bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-acquired methicillin-resistant Staphylococcus aureus invasive infections: a case series from Central-South Chile
Authors: Aguayo-Reyes Alejandro , Morales-León Felipe , Quezada-Aguiluz Mario , Quezada Martha , Mella Sergio , Riedel Gisela , Herrera-Chávez Néstor , Espine Yohana , González-Rocha Gerardo , Opazo-Capurro Andrés
Published: May 2024

The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections at the end of the 20th century represents a significant shift in the epidemiology of staphylococcal infections and, consequently, their clinical management. There are diverse CA-MRSA clones that are widely spread worldwide, showing differences in their regional dissemination, which has been dynamically changing over time. Although the first CA-MRSA description occurred about 30 years ago, its epidemiology in certain regions, such as South America, has been poorly explored, resulting in a gap in the understanding of the epidemiology of CA-MRSA in under-represented countries/regions. This report describes the first four clinical cases of invasive infections caused by CA-MRSA in a tertiary hospital in the central-southern region of Chile. It also associates the clinical characteristics of the infections with the microbiological and molecular features of the isolates. The four S. aureus isolates belong to sequence type 8, which has been widely described as a cause of community-acquired infections. All of them presented a wide resistome and virulome. Additionally, in two of them, it was possible to reconstruct the COMER genetic element, present in the USA300-Latin American variant clone. Considering these findings, it is crucial to prepare for a potential increase in invasive CA-MRSA infections in Chile. This would involve enhancing current surveillance systems and maintaining a low threshold of suspicion for these infections among clinicians.
Development and emerging trends of drug resistance mutations in HIV: a bibliometric analysis based on CiteSpace
Authors: Chen Xuannan , Chen Xi , Lai Yu
Published: May 2024

Background

Antiretroviral therapy has led to AIDS being a chronic disease. Nevertheless, the presence of constantly emerging drug resistance mutations poses a challenge to clinical treatment. A systematic analysis to summarize the advancements and uncharted territory of drug resistance mutations is urgently needed and may provide new clues for solving this problem.

Methods

We gathered 3,694 publications on drug resistance mutations from the Web of Science Core Collection with CiteSpace software and performed an analysis to visualize the results and predict future new directions and emerging trends. Betweenness centrality, count, and burst value were taken as standards.

Results

The number of papers on HIV medication resistance mutations during the last 10 years shows a wave-like trend. In terms of nation, organization, and author, the United States (1449), University of London (193), and Mark A. Wainberg (66) are the most significant contributors. The most frequently cited article is “Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update.” Hot topics in this field include “next-generation sequencing,” “tenofovir alafenamide,” “children,” “regimens,” “accumulation,” “dolutegravir,” “rilpivirine,” “sex,” “pretreatment drug resistance,” and “open label.” Research on drug resistance in teenagers, novel mutation detection techniques, and drug development is ongoing, and numerous publications have indicated the presence of mutations related to current medications. Therefore, testing must be performed regularly for patients who have used medications for a long period. Additionally, by choosing medications with a longer half-life, patients can take fewer doses of their prescription, increasing patient compliance.

Conclusion

This study involved a bibliometric visualization analysis of the literature on drug resistance mutations, providing insight into the field’s evolution and emerging patterns and offering academics a resource to better understand HIV drug resistance mutations and contribute to the field’s advancement.
Bioprospecting of Aspergillus sp. as a promising repository for anti-cancer agents: a comprehensive bibliometric investigation
Authors: Jangid Himanshu , Garg Sonu , Kashyap Piyush , Karnwal Arun , Shidiki Amrullah , Kumar Gaurav
Published: May 2024

Cancer remains a significant global health challenge, claiming nearly 10 million lives in 2020 according to the World Health Organization. In the quest for novel treatments, fungi, especially Aspergillus species, have emerged as a valuable source of bioactive compounds with promising anticancer properties. This study conducts a comprehensive bibliometric analysis to map the research landscape of Aspergillus in oncology, examining publications from 1982 to the present. We observed a marked increase in research activity starting in 2000, with a notable peak from 2005 onwards. The analysis identifies key contributors, including Mohamed GG, who has authored 15 papers with 322 citations, and El-Sayed Asa, with 14 papers and 264 citations. Leading countries in this research field include India, Egypt, and China, with King Saud University and Cairo University as the leading institutions. Prominent research themes identified are “endophyte,” “green synthesis,” “antimicrobial,” “anti-cancer,” and “biological activities,” indicating a shift towards environmentally sustainable drug development. Our findings highlight the considerable potential of Aspergillus for developing new anticancer therapies and underscore the necessity for further research to harness these natural compounds for clinical use.
The Yin and Yang of pathogens and probiotics: interplay between Salmonella enterica sv. Typhimurium and Bifidobacterium infantis during co-infection
Authors: Shaw Claire , Weimer Bart C. , Gann Reed , Desai Prerak T. , Shah Jigna D.
Published: May 2024

