkably enough, hair cells do not simply capture sound energy: they can also exhibit an active process whereby sound signals are amplified, tuned, and scaled. This article describes the active process in detail and offers evidence that its striking features emerge from the operation of hair cells on the brink of an oscillatory instability—one example of the critical phenomena that are widespread in physics. [ABSTRACT FROM AUTHOR]

The critical brain hypothesis states that the brain can benefit from operating close to a second-order phase transition. While it has been shown that several computational aspects of sensory processing (e.g., sensitivity to input) can be optimal in this regime, it is still unclear whether these computational benefits of criticality can be leveraged by neural systems performing behaviorally relevant computations. To address this question, we investigate signatures of criticality in networks optimized to perform efficient coding. We consider a spike-coding network of leaky integrateand-fire neurons with synaptic transmission delays. Previously, it was shown that the performance of such networks varies nonmonotonically with the noise amplitude. Interestingly, we find that in the vicinity of the optimal noise level for efficient coding, the network dynamics exhibit some signatures of criticality, namely, scale-free dynamics of the spiking and the presence of crackling noise relation. Our work suggests that two influential, and previously disparate theories of neural processing optimization (efficient coding and criticality) may be intimately related. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the autoimmune effects of gold aurothiomalate (AuTM) exposure in genetically different mouse strains to understand how gold triggers autoimmune diseases. We focused on two strains, A.TL and A.SW, which share genetic similarities except for H-2-related genes. Here, we show that A.TL mice, when exposed to AuTM, developed specific immune responses, including increased levels of antinuclear antibodies (ANA) compared to A.SW mice. A.TL mice showed a particularly strong response, especially in females, resembling symptoms of human autoimmune diseases like lupus. These findings suggest that A.TL mice could be a valuable model for studying environment-induced autoimmunity, helping to explore the genetic mechanisms behind these conditions and potentially leading to improved diagnosis and treatment of autoimmune diseases in humans. To demonstrate causation or/and assess pathogenic mechanisms of environment-induced autoimmunity, various animal models that mimic the characteristics of the human autoimmune diseases need to be developed. Experimental studies in mice reveal the genetic factors that contribute to autoimmune diseases. Here, the immune response of two mouse strains congenic for non-H-2 genes, A.TL (H-2tl) and A.SW (H-2s), was evaluated after 15 weeks' exposure to gold aurothiomalate (AuTM). AuTM-treated A.TL mice showed anti-nuclear antibodies (ANA) with homogenous and/or fine speckled staining patterns and serum autoantibodies to ds-DNA, chromatin, histones, and ribonucleoproteins (RNP). Female A.TL mice showed a stronger immune response than males, as well as an increase of B cells in their spleen after 15 weeks of gold exposure. A.SW exposed for AuTM showed the induction of anti-nucleolar antibodies (ANoA) with a clumpy staining pattern, as well as an increase in splenic B and T cells. The serum autoantibodies levels in A.SW mice were limited compared to those of A.TL mice. Overall, A.TL presents a stronger immune response after gold exposure than A.SW. The immune response developed in A.TL presents similarities with the clinical manifestations in human autoimmune diseases. Thus, gold-exposed A.TL could constitute a potential experimental mouse model for the study of autoimmunity. [ABSTRACT FROM AUTHOR]

Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different cellular pathways with the goals of increasing treatment options and reducing development of resistance. However, some circumstances can prevent the implementation of combination therapy in clinical practice. These could include the increased risk of adverse effects, drug interactions, and even the promotion of drug resistance. Furthermore, robust clinical evidence supporting the superiority of combination therapy over monotherapy is limited and underscores the need for further research. Despite these challenges, synergies detected with different antifungal classes, such as the azoles and echinocandins, suggest that treatment strategies can be optimized by better understanding the underlying mechanisms. This review provides an overview of multi-targeting combination strategies with a primary focus on Candidozyma auris infections. [ABSTRACT FROM AUTHOR]