Probiotic bacteria have been proposed as an alternative to antibiotics for the control of antimicrobial resistant enteric pathogens. The mechanistic details of this approach remain unclear, in part because pathogen reduction appears to be both strain and ecology dependent. Here we tested the ability of five probiotic strains, including some from common probiotic genera Lactobacillus and Bifidobacterium, to reduce binding of Salmonella enterica sv. Typhimurium to epithelial cells in vitro. Bifidobacterium longum subsp. infantis emerged as a promising strain; however, S. Typhimurium infection outcome in epithelial cells was dependent on inoculation order, with B. infantis unable to rescue host cells from preceding or concurrent infection. We further investigated the complex mechanisms underlying this interaction between B. infantis, S. Typhimurium, and epithelial cells using a multi-omics approach that included gene expression and altered metabolism via metabolomics. Incubation with B. infantis repressed apoptotic pathways and induced anti-inflammatory cascades in epithelial cells. In contrast, co-incubation with B. infantis increased in S. Typhimurium the expression of virulence factors, induced anaerobic metabolism, and repressed components of arginine metabolism as well as altering the metabolic profile. Concurrent application of the probiotic and pathogen notably generated metabolic profiles more similar to that of the probiotic alone than to the pathogen, indicating a central role for metabolism in modulating probiotic-pathogen-host interactions. Together these data imply crosstalk via small molecules between the epithelial cells, pathogen and probiotic that consistently demonstrated unique molecular mechanisms specific probiotic/pathogen the individual associations.
Fighting Salmonella Infantis: bacteriophage-driven cleaning and disinfection strategies for broiler farms
Authors: Sevilla-Navarro Sandra , Torres-Boncompte Jan , Garcia-Llorens Josep , Bernabéu-Gimeno Mireia , Domingo-Calap Pilar , Catalá-Gregori Pablo
Published: May 2024

Introduction

Salmonella is a bacterium that can cause food-borne infections and is responsible for the most common gastrointestinal illnesses. The emergence of multi-drug resistant (MDR) strains worldwide is a major threat, representing a major challenge in public health. To reduce its incidence, the One Health approach is required, and the development of new biocontrol protocols will help prevent or eliminate the spread of Salmonella. Prevention measures, such as on-farm cleaning and disinfection protocols, are a crucial step in reducing infection to new flocks and eliminating bacteria that remain in the facilities. However, MDR Salmonella species, such as S. Infantis, are highly resistant to conventional cleaning and disinfection protocols, with an increased ability to persist in the broiler farm environment. The need for alternative biocontrol methods has led to the use of bacteriophages or phages, viruses that target bacteria, as promising tools. Thus, the aim of this study was to evaluate the efficacy of phages as a biocide against S. Infantis isolates in combination with cleaning and disinfection protocols in 10 commercial poultry farms.

Methods

All commercial farms selected in this study had persistent Salmonella, even after the routinely used cleaning and disinfection procedures. In addition, Salmonella isolated before treatment were phenotypically characterized by antimicrobial resistance patterns.

Results

The results showed that 100% of S. Infantis were resistant to at least one antibiotic, and > 70% were MDR. Phages were then isolated against the in-farm bacteria, purified, and multiplied for each poultry farm. The cleaning and disinfection protocols included the application of the lytic phages (vB_Si_CECAV_FGS009; vB_Si_CECAV_FGS017; vB_Si_CECAV_FGS029 and vB_Si_CECAV _FGS030) twice at 24-h intervals between cleaning and disinfection. Following the cleaning and disinfection procedures, Salmonella detection was reduced from 100% after cleaning to 36% after applying the phages and dropped to 0% after the final step of disinfection, thus eliminating Salmonella from the farm facilities.

Discussion

This study demonstrates that bacteriophage application after cleaning and before disinfection enhances the removal of MDR Salmonella Infantis in commercial broiler farms, suggesting their use as biocontrol agents to reduce Salmonella, a major public health concern.
Prohibitions in the meta-inflammatory response: a review
Authors: Todosenko Natalia , Yurova Kristina , Vulf Maria , Khaziakhmatova Olga , Litvinova Larisa
Published: May 2024