Fungemia remains a major threat in intensive care units (ICUs), with high mortality rates despite advances in diagnostics and treatment. Colonisation by yeasts is an independent risk factor for fungemia; however, its predictive utility requires further research. In this 8-year study, we analysed 38,017 samples from 3206 patients and 171 fungemia episodes as part of a weekly fungal surveillance programme. We evaluated species-specific colonisation patterns, the predictive value of the Colonisation Index (CI) and Corrected Colonisation Index (CCI), and candidemia risks associated with different yeast species and anatomical site colonisation. Our results showed that C. auris, N. glabratus, and C. parapsilosis colonisation increased with longer hospital stays (0.8% to 11.55%, 8.13% to 16.8%, and 1.93% to 5.14%, respectively). The CI and CCI had low discriminatory power (AUROC 67% and 66%). Colonisation by any yeast genera demonstrated high sensitivity (98.32%) and negative predictive value (NPV) (95.90%) but low specificity and positive predictive value (PPV) (23.90% and 6.64%). Tracheal and urine cultures had the highest PPV (15.64% and 12.91%), while inguinal cultures had the highest NPV (98.60%). C. auris (12.32%) and C. parapsilosis (5.5%) were associated with a higher fungemia risk (log-rank < 0.001). These findings support the use of weekly surveillance to better stratify the fungemia risk and optimise antifungal use in ICUs. [ABSTRACT FROM AUTHOR]

Convergent extension of epithelial tissue is a key motif of animal morphogenesis. On a coarse scale, cell motion resembles laminar fluid flow; yet in contrast to a fluid, epithelial cells adhere to each other and maintain the tissue layer under actively generated internal tension. To resolve this apparent paradox, we formulate a model in which tissue flow in the tension-dominated regime occurs through adiabatic remodeling of force balance in the network of adherens junctions. We propose that the slow dynamics within the manifold of force-balanced configurations is driven by positive feedback on myosin-generated cytoskeletal tension. Shifting force balance within a tension network causes active cell rearrangements (T1 transitions) resulting in net tissue deformation oriented by initial tension anisotropy. Strikingly, we find that the total extent of tissue deformation depends on the initial cellular packing order. T1s degrade this order so that tissue flow is self-limiting. We explain these findings by showing that coordination of T1s depends on coherence in local tension configurations, quantified by a geometric order parameter in tension space. Our model reproduces the salient tissue- and cellscale features of germ band elongation during Drosophila gastrulation, in particular the slowdown of tissue flow after approximately twofold elongation concomitant with a loss of order in tension configurations. This suggests local cell geometry contains morphogenetic information and yields experimentally testable predictions. Defining biologically controlled active tension dynamics on the manifold of force-balanced states may provide a general approach to the description of morphogenetic flow. [ABSTRACT FROM AUTHOR]

Obviously, the discussion of different factors that could have contributed to the origin of life and evolution is clear speculation, since there is no way of checking the validity of most of the related hypotheses in practice, as the corresponding events not only already happened, but took place in a very distant past. However, there are a few undisputable facts that are present at the moment, such as the existence of a wide variety of living forms and the abundant presence of intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains and intrinsically disordered regions (IDRs) in all living forms. Since it seems that the currently existing living forms originated from a common ancestor, their variety is a result of evolution. Therefore, one could ask a logical question of what role(s) the structureless and highly dynamic but vastly abundant and multifunctional IDPs/IDRs might have in evolution. This study represents an attempt to consider various ideas pertaining to the potential roles of protein intrinsic disorder in the origin of life and evolution. [ABSTRACT FROM AUTHOR]

Introduction: Drones, or Unmanned Aerial Vehicles (UAVs), have emerged as valuable tools for wildlife monitoring, offering potentially non-intrusive observations in challenging terrains like marine ecosystems. Despite their potential, widespread use is impeded by regulatory constraints, especially in protected areas. Methods: This study aims to assess the impact of varying flight altitudes and flight approaches of two commercial drones on the behaviour of harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) and compare to existing findings for marine mammals. We conducted a comparative analysis of the response to flight altitude from 70 m gradually descending to 10 m and two different flight approaches between the DJI Phantom 4Pro and the Autel EVO II RTK drones in the Danish part of the Wadden Sea. Results: We found varying responses, where species-specific sensitivity and environmental conditions appeared to influence the behavioural reactions of the seals. Our results reveal that seal reactions to drones are complex and depend on several factors, such as flight altitude, drone model, received noise levels, approach, weather conditions, the animals' annual cycle, and geographic location. Discussion: The outcomes hold significance for refining regulatory policies governing drone flights in protected marine environments, balancing conservation efforts with technological advancements in wildlife monitoring and ensuring undisturbed observations of seals. [ABSTRACT FROM AUTHOR]