Prohibitins are the central regulatory element of cellular homeostasis, especially by modulating the response at different levels: Nucleus, mitochondria and membranes. Their localization and interaction with various proteins, homons, transcription and nuclear factors, and mtDNA indicate the globality and complexity of their pleiotropic properties, which remain to be investigated. A more detailed deciphering of cellular metabolism in relation to prohibitins under normal conditions and in various metabolic diseases will allow us to understand the precise role of prohibitins in the signaling cascades of PI3K/Akt, Raf/MAP/ERK, STAT3, p53, and others and to fathom their mutual influence. A valuable research perspective is to investigate the role of prohibitins in the molecular and cellular interactions between the two major players in the pathogenesis of obesity—adipocytes and macrophages - that form the basis of the meta-inflammatory response. Investigating the subtle intercellular communication and molecular cascades triggered in these cells will allow us to propose new therapeutic strategies to eliminate persistent inflammation, taking into account novel molecular genetic approaches to activate/inactivate prohibitins.
Involvement and regulation of the left anterior cingulate cortex in the ultrasonic communication deficits of autistic mice
Authors: Hou Yilin , Li Yuqian , Yang Dingding , Zhao Youyi , Feng Tingwei , Zheng Wei’an , Xian Panpan , Liu Xufeng , Wu Shengxi , Wang Yazhou
Published: May 2024

Introduction

Autism spectrum disorder (ASD) is a group of diseases often characterized by poor sociability and challenges in social communication. The anterior cingulate cortex (ACC) is a core brain region for social function. Whether it contributes to the defects of social communication in ASD and whether it could be physiologically modulated to improve social communication have been poorly investigated. This study is aimed at addressing these questions.

Methods

Fragile X mental retardation 1 (FMR1) mutant and valproic acid (VPA)-induced ASD mice were used. Male–female social interaction was adopted to elicit ultrasonic vocalization (USV). Immunohistochemistry was used to evaluate USV-activated neurons. Optogenetic and precise target transcranial magnetic stimulation (TMS) were utilized to modulate anterior cingulate cortex (ACC) neuronal activity.

Results

In wild-type (WT) mice, USV elicited rapid expression of c-Fos in the excitatory neurons of the left but not the right ACC. Optogenetic inhibition of the left ACC neurons in WT mice effectively suppressed social-induced USV. In FMR1−/−- and VPA-induced ASD mice, significantly fewer c-Fos/CaMKII-positive neurons were observed in the left ACC following USV compared to the control. Optogenetic activation of the left ACC neurons in FMR1−/− or VPA-pretreated mice significantly increased social activity elicited by USV. Furthermore, precisely stimulating neuronal activity in the left ACC, but not the right ACC, by repeated TMS effectively rescued the USV emission in these ASD mice.

Discussion

The excitatory neurons in the left ACC are responsive to socially elicited USV. Their silence mediates the deficiency of social communication in FMR1−/− and VPA-induced ASD mice. Precisely modulating the left ACC neuronal activity by repeated TMS can promote the social communication in FMR1−/− and VPA-pretreated mice.
RGS10 mitigates high glucose-induced microglial inflammation via the reactive oxidative stress pathway and enhances synuclein clearance in microglia
Authors: Chung Jaegwon , Jernigan Janna , Menees Kelly B. , Lee Jae-Kyung
Published: May 2024

Microglia play a critical role in maintaining brain homeostasis but become dysregulated in neurodegenerative diseases. Regulator of G-protein Signaling 10 (RGS10), one of the most abundant homeostasis proteins in microglia, decreases with aging and functions as a negative regulator of microglia activation. RGS10-deficient mice exhibit impaired glucose tolerance, and high-fat diet induces insulin resistance in these mice. In this study, we investigated whether RGS10 modulates microglia activation in response to hyperglycemic conditions, complementing our previous findings of its role in inflammatory stimuli. In RGS10 knockdown (KD) BV2 cells, TNF production increased significantly in response to high glucose, particularly under proinflammatory conditions. Additionally, glucose uptake and GLUT1 mRNA levels were significantly elevated in RGS10 KD BV2 cells. These cells produced higher ROS and displayed reduced sensitivity to the antioxidant N-Acetyl Cysteine (NAC) when exposed to high glucose. Notably, both BV2 cells and primary microglia that lack RGS10 exhibited impaired uptake of alpha-synuclein aggregates. These findings suggest that RGS10 acts as a negative regulator of microglia activation not only in response to inflammation but also under hyperglycemic conditions.
The deletion of AQP4 and TRPV4 affects astrocyte swelling/volume recovery in response to ischemia-mimicking pathologies
Authors: Hermanova Zuzana , Valihrach Lukas , Kriska Jan , Maheta Mansi , Tureckova Jana , Kubista Mikael , Anderova Miroslava
Published: May 2024

Introduction

Astrocytic Transient receptor potential vanilloid 4 (TRPV4) channels, together with Aquaporin 4 (AQP4), are suspected to be the key players in cellular volume regulation, and therefore may affect the development and severity of cerebral edema during ischemia. In this study, we examined astrocytic swelling/volume recovery in mice with TRPV4 and/or AQP4 deletion in response to in vitro ischemic conditions, to determine how the deletion of these channels can affect the development of cerebral edema.

Methods

We used three models of ischemia-related pathological conditions: hypoosmotic stress, hyperkalemia, and oxygenglucose deprivation (OGD), and observed their effect on astrocyte volume changes in acute brain slices of Aqp4–/–, Trpv4–/– and double knockouts. In addition, we employed single-cell RT-qPCR to assess the effect of TRPV4 and AQP4 deletion on the expression of other ion channels and transporters involved in the homeostatic functioning of astrocytes.

Results

Quantification of astrocyte volume changes during OGD revealed that the deletion of AQP4 reduces astrocyte swelling, while simultaneous deletion of both AQP4 and TRPV4 leads to a disruption of astrocyte volume recovery during the subsequent washout. Of note, astrocyte exposure to hypoosmotic stress or hyperkalemia revealed no differences in astrocyte swelling in the absence of AQP4, TRPV4, or both channels. Moreover, under ischemia-mimicking conditions, we identified two distinct subpopulations of astrocytes with low and high volumetric responses (LRA and HRA), and their analyses revealed that mainly HRA are affected by the deletion of AQP4, TRPV4, or both channels. Furthermore, gene expression analysis revealed reduced expression of the ion transporters KCC1 and ClC2 as well as the receptors GABAB and NMDA in Trpv4–/– mice. The deletion of AQP4 instead caused reduced expression of the serine/cysteine peptidase inhibitor Serpina3n.

Discussion

Thus, we showed that in AQP4 or TRPV4 knockouts, not only the specific function of these channels is affected, but also the expression of other proteins, which may modulate the ischemic cascade and thus influence the final impact of ischemia.
Effects of prenatal alcohol exposure on the olfactory system development
Authors: Imamura Fumiaki
Published: May 2024

Fetal Alcohol Spectrum Disorders (FASD), resulting from maternal alcohol consumption during pregnancy, are a prominent non-genetic cause of physical disabilities and brain damage in children. Alongside common symptoms like distinct facial features and neurocognitive deficits, sensory anomalies, including olfactory dysfunction, are frequently noted in FASD-afflicted children. However, the precise mechanisms underpinning the olfactory abnormalities induced by prenatal alcohol exposure (PAE) remain elusive. Utilizing rodents as a model organism with varying timing, duration, dosage, and administration routes of alcohol exposure, prior studies have documented impairments in olfactory system development caused by PAE. Many reported a reduction in the olfactory bulb (OB) volume accompanied by reduced OB neuron counts, suggesting the OB is a brain region vulnerable to PAE. In contrast, no significant olfactory system defects were observed in some studies, though subtle alterations might exist. These findings suggest that the timing, duration, and extent of fetal alcohol exposure can yield diverse effects on olfactory system development. To enhance comprehension of PAE-induced olfactory dysfunctions, this review summarizes key findings from previous research on the olfactory systems of offspring prenatally exposed to alcohol.
Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry
Authors: Hsieh Meng-Tsang , Hsieh Cheng-Yang , Yang Tzu-Hsien , Sung Sheng-Feng , Hsieh Yi-Chen , Lee Chung-Wei , Lin Chun-Jen , Chen Yu-Wei , Lin Kuan-Hung , Sung Pi-Shan , Tang Chih-Wei , Chu Hai-Jui , Tsai Kun-Chang , Chou Chao-Liang , Lin Ching-Huang , Wei Cheng-Yu , Chen Te-Yuan , Yan Shang-Yih , Chen Po-Lin , Hsiao Chen-Yu , Chan Lung , Huang Yen-Chu , Liu Hon-Man , Tang Sung-Chun , Lee I-Hui , Lien Li-Ming , Chiou Hung-Yi , Lee Jiunn-Tay , Jeng Jiann-Shing
Published: May 2024

Background

Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data.

Methods

The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities.

Results

The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6–5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH.

Conclusion

In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.
EPAT: a user-friendly MATLAB toolbox for EEG/ERP data processing and analysis
Authors: Shi Jianwei , Gong Xun , Song Ziang , Xie Wenkai , Yang Yanfeng , Sun Xiangjie , Wei Penghu , Wang Changming , Zhao Guoguang
Published: May 2024

Background

At the intersection of neural monitoring and decoding, event-related potential (ERP) based on electroencephalography (EEG) has opened a window into intrinsic brain function. The stability of ERP makes it frequently employed in the field of neuroscience. However, project-specific custom code, tracking of user-defined parameters, and the large diversity of commercial tools have limited clinical application.

Methods

We introduce an open-source, user-friendly, and reproducible MATLAB toolbox named EPAT that includes a variety of algorithms for EEG data preprocessing. It provides EEGLAB-based template pipelines for advanced multi-processing of EEG, magnetoencephalography, and polysomnogram data. Participants evaluated EEGLAB and EPAT across 14 indicators, with satisfaction ratings analyzed using the Wilcoxon signed-rank test or paired t-test based on distribution normality.