Designing and optimizing the structure of urban transportation networks is a challenging task. In this study, we propose a method inspired by optimal transport theory and the principle of economy of scale that uses little information in input to generate structures that are similar to those of public transportation networks. Contrarily to standard approaches, it does not assume any initial backbone network infrastructure but rather extracts this directly from a continuous space using only a few origin and destination points, generating networks from scratch. Analyzing a set of urban train, tram and subway networks, we find a noteworthy degree of similarity in several of the studied cases between simulated and real infrastructures. By tuning one parameter, our method can simulate a range of different subway, tram and train networks that can be further used to suggest possible improvements in terms of relevant transportation properties. Outputs of our algorithm provide naturally a principled quantitative measure of similarity between two networks that can be used to automatize the selection of similar simulated networks. Planning effective urban network infrastructure often involves optimization principles that use a backbone network as a starting point. The authors propose an approach based on optimal transport theory to simulate real urban rail networks structure without need of initial backbone knowledge. [ABSTRACT FROM AUTHOR]

The problem of solving the equivalent resistance between two points for resistor networks has important significance in physics. This paper mainly changes and rewrites the formula for calculating the resistance between two points of an unconventional m × n cylindrical resistor network with a zero resistor axis and any two left and right boundaries. To enhance the efficiency of calculating the equivalent resistance between two points, Chebyshev polynomials and hyperbolic cosine functions are employed to represent the new formula. And in the inference process, the famous discrete cosine transform of the third kind (DCT-III) is used to process the matrix. We give the equivalent resistance formula for several special cases, and display them by a three-dimensional graph. Subsequently, the calculation efficiency of the original formula and the rewritten formula are compared. At the end of the paper, a heuristic algorithm suitable for robot path planning on cylindrical environment is proposed. [ABSTRACT FROM AUTHOR]

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Candida auris has recently caused major outbreaks in healthcare facilities. Rapid and accurate antifungal susceptibility testing (AST) of C. auris is crucial for proper management of invasive infections. The Commercial Sensititre Yeast One and Vitek 2 methods underestimate or overestimate the resistance of C. auris to fluconazole and amphotericin B (AMB). This study evaluated the AST results of C. auris against fluconazole and AMB by gradient-MIC-strip (Etest) and broth microdilution-based MICRONAUT-AM-EUCAST (MCN-AM) assays. Clinical C. auris isolates (n = 121) identified by phenotypic and molecular methods were tested. Essential agreement (EA, ±1 two-fold dilution) between the two methods and categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints were determined. Fluconazole resistance-associated mutations were detected by PCR-sequencing of ERG11. All isolates identified as C. auris belonged to South Asian clade I and contained the ERG11 Y132F or K143R mutation. The Etest–MCN-AM EA was poor (33%) for fluconazole and moderate (76%) for AMB. The CA for fluconazole was higher (94.2%, 7 discrepancies) than for AMB (91.7%, 10 discrepancies). Discrepancies were reduced when an MCN-AM upper-limit value of 4 µg/mL for fluconazole-susceptible C. auris and an Etest upper-limit value of 8 µg/mL for the wild type for AMB were used. Our data show that resistance to fluconazole was underestimated by MCN-AM, while resistance to AMB was overestimated by Etest when using the CDC's tentative resistance breakpoints of ≥32 µg/mL for fluconazole and ≥2 µg/mL for AMB. Method-specific resistance breakpoints should be devised for accurate AST of clinical C. auris isolates for proper patient management. [ABSTRACT FROM AUTHOR]

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin's functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin's function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation. [ABSTRACT FROM AUTHOR]

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017–2019 to 15.5% in 2020–2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively. [ABSTRACT FROM AUTHOR]

Highlights: The types, working principles, advantages and limitations of pattern recognition methods based on chemiresistive gas sensor array are reviewed and discussed comprehensively. Outstanding and novel advancements in the application of machine learning methods for gas recognition in different important areas are compared, summarized and evaluated. The current challenges and future prospects of machine learning methods in artificial olfactory systems are discussed and justified. As information acquisition terminals for artificial olfaction, chemiresistive gas sensors are often troubled by their cross-sensitivity, and reducing their cross-response to ambient gases has always been a difficult and important point in the gas sensing area. Pattern recognition based on sensor array is the most conspicuous way to overcome the cross-sensitivity of gas sensors. It is crucial to choose an appropriate pattern recognition method for enhancing data analysis, reducing errors and improving system reliability, obtaining better classification or gas concentration prediction results. In this review, we analyze the sensing mechanism of cross-sensitivity for chemiresistive gas sensors. We further examine the types, working principles, characteristics, and applicable gas detection range of pattern recognition algorithms utilized in gas-sensing arrays. Additionally, we report, summarize, and evaluate the outstanding and novel advancements in pattern recognition methods for gas identification. At the same time, this work showcases the recent advancements in utilizing these methods for gas identification, particularly within three crucial domains: ensuring food safety, monitoring the environment, and aiding in medical diagnosis. In conclusion, this study anticipates future research prospects by considering the existing landscape and challenges. It is hoped that this work will make a positive contribution towards mitigating cross-sensitivity in gas-sensitive devices and offer valuable insights for algorithm selection in gas recognition applications. [ABSTRACT FROM AUTHOR]

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection, while computational biology and machine learning have advanced methodologies of predicting virus–host gene and protein interactions. Particular focus is given to the interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in the sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to the resolution of questions regarding the pathogenesis of PASC. [ABSTRACT FROM AUTHOR]

Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are antiviral medications primarily used to treat infections caused by cytomegalovirus (CMV), particularly in immunocompromised individuals such as solid organ transplant (SOT) recipients. Therapy with GCV is associated with significant side effects, including bone marrow suppression. Therefore, therapeutic drug monitoring (TDM) is mandatory for an appropriate balance between subtherapeutic and toxic drug levels. This study aimed to develop and validate three novel methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for GCV determination in serum (reference methodology), dried serum spots (DSS), and VAMS-Mitra™ devices. The methods were optimized and validated in the 0.1–25 mg/L calibration range. The obtained results fulfilled the EMA acceptance criteria for bioanalytical method validation. Assessment of DSS and VAMS techniques extended GCV stability to serum for up to a minimum of 49 days (at room temperature, with desiccant). Developed methods were effectively evaluated using 80 clinical serum samples from pediatric renal transplant recipients. Obtained samples were used for DSS, and dried serum VAMS samples were manually generated in the laboratory. The results of GCV determination using serum-, DSS- and VAMS-LC-MS/MS methods were compared using regression analysis and bias evaluation. The conducted statistical analysis confirmed the interchangeability between developed assays. The DSS and VAMS samples are more accessible and stable during storage, transport and shipment than classic serum samples. [ABSTRACT FROM AUTHOR]

Alternatives to the conventional thermal processing (TT) of food are an area of research that has grown tremendously in recent decades. The impact of these alternative techniques on the sensory profile of fruit juices has been discussed in the literature but only in a fragmented manner. This review takes a macroscopic approach to discuss the influence of emerging thermal and non-thermal techniques currently used by industries on a commercial scale, like high-pressure processing (HPP), ohmic heating (OH), and pulse electric field processing (PEF), on certain sensory characteristics of fruit juices and beverages. A sensory impression of a product is a result of a complex mixture of several compounds. The sensory profile varies with the type of processing technique due to differences in intensities and the inactivation mechanism for enzymes. Heat plays a role in the generation of flavor and odor-active compounds; hence, a different sensory profile is expected with alternative techniques that operate at ambient temperatures (HPP and PEF) or have short treatment time due to rapid heating (OH). HPP, OH, and PEF positively influence the retention of compounds that contribute to a fresh-like sensory experience. However, enzyme inactivation is often challenging with alternative techniques resulting in higher residual activity, affecting sensory quality during storage. Nevertheless, there is evidence in the literature of products with stable sensory properties during storage after processing with alternative techniques. Additionally, some residual enzyme activity may play a role in flavor enhancement during storage, i.e., the release of aglycones from glycoconjugates by pectolytic enzymes. Multiple factors like fruits' cultivar, way of cultivation, external growth conditions, andmaturity stage at the time of harvest influence its sensory quality and, subsequently, the products derived from them. The review concludes with the impression that there is extensive literature on the effects of HPP on the sensory properties of fruit juices. However, the research is limited in discussing the influence of OH and PEF. Additionally, it is difficult to make a fair and systematic comparison among the different preservation technologies because of the lack of standardization and comprehensive sensory evaluation in the studies in the literature. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers. [ABSTRACT FROM AUTHOR]