Results

EPAT eases EEG signal browsing and preprocessing, EEG power spectrum analysis, independent component analysis, time-frequency analysis, ERP waveform drawing, and topological analysis of scalp voltage. A user-friendly graphical user interface allows clinicians and researchers with no programming background to use EPAT.

Conclusion

This article describes the architecture, functionalities, and workflow of the toolbox. The release of EPAT will help advance EEG methodology and its application to clinical translational studies.
Associations of cerebrospinal fluid profiles with severity and mortality risk of amyotrophic lateral sclerosis
Authors: Fu Jiajia , Lai Xiaohui , Wei Qianqian , Chen Xueping , Shang Huifang
Published: May 2024

Background

The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies.

Methods

This study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined.

Results

In ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (β = −0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010–1.470), p = 0.039].

Conclusion

In the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.
Horizontal-cell like Dm9 neurons in Drosophila modulate photoreceptor output to supply multiple functions in early visual processing
Authors: Schnaitmann Christopher , Pagni Manuel , Meyer Patrik B. , Steinhoff Lisa , Oberhauser Vitus , Reiff Dierk F.
Published: May 2024

Dm9 neurons in Drosophila have been proposed as functional homologs of horizontal cells in the outer retina of vertebrates. Here we combine genetic dissection of neuronal circuit function, two-photon calcium imaging in Dm9 and inner photoreceptors, and immunohistochemical analysis to reveal novel insights into the functional role of Dm9 in early visual processing. Our experiments show that Dm9 receive input from all four types of inner photoreceptor R7p, R7y, R8p, and R8y. Histamine released from all types R7/R8 directly inhibits Dm9 via the histamine receptor Ort, and outweighs simultaneous histamine-independent excitation of Dm9 by UV-sensitive R7. Dm9 in turn provides inhibitory feedback to all R7/R8, which is sufficient for color-opponent processing in R7 but not R8. Color opponent processing in R8 requires additional synaptic inhibition by R7 of the same ommatidium via axo-axonal synapses and the second Drosophila histamine receptor HisCl1. Notably, optogenetic inhibition of Dm9 prohibits color opponent processing in all types of R7/R8 and decreases intracellular calcium in photoreceptor terminals. The latter likely results from reduced release of excitatory glutamate from Dm9 and shifts overall photoreceptor sensitivity toward higher light intensities. In summary, our results underscore a key role of Dm9 in color opponent processing in Drosophila and suggest a second role of Dm9 in regulating light adaptation in inner photoreceptors. These novel findings on Dm9 are indeed reminiscent of the versatile functions of horizontal cells in the vertebrate retina.
Exploring AKAPs in visual signaling
Authors: Tomczak Julia , Mackiewicz Joanna , Lisek Malwina , Kaluza Aleksandra , Boczek Tomasz
Published: May 2024

The complex nature of the retina demands well-organized signaling to uphold signal accuracy and avoid interference, a critical aspect in handling a variety of visual stimuli. A-kinase anchoring proteins (AKAPs), known for binding protein kinase A (PKA), contribute to the specificity and efficiency of retinal signaling. They play multifaceted roles in various retinal cell types, influencing photoreceptor sensitivity, neurotransmitter release in bipolar cells, and the integration of visual information in ganglion cells. AKAPs like AKAP79/150 and AKAP95 exhibit distinct subcellular localizations, impacting synaptic transmission and receptor sensitivity in photoreceptors and bipolar cells. Furthermore, AKAPs are involved in neuroprotective mechanisms and axonal degeneration, particularly in retinal ganglion cells. In particular, AKAP6 coordinates stress-specific signaling and promotes neuroprotection following optic nerve injury. As our review underscores the therapeutic potential of targeting AKAP signaling complexes for retinal neuroprotection and enhancement, it acknowledges challenges in developing selective drugs that target complex protein–protein interactions. Overall, this exploration of AKAPs provides valuable insights into the intricacies of retinal signaling, offering a foundation for understanding and potentially addressing retinal disorders.
Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older
Authors: Ghali Fady , Holt Sarah K. , Koehne Elizabeth L. , Chen Jonathan J. , Weg Emily S. , Liao Jay J. , Zeng Jing , Grivas Petros , Hawley Jessica E. , Hsieh Andrew C. , Montgomery Robert Bruce , Wright Jonathan L.
Published: May 2024

Introduction

Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use.

Methods

The linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS).

Results

2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 – 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 – 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 – 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 – 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 – 1.54), higher socioeconomic status (OR 1.31, CI 1.06 – 1.64), and later year of diagnosis (OR 1.09, CI 1.06 – 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone.