Most essential cellular functions are performed by proteins assembled into larger complexes. Fluorescence Polarization Microscopy (FPM) is a powerful technique that goes beyond traditional imaging methods by allowing researchers to measure not only the localization of proteins within cells, but also their orientation or alignment within complexes or cellular structures. FPM can be easily integrated into standard widefield microscopes with the addition of a polarization modulator. However, the extensive image processing and analysis required to interpret the data have limited its widespread adoption. To overcome these challenges and enhance accessibility, we introduce OOPS (Object-Oriented Polarization Software), a MATLAB package for object-based analysis of FPM data. By combining flexible image segmentation and novel object-based analyses with a high-throughput FPM processing pipeline, OOPS empowers researchers to simultaneously study molecular order and orientation in individual biological structures; conduct population assessments based on morphological features, intensity statistics, and FPM measurements; and create publication-quality visualizations, all within a user-friendly graphical interface. Here, we demonstrate the power and versatility of our approach by applying OOPS to punctate and filamentous structures. [ABSTRACT FROM AUTHOR]

Introduction: Insufficient knowledge of intravenous fluid therapy is a significant challenge contributing to morbidity and mortality in hospitalized patients. Nurses play a critical role in evaluating patients' fluid and electrolyte balance as well as in restoring fluid levels. Various studies have indicated a deficiency in nurses' knowledge of intravenous therapy, yet this remains understudied in many settings, including Namibia. Objectives: To assess nurses' knowledge of intravenous fluid therapy and to describe the variables associated with knowledge of intravenous fluid therapy at a teaching hospital in Namibia. Methods: A cross-sectional online survey involving 164 nurses who were recruited using total population sampling. Data were collected between September and November 2021, using a self-administered 14-item validated tool (α = 0.8). Data analysis was conducted using SPSSv28.0 software. Results: The majority of nurses (84%) in this study exhibited an insufficient level of knowledge regarding intravenous therapy, with only a minority (16%) demonstrating a moderately adequate understanding of intravenous fluid therapy. A significant positive correlation was found between educational qualification and knowledge of intravenous therapy (r = 0.21; p =.01). Conclusion: The study's results indicate a worrying trajectory in nurses' knowledge of intravenous therapy. These findings underscore the need for hospitals to establish comprehensive training programs for nurses to guarantee the provision of secure and efficient intravenous therapy. Additional research is needed to investigate how educational qualifications impact patient outcomes related to intravenous therapy. [ABSTRACT FROM AUTHOR]

Despite the potential of neutralizing antibodies in the management of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), clinical research on its efficacy in Chinese patients remains limited. This study is aimed at investigating the therapeutic effect of combination of antiviral therapy with neutralizing monoclonal antibodies for recurrent persistent SARS‐CoV‐2 pneumonia in patients with lymphoma complicated by B cell depletion. A prospective study was conducted on Chinese patients who were treated with antiviral nirmatrelvir/ritonavir therapy and the neutralizing antibody tixagevimab–cilgavimab (tix‐cil). The primary outcome was the rate of recurrent SARS‐CoV‐2 infection. Five patients with lymphoma experienced recurrent SARS‐CoV‐2 pneumonia and received tix‐cil treatment. All patients had a history of CD20 monoclonal antibody use within the year preceding SARS‐CoV‐2 infection, and two patients also had a history of Bruton's tyrosine kinase (BTK) inhibitor use. These patients had notably low lymphocyte counts and exhibited near depletion of B cells. All five patients tested negative for serum SARS‐CoV‐2 IgG and IgM antibodies. None of the patients developed reinfection with SARS‐CoV‐2 pneumonia after antiviral and tix‐cil treatment during the 6‐month follow‐up period. In conclusion, the administration of antiviral and SARS‐CoV‐2‐neutralizing antibodies showed encouraging therapeutic efficacy against SARS‐CoV‐2 pneumonia in patients with lymphoma complicated by B cell depletion, along with the potential preventive effect of neutralizing antibodies for up to 6 months. [ABSTRACT FROM AUTHOR]

Chardonnay is one of the most popular white grape wine varieties in the world, but this wine lacks typical aroma, considered a sensory defect. Our research group identified a Chardonnay bud sport with typical muscat characteristics. The goal of this work was to discover the key candidate genes related to muscat characteristics in this Chardonnay bud sport to reveal the mechanism of muscat formation and guide molecular design breeding. To this end, HS−SPME−GC−MS and RNA−Seq were used to analyze volatile organic compounds and the differentially expressed genes in Chardonnay and its aromatic bud sport. Forty-nine volatiles were identified as potential biomarkers, which included mainly aldehydes and terpenes. Geraniol, linalool, and phenylacetaldehyde were identified as the main aroma components of the mutant. The GO, KEGG, GSEA, and correlation analysis revealed HMGR, TPS1, TPS2, TPS5, novel.939, and CYP450 as key genes for terpene synthesis. MAO1 and MAO2 were significantly downregulated, but there was an increased content of phenylacetaldehyde. These key candidate genes provide a reference for the development of functional markers for muscat varieties and also provide insight into the formation mechanism of muscat aroma. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometritis is defined as a localized inflammatory condition of the endometrium that results in significant financial losses. This investigation used forty buffalo cows with clinical endometritis that were infected and forty seemingly healthy buffalo cows who served as the control group made up the two groups of buffalo cows. The expression levels and the serum characteristics of immune and antioxidant biomarkers linked to clinical endometritis risk varied between the investigated two categories of buffalo cows. The alteration in the profile of explored markers suggests a potential source for uterine health indicators in buffaloes. Determining the gene expression and serum profile of the indicators linked to clinical endometritis susceptibility in Egyptian buffalo cows was the aim of this investigation. The buffalo cows that were enrolled were divided into two groups: forty infected buffalo cows with clinical endometritis and forty seemingly healthy buffalo cows that served as the control group. For the purposes of gene expression and biochemical analysis, ten milliliters of blood was obtained via jugular venipuncture from each buffalo cow. TLR4, IL-8, IL-17, NFKB, SLCA11A1, NCF4, Keap1, HMOX1, OXSR1, ST1P1, and SERP1 were manifestly expressed at much higher levels in the buffaloes with endometritis. On the other hand, the genes that encode SOD, CAT, NDUFS6, Nrf2, and PRDX2 were down-regulated. There was a significant (p < 0.05) elevation of the serum levels of non-esterified fatty acids (NEFAs), beta hydroxy butyric acid (BHBA), triglycerides (TGs), globulin, creatinine, and cortisol, along with a reduction in the serum levels of glucose, cholesterol, total protein albumin, urea, estrogen (E2), progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroxine (T4), prostaglandin F2 α (PGF2α), calcium, iron, and selenium, in the endometritis group in comparison with the control. However, no significant change was observed in the values of phosphorus, magnesium, copper, or zinc in either group. Within the selective breeding of naturally resistant animals, the variation in the genes under study and the changes in the serum profiles of the indicators under investigation may serve as a reference guide for reducing endometritis in Egyptian buffalo cows. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. DLX5 and DLX6 (DLX5/6) encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA DLX6-AS1, which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of Dlx5/6 in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in Dlx5, Dlx6 and Dlx6-AS1 expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental Dlx5 overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in Dlx5/6 expression in GABAergic neurons, which, in turn, has direct consequences on PV expression and on behavioural profiles. Variants in the DLX5/6 regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment. [ABSTRACT FROM AUTHOR]