Conclusion

Over a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.
Use of the Archimedes navigation system to diagnose peripheral pulmonary lesions: preliminary Italian results
Authors: Lanfranchi Filippo , Mancino Laura , Foltran Gabriele , Nicole’ Lorenzo , Michieletto Lucio
Published: May 2024

Diagnosis of peripheral pulmonary lesions (PPL) is one of the most challenging fields in early lung cancer diagnosis. Despite novel techniques and new approaches to the periphery of the lung, almost 25% of PPL remains undiagnosed. Virtual bronchoscopy navigation (VBN) potentially allows to sample PPL previously not reachable with conventional bronchoscopy. In this preliminary report, we described nine cases of PPL (in which conventional bronchoscopy did not reach the lesion) sampled with VBN, from which we obtained a diagnosis in seven out of nine cases (77.8%), consistent with other reported results in literature. More large-scale data are needed to whether VBN can increase diagnostic yield (DY) of PPL.
Pharmacogenetic landscape of pain management variants among Mediterranean populations
Authors: Jmel Haifa , Boukhalfa Wided , Gouiza Ismail , Seghaier Roua Ouled , Dallali Hamza , Kefi Rym
Published: May 2024

Background:

Chronic pain is a major socioeconomic burden in the Mediterranean region. However, we noticed an under-representation of these populations in the pharmacogenetics of pain management studies. In this context, we aimed 1) to decipher the pharmacogenetic variant landscape among Mediterranean populations compared to worldwide populations in order to identify therapeutic biomarkers for personalized pain management and 2) to better understand the biological process of pain management through in silico investigation of pharmacogenes pathways.

Materials and Methods:

We collected genes and variants implicated in pain response using the Prisma guidelines from literature and PharmGK database. Next, we extracted these genes from genotyping data of 829 individuals. Then, we determined the variant distribution among the studied populations using multivariate (MDS) and admixture analysis with R and STRUCTURE software. We conducted a Chi2 test to compare the interethnic frequencies of the identified variants. We used SNPinfo web server, miRdSNP database to identify miRNA-binding sites. In addition, we investigated the functions of the identified genes and variants using pathway enrichment analysis and annotation tools. Finally, we performed docking analysis to assess the impact of variations on drug interactions.

Results:

We identified 63 variants implicated in pain management. MDS analysis revealed that Mediterranean populations are genetically similar to Mexican populations and divergent from other populations. STRUCTURE analysis showed that Mediterranean populations are mainly composed of European ancestry. We highlighted differences in the minor allele frequencies of three variants (rs633, rs4680, and rs165728) located in the COMT gene. Moreover, variant annotation revealed ten variants with potential miRNA-binding sites. Finally, protein structure and docking analysis revealed that two missense variants (rs4680 and rs6267) induced a decrease in COMT protein activity and affinity for dopamine.

Conclusion:

Our findings revealed that Mediterranean populations diverge from other ethnic groups. Furthermore, we emphasize the importance of pain-related pathways and miRNAs to better implement these markers as predictors of analgesic responses in the Mediterranean region.
Time trends and regional variations in prices of anticancer medicines in China
Authors: Zhang Jinwei , Hu Shuchen , Liu Xingyu , Liu Xiaoyong , Zhang Jieqiong , Yang Caijun , Fang Yu
Published: May 2024

Introduction

High prices, as a main factor, contributed to the lack of adequate access to essential anticancer medicines, especially for patients in developing countries. The Chinese Government has introduced a series of policies to control the prices of medicines during the last decade, but the effect on anticancer medicine is not yet clear.

Methods

To evaluate the time trends and regional variation in the price of essential anticancer medicines in China, we used the procurement data of anticancer medicines from 2015 to 2022. We selected 29 anticancer medicines from the 2018 Chinese National Essential Medicines List. To measure the cost of a medicine, we used defined daily dose cost -the cost per defined daily doses. At national level, we focused on the price changes over time and compared the price between medicine categories. At provincial level, we assessed price variation among provinces over time.

Results

For prices at the national level, all 6 targeted medicines exhibited a continuous decrease trend in price. Out of 23 non-targeted medicines, 4 (17·39%) experienced continuous increases in prices, and 9 (39·13%) showed price decreases from 2015 to 2019 and then an upward trend during 2019–2022; Of the remaining non-targeted medicines, 7 (30·43%) had continuous price decreases and 3 (13.04%) had price increases followed by decreases. For prices at the provincial level, provincial price variation became smaller for almost all targeted medicines, except rituximab; for 11 out of 23 non-targeted medicines, provincial price variations became larger. During the study period, the proportion of price-increased medicines in each province was geographically correlated, and no significant relationship between prices and GDP per capita was observed for both targeted and non-targeted anticancer medicines.