The remarkable signal-detection capabilities of the auditory and vestibular systems have been studied for decades. Much of the conceptual framework that arose from this research has suggested that these sensory systems rest on the verge of instability, near a Hopf bifurcation, in order to explain the detection specifications. However, this paradigm contains several unresolved issues. Critical systems are not robust to stochastic fluctuations or imprecise tuning of the system parameters. Further, a system poised at criticality exhibits a phenomenon known in dynamical systems theory as critical slowing down, where the response time diverges as the system approaches the critical point. An alternative description of these sensory systems is based on the notion of chaotic dynamics, where the instabilities inherent to the dynamics produce high temporal acuity and sensitivity to weak signals, even in the presence of noise. This alternative description resolves the issues that arise in the criticality picture. We review the conceptual framework and experimental evidence that supports the use of chaos for signal detection by these systems, and propose future validation experiments. [ABSTRACT FROM AUTHOR]

Candida auris (C. auris) is a yeast that has caused several outbreaks in the last decade. Cell wall chitin plays a primary role in the antifungal resistance of C. auris. Herein, we investigated the potential of chitinase immobilized with UiO-66 to act as a potent antifungal agent against C. auris. Chitinase was produced from Talaromyces varians SSW3 in a yield of 8.97 U/g dry substrate (ds). The yield was statistically enhanced to 120.41 U/g ds by using Plackett–Burman and Box–Behnken design. We synthesized a UiO-66 framework that was characterized by SEM, TEM, XRD, FTIR, a particle size analyzer, and a zeta sizer. The produced framework had a size of 70.42 ± 8.43 nm with a uniform cubic shape and smooth surface. The produced chitinase was immobilized on UiO-66 with an immobilization yield of 65% achieved after a 6 h loading period. The immobilization of UiO-66 increased the enzyme activity and stability, as indicated by the obtained Kd and T1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the Vmax and a decrease in the Km of 2- and 38-fold, respectively. Interestingly, the antifungal activity of the produced chitinase was boosted against C. auris by loading the enzyme on UiO-66, with an MIC50 of 0.89 ± 0.056 U/mL, compared to 5.582 ± 0.57 U/mL for the free enzyme. This study offers a novel promising alternative approach to combat the new emerging pathogen C. auris. [ABSTRACT FROM AUTHOR]

A geometrically symmetric gear with asymmetric surface wettability exhibits one-way spin on a vibrating water bed. On the side face of the gear, a parafilm was coated to create asymmetry in the surface energy. The gear shows fluctuations in both directions within a shorter timescale; however, for a longer timescale, the gear exhibits a one-way spin. This unique motion is generated by a stochastic process with a biased driving force produced by the interaction between the vibrating water surface and the side face of the gear. This new model resembles an active Brownian ratchet. Until now, most ratchet motors, which obtain regular motion from nonthermal fluctuations, utilize a geometrical ratchet structure. However, in this study, the surface energy forms a ratchet that rectifies the noisy motion. [ABSTRACT FROM AUTHOR]

Transport networks, such as vasculature or river networks, provide key functions in organisms and the environment. They usually contain loops whose significance for the stability and robustness of the network is well documented. However, the dynamics of their formation is usually not considered. Such structures often grow in response to the gradient of an external field. During evolution, extending branches compete for the available flux of the field, which leads to effective repulsion between them and screening of the shorter ones. Yet, in remarkably diverse processes, from unstable fluid flows to the canal system of jellyfish, loops suddenly form near the breakthrough when the longest branch reaches the boundary of the system. We provide a physical explanation for this universal behavior. Using a 1D model, we explain that the appearance of effective attractive forces results from the field drop inside the leading finger as it approaches the outlet. Furthermore, we numerically study the interactions between two fingers, including screening in the system and its disappearance near the breakthrough. Finally, we perform simulations of the temporal evolution of the fingers to show how revival and attraction to the longest finger leads to dynamic loop formation. We compare the simulations to the experiments and find that the dynamics of the shorter finger are well reproduced. Our results demonstrate that reconnection is a prevalent phenomenon in systems driven by diffusive fluxes, occurring both when the ratio of the mobility inside the growing structure to the mobility outside is low and near the breakthrough. [ABSTRACT FROM AUTHOR]