Conclusion

The prices and regional disparity of most targeted anticancer medicines were decreasing, while for nearly half of the non-targeted anticancer medicines, the prices were increasing and the regional disparity became wider, which may lead to compromised access to these essential anticancer medicines and raise inequity health outcome among regions.
Essential oils as promising treatments for treating Candida albicans infections: research progress, mechanisms, and clinical applications
Authors: Hou Gao-wei , Huang Ting
Published: May 2024

Candida albicans: (C. albicans) is a prevalent opportunistic pathogen that can cause severe mucosal and systemic fungal infections, leading to high morbidity and mortality rates. Traditional chemical drug treatments for C. albicans infection have limitations, including the potential for the development of drug resistance. Essential oils, which are secondary metabolites extracted from plants, have gained significant attention due to their antibacterial activity and intestinal regulatory effects. It makes them an ideal focus for eco-friendly antifungal research. This review was aimed to comprehensively evaluate the research progress, mechanisms, and clinical application prospects of essential oils in treating C. albicans infections through their antibacterial and intestinal regulatory effects. We delve into how essential oils exert antibacterial effects against C. albicans infections through these effects and provide a comprehensive analysis of related experimental studies and clinical trials. Additionally, we offer insights into the future application prospects of essential oils in antifungal therapy, aiming to provide new ideas and methods for the development of safer and more effective antifungal drugs. Through a systematic literature review and data analysis, we hope to provide insights supporting the application of essential oils in antifungal therapy while also contributing to the research and development of natural medicines. In the face of increasingly severe fungal infections, essential oils might emerge as a potent method in our arsenal, aiding in the effective protection of human and animal health.
Research on electrical capacitance tomography (ECT) detection of cerebral hemorrhage based on symmetrical cancellation method
Authors: Huang Jing , Chen Feng , Wang Ke , Chen Sheng
Published: May 2024

Currently, there is an urgent need for a fast and portable intracerebral hemorrhage (ICH) detection technology for pre-hospital emergency scenarios. Owing to the disproportionately elevated permittivity of blood compared to other brain tissues, Electrical Capacitance Tomography (ECT) offers a viable modality for mapping the spatial distribution of permittivity within the brain, thus facilitating the imaging-based identification of ICH. Currently, ECT is confined to time-differential imaging due to limited sensitivity, and this methodology requires non-hemorrhagic measurements for comparison, data that are frequently inaccessible in clinical contexts. To overcome this limitation, in accordance with the natural bilateral symmetry of the cerebral hemispheres, a symmetrical cancellation scheme is introduced. In this method, electrodes are uniformly arrayed around the cranial periphery and strategically positioned in a symmetrical manner relative to the sagittal suture. Subsequently, the measured capacitances for each electrode pair are subtracted from those of their symmetrical counterparts aligned with the sagittal suture. As a result, this process isolates the capacitance attributable solely to hemorrhagic events within a given hemisphere, permitting the absolute imaging of ICH. To assess the feasibility of this method, simulation and empirical imaging were conducted respectively on a numerical hemorrhage model and three physical models (a water-wrapped hemorrhage model, an isolated porcine fat-wrapped hemorrhage model, and an isolated porcine brain tissue-wrapped hemorrhage model). Traditional absolute imaging, time-differential imaging and symmetrical cancellation imaging were performed on all models. The results substantiate that the proposed imaging modality is capable of obtaining absolute imaging of ICH. But a mirrored artifact, symmetrical to the site of the actual hemorrhage image appeared in each of the imaging results. This mirror artifact was characterized by identical dimensions and an inverted pixel-value schema, an intrinsic consequence of the symmetrical cancellation imaging algorithm. The real image of hemorrhage can be ascertained through pre-judgment with the symptoms of the patient. Additionally, the quality of this imaging is seriously dependent on the precise alignment between the electrodes and the sagittal suture of the brain; even a minor deviation in symmetry could introduce excessive noises. Thus, the complicated operational procedures remain as challenges for practical application.
Hyperparameter tuning using Lévy flight and interactive crossover-based reptile search algorithm for eye movement event classification
Authors: Pradeep V. , Jayachandra Ananda Babu , Askar S. S. , Abouhawwash Mohamed
Published: May 2024

Introduction: Eye movement is one of the cues used in human–machine interface technologies for predicting the intention of users. The developing application in eye movement event detection is the creation of assistive technologies for paralyzed patients. However, developing an effective classifier is one of the main issues in eye movement event detection.

Methods: In this paper, bidirectional long short-term memory (BILSTM) is proposed along with hyperparameter tuning for achieving effective eye movement event classification. The Lévy flight and interactive crossover-based reptile search algorithm (LICRSA) is used for optimizing the hyperparameters of BILSTM. The issues related to overfitting are avoided by using fuzzy data augmentation (FDA), and a deep neural network, namely, VGG-19, is used for extracting features from eye movements. Therefore, the optimization of hyperparameters using LICRSA enhances the classification of eye movement events using BILSTM.

Results and Discussion: The proposed BILSTM–LICRSA is evaluated by using accuracy, precision, sensitivity, F1-score, area under the receiver operating characteristic (AUROC) curve measure, and area under the precision–recall curve (AUPRC) measure for four datasets, namely, Lund2013, collected dataset, GazeBaseR, and UTMultiView. The gazeNet, human manual classification (HMC), and multi-source information-embedded approach (MSIEA) are used for comparison with the BILSTM–LICRSA. The F1-score of BILSTM–LICRSA for the GazeBaseR dataset is 98.99%, which is higher than that of the MSIEA.
The calcineurin–NFATc pathway modulates the lipid mediators in BAL fluid extracellular vesicles, thereby regulating microvascular endothelial cell barrier function
Authors: Karpurapu Manjula , Nie Yunjuan , Chung Sangwoon , Yan Jiasheng , Dougherty Patrick , Pannu Sonal , Wisler Jon , Harkless Ryan , Parinandi Narasimham , Berdyshev Evgeny , Pei Dehua , Christman John W.
Published: May 2024

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse bronchoalveolar lavage fluid (BALF) were analyzed for their lipid mediators by liquid chromatography in conjunction with mass spectrometry (LC-MS/MS). Our data demonstrate that EVs from LPS-treated mice contained significantly higher levels of arachidonic acid (AA) metabolites, which were found in low levels by prior treatment with CNI103. The catalytic activity of lung tissue cytoplasmic phospholipase A2 (cPLA2) increased during ALI, correlating with an increased amount of arachidonic acid (AA) in the EVs. Furthermore, ALI is associated with increased expression of cPLA2, cyclooxygenase 2 (COX2), and lipoxygenases (5-LOX, 12-LOX, and 15-LOX) in lung tissue, and pretreatment with CNI103 inhibited the catalytic activity of cPLA2 and the expression of cPLA2, COX, and LOX transcripts. Furthermore, co-culture of mouse pulmonary microvascular endothelial cell (PMVEC) monolayer and NFAT-luciferase reporter macrophages with BALF EVs from LPS-treated mice increased the pulmonary microvascular endothelial cell (PMVEC) monolayer barrier permeability and luciferase activity in macrophages. However, EVs from CNI103-treated mice had no negative impact on PMVEC monolayer barrier integrity. In summary, BALF EVs from LPS-treated mice carry biologically active NFATc-dependent, AA-derived lipids that play a role in regulating PMVEC monolayer barrier function.
Research on autonomous navigation system of greenhouse electric crawler tractor based on LiDAR
Authors: Guo Huiping , Li Yi , Wang Hao , Wang Tingwei , Rong Linrui , Wang Haoyu , Wang Zihao , Wang Chensi , Zhang Jiao , Huo Yaobin , Guo Shaomeng
Published: May 2024

The application of autonomous navigation technology of electric crawler tractors is an important link in the development of intelligent greenhouses. Aiming at the characteristics of enclosed and narrow space and uneven ground potholes in greenhouse planting, to improve the intelligence level of greenhouse electric crawler tractors, this paper develops a navigation system of electric crawler tractors for the greenhouse planting environment based on LiDAR technology. The navigation hardware system consists of five modules: the information perception module, the control module, the communication module, the motion module, and the power module. The software system is composed of three layers: the application layer, the data processing layer, and the execution layer. The developed navigation system uses LiDAR, Inertial Measurement Unit (IMU) and wheel speed sensor to sense the greenhouse environment and the crawler tractor’s information, employs the Gmapping algorithm to build the greenhouse environment map, and utilizes the adaptive Monte Carlo positioning algorithm for positioning. The simulation test of different global path planning algorithms in Matlab shows that the A* algorithm obtains the optimal overall global path. In the scene of map 5, the path planned by the A* algorithm is the most significant, and the number of inflection points is reduced by 40.00% and 87.50%, respectively; meanwhile, the path length is the same as that of the Dijkstra algorithm, but the runtime is reduced by 68.87% and 81.49%, respectively; compared with the RRT algorithm, the path length is reduced by 7.27%. Therefore, the A* algorithm and the Dynamic Window Approach (DWA) method are used for tractor navigation and obstacle avoidance, which ensures global path optimality while also achieving effective local path planning for obstacle avoidance. The test results suggest that the maximum lateral deviation of the built map is 6 cm, and the maximum longitudinal deviation is 16 cm, which meets the requirement of map accuracy. Additionally, the results of the navigation accuracy test indicate that the maximum lateral deviation of navigation is less than 13 cm, the average lateral deviation is less than 7 cm, and the standard lateral deviation is less than 8 cm. The maximum heading deviation is less than 14°, the average heading deviation is less than 7°, and the standard deviation is less than 8°. These results show that the developed navigation system meets the navigation accuracy requirements of electric crawler tractors in the greenhouse environment.